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Sample records for consta risperidone long-acting

  1. Long-term remission in schizophrenia and schizoaffective disorder: results from the risperidone long-acting injectable versus quetiapine relapse prevention trial (ConstaTRE)

    PubMed Central

    Cavallaro, Roberto; Folnegović-Šmalc, Vera; Bidzan, Leszek; Emin Ceylan, Mehmet; Schreiner, Andreas

    2013-01-01

    Objective: The objective of this study was to report the long-term remission results from the ConstaTRE relapse prevention trial, in which clinically stable adults with schizophrenia or schizoaffective disorder treated with oral risperidone, olanzapine, or oral conventional antipsychotics were randomized to risperidone long-acting injectable (RLAI) or oral quetiapine, dosed according to package-insert recommendations. Methods: In the ConstaTRE trial, efficacy and tolerability were recorded for up to 24 months. This post hoc analysis presents remission data, defined, according to the Schizophrenia Working Group criteria, as achieving and maintaining eight core symptoms of schizophrenia that are mild or less over 6 months. Additional secondary outcome measures are also presented. Results: A total of 710 patients were randomized to RLAI (n = 355) or quetiapine (n = 355). Mean mode ± standard deviation (SD) drug doses were RLAI 33 ± 10 mg every 2 weeks and quetiapine 413 ± 159 mg daily. Full remission was achieved by 51.1% of patients with RLAI and 39.3% with quetiapine (p = 0.003). Mean ± SD of full remission durations were not significantly different with RLAI (540 ± 181 days) and quetiapine (508 ± 188 days). Overall tolerability was similar between treatment groups. Conclusions: Among stable patients with schizophrenia or schizoaffective disorder, remission was more likely after switching to RLAI than quetiapine. PMID:24167692

  2. Combination treatment with risperidone long-acting injection and psychoeducational approaches for preventing relapse in schizophrenia

    PubMed Central

    Zhao, Yueren; Kishi, Taro; Iwata, Nakao; Ikeda, Manabu

    2013-01-01

    A recent meta-analysis showed that long-acting injectable (LAI) antipsychotics were not superior to oral antipsychotics for preventing relapse in patients with schizophrenia. We therefore designed a treatment strategy combining risperidone LAI and COMPASS (COMprehensive Psycho-educational Approach and Scheme Set), an original psychoeducational program supporting treatment with risperidone LAI and evaluating subjective treatment satisfaction, transition of symptoms, and effectiveness in preventing symptomatic relapse. The aim of this study was to examine whether addition of COMPASS to risperidone LAI was more effective in preventing relapse in schizophrenia patients than risperidone LAI alone, with the latter group consisting of patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients were followed up for 6 months, with COMPASS continuously implemented from the transition to the observation phase. The primary efficacy measurements were relapse rate (rates of rehospitalization and discontinuation due to inefficacy). Secondary efficacy measurements were the Brief Psychiatric Rating Scale (BPRS) and Global Assessment of Functioning (GAF) scores. Of the 96 patients originally enrolled, 19 (19.8%) were discontinued from all causes. During the 6-month study period, ten of the 96 patients (10.4%) relapsed, compared with a 12.2% relapse rate in patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients showed significant improvements in BPRS total scores (P = 0.0031), BPRS positive (P = 0.0451), BRPS negative (P < 0.0001), and general subscale scores (P = 0.0031), and GAF (P < 0.0001) from baseline to 6 months. In conclusion, the lower relapse rate observed in patients treated with COMPASS plus risperidone LAI than in patients treated with risperidone LAI alone suggests that COMPASS may have benefits in the treatment of schizophrenia, indicating a need for randomized, controlled trials in larger numbers of patients. PMID:24194642

  3. Long Acting Risperidone in an Adolescent with Conduct Disorder: A Case Report

    PubMed Central

    Tutkunkardaş, Mustafa Deniz; Abali, Osman

    2011-01-01

    Adolescent conduct disorder (CD) is generally hard to manage clinically, as this population often refuses to take oral medications. Families and acquaintances of these adolescents usually suffer from extreme psychological, financial and social difficulties. Oral antipsychotics are the primary drugs of choice clinically, after behavioral treatments. Here we report a case with attention deficit hyperactivity disorder and conduct disorder who refuses to take any medications, was not eligible for behavioral treatments and was treated successfully with long acting risperidone.

  4. Effectiveness of long-acting risperidone in a patient with comorbid intellectual disability, catatonic schizophrenia, and oneiroid syndrome.

    PubMed

    Serata, Daniele; Rapinesi, Chiara; Kotzalidis, Georgios Demetrios; Alessi, Maria Chiara; Janiri, Delfina; Massolo, Anna Claudia; Ferri, Vittoria Rachele; Criscuolo, Silvia; Callovini, Gemma; Angeletti, Gloria; Girardi, Paolo; Del Casale, Antonio

    2015-01-01

    A patient with comorbid intellectual disability, catatonic schizophrenia, and recurrent oneiroid state of consciousness improved on long-acting risperidone and remains well at the three-year follow-up. We report a case treated with 50 mg long-acting risperidone administered every 14 days, who has been followed-up for three years. We studied his regional cerebral blood flow through technetium-99 m hexamethylpropyleneamine oxime single-photon emission computed tomography after two years of treatment. Symptoms of catatonic schizophrenia improved after two months of treatment, followed suit by oneiroid syndrome remission. Two years later, his brain perfusion was normal. No side effect has occurred since the patient was started on long-acting risperidone. Long-acting risperidone proved to be safe and effective in treating symptoms of catatonia and oneiroid syndrome. PMID:26443711

  5. Effects of Discontinuation of Paliperidone Long-Acting Injectable After Switching from Risperidone Long-Acting Injectable Switching

    PubMed Central

    Watanabe, Takafumi; Yamada, Atsurou

    2016-01-01

    Background Risperidone long-acting injection (RLAI) is increasingly being switched to paliperidone palmitate (PP) because of several benefits. However, this switching is not always successful. Methods We examined patient profiles following discontinuation of PP after switching from RLAI. We collected the electronic records of 24 patients with schizophrenia who had switched from RLAI to PP treatment at our hospital between November 2013 and March 2014. Twelve patients continued PP injection for over 1 year (PP-continuers), the other 12 patients discontinued within 1 year (PP-discontinuers), and both groups were followed up until December 31, 2014. Results PP-discontinuers had significantly shorter RLAI-administration period (mean 73.1 ± 59.0 weeks versus 148.5 ± 75.0 weeks), and lower chlorpromazine (CP) equivalent mean doses (mean 553.5 ± 251.0 mg versus 1002.5 ± 529.3 mg) compared with PP-continuers. The CP equivalent mean dose of PP-discontinuers had increased at the time of discontinuation and their social status became significantly worse. Six PP-discontinuers (50%) re-switched to RLAI, and their social status was not significantly worse at the end of the observation period. Conclusions On switching from RLAI to PP, we need to consider that some patients have had a shorter RLAI-administration period and may require lower amounts of antipsychotics. PMID:27738379

  6. Impact of risperidone long acting injection on resource utilization in psychiatric secondary care.

    PubMed

    Taylor, M; Currie, A; Lloyd, K; Price, M; Peperell, Kate

    2008-03-01

    Risperidone long acting injection (RLAI) is the only long acting atypical antipsychotic available in the UK. Its impact on NHS resource use has not been widely studied. This review of medical records was conducted to quantify the impact of RLAI on NHS psychiatric secondary care resource use, primarily in terms of episodes of inpatient hospital care 12 months before and 12 months after RLAI initiation. Data on number of hospitalizations and hospital bed days were collected retrospectively, from patient notes and hospital databases in four acute psychiatric units in the UK for all individuals with a diagnosis of schizophrenia or schizoaffective disorder who were prescribed RLAI more than 12 months previously. Data were collected on 100 individuals (58 male) with a mean age 40.8 years (range 19-70). The median duration of illness before RLAI initiation was 12 years (range six months to 43 years). There were 62 admissions in the 12 months pre-RLAI, falling to 22 admissions in the 12 months post-RLAI. Number of admissions, we argue, offer a more reliable indicator of the impact of treatment than total hospital bed days in this type of study. In this study there were 40 fewer admissions in the 12 months after RLAI was initiated compared with the previous 12 months. This is important as readmission is a good proxy measure of relapse, and adherence to medication is known to be a key factor in relapse prevention. PMID:18308820

  7. Comparison of Subjective Experiences and Effectiveness of First-Generation Long-Acting Injectable Antipsychotics and Risperidone Long-Acting Injectables in Patients With Schizophrenia.

    PubMed

    Chen, Wen-Yin; Lin, Shih-Ku

    2016-10-01

    We conducted a cross-sectional study to compare the subjective experiences and clinical effects of first-generation long-acting injectable (FGA-LAI) antipsychotics with those of risperidone long-acting injectables (RIS-LAIs) in 434 schizophrenia patients. Compared with the RIS-LAI group, the patients treated with FGA-LAIs had a significantly longer duration of illness and LAI treatment and were older. Our results suggest that patients treated with FGA-LAI have more satisfactory subjective experiences compared with patients treated with RIS-LAI and that both FGA-LAI and RIS-LAI treatments can prevent relapses and hospitalization. Additional longitudinal studies determining the long-term benefits of RIS-LAI are warranted. PMID:27580495

  8. Costs and effects of long-acting risperidone compared with oral atypical and conventional depot formulations in Germany.

    PubMed

    Laux, Gerd; Heeg, Bart; van Hout, Ben A; Mehnert, Angelika

    2005-01-01

    Schizophrenia is one of the most expensive psychiatric conditions because of high direct and indirect costs associated with the nature of the illness, its resistance to treatment and the consequences of relapse. Long-acting risperidone is a new formulation of an atypical antipsychotic drug that also offers the improvements in compliance associated with haloperidol depot. The aim of this simulation study was to compare the benefits and costs of three pharmacological treatment strategies comprising first-line treatment with long-acting risperidone injection, a haloperidol depot or an oral atypical antipsychotic agent, over a 5-year period in Germany. A discrete event simulation model was developed to compare three treatment scenarios from the perspective of major third-party payers (sickness funds and social security 'Sozialversicherung'). The scenarios comprised first-line treatment with haloperidol depot (scenario 1), long-acting risperidone (scenario 2) and oral olanzapine (scenario 3). Switches to second or third-line options were allowed when side-effects occurred or a patient suffered more than a fixed number of relapses. The model accounted for fixed patient characteristics, and on the basis of these, simulated patient histories according to several time-dependent variables. The time horizon for this model was limited to 5 years, and in accordance with German guidelines, costs and effects were discounted by between 3 and 10%. Direct costs included medication, type of physician visits and treatment location. Indirect costs were not included. Information on treatment alternatives, transition probabilities, model structure and healthcare utilization were derived from the literature and an expert panel. Outcomes were expressed in terms of the number and duration of psychotic episodes, cumulative symptom scores, costs, and quality-adjusted life-years (QALY). Univariate sensitivity analyses were carried out, as were subgroup analyses based on disease severity and

  9. Antipsychotic-induced metabolic effects in the female rat: Direct comparison between long-acting injections of risperidone and olanzapine.

    PubMed

    Ersland, Kari M; Skrede, Silje; Røst, Therese H; Berge, Rolf K; Steen, Vidar M

    2015-12-01

    Several antipsychotics have well-known adverse metabolic effects. Studies uncovering molecular mechanisms of such drugs in patients are challenging due to high dropout rates, previous use of antipsychotics and restricted availability of biological samples. Rat experiments, where previously unexposed animals are treated with antipsychotics, allow for direct comparison of different drugs, but have been hampered by the short half-life of antipsychotics in rodents. The use of long-acting formulations of antipsychotics could significantly increase the value of rodent models in the molecular characterization of therapeutic and adverse effects of these agents. However, as long-acting formulations have rarely been used in rodents, there is a need to characterize the basic metabolic phenotype of different antipsychotics. Using long-acting olanzapine injections as a positive control, the metabolic effects of intramuscular long-acting risperidone in female rats were investigated for the first time. Like olanzapine, risperidone induced rapid, significant hyperphagia and weight gain, with concomitant increase in several plasma lipid species. Both drugs also induced weight-independent upregulation of several genes encoding enzymes involved in lipogenesis, but this activation was not confirmed at the protein level. Our findings shed light on the role of drug administration, drug dose and nutritional status in the development of rodent models for adverse metabolic effects of antipsychotic agents. PMID:26378122

  10. Effectiveness of long-acting antipsychotics in clinical practice: 2. Effects of antipsychotic polypharmacy on risperidone long-acting injection and zuclopenthixol decanoate

    PubMed Central

    Cordiner, Matthew; Shajahan, Polash; McAvoy, Sarah; Bashir, Muhammad; Taylor, Mark

    2016-01-01

    Objectives: Antipsychotic polypharmacy (APP) is common clinical practice. Theoretically, APP runs the risk of additional side effects, drug interactions, adherence and cost. A limited evidence base is emerging to support the effectiveness of APP in clinical practice. Our companion paper highlighted the extent of APP alongside commonly prescribed long-acting antipsychotic injections (LAIs). We aimed to examine the effects of APP on discontinuation rates and Clinical Global Impression (CGI) outcomes in patients commenced on risperidone long-acting injection (RLAI) and zuclopenthixol decanoate. Method: LAI-naïve patients commenced on RLAI (n = 102) and zuclopenthixol decanoate(n = 105) were identified using our electronic patient record (running from 2002) within NHS Lanarkshire, Scotland, UK. This was a retrospective, electronic case note review with an 18-month follow up. Patient groups were divided into those receiving the LAI as the sole antipsychotic and those who were receiving additional oral antipsychotic polypharmacy (APP) for at least 50% of the duration of the treatment with their LAI. Kaplan–Meier statistics were calculated for discontinuation rates. CGI severity and improvement scores were retrospectively assigned by the investigating team. Results: Antipsychotic polypharmacy occurred with RLAI (37%) and zuclopenthixol decanoate (46%) and was associated with lower discontinuation rates (statistical significant with zuclopenthixol for any cause and adverse effects discontinuation). APP had no adverse outcomes on hospital admissions or CGI ratings. Patients on APP did not have more severe, chronic or treatment resistant illnesses. Conclusions: For RLAI and zuclopenthixol decanoate, APP had some favourable outcomes when examining discontinuation rates for any cause, and adverse effects. This was unexpected as we had considered APP would signal illness chronicity and severity and be associated with increased adverse effects resulting in early

  11. Worsening of myasthenia gravis after administration of injectable long-acting risperidone for treatment of schizophrenia; first case report and a call for caution.

    PubMed

    Al-Hashel, Jasem Y; Ismail, Ismail Ibrahim; John, John K; Ibrahim, Mohammed; Ali, Mahmoud

    2016-01-01

    Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to autoantibodies affecting the neuromuscular junction. Co-occurrence of myasthenia gravis and schizophrenia is very rare and raises a challenge in management of both diseases. Antipsychotic drugs exhibit anticholinergic side effects and have the potentials of worsening myasthenia. Long-acting risperidone is an injectable atypical antipsychotic drug that has not been previously reported to worsen myasthenia gravis in literature. We report the first case report of worsening of myasthenia after receiving long-acting risperidone injection for schizophrenia in a 29-year-old female with both diseases. She started to have worsening 2 weeks following the first injection and her symptoms persisted despite receiving plasma exchange. This could be explained by the pharmacokinetics of the drug. We recommend that long-acting risperidone should be used with caution in patients with myasthenia gravis, and clinicians must be aware of the potential risks of this therapy. PMID:27012182

  12. Worsening of myasthenia gravis after administration of injectable long-acting risperidone for treatment of schizophrenia; first case report and a call for caution.

    PubMed

    Al-Hashel, Jasem Y; Ismail, Ismail Ibrahim; John, John K; Ibrahim, Mohammed; Ali, Mahmoud

    2016-01-01

    Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to autoantibodies affecting the neuromuscular junction. Co-occurrence of myasthenia gravis and schizophrenia is very rare and raises a challenge in management of both diseases. Antipsychotic drugs exhibit anticholinergic side effects and have the potentials of worsening myasthenia. Long-acting risperidone is an injectable atypical antipsychotic drug that has not been previously reported to worsen myasthenia gravis in literature. We report the first case report of worsening of myasthenia after receiving long-acting risperidone injection for schizophrenia in a 29-year-old female with both diseases. She started to have worsening 2 weeks following the first injection and her symptoms persisted despite receiving plasma exchange. This could be explained by the pharmacokinetics of the drug. We recommend that long-acting risperidone should be used with caution in patients with myasthenia gravis, and clinicians must be aware of the potential risks of this therapy.

  13. A Prospective Study Comparing the Long-term Effectiveness of Injectable Risperidone Long-acting Therapy and Oral Aripiprazole in Patients with Schizophrenia

    PubMed Central

    Macfadden, Wayne; Ma, Yi-Wen; Thomas Haskins, J.; Bossie, Cynthia A.

    2010-01-01

    Objective: To test the hypothesis that long-term maintenance with injectable risperidone long-acting therapy is superior to oral daily aripiprazole in stable patients with schizophrenia. Design: This two-year, rater-blinded, open-label, multicenter study (NCT00299702) randomized subjects to injectable risperidone long-acting therapy (25–50mg, injected every 2 weeks) or oral aripiprazole (5–30mg/day), with study visits every two weeks. Subjects who met relapse criteria or discontinued study drug could remain in the study. Setting: Clinical trial. Participants: Stable subjects with schizophrenia not adequately benefiting from current treatment who experienced two or more relapses in the past two years. If recently relapsed, subjects were stabilized (per clinician judgment) for two or more months before entry. Measurements: Primary endpoints: time to relapse and time in remission. Safety assessments included adverse event reporting. Results: Of 355 subjects randomized, 349 were in the intent-to-treat analysis set. Data inspection revealed that 53 (14.9%) randomized subjects deviated from inclusion/exclusion criteria, most commonly not meeting stability requirements. At baseline, mean (standard deviation [SD]) Positive and Negative Syndrome Scale total score was 68.9 (14.6); 115 (33.0%) intent-to-treat subjects met remission criteria. Approximately 29 percent in each group discontinued the study before completing two years. No significant between-group differences were noted in time to relapse or time in remission. No new tolerability issues were identified. Conclusion: Results failed to demonstrate superiority with injectable risperidone long-acting therapy versus oral aripiprazole. The study design did not allow for valid conclusions of equivalence or noninferiority. Although this study attempted to mimic a real-world treatment setting for stable patients, the broad study population, the lack of patient selection for nonadherence, biweekly visits, regular

  14. A prospective, open-label study to evaluate symptomatic remission in schizophrenia with risperidone long-acting injectable in Korea.

    PubMed

    Lee, Nam Young; Kim, Se Hyun; Cho, Seong Jin; Chung, Young-Cho; Jung, In Kwa; Kim, Chang Yoon; Kim, Duk Ho; Lee, Dong Geun; Lee, Yo Han; Lim, Weon Jeong; Na, Young Suk; Shin, Sang Eun; Woo, Jong-Min; Yoon, Jin Sang; Yoon, Bo-Hyun; Ahn, Yong Min; Kim, Yong Sik

    2014-09-01

    This study was designed to investigate long-term clinical outcomes of risperidone long-acting injectable (RLAI) in patients with schizophrenia or schizoaffective disorder. An open-label, 48-week, prospective study of RLAI treatment was carried out at 63 centers in South Korea. Initial and maintenance dosage of RLAI were adjusted according to clinical judgment. Efficacy was measured by the remission rate, continuation rate, and changes in the clinical measurements such as eight items of the Positive and Negative Symptom Scale (PANSS), the Clinical Global Impression - Severity, and the Schizophrenia Quality of Life Scale. In terms of the safety, Simpson-Angus rating Scale, adverse events (AEs), and BMI were investigated. Of the 522 patients who were enrolled, 472 patients who had been assessed on the eight items of PANSS at baseline and at least once during RLAI treatment were included in the intention-to-treat (ITT) population. The per-protocol (PP) population included 184 patients (39.0%), who completed all assessments during 48 weeks of the follow-up period. Total scores of eight items of PANSS, Clinical Global Impression - Severity, and Schizophrenia Quality of Life Scale were reduced significantly from baseline to endpoint in both ITT and PP populations. The mean dose (SD) of RLAI was 33.2 (7.6) mg. In the PP population, the number of patients who scored 1-3 on eight items of PANSS were 47 (25.5%) at baseline and 144 (78.3%) at 48 weeks. According to the remission defining as scores 1-3 on eight items of PANSS sustaining of at least 6 months' duration by Andreasen, the numbers of patients who achieved remission were 45 (24.5%) at 24 weeks and 120 (65.2%) at 48 weeks. A significant decrease in the mean score of Simpson-Angus rating Scale and a significant increase in BMI over time in last observation carried forward were observed, and patients who fulfilled the remission criteria during the study showed more weight gain than those who did not. During the study

  15. Risperidone

    MedlinePlus

    Risperidone is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual ... do not already have diabetes. If you have schizophrenia, you are more likely to develop diabetes than ...

  16. Relapse Prevention in Schizophrenia and Schizoaffective Disorder with Risperidone Long-Acting Injectable vs Quetiapine: Results of a Long-Term, Open-Label, Randomized Clinical Trial

    PubMed Central

    Gaebel, Wolfgang; Schreiner, Andreas; Bergmans, Paul; de Arce, Rosario; Rouillon, Frédéric; Cordes, Joachim; Eriksson, Lars; Smeraldi, Enrico

    2010-01-01

    Chronic management of schizophrenia and schizoaffective disorders is frequently complicated by symptomatic relapse. An open-label, randomized, active-controlled, 2-year trial evaluated 710 patients with schizophrenia or related disorders who were switched from stable treatment with oral risperidone, olanzapine, or conventional neuroleptics to risperidone long-acting injectable (RLAI) or oral quetiapine. Primary effectiveness evaluation was time-to-relapse. Safety evaluations included adverse events (AEs) reported for the duration of the study, Extrapyramidal Symptom Rating Scale (ESRS), clinical laboratory tests, and vital signs. A total of 666 patients (n=329 RLAI, n=337 quetiapine) were evaluable for effectiveness measures. Baseline demographics were similar between treatment groups. Kaplan–Meier estimate of time-to-relapse was significantly longer with RLAI (p<0.0001). Relapse occurred in 16.5% of patients with RLAI and 31.3% with quetiapine. RLAI and quetiapine were both safe and well tolerated. Weight gain affected 7% of patients with RLAI and 6% with quetiapine, with mean end point increases of 1.25±6.61 and 0±6.55 kg, respectively. There were no significant between-group differences in weight gain. ESRS total scores decreased similarly after randomization to either RLAI or quetiapine. Extrapyramidal AEs occurred in 10% of patients with RLAI and 6% with quetiapine. Treatment-emergent potentially prolactin-related AEs were reported in 15 (5%) patients with RLAI and 5 (2%) patients with quetiapine; hyperprolactinemia was reported in 43 (13.1%) patients with RLAI and 5 (1.5%) patients with quetiapine. Somnolence occurred in 2% of patients with RLAI and 11% with quetiapine. To our knowledge, this is the first report of a randomized clinical trial directly comparing relapse prevention with a second-generation long-acting injectable antipsychotic and oral therapy. Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder was

  17. Paliperidone palmitate in non-acute patients with schizophrenia previously unsuccessfully treated with risperidone long-acting therapy or frequently used conventional depot antipsychotics

    PubMed Central

    Bergmans, P; Cherubin, P; Keim, S; Llorca, P-M; Cosar, B; Petralia, A; Corrivetti, G; Hargarter, L

    2015-01-01

    PALMFlexS, a prospective multicentre, open-label, 6-month, phase IIIb interventional study, explored tolerability, safety and treatment response in adults (n = 231) with non-acute but symptomatic schizophrenia switching to flexibly dosed paliperidone palmitate (PP) after unsuccessful treatment with risperidone long-acting injectable therapy (RLAT) or conventional depot antipsychotics (APs). Treatment response was measured by change in Positive and Negative Syndrome Scale (PANSS) total score from baseline (BL) to last-observation-carried-forward (LOCF) endpoint (EP). Safety and tolerability assessments included Extrapyramidal Symptom Rating Scale (ESRS) total score and treatment-emergent adverse events. Significant reductions in mean PANSS total score were observed for all groups (−7.5 to −10.6; p ⩽ 0.01 [BL to LOCF EP]). After switching to PP, more than 50% of all patients achieved ⩾20% and one-third of RLAT-treated patients even achieved ⩾50% improvement in PANSS total score. Across groups, there were significant improvements (p < 0.05) in symptom severity as measured by Clinical Global Impression-Severity (CGI-S; trend for improvement with RLAT; p = 0.0568), subjective well-being, medication satisfaction, and patient functioning with PP. PP was generally well tolerated. Clinically relevant benefits were observed in non-acute patients with schizophrenia switched from RLAT or conventional depot APs to PP. PMID:25999398

  18. Effectiveness of long-acting injectable risperidone versus oral antipsychotics in the treatment of recent-onset schizophrenia: a case-control study.

    PubMed

    Barrio, Pablo; Batalla, Albert; Castellví, Pere; Hidalgo, Diego; García, Marta; Ortiz, Ana; Grande, Iria; Pons, Alexandre; Parellada, Eduard

    2013-07-01

    Long-acting injectable antipsychotics may offer a relevant improvement in treatment adherence in recent-onset psychosis, leading to a decreased rate of hospital readmission, a better rate of clinical remission and improved psychosocial adjustment. The aim of the study was to compare the clinical remission rates, number of hospital readmissions and personal and social functioning after 2 years between patients with recent-onset schizophrenia (<2 years) in treatment with risperidone long-acting injectable (RLAI) and patients with recent-onset schizophrenia receiving oral antipsychotics. This is a case-control study comparing patients with recent-onset schizophrenia who initiated RLAI treatment between 2004 and 2008 (n=26) with a control group matched for age and sex, diagnosed with recent-onset schizophrenia and treated with oral antipsychotics (n=26). Study assessments included sociodemographic variables, the Positive and Negative Syndrome Scale, the Personal and Social Functioning Scale, the number of hospital readmissions and the Andreasen remission criteria. To assess the effect of treatment on each dependent variable, separate generalized estimating equations models were constructed. After 2 years of treatment, and adjusting for educational level, the RLAI group showed a greater reduction in the Positive and Negative Syndrome Scale total scale [mean (SD)=47.7 (12.0) vs. 66.2 (18.5); mean difference =-17.56; 95% confidence interval (CI)=-27.11 to -8.00; P<0.001], as well as in the negative [mean (SD) 14.3 (6.1) vs. 19.4 (6.4); mean difference=-5.02; 95% CI=-8.28 to -1.77; P=0.002] and general psychopathology [mean (SD)=23.4 (6.3) vs. 32.7 (8.1); mean difference=-9.16; 95% CI=-13.3 to -5.03; P<0.001] subscales compared with the oral antipsychotic group. Personal and Social Functioning Scale scores were also higher in the RLAI group [mean (SD)=72.4 (14.8) vs. 59.7 (13.5); mean difference=13.41; 95% CI=5.65-21.18; P<0.001]. Although not statistically significant

  19. An Exploratory, Open-Label, Randomized Trial Comparing Risperidone Long-Acting Injectable with Oral Antipsychotic Medication in the Treatment of Early Psychosis.

    PubMed

    Malla, Ashok; Chue, Pierre; Jordan, Gerald; Stip, Emmanuel; Koczerginski, David; Milliken, Heather; Joseph, Anil; Williams, Richard; Adams, Beverly; Manchanda, Rahul; Oyewumi, Kola; Roy, Marc-André

    2016-01-01

    Few studies have examined effectiveness and tolerability of risperidone long-acting injections (RLAI) in the early phase of a schizophrenia spectrum (SS) disorder using a randomized controlled trial (RCT) design. Eighty-five patients in early phase of an SS disorder were randomized to receive either oral second-generation antipsychotics (SGAs; n=41) or RLAI (n=44) over two years. Analyses were conducted on eligible participants (n=77) for the stabilization (maximum 18 weeks) and maintenance phases (up to Week 104) on primary outcome measures of time to stabilization and relapse, change in symptoms and safety, and comparisons made across the two groups. Both groups showed improvement on Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression-Severity (CGI-S) scores. There were no time X group interactions on any of the primary outcome measures. Post hoc examination revealed that the RLAI group showed greater change on CGI-S and PANSS negative symptom scores during the stabilization phase, while the oral group reached the same level of improvement during the maintenance phase. The current exploratory study suggests that-within an RCT design-RLAI and oral SGAs are equally effective and have similar safety profiles in patients in the early phase of SS disorders. Thus, RLAI offers no advantage to patients in early phase of SS disorders, but is likely to be effective and safe for those who may have problems with adherence and may either choose to take it or be prescribed under conditions of external control such as community treatment orders.

  20. Resource utilization in patients with schizophrenia who initiated risperidone long-acting therapy: results from the Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation (SOURCE)

    PubMed Central

    2011-01-01

    Background Schizophrenia is a chronic mental health disorder associated with increased hospital admissions and excessive utilization of outpatient services and long-term care. This analysis examined health care resource utilization from a 24-month observational study of patients with schizophrenia initiated on risperidone long-acting therapy (RLAT). Methods Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation (SOURCE) was a 24-month observational study designed to examine real-world treatment outcomes by prospectively following patients with schizophrenia initiated on RLAT. At baseline visit, prior hospitalization and ER visit dates were obtained for the previous 12 months and subsequent hospitalization visit dates were obtained at 3-month visits, if available. The health care resource utilization outcomes measures observed in this analysis were hospitalizations for any reason, psychiatric-related hospitalizations, and emergency room (ER) visits. Incidence density analysis was used to assess pre-event and postevent rates per person-year (PY). Results The primary medical resource utilization analysis included 435 patients who had a baseline visit, ≥1 postbaseline visits after RLAT initiation, and valid hospitalization dates. The number of hospitalizations and ER visits per PY declined significantly (p < .0001) after initiation with RLAT. A 41% decrease (difference of -0.29 hospitalizations per PY [95% CI: -0.39 to -0.18] from baseline) in hospitalizations for any reason, a 56% decrease (a difference of -0.35 hospitalizations per PY [95% CI: -0.44 to -0.26] from baseline) in psychiatric-related hospitalizations, and a 40% decrease (-0.26 hospitalizations per PY [95% CI: -0.44 to -0.10] from baseline) in ER visits were observed after the baseline period. The percentage of psychiatric-related hospitalizations decreased significantly after RLAT initiation, and patients had fewer inpatient hospitalizations and ER visits (all p < .0001). Conclusion The

  1. Risperidone Injection

    MedlinePlus

    ... release (long-acting) injection is used to treat schizophrenia (a mental illness that causes disturbed or unusual ... do not already have diabetes. If you have schizophrenia, you are more likely to develop diabetes than ...

  2. Long-acting muscarinic antagonists.

    PubMed

    Melani, Andrea S

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of death and disability worldwide. Inhaled bronchodilators are the mainstay of COPD pharmacological treatment. Long-acting muscarinic antagonists (LAMAs) are a major class of inhaled bronchodilators. Some LAMA/device systems with different characteristics and dosing schedules are currently approved for maintenance therapy of COPD and a range of other products are being developed. They improve lung function and patient-reported outcomes and reduce acute bronchial exacerbations with good safety. LAMAs are used either alone or associated with long-acting β₂-agonists, eventually in fixed dose combinations. Long-acting β₂-agonist/LAMA combinations assure additional benefits over the individual components alone. The reader will obtain a view of the safety and efficacy of the different LAMA/device systems in COPD patients. PMID:26109098

  3. Long-acting hormonal contraception.

    PubMed

    Benagiano, Giuseppe; Gabelnick, Henry; Brosens, Ivo

    2015-11-01

    Today, a new category of fertility-regulating agents has been created: long-acting, reversible hormonal contraceptives; they minimize compliance, while maximize effectiveness. They comprise subdermal implants and intrauterine devices. Other long-acting agents exist, such as Depo Provera and Noristerat. Use of Depo Provera and Noristerat carries great effectiveness, good clinical safety and usefulness in developing countries. They cause no significant increase in breast cancer risk, but they may carry an increased risk of HIV. Subcutaneous delivery systems have two common features: prolongation of effect is obtained by a drug reservoir and for most of their duration of action they provide a continuous, sustained release of the active hormone. Finally, the intrauterine system Mirena represents both a very effective contraceptive and a specific treatment for menorrhagia.

  4. Interpreting serum risperidone concentrations.

    PubMed

    Boerth, Joel M; Caley, Charles F; Goethe, John W

    2005-02-01

    Risperidone is an atypical antipsychotic commonly used for treatment of schizophrenia and other psychotic disorders. Although therapeutic drug monitoring is not routine for any of the atypical antipsychotics, serum antipsychotic concentrations are measured routinely to assess treatment nonadherence. In humans, risperidone is metabolized by cytochrome P450 2D6 to 9-hydroxyrisperidone; together these constitute the active moiety. Dose-proportional increases in serum concentrations have not been reported for the parent drug, but have been reported for 9-hydroxyrisperidone and the active moiety (i.e., the combined concentrations of risperidone and 9-hydroxyrisperidone). We describe a 34-year-old Caucasian man of Sicilian descent with a history of schizophrenia, disorganized type. He was suspected to be noncompliant with his risperidone therapy. Initially, active moiety risperidone concentrations increased linearly with prescribed dosage increases. However, with continued increases, active moiety concentrations adjusted downward and remained 17-36% below anticipated levels. We propose a method for estimating target active moiety concentrations of risperidone based on dosage-a method that may be used to guide clinicians in assessing nonadherence to risperidone treatment.

  5. Long-Acting Injectable Antipsychotics for Prevention of Relapse in Bipolar Disorder: A Systematic Review and Meta-Analyses of Randomized Controlled Trials

    PubMed Central

    Oya, Kazuto; Iwata, Nakao

    2016-01-01

    Background: This meta-analysis of randomized controlled trials aimed to examine the advantages of long-acting injectable antipsychotics over placebo or oral medications regarding efficacy and safety for patients with bipolar disorder. Methods: Two categorical meta-analyses of randomized controlled trials were performed to compare study-defined relapse rate (primary), discontinuation rates, and individual adverse events: (1) risperidone-long-acting injectable vs placebo, and (2) long-acting injectable antipsychotics vs oral medications. Results: We identified 7 randomized controlled trials (n=1016; long-acting injectable antipsychotics [flupenthixol (1 randomized controlled trial) and risperidone (6 randomized controlled trials)=449]; oral medications [mood stabilizers, antidepressants, antipsychotic, or any combination of these agents=283]; and placebo=284). Risperidone-long-acting injectable antipsychotic was superior to placebo for study-defined relapse rate (risk ratio=0.63, P<.0001), relapse of manic symptoms (risk ratio=0.42, P<.00001), and all-cause discontinuation (risk ratio=0.75, P=.007). Risperidone-long-acting injectable was associated with higher incidence of prolactin-related adverse events (risk ratio=4.82, P=.001) and weight gain (risk ratio=3.80, P<.0001) than placebo. The pooled long-acting injectable antipsychotics did not outperform oral medications regarding primary outcome but with significant heterogeneity (I2=74%). Sensitivity analysis, including only studies with rapid cycling or high frequency of relapse patients, revealed that long-acting injectable antipsychotics were superior compared to oral medications (I2=0%, RR=0.58, P=.0004). However, the comparators in this sensitivity analysis did not include second-generation antipsychotic monotherapy. In sensitivity analysis, including only studies with second-generation antipsychotic monotherapy as the comparator, long-acting injectable antipsychotics did not outperform second

  6. Long-acting injectable antipsychotics in the elderly: guidelines for effective use.

    PubMed

    Masand, Prakash S; Gupta, Sanjay

    2003-01-01

    are reduced dramatically with atypical antipsychotics compared with traditional agents, the development of long-acting atypical antipsychotic formulations has been pursued. Of the atypical antipsychotics, risperidone is the first agent to be approved in a long-acting injectable formulation. Unpublished clinical data have revealed that patients treated with long-acting injectable risperidone (25mg, 50mg or 75mg) are more likely to show significant clinical improvement than placebo. In addition, hospitalisation rates decreased continuously and significantly during 1 year of treatment for patients who received long-acting injectable risperidone.Long-acting injectable antipsychotic medication should be considered for older patients for whom long-term treatment is indicated. The choice of which drug to use should be based on patients' history of response and personal preference, clinician's previous experience and pharmacokinetic properties.

  7. In vitro-in vivo correlation of parenteral risperidone polymeric microspheres.

    PubMed

    Shen, Jie; Choi, Stephanie; Qu, Wen; Wang, Yan; Burgess, Diane J

    2015-11-28

    The objective of the present study was to determine whether an in vitro-in vivo correlation (IVIVC) can be established for polymeric microspheres that are equivalent in formulation composition but prepared with different manufacturing processes. Risperidone was chosen as a model therapeutic and poly(lactic-co-glycolic acid) (PLGA) with similar molecular weight as that used in the commercial product Risperdal® Consta® was used to prepare risperidone microspheres. Various manufacturing processes were investigated to produce the risperidone microspheres with similar drug loading (approx. 37%) but distinctly different physicochemical properties (e.g. porosity, particle size and particle size distribution). In vitro release of the risperidone microspheres was investigated using different release testing methods (such as sample-and-separate and USP apparatus 4). In vivo pharmacokinetic profiles of the risperidone microsphere formulations following intramuscular administration were determined using a rabbit model. Furthermore, the obtained pharmacokinetic profiles were deconvoluted using the Loo-Riegelman method and the calculated in vivo release was compared with the in vitro release of these microspheres. Level A IVIVCs were established and validated for the compositionally equivalent risperidone microspheres based on the in vitro release data obtained using USP apparatus 4. The developed IVIVCs demonstrated good predictability and were robust. These results showed that the developed USP apparatus 4 method was capable of discriminating PLGA microspheres that are equivalent in formulation composition but with manufacturing differences and predicting their in vivo performance in the investigated animal model.

  8. Second-generation long-acting injectable antipsychotics in schizophrenia: patient functioning and quality of life

    PubMed Central

    Montemagni, Cristiana; Frieri, Tiziana; Rocca, Paola

    2016-01-01

    Long-acting injectable antipsychotics (LAIs) were developed to make treatment easier, improve adherence, and/or signal the clinician when nonadherence occurs. Second-generation antipsychotic LAIs (SGA-LAIs) combine the advantages of SGA with a long-acting formulation. The purpose of this review is to evaluate the available literature concerning the impact of SGA-LAIs on patient functioning and quality of life (QOL). Although several studies regarding schizophrenia patients’ functioning and QOL have been performed, the quantity of available data still varies greatly depending on the SGA-LAI under investigation. After reviewing the literature, it seems that SGA-LAIs are effective in ameliorating patient functioning and/or QOL of patients with schizophrenia, as compared with placebo. However, while methodological design controversy exists regarding the superiority of risperidone LAI versus oral antipsychotics, the significant amount of evidence in recently published research demonstrates the beneficial influence of risperidone LAI on patient functioning and QOL in stable patients and no benefit over oral treatment in unstable patients. However, the status of the research on SGA-LAIs is lacking in several aspects that may help physicians in choosing the correct drug therapy. Meaningful differences have been observed between SGA-LAIs in the onset of their clinical efficacy and in the relationships between symptoms and functioning scores. Moreover, head-to-head studies comparing the effects of SGA-LAIs on classical measures of psychopathology and functioning are available mainly on risperidone LAI, while those comparing olanzapine LAI with other SGA-LAIs are still lacking. Lastly, some data on their use, especially in first-episode or recent-onset schizophrenia and in refractory or treatment-resistant schizophrenia, is available. PMID:27143893

  9. Long-Acting Growth Hormone: An Update.

    PubMed

    Saenger, Paul H; Mejia-Corletto, Jorge

    2016-01-01

    After the introduction of recombinant human growth hormone (rhGH) in 1985, a myriad of children and adults have benefited from its growth-promoting and metabolic effects. Nowadays, current therapeutic regimens rely on daily subcutaneous GH injections that could be burdensome and inconvenient to pediatric patients. As expected with any long-term parenteral pharmacological treatment, these daily regimens may promote nonadherence, poor compliance, treatment abandonment and/or suboptimal clinical outcomes. In order to improve patient and caregiver acceptance of proposed regimens, simplified dosing schedules could potentially aid in reducing poor compliance and maximize the therapeutic end results. Long-acting GH formulations have been designed and perfected over the last two decades, and currently there are several formulations in advanced stages of research as a reasonable attempt to improve patient's adherence to GH treatment. A long-acting GH preparation allowing for reduced injection frequency is likely to improve treatment adherence and to decrease the distress and inconvenience associated with daily injections. This review presents an update about the status of current and recent efforts that have enabled the formulation of sustained-release, long-acting rhGH as it has been longed for many years in the pediatric endocrinology field.

  10. Microsphere delivery of Risperidone as an alternative to combination therapy.

    PubMed

    D'Souza, Susan; Faraj, Jabar; DeLuca, Patrick

    2013-11-01

    attaining steady state with Risperdal Consta® was attributed to the 3 week latency in drug release from the microspheres and was in accordance with previous studies indicating a good corroboration with clinical findings. Calculated cumulative AUC (area under the curve) levels for Formulation C were similar to the Risperdal Consta®, though there were marked differences in AUC levels at the early time points. Comparison of Risperidal Consta® and Formulation C by multiple dosing in vivo experiments revealed that the marketed preparation demonstrated a substantial delay in providing an initial loading dose, continuous circulating levels, and attainment of steady state; all of which were observed rapidly with Formulation C. Findings from the current study strongly suggest that a microsphere dosage form of Risperidone can be formulated with an optimum particle size and drug loading to provide an initial bolus followed by maintenance levels, thereby eliminating combination therapy and improving patient compliance.

  11. A Systemic Review and Experts’ Consensus for Long-acting Injectable Antipsychotics in Bipolar Disorder

    PubMed Central

    Chou, Yuan Hwa; Chu, Po-Chung; Wu, Szu-Wei; Lee, Jen-Chin; Lee, Yi-Hsuan; Sun, I-Wen; Chang, Chen-Lin; Huang, Chien-Liang; Liu, I-Chao; Tsai, Chia-Fen; Yen, Yung-Chieh

    2015-01-01

    Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician’s clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms. PMID:26243837

  12. Long-acting methods require special care.

    PubMed

    Blaney, C L

    1994-08-01

    Long-acting contraceptive methods including IUDs, implants, and sterilization are among the most effective and convenient contraceptive methods, requiring little or no effort on the part of the user once provided by a trained healthcare provider. Some women, however, oppose the development and use of provider-dependent contraceptive methods due to the potential for method misuse. These methods, for example, could be provided without women's fully informed choice, access to removal could be blocked, or the method could be provided to an inappropriate client. Making a contraceptive method unavailable because of potential abuse instead restricts women's reproductive choices. After all, abuse generally comes from the legal or delivery system, not from the method itself. Efforts should be made to satisfy users with standard norms for performance and without targets for specific methods. Good service delivery along with revised approaches to contraceptive introduction and program evaluation can help prevent inappropriate method use and ensure that women receive adequate information and counseling to help them make reproductive choices without undue influence. The author discusses Norplant delivery, providing IUDs, offering sterilization, and improving access.

  13. Risperidone and Explosive Aggressive Autism.

    ERIC Educational Resources Information Center

    Horrigan, Joseph P.; Barnhill, L. Jarrett

    1997-01-01

    In this study, 11 males with autism and mental retardation were administered risperidone. Substantial clinical improvement was noted almost immediately; patients with aggression, self-injury, explosivity, and poor sleep hygiene were most improved. The modal dose for optimal response was 0.5 mg bid. Weight gain was a significant side effect.…

  14. Multifocal atrial tachycardia caused by risperidone.

    PubMed

    Oner, Taliha; Akdeniz, Celal; Adaletli, Hilal

    2016-01-15

    Risperidone, an atypical antipsychotic drug, is one of the most frequently used atypical neuroleptic drugs for the treatment of symptoms of behavioral disorders seen in autism. Although various cardiovascular side effects have been reported with risperidone, to our knowledge, it has not yet been reported that it can also result in multifocal atrial tachycardia. Based on the case reported herein, our aim is to bring awareness that risperidone may cause multifocal atrial tachycardia.

  15. [Efficiency of a pharmaceutical care program for long-acting parenteral antipsychotics in the health area of Santiago de Compostela].

    PubMed

    Vázquez-Mourelle, Raquel; Parrondo, Carmen Durán; López-Pardo Pardo, Estrella; Carracedo-Martínez, Eduardo

    2016-01-01

    In the healthcare area of Santiago de Compostela (Spain), the therapeutic subgroup "other antipsychotics" represented the fifth largest outpatient expenditure in 2013. More than half of this expenditure corresponded to long-acting parenteral forms of paliperidone and risperidone. Over a 12-month period, the implementation of a pharmaceutical care program based on process management and coordination of actions between health professionals in both levels of care represented savings of € 636,391.01 for the organization and a direct saving of € 16,767.36 and 9,008 trips to the pharmacy for patients. This study shows the efficiency of the program, which was facilitated by its situation in an area of integrated management and the use the unified medical records and electronic prescription, elements that will enable the future implementation of similar programmes. The new registries and healthcare interventions will allow reliable evaluation of their effectiveness in terms of treatment adherence, relapses and hospitalisations.

  16. Moral and policy issues in long-acting contraception.

    PubMed

    Brown, G F; Moskowitz, E H

    1997-01-01

    The advent of reversible long-acting contraceptives-IUDs, injectables and implants-has provided women throughout the world with valuable new fertility regulation options. These highly effective methods, together with male and female sterilization, have proven to be enormously popular and are now used by the majority of women and men who are currently contracepting worldwide. Despite their remarkable popularity, long-acting contraceptives have engendered considerable controversy. Political, ethical, and safety questions have emerged, stemming from the ways in which these contraceptives have been developed and used over the course of this century. At the heart of the concern is the issue of reproductive rights and freedom. This paper reviews the history of the development of long-acting contraceptives, including the prospect of new methods that will likely emerge from ongoing research and development. It also examines the history, in the United States and in developing countries, of the use and abuse of long-acting methods, including sterilization, in the context of eugenics and population control policies. It then describes a new paradigm of reproductive health and rights that has emerged from the International Conference on Population Development in Cairo, and which offers an enlightened approach to future policies and programs. In light of the wide variety of ways in which long-acting contraceptives have been provided, the paper examines the rights and responsibilities of governments, family planning providers, and individuals. An ethical framework for the use of long-acting methods is discussed, and public policies for the future are proposed.

  17. Clinical blood chemistry values and long acting phenothiazines.

    PubMed

    Schneider, S J; Kirby, E J; Itil, T M

    1981-05-01

    Fifty-nine chronic schizophrenic patients received one year of treatment with either fluphenazine enanthate or pipothiazine palmitate IM. Both long acting neuroleptics significantly decreased serum albumin, total protein and creatinine values. Triglycerides were decreased only early in treatment. Pretreatment findings from therapy responders, as compared with those who failed to respond to treatment, included higher albumin values and to a lesser extent, lower lactic dehydrogenase values and greater height. These results were discussed with an eye toward the hepatocellular effects of long acting phenothiazines and the effect of liver function on the pharmacokinetics of these medications. PMID:6114503

  18. Clinical blood chemistry values and long acting phenothiazines.

    PubMed

    Schneider, S J; Kirby, E J; Itil, T M

    1981-05-01

    Fifty-nine chronic schizophrenic patients received one year of treatment with either fluphenazine enanthate or pipothiazine palmitate IM. Both long acting neuroleptics significantly decreased serum albumin, total protein and creatinine values. Triglycerides were decreased only early in treatment. Pretreatment findings from therapy responders, as compared with those who failed to respond to treatment, included higher albumin values and to a lesser extent, lower lactic dehydrogenase values and greater height. These results were discussed with an eye toward the hepatocellular effects of long acting phenothiazines and the effect of liver function on the pharmacokinetics of these medications.

  19. Development of Risperidone PLGA Microspheres

    PubMed Central

    D'Souza, Susan; Faraj, Jabar A.; Giovagnoli, Stefano; DeLuca, Patrick P.

    2014-01-01

    The aim of this study was to design and evaluate biodegradable PLGA microspheres for sustained delivery of Risperidone, with an eventual goal of avoiding combination therapy for the treatment of schizophrenia. Two PLGA copolymers (50 : 50 and 75 : 25) were used to prepare four microsphere formulations of Risperidone. The microspheres were characterized by several in vitro techniques. In vivo studies in male Sprague-Dawley rats at 20 and 40 mg/kg doses revealed that all formulations exhibited an initial burst followed by sustained release of the active moiety. Additionally, formulations prepared with 50 : 50 PLGA had a shorter duration of action and lower cumulative AUC levels than the 75 : 25 PLGA microspheres. A simulation of multiple dosing at weekly or 15-day regimen revealed pulsatile behavior for all formulations with steady state being achieved by the second dose. Overall, the clinical use of Formulations A, B, C, or D will eliminate the need for combination oral therapy and reduce time to achieve steady state, with a smaller washout period upon cessation of therapy. Results of this study prove the suitability of using PLGA copolymers of varying composition and molecular weight to develop sustained release formulations that can tailor in vivo behavior and enhance pharmacological effectiveness of the drug. PMID:24616812

  20. Narcotic tapering in pregnancy using long-acting morphine

    PubMed Central

    Dooley, Roisin; Dooley, Joe; Antone, Irwin; Guilfoyle, John; Gerber-Finn, Lianne; Kakekagumick, Kara; Cromarty, Helen; Hopman, Wilma; Muileboom, Jill; Brunton, Nicole; Kelly, Len

    2015-01-01

    Abstract Objective To document the management of and outcomes for patients receiving narcotic replacement and tapering with long-acting morphine preparations during pregnancy. Design A prospective cohort study over 18 months. Setting Northwestern Ontario. Participants All 600 births at Meno Ya Win Health Centre in Sioux Lookout, Ont, from January 1, 2012, to June 30, 2013, including 166 narcotic-exposed pregnancies. Intervention Narcotic replacement and tapering of narcotic use with long-acting morphine preparations. Main outcome measures Prenatal management of maternal narcotic use, incidence of neonatal abstinence syndrome, and other neonatal outcomes. Results The incidence of neonatal abstinence syndrome fell significantly to 18.1% of pregnancies exposed to narcotics (from 29.5% in a previous 2010 study, P = .003) among patients using narcotic replacement and tapering with long-acting morphine preparations. Neonatal outcomes were otherwise equivalent to those of the nonexposed pregnancies. Conclusion In many patients, long-acting morphine preparations can be safely used and tapered in pregnancy, with a subsequent decrease in observed neonatal withdrawal symptoms. PMID:25821873

  1. Comparison of SGA oral medications and a long-acting injectable SGA: the PROACTIVE study.

    PubMed

    Buckley, Peter F; Schooler, Nina R; Goff, Donald C; Hsiao, John; Kopelowicz, Alexander; Lauriello, John; Manschreck, Theo; Mendelowitz, Alan J; Miller, Del D; Severe, Joanne B; Wilson, Daniel R; Ames, Donna; Bustillo, Juan; Mintz, Jim; Kane, John M

    2015-03-01

    Until relatively recently, long-acting injectable (LAI) formulations were only available for first-generation antipsychotics and their utilization decreased as use of oral second-generation antipsychotics (SGA) increased. Although registry-based naturalistic studies show LAIs reduce rehospitalization more than oral medications in clinical practice, this is not seen in recent randomized clinical trials. PROACTIVE (Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy) relapse prevention study incorporated efficacy and effectiveness features. At 8 US academic centers, 305 patients with schizophrenia or schizoaffective disorder were randomly assigned to LAI risperidone (LAI-R) or physician's choice oral SGAs. Patients were evaluated during the 30-month study by masked, centralized assessors using 2-way video, and monitored biweekly by on-site clinicians and assessors who knew treatment assignment. Relapse was evaluated by a masked Relapse Monitoring Board. Differences between LAI-R and oral SGA treatment in time to first relapse and hospitalization were not significant. Psychotic symptoms and Brief Psychiatric Rating Scale total score improved more in the LAI-R group. In contrast, the LAI group had higher Scale for Assessment of Negative Symptoms Alogia scale scores. There were no other between-group differences in symptoms or functional improvement. Despite the advantage for psychotic symptoms, LAI-R did not confer an advantage over oral SGAs for relapse or rehospitalization. Biweekly monitoring, not focusing specifically on patients with demonstrated nonadherence to treatment and greater flexibility in changing medication in the oral treatment arm, may contribute to the inability to detect differences between LAI and oral SGA treatment in clinical trials. PMID:24870446

  2. Two cases of long-acting paliperidone in adolescence

    PubMed Central

    Fàbrega, Marina; Sugranyes, Gisela; Baeza, Inmaculada

    2015-01-01

    Paliperidone palmitate long-acting injection (PPLAI) is an atypical antipsychotic agent currently approved by the European Medicine Agency for the acute and maintenance treatment of schizophrenia in adults. However, there is no information so far on safety and effectiveness in patients under 18 years of age. We report on two clinical cases of adolescents with a psychotic spectrum disorder treated with PPLAI in an inpatient setting. The cases illustrate that PPLAI may hold potential as an effective and acceptably tolerated antipsychotic drug in adolescents with psychotic spectrum disorders. Given the lack of approved long acting injectable antipsychotics in patients under 18 years of age, reports on the effectiveness and safety of such medications in children and adolescent patients are of importance. PMID:26557986

  3. Status of long-acting-growth hormone preparations--2015.

    PubMed

    Høybye, Charlotte; Cohen, Pinchas; Hoffman, Andrew R; Ross, Richard; Biller, Beverly M K; Christiansen, Jens Sandahl

    2015-10-01

    Growth hormone (GH) treatment has been an established therapy for GH deficiency (GHD) in children and adults for more than three decades. Numerous studies have shown that GH treatment improves height, body composition, bone density, cardiovascular risk factors, physical fitness and quality of life and that the treatment has few side effects. Initially GH was given as intramuscular injections three times per week, but daily subcutaneous injections were shown to be more effective and less inconvenient and the daily administration has been used since its introduction in the 1980s. However, despite ongoing improvements in injection device design, daily subcutaneous injections remain inconvenient, painful and distressing for many patients, leading to noncompliance, reduced efficacy and increased health care costs. To address these issues a variety of long-acting formulations of GH have been developed. In this review we present the current status of long-acting GH preparations and discuss the specific issues related to their development.

  4. Waterborne Risperidone Decreases Stress Response in Zebrafish

    PubMed Central

    Kalichak, Fabiana; Rosa, João Gabriel Santos; de Oliveira, Tiago Acosta; Koakoski, Gessi; Gusso, Darlan; de Abreu, Murilo Sander; Giacomini, Ana Cristina Varrone; Barcellos, Heloísa Helena de Alcântara

    2015-01-01

    The presence of drugs and their metabolites in surface waters and municipal effluents has been reported in several studies, but its impacts on aquatic organisms are not yet well understood. This study investigated the effects of acute exposure to the antipsychotic risperidone on the stress and behavioral responses in zebrafish. It became clear that intermediate concentration of risperidone inhibited the hypothalamic-pituitary-interrenal axis and displayed anxiolytic-like effects in zebrafish. The data presented here suggest that the presence of this antipsychotic in aquatic environments can alter neuroendocrine and behavior profiles in zebrafish. PMID:26473477

  5. Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes

    PubMed Central

    Edagwa, Benson J.; Guo, Dongwei; Puligujja, Pavan; Chen, Han; McMillan, JoEllyn; Liu, Xinming; Gendelman, Howard E.; Narayanasamy, Prabagaran

    2014-01-01

    Eradication of Mycobacterium tuberculosis (MTB) infection requires daily administration of combinations of rifampin (RIF), isoniazid [isonicotinylhydrazine (INH)], pyrazinamide, and ethambutol, among other drug therapies. To facilitate and optimize MTB therapeutic selections, a mononuclear phagocyte (MP; monocyte, macrophage, and dendritic cell)-targeted drug delivery strategy was developed. Long-acting nanoformulations of RIF and an INH derivative, pentenyl-INH (INHP), were prepared, and their physicochemical properties were evaluated. This included the evaluation of MP particle uptake and retention, cell viability, and antimicrobial efficacy. Drug levels reached 6 μg/106 cells in human monocyte-derived macrophages (MDMs) for nanoparticle treatments compared with 0.1 μg/106 cells for native drugs. High RIF and INHP levels were retained in MDM for >15 d following nanoparticle loading. Rapid loss of native drugs was observed in cells and culture fluids within 24 h. Antimicrobial activities were determined against Mycobacterium smegmatis (M. smegmatis). Coadministration of nanoformulated RIF and INHP provided a 6-fold increase in therapeutic efficacy compared with equivalent concentrations of native drugs. Notably, nanoformulated RIF and INHP were found to be localized in recycling and late MDM endosomal compartments. These were the same compartments that contained the pathogen. Our results demonstrate the potential of antimicrobial nanomedicines to simplify MTB drug regimens.—Edagwa, B. J., Guo, D., Puligujja, P., Chen, H., McMillan, J., Liu, X., Gendelman, H. E., Narayanasamy, P. Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes. PMID:25122556

  6. Long-Acting Beta Agonists Enhance Allergic Airway Disease

    PubMed Central

    Knight, John M.; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O.; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A.; Milner, Joshua D.; Zhang, Yuan; Mandal, Pijus K.; Luong, Amber; Kheradmand, Farrah

    2015-01-01

    Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6. PMID:26605551

  7. Risperidone versus other atypical antipsychotics for schizophrenia

    PubMed Central

    Komossa, Katja; Rummel-Kluge, Christine; Schwarz, Sandra; Schmid, Franziska; Hunger, Heike; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second-generation (“atypical”) antipsychotics (SGAs) have become the first line drug treatment for people with schizophrenia. The question as to whether and if so how much the effects of the various SGAs differ is a matter of debate. In this review we examined how the efficacy and tolerability of risperidone differs from that of other SGAs. Objectives To evaluate the effects of risperidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. 2. Reference searching We inspected the references of all identified studies for more trials. 3. Personal contact We contacted the first author of each included study for missing information. 4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. Selection criteria We included all randomised, blinded trials comparing oral risperidone with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated risk ratio (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD), again based on a random-effects model. Main results The review currently includes 45 blinded RCTs with 7760 participants. The number of RCTs available for each comparison varied: four studies compared risperidone with amisulpride, two with aripiprazole, 11 with clozapine, 23 with olanzapine, eleven with

  8. Aripiprazole Lauroxil Long-Acting Injectable: The Latest Addition to Second-Generation Long-Acting Agents.

    PubMed

    Aggarwal, Arpit; Gopalakrishna, Ganesh; Lauriello, John

    2016-01-01

    Antipsychotics have long been the mainstay for the treatment of schizophrenia and other psychotic disorders. Long-acting injectables (LAI) of antipsychotics-provided once every two weeks to once every three months-promise to reduce the incidence of nonadherence. ARISTADA(™) (aripiprazole lauroxil; ALLAI) extended-release injectable suspension was approved by the U.S. Food and Drug Administration in October 2015 for the treatment of schizophrenia, and is the newest entrant in the LAI market. ALLAI is available as a single-use, pre-filled syringe, can be started in three different dosages, and also has the option of every six-week dosing. Treatment with oral aripiprazole is recommended for the first twenty-one days after the first ALLAI injection, which is a potential disadvantage. Adverse effects include sensitivity to extrapyramidal symptoms, especially akathisia, which is well documented in other aripiprazole preparations. There is no available data comparing ALLAI to other antipsychotics, and more head-to-head trials comparing different LAI formulations are needed. Based on the available data, ALLAI is an effective and safe option for treatment of schizophrenia. Further studies and post-marketing data will provide better understanding of this formulation. PMID:27074333

  9. Euprolactinemic Gynecomastia and Galactorrhea with Risperidone-Fluvoxamine Combination

    PubMed Central

    P.J., Pratheesh; Praharaj, Samir Kumar; Srivastava, Ashish

    2011-01-01

    Risperidone is associated with hyperprolactinemia and its consequent symptoms such as gynnecomastia, galactorrhea and sexual dysfunction in adults, and less so in adolescents. Rarely, serotonin reuptake inhibitors are also associated with such adverse effects. We report a case of gynecomastia and galactorrhea in an adolescent male while on a combination of risperidone and fluvoxamine, although the serum prolactin was within normal range. PMID:22506441

  10. Adult Rats Treated with Risperidone during Development Are Hyperactive

    PubMed Central

    Bardgett, Mark E.; Franks-Henry, Julie M.; Colemire, Kristin R.; Juneau, Kathleen R.; Stevens, Rachel M.; Marczinski, Cecile A.; Griffith, Molly S.

    2014-01-01

    Risperidone is an antipsychotic drug approved for use in children, but little is known about the long-term effects of early-life risperidone treatment. In animals, prolonged risperidone administration during development increases forebrain dopamine receptor expression immediately upon the cessation of treatment. A series of experiments was performed to ascertain whether early-life risperidone administration altered locomotor activity, a behavior sensitive to dopamine receptor function, in adult rats. One additional behavior modulated by forebrain dopamine function, spatial reversal learning, was also measured during adulthood. In each study, Long-Evans rats received daily subcutaneous injections of vehicle or one of two doses of risperidone (1.0 and 3.0 mg/kg per day) from postnatal days 14 – 42. Weight gain during development was slightly yet significantly reduced in risperidone-treated rats. In the first two experiments, early-life risperidone administration was associated with increased locomotor activity at one week post-administration through approximately nine months of age, independent of changes in weight gain. In a separate experiment, it was found that the enhancing effect of early-life risperidone on locomotor activity occurred in males and female rats. A final experiment indicated that spatial reversal learning was unaffected in adult rats administered risperidone early in life. These results indicate that locomotor activity during adulthood is permanently modified by early-life risperidone treatment. The findings suggest that chronic antipsychotic drug use in pediatric populations (e.g., treatment for the symptoms of autism) could modify brain development and alter neural set-points for specific behaviors during adulthood. PMID:23750695

  11. Risperidone as a treatment for childhood habitual behavior

    PubMed Central

    Omranifard, Victoria; Najafi, Mostafa; Sharbafchi, Mohammad Reza; Emami, Parisa; Maracy, Mohammad

    2013-01-01

    Objective: The aim of this study was to investigate the effect of adding risperidone to the general behavioral treatment of masturbation in children 3-7 years old. Methods: A 4 week randomized clinical controlled trial was designed in year 2009. Samples have been chosen from children who have been referred to the Child and Adolescence Psychiatric Clinic of Isfahan University of Medical Sciences. Ninety children were recruited at the study and randomly allocated into the risperidone and control groups (44 and 46 respectively). The risperidone group was medicated simultaneously by behavioral treatments and 0.25-1 mg of risperidone daily while the controls only received the behavioral treatments. Findings: The mean ± SD age of the risperidone and control groups was 5.3 ± 1.1 and 4.9 ± 1.1 years, respectively. The mean ± SD of the period of suffering from masturbation was 3.4 ± 1.2 and 3.8 ± 1.7 months in the risperidone and the control groups, respectively. At the beginning of the study, the mean frequency of masturbation in control and the risperidone groups was 2.6 ± 0.9 and 2.7 ± 0.9 times/day, whereas after the 4th week, it decreased to 1.4 ± 0.6 and 1.1 ± 0.5 times/day, respectively. The results showed a more reduction in the mean frequency of masturbation in the risperidone group significantly. Conclusion: In comparison to the general behavioral treatment, risperidone in addition to the behavioral treatment will probably reduce the frequency of masturbation in children more effectively. PMID:24991601

  12. Risperidone in idiopathic and symptomatic dystonia: preliminary experience.

    PubMed

    Grassi, E; Latorraca, S; Piacentini, S; Marini, P; Sorbi, S

    2000-04-01

    Risperidone is a heterocyclic neuroleptic with prominent antiserotoninergic (5HT2) as well as antidopaminergic (D2) activity. We studied the efficacy of risperidone in the treatment of idiopathic and symptomatic dystonias in seven patients using the Fahn and Marsden rating scale for torsion dystonia before and after four weeks of treatment (2-6 mg/day). The twisting and involuntary movements with abnormal postures decreased in all the patients treated, with a statistically significant mean improvement (41%; p = 0.009, CI 95%). Our results suggest that risperidone is useful in idiopathic and symptomatic dystonia. PMID:10938193

  13. Long-acting beta2-agonist in addition to tiotropium versus either tiotropium or long-acting beta2-agonist alone for chronic obstructive pulmonary disease

    PubMed Central

    Karner, Charlotta; Cates, Christopher J

    2014-01-01

    Background Long-acting bronchodilators comprising long-acting beta2-agonists and the anticholinergic agent tiotropium are commonly used for managing persistent symptoms of chronic obstructive pulmonary disease. Combining these treatments, which have different mechanisms of action, may be more effective than the individual components. However, the benefits and risks of combining tiotropium and long-acting beta2-agonists for the treatment of chronic obstructive pulmonary (COPD) disease are unclear. Objectives To assess the relative effects of treatment with tiotropium in addition to long-acting beta2-agonist compared to tiotropium or long-acting beta2-agonist alone in patients with chronic obstructive pulmonary disease. Search methods We searched the Cochrane Airways Group Specialised Register of trials and clinicaltrials.gov up to January 2012. Selection criteria We included parallel group, randomised controlled trials of three months or longer comparing treatment with tiotropium in addition to long-acting beta2-agonist against tiotropium or long-acting beta2-agonist alone for patients with chronic obstructive pulmonary disease. Data collection and analysis Two review authors independently assessed trials for inclusion and then extracted data on trial quality and the outcome results. We contacted study authors for additional information. We collected information on adverse effects from the trials. Main results Five trials were included in this review, mostly recruiting participants with moderate or severe chronic obstructive pulmonary disease. All of them compared tiotropium in addition to long-acting beta2-agonist to tiotropium alone, but only one trial additionally compared a combination of the two types of bronchodilator with long-acting beta2-agonist (formoterol) alone. Two studies used the long-acting beta2-agonist indacaterol, two used formoterol and one used salmeterol. Compared to tiotropium alone (3263 patients), treatment with tiotropium plus long-acting

  14. Recent advances in COPD disease management with fixed-dose long-acting combination therapies.

    PubMed

    Bateman, Eric D; Mahler, Donald A; Vogelmeier, Claus F; Wedzicha, Jadwiga A; Patalano, Francesco; Banerji, Donald

    2014-06-01

    Combinations of two long-acting bronchodilators and long-acting bronchodilators with inhaled corticosteroids (ICS) are recommended therapies in the management of chronic obstructive pulmonary disease (COPD). Three fixed-dose combination products have recently been approved for the treatment of COPD (the long-acting β2-agonist plus long-acting muscarinic antagonist [LABA/LAMA] combinations glycopyrronium/indacaterol [QVA149] and umeclidinium/vilanterol, and the LABA/ICS fluticasone furoate/vilanterol), with others currently in late-stage development. LABA/LAMA and LABA/ICS combination therapies demonstrate positive effects on both lung function and patient-reported outcomes, with significant improvements observed with LABA/LAMA combinations compared with placebo, each component alone and other comparators in current use. No new safety concerns have been observed with combinations of long-acting bronchodilators. Combinations of two long-acting bronchodilators represent a new and convenient treatment option in COPD. This review summarizes published efficacy and safety data from clinical trials of both LABA/LAMA and novel LABA/ICS combinations in patients with COPD.

  15. Long-acting insulins alter milk composition and metabolism of lactating dairy cows.

    PubMed

    Winkelman, L A; Overton, T R

    2013-01-01

    This study investigated the effect of 2 different types of long-acting insulin on milk production, milk composition, and metabolism in lactating dairy cows. Multiparous cows (n=30) averaging 88 d in milk were assigned to one of 3 treatments in a completely randomized design. Treatments consisted of control (C), Humulin-N (H; Eli Lilly and Company, Indianapolis, IN), and insulin glargine (L). The H and L treatments were administered twice daily at 12-h intervals via subcutaneous injection for 10d. Cows were milked twice daily, and milk composition was determined every other day. Mammary biopsies were conducted on d 11, and mammary proteins extracted from the biopsies were analyzed by Western blot for components of insulin and mammalian target of rapamycin signaling pathways. Treatment had no effect on dry matter intake or milk yield. Treatment with both forms of long-acting insulin increased milk protein content and tended to increase milk protein yield over the 10-d treatment period. Analysis of milk N fractions from samples collected on d 10 of treatment suggested that cows administered L tended to have higher yields of milk protein fractions than cows administered H. Milk fat content and yield tended to be increased for cows administered long-acting insulins. Lactose content and yields were decreased by treatment with long-acting insulins. Administration of long-acting insulins, particularly L, tended to shift milk fatty acid composition toward increased short- and medium-chain fatty acids and decreased long-chain fatty acids. Plasma concentrations of glucose and urea N were lower for cows administered long-acting insulins; interactions of treatment and sampling time were indicative of more pronounced effects of L than H on these metabolites. Concentrations of nonesterified fatty acids and insulin were increased in cows administered long-acting insulins. Decreased concentrations of urea N in both plasma and milk suggested more efficient use of N in cows

  16. Long-acting insulins alter milk composition and metabolism of lactating dairy cows.

    PubMed

    Winkelman, L A; Overton, T R

    2013-01-01

    This study investigated the effect of 2 different types of long-acting insulin on milk production, milk composition, and metabolism in lactating dairy cows. Multiparous cows (n=30) averaging 88 d in milk were assigned to one of 3 treatments in a completely randomized design. Treatments consisted of control (C), Humulin-N (H; Eli Lilly and Company, Indianapolis, IN), and insulin glargine (L). The H and L treatments were administered twice daily at 12-h intervals via subcutaneous injection for 10d. Cows were milked twice daily, and milk composition was determined every other day. Mammary biopsies were conducted on d 11, and mammary proteins extracted from the biopsies were analyzed by Western blot for components of insulin and mammalian target of rapamycin signaling pathways. Treatment had no effect on dry matter intake or milk yield. Treatment with both forms of long-acting insulin increased milk protein content and tended to increase milk protein yield over the 10-d treatment period. Analysis of milk N fractions from samples collected on d 10 of treatment suggested that cows administered L tended to have higher yields of milk protein fractions than cows administered H. Milk fat content and yield tended to be increased for cows administered long-acting insulins. Lactose content and yields were decreased by treatment with long-acting insulins. Administration of long-acting insulins, particularly L, tended to shift milk fatty acid composition toward increased short- and medium-chain fatty acids and decreased long-chain fatty acids. Plasma concentrations of glucose and urea N were lower for cows administered long-acting insulins; interactions of treatment and sampling time were indicative of more pronounced effects of L than H on these metabolites. Concentrations of nonesterified fatty acids and insulin were increased in cows administered long-acting insulins. Decreased concentrations of urea N in both plasma and milk suggested more efficient use of N in cows

  17. Effects of Risperidone on Cognitive-Motor Performance and Motor Movements in Chronically Medicated Children

    ERIC Educational Resources Information Center

    Aman, Michael G.; Hollway, Jill A.; Leone, Sarah; Masty, Jessica; Lindsay, Ronald; Nash, Patricia; Arnold, L. Eugene

    2009-01-01

    This study was designed to explore the placebo-controlled effects of risperidone on cognitive-motor processes, dyskinetic movements, and behavior in children receiving maintenance risperidone therapy. Sixteen children aged 4-14 years with disruptive behavior were randomly assigned to drug order in a crossover study of risperidone and placebo for 2…

  18. Resistance to excessive bodyweight gain in risperidone-injected rats.

    PubMed

    Ota, Miyuki; Mori, Keiji; Nakashima, Akira; Kaneko, Yoko S; Takahashi, Hisahide; Ota, Akira

    2005-04-01

    1. The present study was carried out to explain the resistance of rats injected subcutaneously with risperidone, the atypical antipsychotic drug, for 21 consecutive days at 0.1 mg/kg per day (a dose equivalent to the one used for patients) to result in an excessive bodyweight despite the increase in diet-uptake in rats against risperidone-induced decrease in body temperature. 2. Rectal temperature measurements were made in 8-week-old male Sprague-Dawley rats maintained under standard laboratory conditions using a 12 h daylight cycle. A s.c. injection of risperidone (0.05 mg/kg) produced hypothermia in rats, which was observed during the daily injection for 21 consecutive days. 3. Sera, white and brown adipose tissues, skeletal muscle and liver were extracted from 8-week-old male Sprague-Dawley rats injected subcutaneously with risperidone (0.01 or 0.1 mg/kg per day) or a vehicle for 21 consecutive days. Serum levels of lipids, ketones and thyroid hormone were measured. The mRNA expression levels in these tissues and organs of the genes encoding the substances involved in heat production and/or lipid metabolism were investigated by using quantitative real-time polymerase chain reaction amplification. 4. Serum nonesterified fatty acid levels in risperidone 0.1 mg/kg per day s.c. injected rats were significantly lower than those in vehicle-injected ones. Serum beta-hydroxybutyrate levels in risperidone-injected rats tended to decrease compared with those in vehicle-injected ones. The serum level of neither triiodothyronine nor thyroxine was affected by risperidone s.c. injection at the doses examined, although their values were within normal limits. 5. Risperidone injection (0.1 mg/kg per day) for 21 consecutive days upregulated mRNA expressions in white adipose tissue of uncoupling protein 3 which dissipates energy as heat; peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1alpha which activates mitochondrial biogenesis to expand the oxidative

  19. Use of Aripiprazole Long Acting Injection in Negative Symptoms of Schizophrenia

    PubMed Central

    James, Suneeta; Kapugama, Chaya; Al-Uzri, Mohammed

    2016-01-01

    Background. Evidence for the efficacious use of second-generation antipsychotics for the treatment of negative symptoms in schizophrenia is scant. Case Presentation. We report the case of a 34-year-old female of Afro-Caribbean origin, who presented with prominent negative symptoms of schizophrenia and was successfully treated with aripiprazole long acting injection. Within a period of six to nine months, the patient returned to her premorbid level of functioning. Conclusion. Aripiprazole long acting injection promises benefits in the treatment of negative symptoms of schizophrenia. Further research needs to be conducted on the use of this drug. PMID:26981301

  20. [An open trial of risperidone in autistic children].

    PubMed

    Nishimura, Mio; Hashimoto, Toshiaki; Miyazaki, Masahito; Mori, Kenji; Kuroda, Yasuhiro

    2003-11-01

    Clinical effects of risperidone were evaluated in 9 young autistic children under informed consent of their parents. The patients were evaluated by the Children's Behavioral Checklist and Rutter's Autistic Behavioral Rating Scale. After the administration, two subjects (playing and adaptation to change) of the Children's Behavioral Checklist and four (anomalous autistic behavior, destructive behavior, developmental problem and activity level) of the Rutter's Autistic Behavioral Rating Scale were improved significantly. There were no serious side effects such as extrapyramidal symptoms except minor adverse effects including sedation, depression, increased appetite and constipation. Risperidone might be effective for serious behavioral disturbances in young autistic children.

  1. Hypercalcemia appeared in a patient with glucagonoma treated with octreotide acetate long-acting release.

    PubMed

    Rui, Min; Li, Li; Jiang-Feng, Mao; Feng, Gu; Hui-Juan, Zhu; Wen-Hui, Li; Yu-Xiu, Li

    2012-09-01

    PABCREATIC neuroendocrine tumours are uncommon neoplasms of the pancreas. They may cause a clinical syndrome due to hormone overproduction. Glucagonoma is a rare kind of pancreatic tumors. Here we report a case of glucagonoma. Hypercalcemia occurred when the patient underwent octreotide acetate long-acting release.

  2. Does Prolonged Therapy with a Long-Acting Stimulant Suppress Growth in Children with ADHD?

    ERIC Educational Resources Information Center

    Spencer, Thomas J.; Faraone, Stephen V.; Biederman, Joseph; Lerner, Marc; Cooper, Kimberly M.; Zimmerman, Brenda

    2006-01-01

    Objective: To investigate whether prolonged therapy with a long-acting stimulant affects growth in children with attention-deficit/hyperactivity disorder (ADHD). Method: One hundred seventy-eight children ages 6 to 13 years received OROS methylphenidate (OROS MPH, CONCERTA) for at least 21 months. Height and weight were measured monthly during the…

  3. Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrino...

  4. Long-acting muscarinic antagonist + long-acting beta agonist versus long-acting beta agonist + inhaled corticosteroid for COPD: A systematic review and meta-analysis.

    PubMed

    Horita, Nobuyuki; Miyazawa, Naoki; Tomaru, Koji; Inoue, Miyo; Kaneko, Takeshi

    2015-11-01

    Some trials have been conducted to compare long-acting muscarinic antagonist (LAMA) + long-acting beta agonist (LABA) versus LABA + inhaled corticosteroids (ICS) for chronic obstructive pulmonary disease (COPD), but no meta-analysis were reported. Two investigators independently searched for eligible articles using the PubMed, Web of Science and Cochrane databases. Articles in authors' reference files were also regarded as candidates. The eligibility criteria for the current meta-analysis were original trials written in English comparing the impact of LAMA + LABA and LABA + ICS for COPD patients. A pooled value for the continuous value was calculated using the genetic inverse variance method for mean difference. Incidence of events was evaluated using the odds ratio (OR). Minimal clinically important difference were 50 mL for forced expiratory volume in 1 s (FEV1 ), four points for St George Respiratory Questionnaire (SGRQ) and one point for transition dyspnoea index (TDI). We included seven randomized controlled trials and one cross-over trial with follow-up period of 6-26 weeks. Compared with LABA + ICS, LAMA + LABA led to significantly greater improvements of trough FEV1 by 71 (95% CI: 48-95) mL, TDI by 0.38 points (95% CI: 0.17-0.58), less exacerbations with an OR of 0.77 (95% CI: 0.62-0.96) and less pneumonia with an OR of 0.28 (95% CI: 0.12-0.68). Frequencies of any adverse event, serious adverse event, adverse event leading to discontinuation, all-cause death and change of total score of SGRQ were not different in both arms. LAMA + LABA might be a better option for treating COPD than LABA + ICS. PMID:26235837

  5. Development of risperidone liposomes for brain targeting through intranasal route.

    PubMed

    Narayan, Reema; Singh, Mohan; Ranjan, OmPrakash; Nayak, Yogendra; Garg, Sanjay; Shavi, Gopal V; Nayak, Usha Y

    2016-10-15

    The present paper is aimed at development of functionalized risperidone liposomes for brain targeting through nasal route for effective therapeutic management of schizophrenia. The risperidone liposomes were prepared by thin film hydration method. Various parameters such as lipid ratio and lipid to drug ratio were optimized by using Design-Expert(®) Software to obtain high entrapment with minimum vesicle size. The surface of the optimized liposomes was modified by coating stearylamine and MPEG-DSPE for enhanced penetration to the brain. The formulations were evaluated for vesicle size, zeta potential, and entrapment efficiency. The morphology was studied by Transmission Electron Microscopy (TEM). In vivo efficacy was assessed by performing pharmacokinetic study in Wistar albino rats following intranasal administration of the formulations in comparison to intravenous bolus administration of pure drug. The mean vesicle size of optimized liposomes ranged from 90 to 100nm with low polydispersity index (<0.5). The entrapment efficiency of optimized liposomes was between 50 and 60%, functionalized liposomes showed maximum entrapment. The TEM images showed predominantly spherical vesicles with smooth bilayered surface. All formulations showed prolonged diffusion controlled drug release. The in vivo results showed that liposomal formulations provided enhanced brain exposure. Among the formulations studied, PEGylated liposomes (LP-16) had shown greater uptake of risperidone into the brain than plasma. High brain targeting efficiency index for LP-16 indicating preferential transport of the drug to brain. The study demonstrated successful formulation of surface modified risperidone liposomes for nasal delivery with brain targeting potential.

  6. Development of risperidone liposomes for brain targeting through intranasal route.

    PubMed

    Narayan, Reema; Singh, Mohan; Ranjan, OmPrakash; Nayak, Yogendra; Garg, Sanjay; Shavi, Gopal V; Nayak, Usha Y

    2016-10-15

    The present paper is aimed at development of functionalized risperidone liposomes for brain targeting through nasal route for effective therapeutic management of schizophrenia. The risperidone liposomes were prepared by thin film hydration method. Various parameters such as lipid ratio and lipid to drug ratio were optimized by using Design-Expert(®) Software to obtain high entrapment with minimum vesicle size. The surface of the optimized liposomes was modified by coating stearylamine and MPEG-DSPE for enhanced penetration to the brain. The formulations were evaluated for vesicle size, zeta potential, and entrapment efficiency. The morphology was studied by Transmission Electron Microscopy (TEM). In vivo efficacy was assessed by performing pharmacokinetic study in Wistar albino rats following intranasal administration of the formulations in comparison to intravenous bolus administration of pure drug. The mean vesicle size of optimized liposomes ranged from 90 to 100nm with low polydispersity index (<0.5). The entrapment efficiency of optimized liposomes was between 50 and 60%, functionalized liposomes showed maximum entrapment. The TEM images showed predominantly spherical vesicles with smooth bilayered surface. All formulations showed prolonged diffusion controlled drug release. The in vivo results showed that liposomal formulations provided enhanced brain exposure. Among the formulations studied, PEGylated liposomes (LP-16) had shown greater uptake of risperidone into the brain than plasma. High brain targeting efficiency index for LP-16 indicating preferential transport of the drug to brain. The study demonstrated successful formulation of surface modified risperidone liposomes for nasal delivery with brain targeting potential. PMID:27593571

  7. Influence of solvent on crystal nucleation of risperidone.

    PubMed

    Mealey, Donal; Zeglinski, Jacek; Khamar, Dikshitkumar; Rasmuson, Åke C

    2015-01-01

    Over 2100 induction time experiments were carried out for the medium-sized, antipsychotic drug molecule, risperidone in seven different organic solvents. To reach the same induction time the required driving force increases in the order: cumene, toluene, acetone, ethyl acetate, methanol, propanol, and butanol, which reasonably well correlates to the interfacial energies as determined within classical nucleation theory. FTIR spectroscopy has been used to investigate any shifts in the spectra and to estimate the interaction of solute and solvent at the corresponding site. The solution condition has also been investigated by Density Functional Theory (DFT) calculations over (1 : 1) solvent-solute binding interactions at 8 different sites on the risperidone molecule. The DFT computational results agree with the spectroscopic data suggesting that these methods do capture the binding strength of solvent molecules to the risperidone molecule. The difficulty of nucleation correlates reasonably to the DFT computations and the spectroscopic measurements. The results of the different measurements suggest that the stronger the solvent binds to the risperidone molecule in solution, the slower the nucleation becomes. PMID:25886651

  8. Effectiveness of ECT combined with risperidone against aggression in schizophrenia.

    PubMed

    Hirose, S; Ashby, C R; Mills, M J

    2001-03-01

    Aggressive behavior in schizophrenic patients can often be problematic not only for the patients themselves, but for their families and others. This study examined the effect of electroconvulsive therapy (ECT) in combination with risperidone in an open trial in 10 male schizophrenic patients with significant aggressive behaviors. Patients were given bilateral ECT five times a week in combination with risperidone. The mean total number of times of ECT was 6.6 (range 5-9). The aggressive behavior in five of the six patients, who showed positive symptoms, was rapidly ameliorated within 12 days. The ECT/risperidone regimen also eliminated aggressive behavior in four patients showing no positive symptoms within 10 days. These treatment effects lasted for at least 6 months in 9 (of the 10) patients. The results suggest that ECT, combined with risperidone, produce a rapid and effective elimination of aggressive behaviors in schizophrenic patients. In addition, there was a resolution of aggression in four patients with no positive symptoms. This suggests that aggression in some schizophrenic patients develops as a primary symptom of schizophrenia and is not related to other positive symptoms of the disease or the patient's personality traits. PMID:11281510

  9. Serial follow-up of presurgical treatment using pasireotide long-acting release with or without octreotide long-acting release for naïve active acromegaly.

    PubMed

    Chang, Jan-Shun; Tseng, Ham-Min; Chang, Tien-Chun

    2016-06-01

    The aim of the present study was to evaluate the serial changes of GH and IGF-1 in seven patients with naïve, active acromegaly following presurgical treatment of the somatostatin analog pasireotide long-acting release (LAR) and octreotide LAR. The patients were treated with pasireotide LAR with or without octreotide LAR for two years and underwent transsphenoidal adenomectomy. After treatment with the somatostatin analogs, the surgical cure rate was similar to that in patients who underwent transsphenoidal surgery alone. Diabetes insipidus was not identified in any patients after the operation. Pasireotide LAR was effective on GH as well as IGF-1 suppression and tumor size decreasing when used as the primary therapy. Future large-population studies to investigate the surgical curative rate after presurgical treatment with somatostatin analogs in patients with acromegaly and macroadenomas close to the cavernous sinus are warranted. However, that hyperglycemia developed following pre-surgical treatment with pasireotide should take into consideration. PMID:27117887

  10. PHARMACOKINETICS OF CEFTIOFUR CRYSTALLINE FREE ACID, A LONG-ACTING CEPHALOSPORIN, IN AMERICAN FLAMINGOS (PHOENICOPTERUS RUBER).

    PubMed

    Kilburn, Jennifer J; Cox, Sherry K; Backues, Kay A

    2016-06-01

    Antibiotic usage is a vital component of veterinary medicine but the unique anatomy of some species can make administration difficult. The objective of this study was to determine the pharmacokinetic parameters of ceftiofur crystalline free acid (CCFA), a long-acting cephalosporin antibiotic, after parenteral administration in American flamingos ( Phoenicopterus ruber ). A dose of 10 mg/kg of CCFA was administered intramuscularly to 11 birds and blood was collected at various time points from 0 to 192 hr. Pharmacokinetic parameters for ceftiofur equivalents were determined and reached levels above minimum inhibitory concentrations of various bacterial organisms in other avian species through 96 hr in 9/11 birds. Based on these findings and comparison to other avian studies, ceftiofur crystalline free acid appears to be a long-acting antibiotic option for American flamingos. Administration of this antibiotic should be utilized in conjunction with culture and sensitivity of suspected pathogens.

  11. PHARMACOKINETICS OF CEFTIOFUR CRYSTALLINE FREE ACID, A LONG-ACTING CEPHALOSPORIN, IN AMERICAN FLAMINGOS (PHOENICOPTERUS RUBER).

    PubMed

    Kilburn, Jennifer J; Cox, Sherry K; Backues, Kay A

    2016-06-01

    Antibiotic usage is a vital component of veterinary medicine but the unique anatomy of some species can make administration difficult. The objective of this study was to determine the pharmacokinetic parameters of ceftiofur crystalline free acid (CCFA), a long-acting cephalosporin antibiotic, after parenteral administration in American flamingos ( Phoenicopterus ruber ). A dose of 10 mg/kg of CCFA was administered intramuscularly to 11 birds and blood was collected at various time points from 0 to 192 hr. Pharmacokinetic parameters for ceftiofur equivalents were determined and reached levels above minimum inhibitory concentrations of various bacterial organisms in other avian species through 96 hr in 9/11 birds. Based on these findings and comparison to other avian studies, ceftiofur crystalline free acid appears to be a long-acting antibiotic option for American flamingos. Administration of this antibiotic should be utilized in conjunction with culture and sensitivity of suspected pathogens. PMID:27468016

  12. [Intravenous regional anesthesia with long-acting local anesthetics. An update].

    PubMed

    Atanassoff, P G; Lobato, A; Aguilar, J L

    2014-02-01

    Intravenous regional anesthesia is a widely used technique for brief surgical interventions, primarily on the upper limbs and less frequently, on the lower limbs. It began being used at the beginning of the 20th century, when Bier injected procaine as a local anesthetic. The technique to accomplish anesthesia has not changed much since then, although different drugs, particularly long-acting local anesthetics, such as ropivacaine and levobupivacaine in low concentrations, were introduced. Additionally, drugs like opioids, muscle relaxants, paracetamol, neostigmine, magnesium, ketamine, clonidine, and ketorolac, have all been investigated as adjuncts to intravenous regional anesthesia, and were found to be fairly useful in terms of an increased onset of operative anesthesia and longer lasting perioperative analgesia. The present article provides an overview of current knowledge with emphasis on long-acting local anesthetic drugs. PMID:24156887

  13. Fast and long-acting antibacterial properties of chitosan-Ag/polyvinylpyrrolidone nanocomposite films.

    PubMed

    Wang, Bai-Liang; Liu, Xiang-Sheng; Ji, Ying; Ren, Ke-Feng; Ji, Jian

    2012-09-01

    Infection associated with medical devices is one of the most frequent complications of modern medical biomaterials. Preparation of antibacterial films on the medical devices is a great challenge owing to bactericidal efficiency, long acting and biocompatibility. In this study, silver nanoparticles (Ag NPs) doped chitosan/polyvinylpyrrolidone (PVP) films were successfully prepared by dip coating method. The nanocomposite films with spherical Ag NPs (diameters in 10-50 nm) were stable after being immersed in PBS for 35 days. Through regulating the concentration of AgNO3, the nanocomposite films showed good cell compatibility. The nanocomposite films could eliminate 100% Staphylococcus aureus (ATCC 6538) and Escherichia coli (ATCC 8739) in 5 min and had favorable long-acting antibacterial property. The increase of PVP amount obviously enhanced anti-adhesion activity of the nanocomposite film. Such nanocomposite films can be expected to have good potential in biomaterials applications.

  14. Nocturnal Hypoglycemia: Answering the Challenge With Long-acting Insulin Analogs

    PubMed Central

    Brunton, Stephen A.

    2007-01-01

    Background Nocturnal hypoglycemia may be the most common type of hypoglycemia in individuals with diabetes using insulin and is particularly worrisome because it often goes undetected and may lead to unconsciousness and even death in severe cases. Objectives The prevalence, causes, and consequences of nocturnal hypoglycemia as well as detection and prevention strategies are reviewed, including the use of long-acting insulin analogs, which offer more physiologic and predictable time-action profiles than traditional human basal insulin. Data Sources A total of 307 publications (151 PubMed; 104 Adis; 52 BIOSIS) were reviewed. Review Methods Relevant trials were found by searching for “(detemir OR glargine) AND nocturnal AND (hypoglycemia OR hypoglycaemia) AND diabetes.” To capture trials that may not have specified “nocturnal” in the title or abstract text but still reported nocturnal hypoglycemia data, a supplemental search of PubMed using “(detemir OR glargine) AND (nocturnal OR hypoglycemia OR hypoglycaemia) AND diabetes” was undertaken. Results A review of these trials found that patients with type 1 and type 2 diabetes mellitus have a lower risk for nocturnal hypoglycemia when receiving long-acting insulin analogs (insulin detemir or insulin glargine), provided that glycemic control is comparable to that provided by traditional human basal insulin. Long-acting insulin analogs may be the best option to provide basal insulin coverage in patients who do not choose or require continuous subcutaneous insulin infusion. Conclusions Randomized clinical trials suggest that the long-acting insulin analogs are associated with a lower risk for nocturnal hypoglycemia than neutral protamine Hagedorn without sacrificing glycemic control. PMID:17955093

  15. Risperidone is effective for wandering and disturbed sleep/wake patterns in Alzheimer's disease.

    PubMed

    Meguro, Kenichi; Meguro, Mitsue; Tanaka, Yasuhiro; Akanuma, Kyoko; Yamaguchi, Keiichiro; Itoh, Masatoshi

    2004-06-01

    Behavioral and psychological symptoms of dementia (BPSD), especially aggressiveness, wandering, and sleep disturbance, are a major burden for caregivers. Daily sleep/wake patterns and wandering of institutionalized patients with Alzheimer's disease (AD) were visually monitored, and 34 patients who manifested wandering were selected and randomly classified into 2 groups: the risperidone group and the nonrisperidone group. After an administration of low-dose risperidone for the risperidone group, the BPSD were reassessed. The binding potentials of dopamine D2 receptor for preadministration and postadministration of risperidone were assessed using positron emission tomography (PET) for 1 case. After the use of risperidone, aggressiveness and wandering were reduced and the nighttime sleeping hours were increased. The PET revealed that the binding potential of dopamine receptor was increased after administration of the drug, associated with improved sleep/wake patterns and behavioral abnormality. Possible serotonergic modulation of dopaminergic function might explain the neurobiological basis of the effect of risperidone. PMID:15157345

  16. Long-term use of short- and long-acting nitrates in stable angina pectoris.

    PubMed

    Kosmicki, Marek Antoni

    2009-05-01

    Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin (NTG), a short-acting nitrate, is suitable for the immediate relief of angina. In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance. During long-lasting nitrate therapy, except pentaerythritol tetranitrate (PETN), one can observe the development of reactive oxygen species (ROS) inside the muscular cell of a vessel wall, and these bind with nitric oxide (NO). This leads to decreased NO activity, thus, nitrate tolerance. PETN has no tendency to form ROS, and therefore during long-term PETN therapy, there is probably no tolerance or cross-tolerance, as during treatment with other nitrates.

  17. Risperidone Induced Pisa Syndrome in a Male Adolescent

    PubMed Central

    Güneş, Serkan; Ekinci, Özalp; Direk, Meltem Çobanoğulları; Yıldırım, Veli; Okuyaz, Çetin; Toros, Fevziye

    2016-01-01

    Pisa syndrome, a rare dystonic reaction resulting from prolonged exposure to antipsychotic medications, is characterized by persistent dystonia of trunk muscles and abnormal posture. It is called Pisa syndrome, because the abnormal posture resembles the Leaning Tower of Pisa. Different from other types of dystonic reactions, Pisa syndrome is more prevalent in females and in older patients with organic brain changes. A 15-year-old male patient with mental retardation was admitted to pediatric neurology clinic for the complaint of abnormal posturing. He had been taking only risperidone for the last four years. Over the last month, the patient gradually developed tonic flexion of trunk and head toward left and was diagnosed with Pisa syndrome. In this paper, we aimed to discuss the association between risperidone use and Pisa syndrome in light of the available literature. PMID:26792048

  18. The role of inhaled long-acting beta-2 agonists in the management of asthma.

    PubMed Central

    Kelly, H. William; Harkins, Michelle S.; Boushey, Homer

    2006-01-01

    The role of inhaled beta-2 agonists in the management of asthma has changed significantly over the last several years. This review outlines the most recent understanding of the pathophysiology of asthma and the studies that define the roles that both short- and long-acting beta-2 agonists play in therapy for this disease. A concentration on the clinical pharmacology and genetic implications for clinical use of this class of drugs in accordance with the national and international guidelines are described. PMID:16532973

  19. Use of long-acting reversible contraceptives to reduce the rate of teen pregnancy.

    PubMed

    Rome, Ellen

    2015-11-01

    Long-acting reversible contraceptives (LARCs) are safe for use in adolescents and do not rely on compliance or adherence for effectiveness. Continuation rates are higher and pregnancy rates are lower for adolescent users of LARCs compared with short-acting methods such as oral contraceptives. Similarly, repeat pregnancy rates are lower when LARCs are used compared with other forms of contraception. Myths and misconceptions about LARCs and other contraceptives remain a barrier to their use. Health care providers are in a unique position to provide confidential care to adolescents, and should provide education to them about the various contraceptive options, especially LARCs.

  20. Long-Term Safety and Adverse Events of Risperidone in Children, Adolescents, and Adults with Pervasive Developmental Disorders

    ERIC Educational Resources Information Center

    Hellings, Jessica A.; Cardona, Alicia M.; Schroeder, Stephen R.

    2010-01-01

    The objective of this study was to examine long-term adverse events of risperidone in 19 children, adolescents, and adults with Pervasive Developmental Disorders and intellectual disability, continuing risperidone for a mean of 186.5 weeks, following a 46-week risperidone study. Nineteen individuals continued long-term follow-up after our…

  1. Formulation, in vitro and in vivo evaluation of transdermal patches containing risperidone.

    PubMed

    Aggarwal, Geeta; Dhawan, Sanju; Hari Kumar, S L

    2013-01-01

    The efficacy of oral risperidone treatment in prevention of schizophrenia is well known. However, oral side effects and patient compliance is always a problem for schizophrenics. In this study, risperidone was formulated into matrix transdermal patches to overcome these problems. The formulation factors for such patches, including eudragit RL 100 and eudragit RS 100 as matrix forming polymers, olive oil, groundnut oil and jojoba oil in different concentrations as enhancers and amount of drug loaded were investigated. The transdermal patches containing risperidone were prepared by solvent casting method and characterized for physicochemical and in vitro permeation studies through excised rat skin. Among the tested preparations, formulations with 20% risperidone, 3:2 ERL 100 and ERS 100 as polymers, mixture of olive oil and jojoba oil as enhancer, exhibited greatest cumulative amount of drug permeated (1.87 ± 0.09 mg/cm(2)) in 72 h, so batch ROJ was concluded as optimized formulation and assessed for pharmacokinetic, pharmacodynamic and skin irritation potential. The pharmacokinetic characteristics of the optimized risperidone patch were determined using rabbits, while orally administered risperidone in solution was used for comparison. The calculated relative bioavailability of risperidone transdermal patch was 115.20% with prolonged release of drug. Neuroleptic efficacy of transdermal formulation was assessed by rota-rod and grip test in comparison with control and marketed oral formulations with no skin irritation. This suggests the transdermal application of risperidone holds promise for improved bioavailability and better management of schizophrenia in long-term basis.

  2. Early-Life Risperidone Administration Alters Maternal-Offspring Interactions and Juvenile Play Fighting

    PubMed Central

    Gannon, Matthew A.; Brown, Clifford J.; Stevens, Rachel M.; Griffith, Molly S.; Marczinski, Cecile A.; Bardgett, Mark E.

    2015-01-01

    Risperidone is an antipsychotic drug that is approved for use in childhood psychiatric disorders such as autism. One concern regarding the use of this drug in pediatric populations is that it may interfere with social interactions that serve to nurture brain development. This study used rats to assess the impact of risperidone administration on maternal-offspring interactions and juvenile play fighting between cage mates. Mixed-sex litters received daily subcutaneous injections of vehicle or 1.0 or 3.0 mg/kg of risperidone between postnatal days (PNDs) 14-42. Rats were weaned and housed three per cage on PND 21. In observations made between PNDs 14-17, risperidone significantly suppressed several aspects of maternal-offspring interactions at one-hour post-injection. At 23 hours post-injection, pups administered risperidone had lower activity scores and made fewer non-nursing contacts with their moms. In observations of play-fighting behavior made once a week between PNDs 22-42, risperidone profoundly decreased many forms of social interaction at one hour post-injection. At 23 hours post-injection, rats administered risperidone made more non-social contacts with their cage mates, but engaged in less social grooming. Risperidone administration to rats at ages analogous to early childhood through adolescence in humans produces a pattern of abnormal social interactions across the day that could impact how such interactions influence brain development. PMID:25600754

  3. Case Report: Valproic Acid and Risperidone Treatment Leading to Development of Hyperammonemia and Mania

    ERIC Educational Resources Information Center

    Carlson, Teri; Reynolds, Charles A.; Caplan, Rochelle

    2007-01-01

    This case report describes two children who developed hyperammonemia together with frank manic behavior during treatment with a combination of valproic acid and risperidone. One child had been maintained on valproic acid for years and risperidone was added. In the second case, valproic acid was introduced to a child who had been treated with…

  4. Cost and carbon burden of long-acting injections: a sustainable evaluation.

    PubMed

    Maughan, Daniel L; Lillywhite, Rob; Cooke, Matthew

    2016-06-01

    Aims and method This study explores the economic cost and carbon footprint associated with current patterns of prescribing long-term flupentixol decanoate long-acting injections. We conducted an analysis of prescription data from a mental health trust followed by economic and carbon cost projections using local and national data. Results A reduction of £300 000 could be achieved across England by improving prescribing behaviour, which equates to £250 per patient per year and 170 000 kg CO2e. These savings are unlikely to be released as cash from the service, but will lead to higher-value service provision at the same or lower cost. Most of these carbon emissions are attributable to the carbon footprint of the appointment - 88 000 kg CO2e (including energy use and materials used) and the overprescribing of medication - 66 000 kg CO2e. Clinical implications Psychiatrists need to review their prescribing practice of long-acting injections to reduce their impact on the National Health Service financial budget and the environment. PMID:27280033

  5. Adjunctive and Long-Acting Nanoformulated Antiretroviral Therapies for HIV-associated neurocognitive disorders

    PubMed Central

    Gendelman, Howard E.; Gelbard, Harris A.

    2014-01-01

    Purpose of review This review focuses on current and future strategies to modulate neuroinflammation while reducing residual viral burden in the central nervous system (CNS). This has been realized by targeted long acting antiretroviral nano- and adjunctive therapies being developed for HIV infected people. Our ultimate goal is to eliminate virus from its CNS reservoirs and, in so doing, reverse the cognitive and motor dysfunctions seen in HIV-associated neurocognitive disorders (HAND). Recent findings Herein, we highlight our laboratories development of adjunctive and nanomedicine therapies for HAND. An emphasis is placed on drug-drug interactions that target both the viral life cycle and secretory pro-inflammatory neurotoxic factors and signaling pathways. Summary Antiretroviral therapy (ART) has improved the quality and duration of life for people living with HIV-1. A significant long-term comorbid illness is HAND. Symptoms, while reduced in severity, are common. Disease occurs, in part, through continued low-level viral replication inducing secondary glial neuroinflammatory activities. Our recent works and those of others have seen disease attenuated in animal models through the use of adjunctive and long-acting reservoir targeted nanoformulated ART. The translation of these inventions from animals to humans is the focus of this review. PMID:25226025

  6. Cost and carbon burden of long-acting injections: a sustainable evaluation

    PubMed Central

    Maughan, Daniel L.; Lillywhite, Rob; Cooke, Matthew

    2016-01-01

    Aims and method This study explores the economic cost and carbon footprint associated with current patterns of prescribing long-term flupentixol decanoate long-acting injections. We conducted an analysis of prescription data from a mental health trust followed by economic and carbon cost projections using local and national data. Results A reduction of £300 000 could be achieved across England by improving prescribing behaviour, which equates to £250 per patient per year and 170 000 kg CO2e. These savings are unlikely to be released as cash from the service, but will lead to higher-value service provision at the same or lower cost. Most of these carbon emissions are attributable to the carbon footprint of the appointment – 88 000 kg CO2e (including energy use and materials used) and the overprescribing of medication – 66 000 kg CO2e. Clinical implications Psychiatrists need to review their prescribing practice of long-acting injections to reduce their impact on the National Health Service financial budget and the environment. PMID:27280033

  7. The differential effects of short- and long-acting benzodiazepines upon nocturnal sleep and daytime performance.

    PubMed

    Roth, T; Hartse, K M; Zorick, F J; Kaffeman, M E

    1980-01-01

    Hypnotic drugs are the most frequent medical intervention for providing symptomatic relief of insomnia. Both effective amelioration of the insomnia complaint and the minimization of residual effects upon daytime performance must be considered in the selection of these medications. Data are presented here which compare the effects of short- and long-acting benzodiazepines upon sleep and upon waking performance. Unlike short-acting hypnotics with half-lives of up to 10 h (lorazepam, triazolam and temazepam), long-acting hypnotics with half-lives of up to 100 h (flurazepam, ketazolam) produce suppression of both REM and Stage 3--4 sleep which persists during the drug withdrawal (recovery) period. The half-life of hypnotics is also directly related to the duration of residual effects upon daytime performance. Hypnotics with long half-lives (flurazepam) produce more prolonged performance decrements than hypnotics with short half-lives (temazepam). In insomniacs, both effects upon sleep and upon walking performance must be considered in the selection of a hypnotic.

  8. A long-acting GH receptor antagonist through fusion to GH binding protein

    PubMed Central

    Wilkinson, Ian R.; Pradhananga, Sarbendra L.; Speak, Rowena; Artymiuk, Peter J.; Sayers, Jon R.; Ross, Richard J.

    2016-01-01

    Acromegaly is a human disease of growth hormone (GH) excess with considerable morbidity and increased mortality. Somatostatin analogues are first line medical treatment but the disease remains uncontrolled in up to 40% of patients. GH receptor (GHR) antagonist therapy is more effective but requires frequent high-dose injections. We have developed an alternative technology for generating a long acting potent GHR antagonist through translational fusion of a mutated GH linked to GH binding protein and tested three candidate molecules. All molecules had the amino acid change (G120R), creating a competitive GHR antagonist and we tested the hypothesis that an amino acid change in the GH binding domain (W104A) would increase biological activity. All were antagonists in bioassays. In rats all antagonists had terminal half-lives >20 hours. After subcutaneous administration in rabbits one variant displayed a terminal half-life of 40.5 hours. A single subcutaneous injection of the same variant in rabbits resulted in a 14% fall in IGF-I over 7 days. In conclusion: we provide proof of concept that a fusion of GHR antagonist to its binding protein generates a long acting GHR antagonist and we confirmed that introducing the W104A amino acid change in the GH binding domain enhances antagonist activity. PMID:27731358

  9. Serum ghrelin levels in acromegaly: effects of surgical and long-acting octreotide therapy.

    PubMed

    Freda, Pamela U; Reyes, Carlos M; Conwell, Irene M; Sundeen, Robert E; Wardlaw, Sharon L

    2003-05-01

    The orexigenic peptide, ghrelin, is regulated by acute and chronic nutritional state. Although exogenously administered ghrelin stimulates pituitary GH secretion, little is known about the role of ghrelin in endogenous GH secretion or how high GH and IGF-I levels in acromegaly could affect ghrelin secretion and vice versa. Therefore, we evaluated fasting and post oral glucose tolerance test serum ghrelin levels in 19 patients with active acromegaly at baseline and after either surgery in 9 of these or administration of long-acting octreotide (Sandostatin LAR) in the other 10 patients. After surgical cure, fasting ghrelin rose from 312 +/- 56 pg/ml to 548 +/- 97 pg/ml (P = 0.013). Fasting serum ghrelin levels were higher in all patients after surgery and ranged between 112% and 349% of presurgery levels. Ghrelin levels fell significantly during long-acting octreotide therapy from 447 +/- 34 pg/ml to 206 +/- 15 pg/ml (P < 0.0001); ghrelin levels on octreotide ranged between 26% and 70% of baseline levels. Serum ghrelin levels were suppressed significantly during the oral glucose tolerance test in both groups. Pretherapy ghrelin levels correlated negatively with serum insulin levels (r = -0.494; P = 0.03) and insulin resistance as estimated by the homeostasis model assessment score (r = -0.573; P = 0.01). In patients without diabetes mellitus, serum insulin levels in the surgical group were 19.7 +/- 5.4 microU/ml before surgery and fell to 9.7 +/- 0.93 microU/ml after surgery (P = 0.05); levels in the octreotide group were 13.9 +/- 2.8 microU/ml before and fell to 11.2 +/- 2.8 microU/ml on octreotide (P = 0.03). Pretherapy ghrelin levels did not correlate with weight or body mass index, but after therapy in the surgery group ghrelin correlated negatively with weight (r = -0.823, P = 0.012) as has been demonstrated by others in healthy subjects. Ghrelin secretion is dysregulated in active acromegaly; lowered serum levels of ghrelin in active acromegaly rise along with

  10. [Indications and medical survey of long acting progestatives used for contraception (author's transl)].

    PubMed

    Molitor-peffer, M P

    1982-10-01

    About 600 injections per year are administered in a Luxembourg family planning center using 3 types of long acting progestatives: Depo Provera 150 and 450 and Norigest. The method is no longer reserved for women with completed families and the mentally handicapped since its reversibility has been proven. Patients seeking this type of contraception must meet the same criteria as for oral contraceptives except that women with contraindications for estrogens may tolerate progestatives. Long acting progestatives offer the safety of minipills along with high effectiveness since the risk of forgetting a pill is removed. Some women with cardiac disease, diabetes, and circulatory problems are able to use injectables, but caution should be exercised with hypertensives and the obese because of possible weight gain. Women with coagulation problems or suspected fibromas should be excluded. Administered postpartum, pure progestatives do not affect lactation. Menstrual cycles are completely disturbed, with irregular and unpredictable bleeding until amenorrhea appears after 3-6 months. Women who are psychologically unable to accept amenorrhea should not use this method, as they are more likely to experience undesirable side effects. Return of fertility upon termination of use poses no problem and usually occurs after 6-10 months, even after a single injection. Treatment with a sequential contraceptive beginning on the day when the next injection would have been given may help to reestablish menstruation. The physician should determine through a preliminary interview the couple's psychological readiness for this type of contraception. A careful medical history and gynecological examination should be done to rule out contraindications, and treatment should begin in the 1st 3 days of the cycle. Irregular and prolonged bleeding after 6 months of use can be treated with oral administration of estrogen, or by proceeding to the next injection ahead of schedule. Administration of a mild

  11. Aripiprazole long-acting injectable formulations for schizophrenia: aripiprazole monohydrate and aripiprazole lauroxil.

    PubMed

    Citrome, Leslie

    2016-01-01

    Aripiprazole monohydrate (AM) and aripiprazole lauroxil (AL) are two different long-acting injectable formulations of aripiprazole. AM 400 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial, as well as in a double-blind, placebo-controlled, randomized-withdrawal maintenance study, and in two non-inferiority maintenance studies. AL is a prodrug of aripiprazole and available in 441 mg, 662 mg or 882 mg strengths. AL 441 mg and 882 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial. The pharmacokinetic profile of AL also led to approval of dosing intervals of every 6 weeks for the 882 mg dose. The overall tolerability profiles of both products are consistent with what is known about oral aripiprazole.

  12. Long-acting integrase inhibitor protects macaques from intrarectal simian/human immunodeficiency virus.

    PubMed

    Andrews, Chasity D; Spreen, William R; Mohri, Hiroshi; Moss, Lee; Ford, Susan; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Bohm, Rudolf P; Cheng-Mayer, Cecilia; Hong, Zhi; Markowitz, Martin; Ho, David D

    2014-03-01

    GSK1265744 (GSK744) is an integrase strand-transfer inhibitor that has been formulated as a long-acting (LA) injectable suitable for monthly to quarterly clinical administration. GSK744 LA was administered at two time points 4 weeks apart beginning 1 week before virus administration, and macaques were challenged weekly for 8 weeks. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all animals against repeated low-dose challenges. In a second experiment, macaques were given GSK744 LA 1 week before virus administration and challenged repeatedly until infection occurred. Protection decreased over time and correlated with the plasma drug levels. With a quarterly dosing schedule in humans, our results suggest that GSK744 LA could potentially decrease adherence problems associated with daily preexposure prophylaxis (PrEP).

  13. The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal.

    PubMed

    Brissos, Sofia; Veguilla, Miguel Ruiz; Taylor, David; Balanzá-Martinez, Vicent

    2014-10-01

    Despite their widespread use, long-acting injectable (LAI) antipsychotics (APs) are often regarded with some negativity because of the assumption of punishment, control and insufficient evolution towards psychosocial development of patients. However, LAI APs have proved effective in schizophrenia and other severe psychotic disorders because they assure stable blood levels, leading to a reduction of the risk of relapse. Therapeutic opportunities have also arisen after introduction of newer, second-generation LAI APs in recent years. Newer LAI APs are more readily dosed optimally, may be better tolerated and are better suited to integrated rehabilitation programmes. This review outlines the older and newer LAI APs available for the treatment of schizophrenia, with considerations of past and present pharmacological and therapeutic issues. Traditional, evidence-based approaches to systematic reviews and randomized clinical trials are of limited utility in this area so this paper's blending of experimental trials with observational research is particularly appropriate and effective. PMID:25360245

  14. Physiologically-Based Pharmacokinetic Modelling to Inform Development of Intramuscular Long Acting Nanoformulations for HIV

    PubMed Central

    Rajoli, Rajith KR; Back, David J; Rannard, Steve; Meyers, Caren Freel; Flexner, Charles; Owen, Andrew; Siccardi, Marco

    2014-01-01

    Background and Objectives Antiretrovirals (ARVs) are currently used for the treatment and prevention of HIV infection. Poor adherence and low tolerability of some existing oral formulations can hinder their efficacy. Long-acting (LA) injectable nanoformulations could help address these complications by simplifying ARV administration. The aim of this study is to inform the optimisation of intramuscular LA formulations for eight ARVs through physiologically-based pharmacokinetic (PBPK) modelling. Methods A whole-body PBPK model was constructed using mathematical descriptions of molecular, physiological and anatomical processes defining pharmacokinetics. These models were validated against available clinical data and subsequently used to predict the pharmacokinetics of injectable LA formulations Results The predictions suggest that monthly intramuscular injections are possible for dolutegravir, efavirenz, emtricitabine, raltegravir, rilpivirine and tenofovir provided that technological challenges to control release rate can be addressed. Conclusions These data may help inform the target product profiles for LA ARV reformulation strategies. PMID:25523214

  15. Committee Opinion No. 670 Summary: Immediate Postpartum Long-Acting Reversible Contraception.

    PubMed

    2016-08-01

    Immediate postpartum long-acting reversible contraception (LARC) has the potential to reduce unintended and short-interval pregnancy. Women should be counseled about all forms of postpartum contraception in a context that allows informed decision making. Immediate postpartum LARC should be offered as an effective option for postpartum contraception; there are few contraindications to postpartum intrauterine devices and implants. Obstetrician-gynecologists and other obstetric care providers should discuss LARC during the antepartum period and counsel all pregnant women about options for immediate postpartum initiation. Education and institutional protocols are needed to raise clinician awareness and to improve access to immediate postpartum LARC insertion. Obstetrician-gynecologists and other obstetric care providers should incorporate immediate postpartum LARC into their practices, counsel women appropriately about advantages and risks, and advocate for institutional and payment policy changes to support provision. PMID:27454730

  16. Committee Opinion No. 670: Immediate Postpartum Long-Acting Reversible Contraception.

    PubMed

    2016-08-01

    Immediate postpartum long-acting reversible contraception (LARC) has the potential to reduce unintended and short-interval pregnancy. Women should be counseled about all forms of postpartum contraception in a context that allows informed decision making. Immediate postpartum LARC should be offered as an effective option for postpartum contraception; there are few contraindications to postpartum intrauterine devices and implants. Obstetrician-gynecologists and other obstetric care providers should discuss LARC during the antepartum period and counsel all pregnant women about options for immediate postpartum initiation. Education and institutional protocols are needed to raise clinician awareness and to improve access to immediate postpartum LARC insertion. Obstetrician-gynecologists and other obstetric care providers should incorporate immediate postpartum LARC into their practices, counsel women appropriately about advantages and risks, and advocate for institutional and payment policy changes to support provision. PMID:27454734

  17. The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal.

    PubMed

    Brissos, Sofia; Veguilla, Miguel Ruiz; Taylor, David; Balanzá-Martinez, Vicent

    2014-10-01

    Despite their widespread use, long-acting injectable (LAI) antipsychotics (APs) are often regarded with some negativity because of the assumption of punishment, control and insufficient evolution towards psychosocial development of patients. However, LAI APs have proved effective in schizophrenia and other severe psychotic disorders because they assure stable blood levels, leading to a reduction of the risk of relapse. Therapeutic opportunities have also arisen after introduction of newer, second-generation LAI APs in recent years. Newer LAI APs are more readily dosed optimally, may be better tolerated and are better suited to integrated rehabilitation programmes. This review outlines the older and newer LAI APs available for the treatment of schizophrenia, with considerations of past and present pharmacological and therapeutic issues. Traditional, evidence-based approaches to systematic reviews and randomized clinical trials are of limited utility in this area so this paper's blending of experimental trials with observational research is particularly appropriate and effective.

  18. The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal

    PubMed Central

    Veguilla, Miguel Ruiz; Taylor, David; Balanzá-Martinez, Vicent

    2014-01-01

    Despite their widespread use, long-acting injectable (LAI) antipsychotics (APs) are often regarded with some negativity because of the assumption of punishment, control and insufficient evolution towards psychosocial development of patients. However, LAI APs have proved effective in schizophrenia and other severe psychotic disorders because they assure stable blood levels, leading to a reduction of the risk of relapse. Therapeutic opportunities have also arisen after introduction of newer, second-generation LAI APs in recent years. Newer LAI APs are more readily dosed optimally, may be better tolerated and are better suited to integrated rehabilitation programmes. This review outlines the older and newer LAI APs available for the treatment of schizophrenia, with considerations of past and present pharmacological and therapeutic issues. Traditional, evidence-based approaches to systematic reviews and randomized clinical trials are of limited utility in this area so this paper’s blending of experimental trials with observational research is particularly appropriate and effective. PMID:25360245

  19. Let's talk about sex (again): advancing the conversation around long-acting reversible contraception for teenagers.

    PubMed

    Satterwhite, Catherine Lindsey; Ramaswamy, Megha

    2015-11-01

    Long-acting reversible contraception (LARC) has incredible potential for decreasing teenage pregnancy rates in the USA, but use among adolescents remains low. LARC methods, including intrauterine devices and implants, are recommended as first-line choices for teenagers by multiple medical professional associations. Barriers at the system, provider and patient level persist, but new demonstration projects, in addition to provisions of the Affordable Care Act, show great promise in facilitating LARC use. A renewed national discourse should acknowledge the reality that many US teenagers have sex, that LARC is safe and effective and that LARC offers an opportunity to prevent teenage pregnancy. By encouraging widespread access and use, a large, positive impact across multiple health and economic sectors can be achieved.

  20. Plasma corticosteroid levels in rats maintained on a long-acting naltrexone delivery system.

    PubMed

    Misra, A L; Pontani, R B; Vadlamani, N L

    1978-04-01

    A long-acting delivery system for naltrexone has been described, which blocked the antinociceptive action of 10 mg kg-1 s.c. dose of morphine in rats for a period of 2 to 3 months. Male Wistar rats implanted s.c. with such a delivery system showed highly significant depression of plasma corticosteroid levels (40.2% in one week and 22.4 to 27.2% in 3 months) as compared to placebo pellet-implanted animals. Morphine-dependent male rats implanted with 75 mg morphine pellets showed a small (17.5%) but significant increase in plasma corticosteroid levels as compared to the placebo controls 72 hr. after pellet implantation. PMID:663407

  1. Biocompatible riboflavin laurate long-acting injectable nanosuspensions allowing sterile filtration.

    PubMed

    Hu, Xi; Lin, Xia; Gu, Yuechen; Liu, Zitong; Tang, Yilin; Zhang, Yu; Chen, Xi; Wang, Yanjiao; Tang, Xing

    2014-08-01

    The aim of this research was to prepare biocompatible riboflavin laurate (RFL) long-acting injectable nanosuspensions for intramuscular injection with a small particle size allowing sterile filtration. RFL nanosuspensions were manufactured by a precipitation-combined high-pressure homogenization method. Three kinds of mixed stabilizers-d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a primary stabilizer, and egg lecithin (PL-100M), Kollidon VA64, Kollidon S-630 as a secondary stabilizer, were separately applied to avoid further aggregation. In the three optimized formulations, the mean particle size of the RFL nanosuspensions was about 170 nm allowing sterilization by filtration. Results from transmission electron microscopy, differential scanning calorimeter, powder X-ray diffraction and Fourier transform infrared reflectance spectroscopy revealed that RFL existed as rod-like crystals. However, a few nano-spheres under 100 nm were found only when PL-100 was used as a secondary stabilizer, possibly due to TPGS and PL-100, which inserted into RFL during the process of crystallization and homogenization. In irritation testing, RFL long-acting injection (LAI) stabilized by TPGS and PL-100 led to mild paw-licking responses and a slight inflammatory reaction, which returned to normal by 14 d after administration. The endogenous PL-100 and nano-spheres with a small size may have contributed to the excellent biocompatibility. As a result, TPGS and PL-100 were selected as blended stabilizers to prepare the irritation-free RFL-LAI that could be sterilized by passage through a 0.22 μm millipore membrane filter.

  2. Pharmacokinetics of Injectable, Long-Acting Nevirapine for HIV Prophylaxis in Breastfeeding Infants

    PubMed Central

    Cortez, John M.; Quintero, Rafaela; Moss, John A.; Beliveau, Martin; Smith, Thomas J.

    2014-01-01

    Mother-to-child transmission (MTCT) of HIV-1 remains a global health problem. The World Health Organization (WHO) recommendations advise the administration of a once-daily, oral, prophylactic regimen of the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) from birth until 4 to 6 weeks of age for infants born to HIV-infected mothers in regions without access to safe and nutritionally adequate alternatives to breast milk. A critical factor driving the successful implementation of the WHO guidelines involves sustaining high adherence to the frequent dosing. With these challenges in mind, we have developed the first injectable, sustained-release NVP formulations with the goal of providing, for 6 weeks or longer, preventative plasma drug levels from a single subcutaneous administration at birth. The long-acting NVP consists of large (>50 μm), monodisperse NVP particles coated with biocompatible polymers that control the drug release kinetics. Two lead formulations exhibiting burst-free, sustained-release kinetics for up to 75 days in vitro were developed. Subsequent in vivo studies in rats demonstrated no toxicity related to the formulations. Rat plasma NVP concentrations were above the analytical assay's limit of quantification for up to 28 days. Pharmacokinetic analysis of the rat plasma NVP concentration-time data allowed absorption rate constants to be calculated. These data then were used to simulate infant NVP exposure from a single injected dose (<200 mg) of our long-acting formulations, demonstrating preliminary feasibility of the technology to maintain safe, preventative NVP plasma levels (0.2 to 3.0 μg ml−1) for 6 weeks or longer. PMID:25313219

  3. Biocompatible riboflavin laurate long-acting injectable nanosuspensions allowing sterile filtration.

    PubMed

    Hu, Xi; Lin, Xia; Gu, Yuechen; Liu, Zitong; Tang, Yilin; Zhang, Yu; Chen, Xi; Wang, Yanjiao; Tang, Xing

    2014-08-01

    The aim of this research was to prepare biocompatible riboflavin laurate (RFL) long-acting injectable nanosuspensions for intramuscular injection with a small particle size allowing sterile filtration. RFL nanosuspensions were manufactured by a precipitation-combined high-pressure homogenization method. Three kinds of mixed stabilizers-d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a primary stabilizer, and egg lecithin (PL-100M), Kollidon VA64, Kollidon S-630 as a secondary stabilizer, were separately applied to avoid further aggregation. In the three optimized formulations, the mean particle size of the RFL nanosuspensions was about 170 nm allowing sterilization by filtration. Results from transmission electron microscopy, differential scanning calorimeter, powder X-ray diffraction and Fourier transform infrared reflectance spectroscopy revealed that RFL existed as rod-like crystals. However, a few nano-spheres under 100 nm were found only when PL-100 was used as a secondary stabilizer, possibly due to TPGS and PL-100, which inserted into RFL during the process of crystallization and homogenization. In irritation testing, RFL long-acting injection (LAI) stabilized by TPGS and PL-100 led to mild paw-licking responses and a slight inflammatory reaction, which returned to normal by 14 d after administration. The endogenous PL-100 and nano-spheres with a small size may have contributed to the excellent biocompatibility. As a result, TPGS and PL-100 were selected as blended stabilizers to prepare the irritation-free RFL-LAI that could be sterilized by passage through a 0.22 μm millipore membrane filter. PMID:24188474

  4. Persistent High Restenosis After Local Intrawall Delivery of Long-Acting Steroids Before Coronary Stent Implantation.

    PubMed

    Reimers; Moussa; Akiyama; Kobayashi; Albiero; Di Francesco L; Di Mario C; Colombo

    1998-07-01

    OBJECTIVE: This pilot study was performed to evaluate the feasibility and safety of intrawall delivery of long acting steroids before stent implantation, testing the efficacy of this treatment in reducing intimal hyperplasia in lesions at high risk for restenosis. METHODS: In 24 patients (40 lesions) local intrawall drug delivery of methylprednisolone acetate, using a new catheter device, was attempted before elective stent implantation. Treated lesions were compared to a matched control group. RESULTS: Lesions were classified AHA/ACC type C in 47% of cases, had a mean lesion length of 13.6 +/- 9.1 mm, and a mean vessel diameter of 2.85 +/- 0.44 mm. In 9 cases (25%) chronic total occlusions were treated. Methylprednisolone acetate (mean 60 +/- 23 mg) was delivered in 36 lesions (21 patients; delivery success 90%) in the remaining 4 lesions (10%) the delivery device did not cross the lesion. After drug delivery 46 stents were implanted (1.2 stent/lesion; stented segment length 30.1 +/- 18.8 mm) using high pressure for stent expansion (mean 16.4 +/- 3.1 atm). Intracoronary ultrasound guidance was used in 64% of cases. Procedural and in-hospital complications were: Two non Q wave myocardial infarctions (8%) and one (3%) subacute stent thrombosis. Angiographic follow-up was obtained in all 36 treated lesions (100%) and the angiographic restenosis rate (³ 50% diameter stenosis) was 39%. A reduction of the incidence of restenosis compared to the matched control group was not observed. CONCLUSIONS: Long acting steroids could be delivered locally with high success and low complication rates. The restenosis rate remained high in a subset of unfavorable lesions with high risk for restenosis.

  5. Risperidone-associated urinary incontinence in patients with autistic disorder with mental retardation.

    PubMed

    Kumazaki, Hirokazu; Watanabe, Koichiro; Imasaka, Yasushi; Iwata, Kazuhiko; Tomoda, Akemi; Mimura, Masaru

    2014-10-01

    We report several cases in which patients with autistic disorder with mental retardation who received risperidone experienced urinary incontinence. We retrospectively investigated the medical records of patients housed in facilities for patients with autistic disorder with mental retardation. Those who had undergone a medical examination at a hospital in Tokyo from April 1999 to March 2009 were included in the study.Retrospective data were gathered including age, sex, IQ, birth weight, dosage of risperidone, urinary density, as well as existence of urinary and fecal incontinence. We divided the participants into those who did and did not experience urinary incontinence after taking risperidone and compared the 2 groups. Risperidone had been prescribed to 35 patients. In spite of the fact that no patient had a history of urinary incontinence, 14 patients experienced urinary incontinence after receiving risperidone. Moreover, 4 of these 14 patients also had fecal incontinence. Among the variables we examined, the only significant difference between groups was in sex, with significantly more women experiencing incontinence compared with men. When the dose of risperidone was reduced or the patients switched to other drugs, urinary incontinence of the patients improved.Hence, risperidone may have a casual relationship with urinary incontinence. Further research is needed to understand the pathophysiology of possible effect.

  6. “Set it and forget it”: Women’s perceptions and opinions of long-acting topical vaginal gels

    PubMed Central

    van den Berg, Jacob J.; Rosen, Rochelle K.; Bregman, Dana E.; Thompson, Lara A.; Jensen, Kathleen M.; Kiser, Patrick F.; Katz, David F.; Buckheit, Karen; Buckheit, Robert W.; Morrow, Kathleen M.

    2014-01-01

    Women’s initial understandings and anticipated acceptability of long-acting vaginal gels as potential anti-HIV microbicides was investigated by exploring the perceptibility variables associated with prototype formulations. Four focus groups with 29 women, aged 18–45, were conducted to consider gel prototypes with varied physicochemical and rheological properties. Participants responded favorably to the concept of long-acting vaginal gels as microbicides. Distinctions in understandings and stated needs regarding product dosing, characteristics, and effectiveness offer valuable insights into product design. Long-acting vaginal gels capable of protecting against HIV/STIs will be a viable option among potential users, with dosing frequency being an important factor in willingness to use. PMID:24248674

  7. Development and comparison of intramuscularly long-acting paliperidone palmitate nanosuspensions with different particle size.

    PubMed

    Leng, Donglei; Chen, Hongming; Li, Guangjing; Guo, Mengran; Zhu, Zhaolu; Xu, Lu; Wang, Yongjun

    2014-09-10

    The main purpose of this study was to develop and compare the pharmacokinetic behavior of two paliperidone palmitate (PP) nanosuspensions with different particle size after intramuscular (i.m.) administration. PP nanosuspensions were prepared by wet media milling method and the mean particle size of nanosuspension was controlled as 1,041 ± 6 nm (A) and 505 ± 9 nm (B), respectively. The morphology of nanosuspensions was observed by scanning electron microscope (SEM). Differential scanning calorimeter (DSC) and powder X-ray diffraction (PXRD) confirmed the crystallinity of PP in nanosuspensions. The physical and chemical stabilities of nanosuspensions A and B were investigated by particle analyzer and HPLC after storage for 2 months at 25°C, 4°C and mechanical shaking condition. No obvious change in particle size and chemical degradation of drug were observed. Following single-dose i.m. administration to beagle dogs, the release of paliperidone lasted for nearly 1 month. The Tmax of nanosuspensions A and B was 6 (d) and 10 (d). The AUC0-t and Cmax of nanosuspensions A was 2.0-fold and 1.8-fold higher than nanosuspensions B (p<0.05). The results demonstrated that PP nanosuspensions formulation had long-acting effect. Nanosuspension A with a larger particle size performed better than nanosuspension B. As a result, it is important to design appropriate particle size of nanosuspensions for i.m. administration in order to produce larger therapeutic effect.

  8. Permanent Sterilisation to Long-Acting Reversible Contraception: Is a Paradigm Shift Necessary?

    PubMed

    Shantha Kumari, S

    2016-06-01

    The concept of family planning originated as birth control in 1912 to control the size of the family and prevent unplanned pregnancies transformed to family welfare and later on expanded its horizons to reproductive and child health (RCH). A wide spectrum of choices both for male and female, temporary and permanent, have been developed and offered. Developed world having stabilised population faces problem with teenage and adolescent pregnancies. Developing nations are still struggling to stabilise population and traditionally depend on permanent female sterilisation as a major method of contraception. Lot of unmet need is seen in young recently married women, post-delivery, post-abortal states. Long-acting reversible contraception which includes intrauterine device, IUD, and implants has re-emerged strongly as a first choice of contraception for women of all ages including unmarried teenage pregnancies. They are highly efficient with failure rates equivalent or better than permanent methods, cost-effective, reversible, and have the potential to replace permanent sterilisation. PMID:27298522

  9. The long-acting integrase inhibitor GSK744 protects macaques from repeated intravaginal SHIV challenge.

    PubMed

    Radzio, Jessica; Spreen, William; Yueh, Yun Lan; Mitchell, James; Jenkins, Leecresia; García-Lerma, J Gerardo; Heneine, Walid

    2015-01-14

    Daily preexposure prophylaxis (PrEP) with Truvada is a proven HIV prevention strategy; however, its effectiveness is limited by low adherence. Antiretroviral drug formulations that require infrequent dosing may increase adherence and thus PrEP effectiveness. We investigated whether monthly injections of a long-acting formulation of the HIV integrase inhibitor GSK1265744 (GSK744 LA) prevented simian/human immunodeficiency virus (SHIV) infection by vaginal challenge in macaques. Female pigtail macaques (n = 12) were exposed to intravaginal inoculations of SHIV twice a week for up to 11 weeks. Half of the animals received a GSK744 LA injection every 4 weeks, and half received placebo. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all six macaques from infection. Placebo controls were all infected after a median of 4 (range, 2 to 20) vaginal challenges with SHIV. Efficacy was related to high and sustained vaginal and plasma drug concentrations that remained above the protein-adjusted 90% inhibitory concentration during the dosing cycles. These data support advancement of GSK744 LA as a potential PrEP candidate for women. PMID:25589631

  10. Demand for long-acting and permanent contraceptive methods among Kurdish women in Mahabad, Iran.

    PubMed

    Hosseini, Hatam; Torabi, Fatemeh; Bagi, Balal

    2014-11-01

    It is anticipated that the demand for contraceptives in Iran will increase in the near future as the number of women of reproductive age increases and with women wanting smaller families. The aim of this paper was to study the demand for long-acting and permanent contraceptive methods (LAPCMs), and its determinants, among Kurdish women in Mahabad city, Iran. Data were taken from the Mahabad Fertility Survey (MFS) conducted on a sample of over 700 households in April 2012. The results show that the demand for LAPCMs was 71.35% at the time of survey, although only 27.7% of women were using these methods. Thus, the number of unintended pregnancies is likely to increase in the future if this gap is not reduced. The multivariate analysis showed significant impacts on the dependent variables of the number of children ever born, perceived contraceptive costs and childbearing intentions. Moreover, women at the end of their reproductive lives and those with higher education were more likely to desire LAPCMs. It is concluded that despite a growing use of contraceptive methods in Iran in recent decades, the development of reproductive health services and promotion of the quality of family planning services remains a necessity.

  11. Manufacturing process used to produce long-acting recombinant factor VIII Fc fusion protein.

    PubMed

    McCue, Justin; Kshirsagar, Rashmi; Selvitelli, Keith; Lu, Qi; Zhang, Mingxuan; Mei, Baisong; Peters, Robert; Pierce, Glenn F; Dumont, Jennifer; Raso, Stephen; Reichert, Heidi

    2015-07-01

    Recombinant factor VIII Fc fusion protein (rFVIIIFc) is a long-acting coagulation factor approved for the treatment of hemophilia A. Here, the rFVIIIFc manufacturing process and results of studies evaluating product quality and the capacity of the process to remove potential impurities and viruses are described. This manufacturing process utilized readily transferable and scalable unit operations and employed multi-step purification and viral clearance processing, including a novel affinity chromatography adsorbent and a 15 nm pore size virus removal nanofilter. A cell line derived from human embryonic kidney (HEK) 293H cells was used to produce rFVIIIFc. Validation studies evaluated identity, purity, activity, and safety. Process-related impurity clearance and viral clearance spiking studies demonstrate robust and reproducible removal of impurities and viruses, with total viral clearance >8-15 log10 for four model viruses (xenotropic murine leukemia virus, mice minute virus, reovirus type 3, and suid herpes virus 1). Terminal galactose-α-1,3-galactose and N-glycolylneuraminic acid, two non-human glycans, were undetectable in rFVIIIFc. Biochemical and in vitro biological analyses confirmed the purity, activity, and consistency of rFVIIIFc. In conclusion, this manufacturing process produces a highly pure product free of viruses, impurities, and non-human glycan structures, with scale capabilities to ensure a consistent and adequate supply of rFVIIIFc.

  12. Pharmacodynamics of long-acting folic acid-receptor targeted ritonavir boosted atazanavir nanoformulations

    PubMed Central

    Puligujja, Pavan; Balkundi, Shantanu; Kendrick, Lindsey; Baldridge, Hannah; Hilaire, James; Bade, Aditya N.; Dash, Prasanta K.; Zhang, Gang; Poluektova, Larisa; Gorantla, Santhi; Liu, Xin-Ming; Ying, Tianlei; Feng, Yang; Wang, Yanping; Dimitrov, Dimiter S.; McMillan, JoEllyn M.; Gendelman, Howard E.

    2014-01-01

    Long-acting nanoformulated antiretroviral therapy (nanoART) that target monocyte-macrophage could improve the drug’s half-life and protein binding capacities while facilitating cell and tissue depots. To this end, ART nanoparticles that target the folic acid (FA) receptor and permit cell-based drug depots were examined using pharmacokinetic and pharmacodynamic (PD) tests. FA receptor-targeted poloxamer 407 nanocrystals, containing ritonavir-boosted atazanavir (ATV/r), significantly affected several therapeutic factors: drug bioavailability increased as much as 5 times and PD activity improved as much as 100 times. Drug particles administered to human peripheral blood lymphocyte reconstituted NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice and infected with HIV-1ADA at a tissue culture infective dose50 of 104 infectious viral particles/ml led to ATV/r drug concentrations that paralleled FA receptor beta staining in both the macrophage-rich parafollicular areas of spleen and lymph nodes. Drug levels were higher in these tissues than what could be achieved by either native drug or untargeted nanoART particles. The data also mirrored potent reductions in viral loads, tissue viral RNA and numbers of HIV-1p24+ cells in infected and treated animals. We conclude that FA-P407 coating of ART nanoparticles readily facilitate drug carriage and facilitate antiretroviral responses. PMID:25522973

  13. Pharmacokinetics of a long-acting chloramphenicol formulation administered by intramuscular and subcutaneous routes in cattle.

    PubMed

    Sanders, P; Guillot, P; Mourot, D

    1988-06-01

    The pharmacokinetic properties of a long-acting formulation of chloramphenicol were determined in six yearling cattle after a single intravenous (i.v.) administration (40 mg/kg body weight) and after two sequential subcutaneous (s.c.) or intramuscular (i.m.) administrations (90 mg/kg/48 h). The two extravascular routes were studied during a crossover trial for a bioequivalence test. After i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. Mean values were a half-life of 4.1 h, a volume of distribution of 0.86 l/kg and a body clearance of 0.128 l/kg/h. Plasma concentrations of chloramphenicol following i.m. and s.c. administrations increased slowly to a broad peak at 10-15 micrograms/ml between 9 and 12 h. Bioavailability was 19.1% after i.m. injection and 12.4% after s.c. administration. The extent of absorption from the two routes did not differ significantly. The rate of absorption was significantly lower after s.c. application than it was after i.m. injection. The time necessary for the plasma concentration to exceed 5 micrograms/ml was the same for the two routes. Thus, i.m. and s.c. routes are bioequivalent.

  14. Subcutaneously Administered Self-Cleaving Hydrogel-Octreotide Conjugates Provide Very Long-Acting Octreotide.

    PubMed

    Schneider, Eric L; Henise, Jeff; Reid, Ralph; Ashley, Gary W; Santi, Daniel V

    2016-07-20

    We developed a long-acting drug-delivery system that supports subcutaneous administration of the peptidic somatostatin agonist octreotide-a blockbuster drug used to treat acromegaly and neuroendocrine tumors. The current once-a-month polymer-encapsulated octreotide, Sandostatin LAR, requires a painful intragluteal injection through a large needle by a health-care professional. To overcome such shortcomings, Tetra-PEG hydrogel microspheres were covalently attached to the α-amine of d-Phe(1) or the ε-amine of Lys(5) of octreotide by a self-cleaving β-eliminative linker; upon subcutaneous injection in the rat using a small-bore needle, octreotide was slowly released. The released drug from the ε-octreotide conjugate showed a remarkably long serum half-life that exceeded two months. The α-octreotide conjugate had a half-life of ∼2 weeks, and showed an excellent correlation of in vitro and in vivo drug release. Pharmacokinetic models indicate these microspheres should support once-weekly to once-monthly self-administered subcutaneous dosing in humans. The hydrogel-octreotide conjugate shows the favorable pharmacokinetics of Sandostatin LAR without its drawbacks. PMID:27253622

  15. Planning ahead for implementation of long acting HIV prevention: challenges and opportunities

    PubMed Central

    Meyers, Kathrine

    2015-01-01

    Purpose of Review Broad-based access, uptake, and dissemination of daily oral HIV pre-exposure prophylaxis (PrEP) have been slow, despite strong evidence for efficacy. Effective and efficient implementation of long-acting (LA) HIV prevention products will require both analysis of the dynamics and determinants of daily oral PrEP implementation and identification of the distinct challenges and opportunities inherent in emerging technologies. Recent Findings Evidence suggests the importance of addressing implementation issues at three levels: patient, provider, and system. Patient-level factors include targeted education and messaging, tailored supports to enhance acceptability and uptake, and effective strategies for promoting adherence/persistence and retention in care. Provider-level factors include engaging a broad mix of providers, while ensuring adequate training and support for patient assessment, counseling, and follow-up. Systems-level factors include optimal delivery modalities, resource allocation, and ensuring access to populations most in need of new prevention options. Summary Formative social/behavioral research must be undertaken proactively in order to prepare for and address future implementation challenges and reduce the gap between proving efficacy in clinical trials and assuring real-world effectiveness. Conceptualizing new HIV prevention technologies as behavioral interventions at the level of the patient, provider, and system will be paramount to effective and efficient implementation. PMID:26049956

  16. A long-acting cholinesterase inhibitor reverses spatial memory deficits in mice.

    PubMed

    Sweeney, J E; Höhmann, C F; Moran, T H; Coyle, J T

    1988-09-01

    The effects of the long-acting acetylcholinesterase (AChE) inhibitor, galanthamine, on spatial memory were investigated in mice. Mice received ibotenic acid or sham lesions to the nucleus basalis magnocellularis (nBM). Groups of nBM-lesioned and control mice were then trained on a modified Morris swim maze task. Each mouse was first placed on a platform and then into quadrants of the swim tank in a random order. Time required to find the hidden platform was measured. In different phases of testing, the animal had to find a platform that either remained in the same quadrant (reference memory component) or was moved daily (working memory component). The nBM-lesioned mice took significantly longer to find the platform as compared to controls on the working, but not on the reference, memory component of the task. Galanthamine (5.0 mg/kg, IP), given 3.5 hours before testing, improved performance on the working memory task in nBM-lesioned mice by 70% and strikingly impaired performance in controls. Galanthamine's ability to reverse cognitive deficits induced by nBM lesions and its comparatively long half-life suggest that it may be effective in treating the central cholinergic deficits in Alzheimer's disease patients.

  17. Thienorphine is a potent long-acting partial opioid agonist: a comparative study with buprenorphine.

    PubMed

    Yu, Gang; Yue, Yong-Juan; Cui, Meng-Xun; Gong, Ze-Hui

    2006-07-01

    A strategy in the development of new treatment for opioid addiction is to find partial opioid agonists with properties of long duration of action and high oral bioavailability. In a search for such compounds, thienorphine, a novel analog of buprenorphine, was synthesized. Here, we reported that, like buprenorphine, thienorphine bound potently and nonselectively to mu-, delta-, and kappa-opioid receptors stably expressed in CHO (Chinese hamster ovary) cells and behaved as a partial agonist at mu-opioid receptor. However, some differences were observed between the pharmacological profiles of thienorphine and buprenorphine. In vitro, thienorphine was more potent than buprenorphine in inhibiting [3H]diprenorphine and stimulating guanosine 5'-O-(3-[35S]thio)triphosphate binding to rat mu-opioid receptor stably expressed in CHO cells. In vivo, thienorphine exhibited a less potent but more efficacious antinociceptive effect with an ED50 value of 0.25 mg/kg s.c. and more potent antimorphine effect with an ED50 value of 0.64 mg/kg intragastric, compared with buprenorphine. Additionally, the bioavailability of thienorphine was greatly higher than that of buprenorphine after oral administration. Moreover, compared with buprenorphine, thienorphine showed a similar long-lasting antinociceptive effect but a much longer antagonism of morphine-induced lethality (more than 15 days). These results indicate that thienorphine is a potent, long-acting partial opioid agonist with high oral bioavailability and may have possible application in treating addiction. PMID:16569757

  18. Contraception for Adolescents: Focusing on Long-Acting Reversible Contraceptives (LARC) to Improve Reproductive Health Outcomes

    PubMed Central

    Salcedo, Jennifer

    2015-01-01

    Adolescent pregnancy rates in the U.S. have reached an all-time low from their peak in the 1980s and 1990s. However, the U.S. maintains the highest rate of teenage pregnancy among developed nations. Adolescents experience higher typical use failure rates for user-dependent contraceptives compared to their adult counterparts. Long-acting reversible contraception (LARC), IUDs and implants, have failure rates that are both very low and independent of user age. In settings where the most effective methods are prioritized and access barriers are removed, the majority of adolescents initiate LARC. Use of LARC by adolescents significantly reduces rates of overall and repeat teen pregnancy. All methods of contraception are safe for use in teens, including IUDs and DMPA. Dual use of LARC and barrier methods to reduce risk of sexually transmitted infection, is the optimal contraceptive strategy for most adolescents. Adolescent access to evidence-based and confidential contraceptive services, provided in a manner that respects autonomy, is a vital public health goal.

  19. Safety of long-acting beta agonists and inhaled corticosteroids in children and adolescents with asthma.

    PubMed

    Xia, Ying; Kelton, Christina M L; Xue, Liang; Guo, Jeff J; Bian, Boyang; Wigle, Patricia R

    2013-12-01

    The introduction of long-acting beta agonists (LABAs) was considered a major advance in bronchodilator therapy for adult, as well as pediatric, patients with asthma. However, the use of LABAs has raised safety concerns, especially the potential for severe asthma exacerbations (SAEs) resulting in hospitalizations or even death. Meanwhile, the use of inhaled corticosteroids (ICSs), a cornerstone in the treatment of mild-to-severe persistent asthma, has been associated with growth suppression in children. The purpose of this review was to identify and discuss the major published safety studies surrounding LABA, ICS, and combined LABA/ICS usage in children. By way of a critical search for influential published clinical trials, meta-analyses, and observational studies, six studies relevant to the safety of LABA monotherapy, seven studies relevant to ICS monotherapy, and four studies on the subject of LABA/ICS combination usage were identified and reviewed. Based on the reviewed literature, the controversy surrounding these anti-asthma medications was clearly exposed. On the one hand, there is some evidence that LABA monotherapy may be associated with SAEs and asthma-related death, while ICS monotherapy may be associated with a higher risk of growth suppression. On the other hand, the concurrent use of a LABA with an ICS has been associated with positive outcomes including symptom reduction and reduced rate and severity of exacerbations. Further clinical research is warranted and has been called for by the US Food and Drug Administration. PMID:25114786

  20. Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs

    PubMed Central

    Guarnieri, Michael; Tyler, Betty M.; DeTolla, Louis; Zhao, Ming; Kobrin, Barry

    2014-01-01

    Background: Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Objective: Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Methods: Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Results: Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. Discussion: The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Conclusion: Drug implants can retain significant and unintended reservoirs of drugs. PMID:24459402

  1. Contraceptive implants: long acting and provider dependent contraception raises concerns about freedom of choice.

    PubMed Central

    Thompson, M. S.

    1996-01-01

    David Bromham's editorial on contraceptive implants ignores the wider issues to voice concern that trial by media could limit contraceptive choice by jeopardising research into new methods. However, it is more beneficial to the public for points of conflict to be debated openly. Furthermore, the impetus for research into new contraceptive technology is driven by profit and political motives and is only marginally affected by the media. Implanted contraceptives may increase the choice of contraceptive methods, but they put control of fertility increasingly into the hands of the medical profession. Herein lies their greatest problem: their potential to increase providers' control over clients' choice. There is the danger that certain groups of women may be targeted for their use: in the United States the coercive use of Norplant for mothers receiving welfare benefit has been suggested. Long acting contraceptives are a contraceptive of choice only when they are available without pressure, as part of a wider menu; when instant removal on request is guaranteed; and when there is an open and free flow of information and opinions between users, health professionals, and special interest groups. Images p1394-a PMID:8956712

  2. Safety of long-acting beta agonists and inhaled corticosteroids in children and adolescents with asthma

    PubMed Central

    Xia, Ying; Kelton, Christina M. L.; Xue, Liang; Bian, Boyang; Wigle, Patricia R.

    2013-01-01

    The introduction of long-acting beta agonists (LABAs) was considered a major advance in bronchodilator therapy for adult, as well as pediatric, patients with asthma. However, the use of LABAs has raised safety concerns, especially the potential for severe asthma exacerbations (SAEs) resulting in hospitalizations or even death. Meanwhile, the use of inhaled corticosteroids (ICSs), a cornerstone in the treatment of mild-to-severe persistent asthma, has been associated with growth suppression in children. The purpose of this review was to identify and discuss the major published safety studies surrounding LABA, ICS, and combined LABA/ICS usage in children. By way of a critical search for influential published clinical trials, meta-analyses, and observational studies, six studies relevant to the safety of LABA monotherapy, seven studies relevant to ICS monotherapy, and four studies on the subject of LABA/ICS combination usage were identified and reviewed. Based on the reviewed literature, the controversy surrounding these anti-asthma medications was clearly exposed. On the one hand, there is some evidence that LABA monotherapy may be associated with SAEs and asthma-related death, while ICS monotherapy may be associated with a higher risk of growth suppression. On the other hand, the concurrent use of a LABA with an ICS has been associated with positive outcomes including symptom reduction and reduced rate and severity of exacerbations. Further clinical research is warranted and has been called for by the US Food and Drug Administration. PMID:25114786

  3. Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases

    PubMed Central

    Palot, Alain; Sofalvi, Tunde; Pahus, Laurie; Gouitaa, Marion; Tummino, Celine; Martinez, Stephanie; Charpin, Denis; Bourdin, Arnaud; Chanez, Pascal

    2014-01-01

    Acetylcholine (neuronal and non-neuronal origin) regulates bronchoconstriction, and mucus secretion. It has an inflammatory effect by inducing attraction, survival and cytokine release from inflammatory cells. Muscarinic receptors throughout the bronchial tree are mainly restricted to muscarinic M1, M2 and M3 receptors. Three long-acting muscarinic receptor antagonists (LAMAs) were approved for the treatment of chronic obstructive pulmonary disease (COPD) in Europe: once-daily tiotropium bromide; once-daily glycopyrronium bromide; and twice-daily aclidinium bromide. All have higher selectivity for M3 receptors than for M2 receptors, and dissociate more slowly from the M3 receptors than they do from the M2 receptors. Some LAMAs showed anti-inflammatory effects [inhibition of neutrophil chemotactic activity and migration of alveolar neutrophils, decrease of several cytokines in the bronchoalveolar lavage (BAL) including interleukin (IL)-6, tumor necrosis factor (TNF)-α and leukotriene (LT)B4] and antiremodeling effects (inhibition of mucus gland hypertrophy and decrease in MUC5AC-positive goblet cell number, decrease in MUC5AC overexpression). In the clinic, LAMAs showed a significant improvement of forced expiratory volume in 1 second (FEV1), quality of life, dyspnea and reduced the number of exacerbations in COPD and more recently in asthma. This review will focus on the three LAMAs approved in Europe in the treatment of chronic airway diseases. PMID:24587893

  4. Contraception for Adolescents: Focusing on Long-Acting Reversible Contraceptives (LARC) to Improve Reproductive Health Outcomes

    PubMed Central

    Salcedo, Jennifer

    2015-01-01

    Adolescent pregnancy rates in the U.S. have reached an all-time low from their peak in the 1980s and 1990s. However, the U.S. maintains the highest rate of teenage pregnancy among developed nations. Adolescents experience higher typical use failure rates for user-dependent contraceptives compared to their adult counterparts. Long-acting reversible contraception (LARC), IUDs and implants, have failure rates that are both very low and independent of user age. In settings where the most effective methods are prioritized and access barriers are removed, the majority of adolescents initiate LARC. Use of LARC by adolescents significantly reduces rates of overall and repeat teen pregnancy. All methods of contraception are safe for use in teens, including IUDs and DMPA. Dual use of LARC and barrier methods to reduce risk of sexually transmitted infection, is the optimal contraceptive strategy for most adolescents. Adolescent access to evidence-based and confidential contraceptive services, provided in a manner that respects autonomy, is a vital public health goal. PMID:27635305

  5. Global trends in use of long-acting reversible and permanent methods of contraception: Seeking a balance.

    PubMed

    Joshi, Ritu; Khadilkar, Suvarna; Patel, Madhuri

    2015-10-01

    The global trend shows that the use of permanent contraception to prevent unintended pregnancy is high. Although the trend also shows a rise in the use of long-acting reversible methods, these are still underutilized despite having contraceptive as well as non-contraceptive benefits. Lack of knowledge among women, dependence on the provider for information, and provider bias for permanent contraception are cited as reasons for this reduced uptake. Training of healthcare providers and increased patient awareness about the effectiveness of long-acting reversible contraceptive methods will increase their uptake and help prevent unintended pregnancies.

  6. 78 FR 52777 - Draft Guidance for Industry on Bioequivalence Recommendations for Risperidone Injection...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-26

    ... HUMAN SERVICES Food and Drug Administration (Formerly Docket No. 2007D-0168) Draft Guidance for Industry on Bioequivalence Recommendations for Risperidone Injection; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing...

  7. Acute and long-term safety and tolerability of risperidone in children with autism.

    PubMed

    Aman, Michael G; Arnold, L Eugene; McDougle, Christopher J; Vitiello, Benedetto; Scahill, Lawrence; Davies, Mark; McCracken, James T; Tierney, Elaine; Nash, Patricia L; Posey, David J; Chuang, Shirley; Martin, Andres; Shah, Bhavik; Gonzalez, Nilda M; Swiezy, Naomi B; Ritz, Louise; Koenig, Kathleen; McGough, James; Ghuman, Jaswinder K; Lindsay, Ronald L

    2005-12-01

    Treatment-emergent adverse events (AEs) were monitored during an 8-week, double-blind, placebo-controlled trial of risperidone (0.5-3.5 mg/day) in 101 children and adolescents with a lifetime diagnosis of autistic disorder. In addition, 37 placebo nonresponders received open-label risperidone for another 8 weeks. Of all the risperidone responders (n=65), 63 entered an open extension of another 16 weeks (6 months total risperidone exposure), and 32 of them were rerandomized to either continued risperidone therapy (n=16) or gradual replacement with placebo (n=16) over 8 weeks. We collected the following measures of safety and tolerability: (1) laboratory blood assessments (CBC with differential, electrolytes, and liver function tests) and urinalyses, (2) vital signs, (3) Side Effects Review of AEs thought to be associated with risperidone, (4) sleep records, (5) Simpson Angus Neurological Rating Scale (SARS), (6) Abnormal Involuntary Movement Scale (AIMS), and (7) height and weight. No clinically significant changes were found on the lab tests. During the 8-week acute trial, the most common AEs on the Side Effects Review, scored as moderate or higher, were as follows (placebo and risperidone, respectively): Somnolence (12% and 37%), enuresis (29% and 33%), excessive appetite (10% and 33%), rhinitis (8% and 16%), difficulty waking (8% and 12%), and constipation (12% and 10%). "Difficulty falling asleep" and anxiety actually favored the risperidone condition at statistically significant levels. The same AEs tended to recur through 6 months of treatment, although often at reduced levels. Using Centers for Disease Control (CDC) standardized scores, both weight and body mass index (BMI) increased with risperidone during the acute trial (0.5 and 0.6 SDs, respectively, for risperidone; 0.0 and 0.1 SDs, respectively, for placebo) and into open-label extension (0.19 and 0.16 SDs, respectively), although the amount of gain decelerated with time. Extrapyramidal symptoms, as

  8. Change in Plasma Cytokine Levels During Risperidone Treatment in Children with Autism

    PubMed Central

    Choi, Jae Eun; Widjaja, Felicia; Careaga, Milo; Bent, Stephen; Ashwood, Paul

    2014-01-01

    Abstract Background: Atypical antipsychotics decrease irritability in autism. They also affect the cytokine network. Psychological stress, depression, and, possibly, autism spectrum disorder (ASD) are associated with the production of pro-inflammatory cytokines. We sought to determine if risperidone treatment led to changes in plasma cytokine levels. Methods: Forty-five subjects from an open-label study of risperidone treatment of children and adolescents with ASD, ages 4–18 years, had an analysis of 27 different cytokines at baseline and after 8 weeks of treatment using multiplex assays (Millipore) and read on the Luminex 100™ platform. We examined changes in each of the cytokine levels in the entire group, and also compared changes in cytokines in responders versus nonresponders. Results: After 8 weeks of risperidone treatment, 2 of the 27 plasma cytokines showed statistically significant decreases in median levels: Eotaxin (p=0.0003) and monocyte chemoattractant protein-1 (MCP-1) (p=0.0024). Six of the 48 subjects met two criteria for responders to risperidone, and the median values of interleukin (IL)-5 were significantly higher (p=0.005) in the overall responder group than in nonresponders. Conclusions: Two cytokines, eotaxin and MCP-1, which have previously been identified as abnormally elevated in children with autism, decreased during treatment with risperidone. This suggests a possible mechanism of action of risperidone treatment and a balancing of the immune system in affected subjects in this very preliminary study. PMID:24828014

  9. Rate-decreasing effects of the atypical neuroleptic risperidone attenuated by conditions of reinforcement in a woman with mental retardation.

    PubMed

    Yoo, J Helen; Williams, Dean C; Napolitano, Deborah A; Peyton, Robert T; Baer, Donald M; Schroeder, Stephen R

    2003-01-01

    Effects of two doses of risperidone on the performance of a matching task under tangible reinforcement and nonreinforcement conditions were measured in a woman with mental retardation. In both conditions, time to complete the task increased and response rates decreased under two doses of risperidone. Accuracy was generally unchanged. These changes were much smaller in the tangible reinforcement condition; thus, reinforcement seemed to protect performance from the rate-decreasing effects of risperidone.

  10. Substituting a long-acting dopamine uptake inhibitor for cocaine prevents relapse to cocaine seeking.

    PubMed

    Velázquez-Sánchez, Clara; Ferragud, Antonio; Ramos-Miguel, Alfredo; García-Sevilla, Jesús A; Canales, Juan J

    2013-07-01

    The treatment of cocaine addiction remains a challenge. The dopamine replacement approach in cocaine addiction involves the use of a competing dopaminergic agonist that might suppress withdrawal and drug craving in abstinent individuals. Although it has long been postulated that such an approach may be therapeutically successful, preclinical or clinical evidence showing its effectiveness to prevent relapse is scant. We used in rats a procedure that involved substitution of the N-substituted benztropine analog 3α-[bis(4'-fluorophenyl)methoxy]-tropane (AHN-1055), a long-acting dopamine uptake inhibitor (DUI), for cocaine. Maintenance treatment was self-administered. After extinction, reinstatement of drug seeking was induced by cocaine priming. We measured the contents of brain-derived neurotrophic factor (BDNF), c-Fos and Fas-associated death domain (FADD) proteins in the medial prefrontal cortex (mPFC) following reinstatement. DUI, but not amphetamine, substitution led to extinction of active lever presses, as did saline substitution. DUI substitution significantly reduced cocaine-induced reinstatement of drug-seeking behavior, which was strongly elicited after saline substitution. Rats passively yoked to DUI also showed reduced cocaine-primed reinstatement. Reductions in drug seeking during reinstatement were matched by downward shifts in the contents of BDNF, c-Fos and FADD proteins in the mPFC, which were elevated in relapsing rats. These data indicate that DUI substitution not only leads to extinction of self-administration behavior but also prevents reinstatement of drug seeking induced by cocaine re-exposure. Thus, DUI substitution therapy using compounds with low abuse potential, even if received passively in the context previously paired with drug taking, may provide an effective treatment for stimulant addiction.

  11. Blood eosinophils and inhaled corticosteroid/long-acting β-2 agonist efficacy in COPD

    PubMed Central

    Pavord, Ian D; Lettis, Sally; Locantore, Nicholas; Pascoe, Steve; Jones, Paul W; Wedzicha, Jadwiga A; Barnes, Neil C

    2016-01-01

    Objective We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy. Methods Three studies of ≥1-year duration met the inclusion criteria. Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%). At baseline, 57–75% of patients had ≥2% blood eosinophils. Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level. Results For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001). No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively). In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo). No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ. Discussion Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. PMID:26585525

  12. Long-acting Reversible Contraception for Adolescents and Young Adults: Patient and Provider Perspectives

    PubMed Central

    Kavanaugh, Megan L.; Frohwirth, Lori; Jerman, Jenna; Popkin, Ronna; Ethier, Kathleen

    2013-01-01

    Study objective To describe and explore provider- and patient-level perspectives regarding long-acting reversible contraception (LARC) for teens and young adults (ages 16-24). Methods Data collection occurred between June – December 2011. We first conducted telephone interviews with administrative directors at 20 publicly funded facilities that provide family planning services. At six of these sites, we conducted a total of six focus group discussions (FGDs) with facility staff and forty-eight in-depth interviews (IDIs) with facility clients ages 16-24. Results Staff in the FGDs did not generally equate being a teen with ineligibility for IUDs. In contrast to staff, one quarter of the young women did perceive young age as rendering them ineligible. Clients and staff agreed that the “forgettable” nature of the methods and their duration were some of LARC’s most significant advantages. They also agreed that fear of pain associated with both insertion and removal and negative side effects were disadvantages. Some aspects of IUDs and implants were perceived as advantages by some clients but disadvantages by others. Common challenges to providing LARC-specific services to younger patients included extra time required to counsel young patients about LARC methods, outdated clinic policies requiring multiple visits to obtain IUDs, and a perceived higher removal rate among young women. The most commonly cited strategy for addressing many of these challenges was securing supplementary funding to support the provision of these services to young patients. Conclusion Incorporating young women’s perspectives on LARC methods into publicly funded family planning facilities’ efforts to provide these methods to a younger population may increase their use among young women. PMID:23287602

  13. Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors

    PubMed Central

    Cives, M; Kunz, P L; Morse, B; Coppola, D; Schell, M J; Campos, T; Nguyen, P T; Nandoskar, P; Khandelwal, V; Strosberg, J R

    2015-01-01

    Pasireotide long-acting repeatable (LAR) is a novel somatostatin analog (SSA) with avid binding affinity to somatostatin receptor subtypes 1, 2, 3 (SSTR1,2,3) and 5 (SSTR5). Results from preclinical studies indicate that pasireotide can inhibit neuroendocrine tumor (NET) growth more robustly than octreotide in vitro. This open-label, phase II study assessed the clinical activity of pasireotide in treatment-naïve patients with metastatic grade 1 or 2 NETs. Patients with metastatic pancreatic and extra-pancreatic NETs were treated with pasireotide LAR (60 mg every 4 weeks). Previous systemic therapy, including octreotide and lanreotide, was not permitted. Tumor assessments were performed every 3 months using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), overall radiographic response rate (ORR), and safety. Twenty-nine patients were treated with pasireotide LAR (60 mg every 4 weeks) and 28 were evaluable for response. The median PFS was 11 months. The most favorable effect was observed in patients with low hepatic tumor burden, normal baseline chromogranin A, and high tumoral SSTR5 expression. Median OS has not been reached; the 30-month OS rate was 70%. The best radiographic response was partial response in one patient (4%), stable disease in 17 patients (60%), and progressive disease in ten patients (36%). Although grade 3/4 toxicities were rare, pasireotide LAR treatment was associated with a 79% rate of hyperglycemia including 14% grade 3 hyperglycemia. Although pasireotide appears to be an effective antiproliferative agent in the treatment of advanced NETs, the high incidence of hyperglycemia raises concerns regarding its suitability as a first-line systemic agent in unselected patients. SSTR5 expression is a potentially predictive biomarker for response. PMID:25376618

  14. Efficacy and safety of conventional long acting β2- agonists: systematic review and meta-analysis

    PubMed Central

    Karbasi-Afshar, Reza; Aslani, Jafar; Ghanei, Mostafa

    2016-01-01

    Background: Chronic obstructive pulmonary disease (COPD) is usually considered one of the leading causes of death worldwide, so finding proper therapeutic strategies for this disease is of high importance. In this meta-analysis, we reviewed the existing literature on the efficacy and safety of conventional long acting beta agonists (LABAs) in COPD patients. Methods: We searched MEDLINE and Google scholar to identify relevant articles. We limited data to double-blinded randomized controlled trials (RCTs). Data of 14, 832 COPD subjects including 7540 patients under a β2 agonist (cases) and 7292 taking placebo (controls) retrieved from 20 randomized controlled trials and were enrolled into this meta-analysis. Evaluated outcomes included overall mortality, exacerbations and tolerance to the drug. Results: The analysis of survival showed no significant difference between those taking LABAs or placebo (relative risk (RR): 0.945, 95% confidence interval (CI): 0.821-1.088, P=0.432). Exacerbation rate, however, was significantly lower among the cases than among the controls (RR: 0.859, 95%CI: 0.800-0.922, p<0.001). Similar observation was detected in analyzing the rate of drug withdrawal in patients of the two groups with patients under placebo having significantly higher rate of drug discontinuation due to adverse events or disease symptoms (RR:0.821, 95% CI: 0.774-0.871; p<0.007). Conclusion: In conclusion, we found that the use of conventional LABA therapy in COPD patients is associated with a lower exacerbation rate of the disease as well as higher tolerance to the drug, but no survival advantage is expectable. Substitution of LABAs with new agents is recommended. PMID:27386055

  15. Who Is Using Long-Acting Reversible Contraceptive Methods? Findings from Nine Low-Fertility Countries

    PubMed Central

    Eeckhaut, Mieke C. W.; Sweeney, Megan M.; Gipson, Jessica D.

    2014-01-01

    CONTEXT Long-acting reversible contraceptive (LARC) methods—IUDs and implants—are more effective than other reversible methods, yet are little used in the United States. Examining which U.S. women use LARC methods and how they differ from users in other low-fertility countries may help point the way toward increasing use. METHODS Data from married or cohabiting women participating in the National Survey of Family Growth (2008–2010) and in eight countries’ Generations and Gender Programme surveys (2004–2010) were used in bivariate and multinomial logistic regression analyses examining LARC use within each setting. RESULTS The proportion of contraceptive use accounted for by LARC methods was generally greater in Europe (10–32%) than in the United States (10%) and Australia (7%). Compared with LARC use among comparable groups in other countries, use was particularly low among U.S. women who were married, were aged 40–44 or had had three or more children, yet was comparatively high among 18–24-year-olds. Among U.S. women, those aged 35–39 or 40–44 were more likely than 18–29-year-olds to rely on sterilization rather than on LARC methods (odds ratios, 3.0 and 10.7, respectively), those who had had three or more children were more likely to do so than were those who had had none or one (4.9), and women who had completed college were less likely than those who had not finished high school to do so (0.4). CONCLUSIONS Certain subgroups of U.S. women may benefit from the reversibility and effectiveness of LARC methods. PMID:25040454

  16. Pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs

    PubMed Central

    2012-01-01

    Based on its PK/PD ratios, doxycycline hyclate (DOX-h), a time-dependant antibacterial, is ideally expected to achieve both sustained plasma drug concentrations at or slightly above the MIC level for as long as possible between dosing intervals. Pursuing this end, a poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its SC injection to dogs (≤ 0.3 mL per injection site), and results compared with the oral (PO) and IV pharmacokinetics of DOX-h, prepared as tablet or as freshly made solution. A crossover (4 x 4 x 4) study design was employed with 12 Mongrel dogs, with washout periods of 21 days, and at dose of 10 mg/kg in all cases. DOX-h-LA showed the greatest values for bioavailability (199.48%); maximum serum concentration (Cmax) value was 2.8 ± 0.3 with a time to reach Cmax (Tmax) of 2.11 ± 0.12 h and an elimination half-life of 133.61 ± 6.32 h. Considering minimum effective serum concentration of 0.5 μg/mL, a dose-interval of at least 1 week h can be achieved for DOX-h-LA, and only 48 h and 24 h after the IV or PO administration of DOX-h as a solution or as tablets, respectively. A non-painful small bulge, apparently non-inflammatory could be distinguished at injection sites. These lumps dissipated completely in 30 days in all cases. PMID:22682068

  17. Pharmacokinetics of Long-Acting Tenofovir Alafenamide (GS-7340) Subdermal Implant for HIV Prophylaxis

    PubMed Central

    Gunawardana, Manjula; Remedios-Chan, Mariana; Miller, Christine S.; Fanter, Rob; Yang, Flora; Marzinke, Mark A.; Hendrix, Craig W.; Beliveau, Martin; Moss, John A.; Smith, Thomas J.

    2015-01-01

    Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis (PrEP) by reducing dosing frequency. A novel, subdermal implant delivering the potent prodrug tenofovir alafenamide (TAF) with controlled, sustained, zero-order (linear) release characteristics is described. A candidate device delivering TAF at 0.92 mg day−1 in vitro was evaluated in beagle dogs over 40 days for pharmacokinetics and preliminary safety. No adverse events related to treatment with the test article were noted during the course of the study, and no significant, unusual abnormalities were observed. The implant maintained a low systemic exposure to TAF (median, 0.85 ng ml−1; interquartile range [IQR], 0.60 to 1.50 ng ml−1) and tenofovir (TFV; median, 15.0 ng ml−1; IQR, 8.8 to 23.3 ng ml−1), the product of in vivo TAF hydrolysis. High concentrations (median, 512 fmol/106 cells over the first 35 days) of the pharmacologically active metabolite, TFV diphosphate, were observed in peripheral blood mononuclear cells at levels over 30 times higher than those associated with HIV-1 PrEP efficacy in humans. Our report on the first sustained-release nucleoside reverse transcriptase inhibitor (NRTI) for systemic delivery demonstrates a successful proof of principle and holds significant promise as a candidate for HIV-1 prophylaxis in vulnerable populations. PMID:25896688

  18. Physician and patient benefit–risk preferences from two randomized long-acting injectable antipsychotic trials

    PubMed Central

    Katz, Eva G; Hauber, Brett; Gopal, Srihari; Fairchild, Angie; Pugh, Amy; Weinstein, Rachel B; Levitan, Bennett S

    2016-01-01

    Purpose To quantify clinical trial participants’ and investigators’ judgments with respect to the relative importance of efficacy and safety attributes of antipsychotic treatments for schizophrenia, and to assess the impact of formulation and adherence. Methods Discrete-choice experiment surveys were completed by patients with schizophrenia and physician investigators participating in two phase-3 clinical trials of paliperidone palmitate 3-month long-acting injectable (LAI) antipsychotic. Respondents were asked to choose between hypothetical antipsychotic profiles defined by efficacy, safety, and mode of administration. Data were analyzed using random-parameters logit and probit models. Results Patients (N=214) and physicians (N=438) preferred complete improvement in positive symptoms (severe to none) as the most important attribute, compared with improvement in any other attribute studied. Both respondents preferred 3-month and 1-month injectables to oral formulation (P<0.05), irrespective of prior adherence to oral antipsychotic treatment, with physicians showing greater preference for a 3-month over a 1-month LAI for nonadherent patients. Physicians were willing to accept treatments with reduced efficacy for patients with prior poor adherence. The maximum decrease in efficacy (95% confidence interval [CI]) that physicians would accept for switching a patient from daily oral to 3-month injectable was as follows: adherent: 9.8% (95% CI: 7.2–12.4), 20% nonadherent: 25.4% (95% CI: 21.0–29.9), and 50% nonadherent: >30%. For patients, adherent: 10.1% (95% CI: 6.1–14.1), nonadherent: the change in efficacy studied was regarded as unimportant. Conclusion Improvement in positive symptoms was the most important attribute. Patients and physicians preferred LAIs over oral antipsychotics, with physicians showing a greater preference for 3-month over 1-month LAI. Physicians and patients were willing to accept reduced efficacy in exchange for switching a patient from

  19. Pharmacokinetics, Pharmacodynamics, and Efficacy of a Novel Long-Acting Human Growth Hormone: Fc Fusion Protein.

    PubMed

    Kim, Su Jin; Kwak, Hyun-Hee; Cho, Sung Yoon; Sohn, Young Bae; Park, Sung Won; Huh, Rimm; Kim, Jinsup; Ko, Ah-Ra; Jin, Dong-Kyu

    2015-10-01

    The current recombinant human growth hormone (rhGH) therapy requires daily subcutaneous (sc) injections, which results in poor patient compliance, especially in young children. To reduce the dosing frequency, we generated a chimeric protein of rhGH and the Fc-domain of immunoglobulin G (IgG) (rhGH-Fc). The pharmacokinetics and pharmacodynamics of sc-injected rhGH-Fc were assessed in male Sprague-Dawley rats and hypophysectomized rats, respectively. A single sc injection of rhGH-Fc at a dose of 0.2 mg/kg slowly reached a Cmax of 16.80 ng/mL and remained for 7 days with a half-life of 51.1 h. Conversely, a single sc injection of rhGH 0.2 mg/kg rapidly reached a Cmax of 46.88 ng/mL and declined with a half-life of 0.55 h to baseline values in 4 h. In the efficacy study, the sc-injected rhGH-Fc induced rapid weight gain and tibial width growth at a dose of 240 μg/animal. The effect of two injections of rhGH-Fc separated by 1 week was comparable to that of the same dose of 14 daily injections of rhGH. The rhGH-Fc is a novel candidate for long-acting rhGH therapy with more convenient weekly administration, as it reduces glomerular filtration and receptor-mediated clearance while allowing for the rapid reversal of potential adverse events.

  20. Liraglutide, a long-acting GLP-1 mimetic, and its metabolite attenuate inflammation after intracerebral hemorrhage

    PubMed Central

    Hou, Jack; Manaenko, Anatol; Hakon, Jakob; Hansen-Schwartz, Jacob; Tang, Jiping; Zhang, John H

    2012-01-01

    The inflammatory response plays a pivotal role in propagating injury of intracerebral hemorrhage (ICH). Glucagon-like-peptide-1 (GLP-1) is a hormone with antidiabetic effect and may also have antiinflammatory properties. Despite consensus that the glucoregulatory action is mediated by the GLP-1 receptor (GLP-1R), mechanisms in the brain remain unclear. We investigated the effect of a long-acting GLP-1 analog, liraglutide, and its truncated metabolite, GLP-1(9-36)a from dipeptidyl peptidase-4 (DPP-4) cleavage in ICH-induced brain injury. Primary outcomes were cerebral edema formation, neurobehavior, and inflammatory parameters. GLP-1(9-36)a, GLP-1R inhibitor, adenosine monophosphate-activated protein kinase (AMPK) phosphorylation inhibitor and DPP-4 inhibitor were administered to examine the mechanisms of action. Liraglutide suppressed neuroinflammation, prevented brain edema and neurologic deficit following ICH, which were partially reversed by GLP-1R inhibitor and AMPK phosphorylation inhibitor. Liraglutide-mediated AMPK phosphorylation was unaffected by GLP-1R inhibitor, and was found to be induced by GLP-1(9-36)a. GLP-1(9-36)a showed salutary effects on primary outcomes that were reversed by AMPK phosphorylation inhibitor but not by GLP-1R inhibitor. Liraglutide and DPP-4 inhibitor co-administration reversed liraglutide-mediated AMPK phosphorylation and antiinflammatory effects. Liraglutide exerted duals actions and the antiinflammatory effects are partially mediated by its metabolite in a phosphorylated AMPK-dependent manner. Therapies that inhibit GLP-1 degradation may weaken the metabolite-mediated effects. PMID:22968320

  1. Efficacy and Safety of Long-Acting Reversible Contraception in Women With Cardiovascular Conditions.

    PubMed

    Vu, Quyen; Micks, Elizabeth; McCoy, Erin; Prager, Sarah

    2016-01-15

    The physiological changes that occur during pregnancy can be deleterious to women with a cardiovascular condition. Evidence-based contraceptive counseling and provision is essential in this patient population. Although long-acting reversible contraception (LARCs), which include the intrauterine device (IUD) and the etonogestrel contraceptive implant, have been found to be safe and effective in healthy women, there are inadequate data regarding LARC use in patients with cardiovascular conditions. We conducted a retrospective chart review of women diagnosed with cardiovascular disease who had a copper IUD, levonorgestrel-releasing intrauterine system or contraceptive implant placed at the University of Washington Medical Center from 2007 to 2012. We abstracted and analyzed patient demographic characteristics, medical conditions, indications for LARC placement, and complications. The sample included 470 women with cardiovascular conditions. The mean age was 34.6 years. One hundred twenty-four patients (26.11%) were nulligravid and 169 patients (35.58%) were nulliparous. Four hundred ten chose the levonorgestrel-releasing intrauterine system (87.23%), 33 patients (7.02%) opted for the copper IUD, and 23 patients (4.89%) chose the etonogestrel implant. Eighteen patients (3.83%) had a confirmed IUD expulsion, 2 patients (0.43%) became pregnant, and there were 4 cases of pelvic inflammatory disease (0.85%). There were no cases of perforation. There were no confirmed cases of infective endocarditis associated with LARC insertion. In conclusion, LARC devices appear safe with few complications for women with cardiovascular conditions. Clinicians can be reassured that LARC may be offered as an appropriate option when counseling women with cardiovascular disease on safe contraceptive methods.

  2. The management of a case of treatment-resistant paraphilia with a long-acting LHRH agonist.

    PubMed

    Dickey, R

    1992-10-01

    A patient with multiple paraphilias who had been treated for several years with sex drive reducing agents (cyproterone acetate and medroxyprogesterone acetate) with little effect on sexual activity or fantasy was offered treatment with long-acting leuprolide acetate, on LHRH agonist. This produced a marked decrease in all reported sexual thoughts and activities with no significant side-effects.

  3. Pharmacogenetics of Risperidone and Cardiovascular Risk in Children and Adolescents

    PubMed Central

    Dos Santos-Júnior, Amilton; Henriques, Taciane Barbosa; de Mello, Maricilda Palandi; Della Torre, Osmar Henrique; Paes, Lúcia Arisaka; Ferreira-Neto, Adriana Perez; Sewaybricker, Letícia Esposito; Fontana, Thiago Salum; Celeri, Eloisa Helena Rubello Valler; Guerra-Júnior, Gil; Dalgalarrondo, Paulo

    2016-01-01

    Objective. To identify the frequency of obesity and metabolic complications in child and adolescent users of risperidone. Potential associations with clinical parameters and SNPs of the HTR2C, DRD2, LEP, LEPR, MC4R, and CYP2D6 genes were analyzed. Methods. Samples from 120 risperidone users (8–20 years old) were collected and SNPs were analyzed, alongside assessment of chronological and bone ages, prescribed and weight-adjusted doses, use of other psychotropic drugs, waist circumference, BMI z-scores, blood pressure, HOMA-IR index, fasting levels of serum glucose, insulin, cholesterol, triglycerides, transaminases, and leptin. Results. Thirty-two (26.7%) patients were overweight and 5 (4.2%) obese. Hypertension was recorded in 8 patients (6.7%), metabolic syndrome in 6 (5%), and increased waist circumference in 20 (16.7%). The HOMA-IR was high for 22 patients (18.3%), while total cholesterol and triglycerides were high in 20 (16.7%) and 41 (34.2%) patients, respectively. SNP associations were found for LEP, HTR2C, and CYP2D6 with BMI; CYP2D6 with blood pressure, ALT, and HOMA-IR; HTR2C and LEPR with leptin levels; MC4R and DRD2 with HOMA-IR; HTR2C with WC; and LEP with ALT. Conclusions. Although not higher than in the general pediatric population, a high frequency of patients was overweight/obese, with abnormalities in metabolic parameters and some pharmacogenetic associations. PMID:26880915

  4. Pharmacogenetics of Risperidone and Cardiovascular Risk in Children and Adolescents.

    PubMed

    Dos Santos-Júnior, Amilton; Henriques, Taciane Barbosa; de Mello, Maricilda Palandi; Della Torre, Osmar Henrique; Paes, Lúcia Arisaka; Ferreira-Neto, Adriana Perez; Sewaybricker, Letícia Esposito; Fontana, Thiago Salum; Celeri, Eloisa Helena Rubello Valler; Guerra-Júnior, Gil; Dalgalarrondo, Paulo

    2016-01-01

    Objective. To identify the frequency of obesity and metabolic complications in child and adolescent users of risperidone. Potential associations with clinical parameters and SNPs of the HTR2C, DRD2, LEP, LEPR, MC4R, and CYP2D6 genes were analyzed. Methods. Samples from 120 risperidone users (8-20 years old) were collected and SNPs were analyzed, alongside assessment of chronological and bone ages, prescribed and weight-adjusted doses, use of other psychotropic drugs, waist circumference, BMI z-scores, blood pressure, HOMA-IR index, fasting levels of serum glucose, insulin, cholesterol, triglycerides, transaminases, and leptin. Results. Thirty-two (26.7%) patients were overweight and 5 (4.2%) obese. Hypertension was recorded in 8 patients (6.7%), metabolic syndrome in 6 (5%), and increased waist circumference in 20 (16.7%). The HOMA-IR was high for 22 patients (18.3%), while total cholesterol and triglycerides were high in 20 (16.7%) and 41 (34.2%) patients, respectively. SNP associations were found for LEP, HTR2C, and CYP2D6 with BMI; CYP2D6 with blood pressure, ALT, and HOMA-IR; HTR2C and LEPR with leptin levels; MC4R and DRD2 with HOMA-IR; HTR2C with WC; and LEP with ALT. Conclusions. Although not higher than in the general pediatric population, a high frequency of patients was overweight/obese, with abnormalities in metabolic parameters and some pharmacogenetic associations. PMID:26880915

  5. Bioequivalence Study of Two Long-Acting Formulations of Oxytetracycline Following Intramuscular Administration in Bovines

    PubMed Central

    Mestorino, Nora; Marchetti, María Laura; Lucas, Mariana Florencia; Modamio, Pilar; Zeinsteger, Pedro; Fernández Lastra, Cecilia; Segarra, Ignacio; Mariño, Eduardo Luis

    2016-01-01

    The aim of this study was to evaluate the bioequivalence of two commercial long-acting formulations based on oxytetracycline (OTC) hydrochloride between the reference formulation (Terramycin LA, Pfizer) and a test formulation (Cyamicin LA, Fort Dodge Saude Animal). Both formulations were administered in a single intramuscular route at a dose of 20 mg OTC/kg of body weight in clinically healthy bovines. The study was carried out according to a one-period parallel design. Plasma samples were analyzed by high-pressure liquid chromatography. The limit of quantitation was 0.050 μg/mL with an accuracy of 101.67% with a coefficient of variation of 13.15%. Analysis of variance and 90% confidence interval tests were used to compare the bioavailability parameters (maximum plasma concentration, Cmax, and the area under the concentration-versus-time curve extrapolated to infinity, AUC0–∞) of both products. In the case of the time to maximum concentration (Tmax), non-parametric tests based on Wilcoxon’s signed rank test were preferred. The comparison of the mean AUC0–∞ values did not reveal any significant differences (311.40 ± 93.05 μg h/mL and 287.71 ± 45.31 μg h/mL, respectively). The results were similar for the Tmax (3.58 ± 0.90 h versus 3.42 ± 0.51 h). However, when comparing the mean Cmax some significant differences were found (8.73 ± 3.66 μg/mL and 10.43 ± 3.84 μg/mL, respectively). The 90% confidence intervals for the ratio of AUC0–∞ and Tmax values for the reference and test product are within the interval 80–125%, but the 90% confidence intervals for the ratio of Cmax falls outside the proposed interval. It was concluded that Cmax of test product are not within the 20% of those of the reference, thus suggesting that test OTC is not bioequivalent to the reference formulation. PMID:27446938

  6. Inverse association of long-acting natriuretic peptide with metabolic syndrome in congestive heart failure patients

    PubMed Central

    2013-01-01

    Aims Long-acting natriuretic peptide (LANP) is one of the peptide hormones in atrial natriuretic peptide (ANP) pro-hormone. Low levels of natriuretic peptide may lead to reduced lipolysis and excessive weight gain in obese patients. The aim of this study was to investigate the relationship between fasting serum LANP level and the metabolic syndrome (MetS) among congestive heart failure (CHF) patients. Methods Fasting blood samples were obtained from 186 patients with normal renal function in cardiac clinic outpatients. CHF defined by the American College of Cardiology Foundation and the American Heart Association 2005 Guidelines. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Results Ninety-eight patients (52.7%) had CHF. There was a tendency of increased fasting LANP levels as the NYHA CHF functional classes increased (p = 0.002). Forty-six of the CHF patients (46.9%) had MetS. Fasting LANP level negatively correlated with MetS among CHF patients (p < 0.001). Univariate linear regression analysis showed that BUN (p = 0.026) positively correlated with fasting serum LANP levels, while body weight (p = 0.009), BMI (p = 0.004), homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.024) and HOMA-β (p = 0.001) negatively correlated with fasting serum LANP levels among the CHF patients. Multivariate forward stepwise linear regression analysis of the significant variables showed that the HOMA-β (R2 change = 0.292, p < 0.001) and HOMA-IR (R2 change = 0.081, p = 0.019) were independent predictors of fasting serum LANP levels in CHF patients. Conclusions LANP level is significantly reduced in CHF patients affected by MetS. HOMA-β and HOMA-IR were independent predictors of serum LANP levels in CHF patients. PMID:23566312

  7. Vouchers in Fragile States: Reducing Barriers to Long-Acting Reversible Contraception in Yemen and Pakistan.

    PubMed

    Boddam-Whetham, Luke; Gul, Xaher; Al-Kobati, Eman; Gorter, Anna C

    2016-08-11

    In conflict-affected states, vouchers have reduced barriers to reproductive health services and have enabled health programs to use targeted subsidies to increase uptake of specific health services. Vouchers can also be used to channel funds to public- and private-service providers and improve service quality. The Yamaan Foundation for Health and Social Development in Yemen and the Marie Stopes Society (MSS) in Pakistan-both working with Options Consultancy Services-have developed voucher programs that subsidize voluntary access to long-acting reversible contraceptives (LARCs) and permanent methods (PMs) of family planning in their respective fragile countries. The programs focus on LARCs and PMs because these methods are particularly difficult for poor women to access due to their cost and to provider biases against offering them. Using estimates of expected voluntary uptake of LARCs and PMs for 2014 based on contraceptive prevalence rates, and comparing these with uptake of LARCs and PMs through the voucher programs, we show the substantial increase in service utilization that vouchers can enable by contributing to an expanded method choice. In the governorate of Lahj, Yemen, vouchers for family planning led to an estimated 38% increase in 2014 over the expected use of LARCs and PMs (720 vs. 521 expected). We applied the same approach in 13 districts of Punjab, Khyber Pakhtunkhwa (KPK), and Sindh provinces in Pakistan. Our calculations suggest that vouchers enabled 10 times more women than expected to choose LARCs and PMs in 2014 in those areas of Pakistan (73,639 vs. 6,455 expected). Voucher programs can promote and maintain access to family planning services where existing health systems are hampered. Vouchers are a flexible financing approach that enable expansion of contraceptive choice and the inclusion of the private sector in service delivery to the poor. They can keep financial resources flowing where the public sector is prevented from offering services

  8. Bioequivalence Study of Two Long-Acting Formulations of Oxytetracycline Following Intramuscular Administration in Bovines.

    PubMed

    Mestorino, Nora; Marchetti, María Laura; Lucas, Mariana Florencia; Modamio, Pilar; Zeinsteger, Pedro; Fernández Lastra, Cecilia; Segarra, Ignacio; Mariño, Eduardo Luis

    2016-01-01

    The aim of this study was to evaluate the bioequivalence of two commercial long-acting formulations based on oxytetracycline (OTC) hydrochloride between the reference formulation (Terramycin LA, Pfizer) and a test formulation (Cyamicin LA, Fort Dodge Saude Animal). Both formulations were administered in a single intramuscular route at a dose of 20 mg OTC/kg of body weight in clinically healthy bovines. The study was carried out according to a one-period parallel design. Plasma samples were analyzed by high-pressure liquid chromatography. The limit of quantitation was 0.050 μg/mL with an accuracy of 101.67% with a coefficient of variation of 13.15%. Analysis of variance and 90% confidence interval tests were used to compare the bioavailability parameters (maximum plasma concentration, C max, and the area under the concentration-versus-time curve extrapolated to infinity, AUC0-∞) of both products. In the case of the time to maximum concentration (T max), non-parametric tests based on Wilcoxon's signed rank test were preferred. The comparison of the mean AUC0-∞ values did not reveal any significant differences (311.40 ± 93.05 μg h/mL and 287.71 ± 45.31 μg h/mL, respectively). The results were similar for the T max (3.58 ± 0.90 h versus 3.42 ± 0.51 h). However, when comparing the mean C max some significant differences were found (8.73 ± 3.66 μg/mL and 10.43 ± 3.84 μg/mL, respectively). The 90% confidence intervals for the ratio of AUC0-∞ and T max values for the reference and test product are within the interval 80-125%, but the 90% confidence intervals for the ratio of C max falls outside the proposed interval. It was concluded that C max of test product are not within the 20% of those of the reference, thus suggesting that test OTC is not bioequivalent to the reference formulation. PMID:27446938

  9. Vouchers in Fragile States: Reducing Barriers to Long-Acting Reversible Contraception in Yemen and Pakistan

    PubMed Central

    Boddam-Whetham, Luke; Gul, Xaher; Al-Kobati, Eman; Gorter, Anna C

    2016-01-01

    ABSTRACT In conflict-affected states, vouchers have reduced barriers to reproductive health services and have enabled health programs to use targeted subsidies to increase uptake of specific health services. Vouchers can also be used to channel funds to public- and private-service providers and improve service quality. The Yamaan Foundation for Health and Social Development in Yemen and the Marie Stopes Society (MSS) in Pakistan—both working with Options Consultancy Services—have developed voucher programs that subsidize voluntary access to long-acting reversible contraceptives (LARCs) and permanent methods (PMs) of family planning in their respective fragile countries. The programs focus on LARCs and PMs because these methods are particularly difficult for poor women to access due to their cost and to provider biases against offering them. Using estimates of expected voluntary uptake of LARCs and PMs for 2014 based on contraceptive prevalence rates, and comparing these with uptake of LARCs and PMs through the voucher programs, we show the substantial increase in service utilization that vouchers can enable by contributing to an expanded method choice. In the governorate of Lahj, Yemen, vouchers for family planning led to an estimated 38% increase in 2014 over the expected use of LARCs and PMs (720 vs. 521 expected). We applied the same approach in 13 districts of Punjab, Khyber Pakhtunkhwa (KPK), and Sindh provinces in Pakistan. Our calculations suggest that vouchers enabled 10 times more women than expected to choose LARCs and PMs in 2014 in those areas of Pakistan (73,639 vs. 6,455 expected). Voucher programs can promote and maintain access to family planning services where existing health systems are hampered. Vouchers are a flexible financing approach that enable expansion of contraceptive choice and the inclusion of the private sector in service delivery to the poor. They can keep financial resources flowing where the public sector is prevented from

  10. A novel, long-acting glucagon-like peptide receptor-agonist: dulaglutide

    PubMed Central

    Gurung, Tara; Shyangdan, Deepson S; O’Hare, Joseph Paul; Waugh, Norman

    2015-01-01

    Background Dulaglutide is a new, long-acting glucagon-like peptide analogue in the treatment of type 2 diabetes. It is available in two doses, 0.75 and 1.5 mg, given by injection once weekly. This systematic review reports the effectiveness and safety of dulaglutide in type 2 diabetes in dual and triple therapy. Methods MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, and conference abstracts were searched from 2005 to August 2014, and updated in January 2015. Company websites and references of included studies were checked for potentially relevant studies. European Medicines Agency and US Food and Drug Administration websites were searched. Results Four trials were included. All were manufacturer-funded randomized controlled trials from the Assessment of Weekly Administration of Dulaglutide in Diabetes (AWARD) program. AWARD-1 compared dulaglutide 1.5 mg against exenatide 10 µg twice daily and placebo, AWARD-2 compared dulaglutide 0.75 and 1.5 mg against insulin glargine, AWARD-5 compared dulaglutide 0.75 and 1.5 mg against sitagliptin 100 mg and placebo, and AWARD-6 compared dulaglutide 1.5 mg against liraglutide 1.8 mg. The duration of follow-up in the trials ranged from 26 to 104 weeks. The primary outcome of all the included trials was change in HbA1c. At 26 weeks, greater HbA1c reductions were seen with dulaglutide than with twice daily exenatide (dulaglutide 1.5/0.75 mg: −1.5%/−1.3%; exe: 0.99%) and sitagliptin (1.5/0.75 mg −1.22%/−1.01%; sitagliptin: −0.6%). HbA1c change was greater with dulaglutide 1.5 mg (−1.08%) than with glargine (−0.63%), but not with dulaglutide 0.75 mg (−0.76%). Dulaglutide 1.5 mg was found to be noninferior to liraglutide 1.8 mg. More patients treated with dulaglutide achieved HbA1c targets of <7% and ≤6.5%. Reduction in weight was greater with dulaglutide than with sitagliptin and exenatide. Hypoglycemia was infrequent. The main adverse events were nausea, diarrhea, and vomiting. Conclusion

  11. A radio-ligand receptor assay for the long-acting thyroid stimulator. Inhibition by the long-acting thyroid stimulator of the binding of radioiodinated thyroid-stimulating hormone to human thyroid membranes.

    PubMed Central

    Mehdi, S Q; Nussey, S S

    1975-01-01

    Highly purified bovine TSH (thyroid-stimulating hormone) was labelled with 125I by using very low concentrations of chloramine-T. Human thyroid membranes prepared by discontinuous sucrose-density-gradient centrifugation were homogeneous on examination by electron microscopy. Incubation of radioiodinated TSH with the membranes showed that radioactivity could be bound to the membranes. Under the experimental conditions described here, binding was dependent on time and temperature and was a saturable phenomenon. Preincubation of the membranes with unlabelled hormone inhibited the subsequent binding of 125I-labelled TSH. Similarly, inhibition by the long-acting thyroid stimulator also showed a saturation behaviour. A rapid and sensitive method for the detection of the long-acting thyroid stimulator is described. Images PLATE 1 PLATE 2 PMID:1191248

  12. Effects of risperidone on cognitive-motor performance and motor movements in chronically medicated children.

    PubMed

    Aman, Michael G; Hollway, Jill A; Leone, Sarah; Masty, Jessica; Lindsay, Ronald; Nash, Patricia; Arnold, L Eugene

    2009-01-01

    This study was designed to explore the placebo-controlled effects of risperidone on cognitive-motor processes, dyskinetic movements, and behavior in children receiving maintenance risperidone therapy. Sixteen children aged 4-14 years with disruptive behavior were randomly assigned to drug order in a crossover study of risperidone and placebo for 2 weeks each. Dependent measures included tests of sustained attention, memory, visual matching, tremor, seat activity, abnormal movements, and parent behavior ratings. Results were compared by repeated measures ANOVA. Fourteen boys and 2 girls with disruptive behavior and IQRisperidone was superior to placebo on response time (p=0.01, eta(P)(2)=0.43) and seat movement (p<0.05, eta(P)(2)=0.29) on a short-term memory task, and on a measure of static tremor (p=0.05, eta(P)(2)=0.28). There was not a significant difference between treatment conditions on the Abnormal Involuntary Movement scale. Risperidone was superior to placebo on three subscales of the Nisonger Child Behavior Rating Form [Overly Sensitive (p<0.01, eta(P)(2)=0.44), Conduct Problem (p=0.02, eta(P)(2)=0.36), Hyperactivity (p=0.03, eta(P)(2)=0.32)] and on the Hyperactivity/Noncompliance subscale of the Aberrant Behavior Checklist (p=0.01, eta(P)(2)=0.41). Significant increases in heart rate (p=0.05, eta(P)(2)=0.27) and weight (p=0.02, eta(P)(2)=0.36) occurred in the risperidone condition. The findings suggest a beneficial effect of risperidone after several months of treatment on efficiency of responding, activity level, static tremor, and aspects of behavior.

  13. Multispecies resistance of cattle gastrointestinal nematodes to long-acting avermectin formulations in Mato Grosso do Sul.

    PubMed

    Borges, Fernando de Almeida; Borges, Dyego Gonçalves Lino; Heckler, Rafael Pereira; Neves, Juliana Paniago Lordello; Lopes, Fernando Gonçalves; Onizuka, Marcel Kenzo Vilalba

    2015-09-15

    The use of long-acting avermectins (AVMs) in cattle to treat infections with gastrointestinal nematodes was common in Brazil until its prohibition by state authorities. The prohibition; however, was rescinded in 2015, but a scientific discussion of the pros and cons of the use of these formulations is necessary. We evaluated the levels of resistance to 1.0 and 3.5% doramectin and to 3.15% ivermectin in cattle. The worms in animals treated with 3.5% doramectin were characterized by the suppression of oviposition and by a higher proportion of adult females carrying no eggs. Haemonchus placei, Cooperia punctata, C. pectinata, C. spatulata, and Oesophagostomum radiatum were resistant to the above compositions. The administration of long-acting AVM formulations did not result in a higher efficacy against these helminth populations.

  14. The Potential Role of Long-acting Injectable Antipsychotics in People with Schizophrenia and Comorbid Substance Use

    PubMed Central

    Koola, Maju Mathew; Wehring, Heidi J.; Kelly, Deanna L.

    2012-01-01

    Objective Treatment of schizophrenia in patients with comorbid substance use (alcohol/illicit drug use, abuse or dependence) presents challenges for public health systems. Substance use in people with schizophrenia is up to four times greater than the general population and is associated with medication nonadherence and poor outcomes. Therefore, continuous antipsychotic treatment in this population may pose more of a challenge than for those with schizophrenia alone. Many clinical trials and treatment recommendations in schizophrenia do not take into consideration substance use as people with comorbid substance use have typically been excluded from most antipsychotic trials. Nonetheless, antipsychotic treatment appears to be as efficacious in this population, although treatment discontinuation remains high. The objective of this review was to highlight the importance and utility of considering long-acting injectable antipsychotics for patients with schizophrenia and comorbid substance use. Methods We did a literature search using PubMed with key words schizophrenia and substance use/abuse/dependence, nonadherence, antipsychotics, long acting injectables, relapse, and psychosocial interventions. We limited our search to human studies published in English and 4,971 articles were identified. We focused on clinical trials, case reports, case series, reviews and meta-analyses resulting in 125 articles from 1975-2011. Results Our review suggests the potential role of long-acting injectables for people with comorbid substance use and schizophrenia in leading to improvements in psychopathology, relapse prevention, fewer rehospitalizations, and better outcomes. Conclusions While more research is needed, long-acting antipsychotics should be considered an important option in the management of people with schizophrenia and comorbid substance use. PMID:22754405

  15. Risperidone Improves Behavioral Symptoms in Children with Autism in a Randomized, Double-Blind, Placebo-Controlled Trial

    ERIC Educational Resources Information Center

    Pandina, Gahan J.; Bossie, Cynthia A.; Youssef, Eriene; Zhu, Young; Dunbar, Fiona

    2007-01-01

    Subgroup analysis of children (5-12 years) with autism enrolled in an 8-week, double-blind, placebo-controlled trial of risperidone for pervasive developmental disorders. The primary efficacy measure was the Aberrant Behavior Checklist-Irritability (ABC-I) subscale. Data were available for 55 children given risperidone (n = 27) or placebo (n =…

  16. Risperidone Augmentation for Treatment-Resistant Aggression in Attention-Deficit/Hyperactivity Disorder: A Placebo-Controlled Pilot Study

    ERIC Educational Resources Information Center

    Armenteros, Jorge L.; Lewis, John E.; Davalos, Marisabel

    2007-01-01

    Objective: To evaluate the effects of risperidone augmentation for treatment-resistant aggression in children with attention-deficit/hyperactivity disorder (ADHD). Method: Twenty-five children (ages 7-12 years) with attention-deficit/hyperactivity disorder(ADHD) and significant aggressive behaviors were randomized to risperidone or placebo for 4…

  17. Knowledge and perception on long acting and permanent contraceptive methods in adigrat town, tigray, northern ethiopia: a qualitative study.

    PubMed

    Gebremariam, Alem; Addissie, Adamu

    2014-01-01

    Background. Long acting and permanent contraceptive methods have the potential to reduce unintended pregnancies but the contraceptive choice and utilization in Ethiopia are highly dominated by short term contraceptives. Objective. To assess the knowledge and perception on long acting and permanent contraceptives of married women and men in Northern Ethiopia. Method. A qualitative method was conducted in Adigrat on January, 2012. Four focus group discussions with married women and men and six in-depth interviews with family planning providers were conducted. Content analysis was used to synthesize the data. Result. Participants' knowledge on long acting and permanent contraceptives is limited to recognizing the name of the methods. Most of the participants are not able to identify permanent methods as a method of contraception. They lack basic information on how these methods work and how they can use it. Women had fears and rumors about each of these methods. They prefer methods which do not require any procedure. Family planning providers stated as they have weakness on counseling of all contraceptive choices. Conclusion. There are personal barriers and knowledge gaps on these contraceptive methods. Improving the counseling service program can help women to increase knowledge and avoid misconceptions of each contraceptive choice.

  18. Knowledge and Perception on Long Acting and Permanent Contraceptive Methods in Adigrat Town, Tigray, Northern Ethiopia: A Qualitative Study

    PubMed Central

    Addissie, Adamu

    2014-01-01

    Background. Long acting and permanent contraceptive methods have the potential to reduce unintended pregnancies but the contraceptive choice and utilization in Ethiopia are highly dominated by short term contraceptives. Objective. To assess the knowledge and perception on long acting and permanent contraceptives of married women and men in Northern Ethiopia. Method. A qualitative method was conducted in Adigrat on January, 2012. Four focus group discussions with married women and men and six in-depth interviews with family planning providers were conducted. Content analysis was used to synthesize the data. Result. Participants' knowledge on long acting and permanent contraceptives is limited to recognizing the name of the methods. Most of the participants are not able to identify permanent methods as a method of contraception. They lack basic information on how these methods work and how they can use it. Women had fears and rumors about each of these methods. They prefer methods which do not require any procedure. Family planning providers stated as they have weakness on counseling of all contraceptive choices. Conclusion. There are personal barriers and knowledge gaps on these contraceptive methods. Improving the counseling service program can help women to increase knowledge and avoid misconceptions of each contraceptive choice. PMID:25140252

  19. Risperidone and NAP protect cognition and normalize gene expression in a schizophrenia mouse model.

    PubMed

    Vaisburd, Sinaya; Shemer, Zeev; Yeheskel, Adva; Giladi, Eliezer; Gozes, Illana

    2015-11-10

    Mutated disrupted in schizophrenia 1 (DISC1), a microtubule regulating protein, leads to schizophrenia and other psychiatric illnesses. It is hypothesized that microtubule stabilization may provide neuroprotection in schizophrenia. The NAP (NAPVSIPQ) sequence of activity-dependent neuroprotective protein (ADNP) contains the SxIP motif, microtubule end binding (EB) protein target, which is critical for microtubule dynamics leading to synaptic plasticity and neuroprotection. Bioinformatics prediction for FDA approved drugs mimicking SxIP-like motif which displace NAP-EB binding identified Risperidone. Risperidone or NAP effectively ameliorated object recognition deficits in the mutated DISC1 mouse model. NAP but not Risperidone, reduced anxiety in the mutated mice. Doxycycline, which blocked the expression of the mutated DISC1, did not reverse the phenotype. Transcripts of Forkhead-BOX P2 (Foxp2), a gene regulating DISC1 and associated with human ability to acquire a spoken language, were increased in the hippocampus of the DISC1 mutated mice and were significantly lowered after treatment with NAP, Risperidone, or the combination of both. Thus, the combination of NAP and standard of care Risperidone in humans may protect against language disturbances associated with negative and cognitive impairments in schizophrenia.

  20. Optimization and In Vivo Toxicity Evaluation of G4.5 Pamam Dendrimer-Risperidone Complexes

    PubMed Central

    Prieto, Maria Jimena; del Rio Zabala, Nahuel Eduardo; Marotta, Cristian Hernán; Carreño Gutierrez, Hector; Arévalo Arévalo, Rosario; Chiaramoni, Nadia Silvia; Alonso, Silvia del Valle

    2014-01-01

    Risperidone is an approved antipsychotic drug belonging to the chemical class of benzisoxazole. This drug has low solubility in aqueous medium and poor bioavailability due to extensive first-pass metabolism and high protein binding (>90%). Since new strategies to improve efficient treatments are needed, we studied the efficiency of anionic G4.5 PAMAM dendrimers as nanocarriers for this therapeutic drug. To this end, we explored dendrimer-risperidone complexation dependence on solvent concentration, pH and molar relationship. The best dendrimer-risperidone incorporation (46 risperidone molecules per dendrimer) was achieved with a mixture of chloroform:methanol 50∶50 v/v solution pH 3. In addition, to explore the possible effects of this complex, in vivo studies were carried out in the zebrafish model. Changes in the development of dopaminergic neurons and motoneurons were studied using tyrosine hydroxylase and calretinin, respectively. Physiological changes were studied through histological sections stained with hematoxylin-eosin to observe possible morphological brain changes. The most significant changes were observed when larvae were treated with free risperidone, and no changes were observed when larvae were treated with the complex. PMID:24587349

  1. Optimization and in vivo toxicity evaluation of G4.5 PAMAM dendrimer-risperidone complexes.

    PubMed

    Prieto, Maria Jimena; del Rio Zabala, Nahuel Eduardo; Marotta, Cristian Hernán; Carreño Gutierrez, Hector; Arévalo Arévalo, Rosario; Chiaramoni, Nadia Silvia; del Valle Alonso, Silvia

    2014-01-01

    Risperidone is an approved antipsychotic drug belonging to the chemical class of benzisoxazole. This drug has low solubility in aqueous medium and poor bioavailability due to extensive first-pass metabolism and high protein binding (>90%). Since new strategies to improve efficient treatments are needed, we studied the efficiency of anionic G4.5 PAMAM dendrimers as nanocarriers for this therapeutic drug. To this end, we explored dendrimer-risperidone complexation dependence on solvent concentration, pH and molar relationship. The best dendrimer-risperidone incorporation (46 risperidone molecules per dendrimer) was achieved with a mixture of chloroform:methanol 50∶50 v/v solution pH 3. In addition, to explore the possible effects of this complex, in vivo studies were carried out in the zebrafish model. Changes in the development of dopaminergic neurons and motoneurons were studied using tyrosine hydroxylase and calretinin, respectively. Physiological changes were studied through histological sections stained with hematoxylin-eosin to observe possible morphological brain changes. The most significant changes were observed when larvae were treated with free risperidone, and no changes were observed when larvae were treated with the complex. PMID:24587349

  2. Risperidone-induced weight gain and reduced locomotor activity in juvenile female rats: The role of histaminergic and NPY pathways.

    PubMed

    Lian, Jiamei; De Santis, Michael; He, Meng; Deng, Chao

    2015-01-01

    Second generation antipsychotic drugs (SGAs) such as risperidone are increasingly prescribed (mostly for off-label use) to children and adolescents for treating various mental disorders. SGAs cause serious weight gain/obesity and other metabolic side-effects. This study aimed to establish an animal model of risperidone-induced weight gain in female juvenile rats, and to investigate the effects of risperidone on the expression of hypothalamic histaminergic H1 receptors (H1R) and neuropeptides, and their association with weight gain. Female Sprague Dawley rats were treated orally with risperidone (0.3mg/kg, 3 times/day) or vehicle (control) starting from postnatal day (PD) 23 (±1 day) for 3 weeks (a period corresponding to the childhood-adolescent period in humans). In the female juvenile rats, risperidone treatment increased food intake and body weight gain, which started to appear after 12 days' treatment. Risperidone also significantly decreased the locomotor activity of the female rats. Consistently, risperidone significantly elevated mRNA expression of hypothalamic H1R, neuropeptide Y (NPY), and agouti-related peptide (AgRP) compared to controls, and H1R and NPY levels were correlated with risperidone enhanced weight gain and food intake in the female juvenile rats. However, risperidone did not affect hypothalamic proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA expression. Therefore, these results suggested that risperidone elevated appetite and body weight gain in juveniles via regulation of the hypothalamic H1R, NPY and AgRP pathways, as well as by reducing activity.

  3. Aripiprazole and Risperidone for Treatment of Methamphetamine-Associated Psychosis in Chinese Patients.

    PubMed

    Wang, Gang; Zhang, Yao; Zhang, Sheng; Chen, Huijing; Xu, Zaifeng; Schottenfeld, Richard S; Hao, Wei; Chawarski, Marek Cezary

    2016-03-01

    We evaluated tolerability and efficacy of aripiprazole and risperidone for treatment of methamphetamine (METH) associated psychotic symptoms in China. Patients with acute METH-associated psychotic symptoms (N=42) and with Positive and Negative Syndrome Scale (PANSS) total score between 60 and 120 were randomized to aripiprazole (initial dose 5-10mg per day followed by flexible doses 5-15 mg per day) or risperidone (initial dose 2-4 mg per day followed by flexible doses 4-6 mg per day) from day 3 to 25 of inpatient hospital stay. Outcome measures included PANSS and Clinical Global Impressions-Severity of Illness scale (CGI-S), METH craving Visual Analogue Scale (VAS), Simpson Angus Scale (SAS), Barnes Assessments Akathasia Rating Scale (BARS), and self-reported adverse effects evaluated during treatment. Retention was evaluated using Kaplan-Meier survival analysis and the MIXED models procedure was used to compare the groups on measures of psychotic and extra-pyramidal symptoms. Patients in both aripiprazole and risperidone groups showed statistically significant reductions in psychotic symptomatology from baseline during treatment (p<0.001) with no statistically significant differences between the treatment groups (p=0.73 and p=0.15, respectively). Risperidone-treated patients reported significantly greater METH craving reductions (p<0.001). Overall, 71% of patients completed the entire study, but the aripiprazole group had a significantly lower retention than the risperidone group (p=0.007), primarily due to medication related adverse effects. Aripiprazole-treated patients also had significantly more akathisia (p=0.03) and agitation (p=0.02) than risperidone-treated patients. Patients in both groups who tolerated their medications and completed the entire study achieved comparable reductions of psychotic symptoms.

  4. Comparison the effectiveness of aripiprazole and risperidone for the treatment of acute bipolar mania

    PubMed Central

    Rezayat, Amir Akhavan; Hebrani, Paria; Behdani, Fatemeh; Salaran, Mohamad; Marvast, Majid Nabizadeh

    2014-01-01

    Background: Second-generation antipsychotics, approved for the treatment of mania, are associated with adverse effects such as weight gain and metabolic disorders. Aripiprazole, a recently introduced second-generation antipsychotic, are thought to account for its low propensity for weight gain, metabolic disturbances and sedation. The purpose of this study was to investigate the effect of risperidone versus aripiprazole in the treatment of acute mania. Materials and Methods: Fifty patients with acute episodes of mania were enrolled in this study, and they were randomly assigned into a risperidone group of 24 cases and an aripiprazole group of 26 cases. In group A, aripiprazole with a dose of 5-30 mg/day and in group B, risperidone with a dose of 2-8 mg/day was given to patients. The average dose of aripiprazole was 27 mg/day, and the average dose of risperidone was 6 mg/day. The effects of each drug for the treatment of acute mania were assessed on the 1st day of admission and on days 2, 4, 6, 8 and at weeks 2, 4 and 6 after therapy using the young mania rating scale (YMRS) and at the baseline and on weeks 3 and 6 after admission using the clinical global impression (CGI) scale. Results: The mean age of the group of risperidone was 34 ± 8.6 years and in a group of aripiprazole it was 34 ± 9.1 years (P = 0.83). Comparison of YMRS scores over the period of 6 weeks revealed a statistically significant difference in both groups (P < 0.0001). There was also a statistically significant difference in YMRS scores between risperidone and aripiprazole at day 8 (P = 0.026) and weeks 2 (P = 0.035) and 4 (P = 0.042). There was also a statistically significant difference in CGI-Severity scale score at weeks 3 (P = 0.003) and 6 (P = 0.000) and in CGI-Improvement scale score at weeks 3 (P = 0.005) and 6 (P = 0.002). The most common side-effect observed in both groups was headache (0%15/4 in aripiprazole vs. %16/7 in risperidone) Conclusion: Aripiprazole that is readily available

  5. Prevalence and factors affecting use of long acting and permanent contraceptive methods in Jinka town, Southern Ethiopia: a cross sectional study

    PubMed Central

    Mekonnen, Getachew; Enquselassie, Fikre; Tesfaye, Gezahegn; Semahegn, Agumasie

    2014-01-01

    Introduction In Ethiopia, knowledge of contraceptive methods is high though there is low contraceptive prevalence rate. This study was aimed to assess prevalence and associated factors of long acting and permanent contraceptive methods in Jinka town, southern Ethiopia. Methods Community based cross sectional survey was conducted to assess the prevalence and factors affecting long acting and permanent methods of contraceptives utilization from March to April 2008. Eight hundred child bearing age women were participated in the quantitative study and 32 purposively selected focus group discussants were participated in the qualitative study. Face to face interview was used for data collection. Data were analyzed by SPSS version 13.0 statistical software. Descriptive statistics and logistic regression were computed to analyze the data. Results The prevalence of long acting and permanent contraceptive method was 7.3%. Three fourth (76.1%) of the women have ever heard about implants and implant 28 (50%) were the most widely used method. Almost two third of women had intention to use long acting and permanent methods. Knowledge of contraceptive and age of women have significant association with the use of long acting and permanent contraceptive methods. Conclusion The overall prevalence of long acting and permanent contraceptive method was low. Knowledge of contraceptive and age of women have significant association with use of long acting and permanent contraceptive. Extensive health information should be provided. PMID:25404960

  6. Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

    PubMed

    King, Nathan; Tran, Minh-Ha

    2015-10-01

    Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment

  7. Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

    PubMed

    King, Nathan; Tran, Minh-Ha

    2015-10-01

    Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment

  8. Effects of long-acting beta 2-adrenoceptor agonists on mast cells of rat, guinea pig, and human.

    PubMed

    Lau, H Y; Wong, P L; Lai, C K; Ho, J K

    1994-10-01

    The effects of two recently developed long-acting beta 2-adrenoceptor agonists, formoterol and salmeterol, on mast cells from different sources were compared with those of the prototype short-acting analogue, salbutamol. With the exception of high concentrations of salmeterol (> 10(-5) M), none of the tested beta 2-adrenoceptor agonists inhibited the anti-IgE-induced histamine release from rat peritoneal mast cells. In contrast, all three compounds dose dependently inhibited the immunologically induced histamine release from isolated lung mast cells of guinea pig and human at concentrations < or = 10(-5) M.

  9. Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure

    PubMed Central

    Bahr, Sarah M.; Weidemann, Benjamin J.; Castro, Ana N.; Walsh, John W.; deLeon, Orlando; Burnett, Colin M.L.; Pearson, Nicole A.; Murry, Daryl J.; Grobe, Justin L.; Kirby, John R.

    2015-01-01

    Risperidone is a second-generation antipsychotic that causes weight gain. We hypothesized that risperidone-induced shifts in the gut microbiome are mechanistically involved in its metabolic consequences. Wild-type female C57BL/6J mice treated with risperidone (80 μg/day) exhibited significant excess weight gain, due to reduced energy expenditure, which correlated with an altered gut microbiome. Fecal transplant from risperidone-treated mice caused a 16% reduction in total resting metabolic rate in naïve recipients, attributable to suppression of non-aerobic metabolism. Risperidone inhibited growth of cultured fecal bacteria grown anaerobically more than those grown aerobically. Finally, transplant of the fecal phage fraction from risperidone-treated mice was sufficient to cause excess weight gain in naïve recipients, again through reduced energy expenditure. Collectively, these data highlight a major role for the gut microbiome in weight gain following chronic use of risperidone, and specifically implicates the modulation of non-aerobic resting metabolism in this mechanism. PMID:26870798

  10. Enhancement of the anti-immobility action of antidepressants by risperidone in the forced swimming test in mice.

    PubMed

    Rogóż, Zofia; Kabziński, Marcin

    2011-01-01

    The aim of the present study was to examine the effect of antidepressants (ADs) belonging to different pharmacological groups and risperidone (an atypical antipsychotic drug), given separately or jointly, on immobility time in the forced swimming test in male C57BL/6J mice. The antidepressants: citalopram, fluvoxamine, sertraline, reboxetine, milnacipran (5 and 10 mg/kg), or risperidone in low doses (0.05 and 0.1 mg/kg) given alone did not change the immobility time of mice in the forced swimming test. Co-treatment with reboxetine or milnacipran (10 mg/kg) and risperidone in a lower dose of 0.05 mg/kg or with sertraline, reboxetine (5 and 10 mg/kg), citalopram, fluvoxamine, milnacipran (10 mg/kg) and risperidone in a higher dose of 0.1 mg/kg produced antidepressant-like effect in the forced swimming test. WAY100635 (a 5-HT(1A) receptor antagonist) inhibited the effects induced by co-administration of ADs and risperidone. Active behavior in the forced swimming test was not a consequence of an increased general activity, since the combined treatment with ADs and risperidone failed to enhance the locomotor activity of mice. The obtained results indicate that a low dose of risperidone enhances the activity of ADs in an animal model of depression, and that, among other mechanisms, 5-HT(1A) receptors may play a role in these effects. PMID:22358101

  11. Aripiprazole versus risperidone for treating children and adolescents with tic disorder: a randomized double blind clinical trial.

    PubMed

    Ghanizadeh, Ahmad; Haghighi, Alireza

    2014-10-01

    There are some uncontrolled studies about the efficacy and safety of both aripiprazole and risperidone for treating tic disorder. Moreover, the efficacy of these medications has never been compared. This is the first double blind randomized clinical trial comparing the safety and efficacy of aripiprazole and risperidone for treating patients with tic disorder. Sixty children and adolescents with tic disorder were randomly allocated into one of the two groups to receive either aripiprazole or risperidone for 2 months. The primary outcome measure was the score of Yale Global Tic Severity Scale. In addition, health related quality of life and adverse events were assessed. Both aripiprazole and risperidone decreased the Yale Global Tic Severity Scale score during this trial. Moreover, both medications increased the health related quality of life score. Both aripiprazole and risperidone were tolerated well. Aripiprazole [3.22 (1.9) mg/day] decreased tic score as much as risperidone [0.6 (0.2) mg/day]. Their adverse effects and their effects on health related quality of life were comparable. However, risperidone increased the patients' social functioning more than aripiprazole in short term.

  12. Enhancement of the anti-immobility action of antidepressants by risperidone in the forced swimming test in mice.

    PubMed

    Rogóż, Zofia; Kabziński, Marcin

    2011-01-01

    The aim of the present study was to examine the effect of antidepressants (ADs) belonging to different pharmacological groups and risperidone (an atypical antipsychotic drug), given separately or jointly, on immobility time in the forced swimming test in male C57BL/6J mice. The antidepressants: citalopram, fluvoxamine, sertraline, reboxetine, milnacipran (5 and 10 mg/kg), or risperidone in low doses (0.05 and 0.1 mg/kg) given alone did not change the immobility time of mice in the forced swimming test. Co-treatment with reboxetine or milnacipran (10 mg/kg) and risperidone in a lower dose of 0.05 mg/kg or with sertraline, reboxetine (5 and 10 mg/kg), citalopram, fluvoxamine, milnacipran (10 mg/kg) and risperidone in a higher dose of 0.1 mg/kg produced antidepressant-like effect in the forced swimming test. WAY100635 (a 5-HT(1A) receptor antagonist) inhibited the effects induced by co-administration of ADs and risperidone. Active behavior in the forced swimming test was not a consequence of an increased general activity, since the combined treatment with ADs and risperidone failed to enhance the locomotor activity of mice. The obtained results indicate that a low dose of risperidone enhances the activity of ADs in an animal model of depression, and that, among other mechanisms, 5-HT(1A) receptors may play a role in these effects.

  13. Can authorities appreciably enhance the prescribing of oral generic risperidone to conserve resources? Findings from across Europe and their implications

    PubMed Central

    2014-01-01

    Background Generic atypical antipsychotic drugs offer health authorities opportunities for considerable savings. However, schizophrenia and bipolar disorders are complex diseases that require tailored treatments. Consequently, generally there have been limited demand-side measures by health authorities to encourage the preferential prescribing of generics. This is unlike the situation with hypertension, hypercholaesterolaemia or acid-related stomach disorders. The objectives of this study were to compare the effect of the limited demand-side measures in Western European countries and regions on the subsequent prescribing of risperidone following generics; to utilise the findings to provide future guidance to health authorities; and where possible, to investigate the utilisation of generic versus originator risperidone and the prices for generic risperidone. Methods Principally, this was a segmented regression analysis of retrospective time-series data of the effect of the various initiatives in Belgium, Ireland, Scotland and Sweden following the introduction of generic risperidone. The study included patients prescribed at least one atypical antipsychotic drug up to 20 months before and up to 20 months after generic risperidone. In addition, retrospective observational studies were carried out in Austria and Spain (Catalonia) from 2005 to 2011 as well as one English primary care organisation (Bury Primary Care Trust (PCT)). Results There was a consistent steady reduction in risperidone as a percentage of total selected atypical antipsychotic utilisation following generics. A similar pattern was seen in Austria and Spain, with stable utilisation in one English PCT. However, there was considerable variation in the utilisation of generic risperidone, ranging from 98% of total risperidone in Scotland to only 14% in Ireland. Similarly, the price of generic risperidone varied considerably. In Scotland, generic risperidone was only 16% of pre-patent loss prices versus 72

  14. Medical treatment of uterine myoma with long-acting gonadotropin-releasing hormone agonist prior to myomectomy.

    PubMed

    Liu, C H; Lin, Y S; Lin, C C; Tzeng, C C; Chou, C Y

    1993-06-01

    A less bulky uterine myoma is technically easier to deal with during surgery. Recently gonadotropin-releasing hormone agonists (GnRH-a) have been used for the purpose of medical hypophysectomy, thereby reducing the size of uterine myomas. Ten premenopausal women with infertility and intramural-submucous myoma manifesting with menorrhagia and obstruction of the tubal ostia were recruited for this study. A long-acting depot GnRH-a, Decapeptyl, was given intramuscularly every four weeks for three months as an adjunct prior to myomectomy. Luteinizing hormone, follicular stimulating hormone and estradiol declined to the menopausal range following treatment. The size of the myoma decreased to a mean of 32.3 +/- 13.3% of the original volume. Myomectomy was performed in eight patients at the end of the study. Remarkably little blood loss was observed during the surgery. All of the patients had their uteri preserved, and six out of eight patients achieved pregnancy within 12 months after surgery. Our results indicate that monthly administration of long-acting GnRH-a significantly reduces the myoma volume and makes myomectomy technically easier to perform with the possibility of reduced complication rates and better preservation of future fertility.

  15. Long-acting injectables and risk for rehospitalization among patients with schizophrenia in the home care program in Taiwan.

    PubMed

    Ju, Po-Chung; Chou, Frank Huang-Chih; Lai, Te-Jen; Chuang, Po-Ya; Lin, Yung-Jung; Yang, Ching-Wen Wendy; Tang, Chao-Hsiun

    2014-02-01

    We aimed at evaluating the relationship between medication and treatment effectiveness in a home care setting among patients with schizophrenia. Patients with schizophrenia hospitalized between 2004 and 2009 with a primary International Classification of Diseases, Ninth Revision, Clinical Modification code of 295 were identified from Psychiatric Inpatient Medical Claims Data released by the National Health Research Institute in Taiwan. Patients who joined the home care program after discharge and were prescribed long-acting injection (LAI) (the LAI group) or oral antipsychotic medications (the oral group) were included as study subjects. The final sample for the study included 810 participants in the LAI group and 945 in the oral group. Logistic regression was performed to examine the independent effect of LAI medication on the risk for rehospitalization within the 12-month observation window after controlling for patient and hospital characteristics and propensity score quintile adjustment. The unadjusted odds ratio for rehospitalization risk was 0.80 (confidence interval, 0.65-0.98) for the LAI group compared to the oral group. The adjusted odds ratio was further reduced to 0.78 (confidence interval, 0.63-0.97). Results remained unchanged when the propensity score quintiles were entered into the regression for further adjustment. In a home care setting, patients treated with long-acting antipsychotic agents are at a significantly lower risk for psychiatric rehospitalization than those treated with oral medication. Consequently, LAI home-based treatment for the prevention of schizophrenia relapse may lead to substantial clinical and economic benefits. PMID:24145217

  16. Long-acting injectables and risk for rehospitalization among patients with schizophrenia in the home care program in Taiwan.

    PubMed

    Ju, Po-Chung; Chou, Frank Huang-Chih; Lai, Te-Jen; Chuang, Po-Ya; Lin, Yung-Jung; Yang, Ching-Wen Wendy; Tang, Chao-Hsiun

    2014-02-01

    We aimed at evaluating the relationship between medication and treatment effectiveness in a home care setting among patients with schizophrenia. Patients with schizophrenia hospitalized between 2004 and 2009 with a primary International Classification of Diseases, Ninth Revision, Clinical Modification code of 295 were identified from Psychiatric Inpatient Medical Claims Data released by the National Health Research Institute in Taiwan. Patients who joined the home care program after discharge and were prescribed long-acting injection (LAI) (the LAI group) or oral antipsychotic medications (the oral group) were included as study subjects. The final sample for the study included 810 participants in the LAI group and 945 in the oral group. Logistic regression was performed to examine the independent effect of LAI medication on the risk for rehospitalization within the 12-month observation window after controlling for patient and hospital characteristics and propensity score quintile adjustment. The unadjusted odds ratio for rehospitalization risk was 0.80 (confidence interval, 0.65-0.98) for the LAI group compared to the oral group. The adjusted odds ratio was further reduced to 0.78 (confidence interval, 0.63-0.97). Results remained unchanged when the propensity score quintiles were entered into the regression for further adjustment. In a home care setting, patients treated with long-acting antipsychotic agents are at a significantly lower risk for psychiatric rehospitalization than those treated with oral medication. Consequently, LAI home-based treatment for the prevention of schizophrenia relapse may lead to substantial clinical and economic benefits.

  17. Pharmacokinetics of a long-acting oxytetracycline preparation in ring-necked pheasants, great horned owls, and Amazon parrots.

    PubMed

    Teare, J A; Schwark, W S; Shin, S J; Graham, D L

    1985-12-01

    After a single IV or IM dose of a long-acting oxytetracycline (OTC) preparation, serum concentrations were determined at various times in the ring-necked pheasant, great horned owl, and Amazon parrot. Pharmacokinetic parameters, including serum half-life (t1/2) and apparent volume of distribution (Vd) were calculated from the OTC concentration-time curves for each species and route of administration. Significant differences (P less than 0.05) were found in the t1/2 and Vd parameters between species and routes of administration. Dosage regimens to maintain minimum OTC concentration of 5 micrograms/ml of serum were calculated from the t 1/2 and Vd values obtained, using steady-state pharmacokinetics. In the pheasant, the calculated mean IV dose was 23 mg/kg of body weight every 6 hours, whereas the mean IM dose was 43 mg/kg every 24 hours. The mean IM dose was 16 mg/kg every 24 hours for the owl and 58 mg/kg every 24 hours for the parrot. The small volumes required for treatment, the long-dosing interval obtainable, and the broad spectrum of antimicrobial activity of the long-acting OTC preparation studied offered major advantages over other antibiotics commonly used in treating avian species. PMID:4083606

  18. Open, randomized trial of the effects of aripiprazole versus risperidone on social cognition in schizophrenia.

    PubMed

    Maat, Arija; Cahn, Wiepke; Gijsman, Harm J; Hovens, Johannes E; Kahn, René S; Aleman, André

    2014-04-01

    To date, only few studies have examined the impact of medication on social cognition and none have examined the effects of aripiprazole in this respect. The goal of this 8-week, randomized, multicenter, open-label study was to examine the effects of aripiprazole and risperidone on social cognition and neurocognition in individuals with schizophrenia. Eighty schizophrenia patients (DSM-IV-TR) aged 16-50 years were administered multiple computerized measures of social cognition and neurocognition including reaction times at baseline and the end of week 8. Social functioning was mapped with the Social Functioning scale and Quality of Life scale. The study ran from June 2005 to March 2011. Scores on social cognitive and neurocognitive tests improved with both treatments, as did reaction time. There were few differences between the two antipsychotics on (social) cognitive test-scores. The aripiprazole group performed better (more correct items) on symbol substitution (P=.003). Aripiprazole was also superior to risperidone on reaction time for emotional working memory and working memory (P=.006 and P=.023, respectively). Improvements on these tests were correlated with social functioning. In conclusion, aripiprazole and risperidone showed a similar impact on social cognitive test-scores. However, aripiprazole treatment produced a greater effect on patients' processing speed compared to risperidone, with these improvements being associated with concurrent improvements in social functioning. Further research on the long-term effects of aripiprazole on cognition is warranted.

  19. Pregnancy exposure to olanzapine, quetiapine, risperidone, aripiprazole and risk of congenital malformations. A systematic review.

    PubMed

    Ennis, Zandra Nymand; Damkier, Per

    2015-04-01

    To review available data on first-trimester exposure to olanzapine, quetiapine, risperidone and aripiprazole and risk of congenital malformations. We performed a systematic literature search in accordance with PRISMA guidelines identifying studies containing original data on first-trimester exposure and pregnancy outcome with respect to congenital malformations. Cumulated data for olanzapine were 1090 first-trimester-exposed pregnancies with 38 malformations resulting in a malformation rate of 3.5%. The corresponding numbers for quetiapine, risperidone and aripiprazole were 443/16 (3.6%), 432/22 (5.1%) and 100/5 (5.0%), respectively. Relative risk estimates and 95% confidence intervals were 1.0 (0.7-1.4) (olanzapine), 1.0 (0.6-1.7) (quetiapine), 1.5 (0.9-2.2) (risperidone) and 1.4 (0.5-3.1) (aripiprazole). First-trimester exposure to olanzapine is not associated with an increased risk of congenital malformation. Data for quetiapine and risperidone do not suggest a substantially increased risk, while the risk estimate for aripiprazole remains imprecise owing to a low amount of data.

  20. [Risperidone treatment for polydipsia and severe hyponatremia in a schizophrenic patient].

    PubMed

    Chhoumi, Maha; Mrad, Amel; Mechri, Anwar

    2015-01-01

    We report the case of a patient with undifferentiated schizophrenia since 10 years, who presented a polydipsia and severe hyponatremia. This patient responded well to a combination of an atypical antipsychotic (risperidone 4 mg/day) and a behavioral approach based on fluid restriction.

  1. Effects of Risperidone on Aberrant Behavior in Persons with Developmental Disabilities: II. Social Validity Measures.

    ERIC Educational Resources Information Center

    McAdam, David B.; Zarcone, Jennifer R.; Hellings, Jessica; Napolitano, Deborah A.; Schroeder, Stephen R.

    2002-01-01

    Consumer satisfaction and social validity were measured during a double-blind, placebo-controlled evaluation of risperidone in treating aberrant behaviors of persons with developmental disabilities. A survey showed all 17 caregivers felt participation was positive. Community members (n=52) also indicated that when on medication, the 5 participants…

  2. Tic Reduction with Risperidone Versus Pimozide in a Randomized, Double-Blind, Crossover Trial

    ERIC Educational Resources Information Center

    Gilbert, Donald L.; Batterson, J. Robert; Sethuraman, Gopalan; Sallee, Floyd R.

    2004-01-01

    Objective: To compare the tic suppression, electrocardiogram (ECG) changes, weight gain, and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders. Method: This was a randomized, double-blind, crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17 years with Tourette's or chronic…

  3. Polypyrrole Film as a Drug Delivery System for the Controlled Release of Risperidone

    NASA Astrophysics Data System (ADS)

    Svirskis, Darren; Travas-Sejdic, Jadranka; Rodgers, Anthony; Garg, Sanjay

    2009-07-01

    Conducting polymers are finding applications in medicine including drug delivery systems, biosensors and templates for the regeneration of nervous pathways. We aim to develop a novel system where the drug release rate can be controlled by electrical stimulation. Polypyrrole (PPY) is being used as a drug delivery system due to its inherent electrical conductivity, ease of preparation and apparent biocompatibility. Risperidone is an atypical antipsychotic drug used in the treatment of psychosis and related disorders, including schizophrenia. PPY was synthesised using p-toluene sulfonic acid as a primary dopant, in the presence of risperidone. A validated high performance liquid chromatography (HPLC) analytical method was used to quantify risperidone release. It has been demonstrated that the release rate of risperidone can be altered through the application, or absence, of electrical stimulation. Technology such as this would find use in drug-delivering implants where the dose could be adjusted through application of external stimulus, optimising benefit to side effect ratio, while simultaneously ensuring patient adherence (which is a particular challenge in mental health conditions).

  4. Sustained release of risperidone from biodegradable microspheres prepared by in-situ suspension-evaporation process.

    PubMed

    An, Taekun; Choi, Juhyuen; Kim, Aram; Lee, Jin Ho; Nam, Yoonjin; Park, Junsung; Sun, Bo kyung; Suh, Hearan; Kim, Cherng-ju; Hwang, Sung-Joo

    2016-04-30

    Risperidone-loaded poly (D,L-lactide-co-glycolide) (PLGA) microspheres were prepared with a suspension-evaporation process with an aqueous suspension containing an in situ-formed aluminum hydroxide inorganic gel (SEP-AL process) and evaluated for encapsulation efficiency, particle size, surface morphology, glass transition temperature, in vitro drug release profile, and in vivo behavior. The SEP-AL microspheres were compared with conventional oil-in-water (O/W) emulsion solvent evaporation method using polyvinylalcohol (PVA) as an emulsifier (CP-PVA process). The microspheres were spherical in shape. DSC measurements showed that risperidone crystallinity was greatly reduced due to the homogeneous distribution of risperidone in PLGA microspheres. In vitro drug release profile from the microspheres showed a sigmoidal pattern of negligible initial burst up to 24h and minimal release (time-lag) for 7 days. After the lag phase, slow release took a place up to 25 days and then rapid release occurred sharply for 1 week. In vivo rat pharmacokinetic profile from the microspheres showed very low blood concentration level at the initial phase (up to 24h) followed by the latent phase up to 21 days. At the 3rd week, main phase started and the blood concentration of the drug increased up to the 5th week, and then gradually decreased. The risperidone-loaded PLGA microspheres produced by SEP-AL process showed excellent controlled release characteristics for the effective treatment of schizophrenia patients. PMID:26899975

  5. Long-Term Effects of Risperidone in Children with Autism Spectrum Disorders: A Placebo Discontinuation Study

    ERIC Educational Resources Information Center

    Troost, Pieter W.; Lahuis, Bertine E.; Steenhuis, Mark-Peter; Ketelaars, Cees E. J.; Buitelaar, Jan K.; van Engeland, Herman; Scahill, Lawrence; Minderaa, Ruud B.; Hoekstra, Pieter J.

    2005-01-01

    Objective: The short-term benefit of risperidone in ameliorating severe disruptive behavior in pediatric patients with autism spectrum disorders is well established; however, only one placebo-controlled, long-term study of efficacy is available. Method: Thirty-six children with an autism spectrum disorder (5-17 years old) accompanied by severe…

  6. Abnormalities in large scale functional networks in unmedicated patients with schizophrenia and effects of risperidone

    PubMed Central

    Kraguljac, Nina Vanessa; White, David Matthew; Hadley, Jennifer Ann; Visscher, Kristina; Knight, David; ver Hoef, Lawrence; Falola, Blessing; Lahti, Adrienne Carol

    2015-01-01

    Objective To describe abnormalities in large scale functional networks in unmedicated patients with schizophrenia and to examine effects of risperidone on networks. Material and methods 34 unmedicated patients with schizophrenia and 34 matched healthy controls were enrolled in this longitudinal study. We collected resting state functional MRI data with a 3T scanner at baseline and six weeks after they were started on risperidone. In addition, a group of 19 healthy controls were scanned twice six weeks apart. Four large scale networks, the dorsal attention network, executive control network, salience network, and default mode network were identified with seed based functional connectivity analyses. Group differences in connectivity, as well as changes in connectivity over time, were assessed on the group's participant level functional connectivity maps. Results In unmedicated patients with schizophrenia we found resting state connectivity to be increased in the dorsal attention network, executive control network, and salience network relative to control participants, but not the default mode network. Dysconnectivity was attenuated after six weeks of treatment only in the dorsal attention network. Baseline connectivity in this network was also related to clinical response at six weeks of treatment with risperidone. Conclusions Our results demonstrate abnormalities in large scale functional networks in patients with schizophrenia that are modulated by risperidone only to a certain extent, underscoring the dire need for development of novel antipsychotic medications that have the ability to alleviate symptoms through attenuation of dysconnectivity. PMID:26793436

  7. Prolactin variations during risperidone therapy in a sample of drug-naive children and adolescents

    PubMed Central

    Matera, Emilia; Petruzzelli, Maria G.; Simone, Marta; Lamanna, Anna L.; Pastore, Adriana; Palmieri, Vincenzo O.; Margari, Francesco

    2015-01-01

    The aim of this prospective observational study was to investigate the variations of serum prolactin hormone (PRL) in a sample of 34 drug-naive patients (mean age 13 years) who started risperidone therapy assuming that several factors may favor the increase in serum PRL. Serum PRL and hyperprolactinemia clinical signs were examined at baseline (T0) and after almost 3 months of treatment (T1). We considered sex, pubertal status, risperidone dosage, psychiatric diagnosis, and any personal/family history of autoimmune diseases. The mean serum PRL value increased between T0 and T1 (P=0.004). The mean serum PRL was higher in females in the pubertal/postpubertal stage and for risperidone dosage up 1 mg/day. Hyperprolactinemia was found in 20% of patients at T0 and in 38% of patients at T1 (P=0.03). The mean serum PRL increase was greater in early-onset schizophrenia spectrum psychosis patients compared with no-early-onset schizophrenia spectrum psychosis patients (P=0.04). The increase in PRL was higher in patients with a personal and a family history of autoimmune diseases. This study suggests that the increase in serum PRL in patients treated with risperidone may be linked not only to the drug and its dosage but also to several risk factors such as sex, pubertal stage, psychiatric disease, and autoimmune disorders. PMID:25514607

  8. A Crossover Study of Risperidone in Children, Adolescents and Adults with Mental Retardation

    ERIC Educational Resources Information Center

    Hellings, Jessica A.; Zarcone, Jennifer R.; Reese, R. Matthew; Valdovinos, Maria G.; Marquis, Janet G.; Fleming, Kandace K.; Schroeder, Stephen R.

    2006-01-01

    Risperidone has shown safety and efficacy for aggressive and destructive behaviors in short-term studies. This longer-duration study includes a broad sample. Forty subjects, aged 8-56 years (mean=22), all with mental retardation and 36 with autism spectrum disorders participated in this 22-week crossover study, with 24 weeks of open maintenance…

  9. Paediatric European Risperidone Studies (PERS): context, rationale, objectives, strategy, and challenges.

    PubMed

    Glennon, Jeffrey; Purper-Ouakil, Diane; Bakker, Mireille; Zuddas, Alessandro; Hoekstra, Pieter; Schulze, Ulrike; Castro-Fornieles, Josefina; Santosh, Paramala J; Arango, Celso; Kölch, Michael; Coghill, David; Flamarique, Itziar; Penzol, Maria J; Wan, Mandy; Murray, Macey; Wong, Ian C K; Danckaerts, Marina; Bonnot, Olivier; Falissard, Bruno; Masi, Gabriele; Fegert, Jörg M; Vicari, Stefano; Carucci, Sara; Dittmann, Ralf W; Buitelaar, Jan K

    2014-12-01

    In children and adolescents with conduct disorder (CD), pharmacotherapy is considered when non-pharmacological interventions do not improve symptoms and functional impairment. Risperidone, a second-generation antipsychotic is increasingly prescribed off-label in this indication, but its efficacy and tolerability is poorly studied in CD, especially in young people with normal intelligence. The Paediatric European Risperidone Studies (PERS) include a series of trials to assess short-term efficacy, tolerability and maintenance effects of risperidone in children and adolescents with CD and normal intelligence as well as long-term tolerability in a 2-year pharmacovigilance. In addition to its core studies, secondary PERS analyses will examine moderators of drug effects. As PERS is a large-scale academic project involving a collaborative network of expert centres from different countries, it is expected that results will lead to strengthen the evidence base for the use of risperidone in CD and improve standards of care. Challenging issues faced by the PERS consortium are described to facilitate future developments in paediatric neuropsychopharmacology.

  10. Dietary Status and Impact of Risperidone on Nutritional Balance in Children with Autism: A Pilot Study

    ERIC Educational Resources Information Center

    Lindsay, Ronald L.; Arnold, L. Eugene; Aman, Michael G.; Vitiello, Benedetto; Posey, David J.; McDougle, Christopher J.; Scahill, Lawrence; Pachler, Maryellen; McCracken, James T.; Tierney, Elaine; Bozzolo, Dawn

    2006-01-01

    Background: Risperidone may be effective in improving tantrums, aggression, or self-injurious behaviour in children with autism, but often leads to weight gain. Method: Using a quantitative Food Frequency Questionnaire (FFQ), we prospectively examined the nutritional intake of 20 children with autism participating in a randomised…

  11. Celecoxib and omega-3 fatty acids alone and in combination with risperidone affect the behavior and brain biochemistry in amphetamine-induced model of schizophrenia.

    PubMed

    El-Sayed El-Sisi, Alaa; Sokkar, Samia Salem; El-Sayed El-Sayad, Magda; Sayed Ramadan, Ehab; Osman, Enass Yossef

    2016-08-01

    The implications of oxidative stress and neuro-inflammation in the pathogenesis of schizophrenia have been elucidated. Despite their effectiveness against positive symptoms of schizophrenia, antipsychotics have limited effectiveness against negative and cognitive symptoms and are associated with remarkable adverse effects. The use of celecoxib or omega-3 in schizophrenia may have beneficial effects. This study aimed to evaluate the possible efficacies of celecoxib, omega-3 or the combination of celecoxib+risperidone and omega-3+ risperidone compared to risperidone on the behavior and brain biochemistry in rats. In the present study, an amphetamine-induced model of schizophrenia in adult male rats was used to evaluate the effects of celecoxib, omega-3, celecoxib+risperidone and omega-3+ risperidone on the behavior of animals and on brain lipid peroxidation or tumor necrosis factor-alpha. In the water maze task, celecoxib, omega-3, celecoxib+risperidone, omega-3+ risperidone significantly decreased the latency time compared to amphetamine-treated group. Celecoxib, omega-3, celecoxib+risperidone, omega-3+risperidone also significantly reversed the decreased spontaneous alternation induced by amphetamine in the Y-maze task. In the social interaction task, groups treated with celecoxib, omega-3, celecoxib+risperidone, omega-3+ risperidone spent less time to recognize foreign animals than animals in the amphetamine-treated group. Increased brain MDA and TNF-α levels due to amphetamine were significantly reduced in groups treated with celecoxib+risperidone or omega-3+ risperidone. The present findings showed that celecoxib or omega-3 can attenuate amphetamine- induced behavioral impairment and these effects may be associated with their ability to decrease lipid peroxidation and cytokine release. Celecoxib or omega-3 may be promising candidates as adjuvant therapy for schizophrenia.

  12. Sexual Dysfunction in Male Subjects Receiving Trifluoperazine, Risperidone, or Olanzapine: Rates Vary With Assessment Questionnaire

    PubMed Central

    Nebhinani, Naresh; Avasthi, Ajit

    2012-01-01

    Objective: To assess the rate and typology of sexual dysfunction in male subjects receiving trifluoperazine, risperidone, or olanzapine using the Arizona Sexual Experience Scale (ASEX), the Psychotropic Related Sexual Dysfunction Questionnaire (PRSexDQ), and the sexual function section of the modified Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (UKU). Method: The sample included 100 men with psychotic disorders (F2 category of the ICD-10) and receiving trifluoperazine (n = 20), risperidone (n = 30), or olanzapine (n = 50) for at least 3 months’ duration. Subjects with a history of sexual dysfunction prior to antipsychotic intake or chronic medical illness were excluded. A cross-sectional design was employed, and data were collected over a 1½-year period from March 2009 to August 2010. Results: The rate of sexual dysfunction varied from scale to scale among the 100 subjects. The rate of sexual dysfunction was 25% on the ASEX, 37% on the PRSexDQ, and 40% on the UKU. Sexual dysfunction in the trifluoperazine, risperidone, and olanzapine groups was 20%, 43%, and 16%, respectively, on the ASEX; 35%, 50%, and 30%, respectively, on the PRSexDQ; and 40%, 50%, and 34%, respectively, on the UKU. The most common sexual dysfunction as assessed on all scales was decreased libido, except for the risperidone group on the ASEX. Conclusions: Sexual dysfunction is quite prevalent in subjects receiving antipsychotic medications. In our study, rate of sexual dysfunction was highest for risperidone, followed by trifluoperazine and olanzapine. However, the rate of sexual dysfunction varied from scale to scale. Hence, there is a need for a comprehensive instrument to assess sexual dysfunction in patients receiving antipsychotics. PMID:22943029

  13. Patterns of faecal nematode egg shedding after treatment of sheep with a long-acting formulation of moxidectin.

    PubMed

    Crilly, James Patrick; Jennings, Amy; Sargison, Neil

    2015-09-15

    Much of the current information on the effects of long-acting anthelmintics on nematode populations derives either from research farms or mathematical models. A survey was performed with the aim of establishing how moxidectin is currently being used on sheep farms in the south-east of Scotland. A study was undertaken on a subsection of the surveyed farms to examine the effects of long-acting moxidectin treatments in both spring and autumn on faecal nematode egg output. The survey showed that whole flock treatments of injectable 2% moxidectin were used to control sheep scab on 21% of farms. Injectable 2% moxidectin and oral moxidectin were used to control the periparturient rise in faecal nematode egg shedding by ewes on 13% and 55% of farms respectively. The effects of injectable 2% moxidectin treatment on faecal nematode egg shedding post-treatment in both the autumn and spring were investigated by faecal nematode egg counts at the time of treatment and at 2-weekly interval thereafter on eight and six farms in the autumn and spring, respectively. Faecal egg shedding recommenced at 8 weeks (autumn) and 4 weeks (spring) post-treatment. Counts increased to a peak and then declined. The mean (95% confidence interval) peak counts post-treatment were 2.8 (0.6, 5.1), 3.6 (1.7, 5.5) and 53.5 (25.1, 82.0) eggs per gram (EPG) for autumn-treated ewes, autumn-treated lambs and spring-treated ewes respectively. The spring treated sheep showed a statistically significantly earlier return to faecal egg shedding (p=0.0125, p=0.0342) compared to both other groups, statistically significantly higher peak in egg counts than the autumn treated sheep (p<0.001) and a statistically significantly longer period of positive egg counts (p=0.0148). There was no statistically significant difference in the timing of the peak FECs between autumn and spring (p=0.211). The FECs of all groups of sheep treated with an injectable long-acting formulation of moxidectin became positive earlier than

  14. Trabecular bone loss after administration of the second-generation antipsychotic risperidone is independent of weight gain.

    PubMed

    Motyl, Katherine J; Dick-de-Paula, Ingrid; Maloney, Ann E; Lotinun, Sutada; Bornstein, Sheila; de Paula, Francisco J A; Baron, Roland; Houseknecht, Karen L; Rosen, Clifford J

    2012-02-01

    Second generation antipsychotics (SGAs) have been linked to metabolic and bone disorders in clinical studies, but the mechanisms of these side effects remain unclear. Additionally, no studies have examined whether SGAs cause bone loss in mice. Using in vivo and in vitro modeling we examined the effects of risperidone, the most commonly prescribed SGA, on bone in C57BL6/J (B6) mice. Mice were treated with risperidone orally by food supplementation at a dose of 1.25 mg/kg daily for 5 and 8 weeks, starting at 3.5 weeks of age. Risperidone reduced trabecular BV/TV, trabecular number and percent cortical area. Trabecular histomorphometry demonstrated increased resorption parameters, with no change in osteoblast number or function. Risperidone also altered adipose tissue distribution such that white adipose tissue mass was reduced and liver had significantly higher lipid infiltration. Next, in order to tightly control risperidone exposure, we administered risperidone by chronic subcutaneous infusion with osmotic minipumps (0.5 mg/kg daily for 4 weeks) in 7 week old female B6 mice. Similar trabecular and cortical bone differences were observed compared to the orally treated groups (reduced trabecular BV/TV, and connectivity density, and reduced percent cortical area) with no change in body mass, percent body fat, glucose tolerance or insulin sensitivity. Unlike in orally treated mice, risperidone infusion reduced bone formation parameters (serum P1NP, MAR and BFR/BV). Resorption parameters were elevated, but this increase did not reach statistical significance. To determine if risperidone could directly affect bone cells, primary bone marrow cells were cultured with osteoclast or osteoblast differentiation media. Risperidone was added to culture medium in clinically relevant doses of 0, 2.5 or 25 ng/ml. The number of osteoclasts was significantly increased by addition in vitro of risperidone while osteoblast differentiation was not altered. These studies indicate that

  15. Improving Access to Long-Acting Contraceptive Methods and Reducing Unplanned Pregnancy Among Women with Substance Use Disorders.

    PubMed

    Black, Kirsten I; Day, Carolyn A

    2016-01-01

    Much has been written about the consequences of substance use in pregnancy, but there has been far less focus on the prevention of unintended pregnancies in women with substance use disorders (SUDs). We examine the literature on pregnancy incidence for women with SUDs, the clinical and economic benefits of increasing access to long-acting reversible contraceptive (LARC) methods in this population, and the current hurdles to increased access and uptake. High rates of unintended pregnancies and poor physical and psychosocial outcomes among women with SUDs underscore the need for increased access to, and uptake of, LARC methods among these women. A small number of studies that focused on improving access to contraception, especially LARC, via integrated contraception services predominantly provided in drug treatment programs were identified. However, a number of barriers remain, highlighting that much more research is needed in this area. PMID:27199563

  16. Quantitative determination of amorphous nicardipine hydrochloride in long acting formula (NIC-LA) using light anhydrous silicic acid.

    PubMed

    Kohinata, Takeru; Fujii, Mitsuo; Nakamura, Souichiro; Hamada, Noritaka; Yonemochi, Etsuo; Terada, Katsuhide

    2004-12-01

    We investigated a method to quantitatively determine amorphous nicardipine hydrochloride (NIC) in the NIC-long acting formula (LA) model formulas prepared using NIC, light anhydrous silicic acid (LASA) and carboxymethylethylcellulose (CMEC). Consequently, since the quantity of total NIC in the formula can be determined by means of HPLC and crystal NIC can be determined by the differential scanning calorimetry (DSC) method because the heat of fusion (85.08 J/g) of NIC is constant and unaffected by excipients, we developed the HPLC-DSC method by which the quantity of amorphous NIC is calculated as the difference between the quantity of total NIC determined by HPLC and the quantity of crystal NIC determined by DSC. This practical HPLC-DSC method was confirmed to have good accuracy and reproducibility.

  17. PHARMACOKINETIC EVALUATION OF A LONG-ACTING FENTANYL SOLUTION AFTER TRANSDERMAL ADMINISTRATION IN HELMETED GUINEAFOWL (NUMIDA MELEAGRIS).

    PubMed

    Waugh, Lynnette; Knych, Heather; Cole, Gretchen; D'Agostino, Jennifer

    2016-06-01

    The objective of this study was to investigate the pharmacokinetics of a long-acting fentanyl solution in helmeted guineafowl ( Numida meleagris ) after transdermal administration. Twenty-one guineafowl received a single administration of 5 mg/kg of fentanyl transdermal solution. No adverse effects on behavior were appreciated. Plasma fentanyl concentrations were determined by liquid chromatography-mass spectrometry analysis of protein-precipitated samples. Mean maximum plasma concentration was 228.8 ng/ml at 4 hr. The mean plasma terminal half-life was 33.2 hr. At 168 hr the mean plasma concentration was 1.3 ng/ml. A single topical dose of 5 mg/kg appears to be safe for use in this species and maintained plasma concentrations above those reported to be analgesic in dogs for at least 7 days.

  18. Improving Access to Long-Acting Contraceptive Methods and Reducing Unplanned Pregnancy Among Women with Substance Use Disorders

    PubMed Central

    Black, Kirsten I.; Day, Carolyn A.

    2016-01-01

    Much has been written about the consequences of substance use in pregnancy, but there has been far less focus on the prevention of unintended pregnancies in women with substance use disorders (SUDs). We examine the literature on pregnancy incidence for women with SUDs, the clinical and economic benefits of increasing access to long-acting reversible contraceptive (LARC) methods in this population, and the current hurdles to increased access and uptake. High rates of unintended pregnancies and poor physical and psychosocial outcomes among women with SUDs underscore the need for increased access to, and uptake of, LARC methods among these women. A small number of studies that focused on improving access to contraception, especially LARC, via integrated contraception services predominantly provided in drug treatment programs were identified. However, a number of barriers remain, highlighting that much more research is needed in this area. PMID:27199563

  19. Provider Bias in Long-Acting Reversible Contraception (LARC) Promotion and Removal: Perceptions of Young Adult Women

    PubMed Central

    Kramer, Renee D.; Ryder, Kristin M.

    2016-01-01

    Long-acting reversible contraception (LARC) is effective and acceptable. However, concern exists about potential provider bias in LARC promotion. No study has documented contraceptive users’ attitudes toward or experiences with provider influence and bias regarding LARC. We collected qualitative data in 2014 to address this gap. Participants were 50 young adult women with any history of contraceptive use (including LARC) in Dane County, Wisconsin. Women often described providers as a trusted source of contraceptive information. However, several women reported that their preferences regarding contraceptive selection or removal were not honored. Furthermore, many participants believed that providers recommend LARC disproportionately to socially marginalized women. We encourage contraceptive counseling and removal protocols that directly address historical reproductive injustices and that honor patients’ wishes. PMID:27631741

  20. PHARMACOKINETIC EVALUATION OF A LONG-ACTING FENTANYL SOLUTION AFTER TRANSDERMAL ADMINISTRATION IN HELMETED GUINEAFOWL (NUMIDA MELEAGRIS).

    PubMed

    Waugh, Lynnette; Knych, Heather; Cole, Gretchen; D'Agostino, Jennifer

    2016-06-01

    The objective of this study was to investigate the pharmacokinetics of a long-acting fentanyl solution in helmeted guineafowl ( Numida meleagris ) after transdermal administration. Twenty-one guineafowl received a single administration of 5 mg/kg of fentanyl transdermal solution. No adverse effects on behavior were appreciated. Plasma fentanyl concentrations were determined by liquid chromatography-mass spectrometry analysis of protein-precipitated samples. Mean maximum plasma concentration was 228.8 ng/ml at 4 hr. The mean plasma terminal half-life was 33.2 hr. At 168 hr the mean plasma concentration was 1.3 ng/ml. A single topical dose of 5 mg/kg appears to be safe for use in this species and maintained plasma concentrations above those reported to be analgesic in dogs for at least 7 days. PMID:27468018

  1. Risperidone Dosing in Children and Adolescents with Autistic Disorder: A Double-Blind, Placebo-Controlled Study

    ERIC Educational Resources Information Center

    Kent, Justine M.; Kushner, Stuart; Ning, Xiaoping; Karcher, Keith; Ness, Seth; Aman, Michael; Singh, Jaskaran; Hough, David

    2013-01-01

    Efficacy and safety of 2 risperidone doses were evaluated in children and adolescents with autism. Patients (N = 96; 5-17 years), received risperidone (low-dose: 0.125 mg/day [20 to <45 kg], 0.175 mg/day [>45 kg] or high-dose: 1.25 mg/day [20 to <45 kg], 1.75 mg/day [>45 kg]) or placebo. Mean baseline (range 27-29) to endpoint change…

  2. Comparative pharmacokinetics of a new oral long-acting formulation of doxycycline hyclate: A canine clinical trial.

    PubMed

    Arciniegas Ruiz, Sara Melisa; Gutiérrez Olvera, Lilia; Bernad Bernad, María Josefa; Caballero Chacón, Sara Del Carmen; Vargas Estrada, Dinorah

    2015-12-01

    Doxycicline is used in dogs as treatment of several bacterial infections, mycoplasma, chlamydia and rickettsial diseases. However, it requires long treatments and several doses to be effective. The aim of this study was to determine the pharmacokinetics of four formulations of doxycycline hyclate, administered orally, with different proportions of excipients, acrylic acid-polymethacrylate-based matrices, to obtain longer therapeutic levels than conventional formulation. Forty-eight dogs were randomly assigned in five groups to receive a single oral dose (20mg/kg) of doxycycline hyclate without excipients (control) or a long-acting formulation containing doxycycline, acrylic acid polymer, and polymethacrylate in one of the following four proportions: DOX1(1:0.25:0.0035), DOX2(1:0.5:0.0075), DOX3 (1:1:0.015), or DOX4(1:2:0.0225). Temporal profiles of serum concentrations were obtained at several intervals after each treatment. Therapeutic concentrations were observed for 60h for DOX1 and DOX4, 48h for DOX2 and DOX3 and only 24h for DOX-C. None of the pharmacokinetic parameter differed significantly between DOX1 and DOX2 or between DOX3 and DOX4; however, the findings for the control treatment were significantly different compared to all four long-acting formulations. Results indicated that DOX1 had the most adequate pharmacokinetic-pharmacodynamic relationships for a time-dependent drug and had longer release times than did doxycycline alone. However, all four formulations can be effective depend on the minimum effective serum doxycycline concentration of the microorganism being treated. These results suggest that the use of any of these formulations can reduce the frequency of administration, the patient's stress, occurrence of adverse effects and the cost of treatment.

  3. Pharmacodynamic actions of a long-acting PTH analog (LA-PTH) in thyroparathyroidectomized (TPTX) rats and normal monkeys

    PubMed Central

    Shimizu, Masaru; Joyashiki, Eri; Noda, Hiroshi; Watanabe, Tomoyuki; Okazaki, Makoto; Nagayasu, Miho; Adachi, Kenji; Tamura, Tatsuya; Potts, John T.; Gardella, Thomas J.; Kawabe, Yoshiki

    2016-01-01

    Hypoparathyroidism is a disease of chronic hypocalcemia and hyperphosphatemia due to a deficiency of parathyroid hormone (PTH). PTH and analogs of the hormone are of interest as potential therapies. Accordingly, we examined the pharmacological properties of a long-acting PTH analog, [Ala1,3,12,18,22, Gln10,Arg11,Trp14,Lys26]-PTH(1–14)/PTHrP(15–36) (LA–PTH) in thyroparathyroidectomized (TPTX) rats, a model of HP, as well as in normal monkeys. In TPTX rats, a single intra-venous administration of LA-PTH at a dose of 0.9 nmol/kg increased serum calcium (sCa) and decreased serum phosphate (sPi) to near-normal levels for longer than 48 hours, while PTH(1–34) and PTH(1–84), each injected at a dose 80-fold higher than that used for LA-PTH, increased sCa and decreased sPi only modestly and transiently (< 6 hours). LA-PTH also exhibited enhanced and prolonged efficacy versus PTH(1–34) and PTH(1–84) for elevating sCa when administered subcutaneously (SC) into monkeys. Daily SC administration of LA-PTH (1.8 nmol/kg) into TPTX rats for 28-days elevated sCa to near normal levels without causing hypercalciuria or increasing bone resorption markers, a desirable goal in the treatment of hypoparathyroidism. The results are supportive of further study of long-acting PTH analogs as potential therapies for patients with hypoparathyroidism. PMID:26865415

  4. Conversion of daily pegvisomant to weekly pegvisomant combined with long-acting somatostatin analogs, in controlled acromegaly patients.

    PubMed

    Neggers, Sebastian J C M M; de Herder, Wouter W; Feelders, Richard A; van der Lely, A J

    2011-09-01

    The efficacy of combined treatment in active acromegaly with both long-acting somatostatin analogs (SRIF) and pegvisomant (PEG-V) has been well established. The aim was to describe the PEG-V dose reductions after the conversion from daily PEG-V to combination treatment. To clarify the individual beneficial and adverse effects, in two acromegaly patients, who only normalized their insulin like growth factor (IGF-I) levels with high-dose pegvisomant therapy. We present two cases of a 31 and 44 years old male with gigantism and acromegaly that were controlled subsequently by surgery, radiotherapy, SRIF analogs and daily PEG-V treatment. They were converted to combined treatment of monthly SSA and (twice) weekly PEG-V. High dose SSA treatment was added while the PEG-V dose was decreased during carful monitoring of the IGF-I. After switching from PEG-V monotherapy to SRIF analogs plus pegvisomant combination therapy IGF-I remained normal. However, the necessary PEG-V dose, to normalize IGF-I differed significantly between these two patients. One patient needed twice weekly 100 mg, the second needed 60 mg once weekly on top of their monthly lanreotide Autosolution injections of 120 mg. The weekly dose reduction was 80 and 150 mg. After the introducing of lanreotide, fasting glucose and glycosylated haemoglobin concentrations increased. Diabetic medication had to be introduced or increased. No changes in liver tests or in pituitary adenoma size were observed. In these two patients, PEG-V in combination with long-acting SRIF analogs was as effective as PEG-V monotherapy in normalizing IGF-I levels, although significant dose-reductions in PEG-V could be achieved. However, there seems to be a wide variation in the reduction of PEG-V dose, which can be obtained after conversion to combined treatment. PMID:21221818

  5. Long-acting methylphenidate reduces collision rates of young adult drivers with attention-deficit/hyperactivity disorder.

    PubMed

    Cox, Daniel J; Davis, Margaret; Mikami, Amori Yee; Singh, Harsimran; Merkel, Richard L; Burket, Roger

    2012-04-01

    This study investigated whether methylphenidate delivered through a long-acting transdermal system (MTS) would reduce collision rates of young adult drivers with attention-deficit/hyperactivity disorder (ADHD).Seventeen young adults completing the study (mean [SD] age, 20.82 [2.40] years; 14 men and 13 white) met the following inclusion criteria: ADHD diagnoses but not routinely taking ADHD medication, previously responsive to ADHD medication, active drivers with more than 1 collision or citation in the past 2 years, and no significant comorbidities. In this open-labeled, crossover design drivers were randomly assigned either to the no-medication condition for 3 months and then MTS for 3 months or to the reverse sequence. In-car video monitoring of routine driving occurred during these 6 months. At baseline and after each condition, participants completed the Conners Adult ADHD Rating Scale and the Cox Assessment of Risky Driving Scale, and their blood pressure, heart rate, and body weight were monitored.Compared with the no-medication condition, participants in the MTS condition self-reported fewer total ADHD (P < 0.04) and inattentive symptoms (P = 0.014) and a trend for risky driving behaviors (P = 0.059) and had fewer video-recorded collisions (P < 0.005) and other problematic driving events. There were no significant changes in blood pressure, heart rate, or body weight across conditions or any significant skin reactions to the MTS patch.This is the first study demonstrating that long-acting methylphenidate improves activities of daily living among young adults with ADHD. Specifically, methylphenidate improved safety in routine driving while reducing ADHD symptoms with minimal adverse effects. PMID:22367664

  6. Risperidone in the treatment of conduct disorder in preschool children without intellectual disability

    PubMed Central

    2011-01-01

    Background The DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition Textrevision) highlights the especially poor outcomes of early-onset conduct disorder (CD). The strong link between the patient's age at treatment and its efficacy points the importance of early intervention. Risperidone is one of the most commonly studied medications used to treat CD in children and adolescents. The aim of this study is to obtain preliminary data about the efficacy and tolerability of risperidone treatment in otherwise typically developing preschool children with conduct disorder and severe behavioral problems. Method We recruited 12 otherwise normally developing preschoolers (ten boys and two girls) with CD for this study. We could not follow up with 4 children at control visits properly; thus, 8 children (six girls, two boys; mean age: 42.4 months) completed the study. We treated the patients with risperidone in an open-label fashion for 8 weeks, starting with a daily dosage of 0.125 mg/day or 0.25 mg/day depending on the patient's weight (<20 kg children: 0.125 mg/day; >20 kg children: 0.25 mg/day). Dosage titration and increments were performed at 2-week interval clinical assessments. The Turgay DSM-IV Based Disruptive Behavior Disorders Child and Adolescent Rating & Screening Scale (T-DSM-IV-S) as well as the Clinical Global Impression Scale (CGI) assessed treatment efficacy; the Extrapyramidal Symptom Rating Scale (ESRS) and laboratory evaluations assessed treatment safety. Results The mean daily dosage of risperidone at the end of 8 weeks was 0.78 mg/day (SD: 0.39) with a maximum dosage of 1.50 mg/day. Based on the CGI global improvement item, we classified all patients as "responders" (very much or much improved). Risperidone was associated with a 78% reduction in the CGI Severity score. We also detected significant improvements on all of the subscales of the T-DSM-IV-S. Tolerability was good, and serious adverse effects were not observed. We

  7. Neuroleptic malignant syndrome due to risperidone treatment in a child with Joubert syndrome.

    PubMed

    Vurucu, Sebahattin; Congologlu, Ayhan; Altun, Demet; Unay, Bulent; Akin, Ridvan

    2009-03-01

    Joubert syndrome is a rare autosomal recessive disease characterized by hypotonia, ataxia, episodic hyperpnea, psychomotor retardation, abnormal ocular movements, cerebellar vermian hypoplasia, and molar tooth sign on magnetic resonance imaging. Neuroleptic malignant syndrome is an uncommon and potentially fatal idiosynchratic reaction of antipsychotic drugs, in which the clinical scenario encompass muscular rigidity, hyperthermia, autonomic dysfunction, altered consciousness, high creatinine phosphokinase levels, and leukocytosis. This report describes a case of neuroleptic malignant syndrome due to risperidone in a child with Joubert syndrome.

  8. Development of novel risperidone implants using blends of polycaprolactones and in vitro in vivo correlation studies.

    PubMed

    Navitha, Aerrolla; Jogala, Satheesh; Krishnamohan, Chinnala; Aukunuru, Jithan

    2014-04-01

    The objective of this study was to develop a novel implant containing risperidone intended for long-term treatment in Schizophrenia utilizing in vitro in vivo correlation (IVIVC) studies. Different implants (F1-F8) containing an antipsychotic drug, risperidone, were prepared using a hot melt extrusion technique by taking polycaprolactones of different molecular weights (Mwt. 15000, 45000, 80000) either alone or as their blends, and PLGA (75:25). The implants contained 40% of the drug. After fabrication, the implants were characterized for various in vitro properties such as drug release and physical strength. Prior to conducting drug release studies, optimum drug release method was developed based on IVIVC studies. An optimized formulation based on drug release and physical strength at the end of fabrication was selected from the various implants fabricated. The bioactivity, reversibility, and IVIVC of optimized formulation were determined using pharmacokinetic studies in rats. Short-term stability studies were conducted with optimized formulation. Drug release depended on polymer molecular weight. Implant fabricated using 50:50 polycaprolactone 45,000 and polycaprolactone 80,000 was considered optimized implant. Optimized formulation selected released the drug for 3-months in vitro and was physically rigid. The optimized implant was able to release the drug in vivo for a period of 3 months, the implants are reversible throughout the delivery interval and, a 100% IVIVC was achieved with optimized implant, suggesting the development of 3-month drug-releasing implant for risperidone. The optimized implant was stable for 6 months at room temperature (25°C) and 45°C. A novel implant for risperidone was successfully prepared and evaluated. PMID:24959417

  9. Long-lasting sensitization induced by repeated risperidone treatment in adolescent Sprague-Dawley rats: A possible D2 receptor mediated phenomenon?

    PubMed Central

    Zhang, Qinglin; Hu, Gang; Li, Ming

    2014-01-01

    Rationale Risperidone use in children and adolescents for the treatment of various neuropsychiatric disorders (e.g. schizophrenia, autism, disruptive behavior, etc.) has increased substantially in recent decades. However, its long-term effect on the brain and behavioral functions is not well understood. Objective The present study investigated how a short-term risperidone treatment in adolescence impacts antipsychotic response in adulthood in the conditioned avoidance response and PCP-induced hyperlocomotion tests. Methods Male adolescent Sprague-Dawley rats (postnatal days [P] 40-44 or 43-48) were first treated with risperidone (0.3, 0.5 or 1.0 mg/kg, sc) and tested in the conditioned avoidance or PCP (3.2 mg/kg, sc)-induced hyperlocomotion model daily for 5 consecutive days. After they became adults (~P 76-80), they were challenged with risperidone (0.3 mg/kg, sc) to assess their sensitivity to risperidone re-exposure. A quinpirole (a D2/3 receptor agonist, 1.0 mg/kg, sc)-induced hyperlocomotion test was later conducted to assess the risperidone-induced functional changes in D2 receptor. Results In the risperidone challenge test in adulthood, adult rats previously treated with risperidone in adolescence made significantly fewer avoidance responses and exhibited significantly lower PCP-induced hyperlocomotion than those previously treated with vehicle. They also appeared to be more hyperactive than the vehicle-pretreated ones in the quinpirole-induced hyperlocomotion test. Prepulse inhibition of acoustic startle or fear-induced 22 kHz ultrasonic vocalizations in adulthood was not altered by adolescence risperidone treatment. Conclusions Adolescent risperidone exposure induces a long-term increase in behavioral sensitivity to risperidone that persists into adulthood. This long-lasting change might be due to functional upregulation of D2-mediated neurotransmission. PMID:24363078

  10. Effervescent tablet formulation for enhanced patient compliance and the therapeutic effect of risperidone.

    PubMed

    Mohammed, Kareem Abu Bakr; Ibrahim, Howida Kamal; Ghorab, Mahmoud Mohammed

    2016-01-01

    Risperidone is a poorly water soluble atypical antipsychotic drug. This work investigated the potential of developing risperidone effervescent tablets to facilitate drug administration and mask drug taste. The solid dispersion technique was selected to improve drug solubility due to its ease of scaling up, reproducibility and affordable cost. Thirty formulas were prepared adopting a 5(1).2(1).3(1) full factorial design. Trehalose, Inulin, pregelatinized starch, carboxymethylcellulose sodium and Eudragit E100 were used as hydrophilic carriers at different ratios. Rotovap, lyophilization and the kneading-oven were applied as solvent evaporation techniques. Differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy showed that the drug was present as amorphous material entrapped within the carrier matrix. Eight tablet blends were prepared using different effervescent mixture ratios with or without binder and lubricant/glidant mixture. All of the blends had acceptable flowability, acceptable effervescence times and immediate drug release that could not be achieved by any of the control formulas. The formula of choice contained 40% effervescent mixture, 5% starch, 1% boric acid, 1% aspartame and sufficient lactose. The relative bioavailability (RB) of risperidone from this formula was 161.41% with a significantly higher extent of absorption compared to the market conventional tablets. This formula may be promising in improving patient compliance and drug efficiency. PMID:24833273

  11. Adjunctive aripiprazole in risperidone-induced hyperprolactinaemia: double-blind, randomised, placebo-controlled trial

    PubMed Central

    Raghuthaman, G.; Venkateswaran, R.

    2015-01-01

    Background Hyperprolactinaemia is a troublesome side-effect of treatment with antipsychotics. Aims This double-blind, placebo-controlled study aimed at examining the effect of adjunctive treatment with 10 mg aripiprazole on prolactin levels and sexual side-effects in patients with schizophrenia symptomatically maintained on risperidone. Method Thirty patients taking risperidone were enrolled into the trial (CTRI/2012/11/003114). Aripiprazole was administered at a fixed daily dose of 10 mg/day for 8 weeks. Serum prolactin was measured at baseline and at 8 weeks. Hyperprolactinaemia-related problems, psychopathology and side-effects were evaluated every 2 weeks. Results Prolactin levels decreased by 58% in the aripiprazole group compared with an increase by 22% in the placebo group. Prolactin levels normalised in 46% of patients in the aripiprazole group (number needed to treat, NNT=2). Aripiprazole improved erectile dysfunction in five out of six patients. There were no significant differences in change in psychopathology or side-effects between groups. Conclusions Adjunctive aripiprazole reduced prolactin levels in those treated with risperidone, with no effect on psychopathology and extrapyramidal symptoms. This is a potential treatment for hyperprolactinaemia observed during treatment with second-generation antipsychotics. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703744

  12. A comparative study of sexual dysfunction involving risperidone, quetiapine, and olanzapine

    PubMed Central

    Nagaraj, Anil Kumar M.; Pai, Nagesh B.; Rao, Satheesh

    2009-01-01

    Background: With the advent of newer antipsychotic drugs, side effects such as sexual dysfunction have been a major contributor toward treatment compliance. There are only a few studies that have compared different atypical antipsychotic agents regarding sexual dysfunction. We have not come across any data in this area on Indian population. Aims: To determine and compare the frequency of sexual dysfunction associated with risperidone, olanzapine, and quetiapine, among patients with clinically stable schizophrenia. Settings and Design: It is a cross-sectional hospital-based study. The subjects were recruited for the study by the purposive sampling technique. Materials and Methods: The total sample size was 102, consisting of 25 each in the quetiapine and risperidone groups, 22 in the olanzapine group, and 30 healthy volunteers. A Brief Psychiatric Rating Scale and Sexual Functioning Questionnaire (SFQ) were administered. The Kruskal Wallis test was used to compare the variables in the demographic data and the mean chlorpromazine equivalent doses of the study groups. To analyze the sexual dysfunction, the mean scores on all the domains of sexual functioning in SFQ were compared across the study groups using the Chi square test, for proportions. Results and Conclusion: Twenty-three percent of the healthy volunteers had some impairment in one or more domains of sexual functioning. For the medication groups this was 96, 88, and 90%, respectively for risperidone, quetiapine, and olanzapine. However, there was statistically no significant difference across the study groups although it was relatively less with quetiapine. PMID:20048451

  13. Clozapine and risperidone influence on cortisol and estradiol levels in male patients with schizophrenia.

    PubMed

    Piriu, G; Torac, E; Gaman, L E; Iosif, L; Tivig, I C; Delia, C; Gilca, M; Stoian, I; Atanasiu, V

    2015-01-01

    Estrogens role in schizophrenia patients is a subject, which has gained an increased attention from the medical community. Estrogens have been shown to inhibit dopamine actions, improve neuronal regeneration, and overall, have a protective role in the pathology of schizophrenia. The adjunctive estrogen therapy for men is currently under debate. Antipsychotic medication is known to influence the hypothalamo-hypophyseal - gonadal axis by inducing variable degrees of hyperprolactinemia. Several studies have found that some of the atypical antipsychotics lower cortisol levels in patients and also in healthy controls. We have investigated the effects of clozapine and risperidone on estradiol levels in men with schizophrenia. We have also evaluated the levels of prolactin and cortisol, taking into account the possible influence of antipsychotic drugs on both these hormones. Both prolactin and cortisol also have the potential to regulate sexual hormones biosynthesis. Our study found decreased estradiol levels in men with schizophrenia treated with clozapine and risperidone, while prolactin levels were increased only in the risperidone treated group. Cortisol levels are not statistically significant different between groups. PMID:26664488

  14. Effervescent tablet formulation for enhanced patient compliance and the therapeutic effect of risperidone.

    PubMed

    Mohammed, Kareem Abu Bakr; Ibrahim, Howida Kamal; Ghorab, Mahmoud Mohammed

    2016-01-01

    Risperidone is a poorly water soluble atypical antipsychotic drug. This work investigated the potential of developing risperidone effervescent tablets to facilitate drug administration and mask drug taste. The solid dispersion technique was selected to improve drug solubility due to its ease of scaling up, reproducibility and affordable cost. Thirty formulas were prepared adopting a 5(1).2(1).3(1) full factorial design. Trehalose, Inulin, pregelatinized starch, carboxymethylcellulose sodium and Eudragit E100 were used as hydrophilic carriers at different ratios. Rotovap, lyophilization and the kneading-oven were applied as solvent evaporation techniques. Differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy showed that the drug was present as amorphous material entrapped within the carrier matrix. Eight tablet blends were prepared using different effervescent mixture ratios with or without binder and lubricant/glidant mixture. All of the blends had acceptable flowability, acceptable effervescence times and immediate drug release that could not be achieved by any of the control formulas. The formula of choice contained 40% effervescent mixture, 5% starch, 1% boric acid, 1% aspartame and sufficient lactose. The relative bioavailability (RB) of risperidone from this formula was 161.41% with a significantly higher extent of absorption compared to the market conventional tablets. This formula may be promising in improving patient compliance and drug efficiency.

  15. A randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disorders

    PubMed Central

    2013-01-01

    Background This study examined the efficacy and safety of N-acetylcysteine (NAC) augmentation for treating irritability in children and adolescents with autism spectrum disorders (ASD). Method Forty children and adolescents met diagnostic criteria for ASD according to DSM-IV. They were randomly allocated into one of the two groups of NAC (1200 mg/day)+risperidone or placebo+risperidone. NAC and placebo were administered in the form of effervescent and in two divided doses for 8 weeks. Irritability subscale score of Aberrant Behavior Checklist (ABC) was considered as the main outcome measure. Adverse effects were also checked. Results The mean score of irritability in the NAC+risperidone and placebo+risperidone groups at baseline was 13.2(5.3) and 16.7(7.8), respectively. The scores after 8 weeks were 9.7(4.1) and 15.1(7.8), respectively. Repeated measures of ANOVA showed that there was a significant difference between the two groups after 8 weeks. The most common adverse effects in the NAC+risperidone group were constipation (16.1%), increased appetite (16.1%), fatigue (12.9%), nervousness (12.9%), and daytime drowsiness (12.9%). There was no fatal adverse effect. Conclusions Risperidone plus NAC more than risperidone plus placebo decreased irritability in children and adolescents with ASD. Meanwhile, it did not change the core symptoms of autism. Adverse effects were not common and NAC was generally tolerated well. Trial registration This trial was registered at http://www.irct.ir. The registration number of this trial was IRCT201106103930N6 PMID:23886027

  16. Metabolism of risperidone to 9-hydroxyrisperidone by human cytochromes P450 2D6 and 3A4.

    PubMed

    Fang, J; Bourin, M; Baker, G B

    1999-02-01

    Risperidone is a relatively new antipsychotic drug that has been reported to improve both the positive and the negative symptoms of schizophrenia and produces relatively few extrapyramidal side effects at low doses. Formation of 9-hydroxyrisperidone, an active metabolite, is the most important metabolic pathway of risperidone in human. In the present study, in vitro metabolism of risperidone (100 microM) was investigated using the recombinant human cytochrome P450 (CYP) enzymes CYP1A1, CYP1A2, CYP2C8, CYP2C9-arg144, CYP2C9-cys144, CYP2C19, CYP2D6, CYP3A4 and CYP3A5 supplemented with an NADPH-generating system. 9-Hydroxyrisperidone was determined by a new HPLC method with an Hypersil CN column and a UV detector. Of these enzymes, CYPs 2D6, 3A4 and 3A5 were found to be the ones capable of metabolising risperidone to 9-hydroxyrisperidone, with activities of 7.5, 0.4 and 0.2 pmol pmol(-1) CYP min(-1), respectively. A correlation study using a panel of human liver microsomes showed that the formation of 9-hydroxyrisperidone is highly correlated with CYP2D6 and 3A activities. Thus, both CYP2D6 and 3A4 are involved in the 9-hydroxylation of risperidone at the concentration of risperidone used in this study. This observation is confirmed by the findings that both quinidine (inhibitor of CYP2D6) and ketoconazole (inhibitor of CYP3A4) can inhibit the formation of 9-hydroxyrisperidone. Furthermore, inducers of CYP can significantly increase the formation of 9-hydroxyrisperidone in rat. The formation of 9-hydroxyrisperidone is highly correlated with testosterone 6beta-hydroxylase activities, suggesting that inducible CYP3A contributes significantly to the metabolism of risperidone in rat.

  17. Insulin degludec, a long-acting once-daily basal analogue for type 1 and type 2 diabetes mellitus.

    PubMed

    Berard, Lori; MacNeill, Gail

    2015-02-01

    Here, we discuss certain practical issues related to use of insulin degludec, a new long-acting basal insulin analogue. Degludec provides uniform ("peakless") action that extends over more than 24 hours and is highly consistent from dose to dose. Like the 2 previously available basal analogues (detemir and glargine), degludec is expected to simplify dose adjustment and enable patients to reach their glycemic targets with reduced risk of hypoglycemia. Phase 3 clinical trials involving type 1 and type 2 diabetes have demonstrated that degludec was noninferior to glargine in allowing patients to reach a target glycated hemoglobin (A1C) of 7%, and nocturnal hypoglycemia occurred significantly less frequently with degludec. In addition, when dosing intervals vary substantially from day to day, degludec continues to be effective and to maintain a low rate of nocturnal hypoglycemia. Degludec thus has the potential to reduce risk of nocturnal hypoglycemia, to enhance the flexibility of the dosing schedule and to improve patient and caregiver confidence in the stability of glycemic control. A dedicated injector, the FlexTouch prefilled pen, containing degludec 200 units/mL, will be recommended for most patients with type 2 diabetes. Degludec will also be available as 100 units/mL cartridges, to be used in the NovoPen 4 by patients requiring smaller basal insulin doses, including most patients with type 1 diabetes.

  18. Working with State Health Departments on Emerging Issues in Maternal and Child Health: Immediate Postpartum Long-Acting Reversible Contraceptives

    PubMed Central

    Kroelinger, Charlan D.; Waddell, Lisa F.; Goodman, David A.; Pliska, Ellen; Rudolph, Claire; Ahmed, Einas; Addison, Donna

    2016-01-01

    Background Immediate postpartum long-acting reversible contraceptives (LARC) are highly effective in preventing unintended pregnancy. State health departments are in the process of implementing a systems change approach to better apply policies supporting the use of immediate postpartum LARC. Methods Beginning in 2014, a group of national organizations, federal agencies, and six states have convened a LARC Learning Community to share strategies and best practices in immediate postpartum LARC policy development and implementation. Community activities consist of in-person meetings and a webinar series as forums to discuss systems change. Results The Learning Community identified eight domains for discussion and development of resources: training, pay streams, stocking and supply, consent, outreach, stakeholder partnerships, service location, and data and surveillance. The community is currently developing resource materials and guidance for use by other state health departments. Conclusions To effectively implement policies on immediate postpartum LARC, states must engage a number of stakeholders in the process, raise awareness of the challenges to implementation, and communicate strategies across agencies during policy development. PMID:26390378

  19. Introduction of postabortion contraception, prioritizing long-acting reversible contraceptives, in the principal maternity hospital of Gabon.

    PubMed

    Mayi-Tsonga, Sosthène; Obiang, Pamphile Assoumou; Minkobame, Ulysse; Ngouafo, Doris; Ambounda, Nathalie; de Souza, Maria Helena

    2014-07-01

    A prospective, descriptive, analytic study was conducted at the Centre Hospitalier de Libreville in Gabon between February and September 2013 to evaluate acceptance of long-acting reversible contraceptives (LARC) and depot-medroxyprogesterone acetate (DMPA) following abortion. Women received counseling on the combined oral pill, DMPA, copper intrauterine devices (IUDs), and implants. The association between sociodemographic and clinical characteristics, knowledge of contraceptives, and acceptance was analyzed. Of the 383 women admitted with abortion complications, 206 (53.7%) knew of no systemic contraceptives. The best-known method was the oral pill (42.0%). Only 14 women (3.6%) knew of a LARC method (IUD or implants) and only 2 (0.5%) said the injectable was their best-known method. Over 90% accepted a modern contraceptive method after abortion. Two-thirds (66.8%) chose the pill, 14.6% DMPA, and 9.3% a LARC method. Only 9.1% of the women refused to initiate use of any method.

  20. Development of long-acting bioadhesive vaginal gels of oxybutynin: formulation, in vitro and in vivo evaluations.

    PubMed

    Tuğcu-Demiröz, Fatmanur; Acartürk, Füsun; Erdoğan, Deniz

    2013-11-30

    Overactive bladder (OAB) and vaginal dryness are common problems after menopause. Oxybutynin (OXY) is an antimuscarinic agent that has been available for more than 30 years in the treatment of OAB patients. The aim of the work reported in this paper was to develop long acting mucoadhesive gel formulations of OXY and to investigate their effects on blood levels compared to those of oral OXY immediate release tablets, in rabbits. Mucoadhesive gels were prepared with chitosan, hydroxypropyl methylcellulose (HPMC K100M) and Poloxamer 407 (Pluronic F 127). The physicopharmaceutical properties of gels were evaluated. The gel formulation which was prepared with HPMC K100M, exhibited the highest viscosity, the greatest adhesiveness, cohesiveness and mucoadhesion values. The formulation which was prepared from HPMC K100M showed suitable permeation characteristics across the vaginal mucosa. Comparative bioavailability studies were carried out on rabbits with vaginal HPMC gel, vaginal chitosan gel, vaginal OXY solution and commercially available oral Üropan tablets. It was concluded that the highest AUC and relative bioavailability values were obtained for the bioadhesive vaginal gel formulation prepared with HPMC K100M. Therefore, the mucoadhesive vaginal gels of OXY can be a promising and innovative alternative therapeutic system for the treatment of OAB. It can be safely used in cases of overactive bladder and as well as vaginal dryness after menopause.

  1. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy

    PubMed Central

    Li, Tianyuzi; Gendelman, Howard E; Zhang, Gang; Puligujja, Pavan; McMillan, JoEllyn M; Bronich, Tatiana K; Edagwa, Benson; Liu, Xin-Ming; Boska, Michael D

    2015-01-01

    Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory’s development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery. PMID:26082630

  2. Changes in methacholine induced bronchoconstriction with the long acting beta 2 agonist salmeterol in mild to moderate asthmatic patients.

    PubMed Central

    Booth, H.; Fishwick, K.; Harkawat, R.; Devereux, G.; Hendrick, D. J.; Walters, E. H.

    1993-01-01

    BACKGROUND--Beta-2 agonists protect against non-specific bronchoconstricting agents such as methacholine, but it has been suggested that the protection afforded by long acting beta 2 agonists wanes rapidly with regular treatment. METHODS--The changes in airway responsiveness were investigated during and after eight weeks of regular treatment with salmeterol 50 micrograms twice daily in 26 adult asthmatic patients, 19 of whom were receiving maintenance inhaled corticosteroids. The study was of a randomised, placebo controlled, double blind design. Airway responsiveness to methacholine was measured as PD20 by a standardised dosimeter technique 12 hours after the first dose, at four weeks and eight weeks during treatment (12 hours after the last dose of test medication), and at 60 hours, one week and two weeks after stopping treatment. RESULTS--There were no significant differences between the baseline characteristics of the two groups. A significant improvement in PD20 was seen at all points during treatment with salmeterol compared with the placebo group, with no significant fall off with time. PD20 measurements returned to baseline values after cessation of treatment with no significant difference from the placebo group. CONCLUSIONS--Salmeterol gave significant protection against methacholine induced bronchoconstriction 12 hours after administration. This protection was of small magnitude, but there was no significant attenuation with eight weeks of regular use and no rebound increase in airway responsiveness on stopping treatment in a group of moderate asthmatic patients, the majority of whom were receiving inhaled corticosteroids. PMID:8296255

  3. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy.

    PubMed

    Li, Tianyuzi; Gendelman, Howard E; Zhang, Gang; Puligujja, Pavan; McMillan, JoEllyn M; Bronich, Tatiana K; Edagwa, Benson; Liu, Xin-Ming; Boska, Michael D

    2015-01-01

    Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory's development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery. PMID:26082630

  4. [Pharmacodynamics and results of a clinical trial of nitrogranulong, a new Soviet long-acting preparation of nitroglycerin].

    PubMed

    Sokolov, S Ia; Belova, L F; Trumpe, T E; Alibekov, S D; Sakovich, G S; Rusakova, K A; Ivanov, A A; Belozerova, O P

    1990-10-01

    In the USSR, the Research and Production Association "Vitamins" and the Department of Pharmacology, All-Union Research Institute of Medicinal Plants were the first to develop commercial processes for manufacturing trinitroglycerol microgranules on the basis of the raw material available in this country and to design the new long-acting drug Nitrogranulong. Experimental examinations revealed that Nitrogranulong showed the same bioavailability as Nitro-Mack-Retard and sustac, produced a prolonged coronarolytic effect, and caused the hemodynamic and ECG changes typical of trinitroglycerol. The agent was found to be low toxic and well tolerated in a dosage form. Clinical examination of 467 patients indicated that Nitrogranulong exhibited the same antianginal potency, but in some cases it was superior to sustac, nitrong, 2% nitroglycerin ointment, and nitrosorbide. The agent caused significantly less adverse and toxic effects. Nitrogranulong is used in medical practice to prevent anginal episodes. It is produced in tablets in two dosages (2.9 and 5.2 mg trinitroglycerol), its action duration being 7-8 hours.

  5. Radioimmunoassay for octapeptide analogs of somatostatin: Measurement of serum levels after administration of long-acting microcapsule formulations

    SciTech Connect

    Mason-Garcia, M.; Vaccarella, M.; Horvath, J.; Redding, T.W.; Groot, K.; Orsolini, P.; Schally, A.V. )

    1988-08-01

    The development of a long-acting delivery system for D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH{sub 2} (RC-160), an octapeptide analog of somatostatin, required the establishment of a method for determining the concentration of this analog in serum during treatment. A sensitive and specific radioimmunoassay (RIA) for RC-160 was developed and used for following the rate of liberation of this peptide from microcapsules of poly(DL-lactide-coglycolide). Antibodies were generated in a rabbit against RC-160 conjugated to bovine serum albumin with glutaraldehyde. At an antiserum dilution of 1:100,000, the antibodies bound approximately 25% of added radiolabeled RC-160. Somatostatin octapeptide analogs that had a disulfide bridge showed crossreactivity with the antiserum, but analogs without the disulfide bridge and other peptides tested did not crossreact. The minimum detectable dose of RC-160 was 10 pg. Intra- and interassay coefficients of variation ranged from 9.1% to 12.8% and from 14% to 30%, respectively. The RIA was suitable for direct determination of RC-160 in serum. Eleven prototype batches of microcapsules were tested in rats, and the rate of release of the analog from the microcapsules was followed. An improved batch of microcapsules made from RC-160 pamoate maintained high serum levels of RC-160 for more than 30 days after intramuscular injection. The RIA should be of value for monitoring levels of this analog in serum during long-term therapy.

  6. Radioimmunoassay for octapeptide analogs of somatostatin: measurement of serum levels after administration of long-acting microcapsule formulations.

    PubMed Central

    Mason-Garcia, M; Vaccarella, M; Horvath, J; Redding, T W; Groot, K; Orsolini, P; Schally, A V

    1988-01-01

    The development of a long-acting delivery system for D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), an octapeptide analog of somatostatin, required the establishment of a method for determining the concentration of this analog in serum during treatment. A sensitive and specific radioimmunoassay (RIA) for RC-160 was developed and used for following the rate of liberation of this peptide from microcapsules of poly(DL-lactide-coglycolide). Antibodies were generated in a rabbit against RC-160 conjugated to bovine serum albumin with glutaraldehyde. At an antiserum dilution of 1:100,000, the antibodies bound approximately 25% of added radiolabeled RC-160. Somatostatin octapeptide analogs that had a disulfide bridge showed crossreactivity with the antiserum, but analogs without the disulfide bridge and other peptides tested did not crossreact. The minimum detectable dose of RC-160 was 10 pg. Intra- and interassay coefficients of variation ranged from 9.1% to 12.8% and from 14% to 30%, respectively. The RIA was suitable for direct determination of RC-160 in serum. Eleven prototype batches of microcapsules were tested in rats, and the rate of release of the analog from the microcapsules was followed. An improved batch of microcapsules made from RC-160 pamoate maintained high serum levels of RC-160 for more than 30 days after intramuscular injection. The RIA should be of value for monitoring levels of this analog in serum during long-term therapy. PMID:2899894

  7. Can a new ultra-long-acting insulin analogue improve patient care? Investigating the potential role of insulin degludec.

    PubMed

    Robinson, Jennifer D; Neumiller, Joshua J; Campbell, R Keith

    2012-12-24

    The basal-bolus concept of delivering insulin to diabetic patients makes physiological sense, as it mimics normal insulin release in people without diabetes. In line with this concept, a major effort put forth by insulin manufacturers has been to develop the ideal exogenous basal insulin product. The perfect basal insulin product would be injected into subcutaneous tissue without causing irritation, release insulin continuously at a constant rate for at least 24 hours, be stable, not contribute to weight gain, have a low risk of allergic reactions and, very importantly, minimize the risk of hypoglycaemia. While the perfect insulin has not yet been discovered, advancements are still being made. Insulin degludec is an ultra-long-acting basal insulin analogue that possesses a flat, stable glucose-lowering effect in patients with type 1 or type 2 diabetes mellitus. Insulin degludec achieves these pharmacokinetic properties by forming soluble multihexamers upon subcutaneous injection, resulting in the formation of a depot in the subcutaneous tissue that is slowly released and absorbed into circulation. Insulin degludec has been associated with slightly less weight gain and fewer nocturnal hypoglycaemic episodes when compared with insulin glargine in some, but not all, clinical studies. This article briefly reviews current evidence for the use of insulin degludec in patients with type 1 or type 2 diabetes mellitus and discusses the potential impact of this new basal insulin on clinical practice. PMID:23145524

  8. Insulin degludec, a long-acting once-daily basal analogue for type 1 and type 2 diabetes mellitus.

    PubMed

    Berard, Lori; MacNeill, Gail

    2015-02-01

    Here, we discuss certain practical issues related to use of insulin degludec, a new long-acting basal insulin analogue. Degludec provides uniform ("peakless") action that extends over more than 24 hours and is highly consistent from dose to dose. Like the 2 previously available basal analogues (detemir and glargine), degludec is expected to simplify dose adjustment and enable patients to reach their glycemic targets with reduced risk of hypoglycemia. Phase 3 clinical trials involving type 1 and type 2 diabetes have demonstrated that degludec was noninferior to glargine in allowing patients to reach a target glycated hemoglobin (A1C) of 7%, and nocturnal hypoglycemia occurred significantly less frequently with degludec. In addition, when dosing intervals vary substantially from day to day, degludec continues to be effective and to maintain a low rate of nocturnal hypoglycemia. Degludec thus has the potential to reduce risk of nocturnal hypoglycemia, to enhance the flexibility of the dosing schedule and to improve patient and caregiver confidence in the stability of glycemic control. A dedicated injector, the FlexTouch prefilled pen, containing degludec 200 units/mL, will be recommended for most patients with type 2 diabetes. Degludec will also be available as 100 units/mL cartridges, to be used in the NovoPen 4 by patients requiring smaller basal insulin doses, including most patients with type 1 diabetes. PMID:25065475

  9. Long-acting paliperidone palmitate – interim results of an observational study of its effect on hospitalization

    PubMed Central

    Olofinjana, Olubanke

    2014-01-01

    Paliperidone palmitate (PP) is a recently introduced long-acting atypical, or second-generation, antipsychotic. Published data on PP are currently limited to controlled trials and case reports. In this observational study, we followed up 200 consecutive patients prescribed PP in normal practice. After 1 year, 65% of patients were still receiving PP. The number of admissions to hospital in the year following PP initiation was 0.49/patient compared with 0.69/patient/year, 3 years before initiation (P=0.0001). The mean number of bed days fell from 38.78 to 23.09/patient/year over the corresponding period (P=0.0001). The median number of bed days 3 years before PP initiation was 21.50/year and in the year following PP initiation, it was 0. Outcomes were numerically but not statistically better in those continuing PP than in those who ceased PP within a year of initiation. PP was effective and well-tolerated and, given its positive effect on hospital bed days, broadly cost-effective. PMID:24419004

  10. Evolution of opioid risk management and review of the classwide REMS for extended-release/long-acting opioids.

    PubMed

    Stanos, Steven

    2012-11-01

    In 2007, the Food and Drug Administration Amendments Act (FDAAA) afforded the US Food and Drug Administration (FDA) the ability to enforce postmarketing risk management strategies for prescription medicines. Under this policy, certain medications with known or potential risks could be required to have a Risk Evaluation and Mitigation Strategy (REMS), a risk management program designed to ensure that a product's therapeutic benefit outweighs its risks. Prescription opioid analgesics, particularly extended-release (ER)/long-acting (LA) formulations, have undergone scrutiny in recent years due to the serious risks associated with their use, especially when they are prescribed improperly, misused, or abused. In July 2012, the FDA approved a classwide REMS for ER and LA opioids. This ER/LA opioid REMS program is designed to improve prescriber education and patient awareness about safe opioid use to minimize the risks of addiction, unintentional overdose, and death. Because clinicians often encounter patients with moderate-to-severe chronic, noncancer pain who are in need of around-the-clock opioid analgesia, knowledge of the conditions of this classwide REMS may become essential to continue prescribing ER/LA opioids. This article briefly describes the changes in US risk management policies that have shaped today's regulatory environment and provides an overview of the requirements for the classwide ER/LA opioid REMS.

  11. Recombinant factor VIIa reverses the anticoagulant effect of the long-acting pentasaccharide idraparinux in healthy volunteers.

    PubMed

    Bijsterveld, Nick R; Vink, Roel; van Aken, Benien E; Fennema, Hein; Peters, Ron J G; Meijers, Joost C M; Büller, Harry R; Levi, Marcel

    2004-03-01

    We investigated whether the anticoagulant effect of idraparinux, a selective long-acting factor Xa inhibitor, could be neutralized by recombinant factor VIIa (rFVIIa) in healthy male volunteers. We performed a randomized, placebo-controlled trial, comparing idraparinux [7.5 mg subcutaneous (s.c.)] followed at 3 h by rFVIIa [90 microg/kg intravenous (i.v.)] (n = 6), or idraparinux (7.5 mg s.c) followed after 1 week by rFVIIa (90 microg/kg i.v.)(n = 6). rFVIIa, given 3 h after idraparinux, significantly reversed the increased thrombin generation time (TGT), the increased activated partial thromboplastin time (aPTT) and prothrombin time (PT), and the reduced prothrombin fragment 1+2 (F1+2) levels caused by idraparinux, although no clear effect of rFVIIa on the endogenous thrombin potential (ETP) was observed. One week after idraparinux, injection of rFVIIa resulted in a similar relative reduction of the remaining increased aPTT, PT and TGT, with correction to pre-idraparinux values. A clear increase of F1+2 was observed, together with a small increase in ETP. We conclude that rFVIIa has significant effects on the idraparinux-inhibited thrombin generation and clotting parameters. These results suggest that rFVIIa may be useful in serious bleeding complications in idraparinux treated patients.

  12. Efficacy of Zinc Sulfate as an Add-on Therapy to Risperidone Versus Risperidone Alone in Patients With Schizophrenia: A Double-Blind Randomized Placebo-Controlled Trial

    PubMed Central

    Mortazavi, Mehran; Farzin, Davood; Zarhghami, Mehran; Hosseini, Seyed Hamzeh; Mansoori, Parisa; Nateghi, Gholamreza

    2015-01-01

    Background: Zinc can modulate fast-excitatory transmission, facilitate the release of amino butyric acid and potentiate nicotinic acetylcholine receptors. There are also emerging evidences discussing the implication of these neurotransmitters in pathophysiology of schizophrenia. Objectives: The purpose of this study was to evaluate the efficacy of Zn sulfate as an add-on therapy in the treatment of schizophrenia in a 6-week, double-blind and placebo-controlled trial. Patients and Methods: Eligible participants were 30 inpatients with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Patients were randomly allocated into two equal groups; one group of patients received risperidone 6 mg/day plus capsules of Zn sulfate (each containing 50 mg elemental Zn) three times a day and another group received risperidone 6 mg/day plus placebo. The Positive and Negative Syndrome Scale (PANSS) was applied to assess the psychotic symptoms and aggression risk at baseline, week 2, 4, and 6 of the study. Results: The results of this study showed that both protocols significantly decreased the scores on all subscales of the PANSS and supplemental aggression risk subscale as well as PANSS total score over the study. However, this improvement was significantly higher in Zn sulfate receiving group compared to the placebo group. No major clinical side-effects were detected. Conclusions: It may be concluded that Zn is an effective adjuvant agent in the management of patients with schizophrenia. PMID:26576178

  13. The antidepressant- and anxiolytic-like effects following co-treatment with escitalopram and risperidone in rats.

    PubMed

    Kaminska, K; Rogoz, Z

    2016-06-01

    Several clinical reports have documented a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants, in particular selective serotonin reuptake inhibitors (SSRI), in the treatment of drug-resistant depression and treatment-resistant anxiety disorders. In the present study, we investigated the effect of treatment with the antidepressant escitalopram (SSRI) given separately or jointly with a low dose of risperidone (an atypical antipsychotic) in the forced swim test and in the elevated plus-maze test in rats. The obtained results showed that escitalopram at doses of 2.5 or 5 mg/kg evoked antidepressant-like effect in the forced swim test. Moreover, risperidone at low doses (0.05 or 0.1 mg/kg) enhanced the antidepressant-like activity of escitalopram (1 mg/kg) in this test by increasing the swimming time and decreasing the immobility time in those animals. WAY 100635 (a serotonin 5-HT1A receptor antagonist) at a dose of 0.1 mg/kg abolished the antidepressant-like effect induced by co-administration of escitalopram and risperidone. The active behavior in that test did not reflect an increase in general activity, since the combined treatment with escitalopram and risperidone failed to enhance the exploratory activity of rats. In the following experiment, we showed that escitalopram (5 mg/kg) and mirtazapine (5 or 10 mg/kg) or risperidone (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze test, and the combined treatment with an ineffective dose of risperidone (0.05 mg/kg) enhanced the anxiolytic-like effects of escitalopram (2.5 mg/kg) or mirtazapine (1 and 2.5 mg/kg) in this test. The obtained results suggest that risperidone applied at a low dose enhances the antidepressant-like activity of escitalopram in the forced swim test, and that 5-HT1A receptors may play some role in these effects. Moreover, a low dose of risperidone may also enhance the anxiolytic-like action of the studied

  14. The antidepressant- and anxiolytic-like effects following co-treatment with escitalopram and risperidone in rats.

    PubMed

    Kaminska, K; Rogoz, Z

    2016-06-01

    Several clinical reports have documented a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants, in particular selective serotonin reuptake inhibitors (SSRI), in the treatment of drug-resistant depression and treatment-resistant anxiety disorders. In the present study, we investigated the effect of treatment with the antidepressant escitalopram (SSRI) given separately or jointly with a low dose of risperidone (an atypical antipsychotic) in the forced swim test and in the elevated plus-maze test in rats. The obtained results showed that escitalopram at doses of 2.5 or 5 mg/kg evoked antidepressant-like effect in the forced swim test. Moreover, risperidone at low doses (0.05 or 0.1 mg/kg) enhanced the antidepressant-like activity of escitalopram (1 mg/kg) in this test by increasing the swimming time and decreasing the immobility time in those animals. WAY 100635 (a serotonin 5-HT1A receptor antagonist) at a dose of 0.1 mg/kg abolished the antidepressant-like effect induced by co-administration of escitalopram and risperidone. The active behavior in that test did not reflect an increase in general activity, since the combined treatment with escitalopram and risperidone failed to enhance the exploratory activity of rats. In the following experiment, we showed that escitalopram (5 mg/kg) and mirtazapine (5 or 10 mg/kg) or risperidone (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze test, and the combined treatment with an ineffective dose of risperidone (0.05 mg/kg) enhanced the anxiolytic-like effects of escitalopram (2.5 mg/kg) or mirtazapine (1 and 2.5 mg/kg) in this test. The obtained results suggest that risperidone applied at a low dose enhances the antidepressant-like activity of escitalopram in the forced swim test, and that 5-HT1A receptors may play some role in these effects. Moreover, a low dose of risperidone may also enhance the anxiolytic-like action of the studied

  15. Risperidone and Divalproex Differentially Engage the Fronto-Striato-Temporal Circuitry in Pediatric Mania: A Pharmacological Functional Magnetic Resonance Imaging Study

    ERIC Educational Resources Information Center

    Pavuluri, Mani N.; Passarotti, Alessandra M.; Fitzgerald, Jacklynn M.; Wegbreit, Ezra; Sweeney, John A.

    2012-01-01

    Objective: The current study examined the impact of risperidone and divalproex on affective and working memory circuitry in patients with pediatric bipolar disorder (PBD). Method: This was a six-week, double-blind, randomized trial of risperidone plus placebo versus divalproex plus placebo for patients with mania (n = 21; 13.6 [plus or minus] 2.5…

  16. Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study)

    PubMed Central

    García-Cabeza, Ignacio; Gómez, Juan-Carlos; Sacristán, Jose A; Edgell, Eric; González de Chavez, Manuel

    2001-01-01

    Background In order to compare the effectiveness of different antipsychotic drugs in the treatment of schizophrenia it is very important to evaluate subjective response and compliance in patient cohorts treated according to routine clinical practice. Method Outpatients with schizophrenia entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Patients treated with olanzapine, risperidone or haloperidol were included in the analysis. Subjective response was measured using the 10-item version of the Drug Attitude Inventory (DAI-10), and treatment compliance was measured using a physician-rated 4 point categorical scale. Results A total of 2128 patients initiated treatment (as monotherapy) with olanzapine, 417 with risperidone, and 112 with haloperidol. Olanzapine-treated patients had significantly higher DAI-10 scores and significantly better treatment compliance compared to both risperidone- and haloperidol-treated patients. Risperidone-treated patients had a significantly higher DAI-10 score compared to haloperidol-treated patients. Conclusion Subjective response and compliance were superior in olanzapine-treated patients, compared to patients treated with risperidone and haloperidol, in routine clinical practice. Differences in subjective response were explained largely, but not completely, by differences in incidence of EPS. PMID:11835695

  17. Effects of a long-acting, trace mineral, reticulorumen bolus on range cow productivity and trace mineral profiles.

    PubMed

    Sprinkle, J E; Cuneo, S P; Frederick, H M; Enns, R M; Schafer, D W; Carstens, G E; Daugherty, S B; Noon, T H; Rickert, B M; Reggiardo, C

    2006-06-01

    The objectives were to determine if strategic supplementation of range cows with a long-acting (6 mo), trace mineral, reticulorumen bolus containing Cu, Se, and Co would: (1) increase cow BCS and BW, and calf birth, weaning, and postweaning weights, or weight per day of age (WDA); (2) increase liver concentrations of Cu or Zn in cows, or blood Se, Cu, or Zn concentrations in cows and calves; and (3) vary by cow breed for any of these response variables. There were 192 control and 144 bolused Composite cows (C; 25% Hereford, Angus, Gelbevieh, and Senepol or Barzona); 236 control and 158 bolused Hereford (H) cows; and 208 control and 149 bolused Brahman cross (B) cows used in a 3-yr experiment. Cows were weighed and scored for body condition in January, May, and September, and all bolused cows received boluses in January. Each year, from among the 3 breed groups a subset of 15 control and 15 bolused cows (n = 90) had samples obtained in January and May for liver Cu and Zn, blood Se, and serum Cu and Zn. As for cows, blood and serum from the calves of these cows were sampled each year in May and September for Cu, Se, and Zn. There was a significant breed x year x treatment interaction (P = 0.001) for cow weight loss from January to May. Calf WDA, weaning, and postweaning weights did not differ (P > 0.40) between bolused and control cows, but there was a significant (P = 0.022) breed x year x treatment interaction for birth weight. Liver Cu was deficient (< 75 ppm; P < 0.001) in control cows and adequate (< 75 to 90 ppm) for bolused cows. Liver Cu differed by year (P < 0.001). Blood Se was adequate (< 0.1 ppm) for all cows except in January 2001 and 2002. There was no difference (P > 0.50) in blood Se between treatment groups in January, but bolused cows had greater (P < 0.01) blood Se in May. Breed differences for blood Se concentrations existed for bolused cows, with B having greater (P < 0.05) blood Se than either C or H cows. Breed differences also existed for

  18. Pharmacokinetics and the effect of application site on a novel, long-acting transdermal fentanyl solution in healthy laboratory Beagles.

    PubMed

    Freise, K J; Newbound, G C; Tudan, C; Clark, T P

    2012-08-01

    Application of transdermal drugs to different anatomical sites can result in different absorption characteristics. The pharmacokinetics (PKs) and bioequivalence of a single 2.6 mg/kg (50 μL/kg) dose of a novel, long-acting transdermal fentanyl solution were determined when applied topically to the ventral abdominal or dorsal interscapular skin of 40 healthy laboratory Beagles. The PKs were differentiated by a more rapid initial absorption of fentanyl from the dorsal application site. Mean plasma fentanyl concentrations remained above 0.6 ng/mL from 4 to 96 h in the dorsal application group and from 8 to 144 h in the ventral application group. Bioequivalence analysis demonstrated that the sites were not equivalent; the 90% confidence intervals of the ratio of the geometric means for both the maximum concentration (C(max)) and the area under the curve (AUC) were not contained within the 80-125% interval. The C(max) was 2.34 ± 1.29 (mean ± standard deviation) and 2.02 ± 0.84 ng/mL for the ventral and dorsal application groups, respectively. The terminal elimination half-lives (t(1/2)) for both groups were similar with values of 137 ± 58.9 and 117 ± 59.6 h for the ventral and dorsal application site groups, respectively. A mean absorption rate of ≥ 2 μg · kg/h was maintained from 2 to 144 h following dorsal application and from 2 to 264 h following ventral application. These results suggest that transdermal fentanyl solution could be applied as a single dose to the dorsal scapular area 2-4 h prior to surgery with analgesia lasting a minimum of 4 days.

  19. Strengthening Postabortion Family Planning Services in Ethiopia: Expanding Contraceptive Choice and Improving Access to Long-Acting Reversible Contraception

    PubMed Central

    Samuel, Melaku; Fetters, Tamara; Desta, Demeke

    2016-01-01

    ABSTRACT Where unmet need for the safest, most effective, and long-acting reversible contraceptives (LARCs) is very high, the health system and partners need to implement problem-solving, locally feasible, and comprehensive family planning delivery strategies. Because young and unmarried women are most at risk for unintended pregnancy and repeat abortion due to poor access to contraceptive services, postabortion family planning (PAFP) is a key component in such strategies. In Southern Nations, Nationalities, and People’s Region, Ethiopia, Ipas implemented health system strengthening efforts from fiscal year (FY) 2010 (July 2009 to June 2010) to FY 2014 (July 2013 to June 2014) to improve the quality of PAFP services and expand method choice in 101 public facilities. The intervention significantly improved PAFP uptake at the project sites. Specifically, the proportion of abortion clients receiving LARCs progressively improved during the intervention period. The proportion of abortion clients who left the facilities with a contraceptive method increased from 58% in FY 2010 to 83% in FY 2014. The share of method mix for LARCs rose from 2% in FY 2010 to 55% in FY 2014, while the share for condoms, injectables, and oral contraceptives declined from 98% to 45%. Implant use rose from 2% in FY 2010 to 43% in FY 2014, while the use of intrauterine devices increased from 0.1% in FY 2010 to 12% in FY 2014. A larger proportion of PAFP users received LARCs at health centers, where midwives and nurses are the primary providers, than at hospitals (59% versus 37%, respectively). A broader method mix can satisfy clients with a variety of needs, a key factor for higher uptake of more effective methods and program success. Further evidence-based interventions need to be implemented to improve the quality of PAFP in a feasible and replicable strategy that addresses unmet need for modern contraceptive methods. PMID:27540126

  20. A Controlled, Evidence-Based Trial of Paliperidone Palmitate, A Long-Acting Injectable Antipsychotic, in Schizophrenia

    PubMed Central

    Nasrallah, Henry A; Gopal, Srihari; Gassmann-Mayer, Cristiana; Quiroz, Jorge A; Lim, Pilar; Eerdekens, Mariëlle; Yuen, Eric; Hough, David

    2010-01-01

    Paliperidone palmitate is a long-acting injectable antipsychotic agent. This 13-week, multicenter, randomized (1 : 1 : 1 : 1), double-blind, parallel-group study evaluated the efficacy, safety, and tolerability of fixed 25, 50, and 100 milligram equivalent (mg equiv.) doses of paliperidone palmitate vs placebo administered as gluteal injections on days 1 and 8, then every 4 weeks (days 36 and 64) in 518 adult patients with schizophrenia. The intent-to-treat analysis set (N=514) was 67% men and 67% White, with a mean age of 41 years. All paliperidone palmitate dose groups showed significant improvement vs placebo in the Positive and Negative Syndrome Scale (PANSS) total score (primary efficacy measure; 25 and 50 mg equiv., p=0.02; 100 mg equiv., p<0.001), as well as Clinical Global Impression Severity scores (p⩽0.006) and PANSS negative and positive symptom Marder factor scores (p⩽0.04). The Personal and Social Performance scale showed no significant difference between treatment groups. The overall incidence of treatment-emergent adverse events was similar between groups. Parkinsonism, the most frequently reported extrapyramidal symptom, was reported at similar rates for placebo (5%) and paliperidone palmitate (5–6% across doses). The mean body mass index and mean weight showed relatively small dose-related increases during paliperidone palmitate treatment. Investigator-evaluated injection-site pain, swelling, redness, and induration were similar across treatment groups; scores for patient-evaluated injection-site pain (visual analog scale) were similar across groups and diminished with time. All doses of once-monthly paliperidone palmitate were efficacious and generally tolerated, both locally and systemically. Paliperidone palmitate offers the potential to improve outcomes in adults with symptomatic schizophrenia. PMID:20555312

  1. Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein.

    PubMed

    McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D

    2014-07-01

    Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long-acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human- and animal-derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi-step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process-related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non-human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc.

  2. Efficacy of octreotide long-acting repeatable in neuroendocrine tumors: RADIANT-2 placebo arm post hoc analysis

    PubMed Central

    Strosberg, Jonathan R; Yao, James C; Bajetta, Emilio; Aout, Mounir; Bakker, Bert; Hainsworth, John D; Ruszniewski, Philippe B; Van Cutsem, Eric; Öberg, Kjell; Pavel, Marianne E

    2015-01-01

    Somatostatin analogues (SSA) have demonstrated antiproliferative activity in addition to efficacy for carcinoid symptom control in functional neuroendocrine tumors (NET). A post hoc analysis of the placebo arm of the RAD001 In Advanced Neuroendocrine Tumors-2 (RADIANT-2) study was conducted to assess the efficacy of octreotide long-acting repeatable (LAR) on progression-free survival (PFS) and overall survival (OS) estimated using the Kaplan–Meier method. Out of 213 patients randomized to placebo plus octreotide LAR in RADIANT-2, 196 patients with foregut, midgut, or hindgut NET were considered for present analysis. Of these, 41 patients were SSA-treatment naïve and 155 had received SSA therapy before study entry. For SSA-naïve patients, median PFS by adjudicated central review was 13.6 (95% CI 8.2–22.7) months. For SSA-naïve patients with midgut NET (n=24), median PFS was 22.2 (95% CI 8.3–29.5) months. For patients who had received SSA previously, the median PFS was 11.1 (95% CI 8.4–14.3) months. Among the SSA-pretreated patients who had midgut NET (n=119), the median PFS was 12.0 (95% CI 8.4–19.3) months. Median OS was 35.8 (95% CI 32.5–48.9) months for patients in the placebo plus octreotide LAR arm; 50.6 (36.4 – not reached) months for SSA-naïve patients and 33.5 (95% CI 27.5–44.7) months for those who had received prior SSA. This post hoc analysis of the placebo arm of the large phase 3 RADIANT-2 study provides data on PFS and OS among patients with progressive NET treated with octreotide therapy. PMID:26373569

  3. Pharmacokinetics of a long-acting ceftiofur formulation (ceftiofur crystalline free acid) in the ball python (Python regius).

    PubMed

    Adkesson, Michael J; Fernandez-Varon, Emilio; Cox, Sherry; Martín-Jiménez, Tomás

    2011-09-01

    The objective of this study was to determine the pharmacokinetics of a long-acting formulation of ceftiofur crystalline-free acid (CCFA) following intramuscular injection in ball pythons (Python regius). Six adult ball pythons received an injection of CCFA (15 mg/kg) in the epaxial muscles. Blood samples were collected by cardiocentesis immediately prior to and at 0.5, 1, 2, 4, 8, 12, 18, 24, 48, 72, 96, 144, 192, 240, 288, 384, 480, 576, 720, and 864 hr after CCFA administration. Plasma ceftiofur concentrations were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis was applied to the data. Maximum plasma concentration (Cmax) was 7.096 +/- 1.95 microg/ml and occurred at (Tmax) 2.17 +/- 0.98 hr. The area under the curve (0 to infinity) for ceftiofur was 74.59 +/- 13.05 microg x h/ml and the elimination half-life associated with the terminal slope of the concentration-time curve was 64.31 +/- 14.2 hr. Mean residence time (0 to infinity) was 46.85 +/- 13.53 hr. CCFA at 15 mg/kg was well tolerated in all the pythons. Minimum inhibitory concentration (MIC) data for bacterial isolates from snakes are not well established. For MIC values of < or =0.1 microg/ml, a single dose of CCFA (15 mg/kg) provides adequate plasma concentrations for at least 5 days in the ball python. For MICs > or =0.5 microg/ml, more frequent dosing or a higher dosage may be required.

  4. [Slow-release salbutamol in the treatment of nocturnal asthma. Result of a comparative study vs. long-acting theophylline].

    PubMed

    Arnaud, A; Michel, F B; Desfougères, J L; Pappo, M

    1991-01-01

    In a multicentre, randomized, cross-over double-blind, double placebo trial the effectiveness and tolerability of slow-release oral salbutamol (SRS) were compared with those of long-acting (LA) theophylline (T) in the treatment of nocturnal asthma of adults. Forty-nine patients (mean age 37 years) entered the study after a pre-trial period during which a placebo and inhaled salbutamol were used as reference and to test the criteria of inclusion. The number of awakenings due to asthma symptoms was the same with SRS, and T, falling from 1.27 in the pre-trial period to 0.44 under SRS and 0.42 under T. The scores of nocturnal asthma symptoms were improved with both types of treatment. The number of puffs of inhaled salbutamol necessary during the night decreased from 1.94 in the pre-trial period to 1.15 under SRS and 0.92 under T. The number of patients improved was exactly the same in both groups. The ventilatory parameters measured by respiratory function tests at different visits and daily by the patients themselves were also improved. The principal minor side-effects were tremor (5 cases) and irritability (3 cases) with SRS, and nausea (6 cases), headache (3 cases) and asthenia (2 cases) with T; an overdose of T resulted in malaise in one patients. It is concluded that slow-release oral salbutamol administered in doses of 8 mg b.d. is effective in controlling nocturnal asthma, easy to take and very well tolerated.

  5. Strengthening Postabortion Family Planning Services in Ethiopia: Expanding Contraceptive Choice and Improving Access to Long-Acting Reversible Contraception.

    PubMed

    Samuel, Melaku; Fetters, Tamara; Desta, Demeke

    2016-08-11

    Where unmet need for the safest, most effective, and long-acting reversible contraceptives (LARCs) is very high, the health system and partners need to implement problem-solving, locally feasible, and comprehensive family planning delivery strategies. Because young and unmarried women are most at risk for unintended pregnancy and repeat abortion due to poor access to contraceptive services, postabortion family planning (PAFP) is a key component in such strategies. In Southern Nations, Nationalities, and People's Region, Ethiopia, Ipas implemented health system strengthening efforts from fiscal year (FY) 2010 (July 2009 to June 2010) to FY 2014 (July 2013 to June 2014) to improve the quality of PAFP services and expand method choice in 101 public facilities. The intervention significantly improved PAFP uptake at the project sites. Specifically, the proportion of abortion clients receiving LARCs progressively improved during the intervention period. The proportion of abortion clients who left the facilities with a contraceptive method increased from 58% in FY 2010 to 83% in FY 2014. The share of method mix for LARCs rose from 2% in FY 2010 to 55% in FY 2014, while the share for condoms, injectables, and oral contraceptives declined from 98% to 45%. Implant use rose from 2% in FY 2010 to 43% in FY 2014, while the use of intrauterine devices increased from 0.1% in FY 2010 to 12% in FY 2014. A larger proportion of PAFP users received LARCs at health centers, where midwives and nurses are the primary providers, than at hospitals (59% versus 37%, respectively). A broader method mix can satisfy clients with a variety of needs, a key factor for higher uptake of more effective methods and program success. Further evidence-based interventions need to be implemented to improve the quality of PAFP in a feasible and replicable strategy that addresses unmet need for modern contraceptive methods. PMID:27540126

  6. Safety, pharmacokinetic and pharmacodynamic properties of TV-1106, a long-acting GH treatment for GH deficiency

    PubMed Central

    Cohen-Barak, Orit; Sakov, Anat; Rasamoelisolo, Michele; Bassan, Merav; Brown, Kurt; Mendzelevski, Boaz; Spiegelstein, Ofer

    2015-01-01

    Background TV-1106 (Teva Pharmaceuticals) is a genetically fused recombinant protein of human GH (hGH) and human serum albumin, in development for treatment of GH deficiency (GHD). TV-1106 is expected to have an extended duration of action compared to daily GH treatment and may enable a reduction in the frequency of injections and improve compliance and quality of life for adults and children requiring GHD therapy. Objective To assess the safety, local tolerability, pharmacokinetics and pharmacodynamics of TV-1106 following single s.c. injections in healthy male volunteers. Methods Subjects (n=56) were assigned to one of seven ascending dose groups (3–100 mg) and received either a single dose of TV-1106 (n=6) or placebo (n=2) by s.c. injection. Results Eighteen subjects reported 43 adverse effects (AEs), which were mild to moderate; no serious AEs (SAEs) occurred. In 50, 70 and 100 mg groups there were mild to moderate increases in heart rate and systolic blood pressure that significantly correlated with higher levels of IGF1. TV-1106 showed pharmacokinetic characteristics of a long-acting hGH as demonstrated by a terminal elimination half-life of 23–35 h, delayed time of peak concentration, and systemic levels seen up to 7 days after dosing. IGF1 levels increased in a dose-dependent manner, before reaching a plateau, with levels above baseline extending beyond 7 days post dose. Conclusion Single administration of TV-1106 up to 100 mg was safe in healthy volunteers. Pharmacokinetics and pharmacodynamics support once-weekly administration in patients with GHD. PMID:26286586

  7. Investigation of salt formation between memantine and pamoic acid: Its exploitation in nanocrystalline form as long acting injection.

    PubMed

    Mittapelly, Naresh; Rachumallu, Ramakrishna; Pandey, Gitu; Sharma, Shweta; Arya, Abhishek; Bhatta, Rabi Shankar; Mishra, Prabhat Ranjan

    2016-04-01

    In the present work, we prepared memantine-pamoic acid (MEM-PAM) salt by counter ion exchange in the aqueous phase to reduce the water solubility of MEM hydrochloride (native form) to make it suitable for long acting injection. The ratio of MEM to PAM in salt formation was optimized to maximize the loading efficiency and complexation efficiency. The 2:1 molar ratio of MEM to PAM salt form displayed nearly 95% complexation efficiency and 50% drug loading. The solubility was decreased by a ∼1250 folds. Thermo Gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction Analysis (PXRD) studies revealed the formation of new solid phase. Additionally, Nuclear Magnetic Resonance (NMR) spectroscopy confirmed the anhydrous nature of the salt form. Through Fourier transformation infrared spectroscopy (FT-IR) we identified the molecular interactions. Further, the microcrystals of the salt were transformed into nanocrystals (NCs) using high pressure homogenization. The particle size distribution and atomic force microscopy confirmed the monodispersed and spherical shape of the NCs. The in vitro dissolution studies were performed under sink condition in phosphate buffer saline pH 6.8. The results of MTT assay in murine fibroblast 3T3 cell line show that the NCs were less cytotoxic and more tolerable than plain MEM HCl. The in vivo performance of NCs administered as i.m. injection at three different doses in female Sprague-Dawley rats showed that the plasma levels lasted till the 24th day of the study. The pharmacokinetic parameters AUC0-∞ and Cmax increased linearly with increasing dose. Therefore, the results suggest that injectable NCs could represent a therapeutic alternative for the treatment of AD. PMID:26850817

  8. Amelioration of the cardiovascular effects of cocaine in rhesus monkeys by a long-acting mutant form of cocaine esterase.

    PubMed

    Collins, Gregory T; Carey, Kathy A; Narasimhan, Diwahar; Nichols, Joseph; Berlin, Aaron A; Lukacs, Nicholas W; Sunahara, Roger K; Woods, James H; Ko, Mei-Chuan

    2011-04-01

    A long-acting mutant form of a naturally occurring bacterial cocaine esterase (T172R/G173Q CocE; double mutant CocE (DM CocE)) has previously been shown to antagonize the reinforcing, convulsant, and lethal effects of cocaine in rodents. However, the effectiveness and therapeutic characteristics of DM CocE in nonhuman primates, in a more clinically relevant context, are unknown. The current studies were aimed at (1) characterizing the cardiovascular effects of cocaine in freely moving rhesus monkeys, (2) evaluating the capacity of DM CocE to ameliorate these cocaine-induced cardiovascular effects when administered 10 min after cocaine, and (3) assessing the immunological responses of monkeys to DM CocE following repeated administration. Intravenous administration of cocaine produced dose-dependent increases in mean arterial pressure (MAP) and heart rate (HR) that persisted throughout the 2-h observation period following a dose of 3.2 mg/kg cocaine. Cocaine failed to produce reliable changes in electrocardiograph (ECG) parameters, body temperature, and locomotor activity. DM CocE produced a rapid and dose-dependent amelioration of the cardiovascular effects, with saline-like MAP measures restored within 5-10 min, and saline-like HR measures restored within 20-40 min of DM CocE administration. Although administration of DM CocE produced increases in anti-CocE antibodies, they did not appear to have a neutralizing effect on the capacity of DM CocE to reverse the cardiovascular effects of cocaine. In conclusion, these findings in monkeys provide strong evidence to suggest that highly efficient cocaine esterases, such as DM CocE, can provide a potential therapeutic option for treatment of acute cocaine intoxication in humans. PMID:21289605

  9. HelpDesk answers: is it safe to add long-acting β-2 agonists to inhaled corticosteroids in patients with persistent asthma?

    PubMed

    Townsend, Laurie; Madlon-Kay, Diane J

    2015-06-01

    Possibly. Long-acting β-2 agonists (LABAs) used in combination with inhaled corticosteroids (ICS) don't appear to increase all-cause mortality or serious adverse events in patients with persistent asthma compared with ICS alone. Studies showing an increase in catastrophic events had serious methodologic issues. A large surveillance study is ongoing.

  10. The effect of administering long-acting oxytetracycline and tilmicosin either by dart gun or by hand on injection site lesions and drug residues in beef cattle.

    PubMed Central

    Van Donkersgoed, J; VanderKop, M; Salisbury, C; Sears, L; Holowath, J

    1999-01-01

    Forty yearling cattle were injected intramuscularly with long-acting oxytetracycline and subcutaneously with tilmicosin by dart gun or by hand in a chute 28 days prior to slaughter. The drugs caused injection site lesions and antibiotic residues in the neck and thigh that varied by technique, dose, and site. PMID:12001341

  11. Potential Clinical and Economic Value of Long-Acting Preexposure Prophylaxis for South African Women at High-Risk for HIV Infection

    PubMed Central

    Walensky, Rochelle P.; Jacobsen, Margo M.; Bekker, Linda-Gail; Parker, Robert A.; Wood, Robin; Resch, Stephen C.; Horstman, N. Kaye; Freedberg, Kenneth A.; Paltiel, A. David

    2016-01-01

    Background. For young South African women at risk for human immunodeficiency virus (HIV) infection, preexposure prophylaxis (PrEP) is one of the few effective prevention options available. Long-acting injectable PrEP, which is in development, may be associated with greater adherence, compared with that for existing standard oral PrEP formulations, but its likely clinical benefits and additional costs are unknown. Methods. Using a computer simulation, we compared the following 3 PrEP strategies: no PrEP, standard PrEP (effectiveness, 62%; cost per patient, $150/year), and long-acting PrEP (effectiveness, 75%; cost per patient, $220/year) in South African women at high risk for HIV infection (incidence of HIV infection, 5%/year). We examined the sensitivity of the strategies to changes in key input parameters among several outcome measures, including deaths averted and program cost over a 5-year period; lifetime HIV infection risk, survival rate, and program cost and cost-effectiveness; and budget impact. Results. Compared with no PrEP, standard PrEP and long-acting PrEP cost $580 and $870 more per woman, respectively, and averted 15 and 16 deaths per 1000 women at high risk for infection, respectively, over 5 years. Measured on a lifetime basis, both standard PrEP and long-acting PrEP were cost saving, compared with no PrEP. Compared with standard PrEP, long-acting PrEP was very cost-effective ($150/life-year saved) except under the most pessimistic assumptions. Over 5 years, long-acting PrEP cost $1.6 billion when provided to 50% of eligible women. Conclusions. Currently available standard PrEP is a cost-saving intervention whose delivery should be expanded and optimized. Long-acting PrEP will likely be a very cost-effective improvement over standard PrEP but may require novel financing mechanisms that bring short-term fiscal planning efforts into closer alignment with longer-term societal objectives. PMID:26681778

  12. Central nervous system effects of the interaction between risperidone (single dose) and the 5-HT6 antagonist SB742457 (repeated doses) in healthy men

    PubMed Central

    Liem-Moolenaar, Marieke; Rad, Mandana; Zamuner, Stefano; Cohen, Adam F; Lemme, Francesca; Franson, Kari L; van Gerven, Joop M A; Pich, Emilio Merlo

    2011-01-01

    AIM Several lines of evidence suggest a possible role of 5-HT6receptor antagonists in cognitive dysfunction of schizophrenia. Atypical antipsychotics, such as risperidone, are currently used in these disorders. Therefore, the pharmacological interactions between the 5-HT6 antagonist SB-742457 and risperidone were investigated in the light of possible co-medication. METHODS A randomized, double-blind, two-way crossover design was used to study the interaction between multiple doses SB-742457 50 mg and a single dose risperidone 2 mg in 18 healthy subjects. RESULTS Treatment was well tolerated. The most common adverse event was somnolence in 83% during the combination vs. 50% of subjects after risperidone, 32% after placebo and 11% after SB-742457. Combination treatment produced a statistically significant increase in the maximum plasma concentration of risperidone and had no effect on SB-742457 pharmacokinetics. Risperidone decreased saccadic peak velocity, finger tapping, adaptive tracking, subjective alertness, delayed word recognition and body sway and increased electroencephalogram (EEG) theta power and prolactin. The only pharmacodynamic interaction of risperidone and SB-742457 was an increase of absolute EEG alpha (ratio = 1.25, 95% CI = 1.11, 1.40, P = 0.0004) and beta power (ratio = 1.14, 95% CI = 1.03, 1.27, P = 0.016). No significant effects of SB-742457 alone were found. CONCLUSION The pharmacokinetic interactions between SB-742457 and risperidone detected in this study were not clinically relevant. The increase in EEG alpha and beta power is incompatible with enhanced risperidone activity, but could point to mild arousing effects of the combination. Most pharmacodynamic changes of risperidone are consistent with previously reported data. The potential cognitive effects of SB-742457 remain to be established. PMID:21223356

  13. Determinants of long acting and permanent contraceptive methods utilization among married women of reproductive age groups in western Ethiopia: a cross-sectional study

    PubMed Central

    Melka, Alemu Sufa; Tekelab, Tesfalidet; Wirtu, Desalegn

    2015-01-01

    Introduction In Ethiopia information on the level of utilization of the long term and permanent contraceptive methods and associated factorsis lacking. The aim of this study was to understand the determinant factors of long acting and permanent contraceptive methods use among married women of reproductive age in Western Ethiopia. Methods A community based cross- sectional study design was employed. Multi stage sampling was used to select 1003 study participants. Data was collected from April 10 to April 25,2014 using a pre- tested structured questionnaire. The data were entered using Epi-info version 3.5.1 and exported to SPSS version 20 for analysis. Multivariate logistic regression analysis was done to identify predictors of long acting and permanent contraceptive methods at 95% CL. Results Use of long acting and permanent contraceptive methods in this study was found to be 20%. Survey results showed a significant positive association between utilization of long acting and permanent contraceptive methods and women's education (AOR = 1.72, 95%CI = 1.02 - 3.05), women's occupation (AOR = 2.01, 95% CI = 1.11 -3.58), number of live children (AOR = 2.42, 95% CI: 1.46- 4.02), joint fertility related decision (AOR = 6.11, 95% CI: 2.29- 16.30), having radio/TV (AOR = 2.31, 95% CI: 1.40 - 3.80), and discussion with health care provider about long acting and permanent contraceptive methods (AOR = 13.72, 95% CI: 8.37 - 22.47). Conclusion Efforts need to be aimed at women empowerment, health education, and encouraging open discussion of family planning by couples PMID:26523185

  14. Long-acting somatostatin analogues provide significant beneficial effect in patients with refractory small bowel angiodysplasia: Results from a proof of concept open label mono-centre trial

    PubMed Central

    Hall, Barry; Breslin, Niall; McNamara, Deirdre

    2015-01-01

    Introduction Small bowel angiodysplasias account for over 50% of causes of small bowel bleeding and carry a worse prognosis than lesions located elsewhere in the gastrointestinal tract. Re-bleeding rates are high even after first-line endoscopic therapy and are associated with high levels of morbidity for affected patients. Small trials of long-acting somatostatin analogues have shown promising results but have not yet been assessed in patients with refractory small bowel disease. Aim The purpose of this study was to assess the effect of long-acting somatostatin analogues in reducing re-bleeding rates and transfusion requirements, and improving haemoglobin levels in patients with refractory small bowel angiodysplasia. Methods Patients with refractory small bowel angiodysplasia were treated with 20 mg of long-acting octreotide for a minimum of three months. Response was assessed according to: rates of re-bleeding, haemoglobin levels, transfusion requirements, and side effects. Results A total of 24 patients were initially treated and 20 received at least three doses. Rates of complete, partial and non-response were 70%, 20% and 10% respectively. Average haemoglobin rates increased from 9.19 g/dl to 11.35 g/dl (p = 0.0027, 95% confidence interval (CI) −3.5 to −1.1) in the group overall and 70% remained transfusion-free after a mean treatment duration of 8.8 months. The rate of adverse events was higher than previously reported at 30%. Conclusion Long-acting somatostatin analogues offer a therapeutic advantage in a significant proportion of patients with small bowel angiodysplasia. With careful patient selection and close observation, a long-acting somatostatin analogue should be considered in all patients with persistent anaemia attributable to refractory disease in conjunction with other standard treatments. PMID:26966525

  15. Comparative study of the efficacy and safety between blonanserin and risperidone for the treatment of schizophrenia in Chinese patients: A double-blind, parallel-group multicenter randomized trial.

    PubMed

    Li, Huafang; Yao, Chen; Shi, Jianguo; Yang, Fude; Qi, Shuguang; Wang, Lili; Zhang, Honggeng; Li, Jie; Wang, Chuanyue; Wang, Chuansheng; Liu, Cui; Li, Lehua; Wang, Qiang; Li, Keqing; Luo, Xiaoyan; Gu, Niufan

    2015-10-01

    This randomized, double-blind study compared the efficacy and safety of blonanserin and risperidone to treat Chinese schizophrenia patients aged ≥18 and < 65 years. Patients with Positive and Negative Syndrome Scale (PANSS) total scores ≥70 and ≤ 120 were randomized to receive blonanserin or risperidone using a gradual dose-titration method (blonanserin tablets: 8-24 mg/day; risperidone tablets: 2-6 mg/day), twice daily. Treatment populations consisted of 128 blonanserin-treated patients and 133 risperidone-treated patients. Intention-to-treat analysis was performed using the last observation carried forward method. Reductions of PANSS total scores by blonanserin and risperidone treatment were -30.59 and -33.56, respectively. Risperidone treatment was associated with elevated levels of serum prolactin (67.16% risperidone versus 52.31% blonanserin) and cardiac-related abnormalities (22.39% risperidone versus 12.31% blonanserin), and blonanserin patients were more prone to extrapyramidal side effects (48.46% blonanserin versus 29.10% risperidone). In conclusion, blonanserin was as effective as risperidone for the treatment of Chinese patients with schizophrenia. The overall safety profiles of these drugs are comparable, although blonanserin was associated with a higher incidence of EPS and risperidone was associated with a higher incidence of prolactin elevation and weight gain. Thus, blonanserin is useful for the treatment of Chinese schizophrenia patients. PMID:26343601

  16. Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder: fMRI outcomes

    PubMed Central

    Pavuluri, Mani N.; Passarotti, Alessandra M.; Lu, Lisa H.; Carbray, Julie A; Sweeney, John A.

    2011-01-01

    To determine the relative effects of risperidone and divalproex on brain function in pediatric mania. This is a double-blind 6-week fMRI trial with 24 unmedicated manic patients randomized to risperidone or divalproex, and 14 healthy controls (HC) matched for IQ and demographic factors (mean age: 13.1±3.3 years). A pediatric affective color matching task, in which subjects matched the color of a positive, negative or neutral word with one of two colored circles, was administered. The primary clinical measure was the Young Mania Rating Scale (YMRS). The risperidone group, relative to HC, showed an increase in activation from pre- to post-treatment in right pregenual and subgenual anterior cingulate cortex and decreased activation in bilateral middle frontal gyrus during the negative condition; and decreased activation in left inferior and medial, and right middle frontal gyri, left inferior parietal lobe, and right striatum with positive condition. In the divalproex group, relative to HC, there was an increased activation in right superior temporal gyrus in the negative condition; and in left medial frontal gyrus and right precuneus with the positive condition. Greater pre-treatment right amygdala activity with negative and positive condition in the risperidone group, and left amygdala activity with positive condition in divalproex group, predicted poor response on YMRS. Risperidone and divalproex yield differential patterns of prefrontal activity during an emotion processing task in pediatric mania. Increased amygdala activity at baseline is a potential biomarker predicting poor treatment response to both the risperidone and divalproex. PMID:21592741

  17. Choline acetyltransferase expression in rat prefrontal cortex and hippocampus after acute and chronic exposure to amisulpride, haloperidol, and risperidone.

    PubMed

    Huang, Guang-Biao; Zhao, Tong; Li, Chun-Rong; Sui, Zhi-Yan; Kang, Nam-In; Han, Eui-Hyeog; Chung, Young-Chul

    2012-10-24

    Recently, there has been an increasing concern that atypical antipsychotics as well as typical ones may cause detrimental effects on cognitive function. Supporting evidence comes from many preclinical studies demonstrating that long-term administration of haloperidol, risperidone, and ziprasidone reduced choline acetyltransferase (ChAT) expression in rat hippocampus (HIP). However, to the best of our knowledge, no studies have examined the effects of amisulpride on ChAT expression in rats. Therefore, the aim of this study was to investigate the effects of acute and chronic administration of amisulpride, haloperidol, and risperidone on ChAT expression in the rat prefrontal cortex (PFC) and HIP. Animals received daily intraperitoneal (i.p.) injections of amisulpride (5 or 100mg/kg), haloperidol (1 or 2mg/kg), risperidone (1 or 2mg/kg) or vehicle for 7 or 45 days. One day after the last injection, rats were sacrificed. ChAT immunoreactivity was assessed with immunofluorescence staining. Target areas of brain were PFC and HIP (CA1, CA3 and DG). The short-term administration of haloperidol and risperidone produced significant decrease of ChAT immunoreactivity in the PFC and HIP compared to vehicle whereas amisulpride had no effects on ChAT immunoreactivity in the PFC and HIP. In long-term study, haloperidol and risperidone decreased ChAT-positive cells and/or fiber pixel density in the PFC and HIP whereas amisulpride decreased ChAT-positive cells in the PFC and had no effects on fiber pixel density of ChAT in the HIP. The results suggest that both short-term and long-term administration of haloperidol and risperidone, and long-term administration of amisulpride may produce detrimental effects on cognitive function by reducing ChAT expression in the PFC and/or HIP.

  18. Risperidone use in a teaching hospital during its first year after market approval: economic and clinical implications.

    PubMed

    Carter, C S; Mulsant, B H; Sweet, R A; Maxwell, R A; Coley, K; Ganguli, R; Branch, R

    1995-01-01

    Risperidone, a new antipsychotic drug, was recently approved by the Food and Drug Administration (FDA) on the basis of its having comparable efficacy and less toxicity than haloperidol. In a preliminary study to evaluate the therapeutic efficiency of this drug, we conducted a survey of resperidone utilization, cost, and safety during its first year of availability at an academic psychiatric hospital. Data were obtained from a computerized, centralized medical record system, from an adverse drug reaction monitoring system, and from pharmacy purchasing records. In its first year of availability, risperidone became the second most widely used antipsychotic agent at our institution. Most of this use extended beyond the adult schizophrenia population, for whom pre-marketing safety and efficacy data are available. The direct institutional cost of risperidone treatment exceeded the entire budget for antipsychotic drugs during the year before its release. Results from the adverse drug reaction reporting system did not indicate a strong advantage of risperidone over more established antipsychotic agents with respect to extrapyramidal side effects. Furthermore, the mean dose of risperidone associated with extrapyramidal symptoms was 3.5 mg/day, considerably lower than that suggested by pre-marketing studies in a more select patient group. These results confirm that new pharmacological agents are generally used in much broader patient populations than those for which efficacy and safety have been established prior to FDA approval. This study also raises questions about the therapeutic efficiency of risperidone compared with other antipsychotic drugs. We conclude that systematic studies of outcome, safety, and cost of new pharmaceuticals in naturalistic settings are needed to provide the data necessary to establish local standards of cost-effective care.

  19. Changes in Use of Long-Acting Reversible Contraceptive Methods Among U.S. Women, 2009–2012

    PubMed Central

    Kavanaugh, Megan L.; Jerman, Jenna; Finer, Lawrence B.

    2016-01-01

    OBJECTIVE To examine current levels, current correlates of, and changes in long-acting reversible contraceptive (LARC) use, including intrauterine devices and implants, among females aged 15–44 years using contraception between 2008–2010 and 2011–2013 with specific attention to associations between race, income, and age and their LARC use. METHODS We analyzed data from two rounds of the National Survey of Family Growth, nationally representative samples of females aged 15–44 years, consisting of 6,428 females in 2008–2010 and 5,601 females in 2011–2013. We conducted simple and multivariable logistic regression analyses with adjustments for the sampling design to identify demographic characteristics predictive of LARC use and changes in these patterns between the two time periods. In this cross-sectional, descriptive study, our primary outcome of interest was current prevalence of LARC use among all contraceptive users at the time of the interview. RESULTS The prevalence of LARC use among contracepting U.S. females increased from 8.5% in 2009 to 11.6% in 2012 (P<.01). The most significant increases occurred among Hispanic females (from 8.5% to 15.1%), those with private insurance (7.1–11.1%), those with fewer than two sexual partners in the previous year (9.2–12.4%), and those who were nulliparous (2.1–5.9%) (all P<.01). In multivariable analyses adjusting for key demographic characteristics, the strongest associations with LARC use in 2012 were parity (adjusted odds ratios [ORs] 4.3–5.5) and having a history of stopping non-LARC hormonal use (adjusted OR 1.9). Women aged 35–44 years (adjusted OR 0.3) were less likely to be LARC users than their counterparts (all P<.001). Poverty status was not associated with LARC use. There were no differences in discontinuation of LARC methods resulting from dissatisfaction between minority women and non-Hispanic white women. CONCLUSION During the most recent time period surveyed, use of LARC methods

  20. Combined inhaled corticosteroid and long-acting β2-adrenergic agonist therapy for noncystic fibrosis bronchiectasis with airflow limitation

    PubMed Central

    Wei, Ping; Yang, Jia-Wei; Lu, Hai-Wen; Mao, Bei; Yang, Wen-Lan; Xu, Jin-Fu

    2016-01-01

    Abstract Background and objective: There is presently no clear evidence on the effect of combined treatment for non-cystic fibrosis (non-CF) bronchiectasis with inhaled corticosteroid (ICS) and long-acting β2-adrenergic agonist (LABA). The objective of this study is to assess the efficacy and safety of salmeterol-fluticasone combined inhaled therapy for non-CF bronchiectasis with airflow limitation. Methods: An observational study was performed in 120 non-CF bronchiectasis patients diagnosed by high-resolution computed tomography (HRCT) scanning of the chest. Patients received either routine therapy or salmeterol-fluticasone (100/500 μg daily) combined inhaled therapy on the basis of routine therapy. Clinical symptoms, health-related quality of life (HRQL), lung function, short-acting β2-adrenergic agonist (SABA) use, and safety were monitored throughout the study. Results: OF the 120 subjects, 60 received combined inhaled therapy and 60 received routine therapy. Compared to the control group, the combined inhaled therapy group showed significant improvement in their clinical symptom scores (−2.21 vs. −0.31, P = 0.002) and a reduction in number of weekly SABA usage (−4.2 vs. 0.1, P < 0.01). In addition, patients in the inhaled therapy group achieved a significant improvement in HRQL based on mMRC (−1.51 vs. −0.31, P < 0.005) and SGRQ (−7.83 vs. −2.16, P < 0.01) scoring accompanied with no severe adverse events. There were fewer exacerbation frequencies in the combined inhaled therapy group over the 12 months of treatment compared to the control group (1 [0–2] vs. 2 [1–4], P = 0.017). Furthermore, stratified analysis indicated that combined inhaled therapy partially improve lung function for patients for whom it is severely impaired and those with pseudomonas aeruginosa isolated. Conclusion: Our results show that salmeterol-fluticasone combined inhaled therapy should be effective and safe for non-CF bronchiectasis patients

  1. Steroid secretion in polycystic ovarian disease after ovarian suppression by a long-acting gonadotropin-releasing hormone agonist.

    PubMed

    Chang, R J; Laufer, L R; Meldrum, D R; DeFazio, J; Lu, J K; Vale, W W; Rivier, J E; Judd, H L

    1983-05-01

    The principal glandular source of increased serum androgens in polycystic ovarian disease (PCO) is controversial), since complete separation of ovarian from adrenal function has not been achieved. The purpose of this study was to determine whether a long-acting GnRH agonist could be used to selectively inhibit ovarian steroid secretion in PCO and ovulatory women. Each of five typical PCO patients and six ovulatory subjects on day 2 of their menstrual cycles received D-Trp6-Pro9-NEt-LHRH (GnRH-a; 100 micrograms) for 28 consecutive days. Their results were compared to basal serum hormone values in eight oophorectomized women. In response to GnRH-a, PCO and normal subjects exhibited sharp and sustained rises of LH and gradual decreases in FSH. These levels were clearly less than basal levels seen in oophorectomized women. Episodic LH release was significantly attenuated in both groups at the end of GnRH-a treatment. After the administration of agonist, serum estradiol (E2), estrone (E1), androstenedione (A), and testosterone (T) were suppressed to castrate levels in both groups. The decrements of E2 and E1 in PCO were gradual and continuous compared to initial dramatic rises, which reached peaks at 14 days, and subsequent abrupt falls in the ovulatory controls. Serum A and T declined steadily in both groups. Basal serum dehydroepiandrosterone and dehydroepiandrosterone sulfate, but not cortisol, levels were elevated in PCO subjects. The 24-h secretion patterns and responses to ACTH of these hormones in PCO and ovulatory subjects were unaltered by GnRH-a administration. These data demonstrate that 1) in PCO subjects, GnRH-a induced complete suppression of ovarian steroid secretion, as circulating levels at the end of treatment were comparable to those seen in our oophorectomy subjects; 2) elevated A and T levels in PCO patients were derived primarily from the ovary; and 3) adrenal steroid secretion was unaltered by GnRH-a in both PCO and normal women.

  2. The Tupange Project in Kenya: A Multifaceted Approach to Increasing Use of Long-Acting Reversible Contraceptives

    PubMed Central

    Muthamia, Michael; Owino, Kenneth; Nyachae, Paul; Kilonzo, Margaret; Kamau, Mercy; Otai, Jane; Kabue, Mark; Keyonzo, Nelson

    2016-01-01

    ABSTRACT Background: Long-acting reversible contraceptives (LARCs) are safe and highly effective, and they have higher continuation rates than short-acting methods. Because only a small percentage of sexually active women in Kenya use LARCs, the Tupange project implemented a multifaceted approach to increase uptake of LARCs, particularly among the urban poor. The project included on-site mentoring, whole-site orientation, commodity security, quality improvement, and multiple demand-promotion and service-provision strategies, in the context of wide method choice. We report on activities in Nairobi between July 2011 and December 2014, the project implementation period. Methods: We used a household longitudinal survey of women of reproductive age to measure changes in the contraceptive prevalence rate (CPR) and other family planning-related variables. At baseline in July 2010, 2,676 women were interviewed; about 50% were successfully tracked and interviewed at endline in December 2014. A baseline service delivery point (SDP) survey of 112 health facilities and 303 service providers was conducted in July 2011, and an endline SDP survey was conducted in December 2014 to measure facility-based interventions. The SDP baseline survey was conducted after the household survey, as facilities were selected based on where clients said they obtained services. Results: The project led to significant increases in use of implants and intrauterine devices (IUDs). Uptake of implants increased by 6.5 percentage points, from 2.4% at baseline to 8.9% by endline, and uptake of IUDs increased by 2.1 percentage points, from 2.2% to 4.3%. By the endline survey, 37.7% of clients using pills and injectables at baseline had switched to LARCs. Contraceptive use among the poorest and poor wealth quintiles increased by 20.5 and 21.5 percentage points, respectively, from baseline to endline. Various myths and misconceptions reported about family planning methods declined significantly between

  3. Efficacy of 4 Years of Octreotide Long-Acting Release Therapy in Patients With Severe Polycystic Liver Disease

    PubMed Central

    Hogan, Marie C.; Masyuk, Tetyana; Bergstralh, Eric; Li, Bill; Kremers, Walter K.; Vaughan, Lisa E.; Ihrke, Angela; Severson, Amanda L.; Irazabal, Maria V.; Glockner, James; LaRusso, Nicholas F.; Torres, Vicente E.

    2016-01-01

    Objective To observe the effect on total liver volume (TLV) on and off therapy in selected symptomatic patients with autosomal dominant polycystic kidney disease (ADPKD) or autosomal dominant polycystic liver disease (PLD) who received octreotide long-acting release (OctLAR) for up to 4 years. Patients and Methods Twenty-eight of 42 participants in a prospective 2-year clinical trial of OctLAR (40 mg monthly) consisting of double-blind, randomized (year 1) and open-label treatment (year 2) phases reenrolled in a 2-year open-label extension (OLE) study after being off OctLAR a mean of 8.3 months (original study: July 1, 2007, through June 30, 2013). Participants underwent magnetic resonance imaging at baseline, years 1 and 2, reenrollment, and study completion. Primary end point: change in TLV; secondary end points: changes in total kidney volume, glomerular filtration rate, quality of life (QoL), safety, vital signs, and laboratory parameters. Results Twenty-five participants (59.5%) completed the OLE. Off therapy, TLVs increased a mean ± SD of 3.4%±8.2% per year; after resuming therapy, TLVs decreased a mean ± SD of −4.7%±6.1% per year. Despite regrowth off treatment, overall reductions were observed, with a median (interquartile range) TLV of 4047 mL (3107–7402 mL) at baseline and 3477 (2653–7131 mL) at study completion (−13.2%; P<.001) and with improved health-related QoL. Total kidney volumes increased, and glomerular filtration rates declined from 58.2 mL/min to 54.5 mL/min (n=16) in patients with ADPKD on therapy from baseline to study completion. Conclusion Therapy with OctLAR over 4 years in selected patients with symptomatic PLD arrested PLD progression, alleviating symptoms and improving health-related QoL. Discontinuation led to organ regrowth. Trial Registration: clinicaltrials.gov Identifier: NCT00426153. PMID:26166166

  4. Treatment and control of bovine sarcoptic and psoroptic mange infestation with ivermectin long-acting injectable (IVOMEC(®) GOLD).

    PubMed

    Hamel, Dietmar; Joachim, Anja; Löwenstein, Michael; Pfister, Kurt; Silaghi, Cornelia; Visser, Martin; Winter, Renate; Yoon, Stephen; Cramer, Luiz; Rehbein, Steffen

    2015-02-01

    The efficacy of ivermectin long-acting injection (IVM LAI, IVOMEC® GOLD, Merial; 3.15 % ivermectin w/v) formulation was evaluated in cattle with induced Sarcoptes scabiei var. bovis or Psoroptes ovis infestations. A total of 64 cattle were included in this series of four studies, with 16 animals per study. Approximately, 8 weeks following initial induced mite infestation, cattle were allocated to treatment groups based on decreasing pre-treatment bodyweights. Treatments (saline (control) or IVM LAI (630 mcg ivermectin/kg bodyweight) at 1 mL/50 kg bodyweight) were administered by a single subcutaneous injection in front of the right shoulder on Day 0. Skin scrapings were collected prior to treatment and at approximately weekly intervals for 8 weeks thereafter to establish live mite counts. Character and extent of skin lesions were evaluated at each sampling. Animals were weighed before treatment and at the end of the studies. Mite counts of the IVM LAI-treated animals were significantly (p < 0.05) lower than those of the controls in all four studies at all occasions post-treatment. In the two Sarcoptes studies, IVM LAI-treated cattle were free of mites at 14 days after treatment and in the Psoroptes studies at 13 or 28 days post-treatment. All IVM LAI-treated cattle remained free of mites to the end of the studies while all control animals remained infested. Mange lesions of the IVM LAI-treated animals improved significantly (p < 0.05) compared to those of the controls from Day 21 (Sarcoptes studies) and from Days 28 or 34 (Psoroptes studies). In all studies, mean weight gain over the 8 week post-treatment period was significantly (p < 0.05) higher for the IVM LAI-treated animals than for the controls: Sarcoptes studies, 64.1 and 68.6 kg vs. 46.9 and 48.6 kg, respectively; Psoroptes studies, 43.0 and 43.4 kg vs. 20.8 and 34.9 kg, respectively. All animals accepted the treatment well, and no treatment-related health problems and adverse events were

  5. Long-acting anticoagulant rodenticide poisoning: an evidence-based consensus guideline for out-of-hospital management.

    PubMed

    Caravati, E Martin; Erdman, Andrew R; Scharman, Elizabeth J; Woolf, Alan D; Chyka, Peter A; Cobaugh, Daniel J; Wax, Paul M; Manoguerra, Anthony S; Christianson, Gwenn; Nelson, Lewis S; Olson, Kent R; Booze, Lisa L; Troutman, William G

    2007-01-01

    The objective of this guideline is to assist poison center personnel in the out-of-hospital triage and initial management of patients with suspected exposure to long-acting anticoagulant rodenticides (LAAR). An evidence-based expert consensus process was used to create this guideline. It is based on an assessment of current scientific and clinical information. The panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and health professionals providing care. The grade of recommendation is in parentheses. 1) Patients with exposure due to suspected self-harm, abuse, misuse, or potentially malicious administration should be referred to an emergency department immediately regardless of the doses reported (Grade D). 2) Patients with symptoms of LAAR poisoning (e.g., bleeding, bruising) should be referred immediately to an emergency department for evaluation regardless of the doses reported (Grade C). 3) Patients with chronic ingestion of LAAR should be referred immediately to an emergency department for evaluation of intent and potential coagulopathy (Grade B). 4) Patients taking anticoagulants therapeutically and who ingest any dose of a LAAR should have a baseline prothrombin time measured and then again at 48-72 hours after ingestion (Grade D). 5) Patients with unintentional ingestion of less than 1 mg of LAAR active ingredient can be safely observed at home without laboratory monitoring. This includes practically all unintentional ingestions in children less than 6 years of age (Grade C). 6) Pregnant patients with unintentional exposure to less than 1 mg of LAAR active ingredient should be evaluated by their obstetrician or primary care provider as an outpatient. Immediate referral to an ED or clinic is not required (Grade D). 7) Patients with unintentional ingestion of 1 mg or more of active ingredient and are asymptomatic should be evaluated for coagulopathy at 48-72 hours after exposure

  6. Phosphodiesterase 10A inhibitor MP-10 effects in primates: Comparison with risperidone and mechanistic implications

    PubMed Central

    Uthayathas, Subramaniam; Masilamoni, Gunasingh J.; Shaffer, Christopher L.; Schmidt, Christopher J.; Menniti, Frank S.; Papa, Stella M.

    2013-01-01

    Phosphodiesterase 10A (PDE10A) is highly expressed in striatal medium spiny neurons of both the direct and indirect output pathways. Similar to dopamine D2 receptor antagonists acting on indirect pathway neurons, PDE10A inhibitors have shown behavioral effects in rodent models that predict antipsychotic efficacy. These findings have supported the clinical investigation of PDE10A inhibitors as a new treatment for schizophrenia. However, PDE10A inhibitors and D2 antagonists differ in effects on direct pathway and other neurons of the basal ganglia, indicating that these two drug classes may have divergent antipsychotic efficacy and side effect profile. In the present study, we compare the behavioral effects of the selective PDE10A inhibitor MP-10 to those of the clinical standard D2 antagonist risperidone in rhesus monkeys using a standardized motor disability scale for parkinsonian primates and a newly designed “Drug Effects on Nervous System” scale to assess non-motor effects. Behavioral effects of MP-10 correlated with its plasma levels and its regulation of metabolic activity in striatal and cortical regions as measured by FDG-PET imaging. While MP-10 and risperidone broadly impacted similar behavioral domains in the primate, their effects had a different underlying basis. MP-10-treated animals retained the ability to respond but did not engage tasks, whereas risperidone-treated animals retained the motivation to respond but were unable to perform the intended actions. These findings are discussed in light of what is currently known about the modulation of striatal circuitry by these two classes of compounds, and provide insight into interpreting emerging clinical data with PDE10A inhibitors for the treatment of psychotic symptoms. PMID:24490227

  7. Evaluation of teratogenic effects of risperidone following simultaneous administration with antihypertensive and antiemetic drugs.

    PubMed

    Tauqeer, Shaista; Khan, Rafeeq Alam; Siddiqui, Afaq Ahmed

    2012-01-01

    Multiple drug administration is an important aspect of clinical practice particularly in specific physiological situation such as in neonates, elderly or pregnancy, since in all such situations, possibility of unwanted effects increases due to altered body physiology. In present study, the teratogenic effects of multiple drug administration risperidone, meclizine/pyridoxine and hydralazine have been compared with the teratogenic effects of individual drugs in pregnant mice. Moreover the role of folic acid and α-tocopherol if any had also been investigated in reducing the teratogenic effects of these drugs in combinations. PMID:22186339

  8. Comparative efficacy of long-acting muscarinic antagonist monotherapies in COPD: a systematic review and network meta-analysis

    PubMed Central

    Ismaila, Afisi Segun; Huisman, Eline L; Punekar, Yogesh Suresh; Karabis, Andreas

    2015-01-01

    Background Randomized, controlled trials comparing long-acting muscarinic antagonist (LAMA) efficacy in COPD are limited. This network meta-analysis (NMA) assessed the relative efficacy of tiotropium 18 µg once-daily (OD) and newer agents (aclidinium 400 µg twice-daily, glycopyrronium 50 µg OD, and umeclidinium 62.5 µg OD). Methods A systematic literature review identified randomized, controlled trials of adult COPD patients receiving LAMAs. A NMA within a Bayesian framework examined change from baseline in trough forced expiratory volume in 1 second (FEV1), transitional dyspnea index focal score, St George’s Respiratory Questionnaire score, and rescue medication use. Results Twenty-four studies (n=21,311) compared LAMAs with placebo/each other. Aclidinium, glycopyrronium, tiotropium, and umeclidinium, respectively, demonstrated favorable results versus placebo, for change from baseline (95% credible interval) in 12-week trough FEV1 (primary endpoint: 101.40 mL [77.06–125.60]; 117.20 mL [104.50–129.90]; 114.10 mL [103.10–125.20]; 136.70 mL [104.20–169.20]); 24-week trough FEV1 (128.10 mL [84.10–172.00]; 135.80 mL [123.10–148.30]; 106.40 mL [95.45–117.30]; 115.00 mL [74.51–155.30]); 24-week St George’s Respiratory Questionnaire score (−4.60 [−6.76 to −2.54]; −3.14 [−3.83 to −2.45]; −2.43 [−2.92 to −1.93]; −4.69 [−7.05 to −2.31]); 24-week transitional dyspnea index score (1.00 [0.41–1.59]; 1.01 [0.79–1.22]; 0.82 [0.62–1.02]; 1.00 [0.49–1.51]); and 24-week rescue medication use (data not available; −0.41 puffs/day [−0.62 to −0.20]; −0.52 puffs/day [−0.74 to −0.30]; −0.30 puffs/day [−0.81 to 0.21]). For 12-week trough FEV1, differences in change from baseline (95% credible interval) were −12.8 mL (−39.39 to 13.93), aclidinium versus tiotropium; 3.08 mL (−7.58 to 13.69), glycopyrronium versus tiotropium; 22.58 mL (−11.58 to 56.97), umeclidinium versus tiotropium; 15.90 mL (−11.60 to 43

  9. A randomized, double-blind, double-dummy comparison of short- and long-acting dihydrocodeine in chronic non-malignant pain.

    PubMed

    Pedersen, Line; Borchgrevink, Petter Christian; Breivik, Harald Petter; Fredheim, Olav Magnus Søndenå

    2014-05-01

    Guidelines for opioid treatment of chronic non-malignant pain recommend long-acting over short-acting opioid formulations. The evidence for this recommendation is weak. This study is a randomized, double-blind, double-dummy, 8-week comparison of long-acting dihydrocodeine tablets (DHC-Continus) with short-acting dihydrocodeine tablets in 60 patients with chronic non-malignant pain who were referred to a multidisciplinary pain clinic. All patients used codeine-paracetamol tablets before the trial, and paracetamol was added in both groups during the trial. The primary outcome was stability in pain intensity, measured as the difference between the highest and least pain intensity reported on an 11-point numerical rating scale in a 7-day diary. The secondary outcomes were differences in quality of life, quality of sleep, depression, and episodes of breakthrough pain between the 2 formulations. Spontaneously reported adverse events were recorded. In all, 38 patients completed the trial, and 22 withdrew before the end. The reasons for withdrawal were adverse events, lack of efficacy, or both, and were similar between the groups. There were no significant differences in stability of pain intensity between groups. There were no significant differences between groups in quality of sleep, depression, health-related quality of life, or adverse events. Breakthrough pain was experienced in both groups during the trial. Long-acting dihydrocodeine was not observed to be superior for any of the outcomes in this trial. The results of this study do not support current guidelines recommending long-acting opioids.

  10. Tolerability, Safety, and Benefits of Risperidone in Children and Adolescents with Autism: 21-Month Follow-up After 8-Week Placebo-Controlled Trial

    PubMed Central

    Rettiganti, Mallikarjuna; Nagaraja, Haikady N.; Hollway, Jill A.; McCracken, James; McDougle, Christopher J.; Tierney, Elaine; Scahill, Lawrence; Arnold, L. Eugene; Hellings, Jessica; Posey, David J.; Swiezy, Naomi B.; Ghuman, Jaswinder; Grados, Marco; Shah, Bhavik; Vitiello, Benedetto

    2015-01-01

    Abstract Objective: Risperidone has demonstrated efficacy for acute (8 week) and intermediate length (6 month) management of severe irritability and aggression in children and adolescents with autism. Less is known about the long-term effects of risperidone exposure in this population. We examined the tolerability, safety, and therapeutic benefit of risperidone exposure over a 1–2 year follow-up period. Methods: In a naturalistic study, 84 children and adolescents 5–17 years of age (from an original sample of 101) were assessed an average of 21.4 months after initial entry into a placebo-controlled 8 week trial of risperidone for children and adolescents with autism and severe irritability. They were assessed at baseline and at follow-up on safety and tolerability measures (blood, urinalysis, electrocardiogram [ECG], medical history, vital signs, neurological symptoms, other adverse events), developmental measures (adaptive behavior, intelligence quotient [IQ]), and standardized rating instruments. Treatment over the follow-up period, after completion of protocol participation, was uncontrolled. Statistical analyses assessed outcome over time with or without prolonged risperidone therapy. Results: Two-thirds of the 84 subjects continued to receive risperidone (mean 2.47 mg/day, S.D. 1.29 mg). At follow-up, risperidone was associated with more enuresis, more excessive appetite, and more weight gain, but not more adverse neurological effects. No clinically significant events were noted on blood counts, chemistries, urinalysis, ECG, or interim medical history. Regardless of drug condition at follow-up, there was considerable improvement in maladaptive behavior compared with baseline, including core symptoms associated with autism. Height and weight gains were elevated with risperidone. Social skills on Vineland Adaptive Behavior Scale (VABS) improved with risperidone. Parent-rated Aberrant Behavior Checklist (ABC) Irritability subscale scores were reduced in

  11. Comparative study of sexual dysfunction and serum prolactin level associated with olanzapine, risperidone, and clozapine in patients with remitted schizophrenia

    PubMed Central

    Sathish Kumar, S. V.; Sinha, Vinod Kumar

    2015-01-01

    Background: Sexual dysfunctions have been a major side effect of the second generation anti-psychotic drugs which often affects treatment compliance in patients with schizophrenia. There is no/few systematic review or research addressing sexual dysfunction and their effect on serum prolactin level among different atypical antipsychotics in India. Aims: To determine and compare the frequency of sexual dysfunction associated with olanzapine, risperidone, and clozapine and their effect on serum prolactin level in remitted patients with schizophrenia. Settings and Design: Cross-sectional hospital-based study. Recruitment by purposive sampling. Estimation of serum prolactin was done using enzyme-linked immunosorbent assay technique. Materials and Methods: The total sample size was 103, consisting of 31, 23, and 19 patients in olanzapine, risperidone, and clozapine groups, respectively and 30 controls. A Brief Psychiatric Rating Scale, Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and Sexual Functioning Questionnaire were administered. Analysis of variance was used to compare clinical variables. Chi-square test was used to identify the frequency of sexual dysfunction. Kruskal–Wallis test was used to compare UKU side effect, sexual dysfunction, and blood parameters across the study groups. Results and Conclusion: Eighty-six percentage reported sexual dysfunction in one or more domains of sexual functioning in risperidone group as compared to 48.3% in olanzapine and 31% in clozapine groups, respectively. Prolactin level elevation was statistically significant in risperidone group followed by clozapine and olanzapine groups, respectively. PMID:26816428

  12. Add-on effects of a low-dose aripiprazole in resolving hyperprolactinemia induced by risperidone or paliperidone.

    PubMed

    Qiao, Ying; Yang, Fuzhong; Li, Chunbo; Guo, Qian; Wen, Hui; Zhu, Suoyu; Ouyang, Qiong; Shen, Weidi; Sheng, Jianhua

    2016-03-30

    This study investigated the effects of a low-dose aripiprazole adjunctive treatment for risperidone- or paliperidone-induced hyperprolactinemia in Han Chinese women with schizophrenia. After 4 weeks of risperidone or paliperidone treatment, 60 out of 66 patients improved significantly and experienced hyperprolactinemia. They were randomly assigned to the treatment group (aripiprazole adjunctive treatment) (n=30) or control group (non-adjunctive treatment) (n=30). The dosage of risperidone and paliperidone were maintained; and aripiprazole was maintained at 5mg/day during the 8-week study period. The prolactin levels at the end of the 8th week were significantly lower in the treatment group than in the control group. The estradiol level correlated negatively with serum prolactin level both in the treatment group and the control group at the end of the 8th week and the 4th week respectively. The Positive and Negative Syndrome Scale score improved significantly during the 8-week study period in both groups. The incidence of treatment-emergent adverse event was similar in two groups. Low-dose aripiprazole adjunctive treatment is effective in relieving risperidone- and paliperidone-induced hyperprolactinemia in female schizophrenic patients without increasing adverse event.

  13. Using the Diagnostic Assessment of the Severely Handicapped-II (DASH-II) to Measure the Therapeutic Effects of Risperidone

    ERIC Educational Resources Information Center

    Valdovinos, M. G.; Zarcone, J. R.; Hellings, J. A.; Kim, G.; Schroeder, S. R.

    2004-01-01

    Within the scope of a double-blind, placebo-controlled, crossover medication study, the Diagnostic Assessment of the Severely Handicapped-II (DASH-II) was evaluated as a measurement for determining the effectiveness of the medication risperidone in treating the problem behaviour of 21 people with intellectual disabilities (ID). Participants…

  14. Risperidone in Children with Disruptive Behavior Disorders and Subaverage Intelligence: A 1-Year, Open-Label Study of 504 Patients

    ERIC Educational Resources Information Center

    Croonenberghs, Jan; Fegert, Joerg M.; Findling, Robert L.; de Smedt, Goedele; van Dongen, Stefan

    2005-01-01

    Objective: To determine the long-term safety and effectiveness of risperidone for severe disruptive behaviors in children. Method: A multisite, 1-year, open-label study of patients aged 5 to 14 years with disruptive behaviors and subaverage intelligence was conducted. Results: Seventy-three percent of the 504 patients enrolled completed the study.…

  15. A Double-Blind Placebo Controlled Trial of "Ginkgo Biloba" Added to Risperidone in Patients with Autistic Disorders

    ERIC Educational Resources Information Center

    Hasanzadeh, Elmira; Mohammadi, Mohammad-Reza; Ghanizadeh, Ahmad; Rezazadeh, Shams-Ali; Tabrizi, Mina; Rezaei, Farzin; Akhondzadeh, Shahin

    2012-01-01

    "Ginkgo biloba" has been reported to affect the neurotransmitter system and to have antioxidant properties that could impact the pathogenesis of Autism Spectrum Disorder. Based on these studies, we decided to assess the effectiveness of "Ginkgo biloba" extract (Ginko T.D., Tolidaru, Iran) as an adjunctive agent to risperidone in the treatment of…

  16. Memantine as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Ghaleiha, Ali; Asadabadi, Mahtab; Mohammadi, Mohammad-Reza; Shahei, Maryam; Tabrizi, Mina; Hajiaghaee, Reza; Hassanzadeh, Elmira; Akhondzadeh, Shahin

    2013-05-01

    Autism is a neurodevelopmental disorder that causes significant impairment in socialization and communication. It is also associated with ritualistic and stereotypical behaviour. Recent studies propose both hyper-and hypoglutamatergic ideologies for autism. The objective of this study was to assess the effects of memantine plus risperidone in the treatment of children with autism. Children with autism were randomly allocated to risperidone plus memantine or placebo plus risperidone for a 10-wk, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 3 mg/d and memantine was titrated to 20 mg/d. Children were assessed at baseline and after 2, 4, 6, 8 and 10 wk of starting medication protocol. The primary outcome measure was the irritability subscale of Aberrant Behavior Checklist-Community (ABC-C). Difference between the two treatment arms was significant as the group that received memantine had greater reduction in ABC-C subscale scores for irritability, stereotypic behaviour and hyperactivity. Eight side-effects were observed over the trial, out of the 25 side-effects that the checklist included. The difference between the two groups in the frequency of side-effects was not significant. The present study suggests that memantine may be a potential adjunctive treatment strategy for autism and it was generally well tolerated. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N10; www.irct.ir).

  17. Near infrared spectroscopic (NIRS) analysis of drug-loading rate and particle size of risperidone microspheres by improved chemometric model.

    PubMed

    Song, Jia; Xie, Jing; Li, Chenliang; Lu, Jia-Hui; Meng, Qing-Fan; Yang, Zhaogang; Lee, Robert J; Wang, Di; Teng, Le-Sheng

    2014-09-10

    Microspheres have been developed as drug carriers in controlled drug delivery systems for years. In our present study, near infrared spectroscopy (NIRS) is applied to analyze the particle size and drug loading rate in risperidone poly(d,l-lactide-co-glycolide) (PLGA) microspheres. Various batches of risperidone PLGA microspheres were designed and prepared successfully. The particle size and drug-loading rate of all the samples were determined by a laser diffraction particle size analyzer and high performance liquid chromatography (HPLC) system. Monte Carlo algorithm combined with partial least squares (MCPLS) method was applied to identify the outliers and choose the numbers of calibration set. Furthermore, a series of preprocessing methods were performed to remove signal noise in NIR spectra. Moving window PLS and radical basis function neural network (RBFNN) methods were employed to establish calibration model. Our data demonstrated that PLS-developed model was only suitable for drug loading analysis in risperidone PLGA microspheres. Comparatively, RBFNN-based predictive models possess better fitting quality, predictive effect, and stability for both drug loading rate and particle size analysis. The correlation coefficients of calibration set (Rc(2)) were 0.935 and 0.880, respectively. The performance of optimum RBFNN models was confirmed by independent verification test with 15 samples. Collectively, our method is successfully performed to monitor drug-loading rate and particle size during risperidone PLGA microspheres preparation.

  18. Comparison of Risperidone and Methylphenidate for Reducing ADHD Symptoms in Children and Adolescents with Moderate Mental Retardation.

    ERIC Educational Resources Information Center

    Filho, Alceu Gomes Correia; Bodanese, Rafael; Silva, Tatiana Laufer; Alvares, Julia Paglioza; Aman, Michael; Rohde, Luis Augusto

    2005-01-01

    Objective: To evaluate the short-term efficacy and tolerability of risperidone and methylphenidate for reducing symptoms related to attention-deficit/hyperactivity disorder (ADHD) in children and adolescents with moderate mental retardation. Method: In a 4-week, single-blind, parallel-group trial, 45 subjects with moderate mental retardation and…

  19. Time to rehospitalization of clozapine versus risperidone in the naturalistic treatment of comorbid alcohol use disorder and schizophrenia.

    PubMed

    Kim, Jin Hun; Kim, Daeho; Marder, Stephen R

    2008-05-15

    Clozapine is known to be effective in treating schizophrenia patients with comorbid alcohol use disorders (AUD). However, few prospective studies have examined the effect of clozapine on community survival of the patient, which is one of the most important indicators of success for patients with schizophrenia. In this prospective, naturalistic, observational, community-survival-analysis study, we compared the effect of clozapine and risperidone on two-year psychiatric hospitalization rate and time to hospitalization in the treatment of patients with schizophrenia and comorbid AUD. We found that the clozapine treated patients were readmitted to hospital significantly later (mean survival=526.5 days, n=25 patients) than the risperidone treated patients (mean survival=420.4 days, n=36 patients). The survival curve for the clozapine-treated patients was significantly different from that of the risperidone treated patients (log-rank test, df=1, p=.045). At the end of the two-year study period, 75% of the risperidone treated patients had been admitted to the hospital, compared to only 48% of the clozapine treated patients. These findings suggest that clozapine should be considered for the treatment of schizophrenia patients with comorbid AUD. However, due to the limitations of this study, further studies will be required to confirm these findings. PMID:18262321

  20. Open-label treatment with risperidone of 26 psychiatrically-hospitalized children and adolescents with mixed diagnoses and aggressive behavior.

    PubMed

    Buitelaar, J K

    2000-01-01

    Open-label risperidone was administered to 26 subjects (24 boys: 19 with borderline IQ and 5 with mild mental retardation), 10-18 years old, who were hospitalized for treatment of psychiatric disorders associated with aggressive behavior. Risperidone was given in daily doses ranging from 0.5 to 4 mg for periods of 2-12 months. Treatment response was monitored by means of the improvement scale of the CGI and the modified OAS. Extrapyramidal side effects were measured on the ESRS. Fourteen (54%) of 26 subjects had a marked reduction in aggression; 10 subjects had a moderate reduction; two subjects had mild changes; and none worsened. Two subjects had a marked weight gain in the first 8 weeks of treatment. In seven of the 22 children who continued taking risperidone after week 8, tiredness and sedation that necessitated dose reduction emerged between weeks 8 and 16. These results suggest that risperidone may be useful when treating severe aggressive behavior in children and adolescents. Weight gain and sedation can be troublesome side effects.

  1. Cross-reactivity of acetylfentanyl and risperidone with a fentanyl immunoassay.

    PubMed

    Wang, Bei-Tzu; Colby, Jennifer M; Wu, Alan H B; Lynch, Kara L

    2014-01-01

    Fentanyl and its analogs, such as acetylfentanyl, have become a concern for potential abuse. Fentanyl compliance monitoring and urine drug testing are becoming increasingly necessary; however, a limited number of fentanyl immunoassays have been validated for clinical use. The purpose of this study was to validate the use of the DRI® fentanyl immunoassay, determine the potential cross-reactivity of acetylfentanyl and other pharmaceuticals, and investigate acetylfentanyl use in San Francisco. All urine toxicology samples from patients presenting to the emergency department were analyzed using the fentanyl immunoassay for 4 months. Positive samples were analyzed qualitatively using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for fentanyl, fentanyl metabolites, fentanyl analogs and greater than 200 common drugs and metabolites. Subsequently, quantitative analysis was performed using LC-tandem mass spectrometry (LC-MS-MS). Acetylfentanyl, risperidone and 9-hydroxyrisperidone were found to cross-react with the fentanyl immunoassay. No acetylfentanyl was detected in our emergency department patient population. The fentanyl immunoassay demonstrated 100% diagnostic sensitivity in a subset of urines tested; however, the specificity was only 86% due to seven false-positive samples observed. Five of the seven samples were positive for risperidone and 9-hydroxyrisperidone. The DRI® fentanyl immunoassay can be used to screen for fentanyl or acetylfentanyl; however, confirmatory testing should be performed for all samples that screen positive.

  2. Abnormal plasma monoamine metabolism in schizophrenia and its correlation with clinical responses to risperidone treatment.

    PubMed

    Cai, Hua-Lin; Fang, Ping-Fei; Li, Huan-De; Zhang, Xiang-Hui; Hu, Li; Yang, Wen; Ye, Hai-Sen

    2011-07-30

    Abnormalities in plasma monoamine metabolism reflect partly the illness of schizophrenia and sometimes the symptoms. Such studies have been repeatedly reported but have rarely taken both metabolites and parent amines or inter-amine activity ratios into account. In this study, the monoamines, their metabolites, turnovers and between-metabolite ratios in plasma were measured longitudinally in 32 schizophrenic patients treated with risperidone for 6 weeks, to examine possible biochemical alterations in schizophrenia, and to examine the association between treatment responses and psychopathology assessed according to the Positive and Negative Syndrome Scale (PANSS). The results showed lower level of plasma 3,4-dihydroxyphenylacetic acid (DOPAC) in relapsed versus first-episode schizophrenic patients, higher norepinephrine (NE) turnover rate (TR) in undifferentiated in comparison to paranoid schizophrenic patients and relatively higher metabolic activity of dopamine (DA) to serotonin (5-HT) in first-episode versus relapsed schizophrenic patients. Risperidone treatment induced a decrement of plasma DA levels and increments of plasma DOPAC and DA TR in the total group of schizophrenic patients. The turnover rate of 5-HT was was reduced in undifferentiated and relapsed subgroups of schizophrenic patients. The linkages between 5-HT TR, DA/NE relative activity and clinical symptomatology were also identified. These findings are consistent with an involvement of these systems in the pathogenesis of schizophrenia as well as in the responses to treatment, and the usefulness of certain biochemical indices as markers for subgrouping.

  3. Delayed drug interactions in psychiatry: armodafinil and risperidone as a potential case in point.

    PubMed

    Andrade, Chittaranjan

    2015-12-01

    Modafinil or armodafinil (ar/mod) augmentation of antipsychotic medication in schizophrenia patients may be considered with a view to reduce negative symptoms associated with the illness or excessive daytime drowsiness due to any cause. The available data suggest that there is no role for ar/mod in reducing negative symptom burden. A recent pharmacokinetic (PK) study suggested that armodafinil (250 mg/d) reduces key PK parameters of risperidone by about 50%, and key PK parameters of 9-hydroxyrisperidone (paliperidone) by about 20%-30%, probably through induction of CYP3A4. Ar/mod augmentation is therefore best avoided in patients receiving risperidone or paliperidone (and most other atypical antipsychotic drugs, as well, because most atypical antipsychotics are metabolized by enzymes that ar/mod induce). If the ar/mod-antipsychotic drug combination is necessary, for whatever reason, then the dose of the atypical antipsychotic drug may need to be appropriately raised. If this is not done, relapse may occur; because the relapse may postdate the introduction of ar/mod by many months, the causal role of a metabolic drug interaction may not be suspected, and physicians may attribute the relapse to the natural course of the illness. Physicians need to be aware that any agent that induces the metabolism of psychotropic drugs that are used in maintenance therapy may, through lowered psychotropic drug levels, result in a delayed drug interaction that is characterized by illness relapse.

  4. A role for risperidone in the treatment of communication disorder and comorbid mental health problems?

    PubMed

    Moreton, Adam; Imran, Shermin

    2015-01-01

    This case report describes the co-occurrence of a psychiatric disorder with a specific communication disorder in a teenage girl who presented to youth mental health services in crisis, posing a significant risk of harm to herself and others. Description of this case would be of interest to practitioners in youth mental health in relation to the assessment and treatment of young people with similar difficulties. We present the case of a 17-year-old girl previously admitted to an inpatient adolescent unit. Her diagnosis was reformulated 4 months into her second admission to include a specific communication disorder with both receptive and expressive difficulties, evident from her pragmatic use of language. She was started on risperidone in month eight; following this, a significant improvement was seen and the patient was discharged a month later. Prior to the start of risperidone, a referral had been made to low secure adolescent services for further assessment and advice on management, due to the patient's challenging presentation and poor engagement with treatment. PMID:26607198

  5. Efficacy and Safety of Risperidone and Quetiapine in Adolescents With Bipolar II Disorder Comorbid With Conduct Disorder.

    PubMed

    Masi, Gabriele; Milone, Annarita; Stawinoga, Agnieszka; Veltri, Stefania; Pisano, Simone

    2015-10-01

    Although a frequent co-occurrence between bipolar disorder (BD) and conduct disorder (CD) in youth has been frequently reported, data about pharmacological management are scarce and focused on BD type I. Second generation antipsychotics are frequently used in clinical practice, but no comparative studies are available. The aim of this exploratory study was to compare efficacy and safety of risperidone and quetiapine in a sample of adolescents presenting a BD type II comorbid with CD. Twenty-two patients diagnosed with a structured interview according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (male/female ratio, 12/10; mean (SD) age 15.0 (1.4) years) were randomized in 2 treatment groups (quetiapine [n = 12] vs risperidone [n = 10]), treated with flexible doses, and followed up for 12 weeks. Efficacy measures assessed manic symptoms, aggression, anxiety, depression, global clinical severity, and impairment. Safety measures included body mass index, serum prolactin, extrapyramidal adverse effects, and electrocardiogram. At the end of the study, all patients improved in all efficacy measures. Both treatments showed similar efficacy in reducing manic symptoms and aggression. Quetiapine was more effective in improving anxiety and depressive symptoms. A change in body mass index was found, and in a post hoc analysis, it was significant only in the risperidone group. Prolactin significantly increased only in the risperidone group. In BD type II, CD comorbidity, quetiapine, or risperidone monotherapy may be effective and relatively safe, although the small sample size, the limited duration of the study, and the design (lack of a blind assessments and of a placebo group) make it difficult to draw definitive conclusions.

  6. Efficacy and Safety of Risperidone and Quetiapine in Adolescents With Bipolar II Disorder Comorbid With Conduct Disorder.

    PubMed

    Masi, Gabriele; Milone, Annarita; Stawinoga, Agnieszka; Veltri, Stefania; Pisano, Simone

    2015-10-01

    Although a frequent co-occurrence between bipolar disorder (BD) and conduct disorder (CD) in youth has been frequently reported, data about pharmacological management are scarce and focused on BD type I. Second generation antipsychotics are frequently used in clinical practice, but no comparative studies are available. The aim of this exploratory study was to compare efficacy and safety of risperidone and quetiapine in a sample of adolescents presenting a BD type II comorbid with CD. Twenty-two patients diagnosed with a structured interview according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (male/female ratio, 12/10; mean (SD) age 15.0 (1.4) years) were randomized in 2 treatment groups (quetiapine [n = 12] vs risperidone [n = 10]), treated with flexible doses, and followed up for 12 weeks. Efficacy measures assessed manic symptoms, aggression, anxiety, depression, global clinical severity, and impairment. Safety measures included body mass index, serum prolactin, extrapyramidal adverse effects, and electrocardiogram. At the end of the study, all patients improved in all efficacy measures. Both treatments showed similar efficacy in reducing manic symptoms and aggression. Quetiapine was more effective in improving anxiety and depressive symptoms. A change in body mass index was found, and in a post hoc analysis, it was significant only in the risperidone group. Prolactin significantly increased only in the risperidone group. In BD type II, CD comorbidity, quetiapine, or risperidone monotherapy may be effective and relatively safe, although the small sample size, the limited duration of the study, and the design (lack of a blind assessments and of a placebo group) make it difficult to draw definitive conclusions. PMID:26226481

  7. Risk of cardiovascular events after initiation of long-acting bronchodilators in patients with chronic obstructive lung disease: A population-based study

    PubMed Central

    Aljaafareh, Almotasembellah; Valle, Jose Ruben; Lin, Yu-Li; Kuo, Yong-Fang; Sharma, Gulshan

    2016-01-01

    Objectives: Long-acting bronchodilators are mainstay treatment for moderate to severe chronic obstructive pulmonary disease. A growing body of evidence indicates an increased risk of cardiovascular events upon initiation of these medications. We hypothesize that this risk is higher in patients with chronic obstructive pulmonary disease who had a preexisting cardiovascular disease regardless of receipt of any cardiovascular medication. Methods: A retrospective cohort of patients with a diagnosis of chronic obstructive pulmonary disease based on two outpatient visits or one inpatient visit for chronic obstructive pulmonary disease (International Classification of Diseases, 9th Edition, Clinical Modification codes 491.x, 492.x, 496) in any year between 2001 and 2012 from a commercial insurance database. We then selected those initiating long-acting bronchodilator treatments between April 2001 and September 2012. Each patient had a 1 year look back period to determine history of cardiovascular disease or cardiovascular disease treatment from the time of first prescription of long-acting beta agonist, long-acting muscarinic antagonist, or long-acting beta agonist combined with inhaled corticosteroids. Patients were followed for 90 days for hospitalizations or emergency department visits for cardiovascular event. The cohort was divided into four groups based on the presence of cardiovascular disease (including ischemic heart disease, hypertension, ischemic stroke, heart failure, tachyarrhythmias and artery disease based on International Classification of Diseases, 9th Edition, Clinical Modification codes) and cardiovascular disease treatment defined as acetylsalicylic acid, beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antiplatelet, anticoagulants, calcium channel blockers, nitrate, digoxin, diuretics, antiarrhythmics or statins. Odds of emergency department visit or hospitalization in the 90 days after prescription were

  8. Low dose risperidone attenuates cue-induced but not heroin-induced reinstatement of heroin seeking in an animal model of relapse.

    PubMed

    Lai, Miaojun; Chen, Weisheng; Zhu, Huaqiang; Zhou, Xiaoli; Liu, Huifen; Zhang, Fuqiang; Zhou, Wenhua

    2013-08-01

    The aim of the present study was to investigate the effects of pretreatment with risperidone on heroin self-administration and heroin-seeking behaviour induced by cues and heroin priming. Rats were trained to self-administer heroin under a fixed ratio 1 schedule for 2 wk and nose-poke responding was extinguished for 10 d, after which reinstatement of drug seeking was induced by conditioned cues or heroin priming. Acute risperidone administration at doses 10-100 μg/kg potently and dose-dependently inhibited reinstatement of conditioned cue-induced heroin seeking; the minimum dose of inhibition was 30 μg/kg. In contrast, risperidone at the same doses did not attenuate reinstatement induced by two priming doses of heroin (100 or 250 μg/kg s.c.). Risperidone at these doses failed to alter heroin self-administration and locomotion activity. These data demonstrate that acute treatment with low-dose risperidone inhibits conditioned cue-induced heroin seeking and risperidone may be an adjunctive therapy for the treatment of heroin addiction.

  9. A 12-month, open-label, comparative study of quetiapine and risperidone in the acute and long-term treatment of schizophrenia.

    PubMed

    Perez, Victor; Cañas, Fernando; Tafalla, Monica

    2008-05-01

    This multicentre, observational, prospective, nonrandomized study compared the effectiveness and tolerability of quetiapine and risperidone in the acute and long-term treatment of schizophrenia in a clinical setting. Patients admitted to an acute unit with schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV), who were prescribed quetiapine or risperidone (3 : 1 ratio) within the first week of treatment, according to the physician's usual practice, were recruited. In total, 492 patients (quetiapine: 367; risperidone: 125) were followed up at weeks 1 and 2, discharge and 6 and 12 months thereafter. Mean doses at 12 months were: quetiapine 718.5 mg/day and risperidone 7.0 mg/day. Efficacy measures (Brief Psychiatric Rating Scale, Clinical Global Impression Severity of Illness and Improvement) indicated similar results for both agents. No difference was found in rehospitalization rate with either drug. In terms of tolerability, orthostatic hypotension was more frequent with quetiapine, but extrapyramidal symptoms and male sexual dysfunction were more frequent with risperidone. In conclusion, quetiapine and risperidone had comparable effectiveness, but there were differences between treatments in their side effect profile.

  10. Effects of co-treatment with mirtazapine and low doses of risperidone on immobility time in the forced swimming test in mice.

    PubMed

    Rogóż, Zofia

    2010-01-01

    The aim of the present study was to examine the effect of mirtazapine (MIR) and risperidone (an atypical antipsychotic drug), given separately or jointly, on immobility time in the forced swimming test in male C57BL/6J mice. Fluoxetine (FLU) was used as a reference drug. MIR (2.5, 5 and 10 mg/kg) and FLU (5 and 10 mg/kg), or risperidone in low doses (0.05 and 0.1 mg/kg) given alone did not change the immobility time of mice in the forced swimming test. Joint administration of MIR (5 and 10 mg/kg) or FLU (10 mg/kg) and risperidone (0.1 mg/kg) produced antidepressant-like activity in the forced swimming test. WAY100636 (a 5-HT(1A) receptor antagonist) inhibited, while yohimbine (an α(2)-adrenergic receptor antagonist) potentiated the antidepressant-like effect induced by co-administration of MIR and risperidone. Active behavior in that test did not reflect an increase in general activity, since combined administration of antidepressants and risperidone failed to enhance the locomotor activity of mice. The obtained results indicate that risperidone applied in a low dose enhances the antidepressant-like activity of MIR and that, among other mechanisms, 5-HT(1A)-, and α(2)-adrenergic receptors may play a role in this effect.

  11. Demand for long acting and permanent methods of contraceptives and factors for non-use among married women of Goba Town, Bale Zone, South East Ethiopia

    PubMed Central

    2012-01-01

    Background Contraceptive use including short acting, long acting and permanent methods positively influence the socio-economic development of a nation by allowing families to space and limit their family size to their economic capacity. Demand for LAPMs of contraception as detrmined by utilization and unmet need for LAPMs of contraception can provide realiable information for providers. Objective To determine the utilization of long acting and permanent contraception and its associated factors among married women of Goba town, South East Ethiopia. Methods A cross sectional community based study was conducted among 734 systematically selected married women of reproductive age in Goba town in September/ 2009. A structured and pretested, interview questionaire was used to collect data on socio-demographic, behavioral factors and data related to demand for LAPMs of contraception. Data were analyzed using EPI INFO and SPSS version 16. Result The demand for Long Acting and Permanent Methods (LAPMs) of contraception was 18.1%. Utilization of LAPMs of contraception in the town was 64 (8.7%) and the unmet need for LAPMs was 69 (9.4%). Information on LAPMs in the town was 636 (86.6%). Media (radio and television) was the major sources of information 641 (87.3%). The use of LAPMs was significatly associated with ever use AOR[17.43, 95% CI:9.19, 33.03], number of times discussions made on methods AOR[4.6, 95% CI: 1.72,12.17] and main decider of using methods AOR[ 2.2, 95% CI:1.03, 4.65]. It was not associated with socio-demographic variables. Conclusion and recommendation The utilization of LAPMs in the town was less although higher than the Ethiopian demographic and health survey 2005 result. Moreover, there was a considerable unmet need. Increase the method mix of LAPMs by incorporating varaies of implnats in order to increase utilization. Proper counseling of client and partners discussion were some of the recommendation forwarded. PMID:23102166

  12. Reducing Prescriptions of Long-Acting Benzodiazepine Drugs in Denmark: A Descriptive Analysis of Nationwide Prescriptions during a 10-Year Period.

    PubMed

    Eriksen, Sophie Isabel; Bjerrum, Lars

    2015-06-01

    Prolonged consumption of benzodiazepine drugs (BZD) and benzodiazepine receptor agonists (zolpidem, zaleplon, zopiclone; altogether Z drugs) is related to potential physiological and psychological dependence along with other adverse effects. This study aimed to analyse the prescribing of long-acting BZD (half-life >10 hr), compared to short-acting BZD in Denmark during a 10-year period. Descriptive analysis of total sales data from the Danish Register of Medicinal Product Statistics, to individuals in the primary healthcare sector, of all BZD and Z drugs in the period of 2003-2013. Prescription data derive from all community and hospital pharmacies in Denmark. The prescribing of long-acting BZD was reduced from 25.8 defined daily doses (DDD)/1000 inhabitants/day in 2003 to 8.8 DDD/1000 inhabitants/day in 2013, a relative reduction of 66%. The prescribing of short-acting BZD was reduced from 26.1 DDD/1000 inhabitants/day in 2003 to 16.4 DDD/1000 inhabitants/day in 2013, a relative reduction of 37%. Prescription data in this study did not include information about indications for initiating treatments. In addition, due to compliance problems, some of the prescribed drugs may not have been consumed according to the prescription. The observed reduction in BZD use was correlated to the introduction of new national guidelines on prescription of addictive drugs, but this study was not designed to detect a causal relationship. The prescribing of long-acting BZD decreased considerably more than the prescribing of short-acting BZD in the 10-year period. PMID:25382355

  13. Maintenance treatment of chronic schizophrenic patients. A study with the long-acting thioxanthene derivative, cis(Z)-clopenthixol decanoate-sordinol depot.

    PubMed

    Dom, R; De Mesmaecker, L; van den Broucke, M; van Hest, T; Baro, F

    1978-04-01

    The clinical effect of clopenthixol decanoate has been assessed in a 5-month controlled including 21 hospitalized chronic schizophrenic patients. The ratings were done with BPRS, NOSIE 30, the two psychological tests of WAIS and Grübaum, and the rating scale of Simpson & Angus to assess extrapyramidal side effects. Clopenthixol decanoate was found an effective and long-acting antipsychotic compound with few autonomic and neurological side effects. Compared with previous maintenance treatment it also showed a positive influence on depression and facilitation of the social adaptation of the patients.

  14. Utilization, Spending, and Price Trends for Short- and Long-Acting Beta-Agonists and Inhaled Corticosteroids in the Medicaid Program, 1991–2010

    PubMed Central

    Chiu, Shih-Feng; Kelton, Christina M.L.; Guo, Jeff Jianfei; Wigle, Patricia R.; Lin, Alex C.; Szeinbach, Sheryl L.

    2011-01-01

    Background Asthma is a chronic respiratory disease that afflicts millions of people and accounts for substantial utilization of healthcare resources in most industrialized countries, including in the United States. However, the exact cost and utilization of anti-asthma medications in Medicaid in the past 2 decades have not been well studied. Considering the safety issues surrounding the long-acting beta-agonists, guideline updates, and the increase in asthma prevalence, understanding anti-asthma medication prescribing trends is important to payers and patients. Goal The purpose of this study was to analyze the utilization and spending trends for anti-asthmatic agents in the US Medicaid program over the past 2 decades. Methods This study was based on a retrospective, descriptive analysis of trends in utilization of and spending on anti-asthma medications, including short-acting beta-agonists, inhaled corticosteroids, long-acting beta-agonists, and inhaled corticosteroid/long-acting beta-agonist combinations. Quarterly utilization and expenditure data were obtained from the national Medicaid pharmacy files provided by the Centers for Medicare & Medicaid Services from quarter 1 of 1991 through quarter 2 of 2010. Average reimbursement per prescription was calculated each quarter as a proxy for drug price. Results The total number of prescriptions for the studied anti-asthma medications rose from 8.9 million in 1991 to 15.6 million in 2009, peaking at 20.8 million in 2005, the year before Medicare and Medicaid dual-eligible beneficiaries were moved to Medicare Part D. From 1991 to 2009, Medicaid spending on anti-asthma medications overall rose from $180.7 million to $1.3 billion, and spending on inhaled corticosteroid/long-acting beta-agonist combinations rose from $52.8 million in 2001—their first year on the market—to $411.7 million in 2009. The average price per prescription has risen in all the anti-asthma drug classes: overall, spending per prescription has

  15. Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis

    PubMed Central

    Tricco, Andrea C; Ashoor, Huda M; Antony, Jesmin; Beyene, Joseph; Veroniki, Areti Angeliki; Isaranuwatchai, Wanrudee; Harrington, Alana; Wilson, Charlotte; Tsouros, Sophia; Soobiah, Charlene; Yu, Catherine H; Hutton, Brian; Hoch, Jeffrey S; Hemmelgarn, Brenda R; Moher, David; Majumdar, Sumit R

    2014-01-01

    Objective To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes. Design Systematic review and network meta-analysis. Data sources Medline, Cochrane Central Register of Controlled Trials, Embase, and grey literature were searched through January 2013. Study selection Randomized controlled trials or non-randomized studies of long acting (glargine, detemir) and intermediate acting (neutral protamine Hagedorn (NPH), lente) insulin for adults with type 1 diabetes were included. Results 39 studies (27 randomized controlled trials including 7496 patients) were included after screening of 6501 titles/abstracts and 190 full text articles. Glargine once daily, detemir once daily, and detemir once/twice daily significantly reduced hemoglobin A1c compared with NPH once daily in network meta-analysis (26 randomized controlled trials, mean difference −0.39%, 95% confidence interval −0.59% to −0.19%; −0.26%, −0.48% to −0.03%; and −0.36%, −0.65% to −0.08%; respectively). Differences in network meta-analysis were observed between long acting and intermediate acting insulin for severe hypoglycemia (16 randomized controlled trials; detemir once/twice daily versus NPH once/twice daily: odds ratio 0.62, 95% confidence interval 0.42 to 0.91) and weight gain (13 randomized controlled trials; detemir once daily versus NPH once/twice daily: mean difference 4.04 kg, 3.06 to 5.02 kg; detemir once/twice daily versus NPH once daily: −5.51 kg, −6.56 to −4.46 kg; glargine once daily versus NPH once daily: −5.14 kg, −6.07 to −4.21). Compared with NPH, detemir was less costly and more effective in 3/14 cost effectiveness analyses and glargine was less costly and more effective in 2/8 cost effectiveness analyses. The remaining cost effectiveness analyses found that detemir and glargine were more costly but more effective than NPH. Glargine was not cost effective compared with detemir in 2/2 cost effectiveness analyses

  16. Dystonia in an adolescent on risperidone following the discontinuation of methylphenidate: a case report.

    PubMed

    Guler, Gulen; Yildirim, Veli; Kutuk, Meryem Ozlem; Toros, Fevziye

    2015-04-30

    Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with common comorbidities that include oppositional defiant disorder, conduct disorder, anxiety disorder, and affective disorders. Because of these comorbidities, drug combination treatments and drug-drug interactions are becoming increasingly more frequent. The present case report describes an acute dystonic reaction following the abrupt discontinuation of methylphenidate from a drug regimen with risperidone. The patient experienced acute dystonic reactions on three separate occasions when he forgot to take his methylphenidate medication. The present report informs clinicians about the possible side effects, such as dystonia, when psychostimulant and antipsychotic drug combinations are altered and suggests that the abrupt cessation of stimulants may lead to the development of movement disorders. Therefore, appropriate care is necessary when changing the dose of a drug or abruptly discontinuing a drug from a combination of psychostimulants and antipsychotics.

  17. The Effect of Psychostimulants on Skeletal Health in Boys co-Treated with Risperidone

    PubMed Central

    Schlechte, Janet A.; Burns, Trudy L.; Zemel, Babette S.

    2015-01-01

    Objectives To examine the skeletal effects of chronic psychostimulant treatment in children and adolescents. Study design Medically healthy 5 to 17 year-old males from four different clinic-based studies were combined for this analysis. They were divided by psychostimulant use into 3 groups: none to negligible, intermittent, and continuous use. Most (95%) had also received risperidone for six months or more. Treatment history was extracted from medical and pharmacy records. Anthropometric and bone measurements, using dual-energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), were obtained at each research visit. Multivariable linear regression analysis models examined whether age-sex-specific height Z-score and skeletal outcomes differed among the three psychostimulant-use groups. Results The sample consisted of 194 males with a mean age of 11.7±2.8 years at study entry. The majority had an externalizing disorder. There was no significant difference across the three treatment groups in height Z-score or in skeletal outcomes at the radius, lumbar spine, or whole body. One hundred forty-four boys had valid follow-up skeletal data 1.4±0.7 years after study entry. Again, neither height Z-score nor the skeletal outcomes were different among those who remained on psychostimulants between the two visits, started psychostimulants anew, or had not taken psychostimulants. Conclusions Following chronic treatment, psychostimulants did not appear to significantly affect bone mass accrual in children and adolescents taking risperidone. There was a small, but statistically not significant, negative impact on longitudinal growth. PMID:25863660

  18. A Long-Acting BMP-2 Release System Based on Poly(3-hydroxybutyrate) Nanoparticles Modified by Amphiphilic Phospholipid for Osteogenic Differentiation

    PubMed Central

    Peng, Xiaochun; Chen, Yunsu; Li, Yamin; Wang, Yiming

    2016-01-01

    We explored a novel poly(3-hydroxybutyrate) (PHB) nanoparticle loaded with hydrophilic recombinant human BMP-2 with amphiphilic phospholipid (BPC-PHB NP) for a rapid-acting and long-acting delivery system of BMP-2 for osteogenic differentiation. The BPC-PHB NPs were prepared by a solvent evaporation method and showed a spherical particle with a mean particle size of 253.4 nm, mean zeta potential of −22.42 mV, and high entrapment efficiency of 77.18%, respectively. For BPC-PHB NPs, a short initial burst release of BMP-2 from NPs in 24 h was found and it has steadily risen to reach about 80% in 20 days for in vitro test. BPC-PHB NPs significantly reduced the burst release of BMP-2, as compared to that of PHB NPs loading BMP-2 without PL (B-PHB NPs). BPC-PHB NPs maintained the content of BMP-2 for a long-term osteogenic differentiation. The OCT-1 cells with BPC-PHB NPs have high ALP activity in comparison with others. The gene markers for osteogenic differentiation were significantly upregulated for sample with BPC-PHB NPs, implying that BPC-PHB NPs can be used as a rapid-acting and long-acting BMP-2 delivery system for osteogenic differentiation. PMID:27379249

  19. Pituitary apoplexy causing spontaneous remission of acromegaly following long-acting octreotide therapy: a rare drug side effect or just a coincidence.

    PubMed

    Kumar, Sunil; Sharma, Shruti

    2016-04-01

    Pituitary apoplexy is characterized by abrupt onset of haemorrhage or non-haemorrhagic infarction of a pituitary adenoma. The clinical features include acute onset severe headache, visual field defects, meningeal irritation, ophthalmoplegia and hypopituitarism. The pituitary apoplexy may be clinically silent in ∼25% of patients. We report a case of acromegaly due to pituitary macroadenoma. The patient was started on long-acting octreotide therapy. On 3-month follow-up, the patient showed clinical and biochemical remission and the magnetic resonance imaging (MRI) of the brain showed subclinical haemorrhage and resolution of tumour. The octreotide therapy was stopped. On 6-month follow-up, the patient was still in remission and the MRI of brain revealed non-enhancing mixed intensities haemorrhagic and cystic areas of the pituitary gland. In our patient, whether spontaneous remission of acromegaly due to subclinical pituitary haemorrhage was coincidental or due to long-acting octreotide therapy is still a dilemma. We report this case because of rarity and clinical importance of this unusual occurrence. PMID:27123308

  20. Effects of a long-acting trace mineral rumen bolus supplement on growth performance, metabolic profiles, and trace mineral status of growing camels.

    PubMed

    Alhidary, Ibrahim A; Abdelrahman, Mutassim M; Harron, Raafat M

    2016-04-01

    A study was conducted to evaluate the effects of a long-acting trace mineral rumen bolus (TMB) supplement on the productive performance, metabolic profiles, and trace mineral status of growing camels under natural grazing conditions. Fifteen 6-month-old growing male camels (average bodyweight 139.51 ± 26.49 kg) were used in a 150-day trial. Animals were individually housed in a shaded pen and randomly assigned to receive zero (control group, CON), one (TMB1), or two (TMB2) long-acting TMBs. Feed intake was measured weekly, and camels were weighed monthly. Blood samples were collected from all camels on days 1, 30, 60, 90, 120, and 150 to obtain metabolic profiles. Zinc, selenium, copper, cobalt, and manganese concentrations were determined in the diet, serum, and liver. In comparison with controls, giving camels one TMB increased the average daily gain (14.38%; P < 0.04) and feed efficiency (13.68%; P < 0.01). Additionally, the serum and liver concentrations of zinc, copper, selenium, cobalt, and manganese were greater (P < 0.01) in camels in the TMB2 group. These data indicate that TMB supplementation has positive effects on the growth performance and trace mineral profiles of camels. Different levels, sources, and synergistic combinations of trace minerals can be used in further studies to elucidate their abilities to increase productive variables as well as their availability and cost to the camel industry. PMID:26894497

  1. Pituitary apoplexy causing spontaneous remission of acromegaly following long-acting octreotide therapy: a rare drug side effect or just a coincidence

    PubMed Central

    Kumar, Sunil; Sharma, Shruti

    2016-01-01

    Pituitary apoplexy is characterized by abrupt onset of haemorrhage or non-haemorrhagic infarction of a pituitary adenoma. The clinical features include acute onset severe headache, visual field defects, meningeal irritation, ophthalmoplegia and hypopituitarism. The pituitary apoplexy may be clinically silent in ∼25% of patients. We report a case of acromegaly due to pituitary macroadenoma. The patient was started on long-acting octreotide therapy. On 3-month follow-up, the patient showed clinical and biochemical remission and the magnetic resonance imaging (MRI) of the brain showed subclinical haemorrhage and resolution of tumour. The octreotide therapy was stopped. On 6-month follow-up, the patient was still in remission and the MRI of brain revealed non-enhancing mixed intensities haemorrhagic and cystic areas of the pituitary gland. In our patient, whether spontaneous remission of acromegaly due to subclinical pituitary haemorrhage was coincidental or due to long-acting octreotide therapy is still a dilemma. We report this case because of rarity and clinical importance of this unusual occurrence. PMID:27123308

  2. [Efficasy and safety of the use of risperidone (rispoluxe) in demented patients with psychotic and behavioural disorders].

    PubMed

    Bocharov, A V; Kondakova, V E; Tuleninov, E S

    2012-01-01

    Based on the comparison of international and Russian studies, authors present a review on the epidemiology, clinical features, diagnosis and treatment of psychotic and behavioral disorders in patients with dementia. Results of the own study on the efficacy of risperidone (rispolux) in dosage 102 mg daily in patients with dementia with psychotic and behavioral disorders are presented. It has been shown that rispolux reduces psychotic and behavioral disorders, improves cognitive functions. It is well-tolerated and rather safe for elderly patients.

  3. Effects of Environmental Manipulations and Treatment with Bupropion and Risperidone on Choice between Methamphetamine and Food in Rhesus Monkeys.

    PubMed

    Banks, Matthew L; Blough, Bruce E

    2015-08-01

    Preclinical and human laboratory choice procedures have been invaluable in improving our knowledge of the neurobiological mechanisms of drug reinforcement and in the drug development process for candidate medications to treat drug addiction. However, little is known about the neuropharmacological mechanisms of methamphetamine vs food choice. The aims of this study were to develop a methamphetamine vs food choice procedure and determine treatment effects with two clinically relevant compounds: the monoamine uptake inhibitor bupropion and the dopamine antagonist risperidone. Rhesus monkeys (n=6) responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, FR10 schedule) during 7-day bupropion (0.32-1.8 mg/kg/h) and risperidone (0.001-0.0056 mg/kg/h) treatment periods. For comparison, effects of removing food pellets or methamphetamine injections and FR response requirement manipulations were also examined. Under saline treatment conditions, food was preferred over no methamphetamine or small unit methamphetamine doses (0.01-0.032 mg/kg/injection). Larger methamphetamine doses resulted in greater methamphetamine preference and 0.32 mg/kg/injection methamphetamine maintained near exclusive preference. Removing food availability increased methamphetamine choice, whereas removing methamphetamine availability decreased methamphetamine choice. Methamphetamine choice was not significantly altered when the FR response requirements for food and drug were the same (FR100:FR100 or FR10:FR10). Risperidone treatment increased methamphetamine choice, whereas bupropion treatment did not alter methamphetamine choice up to doses that decreased rates of operant behavior. Overall, these negative results with bupropion and risperidone are concordant with previous human laboratory and clinical trials and support the potential validity of this preclinical methamphetamine vs food

  4. Anxiolytic-like property of risperidone and olanzapine as examined in multiple measures of fear in rats

    PubMed Central

    Sun, Tao; He, Wei; Hu, Gang; Li, Ming

    2010-01-01

    Atypical antipsychotics are also used in the treatment of anxiety-related disorders. Clinical and preclinical evidence regarding their intrinsic anxiolytic efficacy has been mixed. In this study, we examined the potential anxiolytic-like effects of risperidone and olanzapine, and compared them with haloperidol, chlordiazepoxide (a prototype of sedative-anxiolytic drug) or citalopram (a selective serotonin reuptake inhibitor). We used a composite of two-way avoidance conditioning and acoustic startle reflex model and examined the effects of drug treatments during the acquisition phase (Experiment1) or extinction phase (Experiment2 and 3) on multiple measures of conditioned and unconditioned fear/anxiety-like responses. In Experiment 4, we further compared risperidone, olanzapine, haloperidol, citalopram and chlordiazepoxide in a standard elevated plus maze test. Results revealed three distinct anxiolytic-like profiles associated with risperidone, olanzapine and chlordiazepoxide. Risperidone, especially at 1.0 mg/kg, significantly decreased the number of avoidance responses, 22 kHz ultrasonic vocalization, avoidance conditioning-induced hyperthermia and startle reactivity, but did not affect defecations or time spent on the open arms. Olanzapine (2.0 mg/kg, sc) significantly decreased the number of avoidance responses, 22 kHz vocalization and amount of defecations, but it did not inhibit startle reactivity and time spent on the open arms. Chlordiazepoxide (10 mg/kg, ip) significantly decreased the number of 22 kHz vocalization, avoidance conditioning-induced hyperthermia and amount of defecations, and increased time spent on the open arms, but did not decrease avoidance responses or startle reactivity. Haloperidol and citalopram did not display any anxiolytic-like property in these tests. The results highlight the importance of using multiple measures of fear-related responses to delineate behavioral profiles of psychotherapeutic drugs. PMID:20167232

  5. A comparison of olanzapine and risperidone on the risk of psychiatric hospitalization in the naturalistic treatment of patients with schizophrenia

    PubMed Central

    Ascher-Svanum, Haya; Zhu, Baojin; Faries, Douglas; Ernst, Frank R

    2004-01-01

    Background Decreasing hospital admissions is important for improving outcomes for people with schizophrenia and for reducing cost of hospitalization, the largest expenditure in treating this persistent and severe mental illness. This prospective observational study compared olanzapine and risperidone on one-year psychiatric hospitalization rate, duration, and time to hospitalization in the treatment of patients with schizophrenia in usual care. Methods We examined data of patients newly initiated on olanzapine (N = 159) or risperidone (N = 112) who continued on the index antipsychotic for at least one year following initiation. Patients were participants in a 3-year prospective, observational study of schizophrenia patients in the US. Outcome measures were percent of hospitalized patients, total days hospitalized per patient, and time to first hospitalization during the one-year post initiation. Analyses employed a generalized linear model with adjustments for demographic and clinical variables. A two-part model was used to confirm the findings. Time to hospitalization was measured by the Kaplan-Meier survival formula. Results Compared to risperidone, olanzapine-treated patients had significantly lower hospitalization rates, (24.1% vs. 14.4%, respectively, p = 0.040) and significantly fewer hospitalization days (14.5 days vs. 9.9 days, respectively, p = 0.035). The mean difference of 4.6 days translated to $2,502 in annual psychiatric hospitalization cost savings per olanzapine-treated patient, on average. Conclusions Consistent with prior clinical trial research, treatment-adherent schizophrenia patients who were treated in usual care with olanzapine had a lower risk of psychiatric hospitalization than risperidone-treated patients. Lower hospitalization costs appear to more than offset the higher medication acquisition cost of olanzapine. PMID:15175112

  6. [Mechanism of interaction between risperidone and tea catechin (2) influence of presence of galloyl group in catechin on insoluble complex formation with risperidone].

    PubMed

    Ikeda, Hirohito; Moriwaki, Hanae; Matsubara, Tomonori; Yukawa, Miho; Iwase, Yukiko; Yukawa, Eiji; Aki, Hatsumi

    2012-01-01

    The influence of the presence of a galloyl group in catechin on complexation with risperidone (RISP) was examined using (--)-epigallocatechin gallate (EGCg) and (--)-epigallocatechin (EGC), which are present in green tea as tea catechins. By quantitative analysis using HPLC, it was found that EGCg formed an insoluble complex with RISP for concentration dependence, whereas EGC did not. The large contribution of the galloyl group of catechin to form an insoluble complex with RISP was recognized in this study. In a molecular modeling study, it was found that the EGCg-R complex (EGCg with RISP) formed three hydrogen bonds between the hydroxyl groups of EGCg and the two N atoms and an O atom of RISP. The hydrogen bond between the hydroxyl group of the galloyl ring in EGCg and the N atom of the piperidine ring in RISP stabilized EGCg-R more energetically. The EGC-R complex (EGC with RISP) also formed three hydrogen bonds, but the N atom of the piperidine ring in RISP did not participate in hydrogen bond formation. According to the calculation using the COSMO-RS method, the water solubility of the EGCg-R complex was 1/26 that of the EGC-R complex. Therefore, the EGCg-R complex was difficult to dissolve in water. In the (1)H-NMR spectra of RISP in DMSO-d(6), although chemical shifts of protons near the N atom on the piperidine ring moved downfield on the addition of EGCg, no change in chemical shifts of these protons was observed on the addition of EGC. Therefore, based on these results, the galloyl group of EGCg contributes to the formation of an insoluble complex between tea catechin and RISP, and this insoluble complex is stabilized by the hydrogen bond between the hydroxyl group of the galloyl ring in EGCg and the N atom of the piperidine ring in RISP. PMID:22214589

  7. Low-Dose Atypical Antipsychotic Risperidone Improves the 5-Year Outcome in Alzheimer's Disease Patients with Sleep Disturbances.

    PubMed

    Yin, You; Liu, Yan; Zhuang, Jianhua; Pan, Xiao; Li, Peng; Yang, Yuechang; Li, Yan-Peng; Zhao, Zheng-Qing; Huang, Liu-Qing; Zhao, Zhong-Xin

    2015-01-01

    Sleep disturbances (SD) accelerate the progression of Alzheimer's disease (AD) and increase the stress of caregivers. However, the long-term outcome of disturbed nocturnal sleep/wake patterns in AD and on increased stress of spousal caregivers is unclear. This study assessed the 5-year effect of nocturnal SD on the long-term outcome in AD patients. A total of 156 donepezil-treated mild-moderate AD patients (93 AD + SD and 63 AD - SD as a control group) were recruited. The AD + SD patients were formed into 4 subgroups according to the preferences of spousal caregivers for treatment with atypical antipsychotics (0.5-1 mg risperidone, n = 22), non-benzodiazepine hypnotic (5-10 mg zolpidem tartrate, n = 33), melatonin (2.55 mg, n = 9), or no-drug treatment (n = 29). SD were evaluated by polysomnography, sleep scale, and cognitive scale examinations. Moreover, all spousal caregivers of AD patients were assessed using a series of scales, including sleep, anxiety, mood, and treatment attitude scales. Our data showed that nocturnal sleep/wake disturbances were significantly associated with lower 5-year outcomes for AD patients, earlier nursing home placement, and more negative emotions of spousal caregivers. Treatment with low-dose atypical antipsychotic risperidone improved the 5-year outcome in AD + SD patients. In conclusion, low-dose atypical antipsychotic risperidone improves the 5-year outcome in AD patients with SD. Moreover, improvement of nocturnal sleep problems in AD patients will also bring better emotional stability for AD caregivers.

  8. Use of a Direct Observational Measure in a Trial of Risperidone and Parent Training in Children with Pervasive Developmental Disorders

    PubMed Central

    Johnson, Cynthia R.; Butter, Eric M.; Lecavalier, Luc; Scahill, Lawrence; Aman, Michael G.; McDougle, Christopher J.; Arnold, L. Eugene; Swiezy, Naomi B.; Sukhodolsky, Denis G.; Mulick, James A.; White, Susan W.; Bearss, Karen; Hollway, Jill A.; Stigler, Kimberly A.; Dziura, James; Yu, Sunkyung; Sacco, Kelley; Vitiello, Benedetto

    2013-01-01

    A Structured Observational Analog Procedure (SOAP), an analogue measure of parent-child interactions, was used to assess treatment outcome in children with Autism Spectrum Disorder and serious behavior problems. It served as a secondary outcome measure in a 24-week, randomized trial of risperidone (MED; N=49) versus risperidone plus parent training (COMB; n=75) (ages 4–13 years). At 24-weeks, there was 28 % reduction in child inappropriate behavior during a Demand Condition (p=.0002) and 12 % increase in compliance to parental requests (p=.004) for the two treatment conditions combined. Parents displayed 64 % greater use of positive reinforcement (p=.001) and fewer repeated requests for compliance (p<.0001). In the analysis of covariance (ANCOVA), COMB parents used significantly more positive reinforcement (p=.01) and fewer restrictive statements (p<.05) than MED parents. The SOAP is sensitive to change in child and parent behavior as a function of risperidone alone and in combination with PMT and can serve as a valuable complement to parent and clinician-based measures. PMID:23730123

  9. Short report: study on the efficacy of a new long-acting formulation of N, N-diethyl-m-toluamide (DEET) for the prevention of tick attachment.

    PubMed

    Salafsky, B; He, Y X; Li, J; Shibuya, T; Ramaswamy, K

    2000-02-01

    The beneficial effects of N, N-diethyl-m-toluamide (DEET) against biting insects of human and animals appear to last <6 hr after a single application to the skin. To prolong the repellent effects of DEET, recently we developed a new long-acting formulation of DEET called LIPODEET. This preparation was retained in the skin for a longer duration of time with minimal systemic absorption. In this study, we have evaluated the protective effect of three compounds (DEET, LIPODEET, and Morpel 220) against attachment of two species of ticks (Amblyomma americanum and Dermacentor variabilis) to rabbit ears. Results show that LIPODEET and Morpel 220 were highly effective in preventing tick attachment to the skin for a longer duration of time (up to 72 hr) than DEET after a single application. Moreover, LIPODEET was found to be acaricidal to both the species of ticks. PMID:10813468

  10. Fabrication of long-acting drug release property of hierarchical porous bioglasses/polylactic acid fibre scaffolds for bone tissue engineering.

    PubMed

    Wang, Dan; Lin, Huiming; Jiang, Jingjie; Jin, Qumei; Li, Lei; Dong, Yan; Qu, Fengyu

    2015-04-01

    Hierarchical porous fibre scaffolds with mesoporous bioglasses (MBGs) and polylactic acid (PLA) were successfully fabricated by the electrospinning method. These compound scaffolds possess macropores with sizes of about 100 nm because of the solvent evaporation from the fibre and the mesoporous structure ( ∼4.0 nm) originated from MBGs. The biomineralisation ability was investigated in simulated body fluid. The fibre structure is beneficial for inducing the growth of hydroxyapatite. In addition, compared with pure MBGs, the materials (MP-1 and MP-2) exhibit a long-acting drug release process up to 140 h and the drug release process corresponds with the Fickian diffusion mechanism. With the special fibre morphology and the hierarchical porous structure, the MBGs/PLA fibre scaffolds are expected to have potential application for bone tissue repair and regeneration.

  11. Degludec, a new ultra-long-acting basal insulin for the treatment of diabetes mellitus type 1 and 2: advances in clinical research.

    PubMed

    Muñoz Torres, Manuel

    2014-03-01

    Degludec is the most recent molecule of the ultra-long-acting basal insulin analogues approved for human use. It forms soluble multihexamers which after subcutaneous injection are converted into monomers, and are thus slowly and continuously absorbed into the bloodstream. This absorption mechanism confers degludec an ultra-long and stable action profile, with no concentration peaks. This paper discusses the most recent studies in patients with type 1 and 2 diabetes mellitus, which showed degludec to be non inferior in decreasing HbA1c, ensuring optimum glycemic control similar to that achieved with insulin glargine or detemir. Degludec also had an improved safety profile, as it was associated to a significantly lower rate of nocturnal hypoglycemia in both types of diabetes and to a potentially lower overall hypoglycemia rate in type 2 DM. Degludec also opens the possibility to use more flexible regimens.

  12. An open-label, randomized, controlled trial of zotepine and risperidone for acutely ill, hospitalized, schizophrenic patients with symptoms of agitation.

    PubMed

    Chan, Hung-Yu; Lin, An-Sheng; Chen, Kun-Po; Cheng, Jror-Serk; Chen, Ying-Yeh; Tsai, Chang-Jer

    2013-12-01

    Acutely ill, schizophrenic patients frequently require management of agitation. This study was conducted to compare the efficacy of oral zotepine and risperidone in hospitalized, acutely ill schizophrenic patients with symptoms of agitation.This was a 6-week, multicenter, randomized, open-label, parallel-group, flexible dosing study. Thirty-nine patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who met the criteria of a Positive and Negative Syndrome Scale (PANSS) total score of greater than or equal to 60 points, PANSS-excitement component (EC) score of greater than or equal to 14 points, and at least 1 PANSS-EC score of greater than or equal to 4 were randomly assigned to either the zotepine or risperidone group. The primary outcome was a comparison of the change in the PANSS-EC total score from baseline to the end of the study between groups.There was no significant between-group difference in dropout rates (zotepine, 15.8% [3/19]; risperidone, 20.0% [4/20]). The mean (SD) daily dose of zotepine from baseline to study end point ranged from 127.6 (62.3) to 236.8 (74.2) mg/d; the corresponding values for risperidone ranged from 3.3 (1.6) to 4.8 (1.7) mg/d. There were no statistically significant differences in patient characteristics, PANSS total score, and PANSS-EC total score between the zotepine and risperidone groups at baseline. Both groups showed significant reductions in the PANSS-EC total scores (zotepine, -10.1 [4.7], P < 0.001; risperidone, -8.0 [5.3], P < 0.001) and PANSS total scores (zotepine, -34.7 [15.8], P < 0.001; risperidone, -28.6 [14.3], P < 0.001). However, there were no significant differences in PANSS-EC total score (P = 0.265) and PANSS total score (P = 0.125) changes from baseline to study end point between the 2 treatment groups. Serum uric acid and prolactin decreased more in the zotepine group than the risperidone group (P < 0.001 and P = 0.018, respectively).Zotepine seemed to be as

  13. An Open-Label Study of Risperidone in the Improvement of Quality of Life and Treatment of Symptoms of Violent and Self-Injurious Behaviour in Adults with Intellectual Disability

    ERIC Educational Resources Information Center

    Read, Stephen G.; Rendall, Maureen

    2007-01-01

    Background: We examined the benefits of risperidone, including quality of life (QoL), in the treatment of violent and self-injurious behaviour in adults with moderate, severe or profound intellectual disability. Methods: Twenty-four participants received open-label, oral, flexible-dose risperidone of 0.5-6 mg/day for 12 weeks. Efficacy was…

  14. Effects of roflumilast in COPD patients receiving inhaled corticosteroid/long-acting β2-agonist fixed-dose combination: RE2SPOND rationale and study design

    PubMed Central

    Rennard, Stephen I; Martinez, Fernando J; Rabe, Klaus F; Sethi, Sanjay; Pizzichini, Emilio; McIvor, Andrew; Siddiqui, Shahid; Anzueto, Antonio; Zhu, Haiyuan

    2016-01-01

    Background Roflumilast, a once-daily, selective phosphodiesterase-4 inhibitor, reduces the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. The RE2SPOND study is examining whether roflumilast, when added to an inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) fixed-dose combination (FDC), further reduces exacerbations. The methodology is described herein. Methods In this Phase IV, multicenter, double-blind, placebo-controlled, parallel-group trial, participants were randomized 1:1 (stratified by long-acting muscarinic antagonist use) to receive roflumilast or placebo, plus ICS/LABA FDC, for 52 weeks. Eligible participants had severe COPD associated with chronic bronchitis, had two or more moderate–severe exacerbations within 12 months, and were receiving ICS/LABA FDC for ≥3 months. The primary efficacy measure is the rate of moderate or severe COPD exacerbations per participant per year. The secondary efficacy outcomes include mean change in prebronchodilator forced expiratory volume in 1 second (FEV1) over 52 weeks, rate of severe exacerbations, and rate of moderate, severe, or antibiotic-treated exacerbations. Additional assessments include spirometry, rescue medication use, the COPD assessment test, daily symptoms using the EXACT-Respiratory symptoms (E-RS) questionnaire, all-cause and COPD-related hospitalizations, and safety and pharmacokinetic measures. Results Across 17 countries, 2,354 participants were randomized from September 2011 to October 2014. Enrollment goal was met in October 2014, and study completion occurred in June 2016. Conclusion This study will further characterize the effects of roflumilast added to ICS/LABA on exacerbation rates, lung function, and health of severe–very severe COPD participants at risk of further exacerbations. The results will determine the clinical benefits of roflumilast combined with standard-of-care inhaled COPD treatment. PMID

  15. A prospective trial of customized adherence enhancement plus long-acting injectable antipsychotic medication in homeless or recently homeless individuals with schizophrenia or schizoaffective disorder

    PubMed Central

    Sajatovic, Martha; Levin, Jennifer; Ramirez, Luis F.; Hahn, David Y.; Tatsuoka, Curtis; Bialko, Christopher S.; Cassidy, Kristin A.; Fuentes-Casiano, Edna; Williams, Tiffany D.

    2014-01-01

    Background Treatment non-adherence in people with schizophrenia is associated with relapse and homelessness. Building upon the usefulness of long-acting medication, and our work in psychosocial interventions to enhance adherence, we conducted a prospective uncontrolled trial of customized adherence enhancement (CAE) plus long-acting injectable antipsychotic (LAI) using haloperidol decanoate in 30 homeless or recently homeless individuals with schizophrenia and schizoaffective disorder. Methods Participants received monthly CAE and LAI (CAE-L) for 6 months. Primary outcomes were adherence as measured by the Tablets Routine Questionnaire (TRQ) and housing status. Secondary outcomes included psychiatric symptoms, functioning, side effects, and hospitalizations. Results Mean age of participants was 41.8 years (SD 8.6), mainly minorities (90% African-American) and mainly single/never married (70%). Most (97%) had past or current substance abuse, and had been incarcerated (97%). Ten individuals (33%) terminated the study prematurely. CAE-L was associated with good adherence to LAI (76% at 6 months) and dramatic improvement in oral medication adherence, which changed from missing 46% of medication at study enrollment to missing only 10% at study end (p = 0.03). There were significant improvements in psychiatric symptoms (p<.001) and functioning (p<.001). Akathisia was a major side effect with LAI. Conclusion While interpretation of findings must be tempered by the methodological limitations, CAE-L appears to be associated with improved adherence, symptoms, and functioning in homeless or recently homeless individuals with schizophrenia or schizoaffective disorder. Additional research is needed on effective and practical approaches to improving health outcomes for homeless people with serious mental illness. PMID:24434094

  16. The reassertion profiles of long acting β2-adrenoceptor agonists in the guinea pig isolated trachea and human recombinant β2-adrenoceptor.

    PubMed

    Patel, S; Summerhill, S; Stanley, M; Perros-Huguet, C; Trevethick, M A

    2011-04-01

    Long acting β(2)-adrenoceptor agonists as exemplified by salmeterol and formoterol, exhibit reassertion behaviour in isolated airway preparations. This phenomenon is the inhibition of relaxation by a β(2)-antagonist (e.g. sotalol), followed by the re-establishment of the relaxation when all drugs have been washed out and in the absence of any further agonist addition to the bathing solution. In this study we have compared the reassertion behaviour of salmeterol and formoterol with the new long acting β(2)-adrenoceptor agonists indacaterol, carmoterol and three Pfizer agonists (PF610,355, PF613,322, UK503590) in the guinea pig isolated trachea and in a novel assay developed in CHO cells expressing the recombinant human β(2)-adrenoceptor. The results obtained can be divided into two groups: salmeterol-like (persistent duration of action following agonist removal--coupled with reassertion behaviour), as exemplified by indacaterol, PF610,355, PF613,322 and UK503,590 and, formoterol-like (short duration of agonist action and little reassertion behaviour unless supramaximal concentrations are used), as exemplified by carmoterol. Results are discussed in the context of the two theories proposed to explain the long duration of action of salmeterol (binding to a specific 'exosite' of the β(2)-adrenoceptor) and formoterol (membrane deposition: micro-kinetic theory). Our data suggest that the micro-kinetic theory is an adequate explanation to explain the long duration of action of the β(2)-adrenoceptor agonists studied in these two assays, although with the current data set we cannot definitively exclude the 'exosite' theory. PMID:21134482

  17. Long-acting neuroleptic use for reproductive management of non-domestic ungulates using the domestic goat (Capra hircus) as a model.

    PubMed

    Weiss, Rachael B; Schook, Mandi W; Wolfe, Barbara A

    2014-01-01

    Fluphenazine decanoate is a long-acting phenothiazine neuroleptic that attenuates the stress response and may be useful during intensive handling for reproductive procedures in non-domestic ungulates. However, phenothiazines are also associated with elevated serum prolactin, which can suppress fertility in some species. For this study, 10 female domestic goats were used as a model for non-domestic caprids to test effects of fluphenazine decanoate on serum cortisol and reproductive cyclicity following estrus synchronization. Two identical trials were conducted during the breeding season, employing a random crossover design. First, females underwent estrus synchronization using a 14-day treatment with progesterone (330 mg; CIDR). After 7 days of CIDR exposure, the treatment group (n = 5) received fluphenazine decanoate (1.0 mg/kg IM) and controls (n = 5) received an equivalent volume of 0.9% saline IM. At CIDR withdrawal (Day 14), animals received 125 mg cloprostenol sodium to lyse any luteal tissue and synchronize estrus. Blood was collected every 2 hr from 36 hr after CIDR withdrawal until 24 hr after standing estrus, or up to 5 days to monitor stress and reproductive hormones. Serum cortisol, prolactin, luteinizing hormone (LH) and progesterone concentrations were determined by enzyme immunoassay. While treatment with fluphenazine was associated with lower cortisol concentrations compared to controls (P = 0.001), 4 of the 10 treated animals experienced elevated serum prolactin, suppression of the LH surge and inhibition of ovulation. These findings suggest that long-acting neuroleptic drugs reduce the adrenal stress response, but may interfere with reproductive responses and negatively influence breeding success. PMID:24644127

  18. Increasing Uptake of Long-Acting Reversible Contraceptives in Cambodia Through a Voucher Program: Evidence From a Difference-in-Differences Analysis

    PubMed Central

    Bajracharya, Ashish; Veasnakiry, Lo; Rathavy, Tung; Bellows, Ben

    2016-01-01

    ABSTRACT Objective: This article evaluates the use of modern contraceptives among poor women exposed to a family planning voucher program in Cambodia, with a particular focus on the uptake of long-acting reversible contraceptives (LARCs). Methods: We used a quasi-experimental study design and data from before-and-after intervention cross-sectional household surveys (conducted in 2011 and 2013) in 9 voucher program districts in Kampong Thom, Kampot, and Prey Veng provinces, as well as 9 comparison districts in neighboring provinces, to evaluate changes in use of modern contraceptives and particularly LARCs in the 12 months preceding each survey. Survey participants in the analytical sample were currently married, non-pregnant women ages 18 to 45 years (N = 1,936 at baseline; N = 1,986 at endline). Difference-in-differences (DID) analyses were used to examine the impact of the family planning voucher. Results: Modern contraceptive use increased in both intervention and control areas between baseline and endline: in intervention areas, from 22.4% to 31.6%, and in control areas, from 25.2% to 31.0%. LARC use also increased significantly between baseline and endline in both intervention (from 1.4% to 6.7%) and control (from 1.9% to 3.5%) areas, but the increase in LARC use was 3.7 percentage points greater in the intervention area than in the control area (P = .002), suggesting a positive and significant association of the voucher program with LARC use. The greatest increases occurred among the poorest and least educated women. Conclusion: A family planning voucher program can increase access to and use of more effective long-acting methods among the poor by reducing financial and information barriers. PMID:27540118

  19. Olanzapine vs. Risperidone in Patients with First-Episode Schizophrenia and a Lifetime History of Cannabis Use Disorders: 16-Week Clinical and Substance Use outcomes

    PubMed Central

    Sevy, Serge; Robinson, Delbert G.; Sunday, Suzanne; Miller, Rachel; McCormack, Joanne; Kane, John M.

    2011-01-01

    The purpose of this study is to compare the efficacy of olanzapine and risperidone for the acute treatment of first-episode schizophrenia patients with cannabis use disorders. This secondary analysis of a previously published study included forty-nine first-episode patients with a diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder and a co-occurring lifetime diagnosis of cannabis use disorders randomly assigned to treatment with either olanzapine (n=28) or risperidone (n=21) for 16 weeks. The olanzapine group did not differ significantly from the risperidone group for initial response rates of positive symptoms, and rates of cannabis use or alcohol use during the study. Positive symptoms and SANS global asociality-anhedonia improved over time but did not differ between study medications. In both groups, cannabis use during the study was higher in patients who used cannabis within 3 months of the admission. Thus, our results suggest that olanzapine and risperidone had a similar initial efficacy on psychotic symptoms and substance use in first-episode patients with co-occurring cannabis use disorders. If clinicians are choosing between olanzapine versus risperidone treatment for this population, their decision should be based upon factors other than symptom response and short-term substance misuse. PMID:21636134

  20. Marked Improvement of Meige Syndrome in a Japanese Male Patient with Schizophrenia After Switching from Risperidone to Paliperidone: A Case Report.

    PubMed

    Yoshimura, Reiji; Hori, Hikaru; Katsuki, Asuka; Atake, Kiyokazu

    2016-09-01

    Meige syndrome is a relatively rare type of oral facial dystonia. The dominant symptoms involve involuntary eye blinking and chin thrusting. Some patients may experience excessive tongue protrusion, squinting, muddled speech, or uncontrollable contraction of the platysma muscle. A 44-year-old Japanese male was suffering from schizophrenia. The initial presentation of his psychosis consisted of auditory hallucinations, delusions of persecution, psychomotor excitement, loosening association, and restlessness. After being prescribed several antipsychotic drugs, risperidone was started and gradually increased to 4 mg/day. The above symptoms were relieved, particularly auditory hallucination and excitement were promptly improved. Persecutory delusion, however persisted, and deteriorated. At one year after the start of this risperidone regimen, he exhibited severe blepharospasm symptoms (increased rate of eye blinking, light sensitivity) and oromandibular symptoms (trismus, jaw pain, dysarthria). He was diagnosed with Meige syndrome. His antipsychotic drug was changed from risperidone to paliperidone. Two months after switching from risperidone to paliperidone, his eye blinking, light sensitivity, jaw pain, and trismus gradually improved, although the dysarthria persisted. Six months after starting paliperidone, his symptoms of Meige syndrome were completely remitted. He has been well without relapse at 12 mg/day of paliperidone. The case suggests that Meige syndrome is relieved by changing from risperidone to paliperidone. The precise mechanism of the relief remains, however, unknown. PMID:27627971

  1. Controlled release formulations of risperidone antipsychotic drug in novel aliphatic polyester carriers: Data analysis and modelling.

    PubMed

    Siafaka, Panoraia I; Barmpalexis, Panagiotis; Lazaridou, Maria; Papageorgiou, George Z; Koutris, Efthimios; Karavas, Evangelos; Kostoglou, Margaritis; Bikiaris, Dimitrios N

    2015-08-01

    In the present study a series of biodegradable and biocompatible poly(ε-caprolactone)/poly(propylene glutarate) (PCL/PPGlu) polymer blends were investigated as controlled release carriers of Risperidone drug (RISP), appropriate for transdermal drug delivery. The PCL/PPGlu carriers were prepared in different weight ratios. Miscibility studies of blends were evaluated through differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolysis studies were performed at 37°C using a phosphate buffered saline solution. The prepared blends have been used for the preparation of RISP patches via solvent evaporation method, containing 5, 10 and 15wt% RISP. These formulations were characterized using FT-IR spectroscopy, DSC and WAXD in order to evaluate interactions taking place between polymer matrix and drug, as well as the dispersion and the physical state of the drug inside the polymer matrix. In vitro drug release studies were performed using as dissolution medium phosphate buffered saline simulating body fluids. It was found that in all cases controlled release formulations were obtained, while the RISP release varies due to the properties of the used polymer blend and the different levels of drug loading. Artificial Neural Networks (ANNs) were used for dissolution behaviour modelling showing increased correlation efficacy compared to Multi-Linear-Regression (MLR). PMID:26159838

  2. Short-term efficacy and safety of risperidone in young children with autistic disorder (AD).

    PubMed

    Mukaddes, Nahit Motavalli; Abali, Osman; Gurkan, Kagan

    2004-10-01

    Recently, atypical antipsychotic treatments have been used in children with autistic disorder (AD). However, data on safety and efficacy of atypical antipsychotic agents in autistic children are limited. In this open, prospective trial, subjects were treated with risperidone for six weeks. Nineteen children (12 male, 7 female) aged 4 to 8 years were started on 0.5 mg daily with individual titration to a maximum of 1.5 mg daily. Behavioural assessments were completed by Conner's parent 10-item index, AD symptom checklist and CGI-Global improvement. Statistically significant improvement was observed in mean total scores of Conner's parent 10-item index from baseline to the end of study (p< 0.001). On the basis of the CGI-Global improvement item, 15 children were considered responders. Statistically significant improvement was also found in some aspects of social contact, impulsive-aggression and repetitive, ritualistic behaviour based on assessment with the AD-symptom checklist. Weight gain and increase in night-time sleep were the most frequent side effects.

  3. Placebo-Controlled Trial of Valproic Acid Versus Risperidone in Children 3–7 Years of Age with Bipolar I Disorder

    PubMed Central

    Scheffer, Russell E.; Monroe, Erin; Delgado, Sergio; Altaye, Mekibib; Lagory, Denise

    2015-01-01

    Abstract Objective: The objective of this study was to determine the efficacy and safety of valproic acid versus risperidone in children, 3–7 years of age, with bipolar I disorder (BPD), during a mixed or manic episode. Methods: Forty-six children with Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text Revision (DSM-IV-TR) diagnosis of bipolar disorder, manic, hypomanic, or mixed episode, were recruited over a 6 year period from two academic outpatient programs for a double-blinded, placebo-controlled trial in which subjects were randomized in a 2:2:1 ratio to risperidone solution, valproic acid, or placebo. Results: After 6 weeks of treatment, the least-mean Young Mania Rating Scale (YMRS) total scores change, adjusted for baseline YMRS scores, from baseline by treatment group was: Valproic acid 10.0±2.46 (p=0.50); risperidone 18.82±1.55 (p=0.008); and placebo 4.29±3.56 (F=3.93, p=0.02). The mixed models for repeated measure (MMRM) analysis found a significant difference for risperidone-treated subjects versus placebo treated subjects (p=0.008) but not for valproic acid-treated subjects versus placebo-treated subjects (p=0.50). Treatment with risperidone over 6 weeks led to increased prolactin levels, liver functions, metabolic measures, and weight/body mass index (BMI). Treatment with valproic acid led to increases in weight/BMI and decreases in total red blood cells (RBC), hemoglobin, and hematocrit. Conclusions: In this small sample of preschool children with BPD, risperidone demonstrated clear efficacy versus placebo, whereas valproic acid did not. The laboratory and weight findings suggest that younger children with BPD are more sensitive to the effects of both of these psychotropics, and that, therefore, frequent laboratory and weight monitoring are warranted. PMID:25978742

  4. Olanzapine and risperidone disrupt conditioned avoidance responding in phencyclidine-pretreated or amphetamine-pretreated rats by selectively weakening motivational salience of conditioned stimulus.

    PubMed

    Li, Ming; He, Wei; Mead, Alexa

    2009-02-01

    The rat conditioned avoidance response model is a well-established preclinical behavioral model predictive of antipsychotic efficacy. All clinically approved antipsychotic drugs disrupt conditioned avoidance responding - a feature that distinguishes them from other psychotherapeutics. We previously showed that the typical antipsychotic drug haloperidol disrupts avoidance responding by progressively attenuating the motivational salience of the conditioned stimulus (CS) in normal rats. In this study, using two pharmacological rat models of schizophrenia [e.g. phencyclidine (PCP) or amphetamine sensitization], we examined whether atypicals such as olanzapine or risperidone disrupt avoidance responding through the same behavioral mechanism. Rats were first pretreated with PCP, amphetamine, or saline under one of two different injection schedules for either 1 or 3 weeks. They were then trained to acquire avoidance responding to two types of CS (CS1 and CS2) that differed in their ability to predict the occurrence of the unconditioned stimulus. Finally, rats were tested repeatedly under olanzapine (1.0 mg/kg, subcutaneously) or risperidone (0.33 mg/kg, subcutaneously) daily for 5 or 7 consecutive days. We found that repeated olanzapine or risperidone treatment produced a progressive across-session decline in avoidance responding to both CS1 and CS2. Olanzapine and risperidone disrupted the CS2 (a less salient CS) avoidance to a greater extent than the CS1 avoidance. Pretreatment with PCP and amphetamine did not affect the disruptive effect of olanzapine or risperidone on avoidance responding. On the basis of these findings, we suggest that the atypical drugs olanzapine and risperidone, like the typical drug haloperidol, also disrupt avoidance responding primarily by attenuating the motivational salience of the CS.

  5. The effect of umeclidinium added to inhaled corticosteroid/long-acting β2-agonist in patients with symptomatic COPD: a randomised, double-blind, parallel-group study.

    PubMed

    Sousa, Ana R; Riley, John H; Church, Alison; Zhu, Chang-Qing; Punekar, Yogesh S; Fahy, William A

    2016-01-01

    Benefits of triple therapy with a long-acting muscarinic antagonist (LAMA), added to inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA), have been demonstrated. Limited data assessing the efficacy of the LAMA umeclidinium (UMEC) added to ICS/LABA are available. The aim of this study is to evaluate the efficacy and safety of UMEC added to ICS/LABAs in patients with moderate-to-very-severe COPD. This is a multicentre, randomised, double-blind, parallel-group study. Patients were symptomatic (modified Medical Research Council Dyspnoea Scale score ⩾2), despite receiving ICS/LABA (fluticasone propionate/salmeterol (FP/SAL, branded) 500/50 mcg, budesonide/formoterol (BD/FOR, branded) 200/6 mcg or 400/12 mcg, or other ICS/LABAs) ⩾30 days before the run-in (7±2 days). Patients were randomised 1:1 to once-daily UMEC 62.5 mcg or placebo (PBO), added to twice-daily open-label ICS/LABA for 12 weeks. Primary end point was trough forced expiratory volume in 1 s (FEV1) at Day 85; secondary end point was weighted mean (WM) 0-6 h FEV1 at Day 84; other end points included COPD Assessment Test (CAT) score and Transition Dyspnoea Index (TDI) score. Adverse events (AEs) were investigated. In the UMEC+ICS/LABA and PBO+ICS/LABA groups, 119 and 117 patients were randomised, respectively. Patients received FP/SAL (40%), BD/FOR (43%) and other ICS/LABAs (17%). UMEC+ICS/LABA resulted in significant improvements in trough FEV1 (Day 85) and in WM 0-6 h FEV1 (Day 84) versus PBO+ICS/LABA (difference: 123 and 148 ml, respectively, both P<0.001). Change from baseline for UMEC+ICS/LABA versus PBO+ICS/LABA was significantly different for CAT score at Day 84 (-1.31, P<0.05), but not for TDI score (0.40, P=0.152). AE incidence was similar with UMEC+ICS/LABA (38%) and PBO+ICS/LABA (42%). UMEC+ICS/LABA improved lung function and CAT score in patients with symptomatic COPD versus PBO+ICS/LABA (ClinicalTrials.gov NCT02257372). PMID:27334739

  6. Two short-acting kappa opioid receptor antagonists (zyklophin and LY2444296) exhibited different behavioral effects from the long-acting antagonist norbinaltorphimine in mouse anxiety tests.

    PubMed

    Huang, Peng; Yakovleva, Tatyana; Aldrich, Jane V; Tunis, Julia; Parry, Christopher; Liu-Chen, Lee-Yuan

    2016-02-26

    Prototypical long-acting kappa opioid receptor (KOPR) antagonists [e.g., norbinaltorphimine (norBNI)] have been reported to exert anxiolytic-like effects in several commonly used anxiety tests in rodents including the novelty-induced hypophagia (NIH) and elevated plus maze (EPM) tests. It remains unknown if the short-acting KOPR antagonists (e.g., zyklophin and LY2444296) have similar effects. In this study effects of zyklophin and LY2444296 (s.c.) were investigated in the NIH and EPM tests in mice 1h post-injection and compared with norBNI (i.p.) 48h post-administration. In the NIH test, zyklophin at 3 and 1mg/kg, but not 0.3mg/kg, or LY2444296 at 30mg/kg decreased the latency of palatable food consumption in novel cages, but had no effect in training cages, similar to norBNI (10mg/kg). Zyklophin at 3 or 1mg/kg increased or had a trend of increasing the amount of palatable food consumption in novel cages, with no effects in training cages, further indicating its anxiolytic-like effect, but norBNI (10mg/kg) and LY2444296 (30mg/kg) did not. In the EPM test, norBNI (10mg/kg) increased open arm time and % open arm entries or time, but zyklophin at all three doses and LY2444296 (30mg/kg) had no effects. In addition, zyklophin at 3mg/kg increased numbers of close and total arm entries on EPM, suggesting increased activity; however, norBNI and LY2444296 had no effects on close and total arm entries. Thus, all three KOPR antagonists had anxiolytic-like effects in the NIH test. However, only the long-acting one (norBNI), but not the short-acting ones (zyklophin and LY2444296), demonstrated anti-anxiety like effects in the EPM test. It remains to be investigated if the differences are due to the differences in their durations of action and/or pharmacodynamic properties.

  7. A New Level A Type IVIVC for the Rational Design of Clinical Trials Toward Regulatory Approval of Generic Polymeric Long-Acting Injectables.

    PubMed

    Somayaji, Mahadevabharath R; Das, Debarun; Przekwas, Andrzej

    2016-10-01

    Chronic neuropsychiatric disorders and diabetes mellitus affect millions of patients and require long-term supervision and expensive medical care. Although repeated drug administration can help manage these diseases, relapses and re-hospitalization owing to patient non-adherence and reduced therapeutic efficacy remain challenging. In response, long-acting injectables, which provide sustained drug release over longer periods at concentrations close to therapeutic ranges, have been proposed. Recent advancements include polymeric long-acting injectables (pLAIs), in which the active pharmaceutical ingredient (API) is encapsulated within U.S. Food and Drug Administration (FDA)-approved biocompatible polymers, such as poly(lactic-co-glycolic acid), or PLGA. Despite significant progress and development in the global pLAI market, FDA guidance for the approval of complex drug products, such as generic pLAIs, is not clearly defined. Although in vitro to in vivo correlation (IVIVC) can facilitate the identification of critical quality attributes (CQAs), drug formulations, and in vitro test platforms for evaluating drug performance in vivo, the application of IVIVC in order to shortlist time- and resource-intensive clinical trials for generic pLAIs has not been reported. Here, we propose a new Level A Type IVIVC that directly correlates the in vitro outcomes, such as drug dissolution, of candidate generic formulations with the clinical characteristics, such as drug absorption, of a reference listed drug (RLD), to help identify the specific generic pLAI formulations with clinical absorptions that are likely to be similar to that of the RLD, thereby reducing the number of clinical trials required for evaluation of clinical bioequivalence (BE). Therefore, the scope of the proposed method is intended only for the rational design of clinical trials, i.e., to shortlist the specific pLAI generic formulations for clinical BE evaluation, and not necessarily to analyze drug performances

  8. A New Level A Type IVIVC for the Rational Design of Clinical Trials Toward Regulatory Approval of Generic Polymeric Long-Acting Injectables.

    PubMed

    Somayaji, Mahadevabharath R; Das, Debarun; Przekwas, Andrzej

    2016-10-01

    Chronic neuropsychiatric disorders and diabetes mellitus affect millions of patients and require long-term supervision and expensive medical care. Although repeated drug administration can help manage these diseases, relapses and re-hospitalization owing to patient non-adherence and reduced therapeutic efficacy remain challenging. In response, long-acting injectables, which provide sustained drug release over longer periods at concentrations close to therapeutic ranges, have been proposed. Recent advancements include polymeric long-acting injectables (pLAIs), in which the active pharmaceutical ingredient (API) is encapsulated within U.S. Food and Drug Administration (FDA)-approved biocompatible polymers, such as poly(lactic-co-glycolic acid), or PLGA. Despite significant progress and development in the global pLAI market, FDA guidance for the approval of complex drug products, such as generic pLAIs, is not clearly defined. Although in vitro to in vivo correlation (IVIVC) can facilitate the identification of critical quality attributes (CQAs), drug formulations, and in vitro test platforms for evaluating drug performance in vivo, the application of IVIVC in order to shortlist time- and resource-intensive clinical trials for generic pLAIs has not been reported. Here, we propose a new Level A Type IVIVC that directly correlates the in vitro outcomes, such as drug dissolution, of candidate generic formulations with the clinical characteristics, such as drug absorption, of a reference listed drug (RLD), to help identify the specific generic pLAI formulations with clinical absorptions that are likely to be similar to that of the RLD, thereby reducing the number of clinical trials required for evaluation of clinical bioequivalence (BE). Therefore, the scope of the proposed method is intended only for the rational design of clinical trials, i.e., to shortlist the specific pLAI generic formulations for clinical BE evaluation, and not necessarily to analyze drug performances

  9. Combination of long-acting microcapsules of the D-tryptophan-6 analog of luteinizing hormone-releasing hormone with chemotherapy: investigation in the rat prostate cancer model.

    PubMed Central

    Schally, A V; Redding, T W

    1985-01-01

    The effect of combining hormonal treatment consisting of long-acting microcapsules of the agonist [D-Trp6]LH-RH (the D-tryptophan-6 analog of luteinizing hormone-releasing hormone) with the chemotherapeutic agent cyclophosphamide was investigated in the Dunning R-3327H rat prostate cancer model. Microcapsules of [D-Trp6]LH-RH formulated from poly(DL-lactide-co-glycolide) and calculated to release a controlled dose of 25 micrograms/day were injected intramuscularly once a month. Cyclophosphamide (Cytoxan) (5 mg/kg of body weight) was injected intraperitoneally twice a week. When the therapy was started 90 days after tumor transplantation--at the time that the cancers were well developed-and was continued for 2 months, tumor volume was significantly reduced by the microcapsules or Cytoxan given alone. The combination of these two agents similarly inhibited tumor growth but did not show a synergistic effect. In another study, the treatment was started 2 months after transplantation, when the developing tumors measured 60-70 mm3. Throughout the treatment period of 100 days, the microcapsules of [D-Trp6]LH-RH reduced tumor volume more than Cytoxan did, and the combination of the two drugs appeared to completely arrest tumor growth. Tumor weights also were diminished significantly in all experimental groups, the decrease in weight being smaller in the Cytoxan-treated group than in rats that received the microcapsules. The combination of Cytoxan plus the microcapsules was 10-100 times more effective than the single agents in reducing tumor weights. In both experiments, testes and ventral prostate weights were significantly diminished, serum testosterone was suppressed to undetectable levels, and prolactin values were reduced by administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Cytoxan. These results in rats suggest that combined administration of long acting microcapsules of [D-Trp6]LH-RH with a chemotherapeutic agent, started soon after the

  10. Comparative safety and effectiveness of long-acting inhaled agents for treating chronic obstructive pulmonary disease: a systematic review and network meta-analysis

    PubMed Central

    Tricco, Andrea C; Strifler, Lisa; Veroniki, Areti-Angeliki; Yazdi, Fatemeh; Khan, Paul A; Scott, Alistair; Ng, Carmen; Antony, Jesmin; Mrklas, Kelly; D'Souza, Jennifer; Cardoso, Roberta; Straus, Sharon E

    2015-01-01

    Objective To compare the safety and effectiveness of long-acting β-antagonists (LABA), long-acting antimuscarinic agents (LAMA) and inhaled corticosteroids (ICS) for managing chronic obstructive pulmonary disease (COPD). Setting Systematic review and network meta-analysis (NMA). Participants 208 randomised clinical trials (RCTs) including 134 692 adults with COPD. Interventions LABA, LAMA and/or ICS, alone or in combination, versus each other or placebo. Primary and secondary outcomes The proportion of patients with moderate-to-severe exacerbations. The number of patients experiencing mortality, pneumonia, serious arrhythmia and cardiovascular-related mortality (CVM) were secondary outcomes. Results NMA was conducted including 20 RCTs for moderate-to-severe exacerbations for 26 141 patients with an exacerbation in the past year. 32 treatments were effective versus placebo including: tiotropium, budesonide/formoterol, salmeterol, indacaterol, fluticasone/salmeterol, indacaterol/glycopyrronium, tiotropium/fluticasone/salmeterol and tiotropium/budesonide/formoterol. Tiotropium/budesonide/formoterol was most effective (99.2% probability of being the most effective according to the Surface Under the Cumulative RAnking (SUCRA) curve). NMA was conducted on mortality (88 RCTs, 97 526 patients); fluticasone/salmeterol was more effective in reducing mortality than placebo, formoterol and fluticasone alone, and was the most effective (SUCRA=71%). NMA was conducted on CVM (37 RCTs, 55 156 patients) and the following were safest: salmeterol versus each OF placebo, tiotropium and tiotropium (Soft Mist Inhaler (SMR)); fluticasone versus tiotropium (SMR); and salmeterol/fluticasone versus tiotropium and tiotropium (SMR). Triamcinolone acetonide was the most harmful (SUCRA=81%). NMA was conducted on pneumonia occurrence (54 RCTs, 61 551 patients). 24 treatments were more harmful, including 2 that increased risk of pneumonia versus placebo; fluticasone and fluticasone

  11. A double-blind placebo controlled trial of piracetam added to risperidone in patients with autistic disorder.

    PubMed

    Akhondzadeh, Shahin; Tajdar, Hamid; Mohammadi, Mohammad-Reza; Mohammadi, Mohammad; Nouroozinejad, Gholam-Hossein; Shabstari, Omid L; Ghelichnia, Hossein-Ali

    2008-09-01

    It has been reported that autism is a hypoglutamatergic disorder. Therefore, it was of interest to assess the efficacy of piracetam, a positive modulator of AMPA-sensitive glutamate receptors in autistic disorder. About 40 children between the ages three and 11 years (inclusive) with a DSM IV clinical diagnosis of autism and who were outpatients from a specialty clinic for children were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to piracetam + risperidone (Group A) or placebo + risperidone (Group B) for a 10-week, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 2 mg/day for children between 10 and 40 kg and 3 mg/day for children weighting above 40 kg. The dose of piracetam was titrated up to 800 mg/day. Patients were assessed at baseline and after 2, 4, 6, 8 and 10 weeks of starting medication. The measure of the outcome was the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale (total score). The ABC-C Rating Scale scores improved with piracetam. The difference between the two protocols was significant as indicated by the effect of group, the between subjects factor (F = 5.85, d.f. = 1, P = 0.02). The changes at the endpoint compared with baseline were: -11.90 +/- 3.79 (mean +/- SD) and -5.15 +/- 3.04 for group A and B respectively. A significant difference was observed on the change in scores in the ABC-C Rating Scale in week 10 compared with baseline in the two groups (t = 6.017, d.f. = 38, P < 0.0001). The results suggest that a combination of atypical antipsychotic medications and a glutamate agent such as piracetam, might have increase synergistic effects in the treatment of autism.

  12. A case of psychosis due to Fahr's syndrome and response to behavioral disturbances with risperidone and oxcarbazepine

    PubMed Central

    Faye, Abhijeet Dhawalram; Gawande, Sushil; Tadke, Rahul; Kirpekar, Vivek C.; Bhave, Sudhir H.

    2014-01-01

    Calcification of basal ganglia or Fahr's syndrome is a rare disease characterized by bilateral and symmetrical intracranial deposition of calcium mainly in cerebral basal ganglia. Motor and neuropsychiatric symptoms are prominent features. We report a case presented with a few motor symptoms, features of delirium and prominent psychiatric symptoms (disorganized behavior) predominantly evident after the improvement in delirium. Radiological findings were suggestive of bilateral basal ganglia calcification. Parathyroid hormone levels were low with no significant findings in other investigations and negative family history. Patient showed significant improvement in behavioral disturbances with risperidone, low dose of lorazepam, oxcarbazepine, and memantine. PMID:24891710

  13. Assessment of pharmacokinetic compatibility of short acting CDRI candidate trioxane derivative, 99–411, with long acting prescription antimalarials, lumefantrine and piperaquine

    PubMed Central

    Taneja, Isha; Raju, Kanumuri Siva Rama; Singh, Sheelendra Pratap; Wahajuddin, Muhammad

    2015-01-01

    The pharmacokinetic compatibility of short-acting CDRI candidate antimalarial trioxane derivative, 99–411, was tested with long-acting prescription antimalarials, lumefantrine and piperaquine. LC-ESI-MS/MS methods were validated for simultaneous bioanalysis of lumefantrine and 99–411 and of piperaquine and 99–411 combinations. The interaction studies were performed in rats using these validated methods. The total systemic exposure of 99–411 increased when administered with either lumefantrine or piperaquine. However, co-administration of 99–411 significantly decreased the systemic exposure of piperaquine by half-fold while it had no effect on the kinetics of lumefantrine. 99–411, thus, seemed to be a good alternative to artemisinin derivatives for combination treatment with lumefantrine. To explore the reason for increased plasma levels of 99–411, an in situ permeability study was performed by co-perfusing lumefantrine and 99–411. In presence of lumefantrine, the absorption of 99–411 was significantly increased by 1.37 times than when given alone. Lumefantrine did not affect the metabolism of 99–411 when tested in vitro in human liver microsomes. Additionally, ATPase assay suggest that 99–411 was a substrate of human P-gp, thus, indicating the probability of interaction at the absorption level in humans as well. PMID:26602250

  14. Reversible competitive α-ketoheterocycle inhibitors of fatty acid amide hydrolase containing additional conformational constraints in the acyl side chain: orally active, long-acting analgesics.

    PubMed

    Ezzili, Cyrine; Mileni, Mauro; McGlinchey, Nicholas; Long, Jonathan Z; Kinsey, Steven G; Hochstatter, Dustin G; Stevens, Raymond C; Lichtman, Aron H; Cravatt, Benjamin F; Bilsky, Edward J; Boger, Dale L

    2011-04-28

    A series of α-ketooxazoles containing conformational constraints in the C2 acyl side chain of 2 (OL-135) were examined as inhibitors of fatty acid amide hydrolase (FAAH). Only one of the two possible enantiomers displayed potent FAAH inhibition (S vs R enantiomer), and their potency is comparable or improved relative to 2, indicating that the conformational restriction in the C2 acyl side chain is achievable. A cocrystal X-ray structure of the α-ketoheterocycle 12 bound to a humanized variant of rat FAAH revealed its binding details, confirmed that the (S)-enantiomer is the bound active inhibitor, shed light on the origin of the enantiomeric selectivity, and confirmed that the catalytic Ser241 is covalently bound to the electrophilic carbonyl as a deprotonated hemiketal. Preliminary in vivo characterization of the inhibitors 12 and 14 is reported demonstrating that they raise brain anandamide levels following either intraperitoneal (ip) or oral (po) administration indicative of effective in vivo FAAH inhibition. Significantly, the oral administration of 12 caused dramatic accumulation of anandamide in the brain, with peak levels achieved between 1.5 and 3 h, and these elevations were maintained over 9 h. Additional studies of these two representative members of the series (12 and 14) in models of thermal hyperalgesia and neuropathic pain are reported, including the demonstration that 12 administered orally significantly attenuated mechanical (>6 h) and cold (>9 h) allodynia for sustained periods consistent with its long-acting effects in raising the endogenous concentration of anandamide.

  15. Low Frequency of Drug-Resistant Variants Selected by Long-Acting Rilpivirine in Macaques Infected with Simian Immunodeficiency Virus Containing HIV-1 Reverse Transcriptase

    PubMed Central

    Melody, Kevin; McBeth, Sarah; Kline, Christopher; Kashuba, Angela D. M.; Mellors, John W.

    2015-01-01

    Preexposure prophylaxis (PrEP) using antiretroviral drugs is effective in reducing the risk of human immunodeficiency virus type 1 (HIV-1) infection, but adherence to the PrEP regimen is needed. To improve adherence, a long-acting injectable formulation of the nonnucleoside reverse transcriptase (RT) inhibitor rilpivirine (RPV LA) has been developed. However, there are concerns that PrEP may select for drug-resistant mutations during preexisting or breakthrough infections, which could promote the spread of drug resistance and limit options for antiretroviral therapy. To address this concern, we administered RPV LA to macaques infected with simian immunodeficiency virus containing HIV-1 RT (RT-SHIV). Peak plasma RPV levels were equivalent to those reported in human trials and waned over time after dosing. RPV LA resulted in a 2-log decrease in plasma viremia, and the therapeutic effect was maintained for 15 weeks, until plasma drug concentrations dropped below 25 ng/ml. RT mutations E138G and E138Q were detected in single clones from plasma virus in separate animals only at one time point, and no resistance mutations were detected in viral RNA isolated from tissues. Wild-type and E138Q RT-SHIV displayed similar RPV susceptibilities in vitro, whereas E138G conferred 2-fold resistance to RPV. Overall, selection of RPV-resistant variants was rare in an RT-SHIV macaque model despite prolonged exposure to slowly decreasing RPV concentrations following injection of RPV LA. PMID:26438501

  16. Is Household Wealth Associated With Use of Long-Acting Reversible and Permanent Methods of Contraception? A Multi-Country Analysis

    PubMed Central

    Ugaz, Jorge I; Chatterji, Minki; Gribble, James N; Banke, Kathryn

    2016-01-01

    Abstract As programs continue to expand access to family planning information, services, and products, it is critical that these efforts be undertaken with an equity lens, ensuring that regardless of socioeconomic status, all women and couples can use the method that meets their needs. This study explores the relationship between household wealth and the use of long-acting and permanent methods (LAPMs) versus short-acting methods of contraception among modern method users, using multivariate analyses based on Demographic Health Survey data from 30 developing countries conducted between 2006 and 2013. Overall, and controlling for relevant individual and household characteristics including age, number of living children, education, and urban/rural residence, we found that wealthier women were more likely than poorer women to use LAPMs instead of short-acting methods: 20 of the 30 countries showed a positive and statistically significant association between wealth and LAPM use. For 10 of those countries, however, LAPM use was significantly higher only for the top (1 or 2) wealthiest quintiles. Eight countries showed no broad pattern of association, while in 2 countries—Bangladesh and India—poorer women were more likely to use LAPMs than wealthier women. The positive association between wealth and LAPM use was found most consistently in the Latin American and the Caribbean countries in our sample. These findings can help program implementers respond better to women’s needs for modern contraception, especially in reaching women from lower- and middle-income households. PMID:27016543

  17. Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-associated acute kidney injury

    PubMed Central

    Nishida, Kento; Watanabe, Hiroshi; Ogaki, Shigeru; Kodama, Azusa; Tanaka, Ryota; Imafuku, Tadashi; Ishima, Yu; Giam Chuang, Victor Tuan; Toyoda, Masao; Kondoh, Masumi; Wu, Qiong; Fukagawa, Masafumi; Otagiri, Masaki; Maruyama, Toru

    2015-01-01

    Rhabdomyolysis-associated acute kidney injury (AKI) is a serious life-threatening condition. As such, more effective strategies are needed for its prevention. Thioredoxin-1 (Trx), a redox-active and macrophage migration inhibitory factor (MIF) modulating protein, has a short retention time in the blood. We examined the renoprotective effect of long acting Trx that was genetically fused with human serum albumin (HSA-Trx) against glycerol-induced AKI. An intravenous HSA-Trx pre-treatment attenuated the glycerol-induced decline in renal function, compared to a PBS, HSA or Trx alone. HSA-Trx caused a reduction in the tubular injuries and in the number of apoptosis-positive tubular cells. Renal superoxide, 8-hydroxy deoxyguanosine, nitrotyrosine and the plasma Cys34-cysteinylated albumin were clearly suppressed by the HSA-Trx treatment. Prior to decreasing TNF-α and IL-6, HSA-Trx suppressed an increase of plasma MIF level. In LLC-PK1 cells, HSA-Trx decreased the level of reactive oxygen species and lactate dehydrogenase release induced by myoglobin. HSA-Trx treatment resulted in a threefold increase in the survival of lethal glycerol-treated mice. The post-administration of HSA-Trx at 1 and 3 hr after glycerol injection exerted a significant renoprotective effect. These results suggest HSA-Trx has potential for use in the treatment of rhabdomyolysis-associated AKI via its extended effects of modulating oxidative stress and MIF. PMID:26412311

  18. PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates.

    PubMed

    Thompson, W Clayton; Zhou, Yingjiang; Talukdar, Saswata; Musante, Cynthia J

    2016-08-01

    PF-05231023, a long-acting FGF21 analogue, is a promising potential pharmacotherapy for the treatment of obesity and associated comorbidities. Previous studies have shown the potential of FGF21 and FGF21-like compounds to decrease body weight in mice, non-human primates, and humans; the precise mechanisms of action remain unclear. In particular, there have been conflicting reports on the degree to which FGF21-induced weight loss in non-human primates is attributable to a decrease in food intake versus an increase in energy expenditure. Here, we present a semi-mechanistic mathematical model of energy balance and body composition developed from similar work in mice. This model links PF-05231023 administration and washout to changes in food intake, which in turn drives changes in body weight. The model is calibrated to and compared with recently published data from cynomolgus macaques treated with PF-05231023, demonstrating its accuracy in describing pharmacotherapy-induced weight loss in these animals. The results are consistent with the hypothesis that PF-05231023 decreases body weight in cynomolgus macaques solely by a reduction in food intake, with no direct effect on energy expenditure. PMID:27405817

  19. A Long-Acting FGF21 Molecule, PF-05231023, Decreases Body Weight and Improves Lipid Profile in Non-human Primates and Type 2 Diabetic Subjects.

    PubMed

    Talukdar, Saswata; Zhou, Yingjiang; Li, Dongmei; Rossulek, Michelle; Dong, Jennifer; Somayaji, Veena; Weng, Yan; Clark, Ronald; Lanba, Adhiraj; Owen, Bryn M; Brenner, Martin B; Trimmer, Jeffrey K; Gropp, Kathryn E; Chabot, Jeffrey R; Erion, Derek M; Rolph, Timothy P; Goodwin, Bryan; Calle, Roberto A

    2016-03-01

    FGF21 plays a central role in energy, lipid, and glucose homeostasis. To characterize the pharmacologic effects of FGF21, we administered a long-acting FGF21 analog, PF-05231023, to obese cynomolgus monkeys. PF-05231023 caused a marked decrease in food intake that led to reduced body weight. To assess the effects of PF-05231023 in humans, we conducted a placebo-controlled, multiple ascending-dose study in overweight/obese subjects with type 2 diabetes. PF-05231023 treatment resulted in a significant decrease in body weight, improved plasma lipoprotein profile, and increased adiponectin levels. Importantly, there were no significant effects of PF-05231023 on glycemic control. PF-05231023 treatment led to dose-dependent changes in multiple markers of bone formation and resorption and elevated insulin-like growth factor 1. The favorable effects of PF-05231023 on body weight support further evaluation of this molecule for the treatment of obesity. Longer studies are needed to assess potential direct effects of FGF21 on bone in humans. PMID:26959184

  20. Celebration Meets Caution: Long Acting Reversible Contraception (LARC)’s Boons, Potential Busts, and the Benefits of a Reproductive Justice Approach

    PubMed Central

    Higgins, Jenny A.

    2014-01-01

    Recent years have witnessed an outpouring of research and funding pertaining to long-acting reversible contraception (LARC). The time is ripe to contextualize LARC’s hype within our broader reproductive health goals and tools—that is, how we can best address the needs of individuals who benefit from the reproductive health services we provide. After reviewing LARC’s major benefits, this commentary presents three potentially problematic aspects of LARC promotion: 1) the notion that increasing LARC use could singlehandedly end unintended pregnancies and their associations with poverty, 2) the clinical emphasis on LARC methods over all others, and 3) inadvertently failing to acknowledge the ways in which poor women of color will experience LARC promotion through legacies of racism and eugenics. The comment concludes by highlighting the benefits of a reproductive justice approach to LARC: an approach devoted to making LARC affordable and accessible while simultaneously respecting women’s decisions not to use LARC, their ability to have LARC removed when they wish, and their ability to determine for themselves where contraception and pregnancies fit into their lives. PMID:24582293

  1. Application of Adaptive Design Methodology in Development of a Long-Acting Glucagon-Like Peptide-1 Analog (Dulaglutide): Statistical Design and Simulations

    PubMed Central

    Skrivanek, Zachary; Berry, Scott; Berry, Don; Chien, Jenny; Geiger, Mary Jane; Anderson, James H.; Gaydos, Brenda

    2012-01-01

    Background Dulaglutide (dula, LY2189265), a long-acting glucagon-like peptide-1 analog, is being developed to treat type 2 diabetes mellitus. Methods To foster the development of dula, we designed a two-stage adaptive, dose-finding, inferentially seamless phase 2/3 study. The Bayesian theoretical framework is used to adaptively randomize patients in stage 1 to 7 dula doses and, at the decision point, to either stop for futility or to select up to 2 dula doses for stage 2. After dose selection, patients continue to be randomized to the selected dula doses or comparator arms. Data from patients assigned the selected doses will be pooled across both stages and analyzed with an analysis of covariance model, using baseline hemoglobin A1c and country as covariates. The operating characteristics of the trial were assessed by extensive simulation studies. Results Simulations demonstrated that the adaptive design would identify the correct doses 88% of the time, compared to as low as 6% for a fixed-dose design (the latter value based on frequentist decision rules analogous to the Bayesian decision rules for adaptive design). Conclusions This article discusses the decision rules used to select the dula dose(s); the mathematical details of the adaptive algorithm—including a description of the clinical utility index used to mathematically quantify the desirability of a dose based on safety and efficacy measurements; and a description of the simulation process and results that quantify the operating characteristics of the design. PMID:23294775

  2. Assessment of pharmacokinetic compatibility of short acting CDRI candidate trioxane derivative, 99-411, with long acting prescription antimalarials, lumefantrine and piperaquine.

    PubMed

    Taneja, Isha; Raju, Kanumuri Siva Rama; Singh, Sheelendra Pratap; Wahajuddin, Muhammad

    2015-01-01

    The pharmacokinetic compatibility of short-acting CDRI candidate antimalarial trioxane derivative, 99-411, was tested with long-acting prescription antimalarials, lumefantrine and piperaquine. LC-ESI-MS/MS methods were validated for simultaneous bioanalysis of lumefantrine and 99-411 and of piperaquine and 99-411 combinations. The interaction studies were performed in rats using these validated methods. The total systemic exposure of 99-411 increased when administered with either lumefantrine or piperaquine. However, co-administration of 99-411 significantly decreased the systemic exposure of piperaquine by half-fold while it had no effect on the kinetics of lumefantrine. 99-411, thus, seemed to be a good alternative to artemisinin derivatives for combination treatment with lumefantrine. To explore the reason for increased plasma levels of 99-411, an in situ permeability study was performed by co-perfusing lumefantrine and 99-411. In presence of lumefantrine, the absorption of 99-411 was significantly increased by 1.37 times than when given alone. Lumefantrine did not affect the metabolism of 99-411 when tested in vitro in human liver microsomes. Additionally, ATPase assay suggest that 99-411 was a substrate of human P-gp, thus, indicating the probability of interaction at the absorption level in humans as well. PMID:26602250

  3. Low Frequency of Drug-Resistant Variants Selected by Long-Acting Rilpivirine in Macaques Infected with Simian Immunodeficiency Virus Containing HIV-1 Reverse Transcriptase.

    PubMed

    Melody, Kevin; McBeth, Sarah; Kline, Christopher; Kashuba, Angela D M; Mellors, John W; Ambrose, Zandrea

    2015-12-01

    Preexposure prophylaxis (PrEP) using antiretroviral drugs is effective in reducing the risk of human immunodeficiency virus type 1 (HIV-1) infection, but adherence to the PrEP regimen is needed. To improve adherence, a long-acting injectable formulation of the nonnucleoside reverse transcriptase (RT) inhibitor rilpivirine (RPV LA) has been developed. However, there are concerns that PrEP may select for drug-resistant mutations during preexisting or breakthrough infections, which could promote the spread of drug resistance and limit options for antiretroviral therapy. To address this concern, we administered RPV LA to macaques infected with simian immunodeficiency virus containing HIV-1 RT (RT-SHIV). Peak plasma RPV levels were equivalent to those reported in human trials and waned over time after dosing. RPV LA resulted in a 2-log decrease in plasma viremia, and the therapeutic effect was maintained for 15 weeks, until plasma drug concentrations dropped below 25 ng/ml. RT mutations E138G and E138Q were detected in single clones from plasma virus in separate animals only at one time point, and no resistance mutations were detected in viral RNA isolated from tissues. Wild-type and E138Q RT-SHIV displayed similar RPV susceptibilities in vitro, whereas E138G conferred 2-fold resistance to RPV. Overall, selection of RPV-resistant variants was rare in an RT-SHIV macaque model despite prolonged exposure to slowly decreasing RPV concentrations following injection of RPV LA. PMID:26438501

  4. Is Household Wealth Associated With Use of Long-Acting Reversible and Permanent Methods of Contraception? A Multi-Country Analysis.

    PubMed

    Ugaz, Jorge I; Chatterji, Minki; Gribble, James N; Banke, Kathryn

    2016-03-01

    As programs continue to expand access to family planning information, services, and products, it is critical that these efforts be undertaken with an equity lens, ensuring that regardless of socioeconomic status, all women and couples can use the method that meets their needs. This study explores the relationship between household wealth and the use of long-acting and permanent methods (LAPMs) versus short-acting methods of contraception among modern method users, using multivariate analyses based on Demographic Health Survey data from 30 developing countries conducted between 2006 and 2013. Overall, and controlling for relevant individual and household characteristics including age, number of living children, education, and urban/rural residence, we found that wealthier women were more likely than poorer women to use LAPMs instead of short-acting methods: 20 of the 30 countries showed a positive and statistically significant association between wealth and LAPM use. For 10 of those countries, however, LAPM use was significantly higher only for the top (1 or 2) wealthiest quintiles. Eight countries showed no broad pattern of association, while in 2 countries-Bangladesh and India-poorer women were more likely to use LAPMs than wealthier women. The positive association between wealth and LAPM use was found most consistently in the Latin American and the Caribbean countries in our sample. These findings can help program implementers respond better to women's needs for modern contraception, especially in reaching women from lower- and middle-income households.

  5. Management of asthma and chronic obstructive pulmonary disease with combination inhaled corticosteroids and long-acting β-agonists: a review of comparative effectiveness research.

    PubMed

    Mapel, Douglas W; Roberts, Melissa H

    2014-05-01

    The value of combination therapy with inhaled corticosteroids and long-acting β-agonists (ICS/LABA) is well recognized in the management of asthma and chronic obstructive pulmonary disease (COPD). Despite differences in the pharmacological properties between two well-established ICS/LABA products (budesonide/formoterol and fluticasone/salmeterol), data from randomized clinical trials (RCTs) and meta-analyses suggest that these two products perform similarly under RCT conditions. In contrast, a few recently reported real-world comparative effectiveness studies have suggested that there are substantial differences between ICS/LABA combination treatments in terms of clinical and healthcare outcomes in patients with asthma or COPD. The purpose of this article is to provide a brief review of the benefits, as well as the limitations, of comparative effectiveness research (CER) in the therapeutic area of asthma and COPD. We conducted a structured literature review of the current CER studies on ICS/LABA combinations in asthma and COPD. These articles were then used to illustrate the unique challenges of CER studies, providing a summary of study results and limitations. We focus particularly on difficult biases and confounding factors that may be introduced before, during, and after the initiation of therapy. Beyond being a review of these two ICS/LABA combination treatments, this article is intended to help those who wish to assess the quality of CER published projects in asthma and COPD, or guide investigators who wish to design new CER studies for chronic respiratory disease treatments.

  6. Targets, attitudes, and goals of psychiatrists treating patients with schizophrenia: key outcome drivers, role of quality of life, and place of long-acting antipsychotics

    PubMed Central

    de Bartolomeis, Andrea; Fagiolini, Andrea; Vaggi, Marco; Vampini, Claudio

    2016-01-01

    Purpose This survey of Italian psychiatrists was conducted to better define drivers of schizophrenia treatment choice in real-life practice, particularly for use of long-acting injectable (LAI) antipsychotics. Methods Between October 15 and December 15, 2014, 1,000 surveys were sent to psychiatrists who treat schizophrenic patients; 709 completed questionnaires were analyzed (71% response rate). Results The two most important factors determining therapy success were efficacy (75% of responses) and tolerability (45%) followed by global functioning (24%) and quality of life (17%). LAI antipsychotics were most often used to facilitate regular treatment monitoring (49%), and 41% of psychiatrists thought that patients with low adherence who had failed oral therapy were well-suited for LAI antipsychotics. Only 4% of respondents saw LAI antipsychotics as appropriate for patients without other therapeutic options. Conclusion Although efficacy and tolerability were the most common factors used to evaluate treatment success in schizophrenia, psychiatrists also consider QoL and global functioning to be important. PMID:26811682

  7. Ethical issues experienced by mental health nurses in the administration of antipsychotic depot and long-acting intramuscular injections: a qualitative study.

    PubMed

    Smith, James Paul; Herber, Oliver Rudolf

    2015-06-01

    The ethical issues experienced by mental health nurses in administering antipsychotic depot and long-acting intramuscular injections (LAI) were explored in the present study. Mental health nurses face ethically-difficult situations when administering these medications. A phenomenological research method guided by Max van Manen's human science approach describes and interprets the ethical issues involved in performing the procedure. Purposive and snowball sampling was used to select eight participants from two mental health hospitals. Semistructured interviews were carried out to collect data. A thematic analysis was conducted on the data. The four main themes that emerged from the analyses were: (i) lack of alternatives; (ii) safety; (iii) feeling uncomfortable; and (iv) difficulty maintaining the therapeutic relationship. The findings suggest that mental health nurses face ethical challenges in administering LAI. The findings raise much needed awareness of the need for mental health nurses and nurse educators to consider the ethical issues experienced while performing the procedure. There is a need for nurse education providers and organizations to provide opportunities for mental health nurses to address their 'lived experiences'. Educational courses are needed to equip mental health nurses with the technical and critical thinking skills to administer safe and effective antipsychotic depot and LAI.

  8. Development of Nutraceutical Emulsions as Risperidone Delivery Systems: Characterization and Toxicological Studies.

    PubMed

    Igartúa, Daniela Edith; Calienni, María Natalia; Feas, Daniela Agustina; Chiaramoni, Nadia Silvia; Valle Alonso, Silvia Del; Prieto, María Jimena

    2015-12-01

    Emulsions are gaining increasing interest to be applied as drug delivery systems. The main goal of this work was the formulation of an oil/water nutraceutical emulsion (NE) for oral administration, enriched in omega 3 (ω3) and omega 6 (ω6), and able to encapsulate risperidone (RISP), an antipsychotic drug widely used in the treatment of autism spectrum disorders (ASD). RISP has low solubility in aqueous medium and poor bioavailability because of its metabolism and high protein binding. Coadministration of ω3, ω3, and vitamin E complexed with RISP might increase its bioavailability and induce a synergistic effect on the treatment of ASD. Here, we developed an easy and quick method to obtain NEs and then optimized them. The best formulation was chosen after characterization by particle size, defects of the oil-in-water interface, zeta potential (ZP), and in vitro drug release. The formulation selected was stable over time, with a particle size of around 3 μm, a ZP lower than -20 mV and controlled drug release. To better understand the biochemical properties of the formulation obtained, we studied in vitro toxicity in the Caco-2 cell line. After 4 h of treatment, an increase in cellular metabolism was observed for all RISP concentrations, but emulsions did not change their metabolic rate, except at the highest concentration without drug (25 μg/mL), which showed a significant reduction in metabolism respect to the control. Additionally, locomotor activity and heart rate in zebrafish were measured as parameters of in vivo toxicity. Only the highest concentration (0.625 μg/mL) showed a cardiotoxic effect, which corresponds to the decrease in spontaneous movement observed previously. As all the materials contained in the formulations were US FDA approved, the NE selected would be good candidate for clinical trials.

  9. Study on the luminescence behavior of sulfobutylether-β-cyclodextrin with risperidone and its analytical application

    NASA Astrophysics Data System (ADS)

    Wu, Min; Chen, Donghua; Song, Zhenghua

    2012-10-01

    The interaction of sulfobutylether-β-cyclodextrin (SBE-β-CD) with risperidone (RISP) was first described with luminol-SBE-β-CD chemiluminescence (CL) system by flow injection analysis (FIA). In luminol-SBE-β-CD CL system, the 1:1 SBE-β-CD⋯luminol∗ complexation could enhance CL intensity of luminol and produce the effect of complexation enhancement of CL (CEC). It was found that RISP could quench the CL intensity of SBE-β-CD⋯luminol∗ and caused the effect of complexation enhancement of quenching (CEQ), the formation constant KR-CD 3.4 × 104 L mol-1 and the stoichiometric ratio 1:1 of RISP⋯SBE-β-CD complex were obtained by the proposed CL model. Association degree α 0.036 of RISP⋯SBE-β-CD complex was also given by CL method. Based on the linear relationship to the decrement of luminol-SBE-β-CD-RISP CL intensity and the logarithm of RISP concentration, RISP also can be quantified in the linear range of 3.0-500.0 nmol L-1 with a detection limit of 1.0 nmol L-1 (3σ). The proposed method was successfully applied to monitoring excreted RISP in human urine. It was found that RISP reached its maximum after oral administration for 1.5 h with the total excretion of 14.26% within 8.5 h; the elimination rate constant k and half-life time t1/2 were 0.474 and 1.5 h, respectively.

  10. A Randomized Comparison of Aripiprazole and Risperidone for the Acute Treatment of First-Episode Schizophrenia and Related Disorders: 3-Month Outcomes.

    PubMed

    Robinson, Delbert G; Gallego, Juan A; John, Majnu; Petrides, Georgios; Hassoun, Youssef; Zhang, Jian-Ping; Lopez, Leonardo; Braga, Raphael J; Sevy, Serge M; Addington, Jean; Kellner, Charles H; Tohen, Mauricio; Naraine, Melissa; Bennett, Natasha; Greenberg, Jessica; Lencz, Todd; Correll, Christoph U; Kane, John M; Malhotra, Anil K

    2015-11-01

    Research findings are particularly important for medication choice for first-episode patients as individual prior medication response to guide treatment decisions is unavailable. We describe the first large-scale double-masked randomized comparison with first-episode patients of aripiprazole and risperidone, 2 commonly used first-episode treatment agents. One hundred ninety-eight participants aged 15-40 years with schizophrenia, schizophreniform disorder, schizoaffective disorder or psychotic disorder Not Otherwise Specified, and who had been treated in their lifetime with antipsychotics for 2 weeks or less were randomly assigned to double-masked aripiprazole (5-30 mg/d) or risperidone (1-6 mg/d) and followed for 12 weeks. Positive symptom response rates did not differ (62.8% vs 56.8%) nor did time to response. Aripiprazole-treated participants had better negative symptom outcomes but experienced more akathisia. Body mass index change did not differ between treatments but advantages were found for aripiprazole treatment for total and low-density lipoprotein cholesterol, fasting glucose, and prolactin levels. Post hoc analyses suggested advantages for aripiprazole on depressed mood. Overall, if the potential for akathisia is a concern, low-dose risperidone as used in this trial maybe a preferred choice over aripiprazole. Otherwise, aripiprazole would be the preferred choice over risperidone in most situations based upon metabolic outcome advantages and some symptom advantages within the context of similar positive symptom response between medications.

  11. Effects of Risperidone on Aberrant Behavior of Persons with Developmental Disabilities: I. A Double-Blind Crossover Study Using Multiple Measures.

    ERIC Educational Resources Information Center

    Zarcone, Jennifer R.; Hellings, Jessica A.; Crandall, Kurt; Reese, R. Matthew; Marquis, Janet; Fleming, Kandace; Shores, Richard; Williams, Dean; Schroeder, Stephen R.

    2001-01-01

    The efficacy of the atypical antipsychotic risperidone was evaluated in the treatment of aberrant behavior (e.g., aggression, self-injury) in 20 individuals with developmental disabilities. The study, a double-blind crossover design, identified 50 percent of participants as responders. Naturalistic observations of five participants showed that…

  12. Risperidone or Aripiprazole in Children and Adolescents with Autism and/or Intellectual Disability: A Bayesian Meta-Analysis of Efficacy and Secondary Effects

    ERIC Educational Resources Information Center

    Cohen, David; Raffin, Marie; Canitano, Roberto; Bodeau, Nicolas; Bonnot, Olivier; Perisse, Didier; Consoli, Angele; Laurent, Claudine

    2013-01-01

    Second-generation antipsychotics (SGAs) induce frequent adverse effects in children and adolescents with each compound appearing to have a specific adverse effect profile. Aripiprazole and risperidone are FDA-approved medications for behavioral disturbances associated with autism and/or intellectual disabilities (ID) in children and adolescents.…

  13. A Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Adolescents and Young Adults with Anorexia Nervosa: A Pilot Study

    ERIC Educational Resources Information Center

    Hagman, Jennifer; Gralla, Jane; Sigel, Eric; Ellert, Swan; Dodge, Mindy; Gardner, Rick; O'Lonergan, Teri; Frank, Guido; Wamboldt, Marianne Z.

    2011-01-01

    Objective: The purpose of this double-blind, placebo-controlled exploratory pilot study was to evaluate the safety and efficacy of risperidone for the treatment of anorexia nervosa. Method: Forty female subjects 12 to 21 years of age (mean, 16 years) with primary anorexia nervosa in an eating disorders program were randomized to receive…

  14. The effect of clozapine and risperidone on attentional bias in patients with schizophrenia and a cannabis use disorder: An fMRI study.

    PubMed

    Machielsen, Marise Wj; Veltman, Dick J; van den Brink, Wim; de Haan, Lieuwe

    2014-07-01

    Cannabis use disorders (CUDs) are highly comorbid in patients with schizophrenia and are associated with poor outcome. Clozapine has been put forward as the first choice antipsychotic in this comorbid group. However, little is known about the mechanisms underlying the assumed superiority of clozapine. We compared the effects of clozapine and risperidone on attentional bias, subjective craving and associated regional brain activity in patients with schizophrenia and CUD. Overall, 36 patients with schizophrenia and 19 healthy controls were included. Patients were randomised to antipsychotic treatment with clozapine or risperidone. At baseline and after 4 weeks of medication use, regional brain responses were measured during a classical Stroop and a cannabis word Stroop using functional magnetic resonance imaging. Clozapine-treated CUD patients showed a larger reduction in craving and in activation of the insula during the cannabis word Stroop, while risperidone-treated patients showed a larger decrease in activation of the right anterior cingulate cortex during the classical Stroop. A significant association was found between decreases in subjective craving and decreases in insula activation during the cannabis word Stroop. These findings strongly suggest that clozapine may be a better treatment choice in patients with schizophrenia and CUD than risperidone. PMID:24646809

  15. Long-Term Risperidone Treatment Induces Visceral Adiposity Associated with Hepatic Steatosis in Mice: A Magnetic Resonance Approach

    PubMed Central

    Auger, Florent; Duriez, Patrick; Martin-Nizard, Françoise; Durieux, Nicolas; Bordet, Régis; Pétrault, Olivier

    2014-01-01

    Although atypical antipsychotic drugs (APDs) have led to significant advances in the treatment of psychotic disorders, they still induce metabolic disturbances. We aimed at characterizing the metabolic consequences of a risperidone treatment and at establishing a link with noninvasive MR markers, in order to develop a tool for predicting symptoms of the metabolic syndrome. Fat deposition and liver morphometry were assessed by T1-weighted imaging. Fatty acid composition and fat accumulations in tissues were determined using MR spectroscopy with and without water suppression, respectively. Risperidone treatment induced a weight gain accompanied with metabolic disturbances such as hyperglycemic status, an increase in visceral adipose tissue (VAT), and liver fat depositions. Correlations using Methylene-Water Ratio (MWR) and Polyunsaturated Index (PUI) demonstrated a concomitant increase in the weight gain, VAT and liver fat depositions, and a decrease in the quantity of polyunsaturated fatty acids. These results were consistent with a hepatic steatosis state. We evaluated the ability of MR techniques to detect subtle metabolic disorders induced by APDs. Thus, our model and methodology offer the possibility to investigate APDs side effects in order to improve the health conditions of schizophrenic patients. PMID:24876962

  16. Use of haloperidol and risperidone in highly aggressive Swiss Webster mice by applying the model of spontaneous aggression (MSA).

    PubMed

    Fragoso, Viviane Muniz da Silva; Hoppe, Luanda Yanaan; de Araújo-Jorge, Tânia Cremonini; de Azevedo, Marcos José; Campos, Jerônimo Diego de Souza; Cortez, Célia Martins; de Oliveira, Gabriel Melo

    2016-03-15

    Aggression is defined as the act in which an individual intentionally harms or injures another of their own species. Antipsychotics are a form of treatment used in psychiatric routine. They have been used for decades in treatment of patients with aggressive behavior. Haloperidol and risperidone promote the control of psychiatric symptoms, through their respective mechanisms of action. Experimental models are obtained by behavioral, genetic, and pharmacological manipulations, and use a reduced number of animals. In this context, we applied the model of spontaneous aggression (MSA), originating the presence of highly aggressive mice (AgR) when reassembled in adulthood. We administered haloperidol and risperidone in escalating doses, for ten consecutive days. Using positive and negative control groups, we evaluated the effectiveness of these drugs and the reversal of the aggressive behavior, performing the tail suspension test (TST) and open field test (OFT) on 10th day of treatment and 10 days after its discontinuation. The results showed that both antipsychotic drugs were effective in AgR and reversed the aggressive phenotype, reducing the number of attacks by AgR and the extent of lesions in the subordinate mice (AgD) exposed to the pattern of aggressive behavior (PAB) of the aggressors. This conclusion is based on the reduction in the animals' motor and exploratory activity, and on the reversal of patterns of aggressive behavior. The association between the MSA and experiments with other therapeutic protocols and different antipsychotics can be an important methodology in the study of aggressive behavior in psychiatric patients.

  17. Drug induced parkinsonism caused by the concurrent use of donepezil and risperidone in a patient with traumatic brain injuries.

    PubMed

    Kang, Si Hyun; Kim, Don-Kyu

    2013-02-01

    A 69-year-old male patient with previous history of traumatic brain injury 5 months ago was admitted to the Department of Neuropsychiatry because of aggressive behavior and delusional features. After starting on 2 mg of risperidone per day, his delusion, anxiety, and aggressive behavior gradually improved. Two weeks later, he was given 10 mg of donepezil per day for his mild cognitive impairment. After 6 weeks of admission in the Department of Neuropsychiatry, he showed parkinsonian features including difficulty in walking, decreased arm swing during walking, narrowed step width, scooped posture, bradykinesia, tremor, and sleep disorder. To rule out the primary Parkinsonism, dopamine transporter imaging technique [18F]fluoropropyl-carbomethoxy-iodopropyl-nor-β-tropane positron emission tomography-computed tomography (18F]FP(IT PET-CT)) was performed, and dopamine transporter activity was not decreased. We considered that his parkinsonian features were associated with the combination of risperidone and donepezil. Both drugs were stopped and symptoms rapidly disappeared in several days. PMID:23526695

  18. Risperidone dosing in children and adolescents with autistic disorder: a double-blind, placebo-controlled study.

    PubMed

    Kent, Justine M; Kushner, Stuart; Ning, Xiaoping; Karcher, Keith; Ness, Seth; Aman, Michael; Singh, Jaskaran; Hough, David

    2013-08-01

    Efficacy and safety of 2 risperidone doses were evaluated in children and adolescents with autism. Patients (N = 96; 5-17 years), received risperidone (low-dose: 0.125 mg/day [20 to <45 kg], 0.175 mg/day [>45 kg] or high-dose: 1.25 mg/day [20 to <45 kg], 1.75 mg/day [>45 kg]) or placebo. Mean baseline (range 27-29) to endpoint change in Aberrant Behavior Checklist-Irritability (primary endpoint) was significantly greater in the high-dose-(-12.4 [6.5]; p < 0.001), but not low-dose (-7.4 [8.1]; p = 0.164) group, versus placebo (-3.5 [10.7]). Clinical Global Impressions-Severity and Children's Yale-Brown Obsessive Compulsive Scale scores improved significantly only in the high-dose group, consistent with ABC-I results. Somnolence, sedation and increased appetite occurred more frequently in high-versus low-dose groups. Overall, increased appetite occurred most frequently.

  19. Efficacy, Safety, and Tolerability of RBP-7000 Once-Monthly Risperidone for the Treatment of Acute Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase 3 Study.

    PubMed

    Nasser, Azmi F; Henderson, David C; Fava, Maurizio; Fudala, Paul J; Twumasi-Ankrah, Philip; Kouassi, Alex; Heidbreder, Christian

    2016-04-01

    RBP-7000 is a sustained-release formulation of risperidone for the treatment of schizophrenia, designed to be administered by once-monthly subcutaneous injection using the ATRIGEL delivery system. This study assessed the efficacy, safety, and tolerability of RBP-7000 compared with placebo in subjects with acute exacerbation of schizophrenia. Inpatients were randomly assigned to 8 weeks of double-blind treatment with subcutaneous 90 or 120 mg of RBP-7000 or placebo. Efficacy was evaluated using a mixed-model repeated-measures analysis of the change from baseline (the last nonmissing value before the first dose of RBP-7000 or placebo on day 1) to end of the study in Positive and Negative Syndrome Scale (PANSS) total score (primary efficacy measure) and Clinical Global Impression-Severity score (secondary efficacy measure). The least-squares means from the repeated-measures analysis for the change from baseline in the PANSS total scores for placebo was -9.219 (SE, 1.2162). RBP-7000 produced statistically and clinically significant differences in mean reductions from baseline in PANSS total scores (90-mg RBP-7000 compared with placebo, -6.148 [-9.982 to -2.314], P = 0.0004; 120-mg RBP-7000 compared with placebo, -7.237 [-11.045 to -3.429], P < 0.0001) and significantly improved Clinical Global Impression-Severity scores (90-mg RBP-7000 compared with placebo, -0.350 [-0.557 to -0.143], P = 0.0002; 120-mg RBP-7000 compared with placebo, -0.396 [-0.602 to -0.190], P < 0.0001). Both RBP-7000 dosages were generally well tolerated. The most frequently reported treatment-emergent adverse events in RBP-7000 groups compared with placebo were somnolence, weight gain, and akathisia. The overall incidence of extrapyramidal syndrome-related effects was low and similar across groups. RBP-7000 may provide a new, long-acting alternative treatment for use in adults with acute schizophrenia.

  20. Expression and Characterization of a Potent Long-Acting GLP-1 Receptor Agonist, GLP-1-IgG2σ-Fc

    PubMed Central

    Yang, Yi; Chen, Fang; Wan, Deyou; Liu, Yunhui; Yang, Li; Feng, Hongru; Cui, Xinling; Gao, Xin; Song, Haifeng

    2016-01-01

    Human GLP-1 (glucagon-like peptide-1) can produce a remarkable improvement in glycemic control in patients with type 2 diabetes. However, its clinical benefits are limited by its short half-life, which is less than 2 min because of its small size and rapid enzymatic inactivation by dipeptidyl peptidase IV. We engineered GLP-1-IgG2σ-Fc, a 68-kDa fusion protein linking a variant human GLP-1 (A8G/G26E/R36G) to a human IgG2σ constant heavy-chain. A stably transfected Chinese hamster ovary cell line was obtained using electroporation. Western blotting showed that the expressed protein was immunoreactive to both GLP-1 and IgG antibodies. GLP-1-IgG2σ-Fc stimulated insulin secretion from INS-1 cells in a dose- and glucose-dependent manner and increased insulin mRNA expression. The half-life of GLP-1-IgG2σ-Fc in cynomolgus monkeys was approximately 57.1 ± 4.5 h. In the KKAy mouse model of diabetes, one intraperitoneal injection of GLP-1-IgG2σ-Fc (1 mg/kg) reduced blood glucose levels for 5 days. A 4-week repeat-administration study identified sustained effects on blood glucose levels. Oral glucose tolerance tests conducted at the beginning and end of this 4-week period showed that GLP-1-IgG2σ-Fc produced a stable glucose lowering effect. In addition, KKAy mice treated with GLP-1-IgG2σ-Fc showed statistically significant weight loss from day 23. In conclusion, these properties of GLP-1-IgG2σ-Fc demonstrated that it represented a potential long-acting GLP-1 receptor agonist for the treatment of type 2 diabetes. PMID:27232339

  1. The effects of a long-acting progestin on the hypothalamic-pituitary-ovarian axis in women with normal menstrual cycles.

    PubMed

    Poindexter, A N; Dildy, G A; Brody, S A; Snabes, M C; Brodyand, S A

    1993-07-01

    This study was performed to determine how a long-acting, slow-release preparation of norethindrone (NET) affects the hypothalamic-pituitary-ovarian axis of normal ovulatory women. Ten women were studied during the luteal phase of their menstrual cycle, and again at six and twelve weeks following intramuscular administration of 100 mg NET microencapsulated in poly-D,L-lactide-co-glycolide. Serial LH samples, serum E, P, and NET were followed by a GnRH stimulation test. Compared to luteal phase values, six and twelve weeks of treatment with NET inhibited serum E2 and P while mean serum LH remained unchanged and mean serum FSH increased significantly (p < 0.05). LH pulse frequency after NET treatment was twice the rate (p < 0.01) as that of the luteal phase, whereas LH pulse amplitude was decreased significantly (p < 0.05). Finally, although there was no significant change in pituitary LH secretion in response to GnRH, NET treatment augmented FSH responsiveness to GnRH at the times studied. Preserved pituitary responsiveness to GnRH in NET-treated patients suggests that inhibited ovarian function results in an increase in GnRH pulse frequency but not GnRH pulse amplitude. Since the progestational milieu is maintained in these patients by NET treatment, the decrease in serum E2 may be responsible for the increase in GnRH pulse frequency. The presence of a critical level of E2 may be necessary for progestins to affect the hypothalamic GnRH pulse generator.

  2. Comparative efficacy of inhaled corticosteroid and long-acting beta agonist combinations in preventing COPD exacerbations: a Bayesian network meta-analysis

    PubMed Central

    Oba, Yuji; Lone, Nazir A

    2014-01-01

    Background A combination therapy with inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) is recommended in severe chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations. Currently, there are five ICS/LABA combination products available on the market. The purpose of this study was to systematically review the efficacy of various ICS/LABA combinations with a network meta-analysis. Methods Several databases and manufacturer’s websites were searched for relevant clinical trials. Randomized control trials, at least 12 weeks duration, comparing an ICS/LABA combination with active control or placebo were included. Moderate and severe exacerbations were chosen as the outcome assessment criteria. The primary analyses were conducted with a Bayesian Markov chain Monte Carlo method. Results Most of the ICS/LABA combinations reduced moderate-to-severe exacerbations as compared with placebo and LABA, but none of them reduced severe exacerbations. However, many studies excluded patients receiving long-term oxygen therapy. Moderate-dose ICS was as effective as high-dose ICS in reducing exacerbations when combined with LABA. Conclusion ICS/LABA combinations had a class effect with regard to the prevention of COPD exacerbations. Moderate-dose ICS/LABA combination therapy would be sufficient for COPD patients when indicated. The efficacy of ICS/LABA combination therapy appeared modest and had no impact in reducing severe exacerbations. Further studies are needed to evaluate the efficacy of ICS/LABA combination therapy in severely affected COPD patients requiring long-term oxygen therapy. PMID:24872685

  3. Impact of extrafine formulations of inhaled corticosteroids/long-acting beta-2 agonist combinations on patient-related outcomes in asthma and COPD

    PubMed Central

    Scichilone, Nicola; Benfante, Alida; Morandi, Luca; Bellini, Federico; Papi, Alberto

    2014-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are among the most common chronic diseases worldwide, characterized by a condition of variable degree of airway obstruction and chronic airway inflammation. A large body of evidence has demonstrated the importance of small airways as a pharmacological target in these clinical conditions. Despite a deeper understanding of the pathophysiological mechanisms, the epidemiological observations show that a significant proportion of asthmatic and COPD patients have a suboptimal (or lack of) control of their diseases. Different factors could influence the effectiveness of inhaled treatment in chronic respiratory diseases: patient-related (eg, aging); disease-related (eg, comorbid conditions); and drug-related/formulation-related factors. The presence of multiple illnesses is common in the elderly patient as a result of two processes: the association between age and incidence of degenerative diseases; and the development over time of complications of the existing diseases. In addition, specific comorbidities may contribute to impair the ability to use inhalers, such as devices for efficient drug delivery in the respiratory system. The inability to reach and treat the peripheral airways may contribute to the lack of efficacy of inhaled treatments. The recent development of inhaled extrafine formulations allows a more uniform distribution of the inhaled treatment throughout the respiratory tree to include the peripheral airways. The beclomethasone/formoterol extrafine formulation is available for the treatment of asthma and COPD. Different biomarkers of peripheral airways are improved by beclomethasone/formoterol extrafine treatment in comparison with equivalent nonextrafine inhaled corticosteroids/long-acting beta-2 agonist (ICS/LABA) combinations. These improvements are associated with improved lung function and clinical outcomes, along with reduced systemic exposure to inhaled corticosteroids. The increased knowledge

  4. Radioimmunoassay for 6-D-tryptophan analog of luteinizing hormone-releasing hormone: measurement of serum levels after administration of long-acting microcapsule formulations

    SciTech Connect

    Mason-Garcia, M.; Vigh, S.; Comaru-Schally, A.M.; Redding, T.W.; Somogyvari-Vigh, A.; Horvath, J.; Schally, A.V.

    1985-03-01

    A sensitive and specific radioimmunoassay for (6-D-tryptophan)luteinizing hormone-releasing hormone ((D-Trp/sup 6/)LH-RH) was developed and used for following the rate of liberation of (D-Trp/sup 6/)LH-RH from a long-acting delivery systems based on a microcapsule formulation. Rabbit antibodies were generated against (D-Trp/sup 6/)LH-RH conjugated to bovine serum albumin with glutaraldehyde. Crossreactivity with LH-RH was less than 1%; there was no significant cross-reactivity with other peptides. The minimal detectable dose of (D-Trp/sup 6/)LH-RH was 2 pg per tube. In tra- and interassay coefficients of variation were 8% and 10%, respectively. The radioimmunoassay was suitable for direct determination of (D-Trp/sup 6/)LH-RH in serum, permitting the study of blood levels of the analog after single injections into normal men and after one-a-month administration of microcapsules to rats. In men, 90 min after subcutaneous injection of 250 ..mu..g of the peptide, serum (D-Trp/sup 6/)LH-RH rose to 6-12 ng/ml. Luteinizing hormone was increased 90 min and 24 hr after the administration of the analog. Several batches of microcapsules were tested in rats and the rate of release of (D-Trp/sup 6/)LH-RH was followed. The improved batch of microcapsules of (D-Trp/sup 6/)LH-RH increased serum concentrations of the analog for 30 days or longer after intramuscular injection.

  5. Induction of regulator of G-protein signaling 2 expression by long-acting β2-adrenoceptor agonists and glucocorticoids in human airway epithelial cells.

    PubMed

    Holden, Neil S; George, Tresa; Rider, Christopher F; Chandrasekhar, Ambika; Shah, Suharsh; Kaur, Manminder; Johnson, Malcolm; Siderovski, David P; Leigh, Richard; Giembycz, Mark A; Newton, Robert

    2014-01-01

    In asthma and chronic obstructive pulmonary disease (COPD) multiple mediators act on Gαq-linked G-protein-coupled receptors (GPCRs) to cause bronchoconstriction. However, acting on the airway epithelium, such mediators may also elicit inflammatory responses. In human bronchial epithelial BEAS-2B cells (bronchial epithelium + adenovirus 12-SV40 hybrid), regulator of G-protein signaling (RGS) 2 mRNA and protein were synergistically induced in response to combinations of long-acting β2-adrenoceptor agonist (LABA) (salmeterol, formoterol) plus glucocorticoid (dexamethasone, fluticasone propionate, budesonide). Equivalent responses occurred in primary human bronchial epithelial cells. Concentrations of glucocorticoid plus LABA required to induce RGS2 expression in BEAS-2B cells were consistent with the levels achieved therapeutically in the lungs. As RGS2 is a GTPase-activating protein that switches off Gαq, intracellular free calcium ([Ca(2+)]i) flux was used as a surrogate of responses induced by histamine, methacholine, and the thromboxane receptor agonist U46619 [(Z)-7-[(1S,4R,5R,6S)-5-[(E,3S)-3-hydroxyoct-1-enyl]-3-oxabicyclo[2.2.1]heptan-6-yl]hept-5-enoic acid]. This was significantly attenuated by salmeterol plus dexamethasone pretreatment, or RGS2 overexpression, and the protective effect of salmeterol plus dexamethasone was abolished by RGS2 RNA silencing. Although methacholine and U46619 induced interleukin-8 (IL-8) release and this was inhibited by RGS2 overexpression, the repression of U46619-induced IL-8 release by salmeterol plus dexamethasone was unaffected by RGS2 knockdown. Given a role for Gαq-mediated pathways in inducing IL-8 release, we propose that RGS2 acts redundantly with other effector processes to repress IL-8 expression. Thus, RGS2 expression is a novel effector mechanism in the airway epithelium that is induced by glucocorticoid/LABA combinations. This could contribute to the efficacy of glucocorticoid/LABA combinations in asthma and

  6. Diphtheria Toxin- and GFP-Based Mouse Models of Acquired Hypoparathyroidism and Treatment With a Long-Acting Parathyroid Hormone Analog.

    PubMed

    Bi, Ruiye; Fan, Yi; Lauter, Kelly; Hu, Jing; Watanabe, Tomoyuki; Cradock, Jim; Yuan, Quan; Gardella, Thomas; Mannstadt, Michael

    2016-05-01

    Hypoparathyroidism (HP) arises most commonly from parathyroid (PT) gland damage associated with neck surgery, and is typically treated with oral calcium and active vitamin D. Such treatment effectively increases levels of serum calcium (sCa), but also brings risk of hypercalciuria and renal damage. There is thus considerable interest in using PTH or PTH analogs to treat HP. To facilitate study of this disease and the assessment of new treatment options, we developed two mouse models of acquired HP, and used them to assess efficacy of PTH(1-34) as well as a long-acting PTH analog (LA-PTH) in regulating blood calcium levels. In one model, we used PTHcre-iDTR mice in which the diphtheria toxin (DT) receptor (DTR) is selectively expressed in PT glands, such that systemic DT administration selectively ablates parathyroid cells. For the second model, we generated GFP-PT mice in which green fluorescent protein (GFP) is selectively expressed in PT cells, such that parathyroidectomy (PTX) is facilitated by green fluorescence of the PT glands. In the PTHcre-iDTR mice, DT injection (2 × 5 μg/kg, i.p.) resulted in moderate yet consistent reductions in serum PTH and sCa levels. The more severe hypoparathyroid phenotype was observed in GFP-PT mice following GFP-guided PTX surgery. In each model, a single subcutaneous injection of LA-PTH increased sCa levels more effectively and for a longer duration (>24 hours) than did a 10-fold higher dose of PTH(1-34), without causing excessive urinary calcium excretion. These new mouse models thus faithfully replicate two degrees of acquired HP, moderate and severe, and may be useful for assessing potential new modes of therapy. © 2015 American Society for Bone and Mineral Research. PMID:26678919

  7. The Use of Long Acting Reversible Contraceptives and the Relationship between Discontinuation Rates due to Menopause and to Female and Male Sterilizations.

    PubMed

    Ferreira, Jessica Mayra; Monteiro, Ilza; Castro, Sara; Villarroel, Marina; Silveira, Carolina; Bahamondes, Luis

    2016-05-01

    Introduction Women require effective contraception until they reach menopause. The long acting reversible contraceptives (LARC) and the depot-medroxyprogesterone acetate (DMPA, Depo-Provera®, Pfizer, Puurs, Belgium) are great options and can replace possible sterilizations. Purpose To assess the relationship between the use of LARCs and DMPA and terminations ascribed to menopause and sterilizations in a Brazilian clinic. Methods We reviewed the records of women between 12 and 50 years of age attending the clinic that chose to use a LARC method or DMPA. Cumulative termination rates due to sterilization or because the woman had reached menopause were computed using single decrement life-table analysis over 32 years. We also examined all records of surgical sterilization at our hospital between the years 1980-2012. Results Three hundred thirty-two women had continuously used the same contraceptive until menopause, and 555 women had discontinued the method because they or their partners underwent sterilization. From year 20 to year 30 of use, levonorgestrel intrauterine-releasing system (LNG-IUS - Mirena®, Bayer Oy, Turku, Finland; available since 1980), copper intrauterine device (IUD - available since 1980) and DMPA users showed a trend of cumulative higher discontinuation rates due to menopause when compared with the discontinuation rates due to sterilization. Over the study period, a steep decline in the use of sterilization occurred. Conclusion Over the past 15 years of research we have observed a trend: women usually preferred to continue using LARC methods or DMPA until menopause rather than decide for sterilization, be it their own, or their partners'. The annual number of sterilizations dropped in the same period. The use of LARC methods and DMPA until menopause is an important option to avoid sterilization, which requires a surgical procedure with potential complications. PMID:27187927

  8. The Comparative Effectiveness of Long-Acting Injectable vs. Oral Antipsychotic Medications in the Prevention of Relapse: A Case Study in CER in Psychiatry

    PubMed Central

    Kane, John M.; Kishimoto, Taishiro; Correll, Christoph U.

    2013-01-01

    Objective As psychopathology and social functioning can worsen with repeated psychotic episodes in schizophrenia, relapse prevention is critical. Because high non-adherence rates limit the efficacy of pharmacotherapy, the use of long-acting injectable antipsychotics (LAIs) is considered an important treatment option. To date, many studies comparing LAIs and oral antipsychotics have been conducted; however, the results are mixed, and careful interpretation of the data is required. Study Design Selective review of existing literature regarding LAIs. We especially focused the discussion on the impact of the design of studies with different approaches comparing LAIs and oral antipsychotics in preventing relapse. Result The results were diverse and were influenced by the design utilized, i.e., randomized controlled trials (RCTs) showed LAIs and oral antipsychotics to have similar effects, whereas mirror-image and some large cohort studies showed LAIs to be superior to oral antipsychotics. Conclusion Divergent results from studies using different methodologies creates a dilemma for comparative effectiveness research, and LAI studies may serve as an example of a situation where a conventional RCT is not the gold standard. Traditional RCTs generally increase adherence compared to clinical practice and, therefore, might not be well suited to detect differences between LAIs and oral medications, because any increase in adherence effects patients on oral medications more than those on LAIs and thus leads to an underestimation of any potential difference in effectiveness. A possible solution would be the implementation of a true effectiveness trial,. in which post-randomization involvement would be kept to a minimum to better reflect routine practice. PMID:23849151

  9. Long-Acting PASylated Leptin Ameliorates Obesity by Promoting Satiety and Preventing Hypometabolism in Leptin-Deficient Lep(ob/ob) Mice.

    PubMed

    Bolze, Florian; Morath, Volker; Bast, Andrea; Rink, Nadine; Schlapschy, Martin; Mocek, Sabine; Skerra, Arne; Klingenspor, Martin

    2016-01-01

    Body weight loss of Lep(ob/ob) mice in response to leptin is larger than expected from the reduction in energy intake alone, suggesting a thermogenic action of unknown magnitude. We exploited the superior pharmacological properties of a novel long-acting leptin prepared via PASylation to study the contribution of its anorexigenic and thermogenic effects. PASylation, the genetic fusion of leptin with a conformationally disordered polypeptide comprising 600 Pro/Ala/Ser (PAS) residues, provides a superior way to increase the hydrodynamic volume of the fusion protein, thus retarding kidney filtration and extending plasma half-life. Here a single PAS(600)-leptin injection (300 pmol/g) resulted in a maximal weight reduction of 21% 6 days after application. The negative energy balance of 300 kJ/(4 d) was driven by a decrease in energy intake, whereas energy expenditure remained stable. Mice that were food restricted to the same extent showed an energy deficit of only 220 kJ/(4 d) owing to recurring torpor bouts. Therefore, the anorexigenic effect of PAS(600)-leptin contributes 75% to weight loss, whereas the thermogenic action accounts for 25% by preventing hypometabolism. In a second experiment, just four injections of PAS(600)-leptin (100 pmol/g) administered in 5- to 6-day intervals rectified the Lep(ob/ob) phenotype. In total, 16 nmol of PAS(600)-leptin per mouse triggered a weight loss of 43% within 20 days and normalized hypothermia and glucose homeostasis as well as hepatic steatosis. The beneficial properties of PAS(600)-leptin are substantiated by a comparison with previous studies in which approximately 400 nmol (∼25-fold) unmodified leptin was mandatory to achieve similar improvements.

  10. Long-Acting PASylated Leptin Ameliorates Obesity by Promoting Satiety and Preventing Hypometabolism in Leptin-Deficient Lep(ob/ob) Mice.

    PubMed

    Bolze, Florian; Morath, Volker; Bast, Andrea; Rink, Nadine; Schlapschy, Martin; Mocek, Sabine; Skerra, Arne; Klingenspor, Martin

    2016-01-01

    Body weight loss of Lep(ob/ob) mice in response to leptin is larger than expected from the reduction in energy intake alone, suggesting a thermogenic action of unknown magnitude. We exploited the superior pharmacological properties of a novel long-acting leptin prepared via PASylation to study the contribution of its anorexigenic and thermogenic effects. PASylation, the genetic fusion of leptin with a conformationally disordered polypeptide comprising 600 Pro/Ala/Ser (PAS) residues, provides a superior way to increase the hydrodynamic volume of the fusion protein, thus retarding kidney filtration and extending plasma half-life. Here a single PAS(600)-leptin injection (300 pmol/g) resulted in a maximal weight reduction of 21% 6 days after application. The negative energy balance of 300 kJ/(4 d) was driven by a decrease in energy intake, whereas energy expenditure remained stable. Mice that were food restricted to the same extent showed an energy deficit of only 220 kJ/(4 d) owing to recurring torpor bouts. Therefore, the anorexigenic effect of PAS(600)-leptin contributes 75% to weight loss, whereas the thermogenic action accounts for 25% by preventing hypometabolism. In a second experiment, just four injections of PAS(600)-leptin (100 pmol/g) administered in 5- to 6-day intervals rectified the Lep(ob/ob) phenotype. In total, 16 nmol of PAS(600)-leptin per mouse triggered a weight loss of 43% within 20 days and normalized hypothermia and glucose homeostasis as well as hepatic steatosis. The beneficial properties of PAS(600)-leptin are substantiated by a comparison with previous studies in which approximately 400 nmol (∼25-fold) unmodified leptin was mandatory to achieve similar improvements. PMID:26492472

  11. Efficacy of moxidectin long-acting injectable formulation (1 mg/kg bodyweight) against first instar larvae of Oestrus ovis in naturally infected sheep.

    PubMed

    Martínez-Valladares, M; Valcárcel, F; Álvarez-Sánchez, M A; Cordero-Pérez, C; Fernández-Pato, N; Frontera, E; Meana, A; Rojo-Vázquez, F A

    2013-03-31

    The objective of the current study was to evaluate the efficacy of a single treatment with a long-acting injectable formulation of moxidectin (MOX) at 1.0 mg/kg bodyweight (b.w.) against natural infection by nasal bots (Oestrus ovis) in sheep with special attention to first instar larvae (L1). Firstly, a local farm with clinical history of oestrosis was chosen to conduct the assay. A total of 49 sheep were pre-selected at the end of the summer according to the presence of evident clinical signs of infection and confirmed later by means of an indirect ELISA against excretory-secretory products from L1 to detect IgG antibodies. After that, 24 sheep were chosen to carry out the study on the basis of positive serology and age since the oldest ones were selected. The day 0 of the assay, the treatment group was administered with the MOX formulation by subcutaneous injection at the base of the left ear and the control group was administered with a saline solution in the same way. All sheep were slaughtered on day 28 post-treatment (pt). At the necropsy, the head of all sheep were cut off and split into two sagital sections and all larvae from nasal passages, septum, middle meatus, conchae and sinuses were recovered. After the necropsy, a significant number of L1 was only found in the control group and therefore the efficacy of the MOX formulation was only calculated against this stage. As a result, the formulation was 90.2% effective against L1 for sheep slaughtered at day 28 pt. PMID:23333136

  12. The long-acting β2-adrenoceptor agonist, indacaterol, enhances glucocorticoid receptor-mediated transcription in human airway epithelial cells in a gene- and agonist-dependent manner

    PubMed Central

    Joshi, T; Johnson, M; Newton, R; Giembycz, M A

    2015-01-01

    Background and Purpose Inhaled glucocorticoid (ICS)/long-acting β2-adrenoceptor agonist (LABA) combination therapy is a recommended treatment option for patients with moderate/severe asthma in whom adequate control cannot be achieved by an ICS alone. Previously, we discovered that LABAs can augment dexamethasone-inducible gene expression and proposed that this effect may explain how these two drugs interact to deliver superior clinical benefit. Herein, we extended that observation by analysing, pharmacodynamically, the effect of the LABA, indacaterol, on glucocorticoid receptor (GR)-mediated gene transcription induced by seven ligands with intrinsic activity values that span the spectrum of full agonism to antagonism. Experimental Approach BEAS-2B human airway epithelial cells stably transfected with a 2× glucocorticoid response element luciferase reporter were used to model gene transcription together with an analysis of several glucocorticoid-inducible genes. Key Results Indacaterol augmented glucocorticoid-induced reporter activation in a manner that was positively related to the intrinsic activity of the GR agonist. This effect was demonstrated by an increase in response maxima without a change in GR agonist affinity or efficacy. Indacaterol also enhanced glucocorticoid-inducible gene expression. However, the magnitude of this effect was dependent on both the GR agonist and the gene of interest. Conclusions and Implications These data suggest that indacaterol activates a molecular rheostat, which increases the transcriptional competency of GR in an agonist- and gene-dependent manner without apparently changing the relationship between fractional GR occupancy and response. These findings provide a platform to rationally design ICS/LABA combination therapy that is based on the generation of agonist-dependent gene expression profiles in target and off-target tissues. PMID:25598440

  13. Effectiveness and safety of a long-acting, once-daily, two-phase release formulation of methylphenidate (Ritalin ® LA) in school children under daily practice conditions.

    PubMed

    Haertling, Fabian; Mueller, Beate; Bilke-Hentsch, Oliver

    2015-06-01

    Long-acting (LA) preparations of methylphenidate allow for once-daily dosing; however, pharmacokinetics may vary and depend on food intake. The objective was to evaluate effectiveness of a two-phase release formulation (Ritalin(®) LA) under daily practice conditions. This was a prospective, multicenter, observational study in Germany. Eligibility and dosing were determined by the physician based on the drug label. Outcomes included changes over 3 months of treatment in assessments of effect duration, clinical global impression (CGI), and quality of life (ILK). In 101 sites, 262 patients (197 boys, 63 girls, and two unknown) with a mean age of 10.9 years were enrolled; 50 were treated for the first time; 212 switched medication to Ritalin(®) LA. After 3 months, CGI improved in 59.4 % of patients, and well-being overall was rated as good by 61.0 % of parents and 63.7 % of children. Based on parents' assessment, the proportion of children suffering from strong disease burden decreased from 40.7 to 15.1 %. In 123 insufficient responders to previous ADHD medications, benefit from Ritalin(®) LA was above average and effect duration was significantly prolonged as compared to pretreatment. Overall, 28 patients (10.7 %) had treatment-related adverse events with one case being serious; 23 patients (8.8 %) discontinued therapy, 7 (2.7 %) due to poor treatment response; and 212 patients (81 %) continued treatment beyond the study. In line with clinical trial data, Ritalin(®) LA provides significant benefit also under routine practice conditions.

  14. Effect of long-acting gonadotropin-releasing hormone analog (leuprolide) therapy on prostatic size and symptoms in 15 men with benign prostatic hypertrophy.

    PubMed

    Gabrilove, J L; Levine, A C; Kirschenbaum, A; Droller, M

    1989-09-01

    To determine the effects of reversible medical castration on prostatic size and symptoms we treated 15 patients with benign prostatic hypertrophy with a long-acting GnRH analog, leuprolide (1 mg/day sc), for a minimum of 4 months. The men's serum testosterone, dihydrotestosterone, and estradiol concentrations fell to very low levels within 4-6 weeks after the initiation of treatment. Transrectal ultrasonography of the prostate demonstrated an average shrinkage of 40% after 4 months of treatment (n = 15) and 46% after 6 months of treatment (n = 11). All 15 men had improvement in urinary flow and, to a lesser extent, in nocturia and frequency. The side-effects of the therapy were decreased potency and flushing. The most dramatic improvement occurred in 4 of the 5 men who had complete urinary obstruction before treatment. One man had a suprapubic cystotomy tube removed during the fifth treatment month. Two other men who had Foley catheters before treatment are voiding well without catheters since their third treatment month. Another man who had a very large prostate (300 g) before treatment had one successful voiding trial, although he still has a suprapubic cystotomy tube. One man decided to stop treatment after 6 months. Two months later his hormone values and prostate size had returned to pretreatment levels. One man treated during the fourth and fifth months with fluoxymesterone in addition to leuprolide had regrowth of his prostate while receiving this androgen. We conclude that leuprolide treatment of men with benign prostatic hypertrophy results in shrinkage of prostatic size and concomitant improvement in the obstructive symptoms of prostatism. The prostatic shrinkage reverses when treatment is discontinued or combined with androgen. PMID:2474565

  15. Dose-related effects of clozapine and risperidone on the pattern of brain regional serotonin and dopamine metabolism and on tests related to extrapyramidal functions in rats.

    PubMed

    Batool, Farhat; Hasnat, Ambreen; Haleem, Muhammad Abdul; Haleem, Darakhshan Jabeen

    2010-06-01

    The present study was designed to evaluate the behavioral and neurochemical profiles of clozapine and risperidone in rats in a dose-dependent manner. Animals injected intraperitoneally (i.p.) with clozapine (2.5, 5.0 and 10.0 mg kg-1) or risperidone (1.0, 2.5 and 5.0 mg kg-1) were sacrificed 1 h later to collect brain samples. Hypolocomotive effects (home cage activity and catalepsy) were successively monitored in each animal after the drug or saline administration. Both drugs significantly (p < 0.01) decreased locomotor activity at high doses and in a dose-dependent manner. Maximum (100%) cataleptic potential was achieved at a high dose (5.0 mg kg-1) of risperidone. Neurochemical estimations were carried out by HPLC with electrochemical detection. Both drugs, at all doses, significantly (p < 0.01) increased the concentration of homovanillic acid (HVA), a metabolite of dopamine (DA), in the striatum. Dihydroxyphenylacetic acid (DOPAC) levels increased in the striatum and decreased in the rest of the brain, particularly in clozapine-injected rats. 5-Hydroxyindoleacetic acid (5-HIAA), the predominant metabolite of serotonin, significantly (p < 0.01) decreased in the striatum. 5-Hydroxytryptamine (5-HT) was significantly (p < 0.01) increased by risperidone and decreased by clozapine in the rest of the brain. Striatal tryptophan (TRP) was significantly (p < 0.01) decreased by risperidone and increased in the rest of the brain. The striatal HVA/DA ratio increased and the 5-HT turnover rate remained unchanged in the rest of the brain. Results suggest that the affinity of the two drugs towards D2/5-HT1A receptors interaction is involved in lower incidence of extrapyramidal side effects. Role of 5-HT1A receptors in the treatment of schizophrenia is discussed. PMID:21134850

  16. Spectroscopic and thermal investigations on the charge transfer interaction between risperidone as a schizophrenia drug with some traditional π-acceptors: Part 2

    NASA Astrophysics Data System (ADS)

    El-Habeeb, Abeer A.; Al-Saif, Foziah A.; Refat, Moamen S.

    2013-03-01

    The focus of present investigation was to assess the utility of non-expensive techniques in the evaluation of risperidone (Ris) in solid and solution states with different traditional π-acceptors and subsequent incorporation of the analytical determination into pharmaceutical formulation for a faster release of risperidone. Charge-transfer complexes (CTC) of risperidone with picric acid (PA), 2,3-dichloro-5,6-dicyano-p-benzoquinon (DDQ), tetracyanoquinodimethane (TCNQ), tetracyano ethylene (TCNE), tetrabromo-p-quinon (BL) and tetrachloro-p-quinon (CL) have been studied spectrophotometrically in absolute methanol at room temperature. The stoichiometries of the complexes were found to be 1:1 ratio by the photometric molar ratio between risperidone and the π-acceptors. The equilibrium constants, molar extinction coefficient (ɛCT) and spectroscopic-physical parameters (standard free energy (ΔGo), oscillator strength (f), transition dipole moment (μ), resonance energy (RN) and ionization potential (ID)) of the complexes were determined upon the modified Benesi-Hildebrand equation. Risperidone in pure form was applied in this study. The results indicate that the formation constants for the complexes depend on the nature of electron acceptors and donor, and also the spectral studies of the complexes were determined by (infrared, Raman, and 1H NMR) spectra and X-ray powder diffraction (XRD). The most stable mono-protonated form of Ris is characterized by the formation of +Nsbnd H (pyrimidine ring) intramolecular hydrogen bonded. In the high-wavenumber spectral region ˜3400 cm-1, the bands of the +Nsbnd H stretching vibrations and of the pyrimidine nitrogen atom could be potentially useful to discriminate the investigated forms of Ris. The infrared spectra of both Ris complexes are confirming the participation of +Nsbnd H pyrimidine ring in the donor-acceptor interaction.

  17. Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia

    PubMed Central

    Honey, Garry D.; Bullmore, Edward T.; Soni, William; Varatheesan, Malini; Williams, Steve C. R.; Sharma, Tonmoy

    1999-01-01

    Antipsychotic drug treatment of schizophrenia may be complicated by side effects of widespread dopaminergic antagonism, including exacerbation of negative and cognitive symptoms due to frontal cortical hypodopaminergia. Atypical antipsychotics have been shown to enhance frontal dopaminergic activity in animal models. We predicted that substitution of risperidone for typical antipsychotic drugs in the treatment of schizophrenia would be associated with enhanced functional activation of frontal cortex. We measured cerebral blood oxygenation changes during periodic performance of a verbal working memory task, using functional MRI, on two occasions (baseline and 6 weeks later) in two cohorts of schizophrenic patients. One cohort (n = 10) was treated with typical antipsychotic drugs throughout the study. Risperidone was substituted for typical antipsychotics after baseline assessment in the second cohort (n = 10). A matched group of healthy volunteers (n = 10) was also studied on a single occasion. A network comprising bilateral dorsolateral prefrontal and lateral premotor cortex, the supplementary motor area, and posterior parietal cortex was activated by working memory task performance in both the patients and comparison subjects. A two-way analysis of covariance was used to estimate the effect of substituting risperidone for typical antipsychotics on power of functional response in the patient group. Substitution of risperidone increased functional activation in right prefrontal cortex, supplementary motor area, and posterior parietal cortex at both voxel and regional levels of analysis. This study provides direct evidence for significantly enhanced frontal function in schizophrenic patients after substitution of risperidone for typical antipsychotic drugs, and it indicates the potential value of functional MRI as a tool for longitudinal assessment of psychopharmacological effects on cerebral physiology. PMID:10557338

  18. Factors affecting women’s intention to use long acting and permanent contraceptive methods in Wolaita Zone, Southern Ethiopia: A cross-sectional study

    PubMed Central

    2014-01-01

    Background The use of long acting and permanent contraceptive methods (LAPMs) has not kept step with that of short-acting methods such as oral pills and injectable in Africa. This study explores the association between women’s awareness, attitude and barriers with their intention to use LAPMs among users of short term methods, in Southern Ethiopia. Methods A cross-sectional study design of mixed methods was conducted in the public health facilities of Wolaita zone, Southern Ethiopia, in January 2013. Women who were using short term contraceptive methods were the study population (n = 416). Moreover, 12 in-depth interviews were conducted among family planning providers and women who have been using short term methods. Data were entered into EPI Info version 3.5.3 and exported to SPSS version 16.0 for analysis. The odds ratios in the binary logistic regression model along with 95% confidence interval were used. Results One hundred fifty six (38%) of women had the intention to use LAPMs while nearly half of them (n = 216) had a negative attitude to use such methods. Moreover, two-third of study participants (n = 276) held myths and misconceptions about such methods. The women who had a positive attitude were found to be 2.5 times more intention to use LAPMs compared to women who had a negative attitude (AOR =2. 47; 95% CI: 1.48- 4.11). Women who had no myths and misconceptions on LAPMs were found to be 1.7 times more intention to use LAPMs compared to women who had myths and misconceptions (AOR = 1.71; 95% CI: 1.08- 2.72). Likewise, women who attained secondary and higher level of education were found to be 2 and 2.8 times more intention to use LAPMs compared to women with no education, respectively (AOR = 2. 10; 95% CI: 1.11- 3.98) and AOR = 2. 80; 95% CI: 1.15- 6.77). Conclusions Intention to use LAPMs was low and nearly half of women had a negative attitude to use such methods. Positive attitude, absence of myths and misconceptions on

  19. Comparison of olanzapine long-acting injection and oral olanzapine: a 2-year, randomized, open-label study in outpatients with schizophrenia.

    PubMed

    Detke, Holland C; Weiden, Peter J; Llorca, Pierre-Michel; Choukour, Moutaz; Watson, Susan B; Brunner, Elizabeth; Ascher-Svanum, Haya

    2014-08-01

    We compared long-term treatment effectiveness of monthly olanzapine long-acting injection (LAI) with that of oral olanzapine. Outpatients with 2 or more episodes of psychotic worsening in the past 24 months with Positive and Negative Syndrome Scale total score of lower than 70 were randomized to 405 mg/4 weeks of olanzapine LAI (n = 264) or 10 mg/d of oral olanzapine (n = 260) for 2 years of open-label treatment. Dosing thereafter was flexible (150-405 mg/4 weeks of LAI vs 5-20 mg/d of oral). Primary outcome was time to all-cause discontinuation. At baseline, patients were clinically stable (mean Positive and Negative Syndrome Scale total score of 57). Seventeen percent of patients had been psychiatrically hospitalized in the previous 6 months, and 4.6% were rated nonadherent in the month before study entry. The groups did not differ significantly in median time to all-cause discontinuation (645 days for LAI, 678 days for oral; P = 0.61), discontinuation rate (53.8% for LAI, 51.2% for oral; P = 0.60), or relapse rate (20.1% for LAI, 18.5% for oral; P = 0.66). Postbaseline psychiatric hospitalization rate was low for both groups (7.6% for LAI, 9.2% for oral), but mean hospitalization duration was significantly longer for oral patients (1.80 days [20 for those hospitalized] vs 0.43 days [6 for those hospitalized], P = 0.02). There were no clinically significant group differences in adverse events or safety measures. No post-injection delirium/sedation syndrome events occurred. In conclusion, olanzapine LAI and oral olanzapine were similarly effective and well tolerated for up to 2 years of treatment in patients with schizophrenia. Treatment discontinuation for olanzapine LAI was similar to that of oral olanzapine, despite the 3-hour post-injection observation period and other precautionary procedures related to risk of post-injection delirium/sedation syndrome. PMID:24781441

  20. Hospitalization resource utilization and costs among Medicaid insured patients with schizophrenia with different treatment durations of long-acting injectable antipsychotic therapy.

    PubMed

    Bera, Rimal; Offord, Steve; Zubek, Donna; Lau, Gina; Lin, Jay; Karson, Craig

    2014-02-01

    This study evaluated the impact of using long-acting injectable (LAI) antipsychotics for a longer treatment duration versus a short duration on health care resource utilization among Medicaid-insured schizophrenia patients. Schizophrenia patients 13 years or older initiating LAI antipsychotics were identified from the Truven Health Analytics MarketScan Research Medicaid database between July 1, 2005, and June 30, 2010. The study population was grouped into 2 study cohorts (longer-usage-duration cohort: ≥ 180 days of supply and short-usage-duration cohort: <180 days of supply). Hospitalization-related resource utilization and costs were determined during a variable follow-up period and compared at the unadjusted and adjusted levels. Of the 5694 patients identified, 2838 patients were treated with LAI antipsychotics for a mean duration of 604 (SD, 432) days (mean age, 38.91 years), and 2856 were treated for 86 (SD, 43) days (mean age, 39.96 days). Total hospital lengths of stay, all cause (6.56 [SD, 18.63] vs 4.93 [SD, 13.40] days, P < 0.001) and schizophrenia related (5.18 [SD, 14.96] vs 4.16 [SD, 11.94] days, P = 0.005), and the mean number of hospitalizations, all cause (0.79 [SD, 1.78] vs 0.61 [SD, 1.41], P < 0.001) and schizophrenia related (0.63 [SD, 1.55] vs 0.51 [SD, 1.26], P = 0.001), were lower for the longer-usage-duration cohort. Cox regression results showed that using LAI antipsychotics for a longer duration was correlated with longer time to the first hospitalization for any cause and for schizophrenia. After multivariate regression, longer usage duration of LAI antipsychotics was associated with a decreased number of hospitalizations (-0.15 per year, P < 0.001), a decreased hospital length of stay (-1.50 days, P < 0.001), and reduced hospital payment (-26%, P < 0.001). Patients who are treated with LAI antipsychotics for a longer versus shorter duration use hospital resources less. PMID:24135840

  1. Strategic applications of long-acting acaricides against Rhipicephalus (Boophilus) microplus in northwestern Argentina, with an analysis of tick distribution among cattle.

    PubMed

    Nava, Santiago; Mangold, Atilio J; Canevari, José T; Guglielmone, Alberto A

    2015-03-15

    Strategic applications of long-acting acaricides for the control of Rhipicephalus (Boophilus) microplus in northwestern Argentina were evaluated for one year. In addition, tick distribution among cattle was analyzed to evaluate if partial selective treatment or culling the small proportion of most heavily infested animals were feasible options to control R. (B.) microplus. Two different treatments schemes based on two applications of fluazuron and one application of 3.15% ivermectin were performed. Treatments were made in late winter and spring so as to act on the small 1st spring generation of R. (B.) microplus, in order to preclude the rise of the larger autumn generation. The overall treatment effect was positively significant in both schemes. The number of ticks observed in the control group was significantly higher than in the treated groups on all post-treatment counts. Group 2 exhibited more than 80% of efficacy almost throughout the study period, whereas Group 1 exhibited an efficacy percentage higher than 80% in September, October, December, February, April and May, but not in November (73.4%), January (58.3%), March (45.2%) or June (53.4%). Absolute control was observed in Group 2 in the counts of September and October, and in Group 1 in the count of February. The control strategies evaluated in this work provide an acceptable control level with only three applications of acaricides; at the same time, they prevent the occurrence of the autumn peak of tick burdens, which is characteristic of R. (B.) microplus in northwestern Argentina. Tick distribution was markedly aggregated in all counts. Although ticks were not distributed evenly among calves, the individual composition of the most heavily infested group was not consistent throughout the study period. In addition, the level of aggregation varied with tick abundance. These results suggest that applying acaricides to a portion of the herd or culling the most infested individuals at a given moment of the

  2. Effect of formoterol, a long-acting β2-adrenergic agonist, on muscle strength and power output, metabolism, and fatigue during maximal sprinting in men.

    PubMed

    Kalsen, Anders; Hostrup, Morten; Backer, Vibeke; Bangsbo, Jens

    2016-06-01

    The aim was to investigate the effect of the long-acting β2-adrenergic agonist formoterol on muscle strength and power output, muscle metabolism, and phosphorylation of CaMKII Thr(287) and FXYD1 during maximal sprinting. In a double-blind crossover study, 13 males [V̇o2 max: 45.0 ± 0.2 (means ± SE) ml·min(-1)·kg(-1)] performed a 30-s cycle ergometer sprint after inhalation of either 54 μg of formoterol (FOR) or placebo (PLA). Before and after the sprint, muscle biopsies were collected from vastus lateralis and maximal voluntary contraction (MVC), and contractile properties of quadriceps were measured. Oxygen uptake was measured during the sprint. During the sprint, peak power, mean power, and end power were 4.6 ± 0.8, 3.9 ± 1.1, and 9.5 ± 3.2% higher (P < 0.05) in FOR than in PLA, respectively. Net rates of glycogenolysis and glycolysis were 45.7 ± 21.0 and 28.5 ± 13.4% higher (P < 0.05) in FOR than in PLA, respectively, and the decrease in ATP content was lower (P < 0.05) in FOR than in PLA (3.7 ± 1.5 vs. 8.0 ± 1.6 mmol/kg dry weight). There was no difference in breakdown of phosphocreatine and oxygen uptake between treatments. Before and after the sprint, MVC and peak twitch force were higher (P < 0.05) in FOR than in PLA. No differences were observed in phosphorylation of CaMKII Thr(287) and FXYD1 between treatments before the sprint, whereas phosphorylation of CaMKII Thr(287) and FXYD1 was greater (P < 0.05) in FOR than in PLA after the sprint. In conclusion, formoterol-induced enhancement in power output during maximal sprinting is associated with increased rates of glycogenolysis and glycolysis that may counteract development of fatigue.

  3. [Preparation and the biological effect of fusion protein GLP-1-exendin-4/ IgG4(Fc) fusion protein as long acting GLP-1 receptor agonist].

    PubMed

    Zheng, Yun-cheng

    2015-12-01

    . It can be used as a long-acting GLP-1 agonists. PMID:27169293

  4. Mentoring, Task Sharing, and Community Outreach Through the TutoratPlus Approach: Increasing Use of Long-Acting Reversible Contraceptives in Senegal

    PubMed Central

    Gueye, Babacar; Wesson, Jennifer; Koumtingue, Djimadoum; Stratton, Sara; Viadro, Claire; Talla, Hawa; Dioh, Etienne; Cissé, Carol; Sebikali, Boniface; Mamadou Daff, Bocar

    2016-01-01

    ABSTRACT Background: To broaden access to family planning in rural areas and improve contraceptive prevalence, Senegal, in the context of wide method choice, is promoting implants and the intrauterine device, currently used throughout the country by only 5.6% of women of reproductive age who are in union, primarily urban women. Methods: The TutoratPlus performance improvement approach strengthens family planning clinical skills, particularly for long-acting reversible contraceptives (LARCs), through mentoring, task sharing, and community outreach. Following a 2013 baseline situation analysis, 290 participating facilities in 12 of Senegal's 14 regions developed action plans to address gaps identified in 3 areas: provider performance, equipment, and infrastructure. Between 2013 and 2014, 85 trained mentors coached, demonstrated skills, and observed 857 providers, including nurses, nonclinical family planning counselors, and community health workers (CHWs), in LARC service provision through two 5-day visits per facility at 21-day intervals. We used routine service delivery data and TutoratPlus mentoring data to assess changes in contraceptive use, including LARCs, 6 months before and 6 months after the mentoring intervention among 100 of the facilities with complete data. Results: The baseline assessment of 290 facilities found that fewer than half (47%) had a provider who could offer at least 1 LARC method, and 64% to 69% lacked kits. Post-intervention, all 290 facilities were adequately equipped and clinically able to offer LARCs. Among the 552 clinical providers, the percentage with acceptable LARC performance (at least 80% of observation checklist items correct) doubled from 32% to 67% over the 2 mentoring visits. In the 100 facilities with available comparison data, the number of new LARC users rose from 1,552 to 2,879 in the 6 months pre- and post-intervention—an 86% increase. Conclusion: Success of the TutoratPlus approach in Senegal is likely in part

  5. Comparative effects of long-acting and short-acting loop diuretics on cardiac sympathetic nerve activity in patients with chronic heart failure

    PubMed Central

    Matsuo, Yae; Kasama, Shu; Toyama, Takuji; Funada, Ryuichi; Takama, Noriaki; Koitabashi, Norimichi; Ichikawa, Shuichi; Suzuki, Yasuyuki; Matsumoto, Naoya; Sato, Yuichi; Kurabayashi, Masahiko

    2016-01-01

    Objective Short-acting loop diuretics are known to enhance cardiac sympathetic nerve activity (CSNA) in patients with chronic heart failure (CHF). The effects of two loop diuretics—long-acting azosemide and short-acting furosemide—on CSNA were evaluated using 123I-metaiodobenzylguanidine (MIBG) scintigraphy in patients with CHF. Methods The present study was a subanalysis of our previously published study, which had reported that serial 123I-MIBG studies were the most useful prognostic indicator in patients with CHF. Patients with CHF (n=208, left ventricular ejection fraction <45%) but no history of cardiac events for at least 5 months prior to the study were identified according to their histories of acute decompensated heart failure requiring hospitalisation. Patients underwent 123I-MIBG scintigraphy immediately before hospital discharge and at a 6-month follow-up. The delayed % denervation, delayed heart/mediastinum count (H/M) ratio and washout rate (WR) were determined using 123I-MIBG scintigraphy. A total of 108 patients were selected, and propensity score matching was used to compare patients treated with either oral azosemide (n=54) or furosemide (n=54). Results After treatment, 123I-MIBG scintigraphic parameters improved in both groups. However, the degree of change in % denervation was −13.8±10.5 in the azosemide group and −5.7±12.7 in the furosemide group (p<0.01), the change in H/M ratio was 0.20±0.16 in the azosemide group and 0.06±0.19 in the furosemide group (p<0.01), and the change in WR was −11.3±9.2% in the azosemide group and −3.0±12.7% in the furosemide group (p<0.01). Moreover, multivariate analysis showed an independent and significant positive relationship between furosemide and δ-WR from hospital discharge to 6 months after treatment in patients with CHF (p=0.001). Conclusions These findings indicate that azosemide suppresses CSNA compared with furosemide in patients with CHF. Trial registration number UMIN000000626

  6. Effect of β2-adrenergic receptor gene (ADRB2) 3′ untranslated region polymorphisms on inhaled corticosteroid/long-acting β2-adrenergic agonist response

    PubMed Central

    2012-01-01

    Background Evidence suggests that variation in the length of the poly-C repeat in the 3′ untranslated region (3′UTR) of the β2-adrenergic receptor gene (ADRB2) may contribute to interindividual variation in β-agonist response. However, methodology in previous studies limited the assessment of the effect of sequence variation in the context of poly-C repeat length. The objectives of this study were to design a novel genotyping method to fully characterize sequence variation in the ADRB2 3′UTR poly-C repeat in asthma patients treated with inhaled corticosteroid and long-acting β2-adrenergic agonist (ICS/LABA) combination therapy, and to analyze the effect of the poly-C repeat polymorphism on clinical response. Methods In 2,250 asthma patients randomized to treatment with budesonide/formoterol or fluticasone/salmeterol in a six-month study (AstraZeneca study code: SD-039-0735), sequence diversity in the ADRB2 poly-C repeat region was determined using a novel sequencing-based genotyping method. The relationship between the poly-C repeat polymorphism and the incidence of severe asthma exacerbations, and changes in pulmonary function and asthma symptoms from baseline to the average during the treatment period, were analyzed. Results Poly-C repeat genotypes were assigned in 97% (2,192/2,250) of patients. Of the 13 different poly-C repeat alleles identified, six alleles occurred at a frequency of >5% in one or more population in this study. The repeat length of these six common alleles ranged from 10 to 14 nucleotides. Twelve poly-C repeat genotypes were observed at a frequency of >1%. No evidence of an association between poly-C repeat genotype and the incidence of severe asthma exacerbations was observed. Patients’ pulmonary function measurements improved and asthma symptoms declined when treated with ICS/LABA combination therapy regardless of poly-C repeat genotype. Conclusions The extensive sequence diversity present in the poly-C repeat region of the ADRB2

  7. Adjunctive Aripiprazole Treatment for Risperidone-Induced Hyperprolactinemia: An 8-Week Randomized, Open-Label, Comparative Clinical Trial

    PubMed Central

    Zhao, Jingyuan; Song, Xueqin; Ai, Xiaoqing; Gu, Xiaojing; Huang, Guangbiao; Li, Xue; Pang, Lijuan; Ding, Minli; Ding, Shuang; Lv, Luxian

    2015-01-01

    Objective The present study aimed to evaluate the efficacy and safety of adjunctive aripiprazole treatment in schizophrenia patients with risperidone-induced hyperprolactinemia. Methods One hundred and thirteen patients who were receiving a stable dose of risperidone were randomly assigned to either adjunctive aripiprazole treatment (10 mg/day) (aripiprazole group) or no additional treatment (control group) at a 1:1 ratio for 8 weeks. Schizophrenia symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Rating scales and safety assessments (RSESE, BARS, UKU) were performed at baseline and at weeks 4 and 8. Serum levels of prolactin were determined at baseline and at weeks 2, 4, 6 and 8. Metabolic parameters were determined at baseline and again at weeks 4 and 8. Results One hundred and thirteen patients were enrolled in this study, and 107 patients completed the study (54 in the aripiprazole group, and 53 in the control group). PANSS-total scores in the aripiprazole group decreased significantly at week 4 (P = 0.003) and week 8 (P = 0.007) compared with the control group. PANSS-negative scores in the aripiprazole group also decreased significantly at week 4 (P = 0.005) and week 8 (P< 0.001) compared with the control group. Serum levels of prolactin in the aripiprazole group decreased significantly at week 2 (P< 0.001), week 4 (P< 0.001), week 6 (P< 0.001) and week 8 (P< 0.001) compared with the control group. There were no significant differences in changes of Fasting Plasma Glucose, Total cholesterol, Triglycerides and High Density Lipoprotein within each group at week 4 and 8 execpt low density lipoproteins. There was no significant difference in the incidence of adverse reactions between the two groups. Conclusions Adjunctive aripiprazole treatment may be beneficial in reducing serum levels of prolactin and improving negative symptoms in schizophrenia patients with risperidone-induced hyperprolactinemia. Trial Registration chictr.org Chi

  8. Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study.

    PubMed

    Bobes, J; Garc A-Portilla, M P; Rejas, J; Hern Ndez, G; Garcia-Garcia, M; Rico-Villademoros, F; Porras, A

    2003-01-01

    Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%). Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment (< 12 weeks). However, data on longer-term treatment (> 12 weeks) are lacking

  9. Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized double-blind trial

    PubMed Central

    Yatham, L N; Beaulieu, S; Schaffer, A; Kauer-Sant'Anna, M; Kapczinski, F; Lafer, B; Sharma, V; Parikh, S V; Daigneault, A; Qian, H; Bond, D J; Silverstone, P H; Walji, N; Milev, R; Baruch, P; da Cunha, A; Quevedo, J; Dias, R; Kunz, M; Young, L T; Lam, R W; Wong, H

    2016-01-01

    Atypical antipsychotic adjunctive therapy to lithium or valproate is effective in treating acute mania. Although continuation of atypical antipsychotic adjunctive therapy after mania remission reduces relapse of mood episodes, the optimal duration is unknown. As many atypical antipsychotics cause weight gain and metabolic syndrome, they should not be continued unless the benefits outweigh the risks. This 52-week double-blind placebo-controlled trial recruited patients with bipolar I disorder (n=159) who recently remitted from a manic episode during treatment with risperidone or olanzapine adjunctive therapy to lithium or valproate. Patients were randomized to one of three conditions: discontinuation of risperidone or olanzapine and substitution with placebo at (i) entry (‘0-weeks' group) or (ii) at 24 weeks after entry (‘24-weeks' group) or (iii) continuation of risperidone or olanzapine for the full duration of the study (‘52-weeks' group). The primary outcome measure was time to relapse of any mood episode. Compared with the 0-weeks group, the time to any mood episode was significantly longer in the 24-weeks group (hazard ratio (HR) 0.53; 95% confidence interval (CI): 0.33, 0.86) and nearly so in the 52-weeks group (HR: 0.63; 95% CI: 0.39, 1.02). The relapse rate was similar in the 52-weeks group compared with the 24-weeks group (HR: 1.18; 95% CI: 0.71, 1.99); however, sub-group analysis showed discordant results between the two antipsychotics (HR: 0.48, 95% CI: 0.17; 1.32 olanzapine patients; HR: 1.85, 95% CI: 1.00, 3.41 risperidone patients). Average weight gain was 3.2 kg in the 52-weeks group compared with a weight loss of 0.2 kg in the 0-weeks and 0.1 kg in the 24-weeks groups. These findings suggest that risperidone or olanzapine adjunctive therapy for 24 weeks is beneficial but continuation of risperidone beyond this period does not reduce the risk of relapse. Whether continuation of olanzapine beyond this period reduces relapse risk remains

  10. Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study.

    PubMed

    Bobes, J; Garc A-Portilla, M P; Rejas, J; Hern Ndez, G; Garcia-Garcia, M; Rico-Villademoros, F; Porras, A

    2003-01-01

    Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%). Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment (< 12 weeks). However, data on longer-term treatment (> 12 weeks) are lacking

  11. MK-801-induced deficits in social recognition in rats: reversal by aripiprazole, but not olanzapine, risperidone, or cannabidiol.

    PubMed

    Deiana, Serena; Watanabe, Akihito; Yamasaki, Yuki; Amada, Naoki; Kikuchi, Tetsuro; Stott, Colin; Riedel, Gernot

    2015-12-01

    Deficiencies in social activities are hallmarks of numerous brain disorders. With respect to schizophrenia, social withdrawal belongs to the category of negative symptoms and is associated with deficits in the cognitive domain. Here, we used the N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801) for induction of social withdrawal in rats and assessed the efficacy of several atypical antipsychotics with different pharmacological profiles as putative treatment. In addition, we reasoned that the marijuana constituent cannabidiol (CBD) may provide benefit or could be proposed as an adjunct treatment in combination with antipsychotics. Hooded Lister rats were tested in the three-chamber version for social interaction, with an initial novelty phase, followed after 3 min by a short-term recognition memory phase. No drug treatment affected sociability. However, distinct effects on social recognition were revealed. MK-801 reduced social recognition memory at all doses (>0.03 mg/kg). Predosing with aripiprazole dose-dependently (2 or 10 mg/kg) prevented the memory decline, but doses of 0.1 mg/kg risperidone or 1 mg/kg olanzapine did not. Intriguingly, CBD impaired social recognition memory (12 and 30 mg/kg) but did not rescue the MK-801-induced deficits. When CBD was combined with protective doses of aripiprazole (CBD-aripiprazole at 12 :  or 5 : 2 mg/kg) the benefit of the antipsychotic was lost. At the same time, activity-related changes in behaviour were excluded as underlying reasons for these pharmacological effects. Collectively, the combined activity of aripiprazole on dopamine D2 and serotonin 5HT1A receptors appears to provide a significant advantage over risperidone and olanzapine with respect to the rescue of cognitive deficits reminiscent of schizophrenia. The differential pharmacological properties of CBD, which are seemingly beneficial in human patients, did not back-translate and rescue the MK-801-induced social memory deficit.

  12. Effects of prenatal exposure to antipsychotic risperidone on developmental neurotoxicity, apoptotic neurodegeneration and neurobehavioral sequelae in rat offspring.

    PubMed

    Singh, K P; Singh, Manoj Kr; Singh, Manish

    2016-08-01

    A tremendous increase has been documented in the recent past in prescribing second generation atypical antipsychotic drugs (AAPDs) to the pregnant women with psychosis, considering their reproductive and teratogenic safety. Among AAPDs, risperidone (RIS) ranked third after olanzapine (OLZ) and quetiapine (QUE) used during pregnancy, as OLZ is associated to substantial weight gain in adults and offspring. Although teratogenic safety of RIS has been established, its potential role in developmental neurotoxicity and related neurobehavioral impairments in adolescents has not been documented so far. Therefore, present study has been undertaken to elucidate the effect of prenatal exposure to risperidone (RIS) on developmental neurotoxicity and apoptotic neurodegeneration in neocortical region of fetal brain; and related functional sequelae in young rat offspring. The pregnant Wistar rats were exposed to RIS at 0.8, 1.0 and 2.0mg/kg, at equivalent therapeutic doses, orally from GD 6 to 21. Half of the pregnant rats were sacrificed and their brains were collected, weighed, and processed for neurohistopathological and apoptotic neurodegenerative evaluation. The remaining dams were allowed to deliver naturally, and their offspring were reared up to 10 weeks for neurobehavioral study. Prenatal exposure to RIS induced significant stunting of fetal body and brain weight, substantial reduction in the thickness of neocortical layers and apoptotic neurodegeneration in fetal brains, and delayed postnatal development and growth of the offspring; as well as long- lasting impact on anxiety like impaired behavioral responses on explorative mazes. Therefore, health care providers should be careful in prescribing atypical antipsychotics in general and RIS in particular, to the pregnant psychotic population. PMID:27184437

  13. Use of haloperidol and risperidone in highly aggressive Swiss Webster mice by applying the model of spontaneous aggression (MSA).

    PubMed

    Fragoso, Viviane Muniz da Silva; Hoppe, Luanda Yanaan; de Araújo-Jorge, Tânia Cremonini; de Azevedo, Marcos José; Campos, Jerônimo Diego de Souza; Cortez, Célia Martins; de Oliveira, Gabriel Melo

    2016-03-15

    Aggression is defined as the act in which an individual intentionally harms or injures another of their own species. Antipsychotics are a form of treatment used in psychiatric routine. They have been used for decades in treatment of patients with aggressive behavior. Haloperidol and risperidone promote the control of psychiatric symptoms, through their respective mechanisms of action. Experimental models are obtained by behavioral, genetic, and pharmacological manipulations, and use a reduced number of animals. In this context, we applied the model of spontaneous aggression (MSA), originating the presence of highly aggressive mice (AgR) when reassembled in adulthood. We administered haloperidol and risperidone in escalating doses, for ten consecutive days. Using positive and negative control groups, we evaluated the effectiveness of these drugs and the reversal of the aggressive behavior, performing the tail suspension test (TST) and open field test (OFT) on 10th day of treatment and 10 days after its discontinuation. The results showed that both antipsychotic drugs were effective in AgR and reversed the aggressive phenotype, reducing the number of attacks by AgR and the extent of lesions in the subordinate mice (AgD) exposed to the pattern of aggressive behavior (PAB) of the aggressors. This conclusion is based on the reduction in the animals' motor and exploratory activity, and on the reversal of patterns of aggressive behavior. The association between the MSA and experiments with other therapeutic protocols and different antipsychotics can be an important methodology in the study of aggressive behavior in psychiatric patients. PMID:26698401

  14. Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators

    PubMed Central

    van der Molen, T.; Postma, D. S.; Turner, M. O.; Jong, B. M.; Malo, J. L.; Chapman, K.; Grossman, R.; de Graaff, C. S.; Riemersma, R. A.; Sears, M. R.

    1997-01-01

    BACKGROUND: The long acting beta 2 agonist formoterol has proved to be an effective bronchodilator with a prolonged action of 12-14 hours. However, the precise role of formoterol in the maintenance treatment of asthma is still under debate. A study was performed to investigate the efficacy and safety of treatment with formoterol for six months in subjects with asthma. METHODS: In a multicentre double blind, placebo controlled, parallel group study 239 subjects with mild to moderate asthma were randomly assigned to treatment with either inhaled formoterol 24 micrograms twice daily (n = 125) or placebo (n = 114) during eight months. The study consisted of a four week run in period, a 24 week treatment period, and a four week washout period. All subjects were using regular inhaled corticosteroids (100-3200 micrograms daily) but were still needing at least five inhalations of short acting beta 2 agonist per week for symptom relief. The study was performed in 10 outpatient clinics in Canada, and five outpatient clinics and one coordinating centre for 44 Dutch general practitioners in The Netherlands. Twice daily self-reported peak expiratory flow (PEF) measurements, symptom scores, and rescue beta 2 agonist use during the last 28 treatment days compared with baseline values were used as main outcome measures. Spirometric values were measured at entry, at the start of treatment, after four, 12 and 24 weeks of treatment, and after four weeks washout. RESULTS: One hundred and twenty five subjects received formoterol 24 micrograms twice daily via Turbohaler and 114 received placebo. Baseline FEV1 was 67.1% predicted and mean bronchodilator reversibility was 26%. The mean total asthma symptom score was 3.6 (maximum possible 21). A significant decrease in symptoms in favour of formoterol (difference from placebo -0.64, 95% CI -0.04 to -1.23, p = 0.04) was observed. Compared with placebo, morning PEF increased (difference from placebo 28 l/min, 95% CI 18.3 to 37.7, p = 0

  15. Combination of a long-acting delivery system for luteinizing hormone-releasing hormone agonist with Novantrone chemotherapy: increased efficacy in the rat prostate cancer model.

    PubMed Central

    Schally, A V; Kook, A I; Monje, E; Redding, T W; Paz-Bouza, J I

    1986-01-01

    The combination of hormonal treatment based on a long-acting delivery system for the agonist [6-D-tryptophan]luteinizing hormone-releasing hormone ([D-Trp6]-LH-RH) with the chemotherapeutic agent Novantrone (mitoxantrone dihydrochloride) was studied in the Dunning R3327H rat prostate cancer model. Microcapsules of [D-Trp6]-LH-RH formulated from poly(DL-lactide-co-glycolide) and calculated to release a controlled dose of 25 micrograms/day were injected intramuscularly once a month. Novantrone (0.25 mg/kg) was injected intravenously once every 3 weeks. Three separate experiments were carried out. When the therapy was started 45 days after transplantation and continued for 70 days, tumor volume in the presence of the microcapsules (966 +/- 219 mm3) or Novantrone (3606 +/- 785 mm3) given alone was significantly decreased compared to controls (14,476 +/- 3045 mm3). However, the combination of microcapsules and Novantrone caused a greater inhibition of tumor growth (189 +/- 31 mm3) than the single agents. Similar effects were seen when the percent increase in tumor volume was examined. Tumor volume increased 10,527 +/- 1803% for the control group. The inhibition of growth caused by the [D-Trp6]LH-RH microcapsules alone (672 +/- 153% increase in volume) was again greater than that caused by Novantrone alone (2722 +/- 421% increase). The combination of the two agents was again the most effective, resulting in an increase in tumor volume of only 105 +/- 29%. Control tumors weighed 30.0 +/- 6.5 g. Tumor weights were much less in the groups treated with either microcapsules (3.28 +/- 0.69 g) or Novantrone (19.53 +/- 3.3 g) alone. The lowest tumor weights after 70 days of treatment were obtained in the group that received the combination of [D-Trp6]LH-RH microcapsules and Novantrone (1.02 +/- 0.2 g). Testes and ventral prostate weights were significantly diminished by the administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Novantrone. In both of these

  16. Comparison between the efficacies of Risperidone with Haloperidol in the treatment of attention-deficit hyperactivity disorder (ADHD) among preschoolers: a randomized double-blind clinical trial

    PubMed Central

    Riahi, Forough; Tashakori, Ashraf; Abdi, Leila

    2016-01-01

    Background Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric disease with a worldwide pooled prevalence of 5.29%. Objective To compare the efficacy of Risperidone with Haloperidol in the treatment of attention-deficit hyperactivity disorder (ADHD) among 3- to 6-year-old children. Methods In a 6-week double-blind clinical trial, the efficacy of Risperidone 0.5–2 mg with a dose of maximum Haloperidol 0.075 mg/kg was assessed in 39 children aged 3–6 years. This study was conducted at the Golestan Psychiatric Clinic (Ahvaz, Iran). Measurement tools included the Conners’ Parent Rating Scale (CPRS-48), Children’s Global Assessment Scale (CGAS), and the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS). Data were analyzed using the Wilcoxon, Mann-Whitney, and Fisher’s exact tests in the SPSS 19. Results During the 6 weeks, the decline in points was seen in Conner’s rating scale and in ADHD-RS score in Risperidone and Haloperidol groups (p<0.001). On the CGAS scale, an increase of performance in both groups for six weeks was statistically significant (p<0.001). In the scales of ADHD-RS and CPRS-48, no statistically significant difference was observed between the two treatment groups; i.e., in terms of reducing the rate during weeks of two, four, and six (p>0.05). Conclusions Haloperidol and Risperidone possibly can be an acceptable treatment choice in the ADHD treatment of 3- to 6-year-old children. Trial registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the Irct ID: IRCT2015082623766N1. Funding This work was financially supported by grant (ref. no.: U-93130) from the vice chancellor for Research Affairs of Ahvaz Jundishapur University of Medical Sciences. PMID:27790334

  17. Comparison of risperidone and aripiprazole in the treatment of preschool children with disruptive behavior disorder and attention deficit-hyperactivity disorder: A randomized clinical trial.

    PubMed

    Safavi, Parvin; Hasanpour-Dehkordi, Ali; AmirAhmadi, Maryam

    2016-01-01

    Although pharmacotherapy with atypical antipsychotics is common in child psychiatry, there has been little research on this issue. To compare the efficacy and safety of risperidone and aripiprazole in the treatment of preschool children with disruptive behavior disorders comorbid with attention deficit-hyperactivity disorder (ADHD). Randomized clinical trial conducted in a university-affiliated child psychiatry clinic in southwest Iran. Forty 3-6-year-old children, diagnosed with oppositional defiant disorder comorbid with ADHD, were randomized to an 8-week trial of treatment with risperidone or aripiprazole (20 patients in each group). Assessment was performed by Conners' rating scale-revised and clinical global impressions scale, before treatment, and at weeks 2, 4, and 8 of treatment. The data were analyzed by SPSS version 16. Mean scores between the two groups were compared by analysis of variance and independent and paired t-test. Mean scores of Conners rating scales were not different between two groups in any steps of evaluation. Both groups had significantly reduced scores in week 2 of treatment (P = 0.00), with no significant change in subsequent measurements. Rates of improvement, mean increase in weight (P = 0.894), and mean change in fasting blood sugar (P = 0.671) were not significantly different between two groups. Mean serum prolactin showed a significant increase in risperidone group (P = 0.00). Both risperidone and aripiprazole were equally effective in reducing symptoms of ADHD and oppositional defiant disorder, and relatively safe, but high rates of side effects suggest the cautious use of these drugs in children. PMID:27144151

  18. A high-performance liquid chromatographic-atmospheric pressure chemical ionization-tandem mass spectrometric method for determination of risperidone and 9-hydroxyrisperidone in human plasma.

    PubMed

    Moody, David E; Laycock, John D; Huang, Wei; Foltz, Rodger L

    2004-09-01

    Risperidone, a benzisoxazole derivative, is an antipsychotic agent used for the treatment of schizophrenia. We developed a liquid chromatographic-atmospheric pressure chemical ionization-tandem mass spectrometric (LC-APCI-MS-MS) method with improved sensitivity, selectivity, and dynamic range for determination of risperidone and 9-hydroxyrisperidone in human plasma. A structural analogue of risperidone, RO68808 (5 ng/mL), is added as the internal standard to 1 mL of human plasma. Plasma is made basic, extracted with pentane/methylene chloride (3:1), the organic phase evaporated to dryness, and the residue is reconstituted in water with 0.1% formic acid/acetonitrile (20:1). For LC-MS-MS analysis, a Metachem Inertsel HPLC column (2.1 x 150 mm, 5-microm particle size) is connected to a Finnigan TSQ7000 tandem MS via the Finnigan API interface. Both electrospray (ESI) and APCI produced predominantly MH(+) ions for the two analytes and the internal standard. Ions detected by selected reaction monitoring correspond to the following transitions: m/z 411 to 191 for risperidone, m/z 427 to 207 for 9-hydroxyrisperidone, and m/z 421 to 201 for the internal standard. APCI provided a larger dynamic range (0.1 to 25 ng/mL) and better precision and accuracy than ESI. Intrarun accuracy and precision determined at 0.1, 0.25, 2.5, and 15 ng/mL were within 12% of target with %CVs not exceeding 10.9%. Interrun accuracy and precision determined at the same concentrations were within 9.6% of target with %CVs not exceeding 6.7%. Analytes were stable in plasma after 24 h at room temperature, 2 freeze-thaw cycles, and 490 days at -20 degrees C. PMID:15516302

  19. Comorbid Anxiety and Social Avoidance in Treatment of Severe Childhood Aggression: Response to Adding Risperidone to Stimulant and Parent Training; Mediation of Disruptive Symptom Response

    PubMed Central

    Gadow, Kenneth D.; Farmer, Cristan A.; Findling, Robert L.; Bukstein, Oscar; Molina, Brooke S.G.; Brown, Nicole V.; Li, Xiaobai; Rundberg-Rivera, E. Victoria; Bangalore, Srihari; Buchan-Page, Kristin; Hurt, Elizabeth A.; Rice, Robert; McNamara, Nora K.; Aman, Michael G.

    2015-01-01

    Abstract Objective: In the four-site Treatment of Severe Childhood Aggression (TOSCA) study, addition of risperidone to stimulant and parent training moderately improved parent-rated disruptive behavior disorder (DBD) symptoms. This secondary study explores outcomes other than DBD and attention-deficit/hyperactivity disorder (ADHD) as measured by the Child and Adolescent Symptom Inventory-4R (CASI-4R). Methods: A total of 168 children ages 6–12 with severe aggression (physical harm), DBD, and ADHD were randomized to parent training plus stimulant plus placebo (basic treatment) or parent training plus stimulant plus risperidone (augmented treatment) for 9 weeks. All received only parent training plus stimulant for the first 3 weeks, then those with room for improvement received a second drug (placebo or risperidone) for 6 weeks. CASI-4R category item means at baseline and week 9 were entered into linear mixed-effects models for repeated measures to evaluate group differences in changes. Mediation of the primary DBD outcome was explored. Results: Parent ratings were nonsignificant with small/negligible effects, but teacher ratings (n=46 with complete data) showed significant augmented treatment advantage for symptoms of anxiety (p=0.013, d=0.71), schizophrenia spectrum (p=0.017, d=0.45), and impairment in these domains (p=0.02, d=0.26), all remaining significant after false discovery rate correction for multiple tests. Improvement in teacher-rated anxiety significantly (p=0.001) mediated the effect of risperidone augmentation on the primary outcome, the Disruptive-total of the parent-rated Nisonger Child Behavior Rating Form. Conclusions: Addition of risperidone to parent training plus stimulant improves not only parent-rated DBD as previously reported, but also teacher-rated anxiety–social avoidance. Improvement in anxiety mediates improvement in DBD, suggesting anxiety-driven fight-or-flight disruptive behavior with aggression, with implications for potential

  20. Adolescent Risperidone treatment alters protein expression associated with protein trafficking and cellular metabolism in the adult rat prefrontal cortex.

    PubMed

    Farrelly, Lorna A; Dicker, Patrick; Wynne, Kieran; English, Jane; Cagney, Gerard; Föcking, Melanie; Cotter, David R

    2014-06-01

    The prefrontal cortex (PFC) is associated with mental health illnesses including schizophrenia, depression, bipolar disorder, and autism spectrum disorders. It richly expresses neuroreceptors which are the target for antipsychotics. However, as the precise mechanism of action of antipsychotic medications is not known, proteomic studies of the effects of antipsychotic drugs on the brain are warranted. In the current study, we aimed to characterize protein expression in the adult rodent PFC (n = 5 per group) following low-dose treatment with Risperidone or saline in adolescence (postnatal days 34-47). The PFC was examined by triplicate 1 h runs of label-free LC-MS/MS. The raw mass spectral data were analyzed with the MaxQuant(TM) software. Statistical analysis was carried out using SAS® Version 9.1. Pathway and functional analysis was performed with IngenuityPathway Analysis and in the Database for Annotation, Visualization and Integrated Discovery (DAVID), respectively, the most implicated pathways were found to be related to mitochondrial function, protein trafficking, and the cytoskeleton. This report adds to the current repertoire of data available concerning the effects of antipsychotic drugs on the brain and sheds light on their biological mechanisms. The MS data have been deposited with the ProteomeXchange Consortium with dataset identifier PXD000480. PMID:24733778

  1. Selection of Rilpivirine-Resistant HIV-1 in a Seroconverter From the SSAT 040 Trial Who Received the 300-mg Dose of Long-Acting Rilpivirine (TMC278LA).

    PubMed

    Penrose, Kerri J; Parikh, Urvi M; Hamanishi, Kristen A; Else, Laura; Back, David; Boffito, Marta; Jackson, Akil; Mellors, John W

    2016-03-15

    The injectable long-acting formulation of rilpivirine (TMC278LA) is a promising preexposure prophylaxis (PrEP) candidate for prevention of human immunodeficiency virus type 1 (HIV-1) infection. We evaluated HIV-1 in plasma obtained from an unexpected seroconverter in the 300-mg arm of the SSAT040 TMC278LA pharmacokinetic study for rilpivirine (RPV) resistance. Infection with wild-type HIV-1 was confirmed on day 84 after TMC278LA injection, and the K101E mutation was detected on day 115. Plasma-derived HIV-1 clones containing K101E had 4-fold increased resistance to RPV and 4-8-fold increased cross-resistance to etravirine, nevirapine, and efavirenz compared with wild type HIV-1 plasma-derived clones from the same individual. This case is a unique instance of infection with wild-type HIV-1 and subsequent selection of resistant virus by persistent exposure to long-acting PrEP. PMID:26563240

  2. Different MK-801 administration schedules induce mild to severe learning impairments in an operant conditioning task: role of buspirone and risperidone in ameliorating these cognitive deficits.

    PubMed

    Rapanelli, Maximiliano; Frick, Luciana Romina; Bernardez-Vidal, Micaela; Zanutto, Bonifacio Silvano

    2013-11-15

    Blockade of N-methyl-d-aspartate receptor (NMDA) by the noncompetitive NMDA receptor (NMDAR) antagonist MK-801 produces behavioral abnormalities and alterations in prefrontal cortex (PFC) functioning. Due to the critical role of the PFC in operant conditioning task learning, we evaluated the effects of acute, repeated postnatal injections of MK-801 (0.1mg/kg) on learning performance. We injected Long-Evans rats i.p. with MK-801 (0.1mg/kg) using three different administration schedules: injection 40 min before beginning the task (during) (n=12); injection twice daily for six consecutive days prior to beginning the experimental procedures (prior) (n=12); or twice daily subcutaneous injections from postnatal day 7 to 11 (postnatal) (n=12). Next, we orally administered risperidone (serotonin receptor 2A and dopamine receptor 2 antagonist, 1mg/kg) or buspirone (serotonin receptor 1A partial agonist, 10mg/kg) to animals treated with the MK-801 schedule described above. The postnatal and prior administration schedules produced severe learning deficits, whereas injection of MK-801 just before training sessions had only mild effects on acquisition of an operant conditioning. Risperidone was able to reverse the detrimental effect of MK-801 in the animals that were treated with MK-801 during and prior training sessions. In contrast, buspirone was only effective at mitigating the cognitive deficits induced by MK-801 when administered during the training procedures. The data demonstrates that NMDA antagonism disrupts basic mechanisms of learning in a simple PFC-mediated operant conditioning task, and that buspirone and risperidone failed to attenuate the learning deficits when NMDA neurotransmission was blocked in the early stages of the postnatal period.

  3. Influence of Aripiprazole, Risperidone, and Amisulpride on Sensory and Sensorimotor Gating in Healthy ‘Low and High Gating' Humans and Relation to Psychometry

    PubMed Central

    Csomor, Philipp A; Preller, Katrin H; Geyer, Mark A; Studerus, Erich; Huber, Theodor; Vollenweider, Franz X

    2014-01-01

    Despite advances in the treatment of schizophrenia spectrum disorders with atypical antipsychotics (AAPs), there is still need for compounds with improved efficacy/side-effect ratios. Evidence from challenge studies suggests that the assessment of gating functions in humans and rodents with naturally low-gating levels might be a useful model to screen for novel compounds with antipsychotic properties. To further evaluate and extend this translational approach, three AAPs were examined. Compounds without antipsychotic properties served as negative control treatments. In a placebo-controlled, within-subject design, healthy males received either single doses of aripiprazole and risperidone (n=28), amisulpride and lorazepam (n=30), or modafinil and valproate (n=30), and placebo. Prepulse inhibiton (PPI) and P50 suppression were assessed. Clinically associated symptoms were evaluated using the SCL-90-R. Aripiprazole, risperidone, and amisulpride increased P50 suppression in low P50 gaters. Lorazepam, modafinil, and valproate did not influence P50 suppression in low gaters. Furthermore, low P50 gaters scored significantly higher on the SCL-90-R than high P50 gaters. Aripiprazole increased PPI in low PPI gaters, whereas modafinil and lorazepam attenuated PPI in both groups. Risperidone, amisulpride, and valproate did not influence PPI. P50 suppression in low gaters appears to be an antipsychotic-sensitive neurophysiologic marker. This conclusion is supported by the association of low P50 suppression and higher clinically associated scores. Furthermore, PPI might be sensitive for atypical mechanisms of antipsychotic medication. The translational model investigating differential effects of AAPs on gating in healthy subjects with naturally low gating can be beneficial for phase II/III development plans by providing additional information for critical decision making. PMID:24801767

  4. Influence of aripiprazole, risperidone, and amisulpride on sensory and sensorimotor gating in healthy 'low and high gating' humans and relation to psychometry.

    PubMed

    Csomor, Philipp A; Preller, Katrin H; Geyer, Mark A; Studerus, Erich; Huber, Theodor; Vollenweider, Franz X

    2014-09-01

    Despite advances in the treatment of schizophrenia spectrum disorders with atypical antipsychotics (AAPs), there is still need for compounds with improved efficacy/side-effect ratios. Evidence from challenge studies suggests that the assessment of gating functions in humans and rodents with naturally low-gating levels might be a useful model to screen for novel compounds with antipsychotic properties. To further evaluate and extend this translational approach, three AAPs were examined. Compounds without antipsychotic properties served as negative control treatments. In a placebo-controlled, within-subject design, healthy males received either single doses of aripiprazole and risperidone (n=28), amisulpride and lorazepam (n=30), or modafinil and valproate (n=30), and placebo. Prepulse inhibiton (PPI) and P50 suppression were assessed. Clinically associated symptoms were evaluated using the SCL-90-R. Aripiprazole, risperidone, and amisulpride increased P50 suppression in low P50 gaters. Lorazepam, modafinil, and valproate did not influence P50 suppression in low gaters. Furthermore, low P50 gaters scored significantly higher on the SCL-90-R than high P50 gaters. Aripiprazole increased PPI in low PPI gaters, whereas modafinil and lorazepam attenuated PPI in both groups. Risperidone, amisulpride, and valproate did not influence PPI. P50 suppression in low gaters appears to be an antipsychotic-sensitive neurophysiologic marker. This conclusion is supported by the association of low P50 suppression and higher clinically associated scores. Furthermore, PPI might be sensitive for atypical mechanisms of antipsychotic medication. The translational model investigating differential effects of AAPs on gating in healthy subjects with naturally low gating can be beneficial for phase II/III development plans by providing additional information for critical decision making.

  5. Alterations in brain extracellular dopamine and glycine levels following combined administration of the glycine transporter type-1 inhibitor Org-24461 and risperidone.

    PubMed

    Nagy, Katalin; Marko, Bernadett; Zsilla, Gabriella; Matyus, Peter; Pallagi, Katalin; Szabo, Geza; Juranyi, Zsolt; Barkoczy, Jozsef; Levay, Gyorgy; Harsing, Laszlo G

    2010-12-01

    The most dominant hypotheses for the pathogenesis of schizophrenia have focused primarily upon hyperfunctional dopaminergic and hypofunctional glutamatergic neurotransmission in the central nervous system. The therapeutic efficacy of all atypical antipsychotics is explained in part by antagonism of the dopaminergic neurotransmission, mainly by blockade of D(2) dopamine receptors. N-methyl-D-aspartate (NMDA) receptor hypofunction in schizophrenia can be reversed by glycine transporter type-1 (GlyT-1) inhibitors, which regulate glycine concentrations at the vicinity of NMDA receptors. Combined drug administration with D(2) dopamine receptor blockade and activation of hypofunctional NMDA receptors may be needed for a more effective treatment of positive and negative symptoms and the accompanied cognitive deficit in schizophrenia. To investigate this type of combined drug administration, rats were treated with the atypical antipsychotic risperidone together with the GlyT-1 inhibitor Org-24461. Brain microdialysis was applied in the striatum of conscious rats and determinations of extracellular dopamine, DOPAC, HVA, glycine, glutamate, and serine concentrations were carried out using HPLC/electrochemistry. Risperidone increased extracellular concentrations of dopamine but failed to influence those of glycine or glutamate measured in microdialysis samples. Org-24461 injection reduced extracellular dopamine concentrations and elevated extracellular glycine levels but the concentrations of serine and glutamate were not changed. When risperidone and Org-24461 were added in combination, a decrease in extracellular dopamine concentrations was accompanied with sustained elevation of extracellular glycine levels. Interestingly, the extracellular concentrations of glutamate were also enhanced. Our data indicate that coadministration of an antipsychotic with a GlyT-1 inhibitor may normalize hypofunctional NMDA receptor-mediated glutamatergic neurotransmission with reduced

  6. Economic consequences of the adverse reactions related with antipsychotics: an economic model comparing tolerability of ziprasidone, olanzapine, risperidone, and haloperidol in Spain.

    PubMed

    Bobes, Julio; Cañas, Fernando; Rejas, Javier; Mackell, Joan

    2004-12-01

    Frequency of adverse reactions (ARs) related with antipsychotics usage is high. Along with clinical implications, economic impact might be important. The purpose of this study was to model the economic consequences of ARs related with ziprasidone, olanzapine, risperidone, and haloperidol in Spain, by means of a cost-effectiveness model developed using a Markov modeling approach. The model simulated treatment of a cohort of 1000 schizophrenics for 12 months, initiating treatment with one of four antipsychotic drugs; haloperidol, risperidone, olanzapine and ziprasidone. Conditional probabilities of developing any of four adverse events were calculated. Treatment was modified (decrease dose, switch medication) according to incidence of ARs and physician judgments, obtained from a local cross-sectional study and clinical trials previously published. The analysis was conducted in year 2002 from a third party payer perspective. Results are shown as annual cost per month with psychotic symptoms controlled and included univariate sensitivity analysis. The therapeutic strategy starting with ziprasidone showed the lower costs and the greater number of months with symptoms controlled in most scenarios evaluated versus the other options considered, although the differences were weak: 9.6, 9.3, 9.5 and 9.5 controlled months per patient in base scenario, with annual cost per patient per month with symptoms controlled of 1035 Euros, 1084 Euros, 1087 Euros and 1090 Euros for ziprasidone, haloperidol, risperidone and olanzapine, respectively. Results were robust to one-way sensitivity analysis. Despite the unlike drug prices of antipsychotics, a considerable economic impact due to adverse reactions was seen in our setting. These results should be taken into account by health decision makers and clinicians in the management of patients with schizophrenia.

  7. Effect of in utero exposure to the atypical anti-psychotic risperidone on histopathological features of the rat placenta.

    PubMed

    Singh, K P; Singh, Manoj K; Gautam, Shrikant

    2016-04-01

    For clinical management of different forms of psychosis, both classical and atypical anti-psychotic drugs (APDs) are available. These drugs are widely prescribed, even during pregnancy considering their minimal extra-pyramidal side effects and teratogenic potential compared to classical APDs. Among AAPDs, risperidone (RIS) is a first-line drug of choice by physicians. The molecular weight of RIS is 410.49 g/mol; hence, it can easily cross the placental barrier and enter the foetal bloodstream. It is not known whether or not AAPDs like RIS may affect the developing placenta and foetus adversely. Reports on this issue are limited and sketchy. Therefore, this study has evaluated the effects of maternal exposure to equivalent therapeutic doses of RIS on placental growth, histopathological and cytoarchitectural changes, and to establish a relationship between placental dysfunction and foetal outcomes. Pregnant rats (n = 24) were exposed to selected doses (0.8, 1.0 and 2.0 mg/kg) of RIS from gestation days 6-21. These dams were sacrificed; their placentas and foetuses were collected, morphometrically examined and further processed for histopathological examination. This study revealed that in utero exposure to equivalent therapeutic doses of RIS during organogenesis-induced placental dystrophy (size and weight), disturbed cytoarchitectural organization (thickness of different placental layers), histopathological lesions (necrosis in trophoblast with disruption of trophoblastic septa and rupturing of maternal-foetal interface) and intrauterine growth restriction of the foetuses. It may be concluded that multifactorial mechanisms might be involved in the dysregulation of structure and function of the placenta and of poor foetal growth and development. PMID:27256515

  8. Participant Satisfaction in a Study of Stimulant, Parent Training, and Risperidone in Children with Severe Physical Aggression

    PubMed Central

    Townsend, Lisa D.; Schneider, Jayne; Farmer, Cristan A.; Molina, Brooke B.S.G.; Findling, Robert L.; Gadow, Kenneth D.; Bukstein, Oscar G.; Kolko, David J.; Buchan-Page, Kristin A.; McNamara, Nora K.; Michel, Chenel; Austin, Adrienne; Kipp, Heidi; Rice, Robert R.; Aman, Michael G.

    2015-01-01

    Abstract Objective: The purpose of this study was to examine the satisfaction of families who participated in the Treatment of Severe Childhood Aggression (TOSCA) study. Methods: TOSCA was a randomized clinical trial of psychostimulant plus parent training plus placebo (basic treatment) versus psychostimulant plus parent training plus risperidone (augmented treatment) for children with severe physical aggression, disruptive behavior disorder, and attention-deficit/hyperactivity disorder. Parents completed a standardized Parent Satisfaction Questionnaire (PSQ). Results: Of the 168 families randomized, 150 (89.3%) provided consumer satisfaction data. When they were asked if they would join the study again if they had the option to repeat, 136 (91%) said “yes,” 11 (7%) said “maybe,” and one (<1%) said “no.” When asked if they would recommend the study to other parents with children having similar problems, 147 (98%) said “yes” and 3 (2%) said “maybe.” Between 71% (rating one aspect of the Parent Training) and 96% (regarding the diagnostic interview) endorsed study procedures using the most positive response option. Asked if there were certain aspects of the study that they especially liked, 64 (43%) spontaneously reported parent training. Treatment assignment (basic vs. augmented) and responder status were not associated with reported satisfaction. However, responder status was strongly associated with parent confidence in managing present (p<0.001) and future (p<0.005) problem behaviors. Conclusions: These findings indicate high levels of satisfaction with TOSCA study involvement and, taken together with previous pediatric psychopharmacology social validity studies, suggest high levels of support for the research experience. These findings may inform research bioethics and may have implications for deliberations of institutional review boards. Trial Registry: Treatment of Severe Childhood Aggression (The TOSCA Study), NCT00796302, clinicaltrials

  9. [Preparation and evaluation of risperidone-loaded microsphere/sucrose acetate isobutyrate in situ forming complex depot with double diffusion barriers].

    PubMed

    Lin, Xia; Tang, Xing; Xu, Yu-hong; Zhang, Yu; Zhang, Yan; He, Hai-bing

    2015-06-01

    In the present study, a risperidone loaded microsphere/sucrose acetate isobutyrate (SAIB) in situ forming complex depot was designed to reduce the burst release of SAIB in situ forming depot and to continuously release risperidone for a long-term period without lagime. The model drug risperidone (Ris) was first encapsulated into microspheres and then the Ris-microspheres were embedded into SAIB depot to reduce the amount of dissolved drug in the depot. The effects of different types of microsphere matrix, including chitosan and poly(lactide-coglycolide) (PLGA), matrix/Ris ratios in microspheres and morphology of microspheres on the drug release behavior of complex depot were investigated. In comparison with the Ris-loaded SAIB depot (Ris-SAIB), the complex depot containing chitosan microspheres (in which chitosan/Ris = 1 : 1, w/w) (Ris-Cm-SAIB) decreased the burst release from 12.16% to 5.80%. However, increased drug release rate after 4 days was observed in Ris-Cm-SAIB, which was caused by the high penetration of the medium to Ris-Cm-SAIB due to the hydrophilie of chitosan. By encapsulation of risperidone in PLGA microspheres, most drugs can be prevented from dissolving in the depot and meanwhile the hydrophobic PLGA can reduce the media penetration effect on the depot. The complex depot containing PLGA microspheres (in which PLGA/ drug=4 : 2, w/w) (Ris-Pm-SAIB) showed a significant effectiveness on reducing the burst release both in vitro and in vivo whereby only 0.64% drug was released on the first day in vitro and a low AUC0-4d value [(105.2± 24.4) ng.mL-1.d] was detected over the first 4 days in vivo. In addition, drug release from Ris-Pm-SAIB can be modified by varying the morphology of microspheres. The porous PLGA microspheres could be prepared by adding medium chain triglyceride (MCT) in the organic phase which served as pore agents during the preparation of PLGA microspheres. The complex depot containing porous PLGA microspheres (which were prepared by

  10. Risperidone ameliorates post-traumatic stress disorder-like symptoms in modified stress re-stress model.

    PubMed

    Krishnamurthy, Sairam; Garabadu, Debapriya; Joy, Keerikkattil P

    2013-12-01

    The management for post-traumatic stress disorder (PTSD) involves chronic administration of drugs. We have modified the stress re-stress (SRS) model to study the effect of chronic administration of risperidone (RIS) after induction of PTSD in rats. On day-1 (D-1) rats underwent training session for elevated-plus maze (EPM) test. On D-2, rats were subjected to stress protocol of 2 h restraint and 20 min forced-swim test (FST) followed by halothane anesthesia. The rats were exposed to re-stress (FST) on D-8 and at six day intervals on D-14, D-20, D-26 and D-32. The rats were treated with RIS (0.01, 0.1 and 1.0 mg/kg; p.o.) and standard drug, paroxetine (PAX; 10.0 mg/kg; p.o.) from D-8 to D-32. RIS (0.1 mg/kg) and PAX ameliorated SRS-induced immobility. RIS in median dose reversed SRS-induced hypocorticosteronemia both in urine and plasma. RIS in median dose improved SRS-induced behavioral perturbations such as memory impairment and anxiety-like behavior in EPM and Y-maze tests. RIS (0.1 mg/kg) reversed SRS-induced increase in amygdalar serotonin level. RIS (0.1 mg/kg) increased the expression of hippocampal MR thereby reversing the SRS-induced decrease in MR/GR ratio. Pearson's analysis of data on D-32 showed that there was significant correlation of plasma corticosterone, amygdalar serotonin and hippocampal ratio of mineralocorticoid (MR)/glucocorticoid receptor (GR) with SRS-induced behavioral abnormalities. Hence, median dose of RIS shows anti-PTSD-like effect in the modified SRS model. PAX had earlier onset of action in ameliorating behavioral effects of PTSD compared to RIS. However, RIS showed anti-PTSD like effect in sub-therapeutic dose. The mode of anti-PTSD action of RIS seems to involve the HPA-axis and serotonergic system, whereas PAX did not show any significant action on these pathways. The effect of repeated treatment of drugs for PTSD can be evaluated using the modified SRS model.

  11. [9-hydroxy-risperidone (9OHRIS) prevents stress-induced β-actin overexpression in rat hippocampus].

    PubMed

    Kalman, Sara; Pakaski, Magdolna; Szucs, Szabina; Kalman, Janos; Fazekas, Orsike; Santha, Petra; Szabo, Gyula; Janka, Zoltan; Kalman, Janos

    2010-09-01

    Alzheimer's disease (AD) is the most frequent form of neurodegenerative dementias. The aetiology and the exact pathomechanism of AD is not known, but stress has been considered recently in the aetiology. Beside the abnormal metabolism of the amyloid protein precursor (APP), the hyperactivity of the mitogen-activated protein kinase 1 (MAPK1) involved in the hyperphosphorylation of the tau proteins, which are considered the major component of neurofibrillary tangles, in addition to β-actin, being involved in synaptogenesis and neuronal plasticity, are all considered important contributors to the development of AD specific neuropathological changes. The chief aim of our present investigation was to examine the effect of stress on the expression of APP, MAPK1 and β-actin mRNAs in the rat hippocampus and cortex. The effect of 9-hydroxy-risperidone (9OHRIS) on the transcription of these genes was also examined. Adult, male Wistar rats were exposed to chronic immobilization stress for 3 weeks. The 9OHRIS (4 mg/bwkg) was administred by gastric tube. Four groups were formed depending on the treatment: (1) control, (2) stress, (3) 9OHRIS, (4) stress and parallel 9OHRIS treatment (n=5-6). The expression of APP, MAPK1, β-actin mRNAs from the perfused brain samples was measured with real-time PCR technique. The β-actin mRNA was significantly overexpressed in the hippocampus after 3 weeks of stress treatment. On the other hand, the stress induced hippocampal β-actin mRNA overexpression was repressed by the 9OHRIS treatment. There were no changes in the cortical or hippocampal expression of APP and MAPK1 mRNAs after neither the stress nor the 9OHRIS treatments. These results emphasize the importance of the stress induced β-actin expression in rat hippocampus. The stress induced alterations in the β-actin RNA expression could be associated with neuronal plasticity and adaptional processes, which could be modified by the 9OHRIS treatment. Our findings indicate that a second

  12. Rapid Contraceptive Uptake and Changing Method Mix With High Use of Long-Acting Reversible Contraceptives in Crisis-Affected Populations in Chad and the Democratic Republic of the Congo.

    PubMed

    Rattan, Jesse; Noznesky, Elizabeth; Curry, Dora Ward; Galavotti, Christine; Hwang, Shuyuan; Rodriguez, Mariela

    2016-08-11

    The global health community has recognized that expanding the contraceptive method mix is a programmatic imperative since (1) one-third of unintended pregnancies are due to method failure or discontinuation, and (2) the addition of a new method to the existing mix tends to increase total contraceptive use. Since July 2011, CARE has been implementing the Supporting Access to Family Planning and Post-Abortion Care (SAFPAC) initiative to increase the availability, quality, and use of contraception, with a particular focus on highly effective and long-acting reversible methods-intrauterine devices (IUDs) and implants-in crisis-affected settings in Chad and the Democratic Republic of the Congo (DRC). This initiative supports government health systems at primary and referral levels to provide a wide range of contraceptive services to people affected by conflict and/or displacement. Before the initiative, long-acting reversible methods were either unknown or unavailable in the intervention areas. However, as soon as trained providers were in place, we noted a dramatic and sustained increase in new users of all contraceptive methods, especially implants, with total new clients reaching 82,855, or 32% of the estimated number of women of reproductive age in the respective catchment areas in both countries, at the end of the fourth year. Demand for implants was very strong in the first 6 months after provider training. During this time, implants consistently accounted for more than 50% of the method mix, reaching as high as 89% in Chad and 74% in DRC. To ensure that all clients were getting the contraceptive method of their choice, we conducted a series of discussions and sought feedback from different stakeholders in order to modify program strategies. Key program modifications included more focused communication in mass media, community, and interpersonal channels about the benefits of IUDs while reinforcing the wide range of methods available and refresher training for

  13. Rapid Contraceptive Uptake and Changing Method Mix With High Use of Long-Acting Reversible Contraceptives in Crisis-Affected Populations in Chad and the Democratic Republic of the Congo.

    PubMed

    Rattan, Jesse; Noznesky, Elizabeth; Curry, Dora Ward; Galavotti, Christine; Hwang, Shuyuan; Rodriguez, Mariela

    2016-08-11

    The global health community has recognized that expanding the contraceptive method mix is a programmatic imperative since (1) one-third of unintended pregnancies are due to method failure or discontinuation, and (2) the addition of a new method to the existing mix tends to increase total contraceptive use. Since July 2011, CARE has been implementing the Supporting Access to Family Planning and Post-Abortion Care (SAFPAC) initiative to increase the availability, quality, and use of contraception, with a particular focus on highly effective and long-acting reversible methods-intrauterine devices (IUDs) and implants-in crisis-affected settings in Chad and the Democratic Republic of the Congo (DRC). This initiative supports government health systems at primary and referral levels to provide a wide range of contraceptive services to people affected by conflict and/or displacement. Before the initiative, long-acting reversible methods were either unknown or unavailable in the intervention areas. However, as soon as trained providers were in place, we noted a dramatic and sustained increase in new users of all contraceptive methods, especially implants, with total new clients reaching 82,855, or 32% of the estimated number of women of reproductive age in the respective catchment areas in both countries, at the end of the fourth year. Demand for implants was very strong in the first 6 months after provider training. During this time, implants consistently accounted for more than 50% of the method mix, reaching as high as 89% in Chad and 74% in DRC. To ensure that all clients were getting the contraceptive method of their choice, we conducted a series of discussions and sought feedback from different stakeholders in order to modify program strategies. Key program modifications included more focused communication in mass media, community, and interpersonal channels about the benefits of IUDs while reinforcing the wide range of methods available and refresher training for

  14. Rapid Contraceptive Uptake and Changing Method Mix With High Use of Long-Acting Reversible Contraceptives in Crisis-Affected Populations in Chad and the Democratic Republic of the Congo

    PubMed Central

    Rattan, Jesse; Noznesky, Elizabeth; Curry, Dora Ward; Galavotti, Christine; Hwang, Shuyuan; Rodriguez, Mariela

    2016-01-01

    ABSTRACT The global health community has recognized that expanding the contraceptive method mix is a programmatic imperative since (1) one-third of unintended pregnancies are due to method failure or discontinuation, and (2) the addition of a new method to the existing mix tends to increase total contraceptive use. Since July 2011, CARE has been implementing the Supporting Access to Family Planning and Post-Abortion Care (SAFPAC) initiative to increase the availability, quality, and use of contraception, with a particular focus on highly effective and long-acting reversible methods—intrauterine devices (IUDs) and implants—in crisis-affected settings in Chad and the Democratic Republic of the Congo (DRC). This initiative supports government health systems at primary and referral levels to provide a wide range of contraceptive services to people affected by conflict and/or displacement. Before the initiative, long-acting reversible methods were either unknown or unavailable in the intervention areas. However, as soon as trained providers were in place, we noted a dramatic and sustained increase in new users of all contraceptive methods, especially implants, with total new clients reaching 82,855, or 32% of the estimated number of women of reproductive age in the respective catchment areas in both countries, at the end of the fourth year. Demand for implants was very strong in the first 6 months after provider training. During this time, implants consistently accounted for more than 50% of the method mix, reaching as high as 89% in Chad and 74% in DRC. To ensure that all clients were getting the contraceptive method of their choice, we conducted a series of discussions and sought feedback from different stakeholders in order to modify program strategies. Key program modifications included more focused communication in mass media, community, and interpersonal channels about the benefits of IUDs while reinforcing the wide range of methods available and refresher

  15. Medullary carcinoma of the thyroid, pancreatic nesidioblastosis and microadenosis, and pancreatic polypeptide hypersecretion: a new association and clinical and hormonal responses to long-acting somatostatin analog SMS 201-995.

    PubMed

    Jerkins, T W; Sacks, H S; O'Dorisio, T M; Tuttle, S; Solomon, S S

    1987-06-01

    We describe a 63-yr-old man with disseminated medullary carcinoma of the thyroid and pancreatic nesidioblastosis and microadenosis with pancreatic polypeptide (PP) hypersecretion. His major symptoms were watery diarrhea, flushing, and abdominal bloating; these and the elevated plasma PP levels did not change after resection of the distal two thirds of the pancreas, which contained a 2-cm mass of nesidioblastotic tissue. Postoperatively, a long-acting somatostatin analog, SMS 201-995 (100 micrograms/day), normalized PP secretion acutely and chronically (7 months) and ameliorated his symptoms. The analog had no side-effects and did not alter glucose tolerance, calcitonin hypersecretion, or growth of the medullary carcinoma, but it did inhibit GH secretion. After withdrawal from therapy for 1 month, PP hypersecretion and all symptoms except diarrhea recurred. The coexistence of medullary carcinoma of the thyroid and PP cell nesidioblastosis represents a new variant of the overlap syndromes between multiple endocrine neoplasia types I and II. Patients with medullary carcinoma and unexplained watery diarrhea should have fasting gastroenteropancreatic hormone assays done to screen for a potential gastrointestinal or pancreatic origin for the diarrhea. PMID:2883196

  16. Adjunctive aripiprazole in the treatment of risperidone-induced hyperprolactinemia: A randomized, double-blind, placebo-controlled, dose-response study.

    PubMed

    Chen, Jing-Xu; Su, Yun-Ai; Bian, Qing-Tao; Wei, Li-He; Zhang, Rong-Zhen; Liu, Yan-Hong; Correll, Christoph; Soares, Jair C; Yang, Fu-De; Wang, Shao-Li; Zhang, Xiang-Yang

    2015-08-01

    Hyperprolactinemia is an unwanted adverse effect associated with several antipsychotics. The addition of partial dopamine receptor agonist aripiprazole may attenuate antipsychotic-induced hyperprolactinemia effectively. However, the ideal dosing regimen for this purpose is unknown. We aimed to evaluate the dose effects of adjunctive treatment with aripiprazole on prolactin levels and hyperprolactinemia in schizophrenia patients. Stable subjects 18-45 years old with schizophrenia and hyperprolactinemia (i.e., >24 ng/ml for females and >20 ng/ml for males) were randomly assigned to receive 8 weeks of placebo (n=30) or oral aripiprazole 5mg/day (n=30), 10mg/day (n=29), or 20mg/day (n=30) added on to fixed dose risperidone treatment. Serum prolactin levels were measured at baseline and after 2, 4 and 8 weeks; clinical symptoms and side effects were assessed at baseline and week 8 using the Positive and Negative Syndrome Scale, Clinical Global Impressions Severity scale, Barnes Akathisia Scale, Simpson-Angus Scale and UKU Side Effects Rating Scale. Of 119 randomized patients, 107 (89.9%) completed the 8-week study. At study end, all three aripiprazole doses resulted in significantly lower prolactin levels (beginning at week 2), higher response rates (≥30% prolactin reduction) and higher prolactin normalization rates than placebo. Effects were significantly greater in the 10 and 20mg/day groups than the 5mg/day group. No significant changes were observed in any treatment groups regarding psychopathology and adverse effect ratings. Adjunctive aripiprazole treatment was effective and safe for resolving risperidone-induced hyperprolactinemia, producing significant and almost maximal improvements by week 2 without significant effects on psychopathology and side effects.

  17. Adjunctive aripiprazole in the treatment of risperidone-induced hyperprolactinemia: A randomized, double-blind, placebo-controlled, dose-response study.

    PubMed

    Chen, Jing-Xu; Su, Yun-Ai; Bian, Qing-Tao; Wei, Li-He; Zhang, Rong-Zhen; Liu, Yan-Hong; Correll, Christoph; Soares, Jair C; Yang, Fu-De; Wang, Shao-Li; Zhang, Xiang-Yang

    2015-08-01

    Hyperprolactinemia is an unwanted adverse effect associated with several antipsychotics. The addition of partial dopamine receptor agonist aripiprazole may attenuate antipsychotic-induced hyperprolactinemia effectively. However, the ideal dosing regimen for this purpose is unknown. We aimed to evaluate the dose effects of adjunctive treatment with aripiprazole on prolactin levels and hyperprolactinemia in schizophrenia patients. Stable subjects 18-45 years old with schizophrenia and hyperprolactinemia (i.e., >24 ng/ml for females and >20 ng/ml for males) were randomly assigned to receive 8 weeks of placebo (n=30) or oral aripiprazole 5mg/day (n=30), 10mg/day (n=29), or 20mg/day (n=30) added on to fixed dose risperidone treatment. Serum prolactin levels were measured at baseline and after 2, 4 and 8 weeks; clinical symptoms and side effects were assessed at baseline and week 8 using the Positive and Negative Syndrome Scale, Clinical Global Impressions Severity scale, Barnes Akathisia Scale, Simpson-Angus Scale and UKU Side Effects Rating Scale. Of 119 randomized patients, 107 (89.9%) completed the 8-week study. At study end, all three aripiprazole doses resulted in significantly lower prolactin levels (beginning at week 2), higher response rates (≥30% prolactin reduction) and higher prolactin normalization rates than placebo. Effects were significantly greater in the 10 and 20mg/day groups than the 5mg/day group. No significant changes were observed in any treatment groups regarding psychopathology and adverse effect ratings. Adjunctive aripiprazole treatment was effective and safe for resolving risperidone-induced hyperprolactinemia, producing significant and almost maximal improvements by week 2 without significant effects on psychopathology and side effects. PMID:25981348

  18. Summary data of potency and parameter information from semi-mechanistic PKPD modeling of prolactin release following administration of the dopamine D2 receptor antagonists risperidone, paliperidone and remoxipride in rats.

    PubMed

    Taneja, Amit; Vermeulen, An; Huntjens, Dymphy R H; Danhof, Meindert; De Lange, Elizabeth C M; Proost, Johannes H

    2016-09-01

    We provide the reader with relevant data related to our recently published paper, comparing two mathematical models to describe prolactin turnover in rats following one or two doses of the dopamine D2 receptor antagonists risperidone, paliperidone and remoxipride, "A comparison of two semi-mechanistic models for prolactin release and prediction of receptor occupancy following administration of dopamine D2 receptor antagonists in rats" (Taneja et al., 2016) [1]. All information is tabulated. Summary level data on the in vitro potencies and the physicochemical properties is presented in Table 1. Model parameters required to explore the precursor pool model are presented in Table 2. In Table 3, estimated parameter comparisons for both models are presented, when separate potencies are estimated for risperidone and paliperidone, as compared to a common potency for both drugs. In Table 4, parameter estimates are compared when the drug effect is parameterized in terms of drug concentration or receptor occupancy. PMID:27617278

  19. Long-term treatment of central precocious puberty with a long-acting analogue of luteinizing hormone release hormone (D-Tryp6-GnRH) in monthly injections. Its possible use in normal puberty.

    PubMed

    Marcondes, J A; Abujamra, A C; Minanni, S L; Mendonca, B B; Nery, M; Lerario, A C; Pereira, M A; Abelin, N; Wajchenberg, B L

    1993-02-01

    The gonadotropin-releasing-hormone-like agonist D-Tryp6-GnRH (GnRHa) has been shown to induce reversible suppression of gonadotropins and gonadal steroids in patients with central precocious puberty. We examined the effect of a long-acting preparation of GnRHa in biodegradable microcapsules. D-Tryptophane6-GnRH, administered intramuscularly at 1 month intervals, for 12 consecutive months, on growth and skeletal maturation in 3 girls and 4 boys with neurogenic or idiopathic precocious puberty. Suppression of gonadotropin release after GnRH stimulation and gonadal steroids was maintained in all subjects. Growth velocity fell from a mean rate (+/- SEM) or 8.60 +/- 0.75 cm/year before treatment to 5.81 +/- 0.60 cm/year (p < 0.005) after 1 year. Bone age advanced a mean of 8.0 +/- 0.45 months during treatment, suggesting an increase in predicted height from the ratio delta bone age/delta chronological age. Two subjects, one of them with compensated Bartter's syndrome with normal hypothalamic pituitary-gonadal-axis, received the analogue to delay pubertal growth with the hope to improve final height. In the first one, the growth velocity fell from 9.9 cm/year to 8 cm/year and delta bone age/delta chronological age decreased from 1.28 to 1.0 and in the other subject, the growth velocity fell from 12 cm/year to 6.0 cm/year in the last year of treatment and delta bone age/delta chronological age fell from 3.2 to 0.75, indicating an improvement in predicted height.

  20. A cross-sectional study of the identification of prevalent asthma and chronic obstructive pulmonary disease among initiators of long-acting β-agonists in health insurance claims data

    PubMed Central

    2014-01-01

    Background Claims data are potentially useful for identifying long-acting β-agonist (LABA) use by patients with asthma, a practice that is associated with increased mortality. We evaluated the accuracy of claims data for classifying prevalent asthma and chronic obstructive pulmonary disease (COPD) among initiators of LABAs. Methods This study included adult LABA initiators during 2005–2008 in a US commercial health plan. Diagnosis codes from the 6 months before LABA initiation identified potential asthma or COPD and a physician adjudicated case status using abstracted medical records. We estimated the positive predictive value (PPV) and 95% confidence intervals (CI) of covariate patterns for identifying asthma and COPD. Results We sought 520 medical records at random from 225,079 LABA initiators and received 370 (71%). The PPV for at least one asthma claim was 74% (CI 63–82), and decreased as age increased. Having at least one COPD claim resulted in a PPV of 82% (CI 72–89), and of over 90% among older patients, men, and recipients of inhaled anticholinergic drugs. Only 2% (CI 0.2–7.6) of patients with a claim for COPD alone were found to have both COPD and asthma, while 9% (CI 4–16) had asthma only. Twenty-one percent (CI 14–30) of patients with claims for both diagnoses had both conditions. Among patients with no asthma or COPD claims, 62% (CI 50–72) had no confirmed diagnosis and 29% (CI 19–39) had confirmed asthma. Conclusions Subsets of patients with asthma, COPD, and both conditions can be identified and differentiated using claims data, although categorization of the remaining patients is infeasible. Safety surveillance for off-label use of LABAs must account for this limitation. PMID:24645984

  1. Familiarity with and Preferences for Oral and Long-Acting Injectable HIV Pre-exposure Prophylaxis (PrEP) in a National Sample of Gay and Bisexual Men in the U.S.

    PubMed

    Parsons, Jeffrey T; Rendina, H Jonathon; Whitfield, Thomas H F; Grov, Christian

    2016-07-01

    We sought to determine preferences for oral versus long-acting injectable (LAI) PrEP among gay and bisexual men (GBM). We surveyed a national U.S. sample of 1071 GBM about forms of PrEP. LAI PrEP was found to be acceptable among 43.2 % of men when injected monthly compared with 53.6 % of men when injected every 3 months. When asked to choose between forms of PrEP, 46.0 % preferred LAI, 14.3 % oral, 21.7 % whichever was most effective, 10.1 % had no preference, and 7.8 % would not take PrEP. There were no differences in PrEP preferences by race/ethnicity, income, region of residence, or relationship status. Those unwilling to take PrEP were significantly older than those who preferred LAI PrEP and those who would take either. Those who preferred the most effective form were younger, had less education, and reported more recent club drug use. Those who reported condomless anal sex and those who thought they were good PrEP candidates were more willing to take PrEP. Long-term health and side effects were of the greatest concern for both LAI and oral PrEP. The availability of LAI PrEP has the potential to increase uptake among GBM. The results of ongoing clinical trials of LAI PrEP will need to demonstrate similar or greater efficacy as daily Truvada for uptake to be maximized.

  2. Bronchial reversibility with a short-acting β2-agonist predicts the FEV1 response to administration of a long-acting β2-agonist with inhaled corticosteroids in patients with bronchial asthma.

    PubMed

    Ohwada, Akihiko; Inami, Kei; Onuma, Emi; Matsumoto-Yamazaki, Mariko; Atsuta, Ryo; Takahashi, Kazuhisa

    2011-07-01

    A long-acting β2-agonist (LABA) combined with an inhaled corticosteroid (ICS) is frequently prescribed as initial therapy in steroid-naïve asthma patients because of its effective control of symptoms and improvement of pulmonary function. However, it is unclear which patients will be responsive to LABAs and whether bronchial responsiveness to LABAs is similar to that to short-acting β2-agonists (SABAs) in a clinical setting. Therefore, the goal of the present study was to compare the changes in spirometric parameters after SABA (salbutamol) inhalation to those after 1-month LABA/ICS (salmeterol/fluticasone propionate) therapy. Spirometric changes were evaluated as absolute values, as the percentage of predicted normal values and as the percentage of baseline values after salbutamol inhalation or 1-month LABA/ICS therapy in 45 patients with asthma. Compared to SABA inhalation, LABA/ICS therapy produced significant improvements in forced expiratory volume in 1 sec (FEV1), peak expiratory flow (PEF), forced expiratory flow at 50% of vital capacity expired (FEF50%) from baseline (expressed as the percentage predicted) in all patients. FEV1 and the FEV1/forced vital capacity (FVC) ratio after SABA or LABA/ICS therapy were inversely related to the corresponding baseline values. Analysis of spirometric changes after SABA inhalation showed that FEV1 was the best among spirometric parameters, such as PEF, correlated with responsiveness to LABA/ICS therapy. Reversibility of FEV1 with SABA inhalation predicts the spirometric response to LABA/ICS as initial therapy in patients with bronchial asthma. LABA/ICS therapy had a greater effect on bronchial reversibility in asthmatic patients, compared to SABA inhalation. This suggested that evaluation of bronchial reversibility after LABA/ICS therapy would be superior to that after SABA inhalation.

  3. Can asthma treatment in sports be doping? The effect of the rapid onset, long-acting inhaled beta2-agonist formoterol upon endurance performance in healthy well-trained athletes.

    PubMed

    Carlsen, K H; Hem, E; Stensrud, T; Held, T; Herland, K; Mowinckel, P

    2001-07-01

    Inhaled beta2-agonists have been subject to restrictions in relationship to sports due to fear of possible improvement in endurance performance. According to the international doping regulations only inhaled salbutamol, terbutaline and salmeterol are allowed for use in sports. Formoterol is a recently introduced rapid onset-long-acting inhaled beta2-agonist. The main aim of the present randomized, double-blind placebo-controlled study was to investigate possible improvement in endurance performance of inhaled formoterol in 24 healthy well-trained competitive male athletes, 21-29 years old. Lung function (flow-volume loops) was measured before, 15 min after each inhaled study drug and before and repeatedly after exercise. On day 1, maximum oxygen uptake (VO2max), peak ventilation (VEpeak) and running time till exhaustion were measured and used to determine the exercise load on days 2 and 3. On days 2 and 3 the subjects inhaled the study drugs, rested for 1 h, then exercised, and VO2max, VEpeak and running time until exhaustion were determined. Inhaled formoterol did not improve any parameter of endurance performance. On the other hand a statistically significant, although not clinically significant (0.05 ml(-1) min kg(-1)), change was found in estimated difference of VO2max between formoterol and placebo in favour of placebo. Lung function increased significantly after inhaled formoterol, and after exercise also for placebo, but without differences between the beta2-agonist and placebo after exercise. In conclusion, inhaled formoterol did not improve endurance performance compared to placebo.

  4. A long-acting β2-adrenergic agonist increases the expression of muscarine cholinergic subtype-3 receptors by activating the β2-adrenoceptor cyclic adenosine monophosphate signaling pathway in airway smooth muscle cells

    PubMed Central

    LIU, YUAN-HUA; WU, SONG-ZE; WANG, GANG; HUANG, NI-WEN; LIU, CHUN-TAO

    2015-01-01

    The persistent administration of β2-adrenergic (β2AR) agonists has been demonstrated to increase the risk of severe asthma, partly due to the induction of tolerance to bronchoprotection via undefined mechanisms. The present study investigated the potential effect of the long-acting β2-adrenergic agonist, formoterol, on the expression of muscarinic M3 receptor (M3R) in rat airway smooth muscle cells (ASMCs). Primary rat ASMCs were isolated and characterized following immunostaining with anti-α-smooth muscle actin antibodies. The protein expression levels of M3R and phospholipase C-β1 (PLCβ1) were characterized by western blot analysis and the production of inositol 1,4,5-trisphosphate (IP3) was determined using an enzyme-linked immunosorbent assay. Formoterol increased the protein expression of M3R in rat ASMCs in a time- and dose-dependent manner, which was significantly inhibited by the β2AR antagonist, ICI118,551 and the cyclic adenosine monophosphate (cAMP) inhibitor, SQ22,536. The increased protein expression of M3R was positively correlated with increased production of PLCβ1 and IP3. Furthermore, treatment with the glucocorticoid, budesonide, and the PLC inhibitor, U73,122, significantly suppressed the formoterol-induced upregulated protein expression levels of M3R and PLCβ1 and production of IP3. The present study demonstrated that formoterol mediated the upregulation of M3R in the rat ASMCs by activating the β2AR-cAMP signaling pathway, resulting in increased expression levels of PLCβ1 and IP3, which are key to inducing bronchoprotection tolerance. Administration of glucocorticoids or a PLC antagonist prevented formoterol-induced bronchoprotection tolerance by suppressing the protein expression of M3R. PMID:25672589

  5. Darbepoetin alpha, a long-acting erythropoeitin derivate, does not alter LPS evoked myocardial depression and gene expression of Bax, Bcl-Xs, Bcl-XL, Bcl-2, and TNF-alpha.

    PubMed

    Brendt, Peter; Frey, Ulrich; Adamzik, Michael; Schäfer, Simon T; Peters, Jürgen

    2009-01-01

    Darbepoetin alpha (DA), a long-acting erythropoietin derivative stimulating erythropoiesis, can, by antiapoptotic effects, mitigate myocardial I/R injury. We tested the hypothesis that DA treatment improves left ventricular function (LV) in LPS evoked cardiomyopathy and alters gene expression of apoptosis-regulating proteins (Bcl-XL, Bcl-2, Bax, and Bcl-Xs) and TNF-alpha. In a prospective, controlled, randomized study in Lewis rats (n = 56; 8 groups), myocardial depression was evoked by LPS administration (serotype O127:B8; 10 mg/kg, i.p.). Darbepoetin alpha or vehicle was injected either 24 h before (pretreatment) or 2 h after LPS injection (treatment). Hearts were isolated 8 h after LPS injection, perfused (Krebs-Henseleit solution) in a Langendorff apparatus, and LV developed pressure and its derivatives were measured. For gene expression analysis, real-time polymerase chain reaction of LV specimen was performed. LPS decreased LV developed pressure (-64.6 +/- 7.9 mmHg) and its derivates by more than 60% in comparison to vehicle (P < 0,01), but this effect was not attenuated by DA pretreatment or DA treatment. LPS administration increased gene expression of Bcl-Xs, Bax, and TNF-alpha, but this was not altered by DA pretreatment. Furthermore, there was no effect on Bcl-Xl and Bcl-2 expression by DA alone. Whereas proapoptotic genes of the myocardium are up-regulated in LPS-induced cardiomyopathy, neither DA pretreatment nor treatment has significant effects on LV function or gene expression. This may suggest cardiac resistance to darbepoetin in LPS-mediated sepsis.

  6. Pharmacological studies of N-(2,5-dimethyl-1H-pyrrol-1-yl)-6-(4-morpholinyl)-3-pyridazinamine hydrochloride (MDL-899), a new long-acting antihypertensive vasodilator.

    PubMed

    Baldoli, E; Bianchi, G; Corsico, N; Di Francesco, G F

    1985-01-01

    N-(2,5-Dimethyl-1H-pyrrol-1-yl)-6-(4-morpholinyl)-3-pyridazinamine hydrochloride (MDL-899) is a new long-acting antihypertensive vasodilator which reduces the blood pressure of conscious hypertensive rats and dogs to normal levels. The oral doses that reduce blood pressure by 50 mmHg are: 4.4 mg/kg in conscious spontaneously hypertensive rats (SHR), 18 mg/kg in conscious Milan hypertensive strain (MHS) and 1.7 mg/kg in conscious renal hypertensive dog (RHD). The i.v. doses are 1.26, 3.2 and 0.9 mg/kg. The reduction in blood pressure is slow (peak effect at 3 h) and long-lasting (more than 7 h) after p.o. or i.v. administration. Tolerance to MDL-899 is seen to develop in hypertensive dogs, whereas in hypertensive rats this phenomenon never occurs. The compound antagonizes the development of hypertension when given to SHR between days 25 and 88. The haemodynamic study in conscious normotensive rats (labelled microspheres) demonstrated that the fall in blood pressure is accompanied by increases in heart rate and cardiac output and a decrease in total peripheral resistance. The lack of alpha-blocking activity, in the rat caudal artery "in vitro"; beta 2-stimulating activity, in SHR pretreated with propranolol, and prostaglandin (PG) release activity, in SHR pretreated with indomethacin, excludes the possibility that the hypotension is due to one of these mechanisms. MDL-899 given orally to rats has no important depressant effects on the CNS at hypotensive or higher doses and induces no adrenergic system stimulation symptoms (midriasis, exophthalmus). In comparison with hydralazine, it is slower in onset and longer lasting, devoid of adrenergic system stimulation, less toxic and nonmutagenic. They are equipotent after p.o. treatment. PMID:2862874

  7. Differential long-term effects of haloperidol and risperidone on the acquisition and performance of tasks of spatial working and short-term memory and sustained attention in rats.

    PubMed

    Hutchings, Elizabeth J; Waller, Jennifer L; Terry, Alvin V

    2013-12-01

    A common feature of the neuropsychiatric disorders for which antipsychotic drugs are prescribed is cognitive dysfunction, yet the effects of long-term antipsychotic treatment on cognition are largely unknown. In the current study, we evaluated the effects of long-term oral treatment with the first-generation antipsychotic haloperidol (1.0 and 2.0 mg/kg daily) and the second-generation antipsychotic risperidone (1.25 and 2.5 mg/kg daily) on the acquisition and performance of two radial-arm maze (RAM) tasks and a five-choice serial reaction-time task (5C-SRTT) in rats during days 15-60 and 84-320 days of treatment, respectively. In the RAM, neither antipsychotic significantly affected the acquisition or performance of a spatial win shift or a delayed non-match-to-position task. Conversely, in the rats administered 5C-SRTT, haloperidol was associated with profound deficits in performance, and the subjects were not able to progress through all stages of task acquisition. Depending on the dose, risperidone was associated with a greater number of trials to meet specific performance criteria during task acquisition compared with vehicle-treated controls; however, most subjects were eventually able to achieve all levels of task acquisition. Both haloperidol and risperidone also increased the number of perseverative and time-out responses during certain stages of task acquisition, and the response and reward latencies were slightly higher than controls during several stages of the study. These results in rats suggest that while long-term treatment with haloperidol or risperidone may not significantly affect spatial working or short-term memory, both antipsychotics can (depending on dose) impair sustained attention, decrease psychomotor speed, increase compulsive-type behaviors, and impair cognitive flexibility. PMID:24042161

  8. A blinded evaluation of the efficacy and safety of glycopyrronium, a once-daily long-acting muscarinic antagonist, versus tiotropium, in patients with COPD: the GLOW5 study

    PubMed Central

    2014-01-01

    Background Two once-daily long-acting muscarinic antagonists (LAMAs) are currently available for the treatment of chronic obstructive pulmonary disease (COPD) – tiotropium and glycopyrronium. Previous studies have compared glycopyrronium with open-label tiotropium. In the GLOW5 study, we compare glycopyrronium with blinded tiotropium. Methods In this blinded, double-dummy, parallel group, 12-week study, patients with moderate-to-severe COPD were randomized 1:1 to glycopyrronium 50 μg once daily or tiotropium 18 μg once daily. The primary objective was to demonstrate the non-inferiority of glycopyrronium versus blinded tiotropium with respect to trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment (non-inferiority margin: –50 mL). Secondary objectives were to evaluate glycopyrronium versus tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea Index; TDI), health status (St George’s Respiratory Questionnaire; SGRQ), daily rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of treatment. Results 657 patients were randomized (glycopyrronium: 327; tiotropium: 330); 96% (630 patients) completed the study. Least squares mean trough FEV1 for both glycopyrronium and tiotropium was 1.405 L at Week 12, meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95% CI: –32, 31 mL). Glycopyrronium demonstrated rapid bronchodilation following first dose on Day 1, with significantly higher FEV1 at all time points from 0–4 h post-dose versus tiotropium (all p < 0.001). FEV1 area under the curve from 0–4 h (AUC0–4h) post-dose with glycopyrronium was significantly superior to tiotropium on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12. Glycopyrronium demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total score, rescue medication use and the rate of COPD exacerbations (all p = not significant). Patients on

  9. The Mayer Hashi Large-Scale Program to Increase Use of Long-Acting Reversible Contraceptives and Permanent Methods in Bangladesh: Explaining the Disappointing Results. An Outcome and Process Evaluation

    PubMed Central

    Rahman, Mizanur; Haider, M Moinuddin; Curtis, Sian L; Lance, Peter M

    2016-01-01

    ABSTRACT Background: Bangladesh has achieved a low total fertility rate of 2.3. Two-thirds of currently married women of reproductive age (CMWRA) want to limit fertility, and many women achieve their desired fertility before age 30. The incidence of unintended pregnancy and pregnancy termination is high, however. Long-acting reversible contraceptives (LARCs), consisting of the intrauterine device and implant, and permanent methods (PM), including female sterilization and vasectomy, offer several advantages in this situation, but only 8% of CMWRA or 13% of method users use these methods. Program: The Mayer Hashi (MH) program (2009–2013) aimed to improve access to and the quality of LARC/PM services in 21 of the 64 districts in Bangladesh. It was grounded in the SEED (supply–enabling environment–demand) Programming Model. Supply improvements addressed provider knowledge and skills, system strengthening, and logistics. Creating an enabling environment involved holding workshops with local and community leaders, including religious leaders, to encourage them to help promote demand for LARCs and PMs and overcome cultural barriers. Demand promotion encompassed training of providers in counseling, distribution of behavior change communication materials in the community and in facilities, and community mobilization. Methods: We selected 6 MH program districts and 3 nonprogram districts to evaluate the program. We used a before–after and intervention–comparison design to measure the changes in key contraceptive behavior outcomes, and we used a difference-in-differences (DID) specification with comparison to the nonprogram districts to capture the impact of the program. In addition to the outcome evaluation, we considered intermediate indicators that measured the processes through which the interventions were expected to affect the use of LARCs and PMs. Results: The use of LARCs/PMs among CMWRA increased between 2010 and 2013 in both program (from 5.3% to 7.5%) and

  10. The in vivo efficacy and side effect pharmacology of GS-5759, a novel bifunctional phosphodiesterase 4 inhibitor and long-acting β 2-adrenoceptor agonist in preclinical animal species.

    PubMed

    Salmon, Michael; Tannheimer, Stacey L; Gentzler, Terry T; Cui, Zhi-Hua; Sorensen, Eric A; Hartsough, Kimberly C; Kim, Musong; Purvis, Lafe J; Barrett, Edward G; McDonald, Jacob D; Rudolph, Karin; Doyle-Eisele, Melanie; Kuehl, Philip J; Royer, Christopher M; Baker, William R; Phillips, Gary B; Wright, Clifford D

    2014-08-01

    Bronchodilators are a central therapy for symptom relief in respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma, with inhaled β 2-adrenoceptor agonists and anticholinergics being the primary treatments available. The present studies evaluated the in vivo pharmacology of (R)-6-[[3-[[4-[5-[[2-Hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino]pent-1-ynyl]phenyl]carbamoyl]phenyl]sulfonyl]-4-[(3-methoxyphenyl)amino]-8-methylquinoline-3-carboxamide (GS-5759), a novel bifunctional compound with both phosphodiesterase 4 (PDE4) inhibitor and long-acting β 2-adrenoceptor agonist (LABA) activity, which has been optimized for inhalation delivery. GS-5759 dose-dependently inhibited pulmonary neutrophilia in a lipopolysaccharide (LPS) aerosol challenge model of inflammation in rats with an ED50 ≤ 10 μg/kg. GS-5759 was also a potent bronchodilator with an ED50 of 0.09 μg/kg in guinea pigs and 3.4 μg/kg in dogs after methylcholine (MCh) and ragweed challenges respectively. In cynomolgus monkeys, GS-5759 was dosed as a fine-particle dry powder and was efficacious in the same dose range in both MCh and LPS challenge models, with an ED50 = 70 μg/kg for bronchodilation and ED50 = 4.9 μg/kg for inhibition of LPS-induced pulmonary neutrophilia. In models to determine therapeutic index (T.I.), efficacy for bronchodilation was evaluated against increased heart rate and GS-5759 had a T.I. of 700 in guinea pigs and >31 in dogs. In a ferret model of emesis, no emesis was seen at doses several orders of magnitude greater than the ED50 observed in the rat LPS inflammation model. GS-5759 is a bifunctional molecule developed for the treatment of COPD, which has both bronchodilator and anti-inflammatory activity and has the potential for combination as a triple therapy with a second compound, within a single inhalation device.

  11. A pilot double-blind placebo-controlled trial of pioglitazone as adjunctive treatment to risperidone: Effects on aberrant behavior in children with autism.

    PubMed

    Ghaleiha, Ali; Rasa, Soudeh Mohebbi; Nikoo, Mohammadali; Farokhnia, Mehdi; Mohammadi, Mohammad-Reza; Akhondzadeh, Shahin

    2015-09-30

    To assess the safety and efficacy of pioglitazone added to risperidone in the treatment of irritability in autistic disorder (AD), we conducted this study. In a 10-week, randomized, double-blind, parallel-group, placebo-controlled clinical trial, 44 outpatients of both genders aged 4-12 years with a diagnosis of AD and a score of ≥12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale were included. Mean change of ABC-C irritability subscale score as primary outcome, change in other ABC-C subscale scores and partial and complete responses were compared between two groups. Twenty patients completed the trial in each group. Level of reduction and effect of time×treatment interaction in the treatment group were significant for irritability (P=0.03), lethargy/social withdrawal (P=0.04) and hyperactivity/non-compliance (P=0.03) but not for stereotypic behavior and inappropriate speech subscales compared with the placebo group. Vomiting and headache were the most frequent reported side-effects. Results of this preliminary study indicate positive effects of pioglitazone compared with placebo in improving the behavioral symptoms of AD.

  12. Use of the second-generation antipsychotic, risperidone, and secondary weight gain are associated with an altered gut microbiota in children

    PubMed Central

    Bahr, S M; Tyler, B C; Wooldridge, N; Butcher, B D; Burns, T L; Teesch, L M; Oltman, C L; Azcarate-Peril, M A; Kirby, J R; Calarge, C A

    2015-01-01

    The atypical antipsychotic risperidone (RSP) is often associated with weight gain and cardiometabolic side effects. The mechanisms for these adverse events are poorly understood and, undoubtedly, multifactorial in etiology. In light of growing evidence implicating the gut microbiome in the host's energy regulation and in xenobiotic metabolism, we hypothesized that RSP treatment would be associated with changes in the gut microbiome in children and adolescents. Thus, the impact of chronic (>12 months) and short-term use of RSP on the gut microbiome of pediatric psychiatrically ill male participants was examined in a cross-sectional and prospective (up to 10 months) design, respectively. Chronic treatment with RSP was associated with an increase in body mass index (BMI) and a significantly lower ratio of Bacteroidetes:Firmicutes as compared with antipsychotic-naïve psychiatric controls (ratio=0.15 vs 1.24, respectively; P<0.05). Furthermore, a longitudinal observation, beginning shortly after onset of RSP treatment, revealed a gradual decrease in the Bacteroidetes:Firmicutes ratio over the ensuing months of treatment, in association with BMI gain. Lastly, metagenomic analyses were performed based on extrapolation from 16S ribosomal RNA data using the software package, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Those data indicate that gut microbiota dominating the RSP-treated participants are enriched for pathways that have been implicated in weight gain, such as short-chain fatty acid production. PMID:26440540

  13. Concurrent determination of olanzapine, risperidone and 9-hydroxyrisperidone in human plasma by ultra performance liquid chromatography with diode array detection method: application to pharmacokinetic study.

    PubMed

    Siva Selva Kumar, M; Ramanathan, M

    2016-02-01

    A simple and sensitive ultra-performance liquid chromatography (UPLC) method has been developed and validated for simultaneous estimation of olanzapine (OLZ), risperidone (RIS) and 9-hydroxyrisperidone (9-OHRIS) in human plasma in vitro. The sample preparation was performed by simple liquid-liquid extraction technique. The analytes were chromatographed on a Waters Acquity H class UPLC system using isocratic mobile phase conditions at a flow rate of 0.3 mL/min and Acquity UPLC BEH shield RP18 column maintained at 40°C. Quantification was performed on a photodiode array detector set at 277 nm and clozapine was used as internal standard (IS). OLZ, RIS, 9-OHRIS and IS retention times were found to be 0.9, 1.4, .1.8 and 3.1 min, respectively, and the total run time was 4 min. The method was validated for selectivity, specificity, recovery, linearity, accuracy, precision and sample stability. The calibration curve was linear over the concentration range 1-100 ng/mL for OLZ, RIS and 9-OHRIS. Intra- and inter-day precisions for OLZ, RIS and 9-OHRIS were found to be good with the coefficient of variation <6.96%, and the accuracy ranging from 97.55 to 105.41%, in human plasma. The validated UPLC method was successfully applied to the pharmacokinetic study of RIS and 9-OHRIS in human plasma.

  14. Regulation of P-glycoprotein expression in brain capillaries in Huntington's disease and its impact on brain availability of antipsychotic agents risperidone and paliperidone.

    PubMed

    Kao, Yu-Han; Chern, Yijuang; Yang, Hui-Ting; Chen, Hui-Mei; Lin, Chun-Jung

    2016-08-01

    Huntington's disease (HD) is a neurodegenerative disease marked by an expanded polyglutamine (polyQ) tract on the huntingtin (HTT) protein that may cause transcriptional dysfunction. This study aimed to investigate the regulation and function of P-glycoprotein, an important efflux transporter, in brain capillaries in HD. The results showed that, compared with the littermate controls, R6/2 HD transgenic mice with the human mutant HTT gene had higher levels of P-glycoprotein mRNA and protein and enhanced NF-κB activity in their brain capillaries. Higher P-glycoprotein expression was also observed in the brain capillaries of human HD patients. Consistent with this enhanced P-glycoprotein expression, brain extracellular levels and brain-to-plasma ratios of the antipsychotic agents risperidone and paliperidone were significantly lower in R6/2 mice than in their littermate controls. Exogenous expression of human mutant HTT protein with expanded polyQ (mHTT-109Q) in HEK293T cells enhanced the levels of P-glycoprotein transcripts and NF-κB activity compared with cells expressing normal HTT-25Q. Treatment with the IKK inhibitor, BMS-345541, decreased P-glycoprotein mRNA level in cells transfected with mHTT-109Q or normal HTT-25Q In conclusion, mutant HTT altered the expression of P-glycoprotein through the NF-κB pathway in brain capillaries in HD and markedly affected the availability of P-glycoprotein substrates in the brain.

  15. Short-term Effects of Risperidone Monotherapy on Spontaneous Brain Activity in First-episode Treatment-naïve Schizophrenia Patients: A Longitudinal fMRI Study

    PubMed Central

    Hu, Mao-Lin; Zong, Xiao-Fen; Zheng, Jun-Jie; Pantazatos, Spiro P.; Miller, Jeffrey M.; Li, Zong-Chang; Liao, Yan-Hui; He, Ying; Zhou, Jun; Sang, De-En; Zhao, Hong-Zeng; Lv, Lu-Xian; Tang, Jin-Song; Mann, J. John; Chen, Xiao-Gang

    2016-01-01

    It is unclear whether abnormal spontaneous neural activation patterns found in chronic schizophrenia patients (CSP) are part of the pathogenesis of disease, consequences of chronic illness, or effects of antipsychotic treatment. We performed a longitudinal resting-state functional magnetic resonance imaging (fMRI) study in 42 treatment-naïve first-episode schizophrenia patients (FESP) at baseline and then after 8-weeks of risperidone monotherapy, and compared the findings to 38 healthy volunteers. Spontaneous brain activity was quantified using the fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) and compared between patients and controls. Pretreatment, patients exhibited higher fALFF in left caudate compared with controls. After treatment, patients had elevated fALFF in bilateral putamen and right caudate, and increased ReHo in right caudate and left putamen. Greater increase of fALFF in the left putamen correlated with less improvement in positive symptoms. Thus, abnormalities of spontaneous neural activity in chronic schizophrenia is at least partly due to a medication effect. The observed post-treatment increase in striatal intrinsic activity may reflect counter-therapeutic functional adaptation to dopamine D2 receptor occupancy required for medication effects on psychosis. PMID:27698361

  16. High performance liquid chromatographic and thin layer densitometric methods for the determination of risperidone in the presence of its degradation products in bulk powder and in tablets.

    PubMed

    El-Sherif, Zeinab A; El-Zeany, Badr; El-Houssini, Ola M

    2005-01-01

    Two reproducible stability indicating methods were developed for the determination of risperidone (RISP) in presence of its degradation products in pure form and in tablets. The first method was based on reversed phase high performance liquid chromatography (HPLC), on Lichrosorb RP C 18 column (250 mm i.d., 4 mm, 10 microm), using methanol:0.05 M potassium dihydrogen phosphate pH 7 (65:35 (v/v)) as the mobile phase at a flow rate of 1 ml min(-1) at ambient temperature. Quantification was achieved with UV detection at 280 nm over a concentration range of 25-500 microg ml(-1) with mean percentage recovery of 99.87 +/- 1.049. The method retained its accuracy in the presence of up to 90% of RISP degradation products. The second method was based on TLC separation of RISP from its degradation products followed by densitometric measurement of the intact drug spot at 280 nm. The separation was carried out on aluminum sheet of silica gel 60F254 using acetonitrile:methanol:propanol:triethanolamine (8.5:1.2:0.6:0.2 (v/v/v/v)), as the mobile phase, over a concentration range of 2-10 microg per spot and mean percentage recovery of 100.1 +/- 1.18. The two methods were simple, precise, sensitive and could be successfully applied for the determination of pure, laboratory prepared mixtures and tablets. The results obtained were compared with the manufacturer's method.

  17. Comparing Effectiveness of Active and Passive Client Follow-Up Approaches in Sustaining the Continued Use of Long Acting Reversible Contraceptives (LARC) in Rural Punjab: A Multicentre, Non-Inferiority Trial

    PubMed Central

    Hameed, Waqas; Azmat, Syed Khurram; Ali, Moazzam; Ishaque, Muhammad; Abbas, Ghazunfer; Munroe, Erik; Harrison, Rebecca; Shamsi, Wajahat Hussain; Mustafa, Ghulam; Khan, Omar Farooq; Ali, Safdar; Ahmed, Aftab

    2016-01-01

    Background The use of long-acting reversible contraceptive (LARC) methods is very low in Pakistan with high discontinuation rates mainly attributed to method-related side effects. Mixed evidence is available on the effectiveness of different client follow-up approaches used to ensure method continuation. We compared the effectiveness of active and passive follow-up approaches in sustaining the use of LARC—and within ‘active’ follow-up, we further compared a telephone versus home-based approach in rural Punjab, Pakistan. Methods This was a 12-month multicentre non-inferiority trial conducted in twenty-two (16 rural- and 6 urban-based) franchised reproductive healthcare facilities in district Chakwal of Punjab province, between November 2013 and December 2014. The study comprised of three groups of LARC clients: a) home-based follow-up, b) telephone-based follow-up, and c) passive or needs-based follow-up. Participants in the first two study groups received counselling on scheduled follow-up from the field workers at 1, 3, 6, 9, and 12 month post-insertion whereas participants in the third group were asked to contact the health facility if in need of medical assistance relating to LARC method use. Study participants were recruited with equal allocation to each study group, but participants were not randomized. The analyses are based on 1,246 LARC (intra-uterine contraceptive device and implant) users that completed approximately 12-months of follow-up. The non-inferiority margin was kept at five percentage points for the comparison of active and passive follow-up and six percentage points for telephone and home-based approach. The primary outcome was cumulative probability of method continuation at 12-month among LARC users. Results Women recruited in home-based, telephone-based, and passive groups were 400, 419 and 427, respectively. The cumulative probability of LARC continuation at 12 month was 87.6% (95% CI 83.8 to 90.6) among women who received home

  18. Risperidone-induced inactivation and clozapine-induced reactivation of rat cortical astrocyte 5-hydroxytryptamine₇ receptors: evidence for in situ G protein-coupled receptor homodimer protomer cross-talk.

    PubMed

    Smith, Carol; Toohey, Nicole; Knight, Jessica A; Klein, Michael T; Teitler, Milt

    2011-02-01

    We have reported previously novel drug-induced inactivation and reactivation of human 5-hydroxytryptamine₇ (5-HT₇) receptors in a recombinant cell line. To explain these novel observations, a homodimer structure displaying protomer-protomer cross-talk was proposed. To determine whether these novel observations and interpretations are due to an artifactual G protein-coupled receptor (GPCR) mechanism unique to the recombinant cell line, we explored the properties of r5-HT₇ receptors expressed by cortical astrocytes in primary culture. As in the recombinant cell line, risperidone, 9-OH-risperidone, methiothepin, and bromocriptine were found to potently inactivate r5-HT₇ receptors. As in the recombinant cell line, exposure of risperidone-inactivated astrocyte r5-HT₇ receptors to competitive antagonists resulted in the reactivation of r5-HT₇ receptors. The potencies of the reactivating drugs closely correlated with their affinities for h5-HT₇ receptors. These results indicate the novel inactivating and reactivating property of drugs is not due to an artifact of the recombinant cell line expressing h5-HT₇ receptors but is an intrinsic property of 5-HT₇ receptors in vitro and ex vivo. This evidence suggests that a native (nonmutated) GPCR, in its native membrane environment (cortical astrocyte primary culture), can function as a homodimer with protomer-protomer cross-talk. Homodimers may be a common GPCR structure. The experimental design used in our studies can be used to explore the properties of other GPCRs in their native forms in recombinant cells, primary cultures expressing the endogenous GPCRs, and possibly in vivo. The homodimer structure and protomer-protomer cross-talk offer new avenues of research into receptor dysfunction in disease states and the development of novel drugs. PMID:21062995

  19. Nicotine and clozapine selectively reverse a PCP-induced deficit of PPI in BALB/cByJ but not NMRI mice: comparison with risperidone.

    PubMed

    Andreasen, J T; Andersen, K K; Nielsen, E Ø; Mathiasen, L; Mirza, N R

    2006-02-15

    Schizophrenic patients have deficits in prepulse inhibition (PPI) that may be alleviated by smoking/nicotine. The effect of nicotinic agents on PPI in rodents is equivocal and few studies in mice have been reported. Thus, we assessed nicotine's (0.03-1mg/kg) effect on PPI in five mouse strains with no effects. We next determined if nicotine would reverse a phencyclidine (PCP)-induced deficit of PPI in BALB/cByJ and NMRI mice. BALB/cByJ mice have a low density of [(125)I]alpha-bungaratoxin binding in the hippocampus and poor inhibitory gating of auditory evoked potentials (AEPs), a model related to PPI. At 1mg/kg, nicotine selectively reversed the PCP-induced deficit of PPI in BALB/cByJ mice. The pharmacokinetic profile of nicotine (T(1/2), C(max), T(max) and AUC) was identical in both strains, obviating this as a factor for the strain-dependent effect observed. Moreover, 1mg/kg nicotine inhibited in vivo [(3)H]epibatidine binding with the same time-course in both strains, indicating no difference in brain "kinetics". Since high doses of nicotine were effective in BALB/cByJ mice a role for low-affinity nicotinic receptors, e.g. alpha(7) receptors, is plausible. Clozapine, but not risperidone, also only reversed the PCP deficit of PPI in BALB/cByJ. Clozapine and nicotine also enhance inhibitory gating of AEPs in DBA/2 mice, and clozapine's effect is antagonized by an alpha(7) antagonist. Our data and previous evidence possibly suggest a role for low-affinity nicotinic receptors in the effects of clozapine and nicotine. Furthermore, BALB/cByJ mice may represent a model to test the effects of nicotinic agents acting at low-affinity nicotinic receptors.

  20. Negative Correlation between Serum S100B and Leptin Levels in Schizophrenic Patients During Treatment with Clozapine and Risperidone: Preliminary Evidence

    PubMed Central

    Hendouei, Narjes; Hosseini, Seyed Hamzeh; Panahi, Amin; Khazaeipour, Zahra; Barari, Fatemeh; Sahebnasagh, Adeleh; Ala, Shahram

    2016-01-01

    Recently, extensive efforts have been made to understand the rate of energy expenditure and the weight gain associated with atypical antipsychotic treatment, including identification of markers of obesity risk. In recent years, leptin, an adipocyte hormone, has gained significant interest in psychiatric disorders. S100B has been considered as a surrogate marker for astrocyte-specific damage in neurologic disorders. Also, S100B has been detected in adipose with concentration as high as nervous tissue as a second release source. In this study we evaluated the relationship between S100B and leptin in schizophrenic patients under treatment with clozapine and risperidone.This study included 19 patients meeting the DSM-IV-TR criteria for schizophrenia, having body mass index (BMI) of 16- 25 kg/m2 and suffering schizophrenia for more than 3 years and from this study. Twenty five healthy controls were group matched for age and gender whose BMI was 16-25 kg/m2. Serum S100B and leptin levels and positive and negative symptom scale (PANSS) were assessed at admission and after six weeks. During the study, S100B showed a strong and negative correlation with leptin (r = -0.5, P = 0.01). Also, there were negative correlation between serum S100B level and PANSS negative subscale after 6 weeks of treatment (r = -0.048, P = 0.8). Positive correlation between leptin level and PANSS suggested a potential role for leptin which can mediate the link between antipsychotic induced weight gain and therapeutic response in schizophrenia. PMID:27610173

  1. Negative Correlation between Serum S100B and Leptin Levels in Schizophrenic Patients During Treatment with Clozapine and Risperidone: Preliminary Evidence

    PubMed Central

    Hendouei, Narjes; Hosseini, Seyed Hamzeh; Panahi, Amin; Khazaeipour, Zahra; Barari, Fatemeh; Sahebnasagh, Adeleh; Ala, Shahram

    2016-01-01

    Recently, extensive efforts have been made to understand the rate of energy expenditure and the weight gain associated with atypical antipsychotic treatment, including identification of markers of obesity risk. In recent years, leptin, an adipocyte hormone, has gained significant interest in psychiatric disorders. S100B has been considered as a surrogate marker for astrocyte-specific damage in neurologic disorders. Also, S100B has been detected in adipose with concentration as high as nervous tissue as a second release source. In this study we evaluated the relationship between S100B and leptin in schizophrenic patients under treatment with clozapine and risperidone.This study included 19 patients meeting the DSM-IV-TR criteria for schizophrenia, having body mass index (BMI) of 16- 25 kg/m2 and suffering schizophrenia for more than 3 years and from this study. Twenty five healthy controls were group matched for age and gender whose BMI was 16-25 kg/m2. Serum S100B and leptin levels and positive and negative symptom scale (PANSS) were assessed at admission and after six weeks. During the study, S100B showed a strong and negative correlation with leptin (r = -0.5, P = 0.01). Also, there were negative correlation between serum S100B level and PANSS negative subscale after 6 weeks of treatment (r = -0.048, P = 0.8). Positive correlation between leptin level and PANSS suggested a potential role for leptin which can mediate the link between antipsychotic induced weight gain and therapeutic response in schizophrenia.

  2. Comorbid Symptomatology Moderates Response to Risperidone, Stimulant, and Parent Training in Children with Severe Aggression, Disruptive Behavior Disorder, and Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Brown, Nicole V.; Gadow, Kenneth D.; Arnold, L. Eugene; Kolko, David G.; Findling, Robert L.; Molina, Brooke S.G.; Buchan-Page, Kristin A.; Rice, Robert R.; Bangalore, Srihari S.; Bukstein, Oscar; Rundberg-Rivera, E. Victoria; McNamara, Nora; Aman, Michael G.

    2015-01-01

    Abstract Objective: In this study, we evaluated parent and child characteristics as predictors and moderators of response in the four-site Treatment of Severe Childhood Aggression (TOSCA) study. Methods: A total of 168 children with severe aggression, disruptive behavior disorder, and attention-deficit/hyperactivity disorder (ADHD) were enrolled in a 9-week trial of basic treatment (n=84, stimulant+parent training+placebo) versus augmented treatment (n=84, stimulant+parent training+risperidone). In the initial report, augmented treatment surpassed basic treatment in reducing the primary outcome of disruptive behavior (D-Total) scores. In the current study, we evaluated parent (income, education, family functioning, employment) and child variables (intelligence quotient [IQ], aggression type, comorbid symptomatology) as predictors or moderators, using linear mixed models and the MacArthur guidelines. Results: Higher scores on ADHD symptom severity and callous/unemotional traits predicted better outcome on D-Total regardless of treatment assignment. Two moderators of D-Total were found: Higher anger/irritability symptoms and lower mania scores were associated with faster response, although not better overall effect at endpoint, in the augmented but not the basic group. Several variables moderated response on secondary outcomes (ADHD severity and prosocial behavior), and were characterized by faster response, although not better outcome, in the augmented but not in the basic group. Maternal education moderated outcome on the measure of positive social behavior; children of mothers with less education benefited more from augmented treatment relative to basic than those with more education. Conclusion: Although these findings require validation, they tentatively suggest that augmented treatment works equally well across the entire sample. Nevertheless, certain child characteristics may be useful indicators for the speed of response to augmented treatment. PMID:25885011

  3. Negative Correlation between Serum S100B and Leptin Levels in Schizophrenic Patients During Treatment with Clozapine and Risperidone: Preliminary Evidence.

    PubMed

    Hendouei, Narjes; Hosseini, Seyed Hamzeh; Panahi, Amin; Khazaeipour, Zahra; Barari, Fatemeh; Sahebnasagh, Adeleh; Ala, Shahram

    2016-01-01

    Recently, extensive efforts have been made to understand the rate of energy expenditure and the weight gain associated with atypical antipsychotic treatment, including identification of markers of obesity risk. In recent years, leptin, an adipocyte hormone, has gained significant interest in psychiatric disorders. S100B has been considered as a surrogate marker for astrocyte-specific damage in neurologic disorders. Also, S100B has been detected in adipose with concentration as high as nervous tissue as a second release source. In this study we evaluated the relationship between S100B and leptin in schizophrenic patients under treatment with clozapine and risperidone.This study included 19 patients meeting the DSM-IV-TR criteria for schizophrenia, having body mass index (BMI) of 16- 25 kg/m(2) and suffering schizophrenia for more than 3 years and from this study. Twenty five healthy controls were group matched for age and gender whose BMI was 16-25 kg/m(2). Serum S100B and leptin levels and positive and negative symptom scale (PANSS) were assessed at admission and after six weeks. During the study, S100B showed a strong and negative correlation with leptin (r = -0.5, P = 0.01). Also, there were negative correlation between serum S100B level and PANSS negative subscale after 6 weeks of treatment (r = -0.048, P = 0.8). Positive correlation between leptin level and PANSS suggested a potential role for leptin which can mediate the link between antipsychotic induced weight gain and therapeutic response in schizophrenia.

  4. Negative Correlation between Serum S100B and Leptin Levels in Schizophrenic Patients During Treatment with Clozapine and Risperidone: Preliminary Evidence.

    PubMed

    Hendouei, Narjes; Hosseini, Seyed Hamzeh; Panahi, Amin; Khazaeipour, Zahra; Barari, Fatemeh; Sahebnasagh, Adeleh; Ala, Shahram

    2016-01-01

    Recently, extensive efforts have been made to understand the rate of energy expenditure and the weight gain associated with atypical antipsychotic treatment, including identification of markers of obesity risk. In recent years, leptin, an adipocyte hormone, has gained significant interest in psychiatric disorders. S100B has been considered as a surrogate marker for astrocyte-specific damage in neurologic disorders. Also, S100B has been detected in adipose with concentration as high as nervous tissue as a second release source. In this study we evaluated the relationship between S100B and leptin in schizophrenic patients under treatment with clozapine and risperidone.This study included 19 patients meeting the DSM-IV-TR criteria for schizophrenia, having body mass index (BMI) of 16- 25 kg/m(2) and suffering schizophrenia for more than 3 years and from this study. Twenty five healthy controls were group matched for age and gender whose BMI was 16-25 kg/m(2). Serum S100B and leptin levels and positive and negative symptom scale (PANSS) were assessed at admission and after six weeks. During the study, S100B showed a strong and negative correlation with leptin (r = -0.5, P = 0.01). Also, there were negative correlation between serum S100B level and PANSS negative subscale after 6 weeks of treatment (r = -0.048, P = 0.8). Positive correlation between leptin level and PANSS suggested a potential role for leptin which can mediate the link between antipsychotic induced weight gain and therapeutic response in schizophrenia. PMID:27610173

  5. Divergent long-term consequences of chronic treatment with haloperidol, risperidone, and bromocriptine on traumatic brain injury-induced cognitive deficits.

    PubMed

    Phelps, Thomas I; Bondi, Corina O; Ahmed, Rashid H; Olugbade, Yewande T; Kline, Anthony E

    2015-04-15

    Antipsychotic drugs (APDs) are provided in the clinic to manage traumatic brain injury (TBI)-induced agitation and aggression. Experimental TBI studies consistently show that daily administration of the APDs, haloperidol (HAL) and risperidone (RISP), hinder recovery. However, it is unknown how long the adverse effects remain after cessation of treatment. To elucidate this clinically relevant issue, anesthetized male rats were randomly assigned to four TBI (controlled cortical impact) and four sham groups administered HAL (0.5 mg/kg), RISP (0.45 mg/kg), bromocriptine (BRO; 5.0 mg/kg, included as a control for D2 receptor action), or vehicle (VEH; 1 mL/kg) 24 h after surgery and once-daily for 19 days. Motor and cognitive recovery was assessed on days 1-5 and 14-19, respectively, and again at 1 and 3 months after drug withdrawal. No overall group differences were observed for motor function among the TBI groups, although the HAL group showed a greater beam-walk deficit on day 5 versus the VEH and BRO groups. Cognitive recovery was significantly impaired in the HAL and RISP groups during the treatment phase versus VEH and BRO. Further, BRO was superior to VEH (p=0.0042). At 1 month, both groups that received APDs continued to exhibit significant cognitive impairment versus VEH and BRO; at 3 months, only the HAL group was impaired. Moreover, the HAL, RISP, and VEH groups continued to be cognitively deficient versus BRO, which also reduced cortical damage. These data replicate previous reports that HAL and RISP impede cognitive recovery after TBI and expand the literature by revealing that the deleterious effects persist for 3 months after drug discontinuation. BRO conferred cognitive benefits when administered concomitantly with behavioral testing, thus replicating previous findings, and also after cessation demonstrating enduring efficacy. PMID:25275833

  6. Marble-burying is enhanced in 3xTg-AD mice, can be reversed by risperidone and it is modulable by handling.

    PubMed

    Torres-Lista, Virginia; López-Pousa, Secundino; Giménez-Llort, Lydia

    2015-07-01

    Translational research on behavioural and psychological symptoms of dementia (BPSD) is relevant to the study the neuropsychiatric symptoms that strongly affect the quality of life of the human Alzheimer's disease (AD) patient and caregivers, frequently leading to early institutionalization. Among the ethological behavioural tests for rodents, marble burying is considered to model the spectrum of anxiety, psychotic and obsessive-compulsive like symptoms. The present work was aimed to study the behavioural interactions of 12 month-old male 3xTg-AD mice with small objects using the marble-burying test, as compared to the response elicited in age-matched non-transgenic (NTg) mice. The distinction of the classical 'number of buried marbles' but also those left 'intact' and those 'changed' of position of marbles or partially buried (the transitional level of interaction) provided new insights into the modelling of BPSD-like alterations in this AD model. The analysis revealed genotype differences in the behavioural patterns and predominant behaviors. In the NTg mice, predominance was shown in the 'changed or partially buried', while interactions with marble were enhanced in 3xTg-AD mice resulting in an increase of marble burying. Besides, genotype-dependent meaningful correlations were found, with the marble test pattern of 3xTg-AD mice being directly related to neophobia in the corner tests. In both genotypes, the increase of burying was reversed by chronic treatment with risperidone (1mg/kg, s.c.). In 3xTg-AD mice, the repetitive handling of animals during the treatment also exerted modulatory effects. These distinct patterns further characterize the modelling of BPSD-like symptoms in the 3xTg-AD mice, and provide another behavioural tool to assess the benefits of preventive and/or therapeutic strategies, as well as the potential action of risk factors for AD, in this animal model.

  7. Risperidone Added to Parent Training and Stimulant Medication: Effects on Attention-Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, Conduct Disorder, and Peer Aggression

    PubMed Central

    Gadow, Kenneth D.; Arnold, L. Eugene; Molina, Brooke S.G.; Findling, Robert L.; Bukstein, Oscar G.; Brown, Nicole V.; McNamara, Nora K.; Rundberg-Rivera, E. Victoria; Li, Xiaobai; Kipp, Heidi; Schneider, Jayne; Farmer, Cristan A.; Baker, Jennifer; Sprafkin, Joyce; Rice, Robert R.; Bangalore, Srihari S.; Butter, Eric M.; Buchan-Page, Kristin A.; Hurt, Elizabeth A.; Austin, Adrienne B.; Grondhuis, Sabrina N.; Aman, Michael G.

    2014-01-01

    Objective In this study, we aimed to expand on our prior research into the relative efficacy of combining parent training, stimulant medication and placebo (Basic) versus parent training, stimulant, and risperidone (Augmented) therapy by examining treatment effects for attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) symptoms and peer aggression, symptom-induced—impairment, and informant discrepancy. Method Children (6-12 years; N=168) with severe physical aggression, ADHD, and co-occurring ODD/CD received an open trial of parent training and stimulant medication for 3 weeks. Participants failing to show optimal clinical response were randomly assigned to Basic or Augmented therapy for an additional 6 weeks. Results Compared with Basic therapy, children receiving Augmented therapy experienced greater reduction in parent-rated ODD severity (p=.02, Cohen's d=0.27) and peer aggression (p=.02, Cohen's d=0.32), but not ADHD or CD symptoms. Fewer children receiving Augmented (16%) than Basic (40%) therapy were rated by their parents as impaired by ODD symptoms at Week 9/endpoint (p=.008). Teacher ratings indicated greater reduction in ADHD severity (p=.02, Cohen's d =0.61) with Augmented therapy, but not for ODD or CD symptoms or peer aggression. Although both interventions were associated with marked symptom reduction, a relatively large percentage of children were rated impaired for at least one targeted disorder at Week 9/endpoint by parents (Basic 47%; Augmented 27%) and teachers (Basic 48%; Augmented 38%). Conclusion Augmented was superior to Basic therapy in reducing severity of ADHD and ODD symptoms, peer aggression, and symptom-induced impairment, but clinical improvement was generally context-specific, and effect sizes ranged from small to moderate. PMID:25151418

  8. Long-acting cocaine hydrolase for addiction therapy

    PubMed Central

    Chen, Xiabin; Xue, Liu; Hou, Shurong; Jin, Zhenyu; Zhang, Ting; Zheng, Fang; Zhan, Chang-Guo

    2016-01-01

    Cocaine abuse is a world-wide public health and social problem without a US Food and Drug Administration-approved medication. An ideal anticocaine medication would accelerate cocaine metabolism, producing biologically inactive metabolites by administration of an efficient cocaine-specific exogenous enzyme. Our recent studies have led to the discovery of the desirable, highly efficient cocaine hydrolases (CocHs) that can efficiently detoxify and inactivate cocaine without affecting normal functions of the CNS. Preclinical and clinical data have demonstrated that these CocHs are safe for use in humans and are effective for accelerating cocaine metabolism. However, the actual therapeutic use of a CocH in cocaine addiction treatment is limited by its short biological half-life (e.g., 8 h or shorter in rats). Here we demonstrate a novel CocH form, a catalytic antibody analog, which is a fragment crystallizable (Fc)-fused CocH dimer (CocH-Fc) constructed by using CocH to replace the Fab region of human IgG1. The CocH-Fc not only has a high catalytic efficiency against cocaine but also, like an antibody, has a considerably longer biological half-life (e.g., ∼107 h in rats). A single dose of CocH-Fc was able to accelerate cocaine metabolism in rats even after 20 d and thus block cocaine-induced hyperactivity and toxicity for a long period. Given the general observation that the biological half-life of a protein drug is significantly longer in humans than in rodents, the CocH-Fc reported in this study could allow dosing once every 2–4 wk, or longer, for treatment of cocaine addiction in humans. PMID:26712009

  9. Long-Acting Reversible Contraception (LARC): IUD and Implant

    MedlinePlus

    ... IUDs work mainly by preventing fertilization of the egg by the sperm . The hormonal IUDs also thicken ... sperm to enter the uterus and fertilize the egg, and keep the lining of the uterus thin, ...

  10. Development of HIV reservoir targeted long acting nanoformulated antiretroviral therapies.

    PubMed

    Edagwa, Benson J; Zhou, Tian; McMillan, JoEllyn M; Liu, Xin-Ming; Gendelman, Howard E

    2014-01-01

    Human immunodeficiency virus (HIV) infection commonly results in a myriad of comorbid conditions secondary to immune deficiency. Infection also affects broad organ system function. Although current antiretroviral therapy (ART) reduces disease morbidity and mortality through effective control of peripheral viral load, restricted infection in HIV reservoirs including gut, lymphoid and central nervous system tissues, is not eliminated. What underlies these events is, in part, poor ART penetrance into each organ across tissue barriers, viral mutation and the longevity of infected cells. We posit that one means to improve these disease outcomes is through nanotechnology. To this end, this review discusses a broad range of cutting-edge nanomedicines and nanomedicine platforms that are or can be used to improve ART delivery. Discussion points include how polymer-drug conjugates, dendrimers, micelles, liposomes, solid lipid nanoparticles and polymeric nanoparticles can be harnessed to best yield cell-based delivery systems. When completely developed, such nanomedicine platforms have the potential to clear reservoirs of viral infection.

  11. Development of HIV Reservoir Targeted Long Acting Nanoformulated Antiretroviral Therapies

    PubMed Central

    Edagwa, Benson J; Zhou, Tian; McMillan, JoEllyn M; Liu, Xin-Ming; Gendelman, Howard E

    2014-01-01

    Human immunodeficiency virus (HIV) infection commonly results in a myriad of comorbid conditions secondary to immune deficiency. Infection also affects broad organ system function. Although current antiretroviral therapy (ART) reduces disease morbidity and mortality through effective control of peripheral viral load, restricted infection in HIV reservoirs including gut, lymphoid and central nervous system tissues, is not eliminated. What underlies these events is, in part, poor ART penetrance into each organ across tissue barriers, viral mutation and the longevity of infected cells. We posit that one means to improve these disease outcomes is through nanotechnology. To this end, this review discusses a broad range of cutting-edge nanomedicines and nanomedicine platforms that are or can be used to improve ART delivery. Discussion points include how polymer-drug conjugates, dendrimers, micelles, liposomes, solid lipid nanoparticles and polymeric nanoparticles can be harnessed to best yield cell-based delivery systems. When completely developed, such nanomedicine platforms have the potential to clear reservoirs of viral infection. PMID:25174930

  12. Long-acting cocaine hydrolase for addiction therapy.

    PubMed

    Chen, Xiabin; Xue, Liu; Hou, Shurong; Jin, Zhenyu; Zhang, Ting; Zheng, Fang; Zhan, Chang-Guo

    2016-01-12

    Cocaine abuse is a world-wide public health and social problem without a US Food and Drug Administration-approved medication. An ideal anticocaine medication would accelerate cocaine metabolism, producing biologically inactive metabolites by administration of an efficient cocaine-specific exogenous enzyme. Our recent studies have led to the discovery of the desirable, highly efficient cocaine hydrolases (CocHs) that can efficiently detoxify and inactivate cocaine without affecting normal functions of the CNS. Preclinical and clinical data have demonstrated that these CocHs are safe for use in humans and are effective for accelerating cocaine metabolism. However, the actual therapeutic use of a CocH in cocaine addiction treatment is limited by its short biological half-life (e.g., 8 h or shorter in rats). Here we demonstrate a novel CocH form, a catalytic antibody analog, which is a fragment crystallizable (Fc)-fused CocH dimer (CocH-Fc) constructed by using CocH to replace the Fab region of human IgG1. The CocH-Fc not only has a high catalytic efficiency against cocaine but also, like an antibody, has a considerably longer biological half-life (e.g., ∼107 h in rats). A single dose of CocH-Fc was able to accelerate cocaine metabolism in rats even after 20 d and thus block cocaine-induced hyperactivity and toxicity for a long period. Given the general observation that the biological half-life of a protein drug is significantly longer in humans than in rodents, the CocH-Fc reported in this study could allow dosing once every 2-4 wk, or longer, for treatment of cocaine addiction in humans.

  13. Long-acting cocaine hydrolase for addiction therapy.

    PubMed

    Chen, Xiabin; Xue, Liu; Hou, Shurong; Jin, Zhenyu; Zhang, Ting; Zheng, Fang; Zhan, Chang-Guo

    2016-01-12

    Cocaine abuse is a world-wide public health and social problem without a US Food and Drug Administration-approved medication. An ideal anticocaine medication would accelerate cocaine metabolism, producing biologically inactive metabolites by administration of an efficient cocaine-specific exogenous enzyme. Our recent studies have led to the discovery of the desirable, highly efficient cocaine hydrolases (CocHs) that can efficiently detoxify and inactivate cocaine without affecting normal functions of the CNS. Preclinical and clinical data have demonstrated that these CocHs are safe for use in humans and are effective for accelerating cocaine metabolism. However, the actual therapeutic use of a CocH in cocaine addiction treatment is limited by its short biological half-life (e.g., 8 h or shorter in rats). Here we demonstrate a novel CocH form, a catalytic antibody analog, which is a fragment crystallizable (Fc)-fused CocH dimer (CocH-Fc) constructed by using CocH to replace the Fab region of human IgG1. The CocH-Fc not only has a high catalytic efficiency against cocaine but also, like an antibody, has a considerably longer biological half-life (e.g., ∼107 h in rats). A single dose of CocH-Fc was able to accelerate cocaine metabolism in rats even after 20 d and thus block cocaine-induced hyperactivity and toxicity for a long period. Given the general observation that the biological half-life of a protein drug is significantly longer in humans than in rodents, the CocH-Fc reported in this study could allow dosing once every 2-4 wk, or longer, for treatment of cocaine addiction in humans. PMID:26712009

  14. DPP-IV-resistant, long-acting oxyntomodulin derivatives.

    PubMed

    Santoprete, Alessia; Capitò, Elena; Carrington, Paul E; Pocai, Alessandro; Finotto, Marco; Langella, Annunziata; Ingallinella, Paolo; Zytko, Karolina; Bufali, Simone; Cianetti, Simona; Veneziano, Maria; Bonelli, Fabio; Zhu, Lan; Monteagudo, Edith; Marsh, Donald J; Sinharoy, Ranabir; Bianchi, Elisabetta; Pessi, Antonello

    2011-04-01

    Obesity is one of the major risk factors for type 2 diabetes, and the development of agents, that can simultaneously achieve glucose control and weight loss, is being actively pursued. Therapies based on peptide mimetics of the gut hormone glucagon-like peptide 1 (GLP-1) are rapidly gaining favor, due to their ability to increase insulin secretion in a strictly glucose-dependent manner, with little or no risk of hypoglycemia, and to their additional benefit of causing a modest, but durable weight loss. Oxyntomodulin (OXM), a 37-amino acid peptide hormone of the glucagon (GCG) family with dual agonistic activity on both the GLP-1 (GLP1R) and the GCG (GCGR) receptors, has been shown to reduce food intake and body weight in humans, with a lower incidence of treatment-associated nausea than GLP-1 mimetics. As for other peptide hormones, its clinical application is limited by the short circulatory half-life, a major component of which is cleavage by the enzyme dipeptidyl peptidase IV (DPP-IV). SAR studies on OXM, described herein, led to the identification of molecules resistant to DPP-IV degradation, with increased potency as compared to the natural hormone. Analogs derivatized with a cholesterol moiety display increased duration of action in vivo. Moreover, we identified a single substitution which can change the OXM pharmacological profile from a dual GLP1R/GCGR agonist to a selective GLP1R agonist. The latter finding enabled studies, described in detail in a separate study (Pocai A, Carrington PE, Adams JR, Wright M, Eiermann G, Zhu L, Du X, Petrov A, Lassman ME, Jiang G, Liu F, Miller C, Tota LM, Zhou G, Zhang X, Sountis MM, Santoprete A, Capitò E, Chicchi GG, Thornberry N, Bianchi E, Pessi A, Marsh DJ, SinhaRoy R. Glucagon-like peptide 1/glucagon receptor dual agonism reverses obesity in mice. Diabetes 2009; 58: 2258-2266), which highlight the potential of GLP1R/GCGR dual agonists as a potentially superior class of therapeutics over the pure GLP1R agonists currently in clinical use.

  15. Design of a Drug-in-Adhesive Transdermal Patch for Risperidone: Effect of Drug-Additive Interactions on the Crystallization Inhibition and In Vitro/In Vivo Correlation Study.

    PubMed

    Weng, Wei; Quan, Peng; Liu, Chao; Zhao, Hanqing; Fang, Liang

    2016-10-01

    The purpose of this work was to develop and design an appropriate drug-in-adhesive patch for transdermal delivery of risperidone (RISP). Various formulation factors were investigated by in vitro permeation study using excised rabbit skin. Increasing the drug concentration in the pressure sensitive adhesive (PSA) was used to enhance the drug permeation. To overcome the high crystallization tendency of the patch, several crystallization inhibitors such as PVP, PEG, and surfactants and fatty acids were evaluated by microscopy study. The mechanism of crystallization inhibition was investigated by differential scanning calorimetry, nuclear magnetic resonance spectrometer, and FT-IR studies. RISP and its active metabolite were determined after topical application of the optimized transdermal patch, and the in vivo pharmacokinetic parameters were compared with the intravenous administration group. The microscopy study indicated that fatty acid greatly inhibited the crystallization of RISP in PSA. The inhibition was attributed to the drug-additive interaction between amino group of RISP and the carboxyl group of fatty acid which was further confirmed by (1)H-NMR and FT-IR studies. The optimal permeation profile was obtained with the patches containing 5% RISP and 5% oleic acid in Duro-Tak(®) 87-2287. The in vivo pharmacokinetic study exhibited a sustained absorption and metabolism profile and well correlated with the in vitro permeation data. PMID:27522527

  16. Prolactin Levels After Switching to Paliperidone Palmitate in Patients with Schizophrenia

    PubMed Central

    Nagamine, Takahiko; Sato, Goro; Besho, Kazue

    2016-01-01

    Objective: The aim of this study was to investigate the tolerability and efficacy of paliperidone palmitate and its effect on the levels of prolactin in patients with schizophrenia. Method: A prospective study was carried out in 22 Japanese middle-aged patients with schizophrenia who were switched from paliperidone-extended release or risperidone long-acting injectable to paliperidone palmitate for a minimum of 12 months. Psychotic symptoms using the 18-item Brief Psychiatric Rating Scale, extrapyramidal symptoms using 9-item Drug-induced Extrapyramidal Symptoms Scale, and plasma prolactin levels using fasting blood samples were assessed at Baseline, and one, three, six, and 12 months. Results: There were significant reductions in prolactin levels at one, three, and six months relative to baseline in the male subjects switched from risperidone long-acting injectable, while prolactin levels in male subjects switched from paliperidone-extended release and the female subjects switched from risperidone long-acting injectable or paliperidone-extended release were largely unchanged. No time-sequential changes were observed in total scores of Brief Psychiatric Rating Scale and Drug-induced Extrapyramidal Symptoms Scale, irrespective of previous antipsychotics treatment. Conclusion: Switching from paliperidone-extended release or risperidone long-acting injectable to paliperidone palmitate did not result in any observed time-sequential changes in psychotic symptoms in study subjects, and prolactin levels decreased in male subjects switched from risperidone long-acting injectable. As measurement of paliperidone concentrations is limited in routine practice, a fluctuation range of prolactin levels may be a useful marker for confirmation of safety maintenance treatment with long-acting injectables in clinical settings.

  17. Levonorgestrel-releasing intrauterine systems for long-acting contraception: current perspectives, safety, and patient counseling

    PubMed Central

    Costescu, Dustin J

    2016-01-01

    Unintended pregnancy is a significant global problem. In 2008, there were over 100 million unplanned pregnancies worldwide, representing approximately 41% of global conceptions. Family planning strategies in many countries are shifting from increasing the uptake of contraception among nonusers to increasing the uptake of the most effective methods among users of less effective methods. One of the most effective and acceptable methods of contraception is the levonorgestrel-releasing intrauterine system (LNG IUS); however, its uptake varies widely by country. This article reviews the currently available LNG IUSs, the rationale for increasing uptake of these methods, and evidence regarding safety, and discusses counseling strategies to best inform women about this option for contraception. PMID:27785107

  18. [Pharmacological studies of long-acting phenothiazines with particular reference to fluphenazine decanoate (author's transl)].

    PubMed

    Chen, P C

    1978-10-01

    A long-term study was performed on the effects of fluphenazine decanoate and the results were compared with those of fluphenazine-2HCl and fluphenazine enanthate. These agents given orally were equipotent in inhibiting the motility of mice. With subcutaneous administration, decanoate and enanthate showed a clearly prolonged action, whereas fluphenazine-2HCl was effective for only 3 days. Decanoate and enanthate did not produce marked hypothermia in rats. Like enanthate, decanoate inhibited, for a long duration, apomorphine-induced stereotyped behavior and methamphetamine group toxicity in mice, as well as induced catalepsy in rats. It was found that fluphenazine-2HCl markedly inhibited certain agonists-induced contraction of isolated preparations while enanthate and decanoate inhibited these contractions almost equally. In rats, enanthate induced a persistent hypotension and marked changes in ECG while decanoate showed a transient hypotension and slight changes in ECG. In the study of rat brain catecholamine turnover, these three drugs significantly increased dopamine turnover, and decanoate and enanthate were found to have prolonged effects. No significant change in noradrenaline turnover was observed. These results indicate that fluphenazine decanoate has the same spectrum of activity as enanthate except for its slower onset, weaker potency and longer duration of action. A prolonged tranquilizing effect was most evident.

  19. Discovery of substituted phenyl urea derivatives as novel long-acting β2-adrenoreceptor agonists.

    PubMed

    Pérez, Daniel; Crespo, Maribel; Solé, Laia; Prat, Maria; Carcasona, Carla; Calama, Elena; Otal, Raquel; Gavaldá, Amadeu; Gómez-Angelats, Mireia; Miralpeix, Montserrat; Puig, Carles

    2011-03-01

    The synthesis of diverse functionalized ureas in a semi-parallel fashion is described, as well as their β(1)/β(2)-adrenergic activities and the corresponding structure-activity relationship (SAR). We have focused on lipophilicity and duration of action, and we have discovered a strong correlation in this series of molecules. A quantitative structure-activity relationship (QSAR) analysis will be presented that quantifies this relationship.

  20. Peripheral Administration of a Long-Acting Peptide Oxytocin Receptor Agonist Inhibits Fear-Induced Freezing

    PubMed Central

    Modi, Meera E.; Majchrzak, Mark J.; Fonseca, Kari R.; Doran, Angela; Osgood, Sarah; Vanase-Frawley, Michelle; Feyfant, Eric; McInnes, Heather; Darvari, Ramin; Buhl, Derek L.

    2016-01-01

    Oxytocin (OT) modulates the expression of social and emotional behaviors and consequently has been proposed as a pharmacologic treatment of psychiatric diseases, including autism spectrum disorders and schizophrenia; however, endogenous OT has a short half-life in plasma and poor permeability across the blood-brain barrier. Recent efforts have focused on the development of novel drug delivery methods to enhance brain penetration, but few efforts have aimed at improving its half-life. To explore the behavioral efficacy of an OT analog with enhanced plasma stability, we developed PF-06655075 (PF1), a novel non–brain-penetrant OT receptor agonist with increased selectivity for the OT receptor and significantly increased pharmacokinetic stability. PF-06478939 was generated with only increased stability to disambiguate changes to selectivity versus stability. The efficacy of these compounds in evoking behavioral effects was tested in a conditioned fear paradigm. Both central and peripheral administration of PF1 inhibited freezing in response to a conditioned fear stimulus. Peripheral administration of PF1 resulted in a sustained level of plasma concentrations for greater than 20 hours but no detectable accumulation in brain tissue, suggesting that plasma or cerebrospinal fluid exposure was sufficient to evoke behavioral effects. Behavioral efficacy of peripherally administered OT receptor agonists on conditioned fear response opens the door to potential peripheral mechanisms in other beh