de Groot, I. W.; van Harten, P. N.
Objective The aim of this study was to investigate to what extent atypical antipsychotics, conventional antipsychotics and anticholinergics are prescribed simultaneously in daily clinical practice in Europe. Method A pharmaco-epidemiological study was carried out in which hospital pharmacists from 45 hospitals in Belgium, Denmark, France, Germany, The Netherlands and Scotland participated. Prescription data for 2,725 patients (mainly inpatients) who had been using an atypical antipsychotic for more than 6 weeks were analysed. Main outcome measure The frequencies of simultaneous prescription of atypical antipsychotics with other antipsychotics and/or anticholinergics. Results In this sample of patients with an atypical antipsychotic 42.1% was prescribed another antipsychotic (24.1% if low-potent antipsychotics were not included in the analysis) and 30.1% was prescribed an anticholinergic. In total 47.1% of patients were prescribed an atypical antipsychotic without any other antipsychotic or anticholinergic. Conclusion It is common practice to prescribe a combination of atypical antipsychotics and conventional antipsychotics and/or anticholinergics. This suggests that monotherapy involving an atypical antipsychotic is not considered to be an adequate treatment for a substantial number of patients in clinical practice. PMID:17333501
Objectives: Non evidence-based prescribing of antipsychotics is common in the UK and internationally with high doses and polypharmacy the norm. These practices often remain even after systematic attempts are made to change. We aimed to establish which factors are linked to antipsychotic prescribing quality so we can identify and target patients for interventions to improve quality and allow us to understand further the drivers of non evidence-based prescribing. Objectives: A cross-sectional survey with a collection of factors potentially affecting antipsychotic prescribing quality outcomes was carried out in eight secondary care units in England. Participants were inpatients prescribed regular antipsychotics on the day of the survey. Antipsychotic dose, polypharmacy, type and route were the main outcome measures. Objectives: Data were collected for 1198 patients. Higher total dose was associated with greater weight, higher number of previous admissions, longer length of admission, noncompliance with medication and use of an atypical antipsychotic. A lower total dose was associated with clozapine use. Polypharmacy was associated with not being a patient at the South London and Maudsley NHS Trust centre, the subject having a forensic history, a greater number of previous admissions and higher total dose. Younger age, not being detained under a Mental Health Act section, atypical antipsychotic use and oral route were predictors of antipsychotic monotherapy. Atypical antipsychotic use was associated with oral route, higher total dose, being administered only one antipsychotic, having had fewer previous antipsychotics and no anticholinergic use. Use of the oral route was associated with not being sectioned under the Mental Health Act, atypical antipsychotic use, younger age, non-schizophrenia diagnosis, fewer previous admissions and a lower total dose. Objectives: In patients with chronic illness who are detained, heavier, noncompliant, not taking clozapine and on a depot antipsychotic, prescribers use larger doses and antipsychotic polypharmacy. We found that use of percentage of licensed maximum doses favours typical antipsychotics arbitrarily, and that high doses and polypharmacy are inextricably linked. PMID:25489476
Kishimoto, Taishiro; Watanabe, Koichiro; Uchida, Hiroyuki; Mimura, Masaru; Kane, John M; Correll, Christoph U
While combining antipsychotics is common in schizophrenia treatment, the literature on the reasons for antipsychotic polypharmacy (APP) is limited. We aimed to identify prescriber attitudes and rationales for APP in Japan where high APP utilization is reported. Two-hundred and seventeen psychiatrists participated in the survey, which assessed APP attitudes and behaviors. Prescribing APP to 47.7±24.7% (mean±S.D.) of their patients, psychiatrists reported that they were "moderately" concerned about APP. The most APP-justifiable factors were (1="not at all" to 5="extreme") cross titration (4.50±0.67), randomized controlled evidence (3.67±0.83), and treatment of comorbid conditions (3.31±0.83). Conversely, APP-discouraging factors were chronic side effects (4.14±0.64), difficulty determining cause and effect (4.07±0.74), and acute side effects (3.99±0.81). Comparing high to low APP prescribers (>50% vs. ?50% of patients), no differences emerged regarding APP justification and concerns. In multivariate analyses, high APP use was associated with practice at a psychiatric hospital (OR: 2.70, 95% CI: 1.29-5.67, p=0.009), concern about potential drug-drug interactions (OR: 1.56, 95% CI: 1.04-2.35, p=0.031), and less reliance on case reports of APP showing efficacy (OR: 0.64, 95% CI: 0.44-0.92, p=0.017) (r(2)=0.111, p=0.001). High and low APP prescribers shared a comparable degree of justifications and concerns. Future research should examine the impact of cultural determinants on APP. PMID:23602697
Verdoux, Hélène; Pambrun, Elodie; Cortaredona, Sébastien; Tournier, Marie; Verger, Pierre
The objectives were to explore in a community-based sample of persons aged 0-25 years: (1) trends in antipsychotic prescribing, (2) characteristics of the zone of residence associated with antipsychotic prescribing rates, and (3) the pattern of antipsychotic prescribing. The study was performed using reimbursement data from the French Insurance Healthcare system. Prescribing trends were investigated over the period 2006-2013. An ecological design was used to assess the impact of the socio-economical and health resource characteristics of the zone of residence (n = 96 administrative subdivisions of French territory) on antipsychotic prescribing rates. The pattern of antipsychotic prescribing was explored in a cohort of youths newly treated with antipsychotics. Over the period 2006-2013, antipsychotic dispensing rates were stable in persons aged 0-25 years (4.8 per 1,000 in 2006 and 4.9 per 1,000 in 2013). First-generation antipsychotic dispensing rates decreased from 3.1 to 2.6 per 1,000 (OR = 0.96, 95 % CI 0.94-0.98), while second-generation antipsychotic dispensing rates increased from 2.7 to 3.4 per 1,000 (OR = 1.03, 95 % CI 1.01-1.05). Antipsychotic prescribing rates were impacted by health resource characteristics of the zone of residence in children aged 10 years and under and by socio-economical characteristics in those aged 16-20 years. In all the age groups, antipsychotics were principally started by hospital practitioners (47 %) and general practitioners (34 %). The rates of psychostimulants concomitantly prescribed with antipsychotics were lower than 5 %. In conclusion, rates of youths exposed to second-generation antipsychotics are still rising. The impact of environmental characteristics on antipsychotics prescribing and appropriateness of these prescriptions in youths should be further investigated. PMID:25564132
Paton, C.; Flynn, A.; Shingleton-Smith, A.; McIntyre, S.; Bhaumik, S.; Rasmussen, J.; Hardy, S.; Barnes, T.
Background: Antipsychotics are perceived to be over-used in the management of behavioural problems in people with an intellectual disability (ID). Published guidelines have set good practice standards for the use of these drugs for behavioural indications. We sought to identify the range of indications for which antipsychotic drugs are prescribed…
Murphy, Andrea Lynn; Gardner, David Martin; Cooke, Charmaine; Kutcher, Stanley Paul; Hughes, Jean
Objectives. To explore the lived experience of youth, caregivers, and prescribers with antipsychotic medications. Design. We conducted a qualitative interpretive phenomenology study. Youth aged 11 to 25 with recent experience taking antipsychotics, the caregivers of youth taking antipsychotics, and the prescribers of antipsychotics were recruited. Subjects. Eighteen youth, 10 caregivers (parents), and 11 prescribers participated. Results. Eleven of 18 youth, six of ten parents, and all prescribers discussed antipsychotic-related weight gain. Participants were attuned to the numeric weight changes usually measured in pounds. Significant discussions occurred around weight changes in the context of body image, adherence and persistence, managing weight increases, and metabolic effects. These concepts were often inextricably linked but maintained the significance as separate issues. Participants discussed tradeoffs regarding the perceived benefits and risks of weight gain, often with uncertainty and inadequate information regarding the short- and long-term consequences. Conclusion. Antipsychotic-related weight gain in youth influences body image and weight management strategies and impacts treatment courses with respect to adherence and persistence. In our study, the experience of monitoring for weight and metabolic changes was primarily reactive in nature. Participants expressed ambiguity regarding the short- and long-term consequences of weight and metabolic changes. PMID:24533223
The shift from first-generation antipsychotic medications to second-generation antipsychotic medications initially caused a wave of excitement about the potential for improved and broader efficacy of these medications concurrent with an improved side-effect profile. Recent data from high-quality research analyses have subsequently raised significant questions about these claims. This research evidence has, however, not altered prescribing behavior in a way that would be expected from fully rational evaluation of the evidence. Prescribing decisions represent poorly understood, complex behaviors influenced by a number of external and internal forces, some of which may be elucidated by advances in social and cognitive psychology. In this article, the decision to prescribe first- versus second-generation antipsychotic medications is examined, and specific social psychological biases and individual cognitive biases are hypothesized to be significant influences on clinicians. These biases may perpetuate disparity between research evidence and clinical practice. PMID:20098227
Bergendal, Annica; Schiöler, Helena; Wettermark, Björn
Objectives: To assess the prevalence of concomitant use of two or more antipsychotic drugs and other psychotropic drugs in the Swedish population. Methods: Data for this observational cohort study were collected from the Swedish Prescribed Drug Register including all dispensed drugs to the entire Swedish population (9.4 million inhabitants). We identified all individuals with at least one dispensed prescription of antipsychotic drug during January to June 2008. After 12 months, a second exposure period was chosen. Individuals who were dispensed two or more antipsychotic drugs in both periods were considered long-time users of antipsychotic polypharmacy. Results: In 2008, 1.5% of the Swedish population was dispensed antipsychotic drugs, the majority (75%) using only one antipsychotic drug. Out of individuals who were dispensed 2 or more antipsychotic drugs during the first period, 62% also was also dispensed at least 2 antipsychotic drugs during the second period. A total of 665 different unique combinations were used in 2008. Individuals prescribed two or more antipsychotic drugs during both periods were more often dispensed anxiolytics and sedatives than those who were dispensed only one antipsychotic drug. Elderly were dispensed antipsychotic drugs much more often than younger persons. Conclusions: In Sweden, 25% of patients dispensed antipsychotic drugs receive a combination of two or more antipsychotic drugs. Individuals who are dispensed antipsychotic polypharmacy are more often dispensed anxiolytics and sedatives than those prescribed only one antipsychotic drug. Long-term observational studies are needed to assess the efficacy and safety of such combinations. PMID:26301078
Lunsky, Yona; Elserafi, Jonny
Antipsychotic medication rates are high in adults with developmental disability. This study considered rates of antipsychotic use in 743 adults with developmental disability who had experienced a psychiatric crisis. Nearly half (49%) of these adults were prescribed antipsychotics. Polypharmacy was common with 22% of those prescribed antipsychotics…
Background: There is no conclusive evidence that either high doses or combinations of antipsychotics are more effective than standard doses or monotherapy alone. Nonetheless, prescription of both remains prevalent in the UK. In 2006 the South London and Maudsley NHS Foundation Trust (SLAM) participated in a national survey of prescription of antipsychotic medications, organized by the Prescribing Observatory for Mental Health. Over half of the patients on SLAM inpatient or psychiatric intensive care units were prescribed a high-dose antipsychotic or a combination of antipsychotics. Prescribing high-dose antipsychotics and polypharmacy in SLAM was found to be among the highest in the UK. Aim: To assess the impact of a 6-year quality improvement programme aimed at reducing the rates of prescribing high-dose antipsychotics and polypharmacy on SLAM inpatients and psychiatric intensive care units. Results: There was a significant reduction between baseline and final survey in the rates of prescription of both high-dose antipsychotics and polypharmacy on SLAM inpatients and intensive care units (58% versus 10% p < 0.0001 and 57% versus 16%, p < 0.0001 respectively). The proportion of patients at final survey prescribed a high-dose antipsychotic and a combination was substantially lower in SLAM than in the national sample (10% versus 28%, p < 0.0001 and 16% versus 38%, p < 0.0001 respectively). Clinical implications: A sustained change in the prescribing culture of an organization can be achieved through a targeted improvement programme. PMID:25653825
Carter, Gregory T; Duong, Vicky; Ho, Stanley; Ngo, Kathryn C; Greer, Christopher L; Weeks, Douglas L
Analgesics, including opioids, steroidal and nonsteroidal anti-inflammatory drugs, aspirin, acetaminophen, antiepileptics, and serotonin-norepinephrine reuptake inhibitors, are medications commonly used to treat many forms of pain. However, all of these agents may have significant adverse side effects. Adverse effects may occasionally be inseparable from desired effects. Side effects are often dose dependent and time dependent. It is critical that the prescribing practitioner and the dispensing pharmacist provide a thorough, understandable review of the potential side effects to all patients before these drugs are administered. Proper monitoring and follow-up during therapy are crucial. PMID:24787343
Background Shared decision making represents a clinical consultation model where both clinician and service user are conceptualised as experts; information is shared bilaterally and joint treatment decisions are reached. Little previous research has been conducted to assess experience of this model in psychiatric practice. The current project therefore sought to explore the attitudes and experiences of consultant psychiatrists relating to shared decision making in the prescribing of antipsychotic medications. Methods A qualitative research design allowed the experiences and beliefs of participants in relation to shared decision making to be elicited. Purposive sampling was used to recruit participants from a range of clinical backgrounds and with varying length of clinical experience. A semi-structured interview schedule was utilised and was adapted in subsequent interviews to reflect emergent themes. Data analysis was completed in parallel with interviews in order to guide interview topics and to inform recruitment. A directed analysis method was utilised for interview analysis with themes identified being fitted to a framework identified from the research literature as applicable to the practice of shared decision making. Examples of themes contradictory to, or not adequately explained by, the framework were sought. Results A total of 26 consultant psychiatrists were interviewed. Participants expressed support for the shared decision making model, but also acknowledged that it was necessary to be flexible as the clinical situation dictated. A number of potential barriers to the process were perceived however: The commonest barrier was the clinician’s beliefs regarding the service users’ insight into their mental disorder, presented in some cases as an absolute barrier to shared decision making. In addition factors external to the clinician - service user relationship were identified as impacting on the decision making process, including; environmental factors, financial constraints as well as societal perceptions of mental disorder in general and antipsychotic medication in particular. Conclusions This project has allowed identification of potential barriers to shared decision making in psychiatric practice. Further work is necessary to observe the decision making process in clinical practice and also to identify means in which the identified barriers, in particular ‘lack of insight’, may be more effectively managed. PMID:24886121
Uttaro, Thomas; Finnerty, Molly; White, Thomas; Gaylor, Rosanne; Shindelman, Lawrence
The New York State Office of Mental Health has implemented the browser based Psychiatric Clinical Knowledge Enhancement System (PSYCKES) medication application throughout its inpatient system of care. PSYCKES provides detailed current medication regimens and histories, as well as medication best practices reports at the patient, psychiatrist, ward, and facility levels. South Beach Psychiatric Center (SBPC) has made specific use of a best practices report which details proportions of caseloads and number of patients on two or more concurrent antipsychotic medications. Psychiatrists received extensive application and desktop support and individual and group training was conducted. PSYCKES current and historical medication regimens were reviewed for individual cases and best practices reports were used in psychiatry supervision from January 2004 to March 2005. SBPC psychiatrists achieved marked reductions in the proportions of their caseloads on two or more concurrent antipsychotics. Although we cannot impute causality from this pre-post implementation design, the results of this evaluation suggest that the use of PSYCKES was effective in reducing such regimens for inpatients. PMID:16807792
Harden, R N; Argoff, C
Skeletal muscle relaxants (SMR) are commonly used drugs prescribed for the treatment of muscle spasm and discomfort. Although many have been in use for decades, physicians may be unaware of the accumulating evidence of their risks, benefits, safety and side effects. This review examines the efficacy, side effects, and safety of three commonly prescribed SMRs: metaxalone, cyclobenzaprine, and carisoprodol. All three appear to have equal efficacy, but their side effects vary considerably. Metaxalone has the fewest reports of side effects, and no reports of major safety issues. Cyclobenzaprine, closely related to the tricyclic antidepressants, causes the expected lethargy and anticholinergic side effects, and may have some toxicity in overdose and in combination with other substances. Carisoprodol raises the greatest concern. Reports in the literature suggest a significant potential for physical and psychological dependence perhaps suggesting a potential for misuse. It also has, perhaps, the greatest toxicity. A secondary goal of this review is to stimulate more discourse about these commonly used, but poorly understood compounds. PMID:22388444
Background The research goal is to better understand prescriber, patient, and caregiver perspectives about long-acting injectable (LAI) antipsychotic therapy and how these perspectives affect LAI use. Addressing these perspectives in the clinic may lead to greater success in achieving therapeutic goals for the patient with schizophrenia. Methods Ethnographic information was collected from a non-random sample of 69 prescriber-patient conversations (60 with community mental health center [CMHC] psychiatrists; 9 with nurse-practitioners) recorded during treatment visits from August 2011 to February 2012, transcribed and analyzed. Discussions were categorized according to 11 predetermined CMHC topics. In-person observations were also conducted at 4 CMHCs, including home visits by researchers (n?=?15 patients) prior to the CMHC visit and observations of patients receiving injections and interacting with staff. Telephone in-depth interviews with psychiatrists, patients, and caregivers to gather additional information on LAI discussion, prescription, or use were conducted. Results Antipsychotic treatment decisions were made without patient or caregiver input in 40 of 60 (67%) of psychiatrist-patient conversations. Involvement of patients or caregivers in treatment decisions was greater when discussing LAI (15 of 60 [25%]) vs oral antipsychotic treatment (5 of 60 [8%]). LAIs were not discussed by psychiatrists in 11 of 22 (50%) patients taking oral antipsychotics. When offered, more LAI-naïve patients expressed neutral (9 of 19 [47%]) rather than favorable (3 of 19 [16%]) or unfavorable (7 of 19 [37%]) responses. Prescribers were most concerned about potentially damaging the therapeutic relationship and side-effects when discussing LAIs while patient resistance was often related to negative feelings about injections. Psychiatrists had some success in overcoming patient objections to LAIs by addressing and decomposing initial resistance. More than half (11 of 19 [58%]) of LAI-naïve patients agreed to start LAI treatment following office visits. Patient-described benefits of LAIs vs orals included perceived rapid symptom improvement and greater overall efficacy. Conclusions In this study, many psychiatrists did not offer LAIs and most patients and caregivers were not involved in antipsychotic treatment decision making. Opportunities to increase active patient engagement, address resistances, guide patient drug-formulation selection, and provide better LAI-relevant information for more individualized approaches to treating the patient with schizophrenia were present. PMID:24131801
Shuster, Sara M.; Davey, Cynthia S.
Objective: Determine the percentage of subjects taking antipsychotics who meet criteria for metabolic syndrome based on point-of-care testing analyses. Evaluate pharmacist comprehensive medication management services using point-of-care tests to reduce the mean difference in number of metabolic syndrome risk parameters at 6 and 12 months. Method: This 12-month, prospective, multisite, randomized, controlled study included 120 subjects taking antipsychotics (mean [SD] age of 42.9 [11.3] years) recruited from 3 community mental health clinics in Minnesota. Subjects consented to receive either pharmacist (PCS; n = 60) or no pharmacist (NCS; n = 60) comprehensive medication management services. Data were collected from February 2010 to January 2012. Results: No statistical differences in metabolic syndrome based on point-of-care tests were observed between the 2 groups at baseline (PCS: 85.2%, n = 46 versus NCS: 71.2%, n = 42, P = .073) or at 12 months (PCS: 84.4%, n = 38 versus NCS: 70.2%, n = 33, P = .104). Subjects, overall, screened positive at baseline for dyslipidemia (85.8%, n = 106), hypertension (52.5%, n = 63), and diabetes (22.5%, n = 27) based on point-of-care testing for metabolic risk criteria. After 12 months, a nonsignificant (P = .099) higher adjusted mean number of metabolic syndrome parameters in PCS subjects compared to NCS subjects (mean difference [95% CI] = 0.41 [?0.08 to 0.90]) were found. Conclusions: A relatively high proportion of subjects met criteria for metabolic syndrome, although no significant improvement was observed between the groups after 12 months. Point-of-care test analyses identified a high proportion of subjects meeting criteria for dyslipidemia, hypertension, and diabetes. Utilizing point-of-care tests in mental health settings and fostering interprofessional partnerships with comprehensive medication management pharmacists may improve identification and long-term management of metabolic risks among patients prescribed antipsychotics. Trial Registration: ClinicalTrials.gov identifier: NCT02029989 PMID:25667811
Chabroux, S; Haffen, E; Penfornis, A
Schizophrenia is a common psychiatric illness (1% of the general population), characterized by the association of positive and negative symptoms and cognitive disorders. Antipsychotics, typical or atypical, are known to induce in patients with schizophrenia weight gain and abnormalities in glucose and lipid metabolisms. These modifications, in addition to metabolic risk factors, intrinsic to the psychiatric illness (physical inactivity, smoking, diabetes), increase the risk of cardiovascular complications. Some antipsychotics are associated with a higher risk of metabolic disorders. Before starting such a medication, all risk factors must be taken into account. In case of even effectiveness, one should consider the risk of inducing metabolic disorders, as well as the intrinsic risk factors of the patient, in order to prescribe the medication associated with the lower metabolic risk. Regarding iatrogenic diabetes, the risk of occurrence seems different, depending on the molecules, being more marked for clozapine, olanzapine, risperidone, quietapine then amisulpride, aripiprazole and finally ziprasidone. The physiopathology seems to involve both an increase in insulin resistance and an alteration of insulin secretion. Nevertheless, the benefit/risk often remains largely in favour of treatment, the atypical antipsychotics are at least equally effective and better tolerated on the cognitive and neurological functions than conventional antipsychotics being. They have particularly far fewer extrapyramidal effects. The reversibility of pathologies induced by atypical antipsychotics led to the formulation of guidelines, leading to regular clinical and biological follow-up. PMID:19700142
New safety concerns over diabetes drugs Two drugs commonly prescribed to treat diabetes double of Type II Diabetes. Prescriptions for the drugs, known as thiazolidinediones, have doubled over the last. The results are published in the August edition of the journal Diabetes Care. Congregation 2007 page 59 Race
Kabbara, Wissam K; Ramadan, Wijdan H; Rahbany, Peggy; Al-Natour, Souhaila
Background Fluoroquinolones are among the most widely prescribed antibiotics. However, concerns about increasing resistant microorganisms and the risk of dysglycemia associated with the use of these agents have emerged. Objective The primary objective of the study was to evaluate the appropriate use of commonly prescribed fluoroquinolones, including appropriate indication, dose, dose adjustment in renal impairment, and duration of treatment. The secondary objective was to investigate the dysglycemic effect of fluoroquinolone use (hypoglycemia and/or hyperglycemia) in diabetic and nondiabetic patients. Methods A prospective observational study at a teaching hospital in Lebanon was conducted over a 6-month period. A total of 118 patients receiving broad-spectrum fluoroquinolones (levofloxacin, ciprofloxacin, and moxifloxacin) were identified. Patients were mainly recruited from internal medicine floors and intensive care units. Results The final percentage for the appropriate indication, dose, and duration of fluoroquinolone therapy was 93.2%, 74.6%, and 57.6%, respectively. A total of 57.1% of the patients did not receive the appropriate dose adjustment according to their level of renal impairment. In addition, dysglycemia occurred in both diabetic and nondiabetic patients. Dysglycemia was more frequently encountered with ciprofloxacin (50.0%), followed by levofloxacin (42.4%) and moxifloxacin (7.6%). Hyperglycemia was more common than hypoglycemia in all groups. The highest incidence of hyperglycemia occurred with levofloxacin (70.0%), followed by ciprofloxacin (39.0%) and moxifloxacin (33.3%). In contrast, hypoglycemia did not occur in the ciprofloxacin group, but it was more common with moxifloxacin (11.1%) and levofloxacin (6.0%). Conclusion The major clinical interventions for the future will adjust the dose and duration of therapy with commonly prescribed fluoroquinolones. The incidence of hypoglycemia was less common than hyperglycemia. PMID:25960658
Background To analyse the extent and profile of outpatient regular dispensation of antipsychotics, both in combination and monotherapy, in the Barcelona Health Region (Spain), focusing on the use of clozapine and long-acting injections (LAI). Methods Antipsychotic drugs dispensed for people older than 18 and processed by the Catalan Health Service during 2007 were retrospectively reviewed. First and second generation antipsychotic drugs (FGA and SGA) from the Anatomical Therapeutic Chemical classification (ATC) code N05A (except lithium) were included. A patient selection algorithm was designed to identify prescriptions regularly dispensed. Variables included were age, gender, antipsychotic type, route of administration and number of packages dispensed. Results A total of 117,811 patients were given any antipsychotic, of whom 71,004 regularly received such drugs. Among the latter, 9,855 (13.9%) corresponded to an antipsychotic combination, 47,386 (66.7%) to monotherapy and 13,763 (19.4%) to unspecified combinations. Of the patients given antipsychotics in association, 58% were men. Olanzapine (37.1%) and oral risperidone (36.4%) were the most common dispensations. Analysis of the patients dispensed two antipsychotics (57.8%) revealed 198 different combinations, the most frequent being the association of FGA and SGA (62.0%). Clozapine was dispensed to 2.3% of patients. Of those who were receiving antipsychotics in combination, 6.6% were given clozapine, being clozapine plus amisulpride the most frequent association (22.8%). A total of 3.800 patients (5.4%) were given LAI antipsychotics, and 2.662 of these (70.1%) were in combination. Risperidone was the most widely used LAI. Conclusions The scant evidence available regarding the efficacy of combining different antipsychotics contrasts with the high number and variety of combinations prescribed to outpatients, as well as with the limited use of clozapine. PMID:22587453
Olfson, Mark; Gerhard, Tobias; Huang, Cecilia; Lieberman, Jeffrey A; Bobo, William V; Crystal, Stephen
Scant information exists to guide pharmacological treatment of early-onset schizophrenia. We examine variation across commonly prescribed second-generation antipsychotic medications in medication discontinuation and psychiatric hospital admission among children and adolescents clinically diagnosed with schizophrenia. A 45-state Medicaid claims file (2001-2005) was analyzed focusing on outpatients, aged 6-17 years, diagnosed with schizophrenia or a related disorder prior to starting a new episode of antipsychotic monotherapy with risperidone (n = 805), olanzapine (n = 382), quetiapine (n = 260), aripiprazole (n = 173), or ziprasidone (n = 125). Cox proportional hazard regressions estimated adjusted hazard ratios of 180-day antipsychotic medication discontinuation and 180-day psychiatric hospitalization for patients treated with each medication. During the first 180 days following antipsychotic initiation, most youth treated with quetiapine (70.7%), ziprasidone (73.3%), olanzapine (73.7%), risperidone (74.7%), and aripirazole (76.5%) discontinued their medication (?(2) = 1.69, df = 4, P = .79). Compared with risperidone, the adjusted hazards of antipsychotic discontinuation did not significantly differ for any of the 4-comparator medications. The percentages of youth receiving inpatient psychiatric treatment while receiving their initial antipsychotic medication ranged from 7.19% (aripiprazole) to 9.89% (quetiapine) (?(2) = 0.79, df = 4, P = .94). As compared with risperidone, the adjusted hazard ratio of psychiatric hospital admission was 0.96 (95% CI: 0.57-1.61) for olanzapine, 1.03 (95% CI: 0.59-1.81) for quetiapine, 0.85 (95% CI: 0.43-1.70) for aripiprazole, and 1.22 (95% CI: 0.60-2.51) for ziprasidone. The results suggest that rapid antipsychotic medication discontinuation and psychiatric hospital admission are common in the community treatment of early-onset schizophrenia. No significant differences were detected in risk of either adverse outcome across 5 commonly prescribed second-generation antipsychotic medications. PMID:21307041
McKean, Andrew; Monasterio, Erik
Atypical antipsychotics (AAP) have become some of the most commonly prescribed medications in primary and specialist care settings. Off-label prescribing accounts for much of the expanded use of AAPs. This has become common in the elderly. Marketing by pharmaceutical companies appears to have contributed to the off-label use of AAPs, in situations where their safety and efficacy is far from established. Although evidence provides varying degrees of support for their use for behavioural and psychological symptoms of dementia, augmentation of antidepressants in depression, anxiety, insomnia and in the management of psychosis in Parkinson's Disease, there are a number of potential problems with their expanded use in the elderly. These include weight gain, type two diabetes mellitus, sudden cardiac death and increased mortality rates in the elderly with dementia. It is recommended that whenever AAPs are used off-label, a review date is identified, informed consent is obtained and treatment and side-effects are closely monitored. PMID:25354148
Kintner, Jennifer; Lajoie, Dawn; Hall, Jennifer; Whittimore, Judy; Schoborg, Robert V.
Chlamydia trachomatis, the most common bacterial sexually transmitted disease agent worldwide, enters a viable, non-dividing and non-infectious state (historically termed persistence and more recently referred to as the chlamydial stress response) when exposed to penicillin G in culture. Notably, penicillin G-exposed chlamydiae can reenter the normal developmental cycle upon drug removal and are resistant to azithromycin-mediated killing. Because penicillin G is less frequently prescribed than other ?-lactams, the clinical relevance of penicillin G-induced chlamydial persistence/stress has been questioned. The goal of this study was to determine whether more commonly used penicillins also induce C. trachomatis serovar E persistence/stress. All penicillins tested, as well as clavulanic acid, induced formation of aberrant, enlarged reticulate bodies (RB) (called aberrant bodies or AB) characteristic of persistent/stressed chlamydiae. Exposure to the penicillins and clavulanic acid also reduced chlamydial infectivity by >95%. None of the drugs tested significantly reduced chlamydial unprocessed 16S rRNA or genomic DNA accumulation, indicating that the organisms were viable, though non-infectious. Finally, recovery assays demonstrated that chlamydiae rendered essentially non-infectious by exposure to ampicillin, amoxicillin, carbenicillin, piperacillin, penicillin V, and clavulanic acid recovered infectivity after antibiotic removal. These data definitively demonstrate that several commonly used penicillins induce C. trachomatis persistence/stress at clinically relevant concentrations. PMID:24783061
Recent data suggest that adverse events (AEs) associated with the use of antimicrobial drugs are a major safety concern, with antibiotics implicated in a significant proportion (approximately 20%) of all drug-related emergency department visits in the United States. Although most of these visits are attributable to allergic reactions (79%), certain commonly prescribed antibiotics are notable contributors to conditions that range in nature from gastrointestinal to neurologic and/or psychiatric--particularly after ED visits are adjusted per outpatient prescription visits. This article reviews medically significant AEs of agents included in the major antimicrobial classes--AEs that may be underappreciated by general practitioners. Considerable attention is devoted to the fluoroquinolone agents. Also discussed are the assessment procedures of regulatory agencies in Europe and the United States that are in place to evaluate antimicrobial safety more accurately. Offsetting potential risks and benefits associated with currently available antimicrobials in a climate in which new agents are desperately needed to combat continually evolving multiresistant pathogens remains an interesting dilemma in antimicrobial therapy. PMID:20350633
Rahman, Tahir; Clevenger, Charles V; Kaklamani, Virginia; Lauriello, John; Campbell, Austin; Malwitz, Kari; Kirkland, Robert S
Special consideration is required when prescribing antipsychotic drugs for patients with an existing diagnosis of breast cancer. The package inserts of all approved antipsychotics contain precautions regarding their administration in this patient group. These drugs are well known to elevate serum prolactin levels to varying degrees. Overexpression of the prolactin receptor is seen in more than 95% of human breast cancers. Many genes that are activated by the prolactin receptor are associated with tumorigenesis and cancer cell proliferation. The authors discuss the pathophysiology, clinical implications, and pertinent preclinical data and make specific recommendations regarding the use of antipsychotics in patients with breast cancer. PMID:24880509
Toteja, Nitin; Gallego, Juan A; Saito, Ema; Gerhard, Tobias; Winterstein, Almut; Olfson, Mark; Correll, Christoph U
Antipsychotic polypharmacy (APP), which is common in adults with psychotic disorders, is of unproven efficacy and raises safety concerns. Although youth are increasingly prescribed antipsychotics, little is known about APP in this population. We performed a systematic PubMed search (last update 26 January 2013) of studies reporting the prevalence of APP in antipsychotic-treated youth. Summary statistics and statistical tests were calculated at the study level and not weighted by sample size. Fifteen studies (n = 58 041, range 68-23 183) reported on APP in youth [mean age = 13.4 ± 1.7 yr, 67.1 ± 10.2% male, 77.9 ± 27.4% treated with second-generation antipsychotics (SGAs)]. Data collected in these studies covered 1993-2008. The most common diagnoses were attention-deficit hyperactivity disorder (ADHD; 39.9 ± 23.5%) and conduct disorder/oppositional defiant disorder (CD/ODD; 33.6 ± 24.8). In studies including predominantly children (mean age = <13 yr, N = 5), the most common diagnosis were ADHD (50.6 ± 25.4%) and CD/ODD (39.5 ± 27.5%); while in studies with predominantly adolescents (mean age = ?13 yr, N = 7) the most common diagnoses were schizophrenia-spectrum disorders (28.6 ± 23.8%), anxiety disorders (26.9 ± 14.9%) and bipolar-spectrum disorders (26.6 ± 7.0%), followed closely by CD/ODD (25.8 ± 17.7). The prevalence of APP among antipsychotic-treated youth was 9.6 ± 7.2% (5.9 ± 4.5% in child studies, 12.0 ± 7.9% in adolescent studies, p = 0.15). Higher prevalence of APP was correlated with a bipolar disorder or schizophrenia diagnosis (p = 0.019) and APP involving SGA+SGA combinations (p = 0.0027). No correlation was found with APP definition [?1 d (N = 10) vs. >30-?90 d (N = 5), p = 0.88]. Despite lacking safety and efficacy data, APP in youth is not uncommon, even in samples predominantly consisting of non-psychotic patients. The duration, clinical motivations and effectiveness of this practice require further study. PMID:23673334
Toteja, Nitin; Gallego, Juan A.; Saito, Ema; Gerhard, Tobias; Winterstein, Almut; Olfson, Mark; Correll, Christoph U.
Antipsychotic polypharmacy (APP), which is common in adults with psychotic disorders, is of unproven efficacy and raises safety concerns. Although youth are increasingly prescribed antipsychotics, little is known about APP in this population. We performed a systematic PubMed search (last update 26 January 2013) of studies reporting the prevalence of APP in antipsychotic-treated youth. Summary statistics and statistical tests were calculated at the study level and not weighted by sample size. Fifteen studies (n=58 041, range 68–23 183) reported on APP in youth [mean age=13.4±1.7 yr, 67.1±10.2% male, 77.9±27.4% treated with second-generation antipsychotics (SGAs)]. Data collected in these studies covered 1993–2008. The most common diagnoses were attention-deficit hyperactivity disorder (ADHD; 39.9±23.5%) and conduct disorder/oppositional defiant disorder (CD/ODD; 33.6±24.8). In studies including predominantly children (mean age=<13 yr, N=5), the most common diagnosis were ADHD (50.6±25.4%) and CD/ODD (39.5±27.5%); while in studies with predominantly adolescents (mean age =?13 yr, N=7) the most common diagnoses were schizophrenia-spectrum disorders (28.6±23.8%), anxiety disorders (26.9±14.9%) and bipolar-spectrum disorders (26.6±7.0%), followed closely by CD/ODD (25.8±17.7). The prevalence of APP among antipsychotic-treated youth was 9.6±7.2% (5.9±4.5% in child studies, 12.0±7.9% in adolescent studies, p=0.15). Higher prevalence of APP was correlated with a bipolar disorder or schizophrenia diagnosis (p=0.019) and APP involving SGA+SGA combinations (p=0.0027). No correlation was found with APP definition [?1 d (N=10) vs. >30–?90 d (N=5), p=0.88]. Despite lacking safety and efficacy data, APP in youth is not uncommon, even in samples predominantly consisting of non-psychotic patients. The duration, clinical motivations and effectiveness of this practice require further study. PMID:23673334
Hsu, Yi-Chien; Chou, Yu-Ching; Chang, Hsin-An; Kao, Yu-Chen; Huang, San-Yuan; Tzeng, Nian-Sheng
Objectives Refractory major depressive disorder (MDD) is a serious problem leading to a heavy economic burden. Antipsychotic augmentation treatment with aripiprazole and quetiapine is approved for MDD patients and can achieve a high remission rate. This study aimed to examine how psychiatrists in Taiwan choose medications and how that choice is influenced by health insurance payments and administrative policy. Design Descriptive study. Outcome measures Eight questions about the choice of treatment strategy and atypical antipsychotics, and the reason to choose aripiprazole. Intervention We designed an augmentation strategy questionnaire for psychiatrists whose patients had a poor response to antidepressants, and handed it out during the annual meeting of the Taiwanese Society of Psychiatry in October 2012. It included eight questions addressing the choice of treatment strategy and atypical antipsychotics, and the reason whether or not to choose aripiprazole as the augmentation antipsychotic. Results Choosing antipsychotic augmentation therapy or switching to other antidepressant strategies for MDD patients with an inadequate response to antidepressants was common with a similar probability (76.1% vs 76.4%). The most frequently used antipsychotics were aripiprazole and quetiapine, however a substantial number of psychiatrists chose olanzapine, risperidone, and sulpiride. The major reason for not choosing aripiprazole was cost (52.1%), followed by insurance official policy audit and deletion in the claims review system (30.1%). Conclusion The prescribing behavior of Taiwanese psychiatrists for augmentation antipsy-chotics is affected by health insurance policy. PMID:25657586
Aguado, Víctor; Rico, Guillem; Labad, Javier; de Pablo, Joan; Vilella, Elisabet
Background The analysis of prescribing patterns in entire catchment areas contributes to global mapping of the use of antipsychotics and may improve treatment outcomes. Objective To determine the pattern of long-term antipsychotic prescription in outpatients with schizophrenia in the province of Tarragona (Catalonia-Spain). Methods A naturalistic, observational, retrospective, non-interventional study based on the analysis of registries of computerized medical records from an anonymized database of 1,765 patients with schizophrenia treated between 2011 and 2013. Results The most used antipsychotic was risperidone, identified in 463 (26.3%) patients, followed by olanzapine in 249 (14.1%), paliperidone in 225 (12.7%), zuclopenthixol in 201 (11.4%), quetiapine in 141 (8%), aripiprazole in 100 (5.7%), and clozapine in 100 (5.7%). Almost 8 out of 10 patients (79.3%) were treated with atypical or second-generation antipsychotics. Long-acting injectable (LAI) formulations were used in 44.8% of patients. Antipsychotics were generally prescribed in their recommended doses, with clozapine, ziprasidone, LAI paliperidone, and LAI risperidone being prescribed at the higher end of their therapeutic ranges. Almost 7 out of 10 patients (69.6%) were on antipsychotic polypharmacy, and 81.4% were on psychiatric medications aside from antipsychotics. Being prescribed quetiapine (OR 14.24, 95% CI 4.94–40.97), LAI (OR 9.99, 95% CI 6.45–15.45), psychiatric co-medications (OR 4.25, 95% CI 2.72–6.64), and paliperidone (OR 3.13, 95% CI 1.23–7.92) were all associated with an increased likelihood of polypharmacy. Being prescribed risperidone (OR 0.54, 95% CI 0.35–0.83) and older age (OR 0.98, 95% CI 0.97–0.99) were related to a low polypharmacy probability. Conclusions Polypharmacy is the most common pattern of antipsychotic use in this region of Spain. Use of atypical antipsychotics is extensive. Most patients receive psychiatric co-medications such as anxiolytics or antidepressants. Polypharmacy is associated with the use of quetiapine or paliperidone, use of a LAI, younger age, and psychiatric co-medication. PMID:26427051
Background To describe the rates, indications, and adverse effects of psychotropic drug prescription in a specialist tertiary hospital child and adolescent eating disorder service. Methods Retrospective case note study of all active eating disorder patients (N?=?115) over the period of treatment from referral to time of study (M?=?2 years), covering patient demographics, clinical characteristics, drug prescriptions, indications, and adverse effects. Results Psychotropic drugs were prescribed in 45% of cases, most commonly antidepressants (41%), followed by anxiolytics (29%) and antipsychotics (22%), with 8% initiated before referral to the specialist eating disorder program. Common indications were depressed mood, agitation, anxiety, and insomnia. Patient clinical severity and complexity was associated with prescribing. Adverse effects, mostly minor, were recorded in 23% of antidepressant prescriptions, 39% of antipsychotic prescriptions, and 13% of anxiolytic prescriptions. Second generation antipsychotic prescription was associated with subsequent new onset binge eating, in this preliminary observational study. Self-harm by overdose of psychotropics occurred in 11% of patients prescribed medication. Conclusions Psychotropic medications were frequently prescribed to adolescent eating disorder patients to treat distressing symptoms. Prospective randomised controlled trials to clarify efficacy and safety are needed. Given the difficulties of conducting clinical trials in this population, services are encouraged to monitor and audit medication safety and efficacy in everyday practice, and to report their findings. PMID:24999406
Jenkins, Timothy C.; Irwin, Amy; Coombs, Letoynia; DeAlleaume, Lauren; Ross, Stephen E.; Rozwadowski, Jeanne; Webster, Brian; Dickinson, L. Miriam; Sabel, Allison L.; MacKenzie, Thomas D.; West, David R.; Price, Connie S.
Background Antibiotic overuse in the primary care setting is common. Our objective was to evaluate the effect of a clinical pathway-based intervention on antibiotic use. Methods Eight primary care clinics were randomized to receive clinical pathways for upper respiratory infection, acute bronchitis, acute rhinosinusitis, pharyngitis, acute otitis media, urinary tract infection, skin infections, and pneumonia and patient education materials (study group) versus no intervention (control group). Generalized linear mixed effects models were used to assess trends in antibiotic prescriptions for non-pneumonia acute respiratory infections and broad-spectrum antibiotic use for all eight conditions during a 2-year baseline and 1-year intervention period. Results In the study group, antibiotic prescriptions for non-pneumonia acute respiratory infections decreased from 42.7% of cases at baseline to 37.9% during the intervention period (11.2% relative reduction) (p <.0001) and from 39.8% to 38.7%, respectively, in the control group (2.8% relative reduction) (p=0.25). Overall use of broad-spectrum antibiotics in the study group decreased from 26.4% to 22.6% of cases, respectively, (14.4% relative reduction) (p <.0001) and from 20.0% to 19.4%, respectively, in the control group (3.0% relative reduction) (p=0.35). There were significant differences in the trends of prescriptions for acute respiratory infections (p<.0001) and broad-spectrum antibiotic use (p=0.001) between the study and control groups during the intervention period, with greater declines in the study group. Conclusions This intervention was associated with declining antibiotic prescriptions for non-pneumonia acute respiratory infections and use of broad-spectrum antibiotics over the first year. Evaluation of the impact over a longer study period is warranted. PMID:23507206
Murphy, Andrea L.; Gardner, David M.; Kisely, Steve; Cooke, Charmaine; Kutcher, Stan P.; Hughes, Jean
Objective: To explore the lived experience of youth who are prescribed antipsychotics. Methods: We conducted an interpretive phenomenology study of young people with recent experience of taking antipsychotics. Youth were interviewed and a staged approach was used for data analysis of transcriptions. We collected approximately 13 hours of audio from 18 youth aged 13 to 26 years between January and August of 2010. Results: Ambivalence was significant and antipsychotic adverse effects frequently tempered benefits. Both illness and antipsychotics had significant impacts on physical and mental wellbeing with adverse effects on relationships and functioning in various contexts (e.g., school). Stigma related to both antipsychotics and illness was also prominent. Participants’ limited knowledge about their antipsychotics and pressure to conform within their youth culture and context affected decisions on starting, adhering to, and persisting with treatment. Conclusions: The lived experience of youth taking antipsychotics is complex and the benefits (e.g., symptom improvement) and consequences (e.g., adverse effects) associated with antipsychotics affect all facets of life. More research is needed to better understand youth priorities in treatment decisions and whether youth who demonstrate substantive gaps in their knowledge about antipsychotics are truly given the opportunity to be informed and engage in management decisions including whether to initiate, persist with, and discontinue treatments.
Goebert, Deborah; Else, Iwalani; Carlton, Barry; Matsu, Courtenay; Guerrero, Anthony
Previous studies have shown significant ethnic differences in prescribing patterns of two or more antipsychotics. This study examined changes in atypical and typical antipsychotic prescriptions among Asian Americans and Pacific Islanders. Five hundred consecutive charts were reviewed for antipsychotics at the time of admission and discharge from each of two inpatient psychiatric facilities in Hawai‘i. Multiple antipsychotic prescription rates were 9% at intake and 6% at discharge. For the ethnic groups studied, there were no statistically significant differences by patient ethnicity regarding antipsychotics at intake (?2 = 29.2, df = 21, P = .110) or discharge (?2 = 20.5, df = 24, P = .667). There were no significant differences in prescription and polypharmacy patterns among Asian Americans and Pacific Islanders ethnic groups in this study. PMID:25285256
Azoulay, Laurent; Yin, Hui; Renoux, Christel; Suissa, Samy
To determine whether atypical antipsychotics, when compared to typical antipsychotics, increase the risk of breast cancer. We conducted a retrospective cohort study using a nested case-control analysis within the United Kingdom General Practice Research Database population. We identified all female patients prescribed at least one antipsychotic (either typical or atypical), between 1 January 1988 and 31 December 2007, with follow-up until 31 December 2010. All incident cases of breast cancer were identified and matched up to 10 controls. Adjusted rate ratios (RR) of breast cancer associated with ever use of atypical antipsychotics was compared to ever use of typical antipsychotics. The cohort included 106,362 patients prescribed antipsychotics during the study period. During a mean follow-up of 5.3 years, 1237 patients were diagnosed with breast cancer (overall rate: 2.7 per 1000/year). Compared to patients who only used typical antipsychotics, exclusive users of atypical antipsychotics were not an increased risk of breast cancer (RR: 0.81, 95% CI: 0.63, 1.05). These results remained consistent after considering specific atypical antipsychotics known to significantly increase prolactin levels such as risperidone (RR: 0.86, 95% CI: 0.60, 1.25). Furthermore, no dose-response was observed in terms of cumulative duration of use and cumulative dose in olanzapine equivalents. The results of this study should provide reassurance that compared to typical antipsychotics, atypical antipsychotics do not increase the risk of breast cancer. PMID:21479550
Rosenbloom, S Trent; Awad, Joseph; Speroff, Ted; Elkin, Peter L; Rothman, Russell; Spickard, Anderson; Peterson, Josh; Bauer, Brent A; Wahner-Roedler, Dietland L; Lee, Mark; Gregg, William M; Johnson, Kevin B; Jirjis, Jim; Erlbaum, Mark S; Carter, John S; Lincoln, Michael J; Brown, Steven H
The National Drug File Reference Terminology contains a novel reference hierarchy to describe physiologic effects (PE) of drugs. The PE reference hierarchy contains 1697 concepts arranged into two broad categories; organ specific and generalized systemic effects. This investigation evaluated the appropriateness of the PE concepts for classifying a random selection of commonly prescribed medications. Ten physician reviewers classified the physiologic effects of ten drugs and rated the accuracy of the selected term. Inter reviewer agreement, overall confidence, and concept frequencies were assessed and were correlated with the complexity of the drug's known physiologic effects. In general, agreement between reviewers was fair to moderate (kappa 0.08-0.49). The physiologic effects modeled became more disperse with drugs having and inducing multiple physiologic processes. Complete modeling of all physiologic effects was limited by reviewers focusing on different physiologic processes. The reviewers were generally comfortable with the accuracy of the concepts selected. Overall, the PE reference hierarchy was useful for physician reviewers classifying the physiologic effects of drugs. Ongoing evolution of the PE reference hierarchy as it evolves should take into account the experiences of our reviewers. PMID:14728237
Background The safety and effectiveness of psychotropic drug use in the paediatric population is widely debated, in particular because of the lack of data concerning long term effects. In Italy the prevalence of psychotropic drug prescriptions increased in the early 2000s and decreased afterwards. In such a context, a study with the aim to estimate the incidence and prevalence of psychotropic drug prescription in the paediatric population and to describe diagnostic and therapeutic approaches was performed. Methods The study population was composed of 76,000 youths less than 18 years and living in the area covered by the local health unit of Verona, Italy. The data source was the Verona local health unit's administrative prescription database. Prevalence and incidence of antidepressant and/or antipsychotic drug prescriptions in the 2004-2008 period were estimated. Children and adolescents receiving antidepressant and/or antipsychotic drug prescriptions between 1 January 2005 and 31 December 2006 were identified and questionnaires were sent to the prescribers with the aim to collect data concerning diagnostic and therapeutic approaches, and care strategies. Results The prevalence of psychotropic drug prescriptions did not change in the 2004-2008 period, while incidence slightly increased (from 7.0 in 2005 to 8.3 per 10,000 in 2008). Between 1 January 2005 and 31 December 2006, 111 youths received at least one psychotropic drug prescription, 91 of whom received antidepressants. Only 28 patients attended child and adolescent psychiatry services. Information concerning diagnostic and therapeutic approaches, and care strategies was collected for 52 patients (47%). Anxiety-depressive syndrome and attention disorders were the diseases for which psychotropic drugs were most commonly prescribed. In all, 75% youths also received psychological support and 20% were prescribed drugs for 2 or more years. Conclusions Despite the low drug prescription prevalence, the finding that most children were not cared for by child and adolescent psychiatric services is of concern and calls for a systematic, continuous monitoring of psychopharmacological treatments. PMID:21605367
Ansbach, Robert K.; Dybus, Karen; Bergeson, Rachel
Treatment of uncomplicated urinary tract infections (UTIs) has changed in the past few years with researchers advocating empiric treatment for shorter periods of time without the use of cultures. Researchers report that antibiotic resistance of Escherichia coli (E coli) to commonly prescribed antibiotics in uncomplicated UTIs has been increasing.…
Correll, Christoph U.; Frederickson, Anne M.; Kane, John M.; Manu, Peter
Objective To determine whether the co-prescribing of two or more antipsychotics, a relatively frequent practice with little data to support its safety and efficacy, is associated with an increased prevalence of metabolic syndrome. Methods 364 newly admitted adults treated with second-generation antipsychotics underwent assessments evaluating antipsychotic polytherapy, and of the presence of metabolic syndrome and triglycerides/high-density lipoprotein cholesterol ratio >3.5 (TG/HDL), a sensitive marker of insulin resistance. The correlates of antipsychotic polytherapy and associations with metabolic syndrome and TG/HDL were determined by univariate comparisons and multiple logistic regression analyses. Results Antipsychotic polytherapy was present in 70 patients (19.2%) and was significantly more likely in patients with schizophrenia and those treated with clozapine, quetiapine or ziprasidone (p<0.0001). Compared with antipsychotic monotherapy, polytherapy was associated with elevated rates of metabolic syndrome (50.0% vs. 34.3%, p=0.015) and TG/HDL (50.7% vs. 35.0%, p=0.016). However, in logistic regression analyses, metabolic syndrome was significantly associated with higher body mass index (BMI), older age, a diagnosis of bipolar disorder or schizophrenia, and cotreatment with a first-generation antipsychotic (r2: 0.25, p<0.0001). The TG/HDL marker of insulin resistance was associated with higher BMI, male sex, Caucasian race and absence of aripiprazole treatment (r2: 0.14, p<0.0001). Antipsychotic polypharmacy dropped out of both multivariate models. Conclusions Compared with patients receiving antipsychotic monotherapy, patients on antipsychotic polytherapy have higher rates of metabolic syndrome and lipid markers of insulin resistance. However, antipsychotic polytherapy is not independently associated with the prevalence of these abnormalities, which are related to known demographic, clinical and anthropometric risk factors. PMID:17070017
Gambassi, Giovanni; Sultana, Janet; Trifirò, Gianluca
Antipsychotics are frequently and increasingly prescribed off-label for the treatment of behavioral and psychological symptoms associated with dementia, despite their modest efficacy. Instead, the safety profile of antipsychotics has been questioned repeatedly in recent years with various concerns, including death. Meta-analyses of randomized controlled trials found that one of the major causes of death associated with atypical antipsychotics use was pneumonia. Only few observational studies, however, have investigated the risk of pneumonia in elderly patients, especially among those receiving conventional antipsychotics. The aim of this editorial is to synthesize the current evidence from observational studies regarding the risk of pneumonia in elderly patients receiving either conventional or atypical antipsychotics. The studies conducted so far document that the risk of pneumonia is two- to threefold increased in a dose-dependent fashion with both classes compared to nonuse, with a possibly higher risk attributable to atypical antipsychotics. The risk seems to peak at the beginning of treatment (e.g., 7 - 30 days), and dissipates over time for both conventional and atypical antipsychotics. The risk-benefit ratio suggests that there will be 1 excess hospitalization for pneumonia for every 2 - 5 patients receiving any clinical improvement in symptoms. Considering the modest improvement in terms of efficacy, the risks associated with antipsychotics in elderly patients may outweigh their benefit. PMID:25431005
Fervaha, Gagan; Takeuchi, Hiroyoshi; Lee, Jimmy; Foussias, George; Fletcher, Paul J; Agid, Ofer; Remington, Gary
Antipsychotic drugs are thought to produce secondary negative symptoms, which can also exacerbate primary negative symptoms. In the present study, we examined whether motivational deficits in particular were related to antipsychotic treatment in patients with schizophrenia in a dose-dependent manner. Five hundred and twenty individuals with schizophrenia who were receiving antipsychotic monotherapy for at least 6 months and followed prospectively were included in the present study. Participants were receiving one of five antipsychotic medications (olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone), and analyses were conducted for patients receiving each drug separately. Analysis of covariance models were constructed to examine the effect of antipsychotic dose on level of motivational impairment, controlling for selected demographic and clinical variables (eg, positive symptoms). Level of motivation, or deficits therein, were evaluated using a derived measure from the Quality of Life Scale, and in addition with scores derived from the Positive and Negative Syndrome Scale. Antipsychotic dose was not related to the level of amotivation for any of the medications examined. Moreover, severity of sedation was not significantly related to the degree of amotivation. One hundred and twenty-one individuals were identified as antipsychotic-free at baseline, and after 6 months of antipsychotic treatment, no change in motivation was found. Chronic treatment with antipsychotics does not necessarily impede or enhance goal-directed motivation in patients with schizophrenia. It is possible that the negative impact of antipsychotics in this regard is overstated; conversely, the present results also indicate that we must look beyond antipsychotics in our efforts to improve motivation. PMID:25567425
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Huskamp, Haiden; O’Malley, A. James; Horvitz-Lennon, Marcela; Taub, Anna Levine; Berndt, Ernest; Donohue, Julie
Objective To examine physician adoption of second-generation antipsychotic medications and identify physician-level factors associated with early adoption. Methods Using IMS Health Xponent™ data, which captures over 70% of all prescriptions filled in the U.S., and AMA Masterfile data on prescriber characteristics for each of 9 second-generation antipsychotics introduced from 1996–2008 for 30,369 physicians who prescribed antipsychotics, we estimate drug-specific Cox proportional hazards models of time to adoption and conduct descriptive analysis of the total number of agents prescribed. Results On average, physicians waited two or more years before prescribing new second-generation antipsychotics, but there was substantial heterogeneity across products in time to adoption. General practitioners were much slower to adopt second-generation antipsychotics than psychiatrists (hazard ratios (HRs) ranged from 0.10–0.35); solo practitioners were slower to adopt most products than group practitioners (HRs ranged from 0.77–0.89). Physicians in the highest quartile of antipsychotic prescribing volume adopted second-generation antipsychotics much faster than physicians in the lowest quartile (HRs ranged from 0.15–0.39). Psychiatrists tended to prescribe a broader set of antipsychotics (median of 6) than other specialties (median of 2 for general practitioners and neurologists and 1 for pediatricians). Conclusions Policymakers are searching for ways to control rapid health spending growth, which is driven primarily by use of new technologies such as second-generation antipsychotics. Understanding the factors that influence physician adoption of new medications will be crucial in the implementation of efforts aimed at maximizing value of care received by individuals with mental disorders as well as efforts to improve medication safety. PMID:23280376
Fazel, Seena; Zetterqvist, Johan; Larsson, Henrik; Långström, Niklas; Lichtenstein, Paul
Summary Background Antipsychotics and mood stabilisers are prescribed widely to patients with psychiatric disorders worldwide. Despite clear evidence for their efficacy in relapse prevention and symptom relief, their effect on some adverse outcomes, including the perpetration of violent crime, is unclear. We aimed to establish the effect of antipsychotics and mood stabilisers on the rate of violent crime committed by patients with psychiatric disorders in Sweden. Methods We used linked Swedish national registers to study 82?647 patients who were prescribed antipsychotics or mood stabilisers, their psychiatric diagnoses, and subsequent criminal convictions in 2006–09. We did within-individual analyses to compare the rate of violent criminality during the time that patients were prescribed these medications versus the rate for the same patients while they were not receiving the drugs to adjust for all confounders that remained constant within each participant during follow-up. The primary outcome was the occurrence of violent crime, according to Sweden's national crime register. Findings In 2006–09, 40?937 men in Sweden were prescribed antipsychotics or mood stabilisers, of whom 2657 (6·5%) were convicted of a violent crime during the study period. In the same period, 41?710 women were prescribed these drugs, of whom 604 (1·4 %) had convictions for violent crime. Compared with periods when participants were not on medication, violent crime fell by 45% in patients receiving antipsychotics (hazard ratio [HR] 0·55, 95% CI 0·47–0·64) and by 24% in patients prescribed mood stabilisers (0·76, 0·62–0·93). However, we identified potentially important differences by diagnosis—mood stabilisers were associated with a reduced rate of violent crime only in patients with bipolar disorder. The rate of violence reduction for antipsychotics remained between 22% and 29% in sensitivity analyses that used different outcomes (any crime, drug-related crime, less severe crime, and violent arrest), and was stronger in patients who were prescribed higher drug doses than in those prescribed low doses. Notable reductions in violent crime were also recorded for depot medication (HR adjusted for concomitant oral medications 0·60, 95% CI 0·39–0·92). Interpretation In addition to relapse prevention and psychiatric symptom relief, the benefits of antipsychotics and mood stabilisers might also include reductions in the rates of violent crime. The potential effects of these drugs on violence and crime should be taken into account when treatment options for patients with psychiatric disorders are being considered. Funding The Wellcome Trust, the Swedish Prison and Probation Service, the Swedish Research Council, and the Swedish Research Council for Health, Working Life and Welfare. PMID:24816046
Background Analysis of the prescribing patterns of antipsychotic drugs can improve therapeutic outcomes. The purpose of this study was to evaluate the prescribing pattern of antipsychotics and its conformance to international treatment guidelines. Methods A cross sectional study at primary psychiatric centers was carried out. Patients’ medical files were used to obtain demographic, medication and clinical information. International guidelines for schizophrenia were used to create conformance indicators. All statistical analyses were conducted using Statistical Package for Social Sciences. Results 250 patients were included in this study. A total of 406 antipsychotic agents were used; 348 (85.7%) were first generation antipsychotics (FGA). The prevalence of antipsychotic combination was 50.4% (n=126). There was no significant difference in positive (p=0.3), negative (p=0.06) and psychopathology (p=0.5) scores of schizophrenia symptoms among patients on monotherapy versus those on antipsychotic combination. Furthermore, no significant difference was observed in the annual cost of antipsychotic monotherapy versus combination therapy. One hundred and five patients (42%) were using optimum dose of (300 – 600 mg CPZeq) while the remaining were using sub or supra therapeutic doses. Analysis showed that use of depot, use of anticholinergic agents and increasing amount of total CPZeq were significant factors associated with antipsychotic combination. Conclusions This study indicated that antipsychotic prescribing was not in conformance with international guidelines with respect to maintenance dose and combination therapy. Type of antipsychotic treatment regimen, combination versus monotherapy, was not associated with better clinical or economic outcome. PMID:23816223
Ajemigbitse, Adetutu A.; Omole, Moses Kayode; Ezike, Nnamdi Chika; Erhun, Wilson O.
Context: Junior doctors are reported to make most of the prescribing errors in the hospital setting. Aims: The aim of the following study is to determine the knowledge intern doctors have about prescribing errors and circumstances contributing to making them. Settings and Design: A structured questionnaire was distributed to intern doctors in National Hospital Abuja Nigeria. Subjects and Methods: Respondents gave information about their experience with prescribing medicines, the extent to which they agreed with the definition of a clinically meaningful prescribing error and events that constituted such. Their experience with prescribing certain categories of medicines was also sought. Statistical Analysis Used: Data was analyzed with Statistical Package for the Social Sciences (SPSS) software version 17 (SPSS Inc Chicago, Ill, USA). Chi-squared analysis contrasted differences in proportions; P < 0.05 was considered to be statistically significant. Results: The response rate was 90.9% and 27 (90%) had <1 year of prescribing experience. 17 (56.7%) respondents totally agreed with the definition of a clinically meaningful prescribing error. Most common reasons for prescribing mistakes were a failure to check prescriptions with a reference source (14, 25.5%) and failure to check for adverse drug interactions (14, 25.5%). Omitting some essential information such as duration of therapy (13, 20%), patient age (14, 21.5%) and dosage errors (14, 21.5%) were the most common types of prescribing errors made. Respondents considered workload (23, 76.7%), multitasking (19, 63.3%), rushing (18, 60.0%) and tiredness/stress (16, 53.3%) as important factors contributing to prescribing errors. Interns were least confident prescribing antibiotics (12, 25.5%), opioid analgesics (12, 25.5%) cytotoxics (10, 21.3%) and antipsychotics (9, 19.1%) unsupervised. Conclusions: Respondents seemed to have a low awareness of making prescribing errors. Principles of rational prescribing and events that constitute prescribing errors should be taught in the practice setting. PMID:24808682
Matson, Johnny L.; Mahan, Sara
Antipsychotic drugs are the most frequently prescribed of the psychotropic drugs among the intellectually disabled (ID) population. Given their widespread use, efforts to systematically assess and report side effects are warranted. Specific scaling methods such as the "Matson Evaluation of Side Effects" ("MEDS"), the "Abnormal Inventory Movement…
Pouget, Jennie G.; Shams, Tahireh A.; Tiwari, Arun K.; Müller, Daniel J.
Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h2~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future. PMID:25733959
Zareba, Wojciech; Lin, David A
The QTc prolongation by antipsychotic drugs is of major concern, especially in light of the data indicating an increased risk of sudden death in psychiatric patients taking these drugs. Sudden death in psychiatric patients could be partially attributed to drug-induced torsades de pointes and for this reason careful evaluation of QTc prolonging properties of antipsychotic drugs is needed. Antipsychotic drugs prolong QT interval usually by blocking the potassium IKr current. Improved understanding of ion channel structure and kinetics and its role in repolarization has tremendous impact on understanding of the mechanisms of drug-induced QT prolongation and torsades de pointes. Proarrhythmia caused by a QT-prolonging drug occurs infrequently, and usually multiple factors need to operate to precipitate such an event including a combination of two or more drugs affecting the same pathway, hypokalemia, and possibly genetic predisposition. Currently prescribed antipsychotics might cause QT prolongation ranging from 4-6 ms for haloperidol and olanzapine to 35 ms for thioridazine. The response of a patient to a drug is very individual and therefore an individualized system of drug administration and monitoring needs to be developed which takes into account baseline QTc duration and its changes after a drug was introduced. A systematic approach while stratifying psychiatric patients as those with short QTc (QTc < or = 0.41 sec), borderline QTc (QTC = 0.42-0.44 sec), and prolonged QTc (0.45 sec) is being proposed to improve the safety of administering antipsychotic drugs and to decrease the risk of drug-related sudden death in psychiatric patients. PMID:12918603
Vasilyeva, Irina; Biscontri, Robert G.; Enns, Murray W.; Metge, Colleen J.; Alessi-Severini, Silvia
Background Despite concerns over the potential for severe adverse events, antipsychotic medications remain the mainstay of treatment of behaviour disorders and psychosis in elderly patients. Second-generation antipsychotic agents (SGAs; e.g., risperidone, olanzapine, quetiapine) have generally shown a better safety profile compared to the first-generation agents (FGAs; e.g., haloperidol and phenothiazines), particularly in terms of a lower potential for involuntary movement disorders. Risperidone, the only SGA with an official indication for the management of inappropriate behaviour in dementia, has emerged as the antipsychotic most commonly prescribed to older patients. Most clinical trials evaluating the risk of movement disorders in elderly patients receiving antipsychotic therapy have been of limited sample size and/or of relatively short duration. A few observational studies have produced inconsistent results. Methods A population-based retrospective cohort study of all residents of the Canadian province of Manitoba aged 65 and over, who were dispensed antipsychotic medications for the first time during the time period from April 1, 2000 to March 31, 2007, was conducted using Manitoba's Department of Health's administrative databases. Cox proportional hazards models were used to determine the risk of extrapyramidal symptoms (EPS) in new users of risperidone compared to new users of FGAs. Results After controlling for potential confounders (demographics, comorbidity and medication use), risperidone use was associated with a lower risk of EPS compared to FGAs at 30, 60, 90 and 180 days (adjusted hazard ratios [HR] 0.38, 95% CI: 0.22–0.67; 0.45, 95% CI: 0.28–0.73; 0.50, 95% CI: 0.33–0.77; 0.65, 95% CI: 0.45–0.94, respectively). At 360 days, the strength of the association weakened with an adjusted HR of 0.75, 95% CI: 0.54–1.05. Conclusions In a large population of elderly patients the use of risperidone was associated with a lower risk of EPS compared to FGAs. PMID:23696870
Herbert Y Meltzer
Recent interest in the role of serotonin (5-HT) in antipsychotic drug action is based mainly upon the fact that antipsychotic drugs such as clozapine, olanzapine, quetiapine, risperidone, sertindole, and ziprasidone are potent 5-HT2a receptor antagonists and relatively weaker dopamine D2 antagonists. These agents share in common low extrapyramidal side effects at clinically effective doses and possibly greater efficacy to reduce
Tejal K. Gandhi; Saul N. Weingart; Andrew C. Seger; Joshua Borus; Elisabeth Burdick; Eric G. Poon; Lucian L. Leape; David W. Bates
BACKGROUND: Medication errors are common among inpatients and many are preventable with computerized prescribing. Relatively little is\\u000a known about outpatient prescribing errors or the impact of computerized prescribing in this setting.\\u000a \\u000a \\u000a OBJECTIVE: To assess the rates, types, and severity of outpatient prescribing errors and understand the potential impact of computerized\\u000a prescribing.\\u000a \\u000a \\u000a \\u000a \\u000a DESIGN: Prospective cohort study in 4 adult primary care
Sera, Leah; Holmes, Holly M.; McPherson, Mary Lynn
Objectives Despite being a common admitting diagnosis, there is very little published literature on medication management in hospice patients admitted with a diagnosis of failure to thrive or debility. The purpose of this study was to describe medication prescribing practices in hospice patients with either of these primary diagnoses by characterizing prescribed medications by name and by pharmaceutical class, and determining whether the patient or the hospice organization provided each medication. Methods A retrospective review of a patient information database compiled by a national hospice organization was conducted. Patients were included in this retrospective study if they were admitted to hospice care with a primary diagnosis of failure to thrive or debility, and if they were admitted on or after 1 January 2010, and discharged by death on or before 31 December 2010. Results Overall 293 patients and 6181 medication entries were evaluated. The most commonly prescribed drugs were acetaminophen, lorazepam, morphine, atropine, prochlorperazine, haloperidol, docusate, aspirin, and bisacodyl. The most commonly prescribed pharmacological classes were opioid and non-opioid analgesics, anxiolytics, anticholinergics, antihypertensives, laxatives, antidepressants, and supplements. The hospice organization provided over 90% of prescriptions for analgesics, antipsychotics, anticholinergics, and anxiolytics, and these medications were discontinued before death in less than 5% of patients. Conclusion Recognized clinical components of failure to thrive syndrome include cognitive impairment, malnutrition, and depression. The hospice organization provided 80% of antidepressants, but infrequently provided appetite stimulants and drugs treating dementia. The most commonly provided drugs were those used for symptoms associated with most end-stage diseases. PMID:24904199
Avasthi, Ajit; Aggarwal, Munish; Grover, Sandeep; Khan, Mohd Khalid Rasheed
Antipsychotic as a class of medications became available for treatment of various psychiatric disorders in the early 1950’s. Over the last 60 years many antipsychotics have become available. In line with the west, Indian researchers have evaluated the efficacy of antipsychotics in various conditions. Additionally, researchers have also evaluated the important safety and tolerability issues. Here, we review data originating from India in the form of drug trials, effectiveness, usefulness, safety and tolerability of antipsychotics. Additionally, data with respect to other important treatment related issues is discussed. PMID:21836703
Mort, Jane R; Sailor, Ryan; Hintz, Lori
In 2012, the Centers for Medicare & Medicaid Services (CMS) established a partnership among stakeholders to decrease the percentage of residents in nursing homes receiving an antipsychotic agent by 15 percent. This goal emanated from concerns including the large percentage of residents taking antipsychotic agents, the questionable use of antipsychotics (e.g., off-label use), the high cost of inappropriate antipsychotic use, and toxicity in patients with dementia (e.g., black box warning regarding mortality). The successful achievement of this goal is evaluated via quality measures, which are greatly influenced by changes in exclusion of residents from the population examined. The partnership is focused on optimizing use of antipsychotic agents by training clinicians on nonpharmacologic approaches, educating on the dangers of antipsychotic medication use and sharing data on antipsychotic medications. In South Dakota, these efforts have yielded a 12 percent relative reduction (21.3 percent to 18.7 percent) in the percent of residents prescribed antipsychotic agents from the second quarter of 2012 to the second quarter of 2013. Future efforts in South Dakota include a Nursing Home Quality Care Collaborative that involves the majority of facilities across the state learning from peers and national experts. The South Dakota Dementia Coalition includes 17 stakeholders who guide education activities and communicate these opportunities to their constituents. PMID:24624602
Erickson, Steven K; Ciccone, J Richard; Schwarzkopf, Steven B; Lamberti, J Steven; Vitacco, Michael J
Advances in the biological sciences have dramatically improved the understanding of schizophrenia and related psychotic illnesses. One of the most compelling findings is the substantial degree to which cognition is impaired in these illnesses and the remedial effects that antipsychotic drugs have in treating these cognitive impairments. Despite these promising discoveries, legal cases and scholarship remain replete with pejorative associations with antipsychotic drug action. References to antipsychotic medications as mind-altering drugs and their effects as "synthetic sanity" misconstrue the beneficial effects these medicines have on cognition. We review the prevailing legal attitude of antipsychotic medications and contrast these views with prevailing scientific knowledge. We conclude that legal opinion is misinformed about the effects of antipsychotic medications on cognition. PMID:17592170
Lindh, Jonatan D.
Background: Although therapeutic drug monitoring (TDM) is considered an underused tool in psychiatric care, the prevalence of TDM is largely unknown. The aim of this study was to analyze the prevalence of TDM for antidepressants and antipsychotics during 2006–2013. Methods: The study population consisted of individuals ?5 years of age residing in Stockholm County. The prevalence of TDM for each study year was calculated with the number of individuals in whom TDM had been performed as nominator (extracted from the TDM database at Karolinska University Laboratory) and the number of treated individuals as denominator (extracted from the Swedish Prescribed Drug Register). All data were obtained at the third and the fifth level of the anatomical therapeutic chemical classification system (pharmacological subgroup and chemical substance, respectively). The prevalence of TDM was compared between substances according to the level of TDM recommendation by guidelines. Results: For antidepressants, the prevalence of TDM decreased from 0.48% (95% confidence interval, 0.45%–0.52%) in 2006 to 0.36% (0.33%–0.39%) in 2013 (among 133,275 and 162,998 treated individuals, respectively). For antipsychotics, the prevalence of TDM increased from 2.3% (2.2%–2.5%) to 4.1% (3.9%–4.3%) (31,463 and 32,534 treated individuals). For both drug groups, TDM was more common in men than in women. The most frequently analyzed drugs were clozapine, perphenazine, zuclopenthixol, nortriptyline, and flupentixol. Although not reaching statistical significance, the TDM prevalence was greater for substances strongly recommended for TDM than for substances with a lower level of recommendation, median (interquartile range): 5.6% (2.8%–22%) versus 1.1% (0.2%–2.2%), P = 0.063. Conclusions: The prevalence of TDM is generally low, more frequent, and increasing for antipsychotics, and more frequent for men and substances where TDM is strongly recommended. PMID:25533882
Synchronized separation of seven medications representing most commonly prescribed antihypertensive classes by using reversed-phase liquid chromatography: Application for analysis in their combined formulations.
Ebeid, Walid M; Elkady, Ehab F; El-Zaher, Asmaa A; El-Bagary, Ramzia I; Patonay, Gabor
A reversed-phase high-performance liquid chromatography method was developed for the simultaneous determination of the diuretic, hydrochlorothiazide, along with six drugs representing the most commonly prescribed antihypertensive pharmacological classes such as atenolol, a selective ?1 blocker, amlodipine besylate, a calcium channel blocker, moexipril hydrochloride, an angiotensin-converting-enzyme inhibitor, valsartan and candesartan cilexetil, which are angiotensin II receptor blockers, and aliskiren hemifumarate, a renin inhibitor, using irbesartan as an internal standard. The chromatographic separation was achieved using acetonitrile/sodium phosphate dibasic buffer (0.02 M, pH 5.5) at a flow rate of 1 mL/min in gradient elution mode at ambient temperature on a stationary phase composed of an Eclipse XDB-C18 (4.6 × 150 mm, 5 ?m) column. UV detection was carried out at 220 nm. The method was validated according to ICH guidelines. Linearity, accuracy, and precision were satisfactory over the concentration ranges of 2-40 ?g/mL for hydrochlorothiazide and candesartan cilexetil, 20-120, 10-160, 5-40, 20-250, and 5-50 ?g/mL for atenolol, valsartan, moexipril hydrochloride, aliskiren hemifumarate, and amlodipine besylate, respectively. The method was successfully applied for the determination of each of the studied drugs in their combined formulations with hydrochlorothiazide. The developed method is suitable for the quality control and routine analysis of the cited drugs in their pharmaceutical dosage forms. PMID:24482404
Scheifes, A.; Stolker, J. J.; Egberts, A. C. G.; Nijman, H. L. I.; Heerdink, E. R.
Background: Behavioural problems are common in people with intellectual disability (ID) and are often treated with antipsychotics. Aim: To establish the frequency and characteristics of people with ID included in randomised controlled trials (RCTs) on antipsychotic treatment for behavioural problems, and to investigate the quality of these RCTs.…
Gury, C; Canceil, O; Iaria, P
Cardiovascular mortality is higher among schizophrenic patients than in the general population, and it is possible that most unexplained sudden deaths among these patients are due to ventricular arrhythmias for which antipsychotic drugs are either the cause or a predisposing factor. Most antipsychotic agents show electrophysiological effects resembling those of class 1a antiarrhythmic agents, and may be responsible for prolonging the QT interval, potentially going on to cause torsades de pointes. Some of the antipsychotic agents carry a high risk of arrhythmias, related to their effects on the QT interval. These include thioridazine, pimozide, sultopride, droperidol, and to a lesser extent haloperidol and chlorpromazine. In the case of the new atypical antipsychotic agents, it is possible to rank the risks of different drugs, with sertindole (now withdrawn from sale) having the highest risk, and ziprasidone somewhat lower, followed by risperidone and finally by quetiapine, clozapine and olanzapine which have negligible effects on the QT interval. A number of risk factors have been demonstrated, particularly: hypokalaemia and hypomagnesaemia, bradycardia, congenital long QT syndrome, and any underlying cardiac pathology. Lastly, the risk associated with any given antipsychotic agent is increased if it is combined either with any other drug known to prolong the QT interval and provoke torsades de pointes, or with any drug capable of inhibiting the hepatic metabolism of the antipsychotic agent. A list of such drugs is provided, together with advice on the action to be taken when prescribing an antipsychotic agent to a patient with a long QT interval. PMID:11217540
Tully, Mary P
Prescribing errors that occur in hospitals have been a source of concern for decades. This narrative review describes some of the recent work in this field. There is considerable heterogeneity in definitions and methods used in research on prescribing errors. There are three definitions that are used most frequently (one for prescribing errors specifically and two for the broader arena of medication errors), although many others have also been used. Research methods used focus primarily on investigating either the prescribing process (such as errors in the dose prescribed) or the outcomes for the patient (such as preventable adverse drug events). This complicates attempts to calculate the overall prevalence or incidence of errors. Errors have been reported in handwritten descriptions of almost 15% and with electronic prescribing of up to 8% of orders. Errors are more likely to be identified on admission to hospital than at any other time (usually failure to continue ongoing medication) and errors of dose occur most commonly throughout the patients' stay. Although there is evidence that electronic prescribing reduces the number of errors, new types of errors also occur. The literature on causes of error shows some commonality with both handwritten and electronic prescribing but there are also causes that are unique to each. A greater understanding of the prevalence of the complex causal pathways found and the differences between the pathways of minor and severe errors is necessary. Such an understanding would underpin theoretically-based interventions to reduce the occurrence of prescribing errors. PMID:22554316
Thomas, Simon H L; Yates, Laura M
Prescribing of medicines during pregnancy is common, and for some groups of women is essential for maintaining maternal and therefore fetal health. Pregnant women and prescribers are rightly concerned, however, about the potential adverse fetal effects of medicines. These may include fetal death or stillbirth, congenital malformations, developmental impairment, neonatal effects or late carcinogenesis. It is therefore essential that the risks and benefits for mother and fetus are considered carefully before prescribing in pregnancy. This is often challenging because of the paucity of information available. To complicate the issue further, drug pharmacokinetics are commonly altered in pregnancy, potentially affecting optimal dosing as well as interpretation of plasma concentration measurements, with specific information on individual drugs seldom available. Most drugs cross the placenta, especially lipophilic drugs and those with low plasma protein binding. Active membrane transporters also have an important role in enhancing or preventing drug transfer, although this is not yet clearly understood. Animal studies have limited applicability to humans because of species-specific effects, and clinical trials in pregnancy are only undertaken in special circumstances. Prescribers therefore need to rely on observational studies of fetal outcomes following drug exposure in human pregnancy. These often involve limited numbers, and data are also subject to confounding and bias, making interpretation difficult. It therefore remains essential that appropriate mechanisms for systematic data collection, including congenital malformation registries, teratology information services, pregnancy registers and linked population registries, are maintained and enhanced to increase the amount and quality of information available. PMID:22607226
... Antipsychotic drugs. Table 1. Medications Evaluated in this Report Generic name Brand name(s) Available as a generic? ... antipsychotic drugs, see these additional Best Buy Drugs reports. ? Use of Antipsychotic Drugs in Children ? Antipsychotic Drugs ...
During the last years, a contribution of antipsychotic drugs in the increase of diabetes prevalence in schizophrenic population has been repetitively suggested. The debate focused mainly on the second-generation antipsychotics. The analysis of the scientific literature indicates however that this discussion is not recent and an increase of diabetes prevalence in schizophrenic populations was already described before the introduction of neuroleptics. Then, after the introduction of the first neuroleptics in the 1950s, an increase of diabetes prevalence was reported among treated patients and the same alarms occurred in the 1990s after the introduction of second-generation antipsychotics. These treatments were related to an increase of glucose tolerance impairment, type II diabetes and diabetic acidoketosis. Recent epidemiological studies have confirmed the increase prevalence of diabetes in schizophrenic patients, particularly in schizophrenic patients before any antipsychotic treatment. Among the suggested mechanisms, there are sedentary life (due to hospitalisation and sedative effects of neuroleptics), food imbalance, shared genetic factors for diabetes and schizophrenia. Moreover, the frequency of the metabolic syndrome is increased in schizophrenic populations. This syndrome associates blood glucose increase, lipid metabolism disorders and android obesity. This could explain--via an increase of the cortisol production--the increase of mortality due to cardiovascular diseases observed in schizoprhenic patients. Thus, it seems well established that schizophrenia is associated with an increased risk for diabetes. It is however more difficult to evaluate the role of antipsychotic treatment as a causative factor of diabetes. Indeed, there are many published case reports or diabetes or diabetic acidoketosis after an antipsychotic treatment, but the level of evidence in controlled trials is low. Many studies were performed on large databases, but were retrospective and subjected to many flaws: concomitant diseases not taken into account, diabetes status evaluated by drug consumption, unknown diabetes status before antipsychotic treatment, etc. In the few prospective studies performed, no significant differences between the atypical versus typical antipsychotics were evidenced for new cases of diabetes. Moreover, in general population, the glucose tolerance impairment is underdiagnosed and it is estimated that people with a glucose tolerance impairment have a 5-10% annual risk of type II diabetes. Thus, this concern has to be replaced among the world epidemic increase of diabetes and in a population of patients whose the disease itself and life style are risk factors for diabetes. Some studies have explored the pathophysiological mechanisms that could support a diabetogenic effect of antipsychotics. Although it does not seem to be a direct effect of antipsychotics on insulin secretion by pancreatic cells, body weight increase has been evidence for both typical and atypical antipsychotics. However, it remains unclear whether this weight increase is responsible for a visceral adiposity, which is a risk factor better fitted to the cardiovascular mortality tha the body weight itself. Other hypotheses involving an effect on the leptin, which regulates the appetite, have been proposed. In waiting of new prospective controlled studies, and without denying the impact of antipsychotics on the glucose and lipid metabolisms (on the weight increase, for example), it should be recognized that the benefit/risk ratio remains largely in favour of the treatment, particularly for the atypical antipsychotics, more effective and better tolerated at the neurological level than the conventional antipsychotics. One of the benefits of the mainly articles in professional media about this concern is to draw attention on the metabolism disorders in schizophrenic patients, which are important risk factor of their frequent cardiovascular surmortality whatever the causes. Consequently, it is advised to monitor glucose and lipid metabolisms of schizophren
Switching antipsychotics is more and more common in our clinical practice. Several reasons can explain this observation. We have more and more antipsychotics available on the market with different receptor binding profiles and also different tolerability issues. Usually, the reasons of the switch are the following: insufficient efficacy or problems of tolerance (weight gain, metabolic disorders, extrapyramidal symptoms, hyperprolactinemia, sedation, sexual dysfunction). So that the switch takes place without complications, it is essential for the clinician to have full knowledge of both the receptor binding profiles of the antipsychotics in question and their half-life. The clinician has to expect a dopaminergic rebound when the introduced antipsychotic has a lesser affinity for the dopaminergic D2 receptor than that which is withdrawn or if it is a partial agonist with a particularly long half-life. On the other hand, a histaminergic or cholinergic rebound can be expected if the new antipsychotic has a lesser affinity for these two receptors. In all these scenarios, a "plateau" switch will often be recommended. Now, if a faster switch is imperative, various medication strategies exist to try to decrease the impact of the rebound effects. PMID:24238644
The typicality of atypical antipsychotic drugs remains debatable. Preclinical studies and findings from randomized, controlled and open trials of clozapine, olanzapine, risperidone, quetiapine, sertindole, ziprasidone and a substituted benzamide were examined. A MEDLINE search was conducted using key words, including "extrapyramidal side effects," "cognition," "schizophrenia" and the generic drug names. Over 140 articles from peer-reviewed journals were reviewed, some of which were based on a meta-analysis. New-generation neuroleptic agents were found to have greater efficacy on the negative symptoms of schizophrenia and to cause fewer unwanted extrapyramidal side effects (EPS) than the traditional antipsychotic drugs. On one hand, atypical neuroleptic agents could be strictly defined as any neuroleptic agent with antipsychotic effects at a dosage that does not cause extrapyramidal side effects. Thus, clozapine is regarded as the "standard" atypical antipsychotic drug. On the other hand, typicality is about dimension rather than category, and we suggest the use of the term "spectrum of atypicality." For example, an emphasis is placed on quetiapine to illustrate where a new compound fits in this spectrum. Although dose-related, atypicality may be more a question of prescription attitude than of a specific characteristic of a compound. The degree to which a new compound is clinically superior to another atypical antipsychotic drug, in terms of improving positive, negative or affective symptoms, cognitive function and long-term outcome, will require further a priori hypotheses based on conceptual frameworks that are clinically meaningful. In addition, the results from industry-sponsored trials should be more comparable to those obtained from investigator-leading trials. Finally, the patient characteristics that define a patient's response to a specific antipsychotic drug are unknown. PMID:10740987
Noggle, Chad A.; Dean, Raymond S.
The use of antipsychotic medications within the school-age population is rapidly increasing. Although typical antipsychotics may be used in rare cases, this influx is largely secondary to the availability of the atypical antipsychotics. Reduction of possible adverse effects and increased efficacy represent the primary basis for the atypical…
Routledge, Philip A
The challenge to achieve safe prescribing merits the adjective ‘titanic’. The organisational and human errors leading to poor prescribing (e.g. underprescribing, overprescribing, misprescribing or medication errors) have parallels in the organisational and human errors that led to the loss of the Titanic 100 years ago this year. Prescribing can be adversely affected by communication failures, critical conditions, complacency, corner cutting, callowness and a lack of courage of conviction, all of which were also factors leading to the Titanic tragedy. These issues need to be addressed by a commitment to excellence, the final component of the ‘Seven C's’. Optimal prescribing is dependent upon close communication and collaborative working between highly trained health professionals, whose role is to ensure maximum clinical effectiveness, whilst also protecting their patients from avoidable harm. Since humans are prone to error, and the environments in which they work are imperfect, it is not surprising that medication errors are common, occurring more often during the prescribing stage than during dispensing or administration. A commitment to excellence in prescribing includes a continued focus on lifelong learning (including interprofessional learning) in pharmacology and therapeutics. This should be accompanied by improvements in the clinical working environment of prescribers, and the encouragement of a strong safety culture (including reporting of adverse incidents as well as suspected adverse drug reactions whenever appropriate). Finally, members of the clinical team must be prepared to challenge each other, when necessary, to ensure that prescribing combines the highest likelihood of benefit with the lowest potential for harm. PMID:22738396
Routledge, Philip A
The challenge to achieve safe prescribing merits the adjective 'titanic'. The organisational and human errors leading to poor prescribing (e.g. underprescribing, overprescribing, misprescribing or medication errors) have parallels in the organisational and human errors that led to the loss of the Titanic 100 years ago this year. Prescribing can be adversely affected by communication failures, critical conditions, complacency, corner cutting, callowness and a lack of courage of conviction, all of which were also factors leading to the Titanic tragedy. These issues need to be addressed by a commitment to excellence, the final component of the 'Seven C's'. Optimal prescribing is dependent upon close communication and collaborative working between highly trained health professionals, whose role is to ensure maximum clinical effectiveness, whilst also protecting their patients from avoidable harm. Since humans are prone to error, and the environments in which they work are imperfect, it is not surprising that medication errors are common, occurring more often during the prescribing stage than during dispensing or administration. A commitment to excellence in prescribing includes a continued focus on lifelong learning (including interprofessional learning) in pharmacology and therapeutics. This should be accompanied by improvements in the clinical working environment of prescribers, and the encouragement of a strong safety culture (including reporting of adverse incidents as well as suspected adverse drug reactions whenever appropriate). Finally, members of the clinical team must be prepared to challenge each other, when necessary, to ensure that prescribing combines the highest likelihood of benefit with the lowest potential for harm. PMID:22738396
Lapane, Kate L.
Prescribing of medicines for older people who live in nursing homes is a very common intervention. Undoubtedly, medicines have contributed to longevity and improved health outcomes in the population, but they are not without their side effects and can give rise to adverse events. The nursing home population is particularly at risk as residents have multiple comorbidities and receive multiple medications. Moreover, the quality of prescribing has been criticised with long-standing concerns about inappropriate prescribing, particularly overuse of medications which are not clinically indicated or which are no longer required. It has been suggested that pharmacists could use their skills to improve prescribing in the nursing home population and this review paper outlines the evidence for this type of intervention. The studies which have been included were rigorously designed and conducted. A number of interventions consisted of medication reviews, which often focused on specific drugs, notably antipsychotics, hypnotics and anxiolytics. In some cases, the pharmacist was solely responsible for the delivery of the intervention while in others a multidisciplinary approach was taken involving other key healthcare professionals. A number of outcome measures were employed to assess the impact of the intervention, ranging from a change in the number of inappropriate medications to differences in hospitalizations or health-related quality of life. Owing to the variation across studies, it is difficult to be definitive about the impact of pharmacy interventions in this setting. In an older, frail population such as nursing home residents, consideration needs to be given to appropriate and relevant outcome measures including a reduction in inappropriate prescribing, optimization of prescribing, reduced costs and improved health-related quality of life. Pharmacists and other healthcare professionals should continue to strive to meet these challenges in this particular demographic. PMID:25083206
Aldridge, M A
This paper discusses the evidence base for interventions addressing non-adherence to prescribed antipsychotics. A case study approach is used, and the extent to which adherence improvement interventions might be used in collaboration with a specific patient is considered. The principles and application of harm-reduction philosophy in mental health are presented in a planned non-adherence harm-reduction intervention. This intervention aims to acknowledge the patient's ability to choose and learn from experience and to reduce the potential harm of antipsychotic withdrawal. The intervention evaluation method is outlined. PMID:22070125
Tse, Lurdes; Procyshyn, Ric M; Fredrikson, Diane H; Boyda, Heidi N; Honer, William G; Barr, Alasdair M
Second-generation antipsychotics (SGAs) are associated with significant comorbid metabolic abnormalities. Adjunct medications may be prescribed to treat these metabolic side effects, but the evidence supporting this practice (especially for the management of antipsychotic-associated dyslipidemia and hypertension) is limited. The purpose of this review was to evaluate the effects of adjunct medications on triglyceride, total cholesterol, low-density lipoprotein, high-density lipoprotein, and blood pressure levels in participants taking SGAs for psychosis. Studies were systematically searched and evaluated. Studies were included for review if participants were taking SGAs and if lipid and/or blood pressure levels were included as outcome measures. Statins, conventional lipid-lowering agents, fluvoxamine, ramelteon, topiramate, valsartan, telmisartan, omega-3 fatty acids, metformin (including both immediate-release and extended-release formulations), and a combination of metformin-sibutramine seemed to have beneficial effects on lipid levels. Valsartan, telmisartan, and topiramate appeared to be effective for controlling increases in blood pressure. The literature on adjunct medications for the treatment of antipsychotic-associated dyslipidemia and hypertension is not exhaustive, and long-term randomized-controlled trials would offer valuable results. PMID:24169026
Strejilevich, Sergio A; Palatnik, Ana; Avila, Rubén; Bustin, Julián; Cassone, Julieta; Figueroa, Soledad; Gimenez, Mariana; de Erausquin, Gabriel A
We compared symptom severity and quality of life (QOL) in schizophrenic patients adequately treated with typical antipsychotics (TAP) or clozapine (CZP). Groups did not differ in symptom severity or QOL. Clozapine caused fewer extrapyramidal symptoms. Negative and extrapyramidal symptoms predicted QOL. Similar outcome in both groups suggests a common ceiling to antipsychotic efficacy. PMID:15741003
Aakre, Jennifer M; Medoff, Deborah R; Dixon, Lisa B; Kreyenbuhl, Julie A
Background This study compared the beliefs held by individuals with coexisting serious mental illness and type 2 diabetes regarding the necessity and risks of taking antipsychotic versus hypoglycemic medications. We also investigated whether nonadherent patients differed from adherent patients in their beliefs about medications. Methods Forty-four individuals with type 2 diabetes and serious mental illness who were prescribed hypoglycemic and antipsychotic medications completed a cross-sectional assessment of medication beliefs and adherence for both medication types. Results Patients perceived a greater need for hypoglycemic versus antipsychotic medications; however, their beliefs were not associated with nonadherence to either medication type. Conclusion These results suggest that individuals with coexisting serious mental illness and type 2 diabetes have stronger convictions regarding the necessity of their diabetes medication for maintaining their health. PMID:22654509
Linck, Viviane M.; Herrmann, Ana P.; Piato, Ângelo L.; Detanico, Bernardo C.; Figueiró, Micheli; Flório, Jorge; Iwu, Maurice M.; Okunji, Christopher O.; Leal, Mirna B.; Elisabetsky, Elaine
Managing schizophrenia has never been a trivial matter. Furthermore, while classical antipsychotics induce extrapyramidal side effects and hyperprolactinaemia, atypical antipsychotics lead to diabetes, hyperlipidaemia, and weight gain. Moreover, even with newer drugs, a sizable proportion of patients do not show significant improvement. Alstonine is an indole alkaloid identified as the major component of a plant-based remedy used in Nigeria to treat the mentally ill. Alstonine presents a clear antipsychotic profile in rodents, apparently with differential effects in distinct dopaminergic pathways. The aim of this study was to complement the antipsychotic profile of alstonine, verifying its effects on brain amines in mouse frontal cortex and striatum. Additionally, we examined if alstonine induces some hormonal and metabolic changes common to antipsychotics. HPLC data reveal that alstonine increases serotonergic transmission and increases intraneuronal dopamine catabolism. In relation to possible side effects, preliminary data suggest that alstonine does not affect prolactin levels, does not induce gains in body weight, but prevents the expected fasting-induced decrease in glucose levels. Overall, this study reinforces the proposal that alstonine is a potential innovative antipsychotic, and that a comprehensive understanding of its neurochemical basis may open new avenues to developing newer antipsychotic medications. PMID:19189988
Birnbaum, Michael L.; Saito, Ema; Gerhard, Tobias; Winterstein, Almut; Olfson, Mark; Kane, John M.; Correll, Christoph U.
Although concern has been raised about antipsychotic prescribing to youth with attention-deficit/hyperactivity disorder (ADHD), the available database is limited to individual studies. Therefore, in order to provide a synthesis of prevalences and time trends, we conducted a systematic review and pooled analysis of pharmaco-epidemiologic data on antipsychotic use in ADHD youth. Of 1806 hits, 21 studies (N) were retained that reported analyzable data for three separate populations: 1) antipsychotic-treated youth (N=15, n=341,586); 2) ADHD youth (N=9, n=6,192,368), and 3) general population youth (N=5, n=14,284,916). Altogether, 30.5±18.5% of antipsychotic-treated youth had ADHD. In longitudinal studies, this percentage increased over time (1998-2007) from 21.7±7.1% to 27.7±7.7%, ratio=1.3±0.4. Furthermore, 11.5±17.5% of ADHD youth received antipsychotics. In longitudinal studies, this percentage also increased (1998-2006) from 5.5±2.6% to 11.4±6.7%, ratio=2.1±0.6. Finally, 0.12±0.07% of youth in the general population were diagnosed with ADHD and received antipsychotics. Again, in longitudinal studies, this percentage increased over time (1993-2007): 0.13±0.09% to 0.44±0.49%, ratio=3.1±2.2. Taken together, these data indicate that antipsychotics are used by a clinically relevant and increasing number of youth with ADHD. Reasons for and risk/benefit ratios of this practice with little evidence base require further investigation. PMID:23881713
Clozapine is the drug of choice in treatment resistant schizophrenia. It reduces hospitalizations. Patients on clozapine are often co-prescribed other psychotropics. This report looks at a sample of twenty patients on clozapine. It finds that almost two thirds were on a psychotropic along with clozapine. Eight individuals were on an antidepressant; seven on an antipsychotic and five were on co-prescribed valproate. The clinical implications are discussed and a need to look at health services involving clozapine is suggested. PMID:18439293
Law, Suzanne; Haddad, Peter M.; Chaudhry, Imran B.; Husain, Nusrat; Drake, Richard J.; Flanagan, Robert J.; David, Anthony S.
Background: This study aimed to explore predictive factors for future use of therapeutic drug monitoring (TDM) and to further examine psychiatrists’ current prescribing practices and perspectives regarding antipsychotic TDM using plasma concentrations. Method: A cross-sectional study for consultant psychiatrists using a postal questionnaire was conducted in north-west England. Data were combined with those of a previous London-based study and principal axis factor analysis was conducted to identify predictors of future use of TDM. Results: Most of the 181 participants (82.9%, 95% confidence interval 76.7–87.7%) agreed that ‘if TDM for antipsychotics were readily available, I would use it’. Factor analysis identified five factors from the original 35 items regarding TDM. Four of the factors significantly predicted likely future use of antipsychotic TDM and together explained 40% of the variance in a multivariate linear regression model. Likely future use increased with positive attitudes and expectations, and decreased with potential barriers, negative attitudes and negative expectations. Scientific perspectives of TDM and psychiatrist characteristics were not significant predictors. Conclusion: Most senior psychiatrists indicated that they would use antipsychotic TDM if available. However, psychiatrists’ attitudes and expectations and the potential barriers need to be addressed, in addition to the scientific evidence, before widespread use of antipsychotic TDM is likely in clinical practice. PMID:26301077
Demland, Jeffery A.; Jing, Yonghua; Kelton, Christina M. L.; Guo, Jeff J.; Li, Hong; Wigle, Patricia R.
Background Postmarketing surveillance that identifies patients at high risk for receiving off-label medications will help ensure that the benefits of such treatment outweigh the risks. Because many off-label uses have little scientific support, tracking the extent to which they occur as well as the particular circumstances under which they occur is important. Objective To describe the drug-use pattern for patients with bipolar disorder, and to identify demographic and clinical factors associated with off-label use of atypical antipsychotics before US Food and Drug Administration approval for this indication. Methods Using the PHARMetrics medical claims database, a total of 105,771 adult patients with a diagnosis of bipolar disorder were evaluated during the 5-year (1998–2002) study period. Study drugs included mood stabilizers, antipsychotics, and antidepressants. Off-label use of an atypical antipsychotic was defined as a patient taking olanzapine before March 2000 (when it received an indication for bipolar disorder) or any other atypical antipsychotic during the entire study period. Logistic regression analysis was used to determine the odds ratio of receiving a drug off-label. Results Utilization of and reimbursement for atypical antipsychotics increased during the 5-year period. Of the 10.5% of patients who took atypical antipsychotics, 7.1% took these drugs off-label. In addition, 11% of patients received lithium, 25% received other anticonvulsants, and 34% received antidepressants. Off-label use of atypical antipsychotics was associated with psychiatry specialist prescribers (odds ratio = 1.52; 95% CI, 1.44–1.59) and certain comorbidities, such as substance abuse (odds ratio = 1.51; 95% CI, 1.38–1.66), anxiety disorder (odds ratio = 1.20; 95% CI, 1.14–1.26), diabetes mellitus (odds ratio = 1.26; 95% CI, 1.16–1.37), cerebral vascular disease (odds ratio = 1.26; 95% CI, 1.10–1.45), and hypertension (odds ratio = 1.12; 95% CI, 1.05–1.20). Over time, there has been an increase in the number of drug therapies, including atypical antipsychotics, used to treat bipolar disorder. Conclusion Because of the significant association found between atypical antipsychotic use and several key comorbidities, it is important for physicians to recognize these associations and weigh the risks and benefits of atypical antipsychotics in their treatment strategies. PMID:25126291
Bernardo, Miquel; Vieta, Eduard; Saiz Ruiz, Jerónimo; Rico-Villademoros, Fernando; Alamo, Cecilio; Bobes, Julio
Switching antipsychotics is common in the clinical practice setting and is associated with potential clinically relevant complications. An expert group selected by Spanish Society of Psychiatry and the Spanish Society of Biological Psychiatry has reviewed the evidence provided by randomized clinical trials and other relevant information to reach consensus recommendations for switching antipsychotics. In this article, we will review all the information that has led to those recommendations and which includes: indications and contraindications for switching antipsychotics, pharmacological issues, switching strategies, switching antipsychotics due to efficacy problems, switching antispychotics due to tolerability issues (including extrapyramidal symptoms and tardive dyskinesia, weight gain, metabolic disorders, hyperprolactinemia, sexual dysfunction, persistent sedation, and QT prolongation), switching antypsychotics due to lack of treatment compliance, and switching antipsychotics in patients with bipolar disorders. PMID:23446195
Kulkarni, Jayashri; Worsley, Roisin; Gilbert, Heather; Gavrilidis, Emorfia; Van Rheenen, Tamsyn E.; Wang, Wei; McCauley, Kay; Fitzgerald, Paul
Background Many women diagnosed with varying psychiatric disorders take antipsychotic medications during pregnancy. The safety of antipsychotic medications in pregnancy is largely unknown. Methods We established the National Register of Antipsychotic Medications in Pregnancy in 2005. Women who are pregnant and taking an antipsychotic medication are interviewed every 6 weeks during pregnancy and then followed until their babies are one year old. The baby's progress is closely followed for the first year of life. Findings As of April 18 2012, 147 pregnancies had been followed through to completion. There were 142 live births and data is available for 100 one year old babies. 18% of babies were born preterm, with a higher dose of antipsychotic medication correlating to an increased likelihood of premature delivery; 43% of babies required special care nursery or intensive care after birth; 37% had any degree of respiratory distress and 15% of babies developed withdrawal symptoms. Congenital anomalies were seen in eight babies. Most pregnancies resulted in the birth of live, healthy babies. The use of mood stabilisers or higher doses of antipsychotics during pregnancy increased the likelihood of babies experiencing respiratory distress or admission to Special Care Nursery or Neonatal Intensive Care Units. Conclusion There is a great need for safety and efficacy information about the use of antipsychotic medications in pregnancy. Live, healthy babies are the most common outcome following the use of antipsychotic medication in pregnancy, but clinicians should be particularly mindful of neonatal problems such as respiratory distress. PMID:24787688
Hanselka, C. Wayne
This leaflet explains how to plan for adequate fuel for a prescribed burn, control the fire, notify the proper authority, manage the burn itself, and conduct follow-up management. A ranch checklist for prescribed burning is included....
Grundmann, Milan; Kacirova, Ivana; Urinovska, Romana
Schizophrenia is a severe psychiatric disorder often associated with cognitive impairment and affective, mainly depressive, symptoms. Antipsychotic medication is the primary intervention for stabilization of acute psychotic episodes and prevention of recurrences and relapses in patients with schizophrenia. Typical antipsychotics, the older class of antipsychotic agents, are currently used much less frequently than newer atypical antipsychotics. Therapeutic drug monitoring (TDM) of antipsychotic drugs is the specific method of clinical pharmacology, which involves measurement of drug serum concentrations followed by interpretation and good cooperation with the clinician. TDM is a powerful tool that allows tailor-made treatment for the specific needs of individual patients. It can help in monitoring adherence, dose adjustment, minimizing the risk of toxicity and in cost-effectiveness in the treatment of psychiatric disorders. The review provides complex knowledge indispensable to clinical pharmacologists, pharmacists and clinicians for interpretation of TDM results. PMID:25531781
Ramdour, S; Duxbury, J A; Becket, G; Wilson, S
Delays in effective treatment of a first episode psychosis can result in more severe symptoms, a longer time to achieve symptom control and a poorer quality of life; yet around 40% do not take antipsychotic medication as prescribed. There is evidence that patients and staff have different perceptions of what affects adherence with medication. Research in adults suggests healthcare professionals and patients understand the importance of good insight in promoting adherence with medication for schizophrenia; however, healthcare staff may overestimate the impact of side effects and underestimate the importance of medication effectiveness. There is also some evidence to suggest that motivations to take prescribed medication may differ in first and multi-episode psychosis. This research therefore sought views of staff working with adolescents diagnosed with first episode psychosis about what factors affected adherence with antipsychotic medication. Staff responding to the survey felt that young people were more likely to take medication if they felt it would make them better, prevent relapse and if they had a positive rapport with staff. As in an adult population, side effects, particularly weight gain, sedation and muscular side effects, were expressed as a common reason for poor adherence. Doctors and nurses assigned differing importance to parameters such as family views of medication, fear of admission and a preference for cannabis over medication suggesting that views may differ between professional groups Views of young people will be obtained in the next phase of the research study to enable comparison with staff views and consideration of staff interventions to better promote medication adherence. Antipsychotic medication is an effective treatment for first episode psychosis; yet 40% of patients do not take medication as prescribed. Previous research in adults with schizophrenia comparing healthcare professional and patient views suggests that while healthcare professionals recognize the importance of insight in promoting medication adherence, they underestimate the importance of medication efficacy and overestimate the impact of side effects. It was hypothesized that staff in this study would also recognize the importance of insight and positive medication attitudes in teenagers with psychosis, but overestimate the impact of side effects on medication adherence. This cross-sectional observational study sought staff views about factors affecting antipsychotic medication adherence in those aged between 14 and 18 years. An online survey was distributed and 60 responses were subsequently returned. Staff felt that good medication insight as well as positive relationships with staff were important determinants of good medication adherence. The most important influences of poor adherence were poor insight, side effects of medication and a wish to exert personal control around medication decisions. The results therefore confirmed the initial hypothesis. Published literature also provides support for some, but not all, of the staff views expressed in survey responses. PMID:25990303
Correll, Christoph U.; Rummel-Kluge, Christine; Corves, Caroline; Kane, John M.; Leucht, Stefan
Context: Despite lacking evidence for its safety and efficacy, antipsychotic cotreatment is common in schizophrenia. Objective: To evaluate therapeutic and adverse effects of antipsychotic cotreatment vs monotherapy in schizophrenia. Data Sources: Cochrane Schizophrenia Group register and hand searches of relevant journals/conference proceedings. Study Selection: Randomized controlled trials comparing antipsychotic monotherapy to cotreatment with a second antipsychotic. Data Extraction and Analysis: Two authors independently extracted data. For homogenous dichotomous data, we calculated random effects, relative risk (RR), 95% confidence intervals (CIs), and numbers needed to treat (NNT). For continuous data, weighted mean differences were calculated. Results: In 19 studies (1229 patients) with 28 monotherapy and 19 cotreatment arms, antipsychotic cotreatment was superior to monotherapy regarding 2 a priori defined coprimary outcomes: less study-specific defined inefficacy (N = 22, n = 1202, RR = 0.76, CI = 0.63–0.90, P = .002, NNT = 7, CI = 4–17, P = .0008, I2 = 78.9%) and all-cause discontinuation (N = 20, n = 1052, RR = 0.65, CI = 0.54–0.78, P < .00001). Results were consistent using Clinical Global Impressions thresholds of less than much (P = .006) and less than minimally (P = .01) improved. Specific psychopathology and adverse event data were insufficient to yield meaningful results. In sensitivity analyses, 5 efficacy moderators emerged: concurrent polypharmacy initiation, clozapine combinations, trial duration >10 weeks, Chinese trials, and second-generation + first-generation antipsychotics. In a meta-regression, similar dose combinations, second-generation + first-generation antipsychotics and concurrent polypharmacy initiation remained significant. Conclusions: In certain clinical situations, antipsychotic cotreatment may be superior to monotherapy. However, the database is subject to possible publication bias and too heterogeneous to derive firm clinical recommendations, underscoring the need for future research. PMID:18417466
... supported by grants from the States Attorney General Consumer and Prescriber Education Grant Program which is funded by the multi-state settlement of consumer fraud claims regarding the marketing of the prescription ...
Karpa, Kelly Dowhower; Felix, Todd Matthew; Lewis, Peter R
Drug use and harms are increasingly common among newborns, infants, children, and adolescents during ambulatory practice, emergency department, and in-hospital treatment, including treatment in pediatric intensive care units. The pharmacokinetic and pharmacodynamic parameters of drugs often are different for children compared with adults and must be considered before prescribing. Drug exposure and the potential for harms also should be considered for fetuses and breastfeeding infants. As with adult patients, a thorough drug and allergy history (including nonprescription drugs and herbal and dietary supplements) should be obtained and reviewed at each medical visit. Children and adolescents are increasingly at risk of drug harm/overdose through accidental or intentional ingestion of nonprescription and prescription drugs (eg, cough and cold preparations, candy-appearing vitamins, stimulants, narcotics). Parents and caregivers should receive training in the proper use, storage, and administration of all drugs. Prescribing clinicians should be vigilant in withholding unnecessary drugs, such as antibiotics for viral infections. When prescribing, clinicians should be aware of common drugs frequently associated with adverse reactions, including stimulants, antipsychotics, analgesics, asthma therapies, acne therapies, and tumor necrosis factor inhibitors. Scientifically based prescribing practices should be used and consultation with evidence-based resources and pharmacists sought as needed. PMID:26375994
Harding, Rosie; Peel, Elizabeth
This paper explores the legal position of the off-label prescription of antipsychotic medications to people with dementia who experience behavioural and psychological symptoms of dementia (BPSD). Dementia is a challenging illness, and BPSD can be very difficult for carers to manage, with evidence that this contributes to carer strain and can result in the early institutionalisation of people with dementia. As a result, the prescription of antipsychotic and other neuroleptic medications to treat BPSD has become commonplace, in spite of these drugs being untested and unlicensed for use to treat older people with dementia. In recent years, it has become apparent through clinical trials that antipsychotic drugs increase the risk of cerebrovascular accident (stroke) and death in people with dementia. In addition, these types of medication also have other risk factors for people with dementia, including over-sedation and worsening of cognitive function. Drawing on recent questionnaire (n = 185), focus group (n = 15), and interview (n = 11) data with carers of people with dementia, this paper explores the law relating to off-label prescription, and the applicability of medical negligence law to cases where adverse events follow the use of antipsychotic medication. It is argued that the practice of off-label prescribing requires regulatory intervention in order to protect vulnerable patients. PMID:23047844
Babu, Girish N.; Desai, Geetha; Chandra, Prabha S.
Research on psychotropic medications during pregnancy and lactation is limited as often involves complex ethical issues. Information on safety of psychotropic drugs during these critical phases is either inconclusive or undetermined. Many women with severe mental illness have unplanned pregnancies and require antipsychotic medication during pregnancy and lactation. Multiple issues have to be considered while choosing safe treatments for pregnant and lactating women and the best approach is to individualize the treatment. Medication should be guided primarily by its safety data and by the psychiatric history of the patient. Important issues to be kept in mind include pre-pregnancy counseling for all women, including planning pregnancies; folate supplementation, discussion with patient and family regarding options, and active liaison with obstetricians, ultrasonologists and pediatricians. Whenever possible, non-pharmacological approaches should be used in addition. PMID:26330648
Yang, Yu-Yin; Lu, Chao-Lin; Lo, Shih-Mao; Peng, Chia-Ho; Liu, Yia-Ping
Schizophrenia is a major mental disorder in which patients' cognitive functions gradually deteriorate. Pharmacological intervention with antipsychotics has proven effective, yet it is still debatable whether to initiate treatment in patients' premorbid stage. Based on the developmental origins of schizophrenia, we hypothesize that for those who are at high risk for schizophrenia, particularly with gating problems, an early pharmacological intervention would be beneficial. We performed a pilot rodent study to evaluate this hypothesis. Our results demonstrated that isolation rearing-induced sensorimotor gating dysfunction could be reversed by a chronic risperidone regimen initiated at different age time points. As expected, interventions that we initiated earlier (in adolescent stage) appeared to have better efficacy than interventions initiated four weeks later (in young adult stage). Our hypothesis may contribute new insight for both prevention and treatment of schizophrenia. PMID:26048359
Commentary Cognition, schizophrenia, and the atypical antipsychotic drugs Herbert Y. Meltzer, Northwestern University, Chicago, IL 60208 The Cognitive Deficit in Schizophrenia Schizophrenia was originally schizophrenia as a neurocogni- tive disorder (1). Recognition of the cen- tral importance of cognitive
Joanna Moncrieff looks at the lack of long-term evidence for antipsychotic medication and considers what is needed to ensure we have the knowledge to maximize benefits and minimize harms. PMID:26241954
Reekie, J; Hosking, S P M; Prakash, C; Kao, K-T; Juonala, M; Sabin, M A
Psychiatric illness in the paediatric population is increasing and the weight effect of medications for these problems is often unclear. A comprehensive literature search was undertaken to identify studies reporting weight in relation to antipsychotic and antidepressant use in children and adolescents. From 636 articles, 42 were selected for review. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) do not cause weight gain and may lead to improvements in weight status over the short, but not, long term. Antipsychotics were generally associated with weight gain. In drug comparison studies, risperidone had a larger weight gain effect than lithium, divalproex sodium and pimozide. Studies assessing the weight-protective effects of augmentation therapy with metformin or topiramate show less weight gain with addition of these agents. In conclusion, prescribing of SSRIs and SNRIs may be associated with improvements in weight status in children and adolescents but trials assessing their use in obesity, outside of established psychiatric illness, are limited and still experimental. Youth prescribed antipsychotic medication should be monitored for exaggerated weight gain and in those where obesity is a pre-existing concern agents other than olanzapine, clozapine and risperidone may be advantageous. PMID:26016407
Leckman-Westin, Emily; Okeke, Edward; Scharf, Deborah M.; Sorbero, Mark; Chen, Qingxian; Chor, Ka Ho Brian; Finnerty, Molly; Wisdom, Jennifer P.
Abstract Objective: The purpose of this study was to examine the impact of prior authorization policies on the receipt of antipsychotic medication for Medicaid-enrolled children. Methods: Using de-identified administrative Medicaid data from two large, neighboring, mid-Atlantic states from November 2007 through June 2011, we identified subjects <18 years of age using antipsychotics, from the broader group of children and adolescents receiving behavioral health services or any psychotropic medication. Prior authorization for antipsychotics was required for children in State A <6 years of age from September 2008, and for children <13 years of age from August 2009. No such prior authorizations existed in State B during that period. Filled prescriptions were identified in the data using national drug codes. Using a triple-difference strategy (using differences among the states, time periods, and differences in antidepressant prescribing rates among states over the same time periods), we examined the effect of the prior authorization policy on the rate at which antipsychotic prescriptions were filled for Medicaid-enrolled children and adolescents. Results: The impact of prior authorization policies on antipsychotic medication use varied by age: Among 6–12 year old children, the impact of the prior authorization policy on antipsychotic medication prescribing was a modest but statistically significant decrease of 0.47% after adjusting for other factors; there was no effect of the prior authorization among children 0–5 years. Conclusions: Prior authorization policies had a modest but statistically significant effect on antipsychotic use in 6–12 year old children, but had no impact in younger children. Future research is needed to understand the utilization and clinical effects of prior authorization and other policies and interventions designed to influence antipsychotic use in children. PMID:25144909
Rat maternal behavior is a complex social behavior. Many clinically used antipsychotic drugs, including the typical drug haloperidol and the atypical drugs clozapine, risperidone, olanzapine, quetiapine, aripiprazole, and amisulpride, disrupt active maternal responses (e.g. pup retrieval, pup licking, and nest building) to various extents. In this review, I present a summary of recent studies on the behavioral effects and neurobiological mechanisms of antipsychotic action on maternal behavior in rats. I argue that antipsychotic drugs at clinically relevant doses disrupt active maternal responses primarily by suppressing maternal motivation. Atypical drug-induced sedation also contributes to their disruptive effects, especially that on pup nursing. Among many potential receptor mechanisms, dopamine D2 receptors and serotonin 5-HT2A/2C receptors are shown to be critically involved in the mediation of the maternal disruptive effects of antipsychotic drugs, with D2 receptors contributing more to typical antipsychotic-induced disruptions, whereas 5-HT2A/2C receptors contributing more to atypical drug-induced disruptions. The nucleus accumbens shell-related reward circuitry is an essential neural network in the mediation of the behavioral effects of antipsychotic drugs on maternal behavior. This research not only helps understand the extent and mechanisms of impact of antipsychotic medications on human maternal care, but is also important for enhancing our understanding of the neurochemical basis of maternal behavior. It is also valuable for understanding the complete spectrum of therapeutic effects and side-effects of antipsychotic treatment. This knowledge may facilitate the development of effective intervening strategies to help patients coping with such undesirable effects. PMID:26221833
Kane, J M; Aguglia, E; Altamura, A C; Ayuso Gutierrez, J L; Brunello, N; Fleischhacker, W W; Gaebel, W; Gerlach, J; Guelfi, J D; Kissling, W; Lapierre, Y D; Lindström, E; Mendlewicz, J; Racagni, G; Carulla, L S; Schooler, N R
These guidelines for depot antipsychotic treatment in schizophrenia were developed during a two-day consensus conference held on July 29 and 30, 1995 in Siena, Italy. Depot antipsychotic medications were developed in the 1960s as an attempt to improve the long-term treatment of schizophrenia (and potentially other disorders benefiting from long-term antipsychotic medication). Depot drugs as distinguishable from shorter acting intramuscularly administered agents can provide a therapeutic concentration of at least a seven day duration in one parenteral dose. The prevention of relapse in schizophrenia remains an enormous public health challenge worldwide and improvements in this area can have tremendous impact on morbidity, mortality and quality of life, as well as direct and indirect health care costs. Though there has been debate as to what extent depot (long-acting injectable) antipsychotics are associated with significantly fewer relapses and rehospitalizations, in our view when all of the data from individual trials and metaanalyses are taken together, the findings are extremely compelling in favor of depot drugs. However in many countries throughout the world fewer than 20% of individuals with schizophrenia receive these medications. The major advantage of depot antipsychotics over oral medication is facilitation of compliance in medication taking. Non-compliance is very common among patients with schizophrenia and is a frequent cause of relapse. In terms of adverse effects, there are not convincing data that depot drugs are associated with a significantly higher incidence of adverse effects than oral drugs. Therefore in our opinion any patient for whom long-term antipsychotic treatment is indicated should be considered for depot drugs. In choosing which drug the clinician should consider previous experience, personal patient preference, patients history of response (both therapeutic and adverse effects) and pharmacokinetic properties. In conclusion the use of depot antipsychotics has important advantages in facilitating relapse prevention. Certainly pharmacotherapy must be combined with other treatment modalities as needed, but the consistent administration of the former is often what enables the latter. PMID:9452941
Pillarella, Jessica; Higashi, Ashley; Alexander, G. Caleb; Conti, Rena
Objective The authors examined trends in the use of second-generation antipsychotics for treatment of bipolar disorder before and after the U.S. Food and Drug Administration’s approval in 2000 of olanzapine for use in treating acute manic episodes of bipolar disorder. Methods The IMS Health National Disease and Therapeutic Index was used to derive monthly patient treatment visits between January 1998 and December 2009 by individuals 18 and older with a diagnosis of bipolar disorder who were treated with one or more pharmacotherapies. Results The percentage of treatment visits in which a second-generation antipsychotic was prescribed increased from 18% in 1998 to 49% in 2009. Use of mood stabilizers and first-generation antipsychotics declined substantially. In the 12 months after approval of olanzapine for bipolar disorder, its use increased by 92%, and use of other second-generation antipsychotics increased by 42%. Conclusions Second-generation antipsychotics are increasingly used for bipolar disorder, and their effectiveness compared with therapeutic alternatives merits further research. PMID:22227765
Penfold, Robert B.; Stewart, Christine; Hunkeler, Enid M.; Madden, Jeanne M.; Cummings, Janet; Owen-Smith, Ashli A.; Rossom, Rebecca C.; Lu, Christine; Lynch, Frances L.; Waitzfelder, Beth E.; Coleman, Karen A.; Ahmedani, Brian K.; Beck, Arne L.; Zeber, John E.; Simon, Greg E.
Recent reports of antipsychotic medication use in pediatric populations describe large increases in rates of use. Much interest in the increasing use has focused on potentially inappropriate prescribing for non FDA-approved uses and use amongst youth with no mental health diagnosis. Different studies of antipsychotic use have used different time periods, geographic and insurance populations of youth, and aggregations of diagnoses. We review recent estimates of use and comment on the similarities and dissimilarities in rates of use. We also report new data obtained on 11 Health Maintenance Organizations that are members of the Mental Health Research Network in order to update and extend the knowledge base on use by diagnostic indication. Results indicate that most use in pediatric populations is for disruptive behaviors and not psychotic disorders. Differences in estimates are likely a function of differences in methodology; however, there is remarkable consistency in estimates of use by diagnosis. PMID:24258527
Shin, Ju-Young; Choi, Nam-Kyong; Lee, Joongyub; Seong, Jong-Mi; Park, Mi-Ju; Lee, Shin Haeng; Park, Byung-Joo
Objective Strong concerns have been raised about whether the risk of ischemic stroke differs between conventional antipsychotics (CAPs) and atypical antipsychotics (AAPs). This study compared the risk of ischemic stroke in elderly patients taking CAPs and AAPs. Method We conducted a retrospective cohort study of 71,584 elderly patients who were newly prescribed the CAPs (haloperidol or chlorpromazine) and those prescribed the AAPs (risperidone, quetiapine, or olanzapine). We used the National Claims Database from the Health Insurance Review and Assessment Service (HIRA) from January 1, 2006 to December 31, 2009. Incident cases for ischemic stroke (ICD-10, I63) were identified. The hazard ratios (HR) for AAPs, CAPs, and for each antipsychotic were calculated using multivariable Cox regression models, with risperidone as a reference. Results Among a total of 71,584 patients, 24,668 patients were on risperidone, 15,860 patients on quetiapine, 3,888 patients on olanzapine, 19,564 patients on haloperidol, and 7,604 patients on chlorpromazine. A substantially higher risk was observed with chlorpromazine (HR = 3.47, 95% CI, 1.97–5.38), which was followed by haloperidol (HR = 2.43, 95% CI, 1.18–3.14), quetiapine (HR = 1.23, 95% CI, 0.78–2.12), and olanzapine (HR = 1.12, 95% CI, 0.59–2.75). Patients who were prescribed chlorpromazine for longer than 150 days showed a higher risk (HR = 3.60, 95% CI, 1.83–6.02) than those who took it for a shorter period of time. Conclusions A much greater risk of ischemic stroke was observed in patients who used chlorpromazine and haloperidol compared to risperidone. The evidence suggested that there is a strong need to exercise caution while prescribing these agents to the elderly in light of severe adverse events with atypical antipsychotics. PMID:25790285
Bruijnzeel, Dawn; Suryadevara, Uma; Tandon, Rajiv
The primary objectives in the treatment of schizophrenia are to reduce the frequency and severity of psychotic exacerbation, ameliorate a broad range of symptoms, and improve functional capacity and quality of life. Treatment includes pharmacotherapy and a range of psychosocial interventions. Antipsychotics are the cornerstone of pharmacological treatment for schizophrenia. The sixty-five antipsychotics available in the world are classified into two major groups: first-generation (conventional) agents (FGAs) and second-generation (atypical) agents (SGAs). Whereas clozapine is found to be more efficacious than other agents among otherwise treatment-refractory schizophrenia patients, other differences in efficacy between antipsychotic agents are minor. There are, however, pronounced differences in adverse effect profiles among the 65 antipsychotic medications. Although the 14 SGAs differ "on average" from the 51 FGAs in terms of being associated with a lower risk of EPS and greater risk of metabolic side-effects, substantial variation within the two classes with regard to both risks and other relevant clinical properties undermines the categorical distinction between SGAs and FGAs. Choice of antipsychotic medication should be based on prior treatment response, individual preference, medical history and individual patient vulnerabilities. An individualized treatment approach with ongoing risk-benefit monitoring and collaborative decision-making is outlined. Even as rapid neuroscience advances promise revolutionary improvements in the future, a thoughtful and disciplined approach can provide enhanced outcomes for all schizophrenia patients today. PMID:25216917
The need to develop new antipsychotics that have fewer motor adverse effects and offer better treatment of negative symptoms has led to a new generation of drugs. Most of these drugs undergo extensive first-pass metabolism and are cleared almost exclusively by metabolism, except for amisulpride whose clearance is largely due to urinary excretion. Risperidone has metabolic routes in common with ziprasidone but shows differences in regard to other main pathways: the benzisoxazole moiety of risperidone is oxidised by cytochrome P450 (CYP) 2D6 to the active 9-hydroxyrisperidone, whereas the benzisothiazole of ziprasidone is primarily oxidised by CYP3A4, yielding sulfoxide and sulfone derivatives with low affinity for target receptors in vitro. Olanzapine, quetiapine and zotepine also have some common metabolic features. However, for the thienobenzodiazepine olanzapine a main metabolic route is direct conjugation at the benzodiazepine nucleus, whereas for the dibenzothiazepine quetiapine and the dibenzothiepine zotepine it is CYP3A4-mediated oxidation, leading to sulfoxidation, hydroxylation and dealkylation for quetiapine, but N-demethylation to the active nor-derivative for zotepine. Although the promising benzisoxazole (iloperidone) and benzisothiazole (perospirone) antipsychotics share some metabolic routes with the structurally related available drugs, they too have pharmacologically relevant compound-specific pathways. For some of the new antipsychotics we know the isoenzymes involved in their main metabolic pathways and the endogenous and exogenous factors that, by affecting enzyme activity, can potentially modify steady-state concentrations of the parent drug or its metabolite(s), but we know very little about others (e.g. amisulpride isomers, nemonapride). For yet others, information is scarce about the activity of the main metabolites and whether and how these contribute to the effect of the parent drug. Aging reduces the clearance of most antipsychotics, except amisulpride (which requires further evaluation) and ziprasidone. Liver impairment has little or no effect on the pharmacokinetics of olanzapine, quetiapine, risperidone (and 9-hydroxy-risperidone) and ziprasidone, but information is lacking for amisulpride. Renal impairment significantly reduces the clearance and prolongs the elimination half-life of amisulpride and risperidone. Again, studies are still not available for some drugs (zotepine) and have focused on the parent drug for others (olanzapine, quetiapine, ziprasidone) despite the fact that renal impairment would be expected to lower the clearance of more polar metabolites. Addressing these issues may assist clinicians in the design of safe and effective regimens for this group of drugs, and in selecting the best agent for each specific population. PMID:10843459
Sheena Derry; R Andrew Moore
BACKGROUND: Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics. METHODS: We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic\\/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due
Charles F. Saller; Andre I. Salama
Seroquel and the atypical antipsychotic clozapine were compared using a number of biochemical measures in rats which are indicative of potential antipsychotic activity and possible extrapyramidal side effect liability. Both in vitro and in vivo, these compounds are low potency D-2 dopamine (DA) receptor antagonists and are relatively more potent 5-HT2 antagonists than typical antipsychotic drugs. Seroquel also exhibited low
Prescribed fire can release herbaceous forages from woody plant competition thus promoting increased forage plant production, vigor, and accessibility. Prescribe fire also consumes standing litter thereby improving forage quality and palatability. Consequently, prescribed fire is commonly consider...
Whitlock, G; Nwokolo, N; McOwan, A
We describe the characteristics of HIV post-exposure prophylaxis (PEP) recipients and PEP indications at 56 Dean Street, a central London sexual health clinic. PEP was prescribed on 577 occasions. Most (97%) was given for unprotected anal intercourse. Over a fifth of exposures involved recreational drug use. Of the patients prescribed PEP, 5.9% were given PEP more than once in this period. As a snapshot of HIV risk behaviour, we note the prevalence of drug use, sex without condom use and group sex among PEP recipients. PMID:26245890
Capel, Margred M.; Colbridge, Mark G.; Henry, John A.
Although the more recently introduced antipsychotic drugs are increasing in popularity, the pattern of symptomatology when taken in overdose is not well defined. We monitored all enquiries to the National Poisons Information Service, London (NPIS, London) concerning antipsychotic drugs over a 9-month period in 1997 and report our findings concerning four drugs (olanzapine, clozapine, risperidone and sulpiride). All overdoses involving a single agent were followed up by a letter to the enquirer requesting details and outcome of the case. Although a total of 574 enquiries involving the selected antipsychotic drugs were received, only 45 of these cases involved overdose with a single agent. There were no fatalities or cases of convulsions in the series. Cardiac arrhythmias were only noted with sulpiride. Symptoms were most marked with clozapine, with a majority of patients experiencing agitation, dystonia, central nervous system (CNS) depression and tachycardia. Olanzapine and sulpiride produced a range of different symptoms, while most patients who had taken risperidone were asymptomatic. Monitoring poisons centre enquiries is a useful way of comparing overdose toxicities. We conclude that at least two of the novel antipsychotic agents, olanzapine and risperidone, appear to have a favourable overdose profile, which suggests that they are safer in overdose than the phenothiazines and butyrophenones. PMID:11343578
Mauri, M.C.; Paletta, S.; Maffini, M.; Colasanti, A.; Dragogna, F.; Di Pace, C.; Altamura, A.C.
This review will concentrate on the clinical pharmacology, in particular pharmacodynamic data, related to atypical antipsychotics, clozapine, risperidone, paliperidone, olanzapine, que¬tiapine, amisulpride, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone and cariprazine. A summary of their acute pharmacokinetics properties are also reported. Four new second-generation antipsychotics are available: iloperidone, asenapine, lurasidone and in the next future cariprazine. Similar to ziprasidone and aripiprazole, these new agents are advisable for the lower propensity to give weight gain and metabolic abnormalities in comparison with older second-generation antipsychotics such as olanzapine or clozapine. Actually lurasidone seems to be best in terms of minimizing unwanted alterations in body weight and metabolic variables. Therapeutic drug monitoring is not strictly necessary for all of the new antipsychotic drugs because there are no unequivocal data supporting a relationship between plasma drug levels and clinical outcomes or side effects. The exception can be represented by clozapine for which plasma levels of 350-420 ng/ml are reported to be associated with an increased probability of a good clinical response. Also for olanzapine an established therapeutic range (20-50 ng/ml) is proposed to yield an optimal response and minimize side effects.
Frölich, L; Hausner, L
In dementia depressive symptoms, anxiety, hallucinations and delusions often occur and are accompanied by unspecific behavioral changes. A targeted pharmacotherapy is complicated by the underlying cognitive impairment and physical comorbidities. The current review focusses on recent evidence on the use of antidepressives and antipsychotics for psychotic disturbances, agitation and depression in dementia and analyzes currently published randomized controlled clinical trials and meta-analyses. The evidence on the use of antipsychotics for different indications favors risperidone, with lower evidence levels for quetiapine and aripiprazole, whereas haloperidol should be avoided. Increased mortality and the risk of cerebrovascular events due to antipsychotics are of major concern. With respect to antidepressives, the benefit of antidepressive pharmacotherapy in dementia is critically discussed because of limited efficacy and increased side effects; however, selective serotonin reuptake inhibitors (SSRI), such as citalopram and sertraline have demonstrated efficacy on neuropsychiatric behavioral symptoms in general. These conclusions on the risk-benefit ratio of antidepressives and antipsychotics in dementia are in accordance with the recommendations of the German Society of Neurology and German Association for Psychiatry, Psychotherapy and Psychosomatics (DGN/DGPPN) S3 guidelines on the treatment of dementia. PMID:25787724
It is a routine matter for undergraduates to find eigenvalues and eigenvectors of a given matrix. But the converse problem of finding a matrix with prescribed eigenvalues and eigenvectors is rarely discussed in elementary texts on linear algebra. This problem is related to the "spectral" decomposition of a matrix and has important technical…
Schiff, Gordon D; Galanter, William L; Duhig, Jay; Lodolce, Amy E; Koronkowski, Michael J; Lambert, Bruce L
Judicious prescribing is a prerequisite for safe and appropriate medication use. Based on evidence and lessons from recent studies demonstrating problems with widely prescribed medications, we offer a series of principles as a prescription for more cautious and conservative prescribing. These principles urge clinicians to (1) think beyond drugs (consider nondrug therapy, treatable underlying causes, and prevention); (2) practice more strategic prescribing (defer nonurgent drug treatment; avoid unwarranted drug switching; be circumspect about unproven drug uses; and start treatment with only 1 new drug at a time); (3) maintain heightened vigilance regarding adverse effects (suspect drug reactions; be aware of withdrawal syndromes; and educate patients to anticipate reactions); (4) exercise caution and skepticism regarding new drugs (seek out unbiased information; wait until drugs have sufficient time on the market; be skeptical about surrogate rather than true clinical outcomes; avoid stretching indications; avoid seduction by elegant molecular pharmacology; beware of selective drug trial reporting); (5) work with patients for a shared agenda (do not automatically accede to drug requests; consider nonadherence before adding drugs to regimen; avoid restarting previously unsuccessful drug treatment; discontinue treatment with unneeded medications; and respect patients' reservations about drugs); and (6) consider long-term, broader impacts (weigh long-term outcomes, and recognize that improved systems may outweigh marginal benefits of new drugs). PMID:21670331
Dahl, Matthew; Schultz, Jennifer; Metge, Colleen; Raymond, Colette
Background. Psychotropic medications, in particular second-generation antipsychotics (SGAs) and benzodiazepines, have been associated with harm in elderly populations. Health agencies around the world have issued warnings about the risks of prescribing such medications to frail individuals affected by dementia and current guidelines recommend their use only in cases where the benefits clearly outweigh the risks. This study documents the use of psychotropic medications in the entire elderly population of a Canadian province in the context of current clinical guidelines for the treatment of behavioural disturbances. Methods. Prevalent and incident utilization of antipsychotics, benzodiazepines and related medications (zopiclone and zaleplon) were determined in the population of Manitobans over age 65 in the time period 1997/98 to 2008/09 fiscal years. Comparisons between patients living in the community and those living in personal care (nursing) homes (PCH) were conducted. Influence of sociodemographic characteristics on prescribing was assessed by generalized estimating equations. Non-optimal use was defined as the prescribing of high dose of antipsychotic medications and the use of combination therapy of a benzodiazepine (or zopiclone/zaleplon) with an antipsychotic. A decrease in intensity of use over time and lower proportions of patients treated with antipsychotics at high dose or in combination with benzodiazepines (or zopiclone/zaleplon) was considered a trend toward better prescribing. Multiple regression analysis determined predictors of non-optimal use in the elderly population. Results. A 20-fold greater prevalent utilization of SGAs was observed in PCH-dwelling elderly persons compared to those living in the community. In 2008/09, 27% of PCH-dwelling individuals received a prescription for an SGA. Patient characteristics, such as younger age, male gender, diagnoses of dementia (or use of an acetylcholinesterase inhibitor) or psychosis in the year prior the prescription, were predictors of non-optimal prescribing (e.g., high dose antipsychotics). During the period 2002/3 and 2007/8, amongst new users of SGAs, 10.2% received high doses. Those receiving high dose antipsychotics did not show high levels of polypharmacy. Conclusions. Despite encouraging trends, the use of psychotropic medications remains high in elderly individuals, especially in residents of nursing homes. Clinicians caring for such patients need to carefully assess risks and benefits. PMID:24109553
Respiratory medicines are expensive and, for common respiratory conditions, such as asthma and chronic obstructive pulmonary disease (COPD), there are opportunities to make significant savings by optimising their use. Responsible and cost-efficient respiratory prescribing can ensure value for money without compromising the quality of care. Nurses should be aware of the differing regimens recommended for patients with asthma and COPD. PMID:23240219
Xiang Rong Zhang; Ying Xin Wang; Zhi Jun Zhang; Lei Li; Gavin P. Reynolds
Antipsychotic-induced sexual dysfunction is a common and serious clinical side effect. It has been demonstrated that both neuronal nitric oxide (nNOS) and dopamine D2 receptor (DRD2) in the medial preoptic area (MPOA) and the paraventricular nucleus (PVN) of the hypothalamus have important roles in the regulation of sexual behaviour. We investigated the influences of 21 days’ antipsychotic drug administration on
Porsolt, Roger D; Moser, Paul C; Castagné, Vincent
Schizophrenia is characterized by three major symptom classes: positive symptoms, negative symptoms, and cognitive deficits. Classical antipsychotics (phenothiazines, thioxanthenes, and butyrophenones) are effective against positive symptoms but induce major side effects, in particular, extrapyramidal symptoms (EPS). The discovery of clozapine, which does not induce EPS and is thought effective against all three classes of symptom, has driven research for novel antipsychotics with a wider activity spectrum and lower EPS liability. To increase predictiveness, current efforts aim to develop translational models where direct parallels can be drawn between the processes studied in animals and in humans. The present article reviews existing procedures in animals for their ability to predict compound efficacy and EPS liability in relation to their translational validity. Rodent models of positive symptoms include procedures related to dysfunction in central dopamine and glutamatergic (N-methyl-D-aspartate) and serotonin (5-hydroxytryptamine) neurotransmission. Procedures for evaluating negative symptoms include rodent models of anhedonia, affective flattening, and diminished social interaction. Cognitive deficits can be assessed in rodent models of attention (prepulse inhibition) and of learning/memory (object and social recognition, Morris water maze and operant-delayed alternation). The relevance of the conditioned avoidance response is also discussed. A final section reviews procedures for assessing EPS liability, in particular, parkinsonism (catalepsy in rodents), acute dystonia (purposeless chewing in rodents, dystonia in monkeys), akathisia (defecation in rodents), and tardive dyskinesia (long-term antipsychotic treatment in rodents and monkeys). It is concluded that, with notable exceptions (attention, learning/memory, EPS liability), current predictive models for antipsychotics fall short of clear translational validity. PMID:20200119
ÜÇOK, ALP; GAEBEL, WOLFGANG
This paper reviews the available evidence concerning the side effects of atypical antipsychotics, including weight gain, type II diabetes mellitus, hyperlipidemia, QTc interval prolongation, myocarditis, sexual side effects, extrapyramidal side effects and cataract. Some recommendations about how to prevent and manage these side effects are also provided. It is concluded that atypical antipsychotics do not represent a homogeneous class, and that differences in side effects should be taken into account by clinicians when choosing an antipsychotic for an individual patient. PMID:18458771
Leucht, Stefan; Heres, Stephan; Hamann, Johannes; Kane, John M.
Every year numerous reports on antipsychotic drug trials are being published in neuropsychiatric journals, adding new information to our knowledge in the field. The information however is often hard for the reader to interpret, sometimes contradictory to comparable available studies and leaves more questions open than it actually answers. Although the overall quality of the studies is rather good, there are manifold options for further improvement in the conception, conduct, and reporting of antipsychotic drug trials. In this survey, we address methodological challenges such as the limited generalizability of outcomes due to patient selection and sample size; the vague or even lacking definition of key outcome parameters such as response, remission or relapse, insufficient blinding techniques, the pitfalls of surrogate outcomes and their assessment tools; the varying complex statistical approaches; and the challenge of balancing various ways of reporting outcomes. The authors present practical examples to highlight the current problems and propose a concrete series of suggestions on how to further optimize antipsychotic drug trials in the future. PMID:18234700
Castagné, Vincent; Moser, Paul C; Porsolt, Roger D
Schizophrenia is a major psychiatric disease that is characterized by three distinct symptom domains: positive symptoms, negative symptoms, and cognitive impairment. Additionally, treatment with classical antipsychotic medication can be accompanied by important side effects that involve extrapyramidal symptoms (EPS). The discovery of clozapine in the 1970s, which is efficacious in all three symptom domains and has a reduced propensity to induce EPS, has driven research for new antipsychotic agents with a wider spectrum of activity and a lower propensity to induce EPS. The following chapter reviews existing behavioral procedures in animals for their ability to predict compound efficacy against schizophrenia symptoms and liability to induce EPS. Rodent models of positive symptoms include procedures related to hyperfunction in central dopamine and serotonin (5-hydroxytryptamine) systems and hypofunction of central glutamatergic (N-methyl-d-aspartate) neurotransmission. Procedures for evaluating negative symptoms include rodent models of anhedonia, affective flattening, and diminished social interaction. Cognitive deficits can be assessed in rodent models of attention (prepulse inhibition (PPI), latent inhibition) and of learning and memory (passive avoidance, object and social recognition, Morris water maze, and operant-delayed alternation). The relevance of the conditioned avoidance response (CAR) is also discussed. A final section reviews animal procedures for assessing EPS liability, in particular parkinsonism (catalepsy), acute dystonia (purposeless chewing in rodents, dystonia in monkeys), akathisia (defecation in rodents), and tardive dyskinesia (long-term antipsychotic treatment in rodents and monkeys). PMID:20230767
Greene, Jeremy A
Surveillance of physicians' prescribing patterns and the accumulation and sale of these data for pharmaceutical marketing are currently the subjects of legislation in several states and action by state and national medical associations. Contrary to common perception, the growth of the health care information organization industry has not been limited to the past decade but has been building slowly over the past 50 years, beginning in the 1940s when growth in the prescription drug market fueled industry interest in understanding and influencing prescribing patterns. The development of this surveillance system was not simply imposed on the medical profession by the pharmaceutical industry but was developed through the interactions of pharmaceutical salesmen, pharmaceutical marketers, academic researchers, individual physicians, and physician organizations. Examination of the role of physicians and physician organizations in the development of prescriber profiling is directly relevant to the contemporary policy debate surrounding this issue. PMID:17502635
Sathapana Kongsamut; Jiesheng Kang; Xiao-Liang Chen; Joachim Roehr; David Rampe
Many antipsychotic drugs produce QT interval prolongation on the electrocardiogram (ECG). Blockade of the human cardiac K+ channel known as human ether-a-go-go-related gene (HERG) often underlies such clinical findings. In fact, HERG channel inhibition is now commonly used as a screen to predict the ability of a drug to prolong QT interval. However, the exact relationship between HERG channel blockade,
Samira S. Valvassori; Laura Stertz; Ana C. Andreazza; Maria I. Rosa; Flávio Kapczinski; Emilio L. Streck; João Quevedo
Schizophrenia is a common and serious mental disorder, in which the majority of patients require long-term antipsychotic treatment.\\u000a Several studies have suggested that schizophrenia is associated with decreased neurotrophins such as brain-derived neurotrophic\\u000a factor (BDNF) and nerve growth factor (NGF). Investigation of the mechanisms of pharmacological agents that are used in the\\u000a treatment of schizophrenia has been used to better
Alkhadhari, Sulaiman; Al Zain, Nasser; Darwish, Tarek; Khan, Suhail; Okasha, Tarek; Ramy, Hisham; Tadros, Talaat Matar
Background Management of acute psychotic episodes in schizophrenic patients remains a significant challenge for clinicians. Despite treatment guidelines recommending that second-generation antipsychotics (SGAs) should be used as monotherapy, first-generation antipsychotics, polypharmacy, and lower than recommended doses are frequently administered in clinical practice. Minimal data exist regarding the use of SGAs in the Middle East. The objective of this study was to examine the discrepancies between current clinical practice and guideline recommendations in the region. Methods RECONNECT-S Beta was a multicenter, noninterventional study conducted in Egypt, Kuwait, Saudi Arabia, and the United Arab Emirates to observe the management of schizophrenic patients who were hospitalized due to an acute psychotic episode. Patients underwent one visit on the day of discharge. Demographic and medical history, together with data on antipsychotic treatment and concomitant medication during the hospitalization period and medication recommendations at discharge were recorded. Results Of the 1,057 patients, 180 (17.0%) and 692 (65.5%) received SGAs as monotherapy and in combination therapy, respectively. Overall, the most frequently administered medications were given orally, and included risperidone (40.3%), olanzapine (32.5%), and quetiapine (24.6%); the doses administered varied between countries and deviated from the recommended guidelines. Upon discharge, 93.9% of patients were prescribed SGAs as maintenance therapy, and 84.8% were prescribed the same medication(s) as during hospitalization. Conclusion Current clinical practice in the Middle East differs from guideline recommendations. Patients frequently received antipsychotics in combination therapy, by various methods of administration, and at doses above and below the recommended guidelines for the management of their acute psychotic episodes. PMID:25897227
Thomson, M.; Smith, W. A.
OBJECTIVE: To describe benzodiazepine prescribing for elderly people living in the community in British Columbia, and to compare such prescribing with an indicator of current guidelines. DESIGN: Descriptive analysis of pharmacy billing data. SETTING: Province of British Columbia. PARTICIPANTS: All elderly persons (age 65 and older) dispensed benzodiazepines by community pharmacies in British Columbia during 1990. MAIN OUTCOME MEASURE: Potentially inappropriate prescriptions were defined by a maximum 2-month limit of 20 diazepam equivalents daily, as determined by the BC Drug Usage Review Program in consultation with experts in the field. Physicians' rates of potentially inappropriate prescribing were determined per 100 benzodiazepine prescriptions written. RESULTS: Almost 24% of elderly people in British Columbia were prescribed benzodiazepines at least once during 1990. Of these, 17.1% were given potentially inappropriate prescriptions. Physicians who prescribed benzodiazepines most frequently had the highest rates of potentially inappropriate prescriptions. CONCLUSION: Prescribing practice does not correspond with our indicator of current guidelines. PMID:7756916
Leckman-Westin, Emily; Kealey, Edith; Gupta, Nitin; Chen, Qingxian; Gerhard, Tobias; Crystal, Stephen; Olfson, Mark; Finnerty, Molly
Purpose Given the metabolic and neurologic side effects of antipsychotics and concerns about the increased risks associated with concomitant use, antipsychotic polypharmacy is a quality concern. This study assessed the operating characteristics of a Medicaid claims-based measure of antipsychotic polypharmacy. Methods A random sample from 10 public mental health clinics and 312 patients met criteria for this study. Medical record extractors were blind to measure status. We examined the prevalence, sensitivity, specificity, and positive predictive value (PPV) in Medicaid claims, testing nine different definitions of antipsychotic polypharmacy, including >14, >60, or >90?days concurrent use of ?2 antipsychotic agents, each with allowable gaps of up to 0, 14, or 32?days in days' supply of antipsychotic medications. Results All Medicaid claims measure definitions tested had excellent specificity and PPV (>91%). Good to excellent sensitivity was dependent upon use of a 32-day gap allowance, particularly as duration of concurrent antipsychotic use increased. The proposed claims-based measure (90-day concurrent use of ?2 or more antipsychotics, allowing for a 32-day gap) had excellent specificity (99.1%, 95%CI: 98.2-99.6) and PPV (90.9%, 95%CI: 83.1-95.7) with good sensitivity (79.4%, 95%CI: 70.4-86.6). The overall level of concordance between claims and medical record-based categorization of antipsychotic polypharmacy was high (96.4%, n?=?301/312 clients, Cohen's K?=?84.7, 95%CI: 75.9-93.5). Discrepant cases were reviewed, and implications are discussed. Conclusions Administrative claims data can be used to construct valid measures of antipsychotic polypharmacy. PMID:24664793
Background In Japan, combination therapy with high doses of antipsychotic drugs is common, but as a consequence, many patients with schizophrenia report extrapyramidal and autonomic nervous system side effects. To resolve this, we proposed a method of safety correction of high dose antipsychotic polypharmacy (the SCAP method), in which the initial total dose of all antipsychotic drugs is calculated and converted to a chlorpromazine equivalent (expressed as milligrams of chlorpromazine, mg CP). The doses of low-potency antipsychotic drugs are then reduced by???25 mg CP/week, and the doses of high-potency antipsychotics are decreased at a rate of ?50 mg CP/week. Although a randomized, case-controlled comparative study has demonstrated the safety of this method, the number of participants was relatively small and its results required further validation. In this study of the SCAP method, we aimed to substantially increase the number of participants. Methods/design The participants were in- or outpatients treated with two or more antipsychotics at doses of 500–1,500 mg CP/day. Consenting participants were randomized into control and dose reduction groups. In the control group, patients continued with their normal regimen for 3 months without a dose change before undergoing the SCAP protocol. The dose reduction group followed the SCAP strategy over 3–6 months with a subsequent 3-month follow-up period. Outcome measures were measured at baseline and then at 3-month intervals, and included clinical symptoms measured on the Manchester scale, the extent of extrapyramidal and autonomic side effects, and quality of life using the Euro QOL scale. We also measured blood drug concentrations and drug efficacy-associated biochemical parameters. The Brief Assessment of Cognition in Schizophrenia, Japanese version, was also undertaken in centers where it was available. Discussion The safety and efficacy of the SCAP method required further validation in a large randomized trial. The design of this study aimed to address some of the limitations of the previous case-controlled study, to build a more robust evidence base to assist clinicians in their efforts to reduce potentially harmful polypharmacy in this vulnerable group of patients. Trial registration UMIN Clinical Trials Registry 000004511. PMID:24708857
Aaron, Lisa; Montepiedra, Grace; Sirois, Patricia A.; Oleske, James M.; Malee, Kathleen; Pearson, Deborah A.; Nichols, Sharon L.; Garvie, Patricia A.; Farley, John; Nozyce, Molly L.; Mintz, Mark; Williams, Paige L.
Abstract Second-generation antipsychotics (SGAs) are increasingly prescribed to treat psychiatric symptoms in pediatric patients infected with HIV. We examined the relationship between prescribed SGAs and physical growth in a cohort of youth with perinatally acquired HIV-1 infection. Pediatric AIDS Clinical Trials Group (PACTG), Protocol 219C (P219C), a multicenter, longitudinal observational study of children and adolescents perinatally exposed to HIV, was conducted from September 2000 until May 2007. The analysis included P219C participants who were perinatally HIV-infected, 3–18 years old, prescribed first SGA for at least 1 month, and had available baseline data prior to starting first SGA. Each participant prescribed an SGA was matched (based on gender, age, Tanner stage, baseline body mass index [BMI] z score) with 1–3 controls without antipsychotic prescriptions. The main outcomes were short-term (approximately 6 months) and long-term (approximately 2 years) changes in BMI z scores from baseline. There were 236 participants in the short-term and 198 in the long-term analysis. In linear regression models, youth with SGA prescriptions had increased BMI z scores relative to youth without antipsychotic prescriptions, for all SGAs (short-term increase?=?0.192, p?=?0.003; long-term increase?=?0.350, p?0.001), and for risperidone alone (short-term?=?0.239, p?=?0.002; long-term?=?0.360, p?=?0.001). Participants receiving both protease inhibitors (PIs) and SGAs showed especially large increases. These findings suggest that growth should be carefully monitored in youth with perinatally acquired HIV who are prescribed SGAs. Future research should investigate the interaction between PIs and SGAs in children and adolescents with perinatally acquired HIV infection. PMID:19827949
Cotes, Robert O; de Nesnera, Alex; Kelly, Michael; Orsini, Karen; Xie, Haiyi; McHugo, Greg; Bartels, Stephen; Brunette, Mary F
Antipsychotic medications can cause serious cardiometabolic side effects. No recent research has broadly evaluated monitoring and strategies to improve monitoring in U.S. public mental health systems. To address this knowledge gap, we evaluated education with audit and feedback to leaders to improve cardiometabolic monitoring in a state mental health system. We used Chi square statistics and logistic regressions to explore changes in monitoring recorded in randomly sampled records over 2 years. In 2009, assessment of patients on antipsychotics was 29.6 % for cholesterol, 40.4 % for glucose, 29.1 % for triglycerides, 54.3 % for weight, 33.6 % for blood pressure, and 5.7 % for abdominal girth. In 2010, four of ten mental health centers improved their rate of adult laboratory monitoring. Overall monitoring in the state did not increase. Education for prescribers with audit and feedback to leaders can improve monitoring in some settings, but more intensive and/or prolonged interventions may be required. PMID:25645893
Florida Department of Forestry
This poster shows how prescribed burns operate, using careful planning and preparation to start a fire that will renew habitat without threatening ecosystems or homes. This image describes the steps required to prepare a prescribed burn, how fire crews set up for the burn, and how the wind is used to help control the fire.
Martin, Daniel J; Park, John; Langan, Julie; Connolly, Moira; Smith, Daniel J; Taylor, Mark
Aims and method To investigate whether socioeconomic status influenced rates of depot medication prescribing, polypharmacy (more than two psychotropic medications), newer (second-generation) antipsychotic prescribing and clozapine therapy. Postcodes, Scottish Index of Multiple Deprivation (SIMD) categories and current medication status were ascertained. Patients in the most deprived SIMD groups (8-10 combined) were compared with those in the most affluent SIMD groups (1-3 combined). Results Overall, 3200 patients with ICD-10 schizophrenia were identified. No clear relationship between socioeconomic status and any of the four prescribing areas was identified, although rates of depot medication use in deprived areas were slightly higher. Clinical implications Contrary to our hypothesis, there was no evidence that patients with schizophrenia within NHS Greater Glasgow and Clyde who live in more deprived communities had different prescribing experiences from patients living in more affluent areas. PMID:25237499
The introduction of a number of new antipsychotics in the last decade has generated considerable excitement regarding the treatment of schizophrenia and related psychotic conditions. Clinically, it has produced changing expectations regarding treatment outcome, while academically it has encouraged a re-evaluation and expansion of theories of the pathophysiology of schizophrenia and antipsychotic activity. In this review, the development of antipsychotics is traced, beginning with chlorpromazine's introduction in the early 1950s, and followed to the present. Despite 50 years of use and a plethora of antipsychotics available worldwide, our conceptualization of their major mode of action remains essentially unchanged. It was shortly after their development that attention turned to the importance of dopamine, and in particular the dopamine D2 receptor. Current thinking has elaborated on this model, with serotonin and glutamate receiving the greatest attention most recently, but D2 antagonism remains the sine qua non of antipsychotic activity. Although the notion of “atypical” remains somewhat of a moving target, we do have at our disposal a new generation of antipsychotics that reflect a different clinical profile from their conventional counterparts. The precise degree of these differences and the underlying mechanisms remain unclear, however. The direction new antipsychotic development takes will undoubtedly hinge on answers to these questions. PMID:12921222
Crespo-Facorro, Benedicto; Prieto, Carlos
Background: Despite the widespread use of antipsychotics, little is known of the molecular bases behind the action of antipsychotic drugs. A genome-wide study is needed to characterize the genes that affect the clinical response and their adverse effects. Methods: Here we show the analysis of the blood transcriptome of 22 schizophrenia patients before and after medication with atypical antipsychotics by next-generation sequencing. Results: We found that 17 genes, among the 21 495 genes analyzed, have significantly-altered expression after medication (p-value adjusted [Padj] <0.05). Six genes (ADAMTS2, CD177, CNTNAP3, ENTPD2, RFX2, and UNC45B) out of the 17 are among the 200 genes that we characterized with differential expression in a previous study between antipsychotic-naïve schizophrenia patients and controls (Sainz et al., 2013). This number of schizophrenia-altered expression genes is significantly higher than expected by chance (Chi-test, Padj 1.19E-50), suggesting that at least part of the antipsychotic beneficial effects is exerted by modulating the expression of these genes. Interestingly, all six of these genes were overexpressed in patients and reverted to control levels of expression after treatment. We also found a significant enrichment of genes related to obesity and diabetes, known adverse affects of antipsychotics. Conclusions: These results may facilitate understanding of unknown molecular mechanisms behind schizophrenia symptoms and the molecular mechanisms of antipsychotic drugs. PMID:25522406
Background To identify patient characteristics and early changes in patients' clinical status that best predict subsequent switching of antipsychotic agents in the long-term treatment of schizophrenia. Methods This post-hoc analysis used data from a one-year randomized, open-label, multisite study of antipsychotics in the treatment of schizophrenia. The study protocol permitted switching of antipsychotics when clinically warranted after the first eight weeks. Baseline patient characteristics were assessed using standard psychiatric measures and reviews of medical records. The prediction model included baseline sociodemographics, comorbid psychiatric and non-psychiatric conditions, body weight, clinical and functional variables, as well as change scores on standard efficacy and tolerability measures during the first two weeks of treatment. Cox proportional hazards modeling was used to identify the best predictors of switching from the initially assigned antipsychotic medication. Results About one-third of patients (29.5%, 191/648) switched antipsychotics before the end of the one-year study. There were six variables identified as the best predictors of switching: lack of antipsychotic use in the prior year, pre-existing depression, female gender, lack of substance use disorder, worsening of akathisia (as measured by the Barnes Akathisia Scale), and worsening of symptoms of depression/anxiety (subscale score on the Positive and Negative Syndrome Scale) during the first two weeks of antipsychotic therapy. Conclusions Switching antipsychotics appears to be prevalent in the naturalistic treatment of schizophrenia and can be predicted by a small and distinct set of variables. Interestingly, worsening of anxiety and depressive symptoms and of akathisia following two weeks of treatment were among the more robust predictors of subsequent switching of antipsychotics. PMID:20920179
Lahti, Adrienne C.; Weiler, Martin A.; Holcomb, Henry H.; Tamminga, Carol A.; Cropsey, Karen L.
The regional neuronal changes taking place in the early and late stages of antipsychotic treatment are still not well characterized in humans. In addition, it is not known whether these regional changes are predictive or correlated with treatment response. Using PET with 15O, we evaluated the time course of regional cerebral blood flow (rCBF) patterns generated by a first (haloperidol) and a second (olanzapine) generation antipsychotic drug (APD) in patients with schizophrenia during a 6 week treatment trial. Patients were initially scanned after withdrawal of all psychotropic medication (two weeks), and then blindly randomized to treatment with haloperidol (n=12) or olanzapine (n=17) for a period of 6 weeks. Patients were scanned again after 1 and 6 weeks of treatment. All assessments, including scanning sessions, were obtained in a double-blind manner. As hypothesized, we observed rCBF changes that were common to both drugs, implicating cortico-subcortical and limbic neuronal networks in antipsychotic action. In addition, in these regions, some patterns seen at week 1 and 6 were distinctive, indexing neuronal changes related to an early (ventral striatum, hippocampus) and consolidated [anterior cingulate/medial frontal cortex (ACC/MFC)] stage of drug response. Finally, both after 1 and 6 weeks of treatment, we observe differential patterns of rCBF activation between good and poor responders. After one week of treatment, greater rCBF increase in ventral striatum and greater decrease in hippocampus were associated with good response. PMID:19675535
Rusz, Jan; Klempí?, Ji?í; Tykalová, Tereza; Baborová, Eva; ?mejla, Roman; R?ži?ka, Evžen; Roth, Jan
Although motor speech impairment is a common manifestation of Huntington's disease (HD), its description remains limited. The aim of the current study was therefore to estimate the occurrence and characteristics of speech disorder in HD and to explore the influence of antipsychotic medication on speech performance. Speech samples, including reading passage and monologue, were acquired from 40 individuals diagnosed with HD and 40 age- and sex-matched healthy controls. Objective acoustic analyses were used to evaluate key aspects of speech including vowel articulation, intensity, pitch and timing. A predictive model was constructed to detect the occurrence and most prominent patterns of speech dysfunction in HD. We revealed that 93% of HD patients manifest some degree of speech impairment. Decreased number of pauses, slower articulation rate, imprecise vowel articulation and excess intensity variations were found to be the most salient patterns of speech dysfunction in HD. We further demonstrated that antipsychotic medication may induce excessive loudness and pitch variations perceptually resembling excess patterns of word stress, and may also accentuate general problems with speech timing. Additionally, antipsychotics induced a slight improvement of vowel articulation. Specific speech alterations observed in HD patients indicate that speech production may reflect the pathophysiology of the disease as well as treatment effects, and may therefore be considered a valuable marker of functional disability in HD. PMID:24809686
Evaluation of the Individual Safe Correction of Antipsychotic Agent Polypharmacy in Japanese Patients with Chronic Schizophrenia: Validation of Safe Corrections for Antipsychotic Polypharmacy and the High-Dose Method
Sukegawa, Tsuruhei; Inagaki, Ataru; Inada, Toshiya; Yoshio, Takashi; Yoshimura, Reiji; Iwata, Nakao
Background: Polypharmacy for schizophrenia treatment is not justified by the available clinical evidence. We evaluated a treatment reduction approach that reduces the dose and number of antipsychotic medications simultaneously prescribed to patients. Methods: In a randomized open study of the Safe Correction of Antipsychotic Polypharmacy and High-Dose Prescriptions program funded by the Japanese Ministry of Health, Labour, and Welfare, we evaluated a drug reduction method consisting of a dose reduction intervention performed on 163 patients with schizophrenia for twelve or 24 weeks. One antipsychotic medication was removed each week from each patient’s treatment regimen by reducing the dose by 0 to 50 chlorpromazine equivalents. Data on health-related indices of quality of life, clinical symptoms, and risk of side effects were analyzed using a two-way repeated-measures mixed linear model. Results: Despite a 23% reduction in antipsychotic dose, no differences in outcomes were observed between the dose reduction and observation groups (effect size = 0.001 – 0.085, P = .24–.97), despite high statistical power (1-? = 0.48–0.97). The findings are limited by the nonuniformity of the participants’ treatment history, duration, and dose reduction amount. Dose reduction protocol patients exhibited no difference in psychotic symptoms or adverse events compared with the observation group. Conclusions: Importantly, the low dropout rate in our study (6.9% of participants withdrew because of patient factors and 23.8% for all secondary reasons) indicates that our “slowly” method is well tolerated. We hope that this approach will result in therapeutic improvements. PMID:25522380
Ponnet, Koen; Wouters, Edwin; Van Hal, Guido; Heirman, Wannes; Walrave, Michel
The non-medical use of methylphenidate for cognitive enhancement becomes a more and more common practice among college and university students. Although physicians are a source of access, little is known about the underlying mechanisms that might lead to physicians' intention and behaviour of prescribing methylphenidate to improve students' academic performance. Applying Ajzen's theory of planned behaviour (TPB), we tested whether attitudes, subjective norms (controllability and self-efficacy) and perceived behavioural control predicted the intention and the prescribing behaviour of physicians. Participants were 130 physicians (62.3% males). Structural equation modelling was used to test the ability of TPB to predict physicians' behaviour. Overall, the present study provides support for the TPB in predicting physicians' prescribing behaviour of methylphenidate for cognitive enhancement. Subjective norms, followed by attitudes, are the strongest predictors of physicians' intention to prescribe methylphenidate. To a lesser extent, controllability predicts the intention of physicians, and self-efficacy predicts the self-reported behaviour. Compared to their male colleagues, female physicians seem to have more negative attitudes towards prescribing methylphenidate for cognitive enhancement, feel less social pressure and perceive more control over their behaviour. Intervention programmes that want to decrease physicians' intention to prescribe methylphenidate for improving academic performance should primarily focus on alleviating the perceived social pressure to prescribe methylphenidate and on converting physician neutral or positive attitudes towards prescribing methylphenidate into negative attitudes. PMID:23713799
Remington, Gary; Agid, Ofer; Foussias, George; Fervaha, Gagan; Takeuchi, Hiroyoshi; Lee, Jimmy; Hahn, Margaret
Objective: To examine how advances in our understanding of schizophrenia have shaped thinking about antipsychotics (APs) and their role in treatment. Method: Three specific developments in the field of schizophrenia are highlighted: advances in knowledge related to the earliest stages of schizophrenia, specifically the prodrome; reconceptualization of schizophrenia as an illness of multiple symptom domains; and greater clarification regarding the efficacy of clozapine and a new generation of APs. Results: Evidence indicating that negative and cognitive symptoms are present during the prodrome suggests that intervention at the time of first-episode psychosis constitutes late intervention. The limited efficacy of APs beyond psychosis argues against a magic bullet approach to schizophrenia and for polypharmacy that is symptom domain–specific. Clozapine’s unique, but limited, efficacy in treatment resistance supports subtyping schizophrenia based on treatment response. Conclusions: Advances in our understanding of schizophrenia have important implications regarding the current use of APs, expectations regarding response, and future drug development. PMID:25886675
Eleanor Bradley; Brian Hynam; Peter Nolan
This qualitative study explores how recently qualified nurse prescribers describe, and rate, the safety of their prescribing. Internationally, the costs of drug errors are enormous and they can have serious implications for staff and patients. Nurses are now undertaking extended prescribing practice throughout the UK. Nurse prescribers work across different work settings and although safe prescribing is a priority in
Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schwarz, Sandra; Bhoopathi, Paranthaman Sethupathi; Kissling, Werner; Leucht, Stefan
Background In many countries of the industrialised world second generation (‘atypical’) antipsychotics 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 new generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of ziprasidone differs from that of other second generation antipsychotics. Objectives To evaluate the effects of ziprasidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Specialised Register (April 2007) and references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information. This search was updated July 2012, 254 citations added to awaiting classification section. Selection criteria We included all randomised, at least single-blind, controlled trials comparing oral ziprasidone with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. Data collection and analysis We extracted data independently. For continuous data, we calculated weighted mean differences (MD) for dichotomous data we calculated relative risks (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. Main results The review currently includes nine randomised controlled trials (RCTs) with 3361 participants. The overall rate of premature study discontinuation was very high (59.1%). Data for the comparisons of ziprasidone with amisulpride, clozapine, olanzapine, quetiapine and risperidone were available. Ziprasidone was a less acceptable treatment than olanzapine (leaving the studies early for any reason: 5 RCTs, n=1937, RR 1.26 CI 1.18 to 1.35, NNH 7 CI 5 to 10) and risperidone (3 RCTs, n=1029, RR 1.11 CI 1.02 to 1.20, NNH 14 CI 8 to 50), but not than the other second generation antipsychotic drugs. Ziprasidone was less efficacious than amisulpride (leaving the study early due to inefficacy: 1 RCT, n=123, RR 4.72 CI 1.06 to 20.98, NNH 8 CI 5 to 50) olanzapine (PANSS total score: 4 RCTs, n=1291, MD 8.32 CI 5.64 to 10.99) and risperidone (PANSS total score: 3 RCTs, n=1016, MD 3.91 CI 0.27 to 7.55). Based on limited data there were no significant differences in tolerability between ziprasidone and amisulpride or clozapine. Ziprasidone produced less weight gain than olanzapine (5 RCTs, n=1659, MD ?3.82 CI ?4.69 to ?2.96), quetiapine (2 RCTs, n=754, RR 0.45 CI 0.28 to 0.74) or risperidone (3 RCTs, n=1063, RR 0.49 CI 0.33 to 0.74). It was associated with less cholesterol increase than olanzapine, quetiapine and risperidone. Conversely ziprasidone produced slightly more extrapyramidal side-effects than olanzapine (4 RCTs, n=1732, RR 1.43 CI 1.03 to 1.99, NNH not estimable) and more prolactin increase than quetiapine (2 RCTs, n=754, MD 4.77 CI 1.37 to 8.16), but less movement disorders (2 RCTs, n=822, RR 0.70 CI 0.51 to 0.97, NNT not estimable) and less prolactin increase (2 RCTs, n=767, MD ?21.97 CI ?27.34 to ?16.60) than risperidone. Note: the 254 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed. Authors’ conclusions Ziprasidone may be a slightly less efficacious antipsychotic drug than amisulpride, olanzapine and risperidone. Its main advantage is the low propensity to induce weight gain and associated adverse effects. However, the high overall rate of participants leaving the studies early limits the validity of any findings. PMID:19821380
... Drugs Will Become More Affordable, Study Predicts With patents expiring, access for Medicaid patients will likely expand ... 4, 2015 FRIDAY, Sept. 4, 2015 (HealthDay News) -- Patent expirations on several leading antipsychotic drugs could save ...
characteristics included use of cholinesterase inhibitors and/or memantine, function, cognition, living situation use was associated with younger age, poorer functioning, and concurrent use of cholinesterase include antihypertensives and antipsychotics in addition to cholinesterase inhibitors and memantine. Key
Elliott Richelson; Terry Souder
Using radioligand binding assays and post-mortem normal human brain tissue, we obtained equilibrium dissociation constants (Kds) for nine new antipsychotic drugs (iloperidone, melperone, olanzapine, ORG 5222, quetiapine, risperidone, sertindole, ziprasidone, and zotepine), one metabolite of a new drug (9-OH-risperidone), and three older antipsychotics (clozapine, haloperidol, and pimozide) at nine different receptors (?1-adrenergic, ?2-adrenergic, dopamine D2, histamine H1, muscarinic, and serotonin
Law, Kung How; How, Choon How; Ng, Chung Sien; Ng, Mark Chung Wai
The healthcare challenges in developed countries centre around the rise of chronic conditions and obesity. There is a call to shift the focus toward the primary prevention of these conditions. Clinicians will need to move beyond the comfort of prescribing pharmaceuticals and expand the scope to prescribing health, i.e. exercise. We discuss an easy-to-follow exercise prescription to highlight some essential principles and useful tools that can help busy family practices achieve this. PMID:23820539
Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Duggan, Lorna; Kissling, Werner; Leucht, Stefan
Background In many countries of the industrialised world second generation (“atypical”) antipsychotics 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 second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics. Objectives To evaluate the effects of olanzapine compared to 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 reference 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 trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, risperidone, 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 relative risks (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 weighted mean differences (WMD) again based on a random effects model. Main results The review currently includes 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole, clozapine, quetiapine, risperidone or ziprasidone). The overall attrition from the included studies was considerable (49.2%) leaving the interpretation of results problematic. Olanzapine improved the general mental state (PANSS total score) more than aripiprazole (2 RCTs, n=794, WMD ?4.96 CI ?8.06 to ?1.85), quetiapine (10 RCTs, n=1449, WMD ?3.66 CI ?5.39 to ?1.93), risperidone (15 RCTs, n=2390, WMD ?1.94 CI ?3.31 to ?0.58) and ziprasidone (4 RCTs, n=1291, WMD ?8.32 CI ?10.99 to ?5.64), but not more than amisulpride or clozapine. This somewhat better efficacy was confirmed by fewer participants in the olanzapine groups leaving the studies early due to inefficacy of treatment compared to quetiapine (8 RCTs, n=1563, RR 0.56 CI 0.44 to 0.70, NNT 11 CI 6 to 50), risperidone (14 RCTs, n=2744, RR 0.78 CI 0.62 to 0.98, NNT 50 CI 17 to 100) and ziprasidone (5 RCTs, n=1937, RR 0.64 CI 0.51 to 0.79, NNT 17, CI 11 to 33). Fewer participants in the olanzapine group than in the quetiapine (2 RCTs, n=876, RR 0.56 CI 0.41 to 0.77, NNT 11 CI 7 to 25) and ziprasidone (2 RCTs, n=766, RR 0.65 CI 0.45 to 0.93, NNT 17 CI 9 to 100) treatment groups, but not in the clozapine group (1 RCT, n=980, RR 1.28 CI 1.02 to 1.61, NNH not estimable), had to be re-hospitalised in the trials. Except for clozapine, all comparators induced less weight gain than olanzapine (olanzapine compared to amisulpride: 3 RCTs, n=671, WMD 2.11kg CI 1.29kg to 2.94kg; aripiprazole: 1 RCT, n=90, WMD 5.60kg CI 2.15kg to 9.05kg; quetiapine: 7 RCTs, n=1173, WMD 2.68kg CI 1.10kg to 4.26kg; risperidone: 13 RCTs, n=2116, WMD 2.61kg CI 1.48kg to 3.74kg; ziprasidone: 5 RCTs, n=1659, WMD 3.82kg CI 2.96kg to 4.69kg). Associated problems such as glucose and cholesterol increase were usually also more frequent in the olanzapine group. Other differences in adverse effects were less well documented. Nevertheless, olanzapine may be associated with slightly more extrapyramidal side effects than quetiapine (use of antiparkinson medication (6
Hassan, Lamiece; Senior, Jane; Frisher, Martin; Edge, Dawn; Shaw, Jenny
While the prevalence of mental illness is higher in prisons than in the community, less is known about comparative rates of psychotropic medicine prescribing. This is the first study in a decade to determine the prevalence and patterns of psychotropic medication prescribing in prisons. It is also the first study to comprehensively adjust for age when making comparisons with the general population. Four East of England prisons, housing a total of 2222 men and 341 women were recruited to the study. On census days, clinical records were used to identify and collect data on all prisoners with current, valid prescriptions for hypnotic, anxiolytic, antipsychotic, antimanic, antidepressant and/or stimulant medication, as listed in chapters 4.1 to 4.4 of the British National Formulary. Data on 280,168 patients were obtained for comparison purposes from the Clinical Practice Research Datalink. After adjusting for age, rates of psychotropic prescribing in prison were 5.5 and 5.9 times higher than in community-based men and women, respectively. We also found marked differences in the individual psychotropic drugs prescribed in prison and community settings. Further work is necessary to determine whether psychotropic prescribing patterns in prison reflect an appropriate balance between managing mental illness, physical health risks and medication misuse. PMID:24569096
Shivakumar, Venkataram; Jayaram, Naveen; Rao, Naren P.; Venkatasubramanian, Ganesan
Antipsychotic induced weight gain is the most common and distressing side effect. This also affects the compliance toward the treatment and hence the prognosis. Non - pharmacological interventions such as exercise and diet modifications alone might not be sufficient most of the times; also ensuring compliance toward this is difficult in patients with psychiatric illness. So, the role of weight - reducing drugs become important. In this case report, we describe the use of low - dose topiramate as a weight - reducing agent, in a patient with a bipolar affective disorder - mania with psychotic symptoms, who had significant risperidone - induced weight gain. PMID:22661816
Bogle, S. M.; Harris, C. M.
OBJECTIVES--To assess the validity of the item as a measure of the volume of a drug prescribed; and to investigate the possibility that higher quantities per item are prescribed for patients who are not exempt from the prescription charge. DESIGN--Five substudies. For the first, a frequency distribution was derived of the different quantities per item of 10 commonly used drugs prescribed by 20 randomly selected practices in each of five family health service authority areas. For the second, the variation in average quantity per item for the same drugs in the same practices was calculated. For the third and fourth, variation in average quantity per item for 90 commonly used drugs was calculated for all 90 family health service authorities and for all 14 regional health authorities in England. For the fifth, the average quantity per item for each of the 90 drugs was regressed on the percentage of items exempt from the prescription charge, at family health service authority level, and the percentage of variation explained by the regression found. MAIN OUTCOME MEASURE--Distribution of quantity per item; variation in average quantity per item between the practices, between family health service authorities, and between regions; and percentage of variation between family health service authorities accounted for by exemption from the prescription charge. RESULTS--Wide variation was found in the quantities per item prescribed by the practices, and in the average quantity per item between practices and between family health service authorities. No family health service authority was consistently high or low in quantity per item across the 90 drugs. Variation in average quantity per item was less at regional than at family health service authority level, though still high for many of the drugs. The proportion of variation accounted for by exemption from prescription charges ranged from 0% to 49% across the 90 drugs. CONCLUSIONS--The item is unsuitable as a measure of prescribing volume, even at regional level: a new measure, based on standard daily dosages, is needed. The percentage of the variation in quantity per item accounted for by exemption is inconsistent, and in over half the 90 drugs it was below 20%--therefore it is not a useful predictor. PMID:8148715
Langebrake, Claudia; Melzer, Simone; Baehr, Michael
The provision of drugs to hospitalised patients is a complex process with the involvement of different healthcare professionals. As pharmacotherapy is (1) one of the most common medical interventions, (2) a high-risk procedure, and (3) affects the majority of hospitalised patients, medication errors have sustainable impact on patient safety. Although medication errors can occur at different stages of drug use (prescribing, dispensing, administration), they are most likely within the prescribing process. According to the Reason's model of accident causation, these errors can be divided into active failures, error-provoking conditions, and latent conditions. Commonly, the complex interaction between lacking knowledge and/or experience, rule-based mistakes, skill-based slips and memory lapses, inadequate working environment (exessive work load, fatigue) as well as poor communication and safety culture is causative for prescribing errors. Therefore, good prescribing should include the following items: Adherence to formal criteria (e. g. avoidance of abbreviations), performance of medication reconciliation, implementation of an electronic prescribing system (computerised physician order entry, CPOE) - preferably combined with a clinical decision support system (CDSS), education and training as well as the establishment of a positive error management culture. The implementation of recommendations to reduce prescribing errors is described on the basis of established processes in hospitals. PMID:24867349
Grasslands of the central Great Plains developed with periodic fire. Prescribed burning is an important tool for managing grasslands to maintain desirable species composition, increase grazing livestock performance, maintain productivity, and control invasive weeds. The safe and effective use of pre...
Hughes, John Clayton
The atypical antipsychotics are a group of second generation drugs used for the treatment of schizophrenia, schizoaffective disorder, as well as some forms of bipolar and major depressive disorder. First generation or the "typical antipsychotics...
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% in Ireland. Conclusion Consistent findings of no increased prescribing of risperidone post generics with limited specific demand-side measures suggests no ‘spillover’ effect from one class to another encouraging the preferential prescribing of generic atypical antipsychotic drugs. This is exacerbated by the complexity of the disease area and differences in the side-effects between treatments. There appeared to be no clinical issues with generic risperidone, and prices inversely reflected measures to enhance their utilisation. PMID:24927744
Montgomery, William; Liu, Li; Stensland, Michael D; Xue, Hai Bo; Treuer, Tamas; Ascher-Svanum, Haya
Background This article describes the personal, societal, and economic burden attributable to schizophrenia in the People’s Republic of China and highlights the potential for effective outpatient treatment to reduce this burden given recent changes in the Chinese health care system. The importance of effective antipsychotic therapy in reducing the burden of schizophrenia is also examined. Methods Published research on the burden, disability, management, and economic costs of schizophrenia in the People’s Republic of China was examined in the context of the larger body of global research. Research written in English or Chinese and published before June 2012 was identified using PubMed, CNKI, and Wanfang Med database searches. The contribution of effective antipsychotic therapy in reducing the risk for relapse and hospitalization and improving patients’ functioning is described. Results Schizophrenia imposes a substantial burden on Chinese society, with indirect costs accounting for the majority of the total cost. Functional impairment is high, leading to lost wages and work impairment. In the People’s Republic of China, schizophrenia is the most common diagnosis among hospitalized psychiatric patients. Ongoing changes in the Chinese health care system may reduce some barriers to effective relapse prevention in schizophrenia and potentially reduce hospitalizations. The use of antipsychotics for acute episodes and maintenance treatment has been shown to decrease symptom severity and reduce the risk for relapse and hospitalization. However, discontinuing antipsychotic medication appears common and is a strong predictor of relapse. Cost-effectiveness research in the People’s Republic of China is needed to examine the potential gains from improved outpatient antipsychotic treatment. Conclusion Schizophrenia is a very costly mental illness in terms of personal, economic, and societal burden, both in the People’s Republic of China and globally. When treated effectively, patients tend to persist longer with antipsychotic treatment, have fewer costly relapses, and have improved functioning. Further research examining the long-term effects of reducing barriers to effective treatments on the societal burden of schizophrenia in the People’s Republic of China is needed. PMID:23983478
General practitioners have a personal list of drugs which they prescribe. As new drugs become available and older drugs are outmoded, the doctor will change this personal list. The reasons for making such changes are discussed, and also the question of the perceived mechanism of action of the drug, particularly in relation to the placebo effect. PMID:19790791
Since 1997, we have been studying the effects of prescribed burns conducted during late winter on shortgrass steppe on the Pawnee National Grassland. During 1997 – 2002, we studied burns on the western (Crow Valley) portion of the Pawnee by comparing plant growth on burns conducted by the Forest Ser...
M. Azermai; M. Petrovic; S. Engelborghs; M. M. Elseviers; S. Van der Mussele; H. Debruyne; L. Van Bortel; R. H. Vander Stichele
Background: Antipsychotic use for behavioural and psychological symptoms of dementia (BPSD) is controversial. Guidelines advise to reduce antipsychotics given the adverse effects and limited efficacy, to limit dose and treatment duration as well as to undertake discontinuation.Methods: A pilot study with 40 hospitalised geriatric cognitively impaired patients, in which the effects of abrupt antipsychotic discontinuation were investigated, using neuropsychiatric inventory
Dobrin, Irina; Dobrin, R P; Chele, Gabriela; Stef?nescu, C; Knieling, A; Chiri??, Roxana
The present study examined the safety of the atypical antipsychotic drugs sertindol, olanzapine and quetiapine used in the treatment of schizophrenia. Haloperidol, a typical antipsychotic drug, was used for comparison. These data may account for the different therapeutic effects and side-effect profiles (cardiovascular risk) of typical and atypical antipsychotic drugs in schizophrenia. PMID:21243790
Christine Konradi; Stephan Heckers
This paper reviews the evidence that antipsychotic drugs induce neuroplasticity. We outline how the synaptic changes induced by the antipsychotic drug haloperidol may help our understanding of the mechanism of action of antipsychotic drugs in general, and how they may help to elucidate the neurobiology of schizophrenia. Studies have provided compelling evidence that haloperidol induces anatomical and molecular changes in
Connor, A J; Fraser, S G
Purpose In 2009, the National Institute for Clinical Excellence (NICE) published guidance on the treatment of ocular hypertension and glaucoma. The aim of the present study was to describe the impact this guidance had on glaucoma prescribing and to describe recent prescribing trends in England. Method Prescribing cost analysis data held by NHS Business Authority for the years 2000–2012 was analysed. Results The number of prescriptions dispensed increased by 67% from 4.76 million in 2000 to 7.96 million in 2012. Over the same time period, drug costs increased by 88% from £55.2 million to £103.7 million. Prescriptions for prostaglandin analogues increased fourfold, while there was a threefold decrease in the use of beta-blockers. The most commonly prescribed glaucoma medication was latanoprost. The introduction of generic latanoprost in 2012 more than halved the cost associated with this medication. NICE guidance appeared to have had no effect on the total number of prescriptions or the classes of medications prescribed. Conclusion The introduction of the NICE guidelines did not change glaucoma prescribing practice, although it is not clear whether this represents non-adherence to the guidelines or whether the guidelines embodied pre-existing practice. PMID:24858531
Nikki J. Radke; David B. Wester; Gad Perry; Sandra Rideout-Hanzak
Prescribed fire is a common land management tool used to reduce undesirable shrubs, improve forage quality, and enhance wildlife habitat for game species. However, it also has impacts on nongame species. We examined whether a prescribed fire would affect the abundance of lizards and invertebrates in central Texas. In February 2004, four sites were treated with low-intensity prescribed fires; four
Hrib, N J; Jurcak, J G; Burgher, K L; Conway, P G; Hartman, H B; Kerman, L L; Roehr, J E; Woods, A T
A series of benzisoxazole- and benzisothiazole-3-carboxamides has been prepared and tested for potential antipsychotic activity. In general, the compounds showed an affinity for dopamine D2 and serotonin 5HT2A and 5HT1A receptors. Several members of this series have demonstrated activity in animal models predictive of potential antipsychotic activity. In addition, compounds 18, 19, 22, 27, 28, 43, and 44 have also shown a potential for reduced EPS liability as suggested by the ratio of activity seen in mesolimbic-mediated vs nigrostriatal-mediated behavioral assays. PMID:7914536
Kim, Jong-Hoon; Yi, Sang Hoon; Park, Kyung Tae; Ahn, Yong Min; Lee, Kyu Young; Yang, Seung Ae; Kim, Yong Sik
The relationship between antipsychotic-induced extrapyramidal syndrome (EPS) and the autonomic neurocardiac function was examined in 57 schizophrenic patients treated with atypical antipsychotics. Comprehensive assessments of EPS and heart rate dynamics were performed. There was a significant negative correlation of non-hypokinetic parkinsonism, akathisia, and dyskinesia with several linear and novel non-linear heart rate dynamics measures, suggesting reduced neurocardiac dynamics associated with some forms of EPS. Assessment of heart rate dynamics may be useful for the detection of these adverse effects and may serve as a useful non-invasive method providing a dynamic window into the alterations of complex neuronal activity. PMID:16343860
Howland, Robert H
This article reviews the use of the new atypical antipsychotic drug paliperidone extended-release (Pal-ER). Pal-ER is a delayed-release formulation that provides continual drug delivery over 24 hours and reduces fluctuations in serum drug concentrations. This delayed release minimizes side effects related to high serum levels that occur with immediate-release formulations. Pal-ER is effective, safe, and relatively well tolerated. Although Pal-ER does not have any major advantages or disadvantages compared with other antipsychotic drugs, it has unique pharmacological properties and may be a beneficial alternative medication for some patients. PMID:17526326
Fernández, Cristina; Vega, José A.; Fonturbel, Teresa
Prescribed burning is commonly used to reduce the risk of severe wildfire. However, further information about the associated environmental effects is required to help forest managers select the most appropriate treatment. To address this question, we evaluated if fire severity during spring prescribed burning significantly affects the resprouting ability of two common shrub species in shrubland under a Mediterranean climate in NW Spain. Fire behaviour and temperatures were recorded in tagged individuals of Erica australis and Pterospartum tridentatum during prescribed burning. The number and length of resprouted shoots were measured three times (6, 12 and 18 months) after the prescribed burning. The influence of a series of fire severity indicators on some plant resprouting vigour parameters was tested by canonical correlation analysis. Six months and one year after prescribed burning, soil burn severity (measured by the absolute reduction in depth of the organic soil layer, maximum temperatures in the organic soil layer and the mineral soil surface during burning and the post-fire depth of the organic soil layer) reduced the resprouting vigour of E. australis and P. tridentatum. In contrast, direct measurements of fire effects on plants (minimum branch diameter, duration of temperatures above 300 °C in the shrub crown and fireline intensity) did not affect the post-fire plant vigour. Soil burn severity during spring prescribed burning significantly affected the short-term resprouting vigour in a mixed heathland in Galicia. The lack of effects eighteen months after prescribed burning indicates the high resilience of these species and illustrates the need to conciliate fire prevention and conservation goals.
Wyatt, T D; Passmore, C M; Morrow, N C; Reilly, P M
OBJECTIVE--To see whether changes in prescribing of oral antibacterials in Northern Ireland show the need for a community antibiotics policy. DESIGN--Analysis of prescribing totals for several oral antibiotics obtained retrospectively from the prescription pricing bureau for the years 1983-7. SETTING--Audit of anti-infective prescribing in general practice in Northern Ireland over five years. MAIN OUTCOME MEASURE--Respective usage of agents defined as "common" and "occasional" in 1983. RESULTS--There was a gradual decrease in the relative use of common agents from 82% of the total in 1983 to 77% in 1987 together with a complementary increase in the use of occasional agents from 5% to 10%. Pronounced changes were noted in the use of amoxycillin, ampicillin, erythromycin, minocycline, doxycycline, and amoxycillin-clavulanic acid. CONCLUSION--Though this survey found reasonably conservative prescribing, the trend towards increased use of occasional agents has both clinical and cost implications which could be addressed by the use of a prescribing formulary. PMID:2107899
Katrina M Wyatt; Paul W Dimmock; Martin Frischer; Paul W Jones; Shaugn PM O'Brien
BACKGROUND: Over 300 therapies have been proposed for premenstrual syndrome. To date there has been only one survey conducted in the UK of PMS treatments prescribed by GPs, a questionnaire-based study by the National Association of Premenstrual Syndrome in 1989. Since then, selective serotonin re-uptake inhibitors have been licensed for severe PMS\\/PMDD, and governmental recommendations to reduce the dosage of
Bond, Christine; Blenkinsopp, Alison; Raynor, David K
There have been widespread changes in society and the roles of professionals. This change is also reflected in health care, where there is now acceptance of the need to involve patients in decision making. In prescribing specifically, the concordance agenda was developed alongside these initiatives to encourage improved medication taking and reduce wastage. However the extent to which these partnerships are delivered in practice remains unclear. This paper explores some of the issues to be considered when preparing patients and professionals for partnership and summarizes the limited evidence of barriers to, and benefits of, this approach. Firstly patients must be given the confidence, skills and knowledge to be partners. They need information about medicines, provided in ways known to be acceptable to them. Likewise professionals may need new skills to be partners. They need to understand the patient agenda and may need training and support to change the ways in which they consult with patients. There are also practical issues such as the perceived increase in time taken when consulting in partnership mode, room layout, computer interfaces and record keeping. Health care professionals other than doctors are also expected to behave in partnership mode, whether this is as prescribers in their own right or in supporting the prescribing of others. Whilst much has been claimed for the benefit of partnership approaches, hard evidence is limited. However whilst there is still much more to understand there will be no going back to the paternalistic model of the mid 20th century. PMID:22621201
Bond, Christine; Blenkinsopp, Alison; Raynor, David K
There have been widespread changes in society and the roles of professionals. This change is also reflected in health care, where there is now acceptance of the need to involve patients in decision making. In prescribing specifically, the concordance agenda was developed alongside these initiatives to encourage improved medication taking and reduce wastage. However the extent to which these partnerships are delivered in practice remains unclear. This paper explores some of the issues to be considered when preparing patients and professionals for partnership and summarizes the limited evidence of barriers to, and benefits of, this approach. Firstly patients must be given the confidence, skills and knowledge to be partners. They need information about medicines, provided in ways known to be acceptable to them. Likewise professionals may need new skills to be partners. They need to understand the patient agenda and may need training and support to change the ways in which they consult with patients. There are also practical issues such as the perceived increase in time taken when consulting in partnership mode, room layout, computer interfaces and record keeping. Health care professionals other than doctors are also expected to behave in partnership mode, whether this is as prescribers in their own right or in supporting the prescribing of others. Whilst much has been claimed for the benefit of partnership approaches, hard evidence is limited. However whilst there is still much more to understand there will be no going back to the paternalistic model of the mid 20th century. PMID:22621201
Pijnenborg, G H M; Timmerman, M E; Derks, E M; Fleischhacker, W W; Kahn, R S; Aleman, A
Although antipsychotics are widely prescribed, their effect of on improving poor illness insight in schizophrenia has seldom been investigated and therefore remains uncertain. This paper examines the effects of low dose haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on insight in first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. The effects of five antipsychotic drugs in first episode psychosis on insight were compared in a large scale open randomized controlled trial conducted in 14 European countries: the European First-Episode Schizophrenia Trial (EUFEST). Patients with at least minimal impairments in insight were included in the present study (n=455). Insight was assessed with item G12 of the Positive and Negative Syndrome Scale (PANSS), administered at baseline and at 1, 3, 6, 9, and 12 months after randomization. The use of antipsychotics was associated with clear improvements in insight over and above improvements in other symptoms. This effect was most pronounced in the first three months of treatment, with quetiapine being significantly less effective than other drugs. Effects of spontaneous improvement cannot be ruled out due to the lack of a placebo control group, although such a large spontaneous improvement of insight would seem unlikely. PMID:25907250
Zajdel, Pawel; Partyka, Anna; Marciniec, Krzysztof; Bojarski, Andrzej J; Pawlowski, Maciej; Wesolowska, Anna
The introduction of typical antipsychotics over six decades ago signaled an important milestone in psychiatry. However, second-generation antipsychotics ameliorated the positive symptoms of schizophrenia but displayed limited effectiveness for the negative and cognitive symptoms. In addition, while the newer antipsychotics produced fewer motor side effects, the atypical antipsychotics still induced weight gain and endocrinopathies. In recent years, a third generation of antipsychotics was identified. Aripiprazole was the first approved drug acting as a D2 partial agonist/functionally selective ligand. This review presents the state of the development of novel antipsychotic dopaminergic and non-dopaminergic agents, supported by an overview of the compounds evaluated under advanced preclinical and clinical development (e.g., cariprazine and brexpiprazole). In line with the recent trends in the development of modern atypical antipsychotics, we present our strategic development of long-chain arylpiperazine-derived quinoline- and isoquinoline-sulfonamide displaying a multireceptor binding profile and partial D2 receptor agonism. PMID:24358948
Just, Marek J
Human sexuality is contingent upon many biological and psychological factors. Such factors include sexual drive (libido), physiological arousal (lubrication/erection), orgasm, and ejaculation, as well as maintaining normal menstrual cycle. The assessment of sexual dysfunction can be difficult due to the intimate nature of the problem and patients’ unwillingness to discuss it. Also, the problem of dysfunction is often overlooked by doctors. Atypical antipsychotic treatment is a key component of mental disorders’ treatment algorithms recommended by the National Institute of Health and Clinical Excellence, the American Psychiatric Association, and the British Society for Psychopharmacology. The relationship between atypical antipsychotic drugs and sexual dysfunction is mediated in part by antipsychotic blockade of pituitary dopamine D2 receptors increasing prolactin secretion, although direct correlations have not been established between raised prolactin levels and clinical symptoms. Variety of mechanisms are likely to contribute to antipsychotic-related sexual dysfunction, including hyperprolactinemia, sedation, and antagonism of a number of neurotransmitter receptors (?-adrenergic, dopaminergic, histaminic, and muscarinic). Maintaining normal sexual function in people treated for mental disorders can affect their quality of life, mood, self-esteem, attitude toward taking medication, and compliance during therapy. PMID:26185449
Pyne, Jeffrey M.; Fischer, Ellen P.; Gilmore, LaNissa; McSweeney, Jean C.; Stewart, Katharine E.; Mittal, Dinesh; Bost, James E.; Valenstein, Marcia
Objective: A substantial gap exists between patients and their mental health providers about patient's perceived barriers, facilitators, and motivators (BFMs) for taking antipsychotic medications. This article describes how we used an intervention mapping (IM) framework coupled with qualitative and quantitative item-selection methods to…
Canfrán-Duque, Alberto; Casado, María E; Pastor, Oscar; Sánchez-Wandelmer, Jana; de la Peña, Gema; Lerma, Milagros; Mariscal, Paloma; Bracher, Franz; Lasunción, Miguel A; Busto, Rebeca
Haloperidol, a typical antipsychotic, has been shown to inhibit cholesterol biosynthesis by affecting ?(7)-reductase, ?(8,7)-isomerase, and ?(14)-reductase activities, which results in the accumulation of different sterol intermediates. In the present work, we investigated the effects of atypical or second-generation antipsychotics (SGA), such as clozapine, risperidone, and ziprasidone, on intracellular lipid metabolism in different cell lines. All the SGAs tested inhibited cholesterol biosynthesis. Ziprasidone and risperidone had the same targets as haloperidol at inhibiting cholesterol biosynthesis, although with different relative activities (ziprasidone > haloperidol > risperidone). In contrast, clozapine mainly affected ?(24)-reductase and ?(8,7)-isomerase activities. These amphiphilic drugs also interfered with the LDL-derived cholesterol egress from the endosome/lysosome compartment, thus further reducing the cholesterol content in the endoplasmic reticulum. This triggered a homeostatic response with the stimulation of sterol regulatory element-binding protein (SREBP)-regulated gene expression. Treatment with SGAs also increased the synthesis of complex lipids (phospholipids and triacylglycerides). Once the antipsychotics were removed from the medium, a rebound in the cholesterol biosynthesis rate was detected, and the complex-lipid synthesis further increased. In this condition, apolipoprotein B secretion was also stimulated as demonstrated in HepG2 cells. These effects of SGAs on lipid homeostasis may be relevant in the metabolic side effects of antipsychotics, especially hypertriglyceridemia. PMID:23175778
Mai, Jaymie; Franklin, Gary; Tauben, David
Recently, there has been a dramatic increase in the use of opioids to treat chronic noncancer pain. Opioids are also being prescribed in stronger potencies and larger doses for musculoskeletal injuries. In some cases, the use of opioids for work-related injuries may actually increase the likelihood of disability. Chronic opioid use is associated with increased risk for overdose morbidity and mortality and other nonfatal adverse outcomes. The risk of dependence and addiction is much more common than previously thought. This guideline provides recommendations for prudent opioid prescribing and addresses issues critical to the care and rehabilitation of injured workers. PMID:26231959
Mattson, Margaret E; Albright, Victoria A; Yoon, Joanna; Council, Carol L
Case reports in medical literature suggest that the atypical antipsychotic quetiapine, a medication not previously considered to have abuse potential, is now being subject to misuse and abuse (MUA; ie, taken when not prescribed for them or used in a way other than instructed by their health professional). Here we present systematic, nationally representative data from the 2005 to 2011 Drug Abuse Warning Network (DAWN) for prevalence of emergency department (ED) visits among the U.S. general population involving quetiapine and related to MUA, suicide attempts, and adverse reactions. Nationally, quetiapine-related ED visits increased 90% between 2005 and 2011, from 35,581 ED visits to 67,497. DAWN data indicate that when used without medical supervision for recreational/self-medication purposes, quetiapine poses health risks for its users, especially among polydrug users and women. These findings suggest that the medical and public health communities should increase vigilance concerning this drug and its potential for MUA. PMID:26056465
Furtado, Vivek A; Srihari, Vinod; Kumar, Ajit
Background Many people (up to 50%) with schizophrenia also have co-morbid depression. It has been suggested that new atypical antipsychotic drugs are beneficial for people with the two diagnoses. Objectives To assess the effects of atypical antipsychotic drugs on people who have a diagnosis of both schizophrenia and depression. Search methods We searched the Cochrane Schizophrenia’s Group Register (to March 2006). We supplemented this by citation searching and personal contact with authors and relevant pharmaceutical companies. Selection criteria We included randomised clinical trials of atypical antipsychotic drugs used specifically for the treatment of people with a diagnosis of both schizophrenia and depression. Data collection and analysis We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). Main results We found 878 citations but were only able to include three studies (five reports). One trial found no significant difference between quetiapine and haloperidol for the outcome of ‘less than 50% reduction in PANSS score’ (n=180, RR 0.91 CI 0.8 to 1.0). Those allocated sulpiride had significantly lower depression scores compared with people given chlorpromazine (1 RCT, n=36, WMD CPRS ?0.70 CI ?1.2 to ?0.2). Again, however, in the quetiapine versus haloperidol comparison, the continuous scoring did not highlight differences (1 RCT, n=180, WMD PANSS depression change ?0.57 CI ?1.4 to 0.30). When clozapine was compared with any other antipsychotic drug plus an antidepressant or placebo, clozapine constantly scored better on Hamilton scores (1 RCT, n=29, WMD vs antipsychotic + mianserin ?5.53 CI ?8.23 to ?2.8; 1 RCT, n=32, WMD vs antipsychotic + meclobemide ?4.35 CI ?6.7 to ?2.03; 1 RCT, n=33, WMD vs antipsychotic + placebo ?6.35 CI ?8.6 to ?4.1). Authors’ conclusions There are too few data to guide patients, carers, clinicians or policy makers. Current practice has to be guided by evidence other than that derived from randomised trials and more trials in this important area are indicated. PMID:18254078
Willett, Gilbert M.; Hyde, Jennifer E.; Uhrlaub, Michael B.; Wendel, Cara L.; Karst, Gregory M.
Examined the relative electromyographic (EMG) activity of upper and lower rectus abdominis (LRA) and external oblique (EOA) muscles during five abdominal strengthening exercises. Isometric and dynamic EMG data indicated that abdominal strengthening exercises activated various abdominal muscle groups. For the LRA and EOA muscle groups, there were…
Michl, Johanna; Scharinger, Christian; Zauner, Miriam; Kasper, Siegfried; Freissmuth, Michael; Sitte, Harald H.; Ecker, Gerhard F.; Pezawas, Lukas
The vast majority of approved antidepressants and antipsychotics exhibit a complex pharmacology. The mechanistic understanding of how these psychotropic medications are related to adverse drug reactions (ADRs) is crucial for the development of novel drug candidates and patient adherence. This study aims to associate in vitro assessed binding affinity profiles (39 compounds, 24 molecular drug targets) and ADRs (n=22) reported in clinical trials of antidepressants and antipsychotics (n>59.000 patients) by the use of robust multivariate statistics. Orthogonal projection to latent structures (O-PLS) regression models with reasonable predictability were found for several frequent ADRs such as nausea, diarrhea, hypotension, dizziness, headache, insomnia, sedation, sleepiness, increased sweating, and weight gain. Results of the present study support many well-known pharmacological principles such as the association of hypotension and dizziness with ?1-receptor or sedation with H1-receptor antagonism. Moreover, the analyses revealed novel or hardly investigated mechanisms for common ADRs including the potential involvement of 5-HT6-antagonism in weight gain, muscarinic receptor antagonism in dizziness, or 5-HT7-antagonism in sedation. To summarize, the presented study underlines the feasibility and value of a multivariate data mining approach in psychopharmacological development of antidepressants and antipsychotics. PMID:25044049
Dobel-Ober, D; Brimblecombe, N; Bradley, E
Mental health nurses can now train to become independent prescribers as well as supplementary prescribers. Independent nurse prescribing can potentially help to reorganize mental health services, increase access to medicines and improve service user information, satisfaction and concordance. However, mental health nursing has been slow to undertake prescribing roles, and there has been little work conducted to look at where nurse prescribing is proving successful, and those areas where it is less so. This survey was designed to collect information from directors of nursing in mental health trusts about the numbers of mental health prescribers in England, gather views about prescribing in practice, and elicit intentions with regards to the development of nurse prescribing. In some Trusts, the number of mental health nurse prescribers has increased to the point where wider impacts on workforce, the configuration of teams and services are inevitable. Currently, the way that prescribing is used within different organizations, services and teams varies and it is unclear which setting is most appropriate for the different modes of prescribing. Future work should focus on the impact of mental health nurse prescribing on service delivery, as well as on service users, colleagues and nurses themselves. PMID:20633075
Dorsey, E. Ray; Rabbani, Atonu; Gallagher, Sarah A.; Conti, Rena M.; Alexander, G. Caleb
Background In April 2005, the US Food and Drug Administration (FDA) issued an advisory and subsequent black box warning regarding the risks of atypical anti-psychotic use among elderly patients with dementia. The impact of these warnings on atypical drug use is unknown. Methods We used quasi-experimental, interrupted time-series analyses to examine nationally representative data from IMS Health’s National Disease and Therapeutic Index from January 2003 through December 2008. The primary measurement from this audit of office-based physicians was the use of an atypical antipsychotic agent. We quantified the impact of the advisory on atypical anti-psychotic use among all individuals and those 65 years or older with dementia. Results From January 2003 to March 2005, mentions of total atypical antipsychotic drugs increased at an annual rate of 34%, and among patients with dementia, 16%. In the year prior to the FDA advisory, there were approximately 13.6 million atypical drug mentions, including 0.8 million among those with dementia. In the year following the advisory, atypical drug mentions fell 2% overall and 19% among those with dementia. In 2004, 19% (0.8 of 4.1 million) of drug mentions for dementia were for an atypical agent. By 2008, this proportion decreased to 9% (0.4 of 4.3 million). Atypical drug use slowed for both FDA-approved and off-label indications and declined through 2008 for all populations examined. Conclusion The FDA advisory was associated with decreases in the use of atypical antipsychotics, especially among elderly patients with dementia. PMID:20065205
Thinning and prescribed fire are common management tools used to eliminate thick fuel loads that could otherwise facilitate and encourage a more severe catastrophic wildfire. The objective of this study was to quantify the lasting effects of prescribed fire on forest floor and soil nutrients approxi...
Background Treatment of psychotic disorders consists primarily of second generation antipsychotics, which are associated with metabolic side effects such as overweight/obesity, diabetes, and dyslipidemia. Evidence-based clinical practice guidelines recommend timely assessment and management of these conditions; however, research studies show deficits and delays in metabolic monitoring and management for these patients. This protocol article describes the project ‘Monitoring and Management for Metabolic Side Effects of Antipsychotics,’ which is testing an approach to implement recommendations for these practices. Methods/Design This project employs a cluster randomized clinical trial design to test effectiveness of an evidence-based quality improvement plus facilitation intervention. Eligible study sites were VA Medical Centers with ?300 patients started on a new antipsychotic prescription in a six-month period. A total of 12 sites, matched in pairs based on scores on an organizational practice survey, were then randomized within pairs to intervention or control conditions. Study participants include VA employees involved in metabolic monitoring and management of patients treated with antipsychotics at participating sites. The intervention involves researchers partnering with clinical stakeholders to facilitate tailoring of local implementation strategies to address barriers to metabolic side-effect monitoring and management. The intervention includes a Design Phase (initial site visit and subsequent development of a local implementation plan); Implementation Phase (guided by an experienced external facilitator); and a Sustainability Phase. Evaluation includes developmental, implementation-focused, progress-focused and interpretative formative evaluation components, as well as summative evaluation. Evaluation methods include surveys, qualitative data collection from provider participants, and quantitative data analysis of data for all patients prescribed a new antipsychotic medication at a study site who are due for monitoring or management of metabolic side effects during the study phases. Changes in rates of recommended monitoring and management actions at intervention and control sites will be compared using time series analyses. Discussion Improving monitoring for metabolic side effects of antipsychotics, as well as promoting timely evidence-based management when these effects emerge, will lead to improved patient safety and long-term outcomes. This article discusses key strengths and challenges of the study. Trial registration NCT01875861 PMID:24103648
Manfredo, M.J.; Fishbein, M.; Haas, G.E.; Watson, A.E.
This article discusses the fire policy of several land management agencies and research done to assess public attitudes toward these policies. Biological information may provide support for a prescribed fire policy in areas managed with a preservation mandate, that alone is not sufficient justification for its implementation. Fire policy has a critical sociopolitical component, and the fact that people appear poorly informed about the outcomes of fire policy and fire effects adds controversy. The fires of 1988 and the subsequent policy reevaluation reinforce what most managers realize: modern forestry is heavily involved in educating and communicating with the public.
Nazar, Hamde; Nazar, Mahdi; Rothwell, Charlotte; Portlock, Jane; Chaytor, Andrew; Husband, Andrew
Prescribing is a characteristic role of a medical practitioner. On graduating from medical school, students are presumed to have acquired the necessary pharmacology knowledge underpinning the therapeutics and developed their personal skills and behaviors in order to write a safe and effective prescription (The Four Ps). However, there are reports of errors in medical prescribing and dissatisfied feedback from recent graduates, which evidence potential flaws in the current training in the practice of prescribing. We examine the Four Ps from a systems approach and offer scope for educators and curriculum designers to review and reflect on their current undergraduate teaching, learning, and assessment strategies in a similar manner. We also adopt a national framework of common competencies required of all prescribers to remain effective and safe in their area of practice as a more objective layer to the broader learning outcomes of the General Medical Council Tomorrow's Doctors 2009. This exercise demonstrates where standard, recognized competencies for safe prescribing can be accommodated pedagogically within existing medical curricula. PMID:25945072
Nazar, Hamde; Nazar, Mahdi; Rothwell, Charlotte; Portlock, Jane; Chaytor, Andrew; Husband, Andrew
Prescribing is a characteristic role of a medical practitioner. On graduating from medical school, students are presumed to have acquired the necessary pharmacology knowledge underpinning the therapeutics and developed their personal skills and behaviors in order to write a safe and effective prescription (The Four Ps). However, there are reports of errors in medical prescribing and dissatisfied feedback from recent graduates, which evidence potential flaws in the current training in the practice of prescribing. We examine the Four Ps from a systems approach and offer scope for educators and curriculum designers to review and reflect on their current undergraduate teaching, learning, and assessment strategies in a similar manner. We also adopt a national framework of common competencies required of all prescribers to remain effective and safe in their area of practice as a more objective layer to the broader learning outcomes of the General Medical Council Tomorrow’s Doctors 2009. This exercise demonstrates where standard, recognized competencies for safe prescribing can be accommodated pedagogically within existing medical curricula. PMID:25945072
Mohamed, Somaia; Rosenheck, Robert A; Lin, Haiqun; Swartz, Marvin; McEvoy, Joseph; Stroup, Scott
No large-scale randomized trial has compared the effect of different second-generation antipsychotic drugs and any first-generation drug on alcohol, drug and nicotine use in patients with schizophrenia. The Clinical Antipsychotic Trial of Intervention Effectiveness study randomly assigned 1432 patients formally diagnosed with schizophrenia to four second-generation antipsychotic drugs (olanzapine, risperidone quetiapine, and ziprasidone) and one first-generation antipsychotic (perphenazine) and followed them for up to 18 months. Secondary outcome data documented cigarettes smoked in the past week and alcohol and drug use severity ratings. At baseline, 61% of patients smoked, 35% used alcohol, and 23% used illicit drugs. Although there were significant effects of time showing reduction in substance use over the 18 months (all p < 0.0001), this study found no evidence that any antipsychotic was robustly superior to any other in a secondary analysis of data on substance use outcomes from a large 18-month randomized schizophrenia trial. PMID:26075840
Remington, Gary; Fervaha, Gagan; Foussias, George; Agid, Ofer; Turrone, Peter
In the field of schizophrenia research, as in other areas of psychiatry, there is a sense of frustration that greater advances have not been made over the years, calling into question existing research strategies. Arguably, many purported gains claimed by research have been “lost in translation,” resulting in limited impact on diagnosis and treatment in the clinical setting. There are exceptions; for example, we would argue that different lines of preclinical and clinical research have substantially altered how we look at antipsychotic dosing. While this story remains a work in progress, advances “found in translation” have played an important role. Detailing these changes, the present paper speaks to a body of evidence that has already shifted clinical practice and raises questions that may further alter the manner in which antipsychotics have been administered over the last 6 decades. PMID:24467943
Mula, Marco; Monaco, Francesco
The potential for drug-drug interactions in psychiatry and patients with epilepsy is very high. Moreover, antiepileptic drugs are widely used outside epilepsy as psychotropic agents and their spectrum of activity on behavior is of considerable interest to psychopharmacology. In both neurologic and psychiatric practice, pharmacotherapy combinations are commonly used to treat comorbid psychiatric and neurologic disorders, to reduce or control the adverse effects of a medication or to increase its efficacy. This paper focuses on the metabolic pharmacokinetic interactions between two classes of psychotropic drugs: antiepileptic and antipsychotic drugs. The degree of documentation varies for many interactions from clinical case-report experiences to well established research outcomes. The evidence and the clinical significance of these interactions are reviewed. In general, it is better to use as few drugs as possible, as multicolored politherapies increase the possible adverse effects of drug interactions and reduce patient compliance. PMID:12410063
Mailman, Richard B.; Murthy, Vishakantha
Functional selectivity is the term that describes drugs that cause markedly different signaling through a single receptor (e.g., full agonist at one pathway and antagonist at a second). It has been widely recognized recently that this phenomenon impacts the understanding of mechanism of action of some drugs, and has relevance to drug discovery. One of the clinical areas where this mechanism has particular importance is in the treatment of schizophrenia. Antipsychotic drugs have been grouped according to both pattern of clinical action and mechanism of action. The original antipsychotic drugs such as chlorpromazine and haloperidol have been called typical or first generation. They cause both antipsychotic actions and many side effects (extrapyramidal and endocrine) that are ascribed to their high affinity dopamine D2 receptor antagonism. Drugs such as clozapine, olanzapine, risperidone and others were then developed that avoided the neurological side effects (atypical or second generation antipsychotics). These compounds are divided mechanistically into those that are high affinity D2 and 5-HT2A antagonists, and those that also bind with modest affinity to D2, 5-HT2A, and many other neuroreceptors. There is one approved third generation drug, aripiprazole, whose actions have been ascribed alternately to either D2 partial agonism or D2 functional selectivity. Although partial agonism has been the more widely accepted mechanism, the available data are inconsistent with this mechanism. Conversely, the D2 functional selectivity hypothesis can accommodate all current data for aripiprazole, and also impacts on discovery compounds that are not pure D2 antagonists. PMID:19909227
Booij, Jan; van Amelsvoort, Thérèse
The results of imaging studies have played an important role in the formulation of hypotheses regarding the etiology of psychosis and schizophrenia, as well as in our understanding of the mechanisms of action of antipsychotics. Since this volume is primarily directed to molecular aspects of psychosis and antipsychotics, only the results of molecular imaging techniques addressing these topics will be discussed here.One of the most consistent findings of molecular imaging studies in schizophrenia is an increased uptake of DOPA in the striatum, which may be interpreted as an increased synthesis of L-DOPA. Also, several studies reported an increased release of dopamine induced by amphetamine in schizophrenia patients. These findings played an important role in reformulating the dopamine hypothesis of schizophrenia. To study the roles of the neurotransmitters ?-aminobutyric acid (GABA) and glutamate in schizophrenia, SPECT as well as MR spectroscopy have been used. The results of preliminary SPECT studies are consistent with the hypothesis of NMDA receptor dysfunction in schizophrenia. Regarding the GABA deficit hypothesis of schizophrenia, imaging results are inconsistent. No changes in serotonin transporters were demonstrated in imaging studies in schizophrenia, but studies of several serotonin receptors showed conflicting results. The lack of selective radiotracers for muscarinic receptors may have hampered examination of this system in schizophrenia as well as its role in the induction of side effects of antipsychotics. Interestingly, preliminary molecular imaging studies on the cannabinoid-1 receptor and on neuroinflammatory processes in schizophrenia have recently been published. Finally, a substantial number of PET/SPECT studies have examined the occupancy of receptors by antipsychotics and an increasing number of studies is now focusing on the effects of these drugs using techniques like spectroscopy and pharmacological MRI. PMID:23129337
Frank P Bymaster; David O Calligaro; Julie F Falcone; Richard D Marsh; Nicholas A Moore; Nicholas C Tye; Philip Seeman; David T Wong
The affinities of olanzapine, clozapine, haloperidol, and four potential antipsychotics were compared on binding to the neuronal receptors of a number of neurotransmitters. In both rat tissues and cell lines transfected with human receptors olanzapine had high affinity for dopamine D1, D2, D4, serotonin (5HT)2A, 5HT2C, 5HT3, ?1-adrenergic, histamine H1, and five muscarinic receptor subtypes. Olanzapine had lower affinity for
MENG, Meiling; LI, Wei; ZHANG, Shaowei; WANG, Hongyan; SHENG, Jianhua; WANG, Jijun; LI, Chunbo
Background Hyperprolactinemia (HPL) is a common side effect of antipsychotic medications. Recent reports suggest that aripiprazole can ameliorate antipsychotic-induced HPL, but results are inconsistent and the single available systematic review only considered five studies. Aim Conduct an updated meta-analysis of all randomized controlled trials (RCTs) about the efficacy and safety of aripiprazole as an adjunctive treatment for antipsychotic-induced hyperprolactinemia. Methods English and Chinese databases were searched for RCTs about the use of aripiprazole in treating antipsychotic-induced HPL published by January 20, 2015. Studies were selected using pre-defined inclusion and exclusion criteria. The Cochrane Risk of Bias tool was used to evaluate risk of biases, the Cochrane GRADE measure was used to assess the quality of evidence, and Review Manager 5.3 software was used for data analysis. Results A total of 21 studies, 19 of which were conducted in mainland China, were included in the analysis. Meta-analysis of data from 8 of the studies with a pooled sample of 604 individuals found that compared to the control condition adjunctive aripiprazole significantly increased the proportion of participants who experienced HPL recovery (risk ratio [RR]=19.2, 95%CI=11.0-33.5). The proportion who experienced any adverse effect during follow-up did not differ between the two groups, but the aripiprazole group was more likely to report somnolence (RR=2.76, 95%CI=1.34-5.69) and headaches (RR=2.31, 95%CI=1.08-4.92). High-dose aripiprazole (>5mg/day) was more effective than low-dose (<5mg/day) aripiprazole (RR=30.0, 95%CI=10.2-120.7 v. RR=15.1, 95%CI=8.1-28.1), but this difference was not statistically significant. The risk of bias in the studies was rated as ‘high’ in 6 of the studies and ‘unclear’ in 15 studies, and the quality of evidence was rated as ‘high’ for only 7 of the 57 outcome measures assessed. Conclusions This study systematically reviewed and evaluated all relevant RCTs and found that adjunctive aripiprazole is effective and safe to use in the treatment of antipsychotic-induced HPL. However, the low quality of some of the studies, the incomplete methodological information provided for most of the studies, and the relatively short follow-up time of the studies raises question about the validity of the results. Further work that resolves these methodological and reporting issues is needed. PMID:25852251
David A Shapiro; Sean Renock; Elaine Arrington; Louis A Chiodo; Li-Xin Liu; David R Sibley; Bryan L Roth; Richard Mailman
Atypical antipsychotic drugs have revolutionized the treatment of schizophrenia and related disorders. The current clinically approved atypical antipsychotic drugs are characterized by having relatively low affinities for D2-dopamine receptors and relatively high affinities for 5-HT2A serotonin receptors (5-HT, 5-hydroxytryptamine (serotonin)). Aripiprazole (OPC-14597) is a novel atypical antipsychotic drug that is reported to be a high-affinity D2-dopamine receptor partial agonist. We
Stefan Weinmann; Volkmar Aderhold
Introduction: Although a range of adverse effects of antipsychotic medication are well documented, less attention has been paid to the issue of reduced life expectancy.Method: The medical literature was searched to identify studies assessing severe somatic side?effects of long?term antipsychotic treatment with a possible impact on mortality, and studies evaluating antipsychotic?associated brain structure changes.Results: Short?term cardiac and long?term metabolic side
Margret SH Harris; Courtney L Wiseman; James L Reilly; Matcheri S Keshavan; John A Sweeney
Studies of procedural learning in medicated schizophrenia patients using predictive saccade paradigms have consistently demonstrated hypometric predictive responses. Findings from antipsychotic-naive schizophrenia patients indicate fewer or no deficits. This pattern of findings suggests that antipsychotic medications might adversely affect frontostriatal systems supporting procedural learning on this task. The accuracy and latency of predictive saccades were assessed in 25 antipsychotic-naive first-episode
Razzouk, Denise; Kayo, Monica; Sousa, Aglaé; Gregorio, Guilherme; Cogo-Moreira, Hugo; Cardoso, Andrea Alves; Mari, Jair de Jesus
Introduction Guidelines for the treatment of psychoses recommend antipsychotic monotherapy. However, the rate of antipsychotic polytherapy has increased over the last decade, reaching up to 60% in some settings. Studies evaluating the costs and impact of antipsychotic polytherapy in the health system are scarce. Objective To estimate the costs of antipsychotic polytherapy and its impact on public health costs in a sample of subjects with psychotic disorders living in residential facilities in the city of Sao Paulo, Brazil. Method A cross-sectional study that used a bottom-up approach for collecting costs data in a public health provider´s perspective. Subjects with psychosis living in 20 fully-staffed residential facilities in the city of Sao Paulo were assessed for clinical and psychosocial profile, severity of symptoms, quality of life, use of health services and pharmacological treatment. The impact of polytherapy on total direct costs was evaluated. Results 147 subjects were included, 134 used antipsychotics regularly and 38% were in use of antipsychotic polytherapy. There were no significant differences in clinical and psychosocial characteristics between polytherapy and monotherapy groups. Four variables explained 30% of direct costs: the number of antipsychotics, location of the residential facility, time living in the facility and use of olanzapine. The costs of antipsychotics corresponded to 94.4% of the total psychotropic costs and to 49.5% of all health services use when excluding accommodation costs. Olanzapine costs corresponded to 51% of all psychotropic costs. Conclusion Antipsychotic polytherapy is a huge economic burden to public health service, despite the lack of evidence supporting this practice. Great variations on antipsychotic costs explicit the need of establishing protocols for rational antipsychotic prescriptions and consequently optimising resource allocation. Cost-effectiveness studies are necessary to estimate the best value for money among antipsychotics, especially in low and middle income countries. PMID:25853709
Domino, Marisa Elena; Frank, Richard G; Rosenheck, Robert
Spending on antipsychotic medications continues to escalate as new products such as atypicals are increasingly used to treat schizophrenia and other conditions. Given that per person spending on behavioral health benefits is shrinking while spending on pharmaceutical products is increasing, the psychotropic portion of mental health expenditures is likely to continue to increase in the future. The diffusion of these new behavioral health technologies, or the rate at which these products have spread through the market, has been very uneven. Differences in adoption and diffusion rates of psychotropic medications across insurance settings, geographic regions, or subpopulations defined by age, gender, or racial or ethnic groups have important implications for the quality of care received by persons with mental illnesses. This article reviews the evidence on the diffusion of antipsychotic medication and discusses the implications of formulary policies on diffusion, addressing the health care service and administrative context in which the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project is being conducted and which it is intended to inform. PMID:12908664
Carbon, Maren; Correll, Christoph U.
The search for clinical outcome predictors for schizophrenia is as old as the field of psychiatry. However, despite a wealth of large, longitudinal studies into prognostic factors, only very few clinically useful outcome predictors have been identified. The goal of future treatment is to either affect modifiable risk factors, or use nonmodifiable factors to parse patients into therapeutically meaningful subgroups. Most clinical outcome predictors are nonspecific and/or nonmodifiable. Nonmodifiable predictors for poor odds of remission include male sex, younger age at disease onset, poor premorbid adjustment, and severe baseline psychopathology. Modifiable risk factors for poor therapeutic outcomes that clinicians can act upon include longer duration of untreated illness, nonadherence to antipsychotics, comorbidities (especially substance-use disorders), lack of early antipsychotic response, and lack of improvement with non-clozapine antipsychotics, predicting clozapine response. It is hoped that this limited capacity for prediction will improve as pathophysiological understanding increases and/or new treatments for specific aspects of schizophrenia become available. PMID:25733955
Angelini, A; Ciofani, G; Conti, P
Multidrug resistance (MDR) mediated by P-glycoprotein (Pgp) remains one of the major obstacles to effective cancer chemotherapy. Several chemosensitizers have been used in vivo and in vitro to reverse MDR but have exhibited several unwanted side effects. Antipsychotics are often administered to treat psychiatric disorders such as delirium, anxiety and sleep disorders in cancer patients during chemotherapy. The present in vitro study, examined the effects of two common antipsychotic compounds, haloperidol and risperidone, and a natural compound such as theobromine on reversing MDR Pgp-mediated, to evaluate their potential use as chemosensitizing agents. The human doxorubicin (doxo) resistant uterine sarcoma cells (MES-SA/Dx5) that overexpress Pgp (100-fold), were treated with the antipsychotic alone (1, 10 and 20 ?M) or in combination with different concentrations of doxo (2, 4 and 8 ?M). The accumulation and cytotoxicity of doxo (MTT assay) and cellular GSH content (GSH assay) in comparison with verapamil, a well-known Pgp inhibitor, used as reference molecule were examined. It was found that the three compounds significantly enhanced the intracellular accumulation of doxo in resistant cancer cells, when compared with cells receiving doxo alone (p<0.05). Furthermore, compounds showed strong potency to increase doxo cytotoxicity toward resistant MES-SA/Dx5 cells, when compared with untreated control cells. The antipsychotic compounds also significantly increased GSH content at all concentrations (> 30%) in resistant cells, when compared to untreated control cells (p<0.05). These findings suggest that the antipsychotics or their derivatives might represent a novel class of reversal agents for overcoming MDR in cancer therapy, in particular theobromine showed to be an effective Pgp inhibitor with the lowest toxicity. PMID:26122223
Ramsey, Timothy L; Brennan, Mark D
Glucagon-like peptide 1 receptor (GLP1R) signaling has been shown to have antipsychotic properties in animal models and to impact glucose-dependent insulin release, satiety, memory, and learning in man. Previous work has shown that two coding mutations (rs6923761 and rs1042044) are associated with altered insulin release and cortisol levels. We identified four frequently occurring haplotypes in Caucasians, haplotype 1 through haplotype 4, spanning exons 4-7 and containing the two coding variants. We analyzed response to antipsychotics, defined as predicted change in PANSS-Total (dPANSS) at 18 months, in Caucasian subjects from the Clinical Antipsychotic Trial of Intervention Effectiveness treated with olanzapine (n=139), perphenazine (n=78), quetiapine (n=14), risperidone (n=143), and ziprasidone (n=90). Haplotype trend regression analysis revealed significant associations with dPANSS for olanzapine (best p=0.002), perphenazine (best p=0.01), quetiapine (best p=0.008), risperidone (best p=0.02), and ziprasidone (best p=0.007). We also evaluated genetic models for the two most common haplotypes. Haplotype 1 (uniquely including the rs1042044 [Leu(260)] allele) was associated with better response to olanzapine (p=0.002), and risperidone (p=0.006), and worse response to perphenazine (p=.03), and ziprasidone (p=0.003), with a recessive genetic model providing the best fit. Haplotype 2 (uniquely including the rs6923761 [Ser(168)] allele) was associated with better response to perphenazine (p=0.001) and worse response to olanzapine (p=.02), with a dominant genetic model providing the best fit. However, GLP1R haplotypes were not associated with antipsychotic-induced weight gain. These results link functional genetic variants in GLP1R to antipsychotic response. PMID:25449714
Leung, Joanne Y T; Barr, Alasdair M; Procyshyn, Ric M; Honer, William G; Pang, Catherine C Y
Cardiovascular disease is the leading cause of death in people with severe mental disorders, and rates are proportionally greater than for other diseases such as cancer. Reports of sudden death in patients receiving antipsychotic treatment have raised concerns about the safety of antipsychotic drugs, leading to a number of recent changes in how such drugs are advertised and marketed. The majority of second generation antipsychotic drugs also have significant metabolic side-effects, such as weight gain, insulin resistance and hyperlipidemia, which may contribute indirectly to cardiovascular complications. As the use of antipsychotic drugs continues to expand into new indications and populations such as children and adolescents, a better understanding is needed of how antipsychotic drugs affect the cardiovascular system. Antipsychotic drugs interact with numerous receptors both centrally and peripherally, including monoamine receptors. The direct, non-specific pharmacological actions of antipsychotic drugs can lead to adverse cardiovascular effects, including orthostatic hypotension, tachycardia and ventricular arrhythmias. The mechanisms responsible for these antipsychotic-induced cardiovascular abnormalities have not been fully elucidated, but likely involve blockade of adrenergic or cholinergic receptors and hERG channels, in addition to impaired autonomic function. The direct and indirect effects of antipsychotic drugs on the cardiovascular system and their possible mechanisms of action are discussed in this review, where both preclinical and clinical findings are integrated. PMID:22565090
antipsychotic drugs and obesity and diabetes. Diabetes Care.Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity.
Kay, C R
Guidelines for prescribing oral contraceptives (Ocs), which take into account recent research findings concerning the relationship between OC use and the development of cervical and breast neoplasia and vascular diseases, were suggested. The findings of M.P. Vessey and his colleagues that the risk of cervical neoplasia increases with the duration of OC use are difficult to interpret. OC is strongly associated with certain types of sexual behavior, e.g., initiation of sexual activity at an early age, frequent intercourse, and intercourse with multiple partners, and these behavioral factors, in turn, are known to be associated with an increased risk of cervical cancer. Although an attempt was made to control for the effects of these behavioral factors, the findings of the study require further substantiation. Even if the findings are correct, OC users would appear to have only a minor excess risk of developing invasive carcinoma, and even this minimal increased risk could be avoided encouraging OC users to have cervical smears taken routinely. The findings of Pike and his colleagues in California concerning the risk of breast cancer among OC users are more controversial, and potentially more serious. The study found that there was a 4-fold increased risk of breast cancer in women, under the age of 37, who had used OCs prior to their 25th birthday, and the risk increased with duration of OC use. A study by McPerson and colleagues also reported that breast cancer was associated with the duration of OC use prior to 1st pregnancy. Other intensive studies have failed to reveal a relationship between breast neoplasia and OC use. Pike and his colleagues also published a table listing OC brands in rank order of their progestogen potency. Pike noted that there was a positive relationship between the occurrence of breast cancer and the level of progestogen potency. The table was harshly criticized because it is not possible to determine the potency level of combined formulations. Nevertheless, those brands associated with a higher risk of breast cancer contained high doses of progestogen as well as estrogen, and their use should be avoided. Furthermore, OCs with high progestogen doses should be avoided in order to reduce the risk of vascular diseases among OC users. The RCGP study demonstrated that there is a positive relationship between progestogen dosage and the development of arteriosclerotic diseases. OC formulations with doses exceeding 1 mg of norethisterone acetate and 150 mcg of levonorgestrel should be avoided. Breakthrough bleeding should be controlled by increasing the estrogen dose to 50 mcg rather than by altering the progesterone level. Effort should also be made to carefully tailor OC prescribing to the specific needs of each patient. The risk of vascular diseases among OC users is almost exclusively confined to older women who smoke. Care must be exercised in prescribing OCs for women who smoke and for women who other characteristics that place them at high risk of developing vascular disease. Since women differ considerably in the way they utilize and metabolize the steroids contained in OCs, efforts should be made to develop an inexpensive and simple technique for measuring serum steriod levels. This would allow physicians to reduce the steriod content of OCs for those women whose systems make maximal use of available steriods. PMID:6502571
Groši?, Vladimir; Folnegovi? Groši?, Petra; Kalember, Petra; Bajs Janovi?, Maja; Radoš, Marko; Mihanovi?, Mate; Henigsberg, Neven
Purpose To investigate the correlates of a clinical therapeutic response by using the parameters measured by proton magnetic resonance spectroscopy after the administration of atypical antipsychotics. Patients and methods Twenty-five antipsychotic-naïve first-episode patients with schizophrenia were monitored for 12 months. The patients were evaluated using 1H magnetic resonance spectroscopy in the dorsolateral prefrontal cortex and Positive and Negative Syndrome Scale, Clinical Global Impression Scale of Severity, Tower of London – Drexel University, Letter–Number Span Test, Trail Making Test A, and Personal and Social Performance Scale. They were administered atypical antipsychotics, starting with quetiapine. In the absence of a therapeutic response, another antipsychotic was introduced. Results After 12 study months, the N-acetylaspartate/creatine (NAA/Cr) level did not significantly change at the whole-group level. Additional analysis revealed a significant rise in the NAA/Cr level in the study group that stayed on the same antipsychotic throughout the study course (P=0.008) and a significant drop in NAA/Cr in the study group that switched antipsychotics (P=0.005). On the whole-group level, no significant correlations between NAA/Cr values and other scores were found at either baseline or after 12 study months. Conclusion One-year treatment with atypical antipsychotics administered to antipsychotic-naïve patients didn’t result in a significant rise in the NAA/Cr ratio. However, a significant rise was witnessed in the study group in which a satisfactory therapeutic response had been achieved with a single antipsychotic administration. PMID:25045268
Paluck, E.; Katzenstein, D.; Frankish, C. J.; Herbert, C. P.; Milner, R.; Speert, D.; Chambers, K.
OBJECTIVE: To investigate whether overprescribing is common in treatment of pediatric upper respiratory infections and to examine factors that influence prescribing antibiotics for children. DESIGN: A random, stratified sample of practising family physicians was surveyed with a mailed questionnaire. Initial nonresponders were mailed a second questionnaire. SETTING: British Columbia. PARTICIPANTS: A total of 608 general and family physicians. Response rate was 64%; 392/612 surveys were completed. MAIN OUTCOME MEASURES: Physicians' self-reported prescribing practices and knowledge of and attitudes toward using antibiotics for children's upper respiratory tract infections. RESULTS: Relative to treatment guidelines developed for the study, most physicians responded appropriately to the cough (94%) and lobar pneumonia (99.1%) vignettes. More than half the physicians (56.5%) reported they would immediately prescribe antibiotics for tympanic membrane dysfunction, and 79.4% indicated they would prescribe antibiotics for pharyngitis without obtaining a laboratory culture. Approximately 25% of physicians in the study did not believe that prior antibiotic use increased personal risk for acquiring drug-resistant infection, and 23.1% did not believe that antibiotic use was an important factor in promoting resistance in their communities. CONCLUSION: Education in current treatment of pediatric upper respiratory tract illnesses and antimicrobial drug resistance is required. The high response to the questionnaire (64%) and the many requests from physicians to receive the project's educational materials (45%) indicate a high level of interest in this subject. PMID:11281085
Kapur, Shitij; Mamo, David
A review of the history of antipsychotics reveals that while the therapeutic effects of chlorpromazine and reserpine were discovered and actively researched almost concurrently, subsequent drug development has been restricted to drugs acting on postsynaptic receptors rather than modulation of dopamine release. The fundamental property of atypical antipsychotics is their ability to produce an antipsychotic effect in the absence of extrapyramidal side effects (EPS) or prolactin elevation. Modulation of the dopamine D2 receptor remains both necessary and sufficient for antipsychotic drug action, with affinity to the D2-receptor being the single most important discriminator between a typical and atypical drug profile. Most antipsychotics, including atypical antipsychotics, show a dose-dependent threshold of D2 receptor occupancy for their therapeutic effects, although the precise threshold is different for different drugs. Some atypical antipsychotics do not appear to reach the threshold for EPS and prolactin elevation, possibly accounting for their atypical nature. To link the biological theories of antipsychotics to their psychological effects, a hypothesis is proposed wherein psychosis is a state of aberrant salience of stimuli and ideas, and antipsychotics, via modulation of the mesolimbic dopamine system, dampen the salience of these symptoms. Thus, antipsychotics do not excise psychosis: they provide the neurochemical platform for the resolution of symptoms. Future generations of antipsychotics may need to move away from a "one-size-fits-all polypharmacy-in-a-pill" approach to treat all the different aspects of schizophrenia. At least in theory a preferred approach would be the development of specific treatments for the different dimensions of schizophrenia (e.g., positive, negative, cognitive, and affective) that can be flexibly used and titrated in the service of patients' presenting psychopathology. PMID:14642968
Morrison, Paul; Meehan, Tom; Stomski, Norman Jay
The present study explores people's experience of living with antipsychotic medication side-effects. Qualitative data were gathered through semistructured interviews with 10 mental health consumers in a community care setting in Australia. The interview transcriptions were content analysed, and enhanced by combining manifest and latent content. Important contextual cues were identified through replaying the audio-recordings. Several main themes emerged from the analysis, including the impact of side-effects, attitudes to the use of medication and side-effects, and coping strategies to manage medication side-effects. Each participant reported between six and seven side-effects on average, which were often pronounced and had a major disruptive impact on their lives. Of these effects, the most commonly mentioned was sedation, which the participants described as leaving them in a 'zombie'-like state. Most participants expressed an attitude of acceptance about the side-effects. The participants' most common strategy to manage side-effects was to change the dosage of the medication. Other common side-effect management strategies involved using other medications to control side-effects, and diverse self-help techniques, the most common of which was relaxation/distraction techniques. PMID:25529392
Harding, J M; Modell, M; Freudenberg, S; MacGregor, R; Rea, J N; Steen, C A; Wojciechowski, M; Yudkin, G D
This paper discusses drawing up a restricted list of 245 drugs for use in an inner London group practice, based on a review of prescribing patterns in November 1982. The likely impact of the recent proposals by the Department of Health and Social Security to limit drugs available for prescription under the National Health Service on this project and on patient care is considered. We conclude that generic prescribing and a limited list of drugs may improve the quality of prescribing and be the only way to curb prescribing costs but that a limited list should be flexible, responsive to patients' needs, and applied to all prescribing. There should also be a mechanism for consumer feedback and regular revision of the list. PMID:3918627
Christopher J. Schmidt; Stephen M. Sorensen; John H. Kenne; Albert A. Carr; Michael G. Palfreyman
The correlation between the clinical activity of antipsychotic agents and their affinity for the D2 dopamine receptor has been the mainstay of the hypothesis that schizophrenia is due to excessive dopaminergic function. More recently, the unique clinical profile of the atypical antipsychotic clozapine has been proposed to involve actions on additional receptor systems. In particular, the high affinity of clozapine
Stip, Emmanuel; Mancini-Marie, Adham
Objective: To investigate which cognitive and affective features contribute most to responder/non-responder group separation during a switching trial with atypical antipsychotic. Design: A prospective open trial with an atypical antipsychotic (olanzapine). Patients: One hundred and thirty-four patients meeting diagnostic criteria for…
Kim, Sangwon F.
intake. atypical antipsychotic drugs obesity hypothalamus The antipsychotic actions of classic gain, predominantly mediated by increased food intake (610). Weight gain elicited by AAPDs is primarily related to increased food intake, although there may also be metabolic alterations (11
Stefan Wilhelm; Alexander Schacht; Thomas Wagner
BACKGROUND: Conventional antipsychotics augmented with benzodiazepines have been the standard acute treatment for psychiatric emergencies for more than 50 years. The inability of patients to give informed consent limits randomised, controlled studies. This observational study on immediate therapy for aggression and impulse control in acutely agitated patients (IMPULSE) evaluated the short-term effectiveness and tolerability of atypical and typical antipsychotic medications
Olfson, Mark; Crystal, Stephen; Huang, Cecilia; Gerhard, Tobias
Objective: This study describes recent trends and patterns in antipsychotic treatment of privately insured children aged 2 through 5 years. Method: A trend analysis is presented of antipsychotic medication use (1999-2001 versus 2007) stratified by patient characteristics. Data are analyzed from a large administrative database of privately insured…
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
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
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
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
Holden, Joseph; Palmer, Sheila M.; Johnston, Kerrylyn; Wearing, Catherine; Irvine, Brian; Brown, Lee E.
Fire is known to impact soil properties and hydrological flow paths. However, the impact of prescribed vegetation burning on blanket peatland hydrology is poorly understood. We studied 10 blanket peat headwater catchments. Five were subject to prescribed burning, while five were unburnt controls. Within the burnt catchments, we studied plots where the last burn occurred ˜2 (B2), 4 (B4), 7 (B7), or greater than 10 years (B10+) prior to the start of measurements. These were compared with plots at similar topographic wetness index locations in the control catchments. Plots subject to prescribed vegetation burning had significantly deeper water tables (difference in means = 5.3 cm) and greater water table variability than unburnt plots. Water table depths were significantly different between burn age classes (B2 > B4 > B7 > B10+) while B10+ water tables were not significantly different to the unburnt controls. Overland flow was less common on burnt peat than on unburnt peat, recorded in 9% and 17% of all runoff trap visits, respectively. Storm lag times and hydrograph recession limb periods were significantly greater (by ˜1 and 13 h on average, respectively) in the burnt catchments overall, but for the largest 20% of storms sampled, there was no significant difference in storm lag times between burnt and unburnt catchments. For the largest 20% of storms, the hydrograph intensity of burnt catchments was significantly greater than those of unburnt catchments (means of 4.2 × 10-5 and 3.4 × 10-5 s-1, respectively), thereby indicating a nonlinear streamflow response to prescribed burning. Together, these results from plots to whole river catchments indicate that prescribed vegetation burning has important effects on blanket peatland hydrology at a range of spatial scales.
Lin, Lewei Allison; Rosenheck, Robert; Sugar, Catherine; Zbrozek, Arthur
The overall impact of first and second generation antipsychotics on quality of life and symptoms of people with schizophrenia remains controversial. We applied health state modeling to data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia study, a randomized trial of antipsychotic medications, and evaluated the likelihood of patients moving to more favorable health states over time. We applied K-means clustering to the data to create discrete groupings of patients with symptom and side effect characteristics that were then validated using quality of life measures. We compared cluster distributions across medications at baseline and 6 months after randomization. 1,049 patients were included in the initial cluster analysis. Five health states were identified: (1) low symptoms and low side effects (LS + LSE) (2) low symptoms and obesity (LS + Ob) (3) high symptoms and low side effects (HS + LSE) (4) high symptoms with depression and akathisia (HS + Dp + Ak) and (5) moderate symptoms and high side effects (MS + HSE). Six-month outcomes among patients randomly assigned to perphenazine, olanzapine, risperidone and quetiapine were compared. At baseline, almost 20% of patients were in the worst health state (HS + Dp + Ak), with greater decreases at 6 months in this health state for perphenazine (9.2% decrease) and olanzapine (11.1%) groups compared to risperidone (4.7%) and quetiapine (6.7%). This study demonstrated that health state analysis can provide insight into the overall clinical state of patients beyond the mere comparison of average scores and largely confirmed original CATIE findings. PMID:25294277
Pugsley, T A; Coughenour, L L; Myers, S L; Shih, Y H; Courtland, G G; Berghoff, W; Stewart, S F
The effects of CI-943 (a novel 8-ethyl-7,8-dihydro-1,3,5-trimethyl-1H-imidazo[1,2-c]pyrazolo[3,4- e]pyrimidine compound exhibiting a favorable antipsychotic profile in animal tests) on neurochemical parameters related to biogenic amine neurons have been studied in rat brain. CI-943 (1-40 mg/kg p.o. and 20 mg/kg i.p.) accelerated the turnover of dopamine (DA) in rat brain as demonstrated by the enhancement of levels of the DA metabolites homovanillic acid, 3,4-dihydroxyphenylacetic acid or 3-methoxytyramine and by the enhancement rate of DA synthesis in either striatum or mesolimbic regions. These increases in DA turnover induced by CI-943 are not due to DA receptor blockade as CI-943, unlike known antipsychotics, did not exhibit affinity for DA receptors either in vitro or in vivo and did not affect rat serum basal prolactin levels. Amfonelic acid enhanced the action of haloperidol in increasing striatal homovanillic acid with no effect on that of CI-943 and clozapine, suggesting that CI-943, like clozapine, would be predicted to have a low risk of extrapyramidal side effects as compared to haloperidol. Chronic administration of CI-943 (40 mg/kg i.p.) to rats for 28 days did not affect the affinity or number of striatal DA receptors; in comparison haloperidol (0.5 mg/kg i.p.) caused an increase in number of DA receptors with no change in affinity. Measures of serotonergic function were increased; noradrenergic function was not affected by CI-943, nor did it exhibit affinity for a number of central nervous system receptors in vitro. The molecular mechanism by which CI-943 increases brain DA turnover is not known at this time but appears to be unique in comparison to known antipsychotic agents. PMID:2571713
Tandon, Rajiv; Belmaker, R H; Gattaz, Wagner F; Lopez-Ibor, Juan J; Okasha, Ahmed; Singh, Bruce; Stein, Dan J; Olie, Jean-Pierre; Fleischhacker, W Wolfang; Moeller, Hans-Juergen
Data from two major government-funded studies of comparative antipsychotic effectiveness in schizophrenia contradict the widely prevalent belief that the newer second-generation medications are vastly superior to the older first-generation drugs. This has caused uncertainty among patients, clinicians and policy-makers about the relative utility of first- and second- generation antipsychotic agents in its treatment. To reduce confusion and provide a contextual understanding of the new data, the World Psychiatry Association Section on Pharmacopsychiatry comprehensively reviewed the literature on the comparative effectiveness of different antipsychotic treatments for schizophrenia and developed this update. Utilizing data from the approximately 1,600 randomized controlled trials of antipsychotic treatment in schizophrenia, we applied the two indirect and one direct method to comparing the effectiveness of 62 currently-available antipsychotic agents. The subclasses of 51 first-generation and 11 second-generation antipsychotics were both found to be very heterogeneous, with substantial differences in side-effect profiles among members. Second-generation antipsychotic agents were found to be inconsistently more effective than first-generation agents in alleviating negative, cognitive, and depressive symptoms and had a lower liability to cause tardive dyskinesia; these modest benefits were principally driven by the ability of second-generation antipsychotics to provide equivalent improvement in positive symptoms along with a lower risk of causing extrapyramidal side-effects. Clozapine was found to be more efficacious than other agents in treatment-refractory schizophrenia. There were no consistent differences in efficacy among other second-generation antipsychotic agents; if such differences exist, they are likely small in magnitude. Dosing was found to be a key variable in optimizing effectiveness of both first- and second- generation antipsychotic agents. There was enormous individual variability in antipsychotic response and vulnerability to various adverse effects. In contrast to their relatively similar efficacy in treating positive symptoms, there were substantial differences among both first- and second- generation antipsychotic agents with regard to their propensity to cause extrapyramidal, metabolic and other adverse effects; second-generation agents have a lower liability to cause acute extrapyramidal symptoms and tardive dyskinesia along with a tendency to cause greater metabolic side-effects than first-generation agents. Based on these data about the comparative effectiveness of different antipsychotic treatment options, we summarize elements of current best antipsychotic practice for the treatment of schizophrenia and discuss the role of government and the pharmaceutical industry in obtaining and disseminating information which can facilitate best practice. PMID:18243663
Kelleher, James P; Centorrino, Franca; Huxley, Nancy A; Bates, John A; Drake, Jennifer Kidwell; Egli, Samy; Baldessarini, Ross J
The preferential dopamine D(3)-agonist pramipexole (4.25±0.38 mg/day) or placebo were added for up to 12 weeks to ongoing antipsychotic treatment for 24 adult patients with DSM-IV schizophrenia or schizoaffective disorder. Pramipexole was generally well-tolerated (82% trial-completion), and yielded greater decreases in PANSS-total scores (drug/placebo=2.1; p=0.04), with similar decreases in PANSS positive and negative scores and 6.7-fold greater reduction of serum prolactin concentrations compared to placebo. There were no differences in ratings of mood, cognition or extrapyramidal symptoms, all of which were low at intake. PMID:22153972
Ahearn, Eileen P; Krohn, Amy; Connor, Kathryn M; Davidson, Jonathan R T
To review the literature on the pharmacologic treatment of posttraumatic stress disorder (PTSD), with a focus on reports of antipsychotic use for this illness. A MEDLINE search (1966-Oct 2002) for English only articles about pharmacologic treatment of PTSD. Antipsychotic medications are being used with some frequency for PTSD. There are few studies and scant evidence to recommend the traditional antipsychotics. There are a number of reports (mostly case reports and open trials) in which atypical antipsychotics improved sleep and decreased the frequency of nightmares and flashbacks. Some studies showed global improvement across symptom clusters. The newer atypical antipsychotics show promise for the treatment of PTSD, mainly ameliorating intrusive symptoms. The paucity of double-blind studies prevents firm conclusions, however, this class of medications may be useful particularly for refractory symptoms. PMID:14971865
Shea, Michael; Fields, Karl B.
Plantar fasciitis is an extremely common, painful injury seen among people in running and jumping sports. While prognosis for recovery with conservative care is excellent, prolonged duration of symptoms affects sports participation. Studies on treatment options show mixed results, so finding effective treatments can be challenging. A logical…
Nihalani, Nikhil; Schwartz, Thomas L.; Siddiqui, Umar A.; Megna, James L.
A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. There is much speculation about the prevalence of weight gain and the degree of weight gain during acute and longitudinal treatment with these agents. There is newer literature looking at the etiology of this weight gain and the potential treatments being used to alleviate this side effect. The authors undertook a comprehensive literature review in order to present epidemiology, etiology, and treatment options of weight gain associated with antipsychotics, mood stabilizers, and antidepressants. PMID:21318056
Babkin, Petr; George Thompson, Alayna M; Iancu, Cristina V; Walters, D Eric; Choe, Jun-Yong
The antipsychotic drug olanzapine is widely prescribed to treat schizophrenia and other psychotic disorders. However, it often causes unwanted side effects, including diabetes, due to disruption of insulin-dependant glucose metabolism through a mechanism yet to be elucidated. To determine if olanzapine can affect the first step in glucose metabolism - glucose transport inside cells - we investigated the effect of this drug on the transport activity of a model glucose transporter. The glucose transporter from Staphylococcus epidermidis (GlcPSe) is specific for glucose, inhibited by various human glucose transporter (GLUT) inhibitors, has high sequence and structure homology to GLUTs, and is readily amenable to transport assay, mutagenesis, and computational modeling. We found that olanzapine inhibits glucose transport of GlcPSe with an IC50 0.9 ± 0.1 mM. Computational docking of olanzapine to the GlcPSe structure revealed potential binding sites that were further examined through mutagenesis and transport assay to identify residues important for olanzapine inhibition. These investigations suggest that olanzapine binds in a polar region of the cytosolic part of the transporter, and interacts with residues R129, strictly conserved in all GLUTs, and N136, conserved in only a few GLUTs, including the insulin-responsive GLUT4. We propose that olanzapine inhibits GlcPSe by impeding the alternating opening and closing of the substrate cavity necessary for glucose transport. It accomplishes this by disrupting a key salt bridge formed by conserved residues R129 and E362, that stabilizes the outward-facing conformation of the transporter. PMID:25941630
... supported by grants from the States Attorney General Consumer and Prescriber Education Grant Program which is funded by the multi-state settlement of consumer fraud claims regarding the marketing of the prescription ...
Ahmadi, Maryam; Samadbeik, Mahnaz; Sadoughi, Farahnaz
Implementation of electronic prescribing system can overcome many problems of the paper prescribing system, and provide numerous opportunities of more effective and advantageous prescribing. Successful implementation of such a system requires complete and deep understanding of work content, human force, and workflow of paper prescribing. The current study was designed in order to model the current business process of outpatient prescribing in Iran and clarify different actions during this process. In order to describe the prescribing process and the system features in Iran, the methodology of business process modeling and analysis was used in the present study. The results of the process documentation were analyzed using a conceptual model of workflow elements and the technique of modeling “As-Is” business processes. Analysis of the current (as-is) prescribing process demonstrated that Iran stood at the first levels of sophistication in graduated levels of electronic prescribing, namely electronic prescription reference, and that there were problematic areas including bottlenecks, redundant and duplicated work, concentration of decision nodes, and communicative weaknesses among stakeholders of the process. Using information technology in some activities of medication prescription in Iran has not eliminated the dependence of the stakeholders on paper-based documents and prescriptions. Therefore, it is necessary to implement proper system programming in order to support change management and solve the problems in the existing prescribing process. To this end, a suitable basis should be provided for reorganization and improvement of the prescribing process for the future electronic systems. PMID:25237369
Fountoulakis, Konstantinos N; Nimatoudis, Ioannis; Iacovides, Apostolos; Kaprinis, George
Introduction With the introduction of newer atypical antipsychotic agents, a question emerged, concerning their use as complementary pharmacotherapy or even as monotherapy in mental disorders other than psychosis. Material and method MEDLINE was searched with the combination of each one of the key words: risperidone, olanzapine and quetiapine with key words that refered to every DSM-IV diagnosis other than schizophrenia and other psychotic disorders, bipolar disorder and dementia and memory disorders. All papers were scored on the basis of the JADAD index. Results The search returned 483 papers. The selection process restricted the sample to 59 papers concerning Risperidone, 37 concerning Olanzapine and 4 concerning Quetiapine (100 in total). Ten papers (7 concerning Risperidone and 3 concerning Olanzapine) had JADAD index above 2. Data suggest that further research would be of value concerning the use of risperidone in the treatment of refractory OCD, Pervasive Developmental disorder, stuttering and Tourette's syndrome, and the use of olanzapine for the treatment of refractory depression and borderline personality disorder. Discussion Data on the off-label usefulness of newer atypical antipsychotics are limited, but positive cues suggest that further research may provide with sufficient hard data to warrant the use of these agents in a broad spectrum of psychiatric disorders, either as monotherapy, or as an augmentation strategy. PMID:14975068
Erba?, Oytun; Akseki, Hüseyin Serdar; Eliküçük, Betül; Ta?k?ran, Dilek
Trimetazidine (TMZ) has been used as an anti-ischemic agent for angina pectoris, chorioretinal disturbances, and vertigo. Also, it can induce extrapyramidal type adverse reaction such as parkinsonism, gait disorder, and tremor via blockade of D2 receptors. In the present study, we evaluated the effect of TMZ on novelty-induced rearing behavior and apomorphine-induced stereotypy behavior in male rats. Four groups of rat (n = 7) were administrated with TMZ (10 and 20 mg/kg, i.p.), chlorpromazine (1?mg/kg, i.p.), or isotonic saline. One hour later, apomorphine (2?mg/kg, s.c.) was administrated to each rat. Our results showed that both doses of TMZ significantly decreased the rearing behavior in rats, whereas the decrease with chlorpromazine was higher. TMZ also decreased the stereotypy scores in a dose-dependent manner. We concluded that TMZ has beneficial effects on rearing behavior and stereotypy, which are accepted to be indicators of antipsychotic effect. Taken together, with its antioxidative and cytoprotective properties, TMZ is worthy of being investigated for its anti-psychotic effects as a primary or an adjunctive drug. PMID:24250273
Rico-Villademoros, F; Calandre, E P; Slim, M
The treatment of fibromyalgia requires pharmacological and nonpharmacological therapies. The pharmacological treatment of fibromyalgia is limited to a few drugs that have been demonstrated to be moderately effective in some but not all dimensions of the disease. Therefore, the search for new drugs to treat this condition is warranted. Atypical antipsychotics offered an attractive alternative because they had been shown to be active against several key symptoms of fibromyalgia. The results of open-label studies, however, appear to indicate that atypical antipsychotics are poorly tolerated in patients with fibromyalgia, and only quetiapine XR has been studied in randomized controlled trials. Quetiapine XR has demonstrated effectiveness in treating comorbid major depression, anxiety and sleep disturbance. However, in two randomized controlled trials, quetiapine XR was not differentiated from placebo and failed to demonstrate noninferiority to amitriptyline in terms of improving overall symptomatology. The effect of quetiapine XR on pain and its usefulness as part of a combination pharmacological regimen should be further evaluated. Overall, the use of quetiapine (initiated at a low dose and slowly titrated) in fibromyalgia should be limited to patients with comorbid major depression or patients who are currently receiving other treatments and have unresolved and disabling depressive and/or anxiety symptoms. PMID:24983591
Hodgkin, Dominic; Volpe-Vartanian, Joanna; Merrick, Elizabeth L.; Horgan, Constance M.; Nierenberg, Andrew A.; Frank, Richard G.; Lee, Sue
For many disorders, patient heterogeneity requires physicians to customize their treatment to each patient’s needs. We test for the existence of customization in physicians’ prescribing for bipolar disorder, using data from a naturalistic clinical effectiveness trial of bipolar disorder treatment (STEP-BD), which did not constrain physician prescribing. Multinomial logit is used to model the physician’s choice among five combinations of drug classes. We find that our observed measure of the patient’s clinical status played only a limited role in the choice among drug class combinations, even for conditions such as mania that are expected to affect class choice. However, treatment of a patient with given characteristics differed widely depending on which physician was seen. The explanatory power of the model was low. There was variation within each physician’s prescribing, but the results do not suggest a high degree of customization in physicians’ prescribing, based on our measure of clinical status. PMID:21506194
... Navigation Bar Home Current Issue Past Issues The Web site your doctor prescribes Past Issues / Summer 2008 ... gov® is a free, comprehensive, up-to-date Web site with health information from the world's largest ...
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...REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS CONTACT LENS RULE § 315.5 Prescriber verification...Prescription requirement. A seller may sell contact lenses only in accordance with a contact lens prescription for the patient that...
...REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS CONTACT LENS RULE § 315.5 Prescriber verification...Prescription requirement. A seller may sell contact lenses only in accordance with a contact lens prescription for the patient that...
... per person than others. SOURCE: IMS, National Prescription Audit (NPA TM ), 2012. View larger image and text. ... prescribe at different levels. SOURCE: IMS, National Prescription Audit (NPA TM ), 2012. View larger image and text. ...
Blain, H; Rambourg, P; Le Quellec, A; Ayach, L; Biboulet, P; Bismuth, M; Blain, A; Boulenger, J-P; Celton, B; Combe, B; Dauvilliers, Y; Davy, J-M; Geny, C; Hemmi, P; Hillaire-Buys, D; Jalabert, A; Jung, B; Leclercq, F; Léglise, M-S; Morel, J; Mourad, G; Ponrouch, M-P; Puisieux, F; Quantin, X; Quéré, I; Renard, E; Ribstein, J; Roch-Torreilles, I; Rolland, Y; Rosant, D; Terminet, A; Thuret, R; Villiet, M; Deshormières, N; Bourret, R; Bousquet, J; Jonquet, O; Millat, B
Drug-induced adverse effects are one of the main avoidable causes of hospitalization in older people. Numerous lists of potentially inappropriate medications for older people have been published, as national and international guidelines for appropriate prescribing in numerous diseases and for different age categories. The present review describes the general rules for an appropriate prescribing in older people and summarizes, for the main conditions encountered in older people, medications that are too often under-prescribed, the precautions of use of the main drugs that induce adverse effects, and drugs for which the benefit to risk ratio is unfavourable in older people. All these data are assembled in educational tables designed to be printed in a practical pocket format and used in daily practice by prescribers, whether physicians, surgeons or pharmacists. PMID:26003377
...prescribed. 5.3 Section 5.3 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF DISTILLED SPIRITS Scope §...
...prescribed. 4.3 Section 4.3 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Scope § 4.3 Forms...
This article suggests that nurse prescribers require an awareness of key concepts in ethics, such as deontology and utilitarianism to reflect on current debates and contribute to them. The principles of biomedical ethics have also been influential in the development of professional codes of conduct. Attention is drawn to the importance of the Association of the British Pharmaceutical Industry's code of practice for the pharmaceutical industry in regulating marketing aimed at prescribers. PMID:21500692
Michael A. Steinman; Seth Landefeld; Gary E. Rosenthal; Saunak Sen; Peter J. Kaboli
OBJECTIVES: To evaluate the relationship between inap- propriate prescribing, medication underuse, and the total number of medications used by patients. DESIGN: Cross-sectional study. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: One hundred ninety-six outpatients aged 65 and older who were taking five or more medica- tions. MEASUREMENTS: Inappropriate prescribing was as- sessed using a combination of the Beers drugs-to-avoid cri- teria
Prescribing medication is embedded in social norms and cultures. In modern Western health care professionals and policy makers have attempted to rationalize medicine by addressing cost-effectiveness of diagnostic and therapeutic treatments and the development of guidelines and protocols based on the outcomes of clinical studies. These notions of cost-effectiveness and evidence-based medicine have also been embedded in technology such as electronic prescribing systems. Such constraining systems may clash with the reality of clinical practice, where formal boundaries of responsibility and authorization are often blurred. Such systems may therefore even impede patient care. Medication is seen as the essence of medical practice. Prescribing is a social act. In a hospital medications may be aimed at treating a patient for a specific condition, in primary care the professional often meets the patient with her or his social and cultural notions of a health problem. The author argues that the design and implementation of electronic prescribing systems should address the social and cultural context of prescribing. Especially in primary care, where health problems are often ill defined and evidence-based medicine guidelines do not always work as intended, studies need to take into account the sociotechnical character of electronic prescribing systems. PMID:23388308
Hassiotis, Angela; Walters, Kate; Osborn, David; Strydom, André; Horsfall, Laura
Objectives To describe the incidence of recorded mental illness and challenging behaviour in people with intellectual disability in UK primary care and to explore the prescription of psychotropic drugs in this group. Design Cohort study. Setting 571 general practices contributing data to The Health Improvement Network clinical database. Participants 33?016 adults (58% male) with intellectual disability who contributed 211?793 person years’ data. Main outcome measures Existing and new records of mental illness, challenging behaviour, and psychotropic drug prescription. Results 21% (7065) of the cohort had a record of mental illness at study entry, 25% (8300) had a record of challenging behaviour, and 49% (16?242) had a record of prescription of psychotropic drugs. During follow-up, the rate of new cases of mental illness in people without a history at cohort entry was 262 (95% confidence interval 254 to 271) per 10?000 person years and the rate of challenging behaviour was 239 (231 to 247) per 10?000 person years. The rate of new psychotropic drug prescription in those without a previous history of psychotropic drug treatment was 518 (503 to 533) per 10?000 person years. Rates of new recording of severe mental illness declined by 5% (95% confidence interval 3% to 7%) per year (P<0.001), and new prescriptions of antipsychotics declined by 4% (3% to 5%) per year P<0.001) between 1999 and 2013. New prescriptions of mood stabilisers also decreased significantly. The rate of new antipsychotic prescribing was significantly higher in people with challenging behaviour (incidence rate ratio 2.08, 95% confidence interval 1.90 to 2.27; P<0.001), autism (1.79, 1.56 to 2.04; P<0.001), and dementia (1.42, 1.12 to 1.81; P<0.003) and in those of older age, after control for other sociodemographic factors and comorbidity. Conclusions The proportion of people with intellectual disability who have been treated with psychotropic drugs far exceeds the proportion with recorded mental illness. Antipsychotics are often prescribed to people without recorded severe mental illness but who have a record of challenging behaviour. The findings suggest that changes are needed in the prescribing of psychotropics for people with intellectual disability. More evidence is needed of the efficacy and safety of psychotropic drugs in this group, particularly when they are used for challenging behaviour. PMID:26330451
Attard, Azizah; Taylor, David M
Real-world, effectiveness studies add an important new dimension to the evaluation of the benefits of individual antipsychotics. Efficacy studies have already shown the unique effectiveness of clozapine, and suggested improved outcomes for olanzapine compared with some atypical antipsychotics and a reduced tendency to produce acute and chronic movement disorders for atypical compared with typical drugs. Recent effectiveness studies largely confirm these prior observations. The CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness), CUtLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study) and SOHO (Schizophrenia Outpatient Health Outcomes) programmes confirmed the superiority of clozapine over other antipsychotics; CATIE and SOHO also confirmed olanzapine as probably the second most effective antipsychotic. Effectiveness studies have confirmed the high incidence of adverse metabolic effects with clozapine, olanzapine and (with less certainty) quetiapine but the ZODIAC (Ziprasidone Observational Study of Cardiac Outcomes) study found no excess cardiovascular events or deaths for olanzapine compared with ziprasidone. Prior observations on reduced frequency of movement disorders for second-generation versus first-generation antipsychotics were also largely (but not uniformly) supported. Overall, recent real-world studies have done much to confirm prior observations from efficacy-based randomized, controlled trials. PMID:22668246
Gallini, Adeline; Huskamp, Haiden A.; Donohue, Julie M.
Objective Second generation antipsychotics captured the majority of the US antipsychotic market shortly after their introduction. Little is known about how second generation antipsychotics diffused in other countries with different health systems. The objective was to describe trends in antipsychotic use in the US and France from 1998 to 2008. Methods After presenting a brief background section on pharmaceutical policies in France and the US, descriptive data on quarterly prescriptions dispensed between 01/1998–09/2008 for oral antipsychotics from Xponent™ for the US, and sales recorded in the GERS database for France are presented. Trends in the share of antipsychotic use for first vs. second generation antipsychotics, and in ingredient-level of second generation antipsychotics use are reported. Results In the US, between 1998 and 2008, total antipsychotic use increased by 78%. Total use was consistently higher in France despite a 9% decrease during the period. By 2008, second generation antipsychotics represented 90% of the antipsychotic US market vs. only 40% in France. However, average annual growth rates in second generation antipsychotics use were similar in the two countries. In France, there was a steady increase in use of all but one second generation antipsychotic; whereas trends in the use of newer drugs varied substantially by drug in the US (e.g. use of olanzapine decreased after 2003 whereas use of quetiapine increased). Conclusions These results highlight markedly divergent trends in the diffusion of new antipsychotics in France and the US. Some of these differences may be explained by differences in health systems, while others may reflect physicians’ preferences and norms of practice. PMID:23584568
Sørensen, Merete Juul; Kjaersgaard, Maiken Ina Siegismund; Pedersen, Henrik Søndergaard; Vestergaard, Mogens; Christensen, Jacob; Olsen, Jørn; Parner, Erik; Pedersen, Lars Henning; Bech, Bodil Hammer
Background Antipsychotic medications are increasingly used during pregnancy. Nevertheless, fetal risks are still not fully studied. It is currently unclear whether the antipsychotic treatment might induce a higher risk of fetal death. We aimed to determine if use of antipsychotic medication during pregnancy is associated with an increased risk of spontaneous abortion or stillbirth. Methods In a historical cohort study, we identified all clinically recognized pregnancies registered in the nationwide Danish registries from 1997 to 2008 (N = 1,005,319). Exposure was defined as any prescription of antipsychotic medications redeemed by the pregnant women during the exposure window, and recorded in the Danish National Prescription Register. Outcome was defined as any spontaneous abortion or stillbirth recorded in the Danish National Hospital Register and the Danish Medical Birth Register respectively. Results Women exposed to antipsychotic medications during pregnancy had a 34% higher risk of spontaneous abortion (adjusted relative risk = 1.34; 95% confidence interval = 1.22; 1.46) compared to unexposed women, but a similar risk compared to women exposed prior to (but not during) pregnancy (adjusted relative risk = 1.04; 95% confidence interval = 0.93; 1.17). The risk of spontaneous abortion was not increased in exposed pregnancies when compared to unexposed pregnancies in the same women (adjusted hazard ratio = 1.11; 95% CI = 0.94; 1.31). A twofold higher risk of stillbirth was found in women exposed to antipsychotic medications compared with unexposed women (relative risk = 2.27; 95% confidence interval = 1.45; 3.55) and compared with women exposed only prior to pregnancy (relative risk = 2.06; 95% confidence interval = 1.01; 4.19). Conclusions The increased risk of spontaneous abortion found in women treated with antipsychotic medications during pregnancy is most likely due to confounding factors. The risk of stillbirth was twofold higher in pregnancies exposed to antipsychotic medication during pregnancy. Treatment with antipsychotic medications during pregnancy requires careful consideration. PMID:26162087
Chiu, Yunwen; Bero, Lisa; Hessol, Nancy A; Lexchin, Joel; Harrington, Charlene
The benefits and harms of antipsychotic medication (APM) use in nursing home residents need to be examined because, although commonly used, APMs are considered an off-label use by the Food and Drug Administration for residents with dementia and behavioral problems. The objective of this study was to provide a realist literature review, summarizing original research studies on the clinical effects of conventional and atypical APM use in nursing home residents. Searches of multiple databases identified 424 potentially relevant research articles, of which 25 met the inclusion criteria. Antipsychotic medication use in nursing home residents was found to have variable efficacy when used off-label with an increased risk of many adverse events, including mortality, hip fractures, thrombotic events, cardiovascular events and hospitalizations. Findings suggested certain APM dosing regimens (e.g. fixed-dose) and shorter duration of use might have fewer adverse events. Non-pharmacological interventions should still be considered the first-line treatment option for nursing home residents with dementia related behavioral disturbances, as more studies are needed to establish safer criteria for APM use in nursing homes residents. PMID:25791166
de Jong, Simone; Boks, Marco P. M.; Fuller, Tova F.; Strengman, Eric; Janson, Esther; de Kovel, Carolien G. F.; Ori, Anil P. S.; Vi, Nancy; Mulder, Flip; Blom, Jan Dirk; Glenthøj, Birte; Schubart, Chris D.; Cahn, Wiepke; Kahn, René S.; Horvath, Steve; Ophoff, Roel A.
Despite large-scale genome-wide association studies (GWAS), the underlying genes for schizophrenia are largely unknown. Additional approaches are therefore required to identify the genetic background of this disorder. Here we report findings from a large gene expression study in peripheral blood of schizophrenia patients and controls. We applied a systems biology approach to genome-wide expression data from whole blood of 92 medicated and 29 antipsychotic-free schizophrenia patients and 118 healthy controls. We show that gene expression profiling in whole blood can identify twelve large gene co-expression modules associated with schizophrenia. Several of these disease related modules are likely to reflect expression changes due to antipsychotic medication. However, two of the disease modules could be replicated in an independent second data set involving antipsychotic-free patients and controls. One of these robustly defined disease modules is significantly enriched with brain-expressed genes and with genetic variants that were implicated in a GWAS study, which could imply a causal role in schizophrenia etiology. The most highly connected intramodular hub gene in this module (ABCF1), is located in, and regulated by the major histocompatibility (MHC) complex, which is intriguing in light of the fact that common allelic variants from the MHC region have been implicated in schizophrenia. This suggests that the MHC increases schizophrenia susceptibility via altered gene expression of regulatory genes in this network. PMID:22761806
Schizophrenia is a chronic mental disorder generally treated with antipsychotic medication. However, non-adherence and partial adherence to antipsychotic medication treatment is common and long-acting injectable “depot” preparations of antipsychotic medications have been used as an alternative to oral medication therapy for patients for whom adherence is a clinically significant problem, as well as for the sake of convenience and in response to patient preference. Olanzapine long-acting injection (OLAI) is a new treatment option and has been approved by several regulatory agencies for the treatment of schizophrenia. OLAI is a crystalline salt formulation of olanzapine and pamoic acid. Efficacy was established in 2 double-blind randomized clinical trials of OLAI for the treatment of acute schizophrenia and for the maintenance of response. The therapeutic OLAI dosages are 150 mg q2 weeks, 210 mg q2 weeks, 300 mg q2 weeks or q4 weeks, and 405 mg q4 weeks, administered by deep intramuscular gluteal injection with a 19-gauge needle. Injection volume ranges from 1 to 2.7 mL. OLAI has essentially the same general tolerability as that of oral olanzapine; however with the depot there is the additional risk of a post-injection delirium sedation syndrome occurring at a rate of 0.07% of injections, requiring a risk management plan that includes observing the patient for 3 hours post injection. PMID:20016798
Background Schizophrenia is a severe form of mental illness which is associated with significant and long-lasting health, social and financial burdens. The aim of this project is to assess the efficiency of the antipsychotics used in Spain in reducing schizophrenia relapses under the Spanish Health System perspective. Material and methods A decision-analytic model was developed to explore the relative cost-effectiveness of five antipsychotic medications, amisulpride, aripiprazole, olanzapine, paliperidone Extended-Release (ER) and risperidone, compared to haloperidol, over a 1-year treatment period among people living in Spain with schizophrenia. The transition probabilities for assessed therapies were obtained from the systemic review and meta-analysis performed by National Institute for Health and Clinical Excellence (NICE). Results Paliperidone ER was the option that yielded more quality-adjusted life years (QALYs) gained per patient (0.7573). In addition, paliperidone ER was the least costly strategy (€3,062), followed by risperidone (€3,194), haloperidol (€3,322), olanzapine (€3,893), amisulpride (€4,247) and aripiprazole (€4,712). In the incremental cost-effectiveness (ICE) analysis of the assessed antipsychotics compared to haloperidol, paliperidone ER and risperidone were dominant options. ICE ratios for other medications were €23,621/QALY gained, €91,584/QALY gained and €94,558/QALY gained for olanzapine, amisulpride and aripiprazole, respectively. Deterministic sensitivity analysis showed that risperidone is always dominant when compared to haloperidol. Paliperidone ER is also dominant apart from the exception of the scenario with a 20% decrease in the probability of relapses. Conclusions Our findings may be of interest to clinicians and others interested in outcomes and cost of mental health services among patients with schizophrenia. Paliperidone ER and risperidone were shown to be dominant therapies compared to haloperidol in Spain. It is worthwhile to highlight that schizophrenia is a highly incapacitating disease and choosing the most appropriate drug and formulation for a particular patient is crucial. The availability of more accurate local epidemiological data on schizophrenia would allow a better adaptation of the model avoiding some of the assumptions taken in our work. Future research could be focused on this. PMID:22828390
Background Major depressive disorder (MDD) is a debilitating and costly mental disorder. Although commercially available antidepressants have proliferated over the last 20 years, a substantial number of patients either do not respond adequately to these drugs or are unable to tolerate their adverse effects. One common approach has been to augment conventional antidepressants with an adjunctive agent, but the optimal selection of atypical antipsychotic agents for adjunctive treatment of treatment-resistant depression (TRD) remains controversial. Methods/Design An electronic literature search of PubMed, the Cochrane Library, Embase, Web of Science, LiLACS, CINAHL, and PsycINFO for studies will be conducted with no restrictions on language, publication year, or publication type. Several clinical trial registry agencies, pharmaceutical company websites, and FDA reports will also be reviewed. Randomized clinical trials (RCTs) with atypical antipsychotic augmentation treatment for treatment-resistant depression will be considered. Data will be independently extracted by two reviewers. Traditional pairwise meta-analyses will be performed for RCTs that directly compare different treatment arms. Then, Bayesian network meta-analyses will be performed to compare the relative efficacy and acceptability of different atypical antipsychotic agents (and doses). A sensitivity analysis will be performed by excluding studies classified as a small sample size, having a high placebo effect. Discussion This systematic review and network meta-analysis will comparatively analyze the efficacy, quality of life, and acceptability profiles of atypical antipsychotic medications used for the adjunctive treatment of TRD. The findings should provide clinically relevant implications for comprehensively understanding the risk–benefit profiles of these adjunctive treatments. Systematic review registration PROSPERO CRD 42014009666. PMID:25373601
Cooper, Richard J; Lymn, Joanne; Anderson, Claire; Avery, Anthony; Bissell, Paul; Guillaume, Louise; Hutchinson, Allen; Murphy, Elizabeth; Ratcliffe, Julie; Ward, Paul
Background The introduction of non-medical prescribing for professions such as pharmacy and nursing in recent years offers additional responsibilities and opportunities but attendant training issues. In the UK and in contrast to some international models, becoming a non-medical prescriber involves the completion of an accredited training course offered by many higher education institutions, where the skills and knowledge necessary for prescribing are learnt. Aims: to explore pharmacists' perceptions and experiences of learning to prescribe on supplementary prescribing (SP) courses, particularly in relation to inter-professional learning, course content and subsequent use of prescribing in practice. Methods A postal questionnaire survey was sent to all 808 SP registered pharmacists in England in April 2007, exploring demographic, training, prescribing, safety culture and general perceptions of SP. Results After one follow-up, 411 (51%) of pharmacists responded. 82% agreed SP training was useful, 58% agreed courses provided appropriate knowledge and 62% agreed that the necessary prescribing skills were gained. Clinical examination, consultation skills training and practical experience with doctors were valued highly; pharmacology training and some aspects of course delivery were criticised. Mixed views on inter-professional learning were reported – insights into other professions being valued but knowledge and skills differences considered problematic. 67% believed SP and recent independent prescribing (IP) should be taught together, with more diagnostic training wanted; few pharmacists trained in IP, but many were training or intending to train. There was no association between pharmacists' attitudes towards prescribing training and when they undertook training between 2004 and 2007 but earlier cohorts were more likely to be using supplementary prescribing in practice. Conclusion Pharmacists appeared to value their SP training and suggested improvements that could inform future courses. The benefits of inter-professional learning, however, may conflict with providing profession-specific training. SP training may be perceived to be an instrumental 'stepping stone' in pharmacists' professional project of gaining full IP status. PMID:19061487
Johnson, Stacy A; Yarbrough, Peter M; Rose, Richard S; Lanspa, Michael J
Target-specific oral anticoagulants have been rapidly adopted into clinical practice for stroke prophylaxis and venous thromboembolism treatment, raising concerns about off-label prescribing practices. We conducted a retrospective review of consecutive patients prescribed dabigatran, rivaroxaban or apixaban prior to inpatient hospitalization over an 18-month period to examine the off-label prescribing frequency, contraindications and related complications. Chart review included baseline demographics, hospital admitting service, outpatient prescribing service, renal function, therapeutic indication, echocardiographic findings, contraindications, major bleeding events and vital status. We identified 160 patients who received a target-specific oral anticoagulant prior to hospitalization. Over half (53.1%) of the patients received rivaroxaban, 43.7% received dabigatran and 3.1% received apixaban. Atrial fibrillation (68.1%) and venous thromboembolism treatment (25.6%) were the most common indications. Ninety percent of patients had a U.S. Foods and Drugs Administration (FDA)-approved indication for therapy. Major bleeding events occurred in 4.4% of patients. Cardiology was the most common prescribing and admitting service (43.8 and 31.3%), and more frequently adhered to FDA-approved indications (97 vs. 84%, P?=?0.01). There were no significant differences between prescribing services regarding major contraindications (P?=?0.14) and major bleeding events (P?=?0.77). Off-label prescription rates for target-specific oral anticoagulants were infrequent and not associated with increased adverse events. PMID:26414695
Liang, Shu-Yuan; Wu, Shu-Fang; Tsay, Shiow-Luan; Wang, Tsae-Jyy; Tung, Heng-Hsin
The purpose of this study was to evaluate adherence to prescribed opioids in Taiwanese oncology outpatients and to examine the associations between various demographic and medical characteristics and prescribed opioids adherence. Ninety-two outpatients who had taken prescribed opioid analgesics for cancer-related pain at least once in the past week participated in this study. Patients were asked to recall the dose of each opioid analgesic that they had taken in the past 24 hours. Mean adherence rates were calculated for analgesic adherence. For mean adherence rates, all opioid analgesics were converted to morphine equivalents. The results of this study reveal a priority issue of poor opioid analgesic adherence. The adherence rate of 63.6% for the around-the-clock opioid analgesics in this study is well below acceptable levels. Also, an adherence rate of 30.9% for the as-needed opioid analgesics is very low. This study identified that women tend to be less adherent to their prescribed opioid analgesic regimen than men. Findings of this study suggest that to improve pain control, efforts to promote patients' opioid regimen adherence should be given high priority. Clinicians should be particularly aware that there may be some gender difference in adherence to prescribed opioid analgesics. There is a need for better programmatic efforts to improve analgesic adherence. PMID:23972866
Rissmann, Robert; Dubois, Eline A; Franson, Kari L; Cohen, Adam F
The variability of drug response in different patients can be caused by various factors including age, change in renal function, co-medication and genotype. Traditionally, these personal variables are considered by clinicians prior to issuing a prescription. This paper provides an overview of a process to individualize prescribing for a patient with an emphasis on how to train (learning) clinicians in skillful rational prescribing. For this purpose the 6STEP methodology, a concept-based learning strategy to achieve a structured therapeutic plan, has been introduced. In contrast to older educational approaches which focused primarily on the drugs or the process of prescribing, the 6STEP is a patient-centred method resulting in individualized therapy. The six interlinked steps provide the (training) prescriber with a structured framework that facilitates a rationalized therapeutic decision by focusing on the individual patient parameters that influence drug response. Educational tools for rational prescribing involve understanding of basic and clinical pharmacological principles, practicing to write 6STEP therapeutic plans, learning from feedback sessions on these plans and actively obtaining up to date information on drugs and therapeutic standards from online resources. PMID:22420749
Zhong, Wenjun; Maradit-Kremers, Hilal; St. Sauver, Jennifer L.; Yawn, Barbara P.; Ebbert, Jon O.; Roger, Véronique L.; Jacobson, Debra J.; McGree, Michaela E.; Brue, Scott M.; Rocca, Walter A.
Objective To describe age and sex patterns of drug prescribing in Olmsted County, MN. Prescription drugs are an important component of health care delivery, yet little is known about the prescribing patterns in the general population. Patients and Methods Population-based drug prescription records for the Olmsted County population in the year 2009 were obtained using the Rochester Epidemiology Project medical records-linkage system (n = 142,377). Drug prescriptions were classified using RxNorm codes and grouped using the National Drug File – Reference Terminology (NDF-RT). Results Overall, 68% of the population received a prescription from at least one drug group, 52% received prescriptions from 2 or more groups, and 21% received prescriptions from 5 or more groups. The most commonly prescribed drug groups in the entire population were penicillins and beta-lactam antimicrobials (17%), antidepressants (13%), opioid analgesics (12%), antilipemic agents (11%), and vaccines/toxoids (11%). However, prescribing patterns differed by age and sex. Vaccines/toxoids, penicillins and beta-lactam antimicrobials, and anti-asthmatic drugs were most commonly prescribed in persons younger than 19 years. Antidepressants and opioid analgesics were most commonly prescribed in young and middle-aged adults. Cardiovascular drugs were most commonly prescribed in older adults. Women received more prescriptions than men for several groups of drugs, in particular for antidepressants. For several groups of drugs, the use increased with advancing age. Conclusion This study provides valuable baseline information for future studies of drug utilization and drug-related outcomes in this population. PMID:23790544
Haddad, Peter M; Brain, Cecilia; Scott, Jan
Nonadherence with medication occurs in all chronic medical disorders. It is a particular challenge in schizophrenia due to the illness's association with social isolation, stigma, and comorbid substance misuse, plus the effect of symptom domains on adherence, including positive and negative symptoms, lack of insight, depression, and cognitive impairment. Nonadherence lies on a spectrum, is often covert, and is underestimated by clinicians, but affects more than one third of patients with schizophrenia per annum. It increases the risk of relapse, rehospitalization, and self-harm, increases inpatient costs, and lowers quality of life. It results from multiple patient, clinician, illness, medication, and service factors, but a useful distinction is between intentional and unintentional nonadherence. There is no gold standard approach to the measurement of adherence as all methods have pros and cons. Interventions to improve adherence include psychoeducation and other psychosocial interventions, antipsychotic long-acting injections, electronic reminders, service-based interventions, and financial incentives. These overlap, all have some evidence of effectiveness, and the intervention adopted should be tailored to the individual. Psychosocial interventions that utilize combined approaches seem more effective than unidimensional approaches. There is increasing interest in electronic reminders and monitoring systems to enhance adherence, eg, Short Message Service text messaging and real-time medication monitoring linked to smart pill containers or an electronic ingestible event marker. Financial incentives to enhance antipsychotic adherence raise ethical issues, and their place in practice remains unclear. Simple pragmatic strategies to improve medication adherence include shared decision-making, regular assessment of adherence, simplification of the medication regimen, ensuring that treatment is effective and that side effects are managed, and promoting a positive therapeutic alliance and good communication between the clinician and patient. These elements remain essential for all patients, not least for the small minority where vulnerability and risk issue dictate that compulsory treatment is necessary to ensure adherence. PMID:25061342
Haddad, Peter M; Brain, Cecilia; Scott, Jan
Nonadherence with medication occurs in all chronic medical disorders. It is a particular challenge in schizophrenia due to the illness’s association with social isolation, stigma, and comorbid substance misuse, plus the effect of symptom domains on adherence, including positive and negative symptoms, lack of insight, depression, and cognitive impairment. Nonadherence lies on a spectrum, is often covert, and is underestimated by clinicians, but affects more than one third of patients with schizophrenia per annum. It increases the risk of relapse, rehospitalization, and self-harm, increases inpatient costs, and lowers quality of life. It results from multiple patient, clinician, illness, medication, and service factors, but a useful distinction is between intentional and unintentional nonadherence. There is no gold standard approach to the measurement of adherence as all methods have pros and cons. Interventions to improve adherence include psychoeducation and other psychosocial interventions, antipsychotic long-acting injections, electronic reminders, service-based interventions, and financial incentives. These overlap, all have some evidence of effectiveness, and the intervention adopted should be tailored to the individual. Psychosocial interventions that utilize combined approaches seem more effective than unidimensional approaches. There is increasing interest in electronic reminders and monitoring systems to enhance adherence, eg, Short Message Service text messaging and real-time medication monitoring linked to smart pill containers or an electronic ingestible event marker. Financial incentives to enhance antipsychotic adherence raise ethical issues, and their place in practice remains unclear. Simple pragmatic strategies to improve medication adherence include shared decision-making, regular assessment of adherence, simplification of the medication regimen, ensuring that treatment is effective and that side effects are managed, and promoting a positive therapeutic alliance and good communication between the clinician and patient. These elements remain essential for all patients, not least for the small minority where vulnerability and risk issue dictate that compulsory treatment is necessary to ensure adherence. PMID:25061342
Ko, You-Kyung; Soh, Min-Ah; Kang, Shi-Hyun
Objective To examine the prevalence of metabolic syndrome and its risk factors in a large group of schizophrenic patients. Methods Sociodemographic and treatment data were collected from medical records of 1,103 inpatients and outpatients treated for schizophrenia at Seoul National Hospital in Seoul, Korea. Anthropometric measurement and blood testing were conducted for collection of physical and biochemical data and diagnosis of metabolic syndrome. Data for metabolic syndrome prevalence were compared by sex, age, metabolic syndrome markers present, treatment of markers, and types of antipsychotics and individual drug agents used. Results Mean prevalence of metabolic syndrome in all subjects was 43.9% and 40.1% according to adapted Adult Treatment Panel III (ATP-IIIa) and International Diabetes Federation criteria, respectively. No significant differences were found in prevalence according to ATP-IIIa criteria between men (42.6%) and woman (45.9%). A trend toward higher prevalence with age was observed for both sexes until 50 years, followed by a continued increase for women but a decrease for men. Use of a combination of atypical antipsychotics was associated with the highest metabolic syndrome prevalence and use of aripiprazole with the lowest. High percentages of subjects with hypertension and dyslipidemia were not being treated for these conditions. Conclusion Despite their higher prevalence in schizophrenic patients, metabolic syndrome and its markers are not being adequately managed in these patients. Treatment of schizophrenic patients requires attention to not only their psychiatric conditions but also associated medical conditions by individual health care practitioners and hospitals as well as the public health care sector as a whole. PMID:24023552
Versporten, A.; Doerholt, K.; Warris, A.; Roilides, E.; Sharland, M.; Bielicki, J.; Goossens, H.
The appropriate use of systemic antifungals is vital in the prevention and treatment of invasive fungal infection (IFI) in immunosuppressed children and neonates. This multicenter observational study describes the inpatient prescribing practice of antifungal drugs for children and neonates and identifies factors associated with prescribing variability. A single-day point prevalence study of antimicrobial use in hospitalized neonates and children was performed between October and December 2012. The data were entered through a study-specific Web-based portal using a standardized data entry protocol. Data were recorded from 17,693 patients from 226 centers. A total of 136 centers recorded data from 1,092 children and 380 neonates receiving at least one antifungal agent. The most frequently prescribed systemic antifungals were fluconazole (n = 355) and amphotericin B deoxycholate (n = 195). The most common indications for antifungal administration in children were medical prophylaxis (n = 325), empirical treatment of febrile neutropenia (n = 122), and treatment of confirmed or suspected IFI (n = 100 [14%]). The treatment of suspected IFI in low-birthweight neonates accounted for the majority of prescriptions in the neonatal units (n = 103). An analysis of variance (ANOVA) demonstrated no significant effect of clinical indication (prophylaxis or treatment of systemic or localized infection) on the total daily dose (TDD). Fewer than one-half of the patients (n = 371) received a TDD within the dosing range recommended in the current guidelines. Subtherapeutic doses were prescribed in 416 cases (47%). The predominance of fluconazole and high incidence of subtherapeutic doses in participating hospitals may contribute to suboptimal clinical outcomes and an increased predominance of resistant pathogenic fungi. A global consensus on antifungal dosing and coordinated stewardship programs are needed to promote the consistent and appropriate use of antifungal drugs in neonates and children. PMID:25403672
Xu, Su; Gullapalli, Rao P; Frost, Douglas O
Atypical antipsychotic drugs (AAPDs) are widely used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of AAPD treatment before the brain is fully developed. Indeed, we and others have previously reported that treatment of adolescent rats with olanzapine (OLA; a widely prescribed AAPD) on postnatal days 28-49, under dosing conditions that approximate those employed therapeutically in humans, causes long-term behavioral and neurobiological perturbations. We have begun to study the mechanisms of these effects. Dopamine (DA) and serotonin (5HT) regulate many neurodevelopmental processes. Currently approved AAPDs exert their therapeutic effects principally through their DAergic activities, although in schizophrenia (SZ) and some other diseases for which AAPDs are prescribed, DAergic dysfunction is accompanied by abnormalities of glutamatergic (GLUergic) and ?-aminobutyric acidergic (GABAergic) transmission. Here, we use proton magnetic resonance spectroscopy ((1)H MRS) to investigate the effects of adolescent OLA administration on GABA and GLU levels. We found that the treatment caused long-term reductions in the levels of both GLU and GABA in the nucleus accumbens (NAc) of adult rats treated with OLA during adolescence. The NAc is a key node in the brain's "reward" system, whose function is also disrupted in schizophrenia. Further research into potential, OLA-induced changes in the levels of GLU and GABA in the NAc and other brain areas, and the dynamics and mechanisms of those changes, are an essential step for devising new adjunct therapies for existing AAPDs and for designing new drugs that increase therapeutic effects and reduce long-term abnormalities when administered to pediatric patients. PMID:25487700
Tsiantou, Vasiliki; Moschandreas, Joanna; Bertsias, Antonis; Papadakaki, Maria; Saridaki, Aristoula; Agius, Dominic; Alper, Zuleyha; Faresjo, Tomas; Klimkova, Martina; Martinez, Luc; Samoutis, George; Vl?ek, Ji?í; Lionis, Christos
The aim of this paper is to explore general practitioners' (GPs) prescribing intentions and patterns across different European regions using the Theory of Planned Behavior (TPB). A cross-sectional study was undertaken in selected geographically defined Primary Health Care areas in Cyprus, Czech Republic (CZ), France, Greece, Malta, Sweden and Turkey. Face-to-face interviews were conducted using a TPB-based questionnaire. The number of GP participants ranged from 39 to 145 per country. Possible associations between TPB direct measures (attitudes, subjective norms (SN) and perceived behavioral control (PBC)) and intention to prescribe were assessed by country. On average, GPs thought positively of, and claimed to be in control of, prescribing. Correlations between TPB explanatory measures and prescribing intention were weak, with TPB direct measures explaining about 25% of the variance in intention to prescribe in Malta and CZ but only between 3% and 5% in Greece, Sweden and Turkey. SN appeared influential in GPs from Malta; attitude and PBC were statistically significant in GPs from CZ. GPs' prescribing intentions and patterns differed across participating countries, indicating that country-specific interventions are likely to be appropriate. Irrational prescribing behaviors were more apparent in the countries where an integrated primary care system has still not been fully developed and policies promoting the rational use of medicines are lacking. Demand-side measures aimed at modifying GPs prescribing behavior are deemed necessary. PMID:26188356
Stone, Jamie A.; Chui, Michelle A.
Objective To explore types of e-prescribing errors in community pharmacies and their potential consequences, as well as the factors that contribute to e-prescribing errors. Methods Data collection involved performing 45 total hours of direct observations in five pharmacies. Follow-up interviews were conducted with 20 study participants. Transcripts from observations and interviews were subjected to content analysis using NVivo 10. Results Pharmacy staff detected 75 e-prescription errors during the 45 hour observation in pharmacies. The most common e-prescribing errors were wrong drug quantity, wrong dosing directions, wrong duration of therapy, and wrong dosage formulation. Participants estimated that 5 in 100 e-prescriptions have errors. Drug classes that were implicated in e-prescribing errors were antiinfectives, inhalers, ophthalmic, and topical agents. The potential consequences of e-prescribing errors included increased likelihood of the patient receiving incorrect drug therapy, poor disease management for patients, additional work for pharmacy personnel, increased cost for pharmacies and patients, and frustrations for patients and pharmacy staff. Factors that contribute to errors included: technology incompatibility between pharmacy and clinic systems, technology design issues such as use of auto-populate features and dropdown menus, and inadvertently entering incorrect information. Conclusion Study findings suggest that a wide range of e-prescribing errors are encountered in community pharmacies. Pharmacists and technicians perceive that causes of e-prescribing errors are multidisciplinary and multifactorial, that is to say e-prescribing errors can originate from technology used in prescriber offices and pharmacies. PMID:24657055
Little, Paul; Watson, Louise; Morgan, Stephen; Williamson, Ian
BACKGROUND: Systematic reviews of antibiotic treatment of common acute respiratory tract infections (RTIs) suggest modest symptomatic benefit, but provide limited evidence that prescribing prevents complications. AIM: To assess the relationship between penicillin prescribing (the most commonly used group of antibiotics for RTIs) and hospital admission with complications. DESIGN OF STUDY: Data linkage study. SETTING: Ninety-six health authorities of England for the year 1997-1998. METHOD: Hospital admissions related to RTIs were linked with prescribing analysis and cost (PACT) data. RESULTS: There was close correlation between items of penicillin use and total antibiotic use (r = 0.96). After controlling for SMR, age, sex, and Townsend score, a one-unit increase in penicillin use (items dispensed per capita) was associated with a reduction in annual incidence per 10,000 of admissions for quinsy (-3.55 admissions, 95% confidence interval [CI] = -6.85 to -0.26), and mastoiditis (square root of incidence of admissions = -1.05, 95% CI = -1.82 to -0.27). This does not represent lower referral thresholds among higher prescribers as higher prescribing was associated with more admissions for tonsillectomy and overall admissions. Increasing prescribing by 2000 items of penicillin for a practice of 10,000 patients could possibly prevent one admission for either mastoiditis or quinsy. CONCLUSION: Higher antibiotic prescribing is associated with significantly fewer admissions with major complications. However, the overall size of the effect is modest and it is difficult to advocate an overall increase in prescribing to prevent complications. Future research should concentrate on finding better methods of targeting antibiotics to individuals at risk of poor outcome. PMID:12030660
Czarniak, Petra; Bint, Lewis; Favié, Laurent; Parsons, Richard; Hughes, Jeff; Sunderland, Bruce
Purpose To estimate the prevalence of off-label and unlicensed prescribing during 2008 at a major paediatric teaching hospital in Western Australia. Methods A 12-month retrospective study was conducted at Princess Margaret Hospital using medication chart records randomly selected from 145,550 patient encounters from the Emergency Department, Inpatient Wards and Outpatient Clinics. Patient and prescribing data were collected. Drugs were classified as off-label or unlicensed based on Australian registration data. A hierarchical system of age, indication, route of administration and dosage was used. Drugs were classified according to the Anatomical Therapeutic Chemical Code. Results A total of 1,037 paediatric patients were selected where 2,654 prescriptions for 330 different drugs were prescribed to 699 patients (67.4%). Most off-label drugs (n = 295; 43.3%) were from the nervous system; a majority of unlicensed drugs were systemic hormonal preparations excluding sex hormones (n = 22, 32.4%). Inpatients were prescribed more off-label drugs than outpatients or Emergency Department patients (p < 0.0001). Most off-label prescribing occurred in infants and children (31.7% and 35.9% respectively) and the highest percentage of unlicensed prescribing (7.2%) occurred in infants (p < 0.0001). There were 25.7% of off-label and 2.6% of unlicensed medications prescribed across all three settings. Common reasons for off-label prescribing were dosage (47.4%) and age (43.2%). Conclusion This study confirmed off-label and unlicensed use of drugs remains common. Further, that prevalence of both is influenced by the clinical setting, which has implications in regards to medication misadventure, and the need to have systems in place to minimise medication errors. Further, there remains a need for changes in the regulatory system in Australia to ensure that manufacturers incorporate, as it becomes available, evidence regarding efficacy and safety of their drugs in children in the official product information. PMID:25756896
Ganem, Victoria J; Mora, Alejandra G; Varney, Shawn M; Bebarta, Vikhyat S
Chronic pain is a common reason for emergency department (ED) visits. Our objective was to describe opioid prescribing practices of ED providers when treating patients with chronic pain. We retrospectively evaluated opioid prescriptions from EDs at two tertiary care military hospitals. We queried the outpatient record database to obtain a list of opioid medications prescribed and ICD-9 codes associated with visits for chronic pain. We collected provider type and gender, number of pills, opioid type, and refills. We compared the incidence with chi-square or Fisher's exact tests. Wilcoxon test was used for non-parametric continuous variables. Over 3 years, 28,103 visits generated an opioid prescription. One thousand three hundred twenty-two visits were associated with chronic pain, and 443 (33 %) visits were associated with an opioid prescription. Providers were 79 % physicians, 19 % physician assistants (PAs), 81 % male, and 69 % active duty military. Medications were 43 % oxycodone, 30 % hydrocodone, 9.5 % tramadol, 2.5 % codeine, and 15 % other. The number of pills was 20 [interquartile range (IQR) 15-30] (range 1-240), morphine equivalents (M.E.) per pill was 7.5 [7.5-7.5] (2.5-120) and total M.E. per prescription was 150 [112.5-270] (15-6000). Physicians were more likely to prescribe a non-opioid than PAs (77 vs 45 %, p?0.0001). Civilian providers were more likely to prescribe an opioid than active duty providers (58 vs 42 %, p?0.0001). Providers prescribed a median of 20 pills per prescription and most commonly prescribed oxycodone. PAs were more likely to prescribe an opioid for chronic pain than physicians. Civilian providers were more likely to prescribe an opioid than active duty providers. PMID:25468314
Latif, Shaheen Azhar
In contrast to other atypical antipsychotics, aripiprazole (ARZ) acts as a partial agonist, rather than an antagonist, at dopamine D2 receptors (Burris et al, 2002; Jordan et al, 2002). This unique pharmacology is thought ...
... Second-Generation Antipsychotics in Adults: Comparative Effectiveness Full Report Research Review Aug. 14, 2012 Related Products for ... 1, 2010 Slide Presentation Aug. 20, 2013 Surveillance Report Mar. 30, 2015 Clinician Summary Apr. 10, 2013 ...
... Generation Antipsychotics for Children and Young Adults Full Report Research Review Feb. 20, 2012 Related Products for ... 20, 2012 Executive Summary Feb. 20, 2012 Related Reports Future Research Needs for First- and Second- Generation ...
Holbrook, A M; MacLeod, S M; Fisher, P; Levine, M A
Expenditure on drug therapy in Canada has been growing at a faster rate than spending on any other aspect of health care. Increasing societal pressure to use scarce resources more efficiently, advances in communication technology and data indicating that there is room for improvement in drug prescribing suggest that the time has come for an organized linkage of the available drug-utilization and health-outcomes data-bases across the country. A national prescribing practices network would assist prescribers, researchers and policymakers to optimize prescribing with respect to both cost effectiveness and health outcomes. The authors outline the main concerns addressed in the 1994 report to the National Pharmaceutical Strategy and present the results of discussions by the Canadian Prescribing Practices Network Project with respect to the potential users and data sources of a national network and the communications technology on which it would rely. PMID:8616735
Maxwell, Simon; Mucklow, John
Preparing medical students to prescribe is a major challenge of undergraduate education. They must develop an understanding of clinical pharmacology and acquire knowledge about drugs and therapeutics, as well as the skills to prescribe for individual patients in the face of multiple variables. The task of delivering the learning required to achieve these attributes relies upon limited numbers of teachers, who have increasingly busy clinical commitments. There is evidence that training is currently insufficient to meet the demands of the workplace. e-Learning provides an opportunity to improve the learning experience. The advantages for teachers are improved distribution of learning content, ease of update, standardization and tracking of learner activities. The advantages for learners are ease of access, greater interactivity and individual choice concerning the pace and mix of learning. Important disadvantages are the considerable resource required to develop e-Learning projects and difficulties in simulating some aspects of the real world prescribing experience. Pre-requisites for developing an e-Learning programme to support prescribing include academic expertise, institutional support, learning technology services and an effective virtual learning environment. e-Learning content might range from complex interactive learning sessions through to static web pages with links. It is now possible to simulate and provide feedback on prescribing decisions and this will improve with advances in virtual reality. Other content might include a student formulary, self-assessment exercises (e.g. calculations), a glossary and an on-line library. There is some evidence for the effectiveness of e-Learning but better research is required into its potential impact on prescribing. PMID:22509885
Background Long-acting injectable (LAI) formulations are not widely used in routine practice even though they offer advantages in terms of relapse prevention. As part of a process to improve the quality of care, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) elaborated guidelines for the use and management of antipsychotic depots in clinical practice. Methods Based on a literature review, a written survey was prepared that asked about 539 options in 32 specific clinical situations concerning 3 fields: target-population, prescription and use, and specific populations. We contacted 53 national experts, 42 of whom (79%) completed the survey. The options were scored using a 9-point scale derived from the Rand Corporation and the University of California in the USA. According to the answers, a categorical rank (first-line/preferred choice, second-line/alternate choice, third-line/usually inappropriate) was assigned to each option. The first-line option was defined as a strategy rated as 7–9 (extremely appropriate) by at least 50% of the experts. The following results summarize the key recommendations from the guidelines after data analysis and interpretation of the results of the survey by the scientific committee. Results LAI antipsychotics are indicated in patients with schizophrenia, schizoaffective disorder, delusional disorder and bipolar disorder. LAI second-generation antipsychotics are recommended as maintenance treatment after the first episode of schizophrenia. LAI first-generation antipsychotics are not recommended in the early course of schizophrenia and are not usually appropriate in bipolar disorder. LAI antipsychotics have long been viewed as a treatment that should only be used for a small subgroup of patients with non-compliance, frequent relapses or who pose a risk to others. The panel considers that LAI antipsychotics should be considered and systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated. Recommendations for medication management when switching oral antipsychotics to LAI antipsychotics are proposed. Recommendations are also given for the use of LAI in specific populations. Conclusion In an evidence-based clinical approach, psychiatrists, through shared decision-making, should be systematically offering to most patients that require long-term antipsychotic treatment an LAI antipsychotic as a first-line treatment. PMID:24359031
On October 25, 2011, the Center for Drug Evaluation and Research (CDER) of the Food and Drug Administration (FDA) posted online this Blueprint for Prescriber Continuing Education, labeled "final," relating to extended-release and long-acting opioids. The pending FDA Risk Evaluation Management Strategy (REMS) requires prescriber education. This document provides guidance to sponsors of these dosage forms in developing the prescvriber education component of their REMS. This report was posted online by the federal agency on October 25, 2011 at: http://www.fda.gov/downloads/drugs/drugsafety/informationbydrugclass/ucm277916.pdf. It is in the public domain. PMID:22764849
Massoni, F; Simeone, C; Luzi, E; Palla, C; Ricci, S
The public health spending has now reached very significant levels, in this sense, the responsibility of the medical doctor assumes a significant importance in medical law. The aim of this paper is to analyze the profile of responsibilities of the medical doctor in the light of recent case law. The appropriateness of prescribing and risk assessment are, according to the authors, the real test on which to test the skill, prudence and diligence which are called prescribers. Guidelines can be a valuable tool for the professional help, knowing, however, limits application of the recommendations where to be reconciling with the prevailing protection of personal rights of the user. PMID:23007826
Pulcini, Céline; Rabaud, Christian
France remains one of the European countries with the highest antibiotic use. It is a matter of emergency to use less antibiotics and in a more wisely manner, given the current worldwide bacterial resistance crisis. The following points are key in order to better prescribe antibiotics: use of a structured approach when prescribing an antibiotic, use of diagnostic tests when needed, compliance to recommendations, request for specialist advice in complicated cases, education of patients and continuous medical education/assessment of practice for the physicians. PMID:23236873
Citrome, Leslie; Volavka, Jan
Five new antipsychotic drugs introduced in the United States in the last decade offer physicians the ability to treat patients with schizophrenia and bipolar mania without the adverse effects of the first-generation antipsychotics. In this article, the authors discuss the advantages and side effects of these agents and present a guide to help physicians choose the optimal drug in the most favorable formulation for each patient. PMID:15510593
Junji Ichikawa; Toshihide Kuroki; Jin Dai; Herbert Y Meltzer
Amperozide, clozapine, olanzapine and risperidone are more potent serotonin (5-hydroxytryptamine, 5-HT)2A receptor antagonists than dopamine D2-like receptor antagonists. Haloperidol and S(?)-sulpiride are potent or selective dopamine D2-like receptor antagonists and lack 5-HT2A receptor antagonist properties. We studied the effect of these five proven antipsychotic drugs and one putative (amperozide) antipsychotic drug on extracellular 5-HT levels in the medial prefrontal cortex
Schuhmacher, Anna; Becker, Tim; Rujescu, Dan; Quednow, Boris B; Lennertz, Leonhard; Wagner, Michael; Benninghoff, Jens; Rietschel, Marcella; Häfner, Heinz; Franke, Petra; Wölwer, Wolfgang; Gaebel, Wolfgang; Maier, Wolfgang; Mössner, Rainald
Serotonergic transmission is considered relevant in the pathophysiology and the treatment of schizophrenia. Tryptophan hydroxylase (TPH) is the rate limiting enzyme in the biosynthesis of serotonin. While the TPH1 gene has been found to be associated with schizophrenia, studies focusing on TPH2 variants did not yield conclusive results for schizophrenia or the response to antipsychotic medication. We analyzed eleven TPH2 SNPs in two case-control samples consisting of 4453 individuals in total. Six SNPs were selected because of their potential functional relevance (rs4570625, rs11178997, rs11178998, rs7954758, rs7305115, and, rs4290270) and were supported by another 5 tagging SNPs selected based on HapMap LD information. In the discovery sample (1476 individuals), we observed a significant association with schizophrenia for rs10784941 (p = 0.009, OR minor G-allele 0.82 [0.71-0.95]) and rs4565946 (p = 0.011, OR minor T-allele 0.83 [0.71-0.96]). Association was also observed with a common rs4570625-rs4565946 haplotype (OR G-C haplotype 1.20 [1.02-1.40]; p = 0.0046). Single-marker associations could not be replicated in the replication sample consisting of 2977 individuals, but there was a strong trend regarding the rs4570625-rs4565946 G-C haplotype (OR 1.10 [0.98-1.24]; p(one-sided test) = 0.054). In smaller sub-samples, the rare rs4570625-rs4565946 T-T haplotype was associated with reduced processing speed (n = 193, p = 0.004) and sensorimotor gating (n = 68, p = 0.006) of schizophrenia patients. TPH2 variants and the rs4570625-rs4565946 G-C haplotype did not influence the beneficial response to antipsychotic drugs (n = 210) after four weeks of treatment administering the Positive and Negative Syndrome Scale of Schizophrenia (PANSS). We also investigated the association of the SNPs to treatment response, but did not get significant results. In sum, our results argue for only a minor role of TPH2 in schizophrenia. PMID:22655589
Kjelby, Eirik; Wentzel-Larsen, Tore; Mellesdal, Liv S.; Jørgensen, Hugo A.; Johnsen, Erik
Background Rates of discontinuation of antipsychotic treatment for patients with schizophrenia are high and evidence is limited by selective inclusion and high attrition in randomized controlled trials. Aims To study time to discontinuation of antipsychotic treatment for patients with schizophrenia. Method All patients with schizophrenia (n = 396) discharged between 2005 and 2011 were followed until discontinuation (clinician or patient decided) of antipsychotic treatment or other endpoints. Univariate and multivariate survival analyses (with time on antipsychotic treatment as the dependent variable) using time-dependent variables were performed. Results Clozapine displayed lower risk for all-cause (p < 0.001), clinician-decided (p = 0.012) and patient-decided (p = 0.039) discontinuation versus olanzapine oral treatment in the multivariate Cox regression. Second-generation long-acting injection antipsychotics (LAI) (p = 0.015) and first-generation long-acting injection antipsychotics (p = 0.013) showed significantly lower risks for patient-decided discontinuation than olanzapine oral. Conclusion Higher effectiveness of clozapine and LAI treatment versus oral olanzapine were identified in a clinical cohort of patients with schizophrenia. PMID:25489474
Gauthé, M; Goldberger, C; Olié, J P; Lôo, H; Gury, C; Poirier, M F
Conventional and atypical antipsychotics are known to induce weight gain, cause glucose and lipid impairments among schizophrenic patients. These impairments contribute to the intrinsic risk factors linked to the psychiatric pathology (sedentary state, nicotin addiction, diabetes) increasing numbers of cardiovascular complications. We propose to study ponderal modifications and presence of metabolic abnormalities in a population of schizophrenic patients treated by conventional or atypical antipsychotics, depending on the received treatment; 32 patients, whose schizophrenia diagnosis had been previously made, were consecutively included over a 4 months period. They were divided into three groups: patients treated by conventional antipsychotics (n = 6), by atypical antipsychotics (n = 16) or by a combination of both (n = 10); 6 patients (18%) display overweight problems, 4 patients (12.5%) got hypertriglyceridemia and 4 other patients (12.5%) have hypercholesterolemia. No particular drug could be directly targeted, partly because of the restricted size of our sample, but the patients presenting metabolism impairment were treated by atypical antipsychotic. The observance of these abnormalities is reflected in publications and lead to some antipsychotic treatments monitoring rules. PMID:15971636
Spyker, Daniel A; Riesenberg, Robert A; Cassella, James V
This randomized, double-blind, placebo-controlled, parallel-group study was to determine the pharmacokinetic characteristics, safety, and tolerability of multiple doses of inhaled loxapine aerosol in subjects on a stable, oral, chronic antipsychotic regimen. Loxapine was delivered by means of a unique thermally generated aerosol comprising drug particles of a size designed for deep lung delivery and absorption. Thirty-two subjects were randomized 1:1:1:1 to receive inhaled loxapine (total doses of 15, 20, or 30?mg) or inhaled placebo administered in 3 divided doses, given 4 hours apart. Following inhalation, the median Tmax was 2 minutes, and concentrations declined to about half Cmax approximately 5 minutes later across the 3 dose levels. The dose proportionality across data from this study combined with data from the single-dose study showed a slope (90%CI) of log AUCinf versus log dose of 0.818 (0.762-0.875) across the 8 doses (n?=?60 subjects) studied, indicating reasonable dose proportionality. The most common adverse events were cough (3 of 32, 9%), sedation (3 of 32, 9%), and dysgeusia (2 of 32, 6%). The inhalation of multiple doses of inhaled loxapine were well tolerated in study subjects and provided a safe, well-tolerated means for rapidly and reliably achieving therapeutic plasma concentrations of loxapine. ClinicalTrials.gov identifier: NCT00555412. PMID:25808074
Smith, W. E.
General mathematical expression found for energy storage shows that for linear, passive networks there is a minimum possible energy storage corresponding to a prescribed impedance. The electromagnetic energy storage is determined at different excitation frequencies through analysis of the networks terminal and reactance characteristics.
...TOBACCO PRODUCTS AND CIGARETTE PAPERS AND TUBES Administrative Provisions § 46.22...prescribe all forms required by this part. You must furnish all of the information...the form, and as required by this part. You must file each form in accordance...
...TOBACCO PRODUCTS AND CIGARETTE PAPERS AND TUBES Administrative Provisions § 46.22...prescribe all forms required by this part. You must furnish all of the information...the form, and as required by this part. You must file each form in accordance...
...TOBACCO PRODUCTS AND CIGARETTE PAPERS AND TUBES Administrative Provisions § 46.22...prescribe all forms required by this part. You must furnish all of the information...the form, and as required by this part. You must file each form in accordance...
...TOBACCO PRODUCTS AND CIGARETTE PAPERS AND TUBES, WITHOUT PAYMENT OF TAX, FOR USE OF THE...prescribe all forms required by this part. You must furnish all of the information required...the form, and as required by this part. You must file each form in accordance...
...TOBACCO PRODUCTS AND CIGARETTE PAPERS AND TUBES, WITHOUT PAYMENT OF TAX, FOR USE OF THE...prescribe all forms required by this part. You must furnish all of the information required...the form, and as required by this part. You must file each form in accordance...
...TOBACCO PRODUCTS AND CIGARETTE PAPERS AND TUBES, WITHOUT PAYMENT OF TAX, FOR USE OF THE...prescribe all forms required by this part. You must furnish all of the information required...the form, and as required by this part. You must file each form in accordance...
Livingston Univ., AL. Coll. of Education.
This document contains 59 individually prescribed instructional modules for use in teacher aide education programs. Each module has six sections: 1) Behavioral objectives, 2) purpose, 3) performance criteria, 4) experiences, 5) resources, and 6) taxonomy. The subjects covered include the use of instructional equipment such as language master,…
LUBRICATION APPROXIMATION WITH PRESCRIBED NONZERO CONTACT ANGLE Felix Otto Department--time existence for a weak solution s(t; x) â?? 0 of the lubrication approximation @ t s + @ x (s @ 3 x s) = 0 in fs will later motivate the way we construct approximate solutions for the lubrication approximation we are going
Hultgren, Philip B.; Burke, Edmund J., Jr.
This paper compares the methods for prescribing exercise according to various contemporary authorities. The programs are compared as to their goals, the testing modalities and physiological parameters used for prescription of the initial training session, and the methods and the progression of training. Regarding goals, there is a general…
We evaluated Japanese tendencies regarding prescription of hypnotics and anxiolytics. Four common features were recognized: (1) high-dose polypharmacy of hypnotics and anxiolytics is common in sleep and anxiety disorders; (2) the prevalence of prescriptions for elderly patients is especially high; (3) more than half of the prescriptions are written by physicians; and (4) the prescription of long-term benzodiazepines is still widespread in spite of international clinical guidelines recommending benzodiazepine treatment to be limited to only a few weeks. All these features should be considered when clinicians prescribe hypnotics and anxiolytics. The prescription of minimal dosages is essential both for obtaining clinical benefit and avoiding adverse events, such drug-dependency, falls and hip fractures, and withdrawal symptoms. PMID:26065141
Grossman, Joy M; Boukus, Ellyn R; Cross, Dori A; Cohen, Genna R
Hoping to reduce medication errors and contain health care costs, policy makers are promoting electronic prescribing through Medicare and Medicaid financial incentives. Many e-prescribing systems provide electronic access to important information--for example, medications prescribed by physicians in other practices, patient formularies and generic alternatives--when physicians are deciding what medications to prescribe. However, physician practices with e-prescribing face challenges using these features effectively, according to a new qualitative study by the Center for Studying Health System Change (HSC) funded by the Agency for Healthcare Research and Quality (AHRQ). While most of the 24 practices studied reported that physicians had access to patient formulary information, only slightly more than half reported physician access to patient medication histories, and many physicians did not routinely review these sources of information when making prescribing decisions. Study respondents highlighted two barriers to use: (1) tools to view and import the data into patient records were cumbersome to use in some systems; and (2) the data were not always perceived as useful enough to warrant the additional time to access and review them, particularly during time-pressed patient visits. To support generic prescribing, practices typically set their system defaults to permit pharmacist substitution of generics; many practices also used other tools to more proactively identify and select generic alternatives at the point of prescribing. Overall, physicians who more strongly perceived the need for third-party data, those in practices with greater access to complete and accurate data, and those with easier-to-use e-prescribing systems were more likely to use these features consistently. PMID:21545050
Åstrand, Bengt; Petersson, Göran
Background The increased application of eServices in health care, in general, and ePrescribing (electronic prescribing) in particular, have brought quality and interoperability to the forefront. The application of standards has been put forward as one important factor in improving interoperability. However, less focus has been placed on other factors, such as stakeholders’ involvement and the measurement of interoperability. An information system (IS) can be regarded to comprise an instrument for technology-mediated work communication. In this study, interoperability refers to the interoperation in the ePrescribing process, involving people, systems, procedures and organizations. We have focused on the quality of the ePrescription message as one component of the interoperation in the ePrescribing process. Objective The objective was to analyze how combined efforts in improving interoperability with the introduction of the new national ePrescription format (NEF) have impacted interoperability in the ePrescribing process in Sweden, with the focus on the quality of the ePrescription message. Methods Consecutive sampling of electronic prescriptions in Sweden before and after the introduction of NEF was undertaken in April 2008 (pre-NEF) and April 2009 (post-NEF). Interoperability problems were identified and classified based on message format specifications and prescription rules. Results The introduction of NEF improved the interoperability of ePrescriptions substantially. In the pre-NEF sample, a total of 98.6% of the prescriptions had errors. In the post-NEF sample, only 0.9% of the prescriptions had errors. The mean number of errors was fewer for the erroneous prescriptions: 4.8 in pre-NEF compared to 1.0 in post-NEF. Conclusions We conclude that a systematic comprehensive work on interoperability, covering technical, semantical, professional, judicial and process aspects, involving the stakeholders, resulted in an improved interoperability of ePrescriptions. PMID:23612314
Finucane, Anne M; Stevenson, Barbara; Gardner, Hilary; McArthur, Dorothy; Murray, Scott A
Common symptoms at the end of life include pain, breathlessness, anxiety, respiratory secretions and nausea. National end-of-life care strategies advocate anticipatory prescribing for timely management of these symptoms to enhance patient care by preventing unnecessary distress. This study investigated the extent to which residents in eight Lothian care homes had anticipatory medications prescribed prior to death. Data were collected as part of a service development project to improve palliative care in nursing care homes in Edinburgh. Of the 77 residents who died in the care homes, 54% had anticipatory medicines prescribed. Only 15% had prescriptions for all four nationally recommended anticipatory medications. Many care home residents do not have the recommended anticipatory medications in place in the last days of life and thus may experience inadequate symptom control. Interventions that increase the availability of anticipatory medicines to manage common symptoms at the end of life for care home residents are required. PMID:25381850
Gidengil, Courtney A; Linder, Jeffrey A; Hunter, Gerald; Setodji, Claude; Mehrotra, Ateev
For many surgeries and high-risk medical conditions, higher volume providers provide higher quality care. The impact of volume on more common medical conditions such as acute respiratory infections (ARIs) has not been examined. Using electronic health record data for adult ambulatory ARI visits, we divided primary care physicians into ARI volume quintiles. We fitted a linear regression model of antibiotic prescribing rates across quintiles to assess for a significant difference in trend. Higher ARI volume physicians had lower quality across a number of domains, including higher antibiotic prescribing rates, higher broad-spectrum antibiotic prescribing, and lower guideline concordance. Physicians with a higher volume of cases manage ARI very differently and are more likely to prescribe antibiotics. When they prescribe an antibiotic for a diagnosis for which an antibiotic may be indicated, they are less likely to prescribe guideline-concordant antibiotics. Given that high-volume physicians account for the bulk of ARI visits, efforts targeting this group are likely to yield important population effects in improving quality. PMID:25672338
Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI) forms of antipsychotics allow for rapid identification of non-adherence, obviate the need for the patient to take the medication on a daily basis and increase adherence to some significant degree. Eli Lilly has developed a long-acting depot formulation of olanzapine, olanzapine pamoate, which has recently been approved by the FDA for the US market, and which will be reviewed here. Olanzapine LAI appears to be an effective antipsychotic at dosages of 210 mg every 2 weeks, 300 mg every 2 weeks and 405 mg every 4 weeks in patients with acute schizophrenia, and at 150 mg every 2 weeks, 300 mg every 2 weeks and at 405 mg every 4 weeks for the maintenance treatment of stable patients. Oral supplementation appears not to be needed, particularly not at the onset of treatment with the LAI as is necessary with risperidone LAI. Its efficacy is in general comparable to the efficacy seen with oral olanzapine at a corresponding dose. The side effect profile is also comparable to the side effects observed with oral olanzapine, including lower rates of extrapyramidal symptoms, prolactin elevation and cardiovascular side effects, but significant metabolic effects. The latter include significant weight gain, lipid abnormalities and glucose dysregulation. While the injection site adverse events are overall mild, the most significant serious adverse event is the post-injection delirium sedation syndrome (PDSS). While rare, this syndrome results from inadvertent intravascular injection of olanzapine LAI and can cause a range of olanzapine overdose-type of symptoms. Olanzapine LAI needs therefore to be administered by trained personnel in settings where a post-injection observation period for at least 3 hours by medical personnel is available. The overall use of olanzapine LAI will probably be limited by the possibility of a PDSS event. Patients who have a history of good response to oral olanzapine and are in need of assured medication administration may present a good indication for its use, provided that the appropriate mental health delivery setting is available. PMID:20628628
Food and Drug Administration–approved information and public advertisements belie neurodegenerative risks for second-generation antipsychotics in affective illness. Package inserts label tardive syndromes “potentially reversible” while uniformly omitting patient counseling for long-term neurodegenerative side effects. I found that only 2 of 78 outpatients exposed to second-generation antipsychotics reported awareness of tardive syndromes. Updated literature challenges safety advantages of atypical versus typical antipsychotics. Physician and patient information regarding tardive syndromes from second-generation antipsychotics approved for affective illness is inadequate. PMID:25521884
Silva, Maria das Dores Graciano; Rosa, Mário Borges; Franklin, Bryony Dean; Reis, Adriano Max Moreira; Anchieta, Lêni Márcia; Mota, Joaquim Antônio César
OBJECTIVE: To analyze the prevalence and types of prescribing and dispensing errors occurring with high-alert medications and to propose preventive measures to avoid errors with these medications. INTRODUCTION: The prevalence of adverse events in health care has increased, and medication errors are probably the most common cause of these events. Pediatric patients are known to be a high-risk group and are an important target in medication error prevention. METHODS: Observers collected data on prescribing and dispensing errors occurring with high-alert medications for pediatric inpatients in a university hospital. In addition to classifying the types of error that occurred, we identified cases of concomitant prescribing and dispensing errors. RESULTS: One or more prescribing errors, totaling 1,632 errors, were found in 632 (89.6%) of the 705 high-alert medications that were prescribed and dispensed. We also identified at least one dispensing error in each high-alert medication dispensed, totaling 1,707 errors. Among these dispensing errors, 723 (42.4%) content errors occurred concomitantly with the prescribing errors. A subset of dispensing errors may have occurred because of poor prescription quality. The observed concomitancy should be examined carefully because improvements in the prescribing process could potentially prevent these problems. CONCLUSION: The system of drug prescribing and dispensing at the hospital investigated in this study should be improved by incorporating the best practices of medication safety and preventing medication errors. High-alert medications may be used as triggers for improving the safety of the drug-utilization system. PMID:22012039
Gallini, Adeline; Andrieu, Sandrine; Donohue, Julie M; Oumouhou, Naïma; Lapeyre-Mestre, Maryse; Gardette, Virginie
Based on evidence of an increased risk of death, drug agencies issued safety warnings about the use of second generation antipsychotics (SGAs) in the elderly with dementia. The French agency issued a warning in 2004. which was extended to all antipsychotics in 2008. Little is known about the impact of these warnings on use. We conducted a quasi-experimental study (interrupted time-series) in France, for 2003-2011, including subjects aged ?65 with dementia and subjects aged ?65 without dementia in the EGB database (1/97th representative random sample of claims from the main Health Insurance scheme). Outcomes were monthly rates of use of antipsychotics (by class and agent) and of five comparison drug classes (antidepressants, benzodiazepines, dermatologicals, antidiabetics, antiasthmatics). Trends were analyzed by joinpoint regression, impact of warnings by linear segmented regression. In patients with dementia (n=7169), there was a 40% reduction in antipsychotic use from 14.2% in 2003 to 10.2% in 2011. The reduction began before 2004 and was unaffected by the warnings. Use of first generation antipsychotics declined over the period, while use of SGAs increased and leveled off from 2007. Use of the five comparison drug classes increased on the period. In subjects without dementia (n=91,942), rates of overall antipsychotic use decreased from 2.3% in 2003 to 1.8% in 2011 with no effect of the warnings. Meanwhile, use of SGAs continuously increased from 0.37% to 0.64%. Antipsychotic use decreased in the elderly between 2003 and 2011, especially in dementia. The timing of the decrease, however, did not coincide with safety warnings. PMID:24126116
Gallini, Adeline; Andrieu, Sandrine; Donohue, Julie M; Oumouhou, Naïma; Lapeyre-Mestre, Maryse; Gardette, Virginie
Based on evidence of an increased risk of death, drug agencies issued safety warnings about the use of second generation antipsychotics (SGAs) in the elderly with dementia in 2004. This warning was extended to all antipsychotics in 2008. Little is known about the impact of these warnings on use. We conducted a quasi-experimental study (interrupted time-series) in France, for 2003–2011, including subjects aged ?65 with dementia and subjects aged ?65 without dementia in the EGB database (1/97th representative random sample of claims from the main Health Insurance scheme). Outcomes were monthly rates of use of antipsychotics (by class and agent) and of 5 comparison drug classes (antidepressants, benzodiazepines, dermatologicals, antidiabetics, antiasthmatics). Trends were analyzed by joinpoint regression, impact of warnings by linear segmented regression. In patients with dementia (n=7169), there was a 40% reduction in antipsychotic use from 14.2% in 2003 to 10.2% in 2011. The reduction began before 2004 and was unaffected by the warnings. Use of first generation antipsychotics declined over the period, while use of SGAs increased and leveled off from 2007. Use of the 5 comparison drug classes increased on the period. In subjects without dementia (n=91942), rates of overall antipsychotic use decreased from 2.3% in 2003 to 1.8% in 2011 with no effect of the warnings. Meanwhile, use of SGAs continuously increased from 0.37% to 0.64%. Antipsychotic use decreased in the elderly between 2003 and 2011, especially in dementia. The timing of the decrease, however, did not coincide with safety warnings. PMID:24126116
Ghate, Sameer R; Porucznik, Christina A; Said, Qayyim; Hashibe, Mia; Joy, Elizabeth; Brixner, Diana I
Objective To assess the frequency and predictors of regular monitoring of metabolic parameters as recommended by the American Diabetes Association (ADA)/American Psychiatric Association (APA) guidelines in adolescents receiving antipsychotics compared with an untreated comparison group in a primary care setting. Method A retrospective cohort study was conducted using an electronic medical record database in the USA from January 2004 to July 2009. The exposure group consisted of adolescents with a first prescription for second-generation antipsychotics (SGAs). The comparison group, without antipsychotics, was matched (3:1) to the exposed. Baseline and follow-up metabolic measurements were assessed and patients were categorised as being regularly monitored based on recommendations by the ADA/APA guidelines. Multivariate logistic regression was conducted to assess the predictors of regular monitoring, adjusting for demographic characteristics, baseline medications and medical conditions. Results The frequency of regular monitoring of body mass index (BMI), blood pressure, total cholesterol and fasting blood glucose, as recommended by ADA/APA guidelines among antipsychotic users (25, 55, 2.4 and 1.7%) was low but significantly higher compared with the matched comparison group (9.5, 37.4, 0.8 and 0.7%, respectively) (P < 0.05). Overall, antipsychotic treatment was associated with 1.5- to 4.26-fold increase in the likelihood of metabolic monitoring compared with the comparison group (P < 0.05). Other predictors included oral antidiabetic use for BMI monitoring and dyslipidaemia for blood pressure, total cholesterol and fasting blood glucose. Conclusion The majority of adolescents on antipsychotics were under-monitored for BMI, lipids and glucose levels. Antipsychotic users with pre-existing and newly diagnosed metabolic conditions were more likely to be regularly monitored for metabolic parameters. PMID:23997820
Mahoney, Diane Feeney; Ladd, Elissa
The purpose of this study was to gain understanding about nurse practitioners' (NPs') prescriptive decision making for geriatric patients with attention to pharmaceutical marketing influences. Prior research has focused on physician prescribers and identified suboptimal practices. Because the majority of medications are prescribed to older adults, NPs in geriatric practice were targeted as an information-rich group to interview about prescribing issues. Given the exploratory nature of this research, qualitative focus group methods were employed using content analysis. Fifteen NPs were recruited at an annual national geriatric NP conference. They worked in all regions of the United States, had an average of 9 years prescribing experience, and participated in 1 of the 2 focus groups. The key theme that emerged was that they were more than a prescriber. Findings revealed overwhelming consistency among the NP participants that their nursing background instilled a holistic approach that encompassed both nondrug and therapeutic drug options and skepticism about drug marketing, as well as offered a positive difference by tailoring to their patients' biophysical, psychological, and economic needs with an involvement in the interplay of geriatric care issues not typically addressed by physicians. The participants' reported approaches were in alignment with geriatric prescribing recommendations. PMID:20159350
Picada, Jaqueline Nascimento; Dos Santos, Bruna de Jesus Neto; Celso, Franciele; Monteiro, Jéssica Dias; Da Rosa, Kelly Morais; Camacho, Leandro Rosa; Vieira, Luciana Rodrigues; Freitas, Taís Madelon; Da Silva, Tatiana Grasiela; Pontes, Viviane Minuzzo; Pereira, Patrícia
Aim: Aripiprazole is an antipsychotic agent to treat schizophrenia, which acts through dopamine D2 partial agonism, serotonin 5-HT1A partial agonism and 5-HT2A antagonism. This study was designed to evaluate the neurobehavioral effects and genotoxic/mutagenic activities of the agent, as well as its effects on lipoperoxidation. Methods: Open field and inhibitory avoidance tasks were used. Thirty min before performing the behavioral tasks, adult male CF-1 mice were administered aripiprazole (1, 3 or 10 mg/kg, ip) once for the acute treatment, or the same doses for 5 d for the subchronic treatment. Genotoxic effects were assessed using comet assay in the blood and brain tissues. Mutagenic effects were evaluated using bone marrow micronucleus test. Lipoperoxidation was assessed with thiobarbituric acid reactive substances (TBARS). Results: Acute and subchronic treatments significantly decreased the number of crossing and rearing in the open field task. Acute treatment significantly increased the step-down latency for both the short- and long-term memory in the inhibitory avoidance task. Subchronic treatments with aripiprazole (3 and 10 mg/kg) caused significant DNA strain-break damage in peripheral blood but not in the brain. Mutagenic effect was not detected in the acute and subchronic treatments. Nor TBARS levels in the liver were affected. Conclusion: Aripiprazole improved memory, but could impair motor activities in mice. The drug increased DNA damage in blood, but did not show mutagenic effects, suggesting that it might affect long-term genomic stability. PMID:21841809
Miles D. Houslay (University of Glasgow; Faculty of Biomedical and Life Sciences REV)
Heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) are the largest group of structurally related proteins encoded by the human genome. As signal effectors and allosteric regulators, GPCRs dynamically recruit not only specific heterotrimeric G proteins but also the cytosolic scaffold proteins, ?-arrestin 1 and 2, which were originally thought only to serve as negative regulators of GPCR signaling. Although about half of currently available therapeutics target GPCR function, usually at the ligand-binding, orthosteric site, evidence suggests that ?-arrestins may be therapeutic targets themselves. Indeed, a hitherto undiscovered action of various antipsychotics is to inhibit the ability of the dopamine D2 receptor to engage ?-arrestin 2 and activate glycogen synthase kinase 3, which may be a target for developing therapeutics for schizophrenia. Also, certain ?-antagonists (blockers) used to treat heart failure, such as carvedilol, have the added effect of promoting activation of extracellular signal-regulated kinase through ?-arrestin. It seems likely that the structure of ?-arrestins allows them to detect different types and conformational states of GPCRs and to respond in functionally distinct fashions by using separate cohorts of signaling proteins, thus generating additional possibilities for therapeutic intervention.
Thomas, Dierk; Wu, Kezhong; Kathöfer, Sven; Katus, Hugo A; Schoels, Wolfgang; Kiehn, Johann; Karle, Christoph A
Acquired long QT syndrome (aLQTS) is caused by prolongation of the cardiac action potential because of blockade of cardiac ion channels and delayed repolarization of the heart. Patients with aLQTS carry an increased risk for torsade de pointes arrhythmias and sudden cardiac death. Several antipsychotic drugs may cause aLQTS. Recently, cases of QTc prolongation and torsade de pointes associated with chlorpromazine treatment have been reported. Blockade of human ether-a-go-go-related gene (HERG) potassium channels, which plays a central role in arrhythmogenesis, has previously been reported to occur with chlorpromazine, but information on the mechanism of block is currently not available. We investigated the effects of chlorpromazine on cloned HERG potassium channels to determine the biophysical mechanism of block. HERG channels were heterologously expressed in Xenopus laevis oocytes, and ion currents were measured using the two-microelectrode voltage-clamp technique. Chlorpromazine blocked HERG potassium channels with an IC50 value of 21.6 ?M and a Hill coefficient of 1.11. Analysis of the voltage dependence of block revealed a reduction of inhibition at positive membrane potentials. Inhibition of HERG channels by chlorpromazine displayed reverse frequency dependence, that is, the amount of block was lower at higher stimulation rates. No marked changes in electrophysiological parameters such as voltage dependence of activation or inactivation, or changes of the inactivation time constant were observed. In conclusion, HERG channels were blocked in the closed and activated states, and unblocking occurred very slowly. PMID:12788816
Mayol, R F; Jajoo, H K; Klunk, L J; Blair, I A
Metabolism of the antipsychotic drug tiospirone was studied in humans after a single 60-mg oral dose of [14C]tiospirone. Metabolites were isolated from a 0-24 hr pooled urine from eight subjects, which represented 39% of the dose, and purified to homogeneity by HPLC. Purified metabolites were identified by desorption chemical ionization mass spectrometry in the positive ion mode with methane as a reagent gas. Structures of the metabolites were confirmed by coelution on HPLC in several systems with synthetic standards. In addition to unchanged tiospirone, five metabolites of tiospirone were identified and one additional metabolite was partially identified. Based on the structures of these metabolites, five routes of metabolism of tiospirone were identified: N-dealkylation of the butyl side chain attached to the piperazinyl nitrogen, hydroxylation alpha to the glutarimidyl carbonyl at the 6'-position on the spiro ring, hydroxylation at the 3'-position on the spiro ring, oxidation at sulfur resulting in the formation of sulfones, and oxidation at carbon alpha to the piperazinyl nitrogen resulting in the formation of a lactam-sulfone. The major urinary metabolites were benzisothiazole piperazine sulfone and its lactam derivative, accounting for 5.0 and 4.3% of the dose, respectively. The identified metabolites accounted for 50% of the total radioactivity in the urine (approximately 20% of the dose). The remaining radioactive components were extremely heterogeneous and could not be isolated in sufficient quantities to characterize. A scheme for the metabolism of tiospirone in humans is proposed. PMID:1676643
Are Antipsychotics or Antidepressants Needed for Psychotic Depression? - A Systematic Review and Meta-Analysis of Trials Comparing Antidepressant or Antipsychotic Monotherapy with Combination Treatment
Farahani, Arusha; Correll, Christoph U.
Objective To perform a meta-analysis of antidepressant-antipsychotic cotreatment versus antidepressant or antipsychotic monotherapy for psychotic depression. Data Sources We performed an electronic search in PubMed/Medline, Cochrane Library and PsycINFO from inception of the data bases until 02/20/2012, without language/time restrictions. Key words were: (psychosis OR psychotic OR hallucinations OR hallucinating OR delusions or delusional) AND (depression OR depressed OR major depressive disorder) AND (random OR randomized OR randomly). Study Selection Eight randomized, placebo-controlled acute phase studies (n=762) in adults with standardized criteria-defined psychotic depression were meta-analyzed, yielding 10 comparisons. Antidepressant-antipsychotic cotreatment was compared in 5 trials with 6 treatment arms (n=337) with antidepressant monotherapy and in 4 trials and treatment arms (n=447) with antipsychotic monotherapy. Data Extraction Primary outcome was study-defined inefficacy; secondary outcomes included all-cause discontinuation, specific psychopathology ratings and side effects. Using random effects models, we calculated risk ratios (RR) with 95% confidence intervals (CI), numbers-needed-to-treat/harm (NNT/NNH) and effect sizes (ES). Results Antipsychotic-antidepressant co-treatment outperformed antidepressant monotherapy regarding less study-defined inefficacy (N=6, n=378, RR:0.76, CI:0.60,0.96, p=0.03, I2=34%; NNT=7, CI:4-20, p=0.009) and Clinical Global Impressions-Severity (N=4, n=289, ES:-0.25, CI:-0.49,-0.02, p=0.03, I2=0%), with trend-level superiority for depression ratings (N=5, n=324, ES:-0.20, CI:-0.44,0.03, p=0.09, I2=10%), but not psychosis (N=3, n=161, ES:-0.24, CI:-0.85,0.38, p=0.45, I2=70%). Antidepressant-antipsychotic co-treatment also outperformed antipsychotic monotherapy regarding less study-defined inefficacy (N=4, n=447, RR:0.73, CI:0.63,0.84, p<0.0001, I2=0%; NNT=5, CI:4-8, p<.0001) and depression (N=4, n=428, ES:-0.49, CI:-0.75,-0.23, p=0.0002, I2=27), while anxiety (p=0.11) and psychosis ratings (p=0.06) only trended favoring co-treatment. All-cause-discontinuation and reported side effect rates were similar, except for more somnolence with antipsychotic-antidepressant co-treatment versus antidepressants (p=0.02). Only one open, 4-month extension study (n=59) assessed maintenance/relapse prevention efficacy of antidepressant-antipsychotic cotreatment versus antidepressant monotherapy, without group differences. Conclusions Antidepressant-antipsychotic cotreatment was superior to monotherapy of either class in the acute treatment of psychotic depression. These results support recent treatment guidelines, but more studies are needed to assess specific combinations and maintenance/relapse prevention efficacy. PMID:22579147
MICHAEL S. ROBERTS; MICHELLE KING; JUUE A. STOKES; TERESA A. LYNNE; CHRISTOPHER J. BONNER; SEAN MCCARTHY; ANDREW WILSON; PAUL GLASZIOU; W. JOHN PUGH
Objective: to examine the key determinants of pharmaco-epidemiology in Australian nursing homes. Design: a cross-sectional survey of medication use in 998 residents in 15 nursing homes in Southern Queensland and Northern New South Wales. Results: the total, laxative, digoxin\\/diuretic, benzodiazepine and psycholeptic medication prescribed and administered to residents of nursing homes was affected to differing extents by age and gender,
Powell, J H
Recent interest in the relevancy of near vision tests for presbyopic aircrew members has led to the development of a photographic cockpit model. This model is used to prescribe more accurately for flying personnel. Prescriptions can be evaluated by use of trial lenses. This allows the aircrew members to experience the effect of viewing instruments in the cockpit of a C-130 aircraft. PMID:1603370
Dixie L. Bounds; Douglas E. Ruby
The effects of fire on wetland vegetation in the mid-Atlantic region of the United States are poorly known, despite the historical\\u000a use of fire by federal, state, and private landowners in the Chesapeake Bay Region. Prescribed fire is widely used by land\\u000a managers to promote vegetation that is beneficial to migratory waterfowl, muskrats, and other native wildlife and to reduce
Moiduddin, Adil; Dullabh, Prashila; Woolley, Rochelle
In 2006 CMS and AHRQ funded the National Resource Center for Health IT (NRC) to evaluate the findings from the 5 CMS ePrescribing (eRx) pilots. During this evaluation, the NRC identified research areas from: 1) questions left unanswered by the pilot contractors, 2) gaps in knowledge identified by the evaluation team and, 3) areas requiring additional industry experience. The research areas encompass standards, implementation considerations and outcomes such as ADEs, pharmacy workflow and physician adoption. PMID:18999210
Magdalan, Jan; Wasyko-Smolarek, Ma?gorzata; Anto?czyk, Andrzej; Kochman, Krystyna; Przew?ocki, Micha?; Porebska, Barbara
Recently, atypical antipsychotic agents have largely replaced traditional agents as first-line drugs for the treatment of schizophrenia and psychotic mood disorders. Considering the increase in atypical antipsychotics prescriptions and the increased risk of suicide in this patient population, the number of reported cases of antipsychotic drugs may be expected to increase. This paper describes the clinical course of atypical antipsychotic agents intoxication, chiefly clozapine, risperidone and olanzapine. Clozapine was the ingestant in 11 cases of atypical antipsychotics overdose in our material. The major observed effects in this group included deep coma, tachycardia, hypersalivation, delirium and shock. Clozapine has a small therapeutic index; in our patients the mortality rate was 27%. Ten patients with risperidone overdose were identified. Our data show that risperidone toxicity manifests mainly as mild central nervous system effects: somnolence, vertigo and tardive dyskinesia. Olanzapine has been considered to be similar to clozapine, but olanzapine intoxication appeared to have a relatively benign clinical course as compared with clozapine intoxication. In olanzapine intoxications deep coma, myosis and mild cardiovascular effects (hypotonia) were observed. PMID:15521612
Dietz, David M; Kennedy, Pamela J; Sun, HaoSheng; Maze, Ian; Gancarz, Amy M; Vialou, Vincent; Koo, Ja Wook; Mouzon, Ezekiell; Ghose, Subroto; Tamminga, Carol A; Nestler, Eric J
?FosB, a FosB gene product, is induced in the prefrontal cortex (PFC) by repeated exposure to several stimuli including antipsychotic drugs such as haloperidol. However, the functional consequences of increased ?FosB expression following antipsychotic treatment have not been explored. Here, we assessed whether ?FosB induction by haloperidol mediates the positive or negative consequences or clinical-related actions of antipsychotic treatment. We show that individuals with schizophrenia who were medicated with antipsychotic drugs at their time of death display increased ?FosB levels in the PFC, an effect that is replicated in rats treated chronically with haloperidol. In contrast, individuals with schizophrenia who were medication-free did not exhibit this effect. Viral-mediated overexpression of ?FosB in the PFC of rodents induced cognitive deficits as measured by inhibitory avoidance, increased startle responses in prepulse inhibition tasks, and increased MK-801-induced anxiety-like behaviors. Together, these results suggest that ?FosB induction in the PFC by antipsychotic treatment contributes to the deleterious effects of these drugs and not to their therapeutic actions. PMID:24067299
Anderson, George; Maes, Michael
This paper reviews melatonin as an overlooked factor in the developmental etiology and maintenance of schizophrenia; the neuroimmune and oxidative pathophysiology of schizophrenia; specific symptoms in schizophrenia, including sleep disturbance; circadian rhythms; and side effects of antipsychotics, including tardive dyskinesia and metabolic syndrome. Electronic databases, i.e. PUBMED, Scopus and Google Scholar were used as sources for this review using keywords: schizophrenia, psychosis, tardive dyskinesia, antipsychotics, metabolic syndrome, drug side effects and melatonin. Articles were selected on the basis of relevance to the etiology, course and treatment of schizophrenia. Melatonin levels and melatonin circadian rhythm are significantly decreased in schizophrenic patients. The adjunctive use of melatonin in schizophrenia may augment the efficacy of antipsychotics through its anti-inflammatory and antioxidative effects. Further, melatonin would be expected to improve sleep disorders in schizophrenia and side effects of anti-psychotics, such as tardive dyskinesia, metaboilic syndrome and hypertension. It is proposed that melatonin also impacts on the tryptophan catabolic pathway via its effect on stress response and cortisol secretion, thereby impacting on cortex associated cognition, amygdala associated affect and striatal motivational processing. The secretion of melatonin is decreased in schizophrenia, contributing to its etiology, pathophysiology and management. Melatonin is likely to have impacts on the metabolic side effects of anti-psychotics that contribute to subsequent decreases in life-expectancy. PMID:22527998
Gill, Kathryn M.
Trials of novel compounds for the treatment of schizophrenia are typically tested in patients following brief withdrawal of ongoing medication despite known long-term changes in the dopamine (DA) system following chronic antipsychotic drug therapy. The present study explored the impact of withdrawal from repeated haloperidol (HAL) treatment, as well as the response to a novel ?5 gamma-aminobutyric acid (GABAA) receptor positive allosteric modulator (?5PAM), on the activity of the DA system in the methylazoxymethanol acetate (MAM) neurodevelopmental model of schizophrenia. Electrophysiological recordings were conducted from DA neurons in the ventral tegmental area of MAM and saline (SAL) rats following 7-day withdrawal from repeated HAL (21 d, 0.6mg/kg, orally). In separate animals, amphetamine-induced locomotion was measured to assess changes in DA behavioral sensitivity. SAL rats withdrawn from HAL demonstrated reduced spontaneous DA neuron activity along with an enhanced locomotor response to amphetamine, indicative of the development of DA supersensitivity. Both ?5PAM treatment and ventral hippocampal (vHPC) inactivation reversed the DA neuron depolarization block following HAL withdrawal in SAL rats. In contrast, MAM rats withdrawn from HAL exhibited reduced spontaneous DA activity and enhanced locomotor response to amphetamine compared with untreated SAL rats; however, this condition was unresponsive to ?5PAM treatment or vHPC inactivation. Withdrawal from prior HAL treatment interferes with the therapeutic actions of this novel treatment in the MAM model of schizophrenia. Consequently, testing novel compounds on chronically treated schizophrenia patients may be ineffective. PMID:24464874
Toledo, David; Kreuter, Urs P; Sorice, Michael G; Taylor, Charles A
Risk and liability concerns regarding fire affect people's attitudes toward fire and have led to human-induced alterations of fire regimes. This has, in turn, contributed to brush encroachment and degradation of many grasslands and savannas. Efforts to successfully restore such degraded ecosystems at the landscape scale in regions of the United States with high proportions of private lands require the reintroduction of fire. Prescribed Burn Associations (PBA) provide training, equipment, and labor to apply fire safely, facilitating the application of this rangeland management tool and thereby reducing the associated risk. PBAs help build networks and social capital among landowners who are interested in using fire. They can also change attitudes toward fire and enhance the social acceptability of using prescribed fire as a management practice. PBAs are an effective mechanism for promoting the widespread use of prescribed fire to restore and maintain the biophysical integrity of grasslands and savannas at the landscape scale. We report findings of a project aimed at determining the human dimensions of using prescribed fire to control woody plant encroachment in three different eco-regions of Texas. Specifically, we examine membership in PBAs as it relates to land manager decisions regarding the use of prescribed fire. Perceived risk has previously been identified as a key factor inhibiting the use of prescribed fire by landowners. Our results show that perceived constraints, due to lack of skill, knowledge, and access to equipment and membership in a PBAs are more important factors than risk perceptions in affecting landowner decisions about the use of fire. This emphasizes the potential for PBAs to reduce risk perceptions regarding the application of prescribed fire and, therefore, their importance for restoring brush-encroached grasslands and savannas. PMID:24333743
A. V. Pavlenko; V. P. Grinchenkov; A. A. Gummel; I. A. Pavlenko; E. Kallenbakh
The design principals of fast-operating electromagnetic drives with prescribed dynamic performances are examined. The represented\\u000a procedure permits the command parameters to be to determined with the guaranteed prescribed parameters of the drive.
Klein, Lawrence E.; And Others
Physicians in an experimental group were surveyed to assess their knowledge of the effectiveness, cost, and side effects of antibiotics, and a tutorial was developed to modify some prescribing patterns. Prescribing patterns were statistically different. (Author/MLW)
...benefits. (c) Acceptable reasons for failure to follow prescribed treatment. ...determining if you have an acceptable reason for failure to follow prescribed treatment. The...because of its enormity (e.g. open heart surgery), unusual nature...
...benefits. (c) Acceptable reasons for failure to follow prescribed treatment. ...determining if you have an acceptable reason for failure to follow prescribed treatment. The...because of its magnitude (e.g., open heart surgery), unusual nature...
...benefits. (c) Acceptable reasons for failure to follow prescribed treatment. ...determining if you have an acceptable reason for failure to follow prescribed treatment. The...because of its magnitude (e.g., open heart surgery), unusual nature...
...benefits. (c) Acceptable reasons for failure to follow prescribed treatment. ...determining if you have an acceptable reason for failure to follow prescribed treatment. The...because of its enormity (e.g. open heart surgery), unusual nature...
...benefits. (c) Acceptable reasons for failure to follow prescribed treatment. ...determining if you have an acceptable reason for failure to follow prescribed treatment. The...because of its enormity (e.g. open heart surgery), unusual nature...
...benefits. (c) Acceptable reasons for failure to follow prescribed treatment. ...determining if you have an acceptable reason for failure to follow prescribed treatment. The...because of its magnitude (e.g., open heart surgery), unusual nature...
Kapetanovic, Suad; Aaron, Lisa; Williams, Paige L; Farley, John; Sirois, Patricia A; Garvie, Patricia A; Pearson, Deborah A; Oleske, James M; Montepiedra, Grace
Purpose Perinatally HIV-infected children, who are increasingly aging into adolescence and early adulthood, have significant rates of psychiatric co-morbidities, some of which are treated with second-generation antipsychotics (SGAs). SGAs have been associated with elevated total cholesterol (TC) in youth, but no studies have examined this association in perinatally HIV-infected youth. This study examined changes in TC levels of youth with perinatally acquired HIV infection and co-morbid psychiatric conditions treated with SGAs. Patients and methods Long-term changes in TC levels were examined using data from the US multisite prospective Pediatric AIDS Clinical Trials Group 219C cohort study. The change in TC levels from baseline to 12 months after initiating SGA use was compared between 52 SGA-exposed and 148 matched SGA-unexposed perinatally HIV-infected youth, using generalized estimating equation models adjusting for other covariates. The prevalence and time to incident hypercholesterolemia were also compared between these 2 groups. Results After adjustment for confounders, 52 youth with prescriptions for SGAs had a larger increase in TC levels than 148 matched youth without antipsychotic prescriptions (mean difference = 9 mg/dL, z = 1.96, df = 1, P = 0.0496). Among youth with TC below 220 mg/dL at baseline, 27% of SGA-exposed youth developed hypercholesterolemia (defined as two consecutive TC measurements ?220 mg/dL), compared with 13% of SGA-unexposed patients (Fisher's exact test, P = 0.046). Conclusions Caution should be used in prescribing SGAs to perinatally HIV-infected youth with psychiatric co-morbidities due to increased risk of hypercholesterolemia. Patients should be monitored, and alternative evidence-based treatments considered when available. PMID:20865061
Price, Rae; Salavati, Bahar; Graff-Guerrero, Ariel; Blumberger, Daniel M; Mulsant, Benoit H; Daskalakis, Zafiris J; Rajji, Tarek K
In people with schizophrenia, cognitive abilities - including memory - are strongly associated with functional outcome. Long-term potentiation (LTP) is a form of neuroplasticity that is believed to be the physiological basis for memory. It has been postulated that antipsychotic medication can impair long-term potentiation and cognition by altering dopaminergic transmission. Thus, a systematic review was performed in order to assess the relationship between antipsychotics and D2 antagonists on long-term potentiation. The majority of studies on LTP and antipsychotics have found that acute administration of antipsychotics was associated with impairments in LTP in wild-type animals. In contrast, chronic administration and acute antipsychotics in animal models of schizophrenia were not. Typical and atypical antipsychotics and other D2 antagonists behaved similarly, with the exception of clozapine and olanzapine. Clozapine caused potentiation independent of tetanization, while olanzapine facilitated tetanus-induced potentiation. These studies are limited in their ability to model the effects of antipsychotics in patients with schizophrenia as they were largely performed in wild-type animals as opposed to humans with schizophrenia, and assessed after acute rather than chronic treatment. Further studies using patients with schizophrenia receiving chronic antipsychotic treatment are needed to better understand the effects of these medications in this population. PMID:24819820
de Matos, Luiza P R; Santana, Cinthia V N; Souza, Renan P
Previous association results between dopamine D1 receptor (DRD1) rs4532 polymorphism and antipsychotic treatment response in schizophrenia and schizoaffective subjects have been conflicting. Thus, we have conducted a systematic review followed by a meta-analysis. Our results indicated no association between DRD1 rs4532 polymorphism and overall antipsychotic response or clozapine monotherapy response. PMID:26213377
de Kuijper, G.; Hoekstra, P.; Visser, F.; Scholte, F. A.; Penning, C.; Evenhuis, H.
Background: We investigated antipsychotic drug prescription practice of Dutch ID physicians, studying prevalence of antipsychotic drug use, reasons for prescription and the relationship between these reasons and patient characteristics. Methods: A cross-sectional study of medical and pharmaceutical records in a population living in residential…
Rajender R. Aparasu; Jane R. Mort; Scott Sitzman
This study employed data from the National Ambulatory Medical Care Survey (NAMCS) 1995 to (1) determine the prevalence of the prescribing of psychotropic drugs for elderly patients by office-based physicians in the United States; (2) estimate the prevalence of the prescribing of potentially inappropriate psychotropic drugs in this patient population; and (3) identify any factors that predict such prescribing. For
Garry D. Honey; Edward T. Bullmore; William Soni; Malini Varatheesan; Steve C. R. Williams; Tonmoy Sharma
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
Czekalla, J; Kollack-Walker, S; Beasley, C M
Alterations of electrocardiogram results and cases of sudden cardiac death have been reported since the beginning of neuroleptic treatment. In particular, a temporal association exists between some antipsychotics and prolongation of the heart rate-corrected QT interval (QTc), an event that may increase the risk for developing a potentially fatal ventricular tachycardia arrhythmia known as torsades de pointes if it significantly exceeds normal intraindividual and interindividual variation. Although the incidence of serious adverse cardiac events in response to antipsychotic medications is relatively low, any possibility for the occurrence of cardiotoxicity warrants continued study. The present article reviews important differences among antipsychotic drugs in the potential for, and occurrence of, serious adverse cardiac outcomes and suggests that olanzapine, as therapeutically administered to patients with schizophrenia and related psychoses, does not contribute significantly to a QTc prolongation that could result in potentially fatal ventricular arrhythmias. PMID:11232751
Rosenheck, Robert; Lin, Haiqun
Noninferiority analysis is a statistical method of growing importance in comparative effectiveness research that has rarely been used in psychopharmacology. This method is used here to evaluate whether first-generation antipsychotics are clinically not inferior to second-generation antipsychotics (SGAs) using data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). A conservative noninferiority margin (NIM) on the Positive and Negative Syndrome Scale (PANSS) was derived from the smallest published value for the minimal clinically important difference, further reduced by 25%. This NIM was used to assess whether perphenazine is noninferior to olanzapine, risperidone, and quetiapine on the basis of the 95% confidence intervals of differences in mean PANSS outcomes (N = 1049). Perphenazine was noninferior to all three SGAs during 18 months of intention-to-treat analysis and in several subanalyses. Noninferiority can be evaluated from studies designed as superiority trials. Power was available in the CATIE to conduct noninferiority analysis. PMID:24375207
Mizoguchi, Yoshito; Kato, Takahiro A.; Horikawa, Hideki; Monji, Akira
Microglia are resident innate immune cells which release many factors including proinflammatory cytokines, nitric oxide (NO) and neurotrophic factors when they are activated in response to immunological stimuli. Recent reports show that pathophysiology of schizophrenia is related to the inflammatory responses mediated by microglia. Intracellular Ca2+ signaling, which is mainly controlled by the endoplasmic reticulum (ER), is important for microglial functions such as release of NO and cytokines, migration, ramification and deramification. In addition, alteration of intracellular Ca2+ signaling underlies the pathophysiology of schizophrenia, while it remains unclear how typical or atypical antipsychotics affect intracellular Ca2+ mobilization in microglial cells. This mini-review article summarizes recent findings on cellular mechanisms underlying the characteristic differences in the actions of antipsychotics on microglial intracellular Ca2+ signaling and reinforces the importance of the ER of microglial cells as a target of antipsychotics for the treatment of schizophrenia. PMID:25414641
Shulman, Matisyahu; Miller, Avraham; Misher, Jason; Tentler, Aleksey
Background The use of antipsychotic medication in the United States and throughout the world has greatly increased over the last fifteen years. These drugs have significant side effect burdens, many of them relating to cardiovascular health. Objective To review the available evidence on the major cardiovascular issues that arise in patients taking antipsychotic medication. Method A PubMed literature review was performed to identify recent meta-analyses, review articles, and large studies. Further articles were identified through cited papers and based on expert consultation when necessary. Results Clinical guidance on the following adverse effects and antipsychotics was reviewed: electrocardiogram (ECG) changes, (specifically, prolonged QT and risk of torsades de pointes), weight gain, dyslipidemia, metabolic syndrome, and myocarditis. Specific attention was paid to monitoring guidelines and treatment options in the event of adverse events, including dose change, medication switch, or adjuvant therapy. PMID:25382979
Friesen, Kevin J; Bugden, Shawn C
Background Citalopram is the most commonly prescribed antidepressant in Canada. Concerns have been raised about its cardiac safety, and a dose-dependent prolongation of the QT interval has been documented. Drug interactions involving concomitant use of other medications that prolong the QT interval or increase citalopram levels by interfering with its metabolism increase the cardiac risk. Regulatory bodies (Health Canada and the US Food and Drug Administration) issued warnings and required labeling changes in 2011/2012, suggesting maximum citalopram doses (<40 mg for those <65 years; <20 mg for those ?65 years) and avoiding drug interactions that increase cardiac risk. The purpose of this study is to assess the impact of these warnings on citalopram prescribing practices. Methods A quasi-experimental interrupted time series analysis was conducted using all citalopram prescribing data from the population of Manitoba, Canada from 1999 to 2014. This allowed for the examination of high-dose prescribing (above regulatory warning levels) and the number of interacting medications per citalopram prescription. Results There was a dramatic decline in the prescribing of high doses in both age groups, with a 64.8% decline in those <65 years and 33.6% in those ?65 years. Segmented regression models indicated significant breakpoints in the third quarter of 2011 for both age groups (P<0.0001), corresponding to the time the regulatory warnings were issued. There appeared to be no impact of the warnings on the prescribing of interacting medications. The number of interacting medications actually increased in the postwarning period (<65, 0.78–0.81 interactions per citalopram prescription; ?65, 0.93–0.94, P<0.001). Conclusion Regulatory changes appear to have produced an important reduction in the high-dose prescribing of citalopram. In contrast to this relatively simple dosage change, there was no indication that the more complex issue of resolving drug–drug interactions was impacted by regulatory warnings. PMID:26316822
Lewis, Penny J; Ashcroft, Darren M; Dornan, Tim; Taylor, David; Wass, Val; Tully, Mary P
Aims Prescribing errors are common and can be detrimental to patient care and costly. Junior doctors are more likely than consultants to make a prescribing error, yet there is only limited research into the causes of errors. The aim of this study was to explore the causes of prescribing mistakes made by doctors in their first year post graduation. Methods As part of the EQUIP study, interviews using the critical incident technique were carried out with 30 newly qualified doctors. Participants were asked to discuss in detail any prescribing errors they had made. Participants were purposely sampled across a range of medical schools (18) and hospitals (15). A constant comparison approach was taken to analysis and Reason's model of accident causation was used to present the data. Results More than half the errors discussed were prescribing mistakes (errors due to the correct execution of an incorrect plan). Knowledge-based mistakes (KBMs) appeared to arise from poor knowledge of practical aspects of prescribing such as dosing, whereas rule-based mistakes (RBMs) resulted from inappropriate application of knowledge. Multiple error-producing and latent conditions were described by participants for RBMs and KBMs. Poor/absent senior support and a fear of appearing incompetent occurred with KBMs. Following erroneous routines or seniors' orders were major contributory factors in RBMs. Conclusions Although individual factors such as knowledge and expertise played a role in prescribing mistakes, there were many perceived interrelated factors contributing to error. We conclude that multiple interventions are necessary to address these and further research is essential. PMID:24517271
Thomas, Sarah K; McDowell, Sarah E; Hodson, James; Nwulu, Ugochi; Howard, Rachel L; Avery, Anthony J; Slee, Ann; Coleman, Jamie J
Aims To develop a list of prescribing indicators specific for the hospital setting that would facilitate the prospective collection of high-severity and/or high-frequency prescribing errors, which are also amenable to electronic clinical decision support. Methods A two-stage consensus technique (electronic Delphi) was carried out with 20 experts across England. Participants were asked to score prescribing errors using a five-point Likert scale for their likelihood of occurrence and the severity of the most likely outcome. These were combined to produce risk scores, from which median scores were calculated for each indicator across the participants in the study. The degree of consensus between the participants was defined as the proportion that gave a risk score in the same category as the median. Indicators were included if a consensus of 80% or more was achieved. Results A total of 80 prescribing errors were identified by consensus as being high or extreme risk. The most common drug classes named within the indicators were antibiotics (n = 13), antidepressants (n = 8), nonsteroidal anti-inflammatory drugs (n = 6) and opioid analgesics (n = 6). The most frequent error type identified as high or extreme risk were those classified as clinical contraindications (n = 29 of 80). Conclusions Eighty high-risk prescribing errors in the hospital setting have been identified by an expert panel. These indicators can serve as a standardized, validated tool for the collection of prescribing data in both paper-based and electronic prescribing processes. This can assess the impact of safety improvement initiatives, such as the implementation of electronic clinical decision support. PMID:23362926
Briggs, Paula Elizabeth; Praet, Cecile Aude; Humphreys, Samantha Charlotte; Zhao, Changgeng
Objectives Combined hormonal contraceptives (CHCs) are the most widely prescribed contraceptive methods in the UK; however, their use is associated with significant cardiovascular risk for women with some medical conditions and risk factors. The objective of this study was to assess the potential change in CHC prescribing among higher-risk women following publication of the UK Medical Eligibility Criteria for Contraceptive Use (UKMEC) in 2006. Methods A cross-sectional study was conducted using the General Practice Research Database to analyse UK women aged 15–49 years who were prescribed CHCs during the period 2004–2010. Of women prescribed CHCs, those at higher risk of cardiovascular events (with UKMEC Category 3 or 4 risk factors) were identified. The percentage of higher-risk CHC users, among all CHC users, in 2005 (pre-UKMEC) was compared to that in 2010 (post-UKMEC). Results The percentage of higher-risk CHC users significantly decreased by 0.8% (95% CI 0.68% to 1.02%) following publication of UKMEC [8.1% (95% CI 7.98% to 8.22%) in 2005 vs 7.3% (95% CI 7.14% to 7.38%) in 2010; p<0.001]. However, an estimated 1?74?472 women in the UK were prescribed CHCs in 2010 despite having Category 3 or 4 risk factors. The most common Category 3 or 4 risk factors were body mass index ?35?kg/m2, hypertension and smoking in women aged ?35?years. Conclusions Despite the observed reduction in prescribing of CHCs to higher-risk women after publication of UKMEC, a large number of women with Category 3 or 4 risk factors are still prescribed CHCs. The increased risk of cardiovascular events is unnecessary for many of these women given the availability of alternative contraceptive methods. PMID:23299629
Background Prescribing is a core activity for general practitioners, yet significant variation in the quality of prescribing has been reported. This suggests there may be room for improvement in the application of the current best research evidence. There has been substantial investment in technologies and interventions to address this issue, but effect sizes so far have been small to moderate. This suggests that prescribing is a decision-making process that is not sufficiently understood. By understanding more about prescribing processes and the implementation of research evidence, variation may more easily be understood and more effective interventions proposed. Methods An ethnographic study in three Scottish general practices with diverse organizational characteristics. Practices were ranked by their performance against Audit Scotland prescribing quality indicators, incorporating established best research evidence. Two practices of high prescribing quality and one practice of low prescribing quality were recruited. Participant observation, formal and informal interviews, and a review of practice documentation were employed. Results Practices ranked as high prescribing quality consistently made and applied macro and micro prescribing decisions, whereas the low-ranking practice only made micro prescribing decisions. Macro prescribing decisions were collective, policy decisions made considering research evidence in light of the average patient, one disease, condition, or drug. Micro prescribing decisions were made in consultation with the patient considering their views, preferences, circumstances and other conditions (if necessary). Although micro prescribing can operate independently, the implementation of evidence-based, quality prescribing was attributable to an interdependent relationship. Macro prescribing policy enabled prescribing decisions to be based on scientific evidence and applied consistently where possible. Ultimately, this influenced prescribing decisions that occur at the micro level in consultation with patients. Conclusion General practitioners in the higher prescribing quality practices made two different ‘types’ of prescribing decision; macro and micro. Macro prescribing informs micro prescribing and without a macro basis to draw upon the low-ranked practice had no effective mechanism to engage with, reflect on and implement relevant evidence. Practices that recognize these two levels of decision making about prescribing are more likely to be able to implement higher quality evidence. PMID:23799906
Kooiker, C H; Scutchfield, F D
From a questionnaire sent to all obstetricians and gynecologists and all family and general practitioners in San Diego County, California, regarding the Copper T 380A intrauterine device, substantial barriers to prescribing it were identified. Of all physicians responding, 40% reported that they were not recommending the Copper T 380A to anyone, the single most common reason given being concern about medical liability. A lack of knowledge about the new device, a lack of intrauterine device insertion skills, and certain medical practice settings were also important barriers to prescribing it. The new intrauterine device is considered in the context of innovation-diffusion theory. Substantial amounts of education and training and improvement in the medical-legal climate are needed before current barriers to prescribing the new device are removed. PMID:2219892
Smith, R; Barnsley, L; Kannangara, S; Mace, A
Rheumatologists, with their musculoskeletal background, often care for athletes. The effect of a positive anti-doping test, whether through illegitimate use or accidental prescribing of banned drugs, is devastating to an athlete's career. It is therefore incumbent upon rheumatologists to be aware of issues relating to drugs in sport. This involves both therapeutic drugs and doping. It is vital to ensure that any substance prescribed should be approved for use and should not adversely affect (or benefit) the athlete's performance. In March 2004, 5 months prior to the 2004 Olympic Games in Athens, the joint World Anti-Doping Agency/International Olympic Committee published the revised list of banned substances in athletes. This article aims to provide an overview of the current status of medications commonly prescribed in rheumatological practice. PMID:15292526
Anderson, Kristen; Stowasser, Danielle; Freeman, Christopher; Scott, Ian
Objective To synthesise qualitative studies that explore prescribers’ perceived barriers and enablers to minimising potentially inappropriate medications (PIMs) chronically prescribed in adults. Design A qualitative systematic review was undertaken by searching PubMed, EMBASE, Scopus, PsycINFO, CINAHL and INFORMIT from inception to March 2014, combined with an extensive manual search of reference lists and related citations. A quality checklist was used to assess the transparency of the reporting of included studies and the potential for bias. Thematic synthesis identified common subthemes and descriptive themes across studies from which an analytical construct was developed. Study characteristics were examined to explain differences in findings. Setting All healthcare settings. Participants Medical and non-medical prescribers of medicines to adults. Outcomes Prescribers’ perspectives on factors which shape their behaviour towards continuing or discontinuing PIMs in adults. Results 21 studies were included; most explored primary care physicians’ perspectives on managing older, community-based adults. Barriers and enablers to minimising PIMs emerged within four analytical themes: problem awareness; inertia secondary to lower perceived value proposition for ceasing versus continuing PIMs; self-efficacy in regard to personal ability to alter prescribing; and feasibility of altering prescribing in routine care environments given external constraints. The first three themes are intrinsic to the prescriber (eg, beliefs, attitudes, knowledge, skills, behaviour) and the fourth is extrinsic (eg, patient, work setting, health system and cultural factors). The PIMs examined and practice setting influenced the themes reported. Conclusions A multitude of highly interdependent factors shape prescribers’ behaviour towards continuing or discontinuing PIMs. A full understanding of prescriber barriers and enablers to changing prescribing behaviour is critical to the development of targeted interventions aimed at deprescribing PIMs and reducing the risk of iatrogenic harm. PMID:25488097
Dlugacz, Henry; Wimmer, Christopher
The administration of antipsychotic medications to jail and prison inmates involves two related components: conducting the informed consent process in a coercive environment and, where consent is not obtained, forcible administration of medication if needed. In the United States, both involve common law, statutory, and constitutional principles. Obtaining informed consent in correctional institutions is complicated. Patients in correctional institutions lack access to alternate sources of information, and depend on the correctional system completely - a system which they may distrust. This may influence the patient's view of the administering physician. Where consent cannot be obtained, forcible administration may be legally permissible for two primary reasons: to restore a criminal defendant to competency in order to stand trial and to ameliorate severe symptoms of mental disability, particularly when they threaten the safety of self, others, or in some instances, property. The interests at stake for the individual and the government, and the legal standards developed to balance these interests, differ between the two situations. When considering challenges to forcible medication of inmates serving a prison sentence, the United States Supreme Court has treated the interest of the institution in maintaining security as paramount. By contrast, when considering challenges to forcible medication of pretrial detainees, the Court's concern for the fair trial rights guaranteed by the Sixth Amendment has seemingly led it to moderate its emphasis on security. However, this distinction is not stable and may in fact be breaking down, as the recent case of Jared Loughner demonstrates. This article discusses the various federal, state, and international legal standards applicable to both informed consent and forcible medication, and their implementation in the correctional setting, focusing on issues related to the United States. PMID:23683884
The first chapter of the following article discusses measures in terms of substitution treatment of a program of the Austrian Minister of the Interior. The relevance of psychosocial measures and aims of substitution treatment for opioid-dependent patients is illuminated. The abstinence as the only goal definition is modified and by the results of the study PREMOS a target differentiation at addiction work is illustrated. The second chapter addresses the misuse of prescribed drugs. Thereby police report data will be analyzed and the market situation of opioids will be outlined. PMID:25377373
Rossi, Alessandro; Maggio, Roberto; Riccardi, Ilaria; Allegrini, Fabio; Stratta, Paolo
Because natural disasters provoke an increase in mental and medical disorders in survivors, an increase in psychotropic prescriptions has been observed following disasters. This study assesses the pharmacoepidemiology of antidepressant and antipsychotic drug prescriptions after an earthquake in Italy by using an administrative database. Statins and diabetic medications served as control medications. Comparison of the rates in the 6 months after the earthquake to the same period one year before revealed a 37% increase of new prescriptions for antidepressants and a 129% increase for antipsychotic prescriptions. Older age and female gender was associated with the increased number of prescriptions. PMID:21351173
Background Youth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) study, a federally funded, randomized trial comparing two pharmacologic strategies against a control condition to manage SGA-related weight gain. Methods The design and methodology considerations of the IMPACT trial are described and embedded in a description of health risks associated with antipsychotic-related weight gain and the limitations of currently available research. Results The IMPACT study is a 4-site, six month, randomized, open-label, clinical trial of overweight/obese youth ages 8–19 years with pediatric schizophrenia-spectrum and bipolar-spectrum disorders, psychotic or non-psychotic major depressive disorder, or irritability associated with autistic disorder. Youth who have experienced clinically significant weight gain during antipsychotic treatment in the past 3 years are randomized to either (1) switch antipsychotic plus healthy lifestyle education (HLE); (2) add metformin plus HLE; or (3) HLE with no medication change. The primary aim is to compare weight change (body mass index z-scores) for each pharmacologic intervention with the control condition. Key secondary assessments include percentage body fat, insulin resistance, lipid profile, psychiatric symptom stability (monitored independently by the pharmacotherapist and a blinded evaluator), and all-cause and specific cause discontinuation. This study is ongoing, and the targeted sample size is 132 youth. Conclusion Antipsychotic-related weight gain is an important public health issue for youth requiring ongoing antipsychotic treatment to maintain psychiatric stability. The IMPACT study provides a model for pediatric research on adverse event management using state-of-the art methods. The results of this study will provide needed data on risks and benefits of two pharmacologic interventions that are already being used in pediatric clinical settings but that have not yet been compared directly in randomized trials. Trial registration Clinical Trials.gov NCT00806234 PMID:23947389
Khazaal, Y; Chatton, A; Claeys, F; Ribordy, F; Khan, R; Zullino, D
The present study explores sweet stimuli effects on hunger and negative alliesthesia in patients treated with antipsychotic drugs and controls. Those phenomena were examined in relation to previous weight gain, eating and weight-related cognitions and type of sweet stimuli: aspartame or sucrose. Alliesthesia is delayed in participants who gained weight regardless of cross group differences. A similar reduction of hunger was observed after the intake of two kinds of sweet stimuli (aspartame or sucrose) whereas alliesthesia measures were not affected. Whereas atypical antipsychotic drug-induced weight gain is linked to delayed satiety, the phenomenon is similar in magnitude in non-psychiatric controls who gained weight. PMID:20179410
Shearer, David S
The present article discusses the integration of a civilian prescribing psychologist into a primary care clinic at Madigan Army Medical Center. A description of the role of the prescribing psychologist in this setting is provided. The author asserts that integrating prescribing psychology into primary care can improve patient access to skilled behavioral health services including psychotherapeutic and psychopharmacologic treatment. Potential benefits to the primary care providers (PCPs) working in primary care clinics are discussed. The importance of collaboration between the prescribing psychologist and PCP is emphasized. Initial feedback indicates that integration of a prescribing psychologist into primary care has been well received in this setting. PMID:23179076
Objective: Neuroleptics were introduced into North America 60 years ago. The credit for this advance is generally accorded to Heinz Lehmann. I sought to explore whether Lehmann really was the first North American psychiatrist to study the effects of chlorpromazine (CPZ) and to provide a more balanced view of its application in a clinical context. Method: I searched for historical documents and published articles in several libraries and interviewed psychiatrists active from 1952–1970. Results: The first article in English was published in the July volume of the Archives of Neurology and Psychiatry in 1954 (n = 71). Another article, written in French by Roland Saucier and published in a journal called Le Saguenay Médical, also described the effects of CPZ on a Canadian psychiatric population in August 1954 (n > 200). However, the first prescription for CPZ was written by Roland Saucier, who brought the product back from Paris after a fellowship there. Ruth Kajander, in Ontario, was also one of the first prescribers of this drug, following her study of its use in anesthesia and a publication in the proceedings of a symposium. Conclusion: The contents of the 2 naturalistic studies were compared. Lehmann’s study started 1 month before that of Saucier. Lehmann was the first North American psychiatrist to publish an article on CPZ, but Roland Saucier nevertheless made an important contribution, being the first to prescribe this drug in North America and reporting results for a study with a sample size 3 times that of Lehmann’s study. PMID:25886681
Gill, Kathryn M; Cook, James M; Poe, Michael M; Grace, Anthony A
Trials of novel compounds for the treatment of schizophrenia are typically tested in patients following brief withdrawal of ongoing medication despite known long-term changes in the dopamine (DA) system following chronic antipsychotic drug therapy. The present study explored the impact of withdrawal from repeated haloperidol (HAL) treatment, as well as the response to a novel ?5 gamma-aminobutyric acid (GABA(A)) receptor positive allosteric modulator (?5PAM), on the activity of the DA system in the methylazoxymethanol acetate (MAM) neurodevelopmental model of schizophrenia. Electrophysiological recordings were conducted from DA neurons in the ventral tegmental area of MAM and saline (SAL) rats following 7-day withdrawal from repeated HAL (21 d, 0.6 mg/kg, orally). In separate animals, amphetamine-induced locomotion was measured to assess changes in DA behavioral sensitivity. SAL rats withdrawn from HAL demonstrated reduced spontaneous DA neuron activity along with an enhanced locomotor response to amphetamine, indicative of the development of DA supersensitivity. Both ?5PAM treatment and ventral hippocampal (vHPC) inactivation reversed the DA neuron depolarization block following HAL withdrawal in SAL rats. In contrast, MAM rats withdrawn from HAL exhibited reduced spontaneous DA activity and enhanced locomotor response to amphetamine compared with untreated SAL rats; however, this condition was unresponsive to ?5PAM treatment or vHPC inactivation. Withdrawal from prior HAL treatment interferes with the therapeutic actions of this novel treatment in the MAM model of schizophrenia. Consequently, testing novel compounds on chronically treated schizophrenia patients may be ineffective. PMID:24464874
Flores, C.; Bounds, D.L.; Ruby, D.E.
The effects of fire on wetland vegetation in the mid-Atlantic region of the United States are poorly known, despite the historical use of fire by federal, state, and private landowners in the Chesapeake Bay Region. Prescribed fire is widely used by land managers to promote vegetation that is beneficial to migratory waterfowl, muskrats, and other native wildlife and to reduce competition from less desirable plant species. We compared vegetative response to two fire rotations, annual burns and 3-year burns, and two control sites, Control 1 and Control 2. We tested the effects of fire within six tidal marsh wetlands at Blackwater National Wildlife Refuge and Fishing Bay Wildlife Management Area in Maryland. We examined changes in total live biomass (all species), total stem density, litter, and changes in live biomass and stem density of four dominant wetland plant species (11 variables). Our results suggest that annual prescribed fires will decrease the accumulation of litter, increase the biomass and stem densities of some wetland plants generally considered less desirable for wildlife, and have little or no effect on other wetland plants previously thought to benefit from fire. ?? 2011 US Government.
Nicholson, R G H; Thomas, G P L; Potter, M J; Norris, J H
Aims Prescribing for athletes requires an up-to-date knowledge of the World Anti-Doping Agency's list of prohibited substances. As the London 2012 Olympic Games attract athletes from around the world, we review the current guidelines with respect to all medications licensed for ophthalmic use in the United Kingdom. We describe the process that an ophthalmologist can use to check for permissible medications and also highlight treatments that are contraindicated. Methods We systematically reviewed all 77 drugs listed in Section 11 of the British National Formulary (Issue 63) for use in the treatment of ophthalmic conditions, and referenced these against the 2012 Prohibited List published by the World Anti-Doping Agency. Results The majority of ophthalmic preparations are suitable for use in- and out-of-competition. Some preparations, such as glucocorticoids, are prohibited when administered systemically but permitted for topical administration. Beta-blockers are prohibited in-competition and oral carbonic anhydrase inhibitors are prohibited in- and out-of competition. Conclusion The 2012 Prohibited List has important implications for the pharmacological treatment of ophthalmic conditions in athletes. Clinicians prescribing for athletes have a duty to familiarise themselves with the list in order to avoid causing significant damage to their patient's career and reputation. PMID:22744394
Cobaugh, Daniel J; Erdman, Andrew R; Booze, Lisa L; Scharman, Elizabeth J; Christianson, Gwenn; Manoguerra, Anthony S; Caravati, E Martin; Chyka, Peter A; Woolf, Alan D; Nelson, Lewis S; Troutman, William G
The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and out-of-hospital management of patients with suspected acute ingestions of atypical antipsychotic medications by 1) describing the process by which an ingestion of an atypical antipsychotic medication might be evaluated, 2) identifying the key decision elements in managing cases of atypical antipsychotic medication ingestion, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This guideline applies to ingestion of atypical antipsychotic medications alone. Co-ingestion of additional substances could require different referral and management recommendations depending on the combined toxicities of the substances. This guideline is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions might be at variance with this guideline and are the prerogative of the patient and the health professionals providing care, considering all of the circumstances involved. This guideline does not substitute for clinical judgment. The grade of recommendation is in parentheses. 1) Patients with stated or suspected self-harm or the recipient of a potentially malicious administration of an atypical antipsychotic medication should be referred to an emergency department immediately. This activity should be guided by local poison center procedures. In general, this should occur regardless of the dose reported (Grade D). 2) Patients without evidence of self-harm should have further evaluation, including determination of the precise dose ingested, presence of signs or symptoms of toxicity, history of other medical conditions, and the presence of co-ingestants (Grade C). 3) Asymptomatic patients without evidence of attempted self-harm are unlikely to develop symptoms if the interval between the ingestion and the call is greater than 6 hours. These patients do not need referral and should receive follow-up based on local poison center protocols (Grade C). 4) All patients less than 12 years of age who are naïve to atypical antipsychotic medications and are experiencing no more than mild drowsiness (lightly sedated and can be aroused with speaking voice or light touch) can be observed at home unless they have ingested more than four times the initial adult dose for the implicated antipsychotic medication or a dose that is equal to or more than the lowest reported acute dose that resulted in at least moderate toxicity, whichever dose is smaller (i.e., aripiprazole 15 mg, clozapine 50 mg, olanzapine 10 mg, quetiapine 100 mg, risperidone 1 mg, ziprasidone 80 mg) (Grade D). 5) All patients 12 years of age or older who are naïve to atypical antipsychotic medications and are experiencing no more than mild drowsiness can be observed at home unless they have ingested more than five times the initial adult dose for the implicated antipsychotic medication (i.e., aripiprazole 50 mg, clozapine 62.5 mg, olanzapine 25 mg, quetiapine 125 mg, risperidone 5 mg, ziprasidone 100 mg) (Grade D). 6) Patients who use atypical antipsychotic medications on a chronic basis can be observed at home unless they have acutely ingested more than 5 times their current single dose (not daily dose) of the implicated antipsychotic medication (Grade C). 7) Patients who have ingested less than a threshold dose (see Recommendations 4-6) and are exhibiting no more than mild drowsiness can be observed at home with instructions to call the poison center if symptoms develop or worsen. If mild drowsiness is present at the time of the initial call, the poison center should make follow-up calls until at least 6 hours after ingestion. Consideration should be given to the time of day that home observation will take place. Observation during normal sleep hours might not be reliable. Depending on local poison center policy, patients could be referred to an emergency department if the observation would take place during no
Greenbaum, L; Smith, R C; Rigbi, A; Strous, R; Teltsh, O; Kanyas, K; Korner, M; Lancet, D; Ben-Asher, E; Lerer, B
RGS2 (regulator of G-protein signaling 2) modulates dopamine receptor signal transduction. Functional variants in the gene may influence susceptibility to extrapyramidal symptoms (EPS) induced by antipsychotic drugs. To further investigate our previous report of association of the RGS2 gene with susceptibility to antipsychotic-induced EPS, we performed a replication study. EPS were rated in 184 US patients with schizophrenia (115 African Americans, 69 Caucasian) treated for at least a month with typical antipsychotic drugs (n=45), risperidone (n=46), olanzapine (n=50) or clozapine (n=43). Six single nucleotide polymorphisms (SNPs) within or flanking RGS2 were genotyped (rs1933695, rs2179652, rs2746073, rs4606, rs1819741 and rs1152746). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. Our results indicate association of SNP rs4606 with antipsychotic-induced parkinsonism (AIP), as measured by the Simpson Angus scale, in the overall sample and in the African-American subsample, the G (minor) allele having a protective effect. ORs for AIP among rs4606 G-allele carriers were 0.23 (95% CI 0.10-0.54, P=0.001) in the overall sample, and 0.20 (0.07-0.57, P=0.003) in the African-American subsample. In the previously studied Israeli sample the OR was 0.31 (0.11-0.84, P=0.02). We completely sequenced the RGS2 gene in nine patients with AIP and nine patients without, from the Israeli sample. No common coding polymorphisms or additional regulatory variants were revealed, suggesting that association of the rs4606 C/G polymorphism with AIP is biologically meaningful and not a consequence of linkage disequilibrium with another functional variant. Taken together, the findings of the current study support the association of RGS2 with AIP and focus on a possible protective effect of the minor G allele of SNP rs4606. This SNP is located in the 3'-regulatory region of the gene, and is known to influence RGS2 mRNA levels and protein expression. PMID:18347610
Downs, P. W.; Sklar, L.; Braudrick, C. A.
Flow prescriptions for environmental benefit in regulated rivers are commonly focused on the provision of minimum flow depths to achieve fish passage and holding habitat objectives. Assessment of these flows can be achieved readily and with reasonable confidence by using low-flow hydrological records and channel morphology data in combination with one dimensional hydraulic modeling. More recently, as understanding has increased of the critical role played by high flows in maintaining a wide range of habitats for instream and riparian flora and fauna, attention has turned to prescribing high flows to invoke the geomorphic processes that maintain suitable habitat niches. Prediction of the effects of these flows may require high-flow discharge and sediment transport data, high resolution topographic data, hydraulic and sediment transport modeling (often in two or three spatial dimensions), knowledge of the watershed historical context, and an understanding of the thresholds for channel morphological change. Not surprisingly, the associated level of uncertainty in this analysis increases tremendously. High flows are defined by a combination of magnitude, frequency, timing and duration parameters and their impact varies according to antecedent events. High flow bedload sediment transport records are rare, sediment transport equations are reliable usually to only an order of magnitude, practical applications of two and three-dimensional sediment transport models are in their infancy, the watershed historical record may be patchy with the link between cause and effect difficult to ascertain, and thresholds of channel morphological change are poorly understood. As the first step in reducing uncertainty, it is essential to state precisely the ecological target objectives of prescribed high flows, and to link these objectives to the hydraulic and geomorphic thresholds to be achieved or exceeded. Such thresholds provide the basis for a systematic classification of high flows. Here we recognize a spectrum of ten high flow types grouped in four classes encompassing flows to maintain: flow depth and velocity, channel bed texture and mobility, channel width and bar morphology and migration, and floodplain sedimentation and disturbance regime. We review the predictive ability associated with a selection of flow types to illustrate the difficulties faced. Progressively greater flows are required in each class to achieve the habitat objectives and the level of uncertainly increases in parallel. In general, because of a lack of suitable data and predictive process models, the primary practical means of reducing uncertainty is to prescribe high flow releases using best available understanding, to treat high flow releases as experiments as much as restoration projects and to be rigorous in generating hypotheses against which to monitor and evaluate their geomorphic impact.
Coull, Alison; Murray, Ian; Turner-Halliday, Fiona; Watterson, Andrew
Medicine prescribing by community nurses commenced in the UK in 1996. By 2001, nurse prescribing was extended to include more nurses and to cover a wider formulary. This research project provides an evaluation of the extension of prescribing powers to nurses in Scotland, following the introduction of legislation in 2001. It aimed to evaluate the impact of nurse prescribing powers on patients, nurses, prescribers, and other stakeholders. A range of methods were used, including two public surveys, stakeholder interviews, postal questionnaires and case studies. The benefits of extended nurse prescribing include: improved patient access to treatment; enhanced patient care; enabled more effective use of medical staff time and greater professional satisfaction for nurses who used nursing skills; and built inter-professional working. Some obstacles existed, including organisational, institutional and resource factors that restricted the overall success of the extension of nurse prescribing. There are high levels of agreement between patients, the public, nurse prescribers, physicians and other health professionals about the benefits of nurse prescribing to patients. The extension of nurse prescribing has been largely successful, with some organisational and procedural areas that could be addressed. PMID:23772448
Mirabzadeh, Arash; Bakhshi, Enayatollah; Khodae, Mohamad Reza; Kooshesh, Mohamad Reza; Mahabadi, Bibi Riahi; Mirabzadeh, Hossein; Biglarian, Akbar
Background: Antipsychotic monotherapy or polypharmacy (concurrent use of two or more antipsychotics) are used for treating patients with psychiatric disorders (PDs). Usually, antipsychotic monotherapy has a lower cost than polypharmacy. This study aimed to predict the cost of antipsychotic medications (AM) of psychiatric patients in Iran. Materials and Methods: For this purpose, 790 patients with PDs who were discharged between June and September 2010 were selected from Razi Psychiatric Hospital, Tehran, Iran. For cost prediction of AM of PD, neural network (NN) and multiple linear regression (MLR) models were used. Analysis of data was performed with R 2.15.1 software. Results: Mean ± standard deviation (SD) of the duration of hospitalization (days) in patients who were on monotherapy and polypharmacy was 31.19 ± 15.55 and 36.69 ± 15.93, respectively (P < 0.001). Mean and median costs of medication for monotherapy (n = 507) were $8.25 and $6.23 and for polypharmacy (n =192) were $13.30 and $9.48, respectively (P = 0.001). The important variables for cost prediction of AM were duration of hospitalization, type of treatment, and type of psychiatric ward in the MLR model, and duration of hospitalization, type of diagnosed disorder, type of treatment, age, Chlorpromazine dosage, and duration of disorder in the NN model. Conclusion: Our findings showed that the artificial NN (ANN) model can be used as a flexible model for cost prediction of AM. PMID:24381622
Malekshahi, Tara; Tioleco, Nina; Ahmed, Nahima; Campbell, Aimee N C; Haller, Deborah
Non-medical use of atypical antipsychotics by substance abusers has been reported in the literature, although no detailed studies exist. Among 429 addiction treatment inpatients screened, 73 (17.0%) reported misuse of antipsychotics with alcohol, opioids, cocaine, methamphetamine and/or cannabis; 39 (9.1%) within the past year. Of past year misusers, 25 (64.1%) were interviewed. Most were male (76.0%), non-Caucasian (56.0%), and polysubstance abusers (84.0%). Quetiapine, the most abused drug (96.0%), was obtained primarily from doctors (52.0%) and family/friends (48.0%). Reasons for use included to "recover" from other substances (66.7%), "enhance" the effects of other substances (25.0%), and "experiment" (20.8%). The most frequently reported positive effect was "feeling mellow" (75.0%); negative effects were consistent with antipsychotic use (e.g., feeling thirsty, trouble concentrating). Compared to a normative sample of inpatient substance abusers, ASI composite scores were higher. Findings suggest that physicians should assess for use/misuse of atypical antipsychotics among patients with addiction. PMID:25216812
Luchins, Daniel J.; And Others
Records covering a five-year period of adults with mental retardation in a residential program were reviewed to determine differences in antipsychotic dosages over time. Findings suggest that individuals with mental retardation who do not have psychoses are a suitable group for dosage reduction and that use of alternative medications facilitates…
Danov, Stacy E.; Tervo, Raymond; Meyers, Stephanie; Symons, Frank J.
The atypical antipsychotic medication aripiprazole was evaluated using a randomized AB multiple baseline, double-blind, placebo-controlled design for the treatment of severe problem behavior with 4 children with intellectual and developmental disabilities. Functional analysis (FA) was conducted concurrent with the medication evaluation to…
Canfrán-Duque, Alberto; Casado, María E.; Pastor, Óscar; Sánchez-Wandelmer, Jana; de la Peña, Gema; Lerma, Milagros; Mariscal, Paloma; Bracher, Franz; Lasunción, Miguel A.; Busto, Rebeca
Haloperidol, a typical antipsychotic, has been shown to inhibit cholesterol biosynthesis by affecting ?7-reductase, ?8,7-isomerase, and ?14-reductase activities, which results in the accumulation of different sterol intermediates. In the present work, we investigated the effects of atypical or second-generation antipsychotics (SGA), such as clozapine, risperidone, and ziprasidone, on intracellular lipid metabolism in different cell lines. All the SGAs tested inhibited cholesterol biosynthesis. Ziprasidone and risperidone had the same targets as haloperidol at inhibiting cholesterol biosynthesis, although with different relative activities (ziprasidone > haloperidol > risperidone). In contrast, clozapine mainly affected ?24-reductase and ?8,7-isomerase activities. These amphiphilic drugs also interfered with the LDL-derived cholesterol egress from the endosome/lysosome compartment, thus further reducing the cholesterol content in the endoplasmic reticulum. This triggered a homeostatic response with the stimulation of sterol regulatory element-binding protein (SREBP)-regulated gene expression. Treatment with SGAs also increased the synthesis of complex lipids (phospholipids and triacylglycerides). Once the antipsychotics were removed from the medium, a rebound in the cholesterol biosynthesis rate was detected, and the complex-lipid synthesis further increased. In this condition, apolipoprotein B secretion was also stimulated as demonstrated in HepG2 cells. These effects of SGAs on lipid homeostasis may be relevant in the metabolic side effects of antipsychotics, especially hypertriglyceridemia. PMID:23175778
Haloperidol is a butyrophenone antipsychotic drug used for the treatment of human hyperactive and manic disorders, agitation, and schizophrenia. The drug is thought to act through antagonism of dopaminergic receptors. We have studied a variety of endocrine-disrupting chemicals wi...
Kim, Sangwon F.
Atypical antipsychotics and the neural regulation of food intake and peripheral metabolism Karen L with weight gain and an increased incidence of metabolic disease including type 2 diabetes mellitus, cause the most dramatic weight gain and metabolic impairments including increased fasting glucose
Ruedrich, S. L.; Swales, T. P.; Rossvanes, C.; Diana, L.; Arkadiev, V.; Lim, K.
Objective: Atypical antipsychotic medications have largely supplanted their typical counterparts, both for psychosis and for the treatment of aggression and/or self-injurious behaviour (SIB), in persons with intellectual disabilities (ID). However, with the exception of risperidone, little systematic research supports their use in such persons.…
Kempton, Matthew J; Mehta, Mitul A
Social cognition, including emotion processing, is a recognised deficit observed in patients with schizophrenia. It is one cognitive domain which has been emphasised as requiring further investigation, with the efficacy of antipsychotic treatment on this deficit remaining unclear. Nine studies met our criteria for entry into a meta-analysis of the effects of medication on facial affect processing, including data from 1162 patients and six antipsychotics. Overall we found a small, positive effect (Hedge’s g = 0.13, 95% CI 0.05 to 0.21, p = 0.002). In a subgroup analysis this was statistically significant for atypical, but not typical, antipsychotics. It should be noted that the pooled sample size of the typical subgroup was significantly lower than the atypical. Meta-regression analyses revealed that age, gender and changes in symptom severity were not moderating factors. For the small, positive effect on facial affect processing, the clinical significance is questionable in terms of treating deficits in emotion identification in schizophrenia. We show that antipsychotic medications are poor at improving facial affect processing compared to reducing symptoms. This highlights the need for further investigation into the neuropharmacological mechanisms associated with accurate emotion processing, to inform treatment options for these deficits in schizophrenia. PMID:25492885
in schizophrenia remains poorly understood at both the cognitive and neurobio- logical levels. Thus, a centralLearning and Generalization in Schizophrenia: Effects of Disease and Antipsychotic Drug Treatment Background: Schizophrenia involves alterations in hippocampal function. The implications of these alterations
Tatara, Ayaka; Shimizu, Saki; Shin, Noriyuki; Sato, Maho; Sugiuchi, Tomone; Imaki, Junta; Ohno, Yukihiro
Antipsychotic drugs are widely used not only for schizophrenia, but also for mood disorders such as bipolar disorder and depression. To evaluate the interactions between antipsychotics and drugs for mood disorders in modulating extrapyramidal side effects (EPS), we examined the effects of antidepressants and mood-stabilizing drugs on haloperidol (HAL)-induced bradykinesia and catalepsy in mice and rats. The selective serotonin reuptake inhibitors (SSRIs), fluoxetine and paroxetine, and the tricyclic antidepressant (TCA) clomipramine, which showed no EPS by themselves, significantly potentiated HAL-induced bradykinesia and catalepsy in a dose-dependent manner. In contrast, the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine failed to augment, but rather attenuated HAL-induced bradykinesia and catalepsy. Mianserin also tended to reduce the EPS induction. In addition, neither treatment with lithium, sodium valproate nor carbamazepine potentiated HAL-induced EPS. Furthermore, treatment of animals with ritanserin (5-HT2A/2C antagonist), ondansetron (5-HT3 antagonist), and SB-258585 (5-HT6 antagonist) significantly antagonized the EPS augmentation by fluoxetine. Intrastriatal injection of ritanserin or SB-258585, but not ondansetron, also attenuated the EPS induction. The present study suggests that NaSSAs are superior to SSRIs or TCAs in combined therapy for mood disorders with antipsychotics in terms of EPS induction. In addition, 5-HT2A/2C, 5-HT3 and 5-HT6 receptors seem to be responsible for the augmentation of antipsychotic-induced EPS by serotonin reuptake inhibitors. PMID:22542492
Fernandez-Egea, Emilio; Bernardo, Miguel; Heaphy, Christopher M.; Griffith, Jeffrey K.; Parellada, Eduard; Esmatjes, Enric; Conget, Ignacio; Nguyen, Linh; George, Varghese; Stöppler, Hubert; Kirkpatrick, Brian
Introduction: Recent studies suggest that in addition to factors such as treatment side effects, suicide, and poor health habits, people with schizophrenia may have an increased risk of diabetes prior to antipsychotic treatment. Diabetes is associated with an increased pulse pressure (PP) and a shortened telomere. We tested the hypothesis that prior to antipsychotic treatment, schizophrenia and related disorders are associated with a shortened telomere, as well as an increased PP. Methods: Telomere content (which is highly correlated with telomere length) and PP were measured in newly diagnosed, antipsychotic-naive patients with schizophrenia and related disorders on first clinical contact and in matched control subjects. Both groups were also administered an oral glucose tolerance test. Results: Compared with control subjects, the patients with psychosis had decreased telomere content and an increased PP. As previously reported, they also had increased glucose concentrations at 2 hours. These differences could not be attributed to differences in age, ethnicity, smoking, gender, body mass index, neighborhood of residence, socioeconomic status, aerobic conditioning, or an increased cortisol concentration in the psychotic subjects. Discussion: These results suggest that prior to antipsychotic use, nonaffective psychosis is associated with reduced telomere content and increased PP, indices that have been linked to an increased risk of diabetes and hypertension. PMID:19279086
Favor, David A; Powers, James J; White, Andrew D; Fitzgerald, Lawrence W; Groppi, Vincent; Serpa, Kevin A
A series of 6-alkoxyisoindolin-1-ones with a magic shotgun pharmacological profile are presented as potential antipsychotics. The in vitro pharmacological profile includes D(2) partial agonism (30-55%), 5-HT(1A) partial agonism (60-90%), and 5-HT(2A) antagonism. Selected compounds in this series displayed good in vivo activity and potency. PMID:20801650
Shimizu, Saki; Mizuguchi, Yuto; Sobue, Akira; Fujiwara, Mai; Morimoto, Tomoki; Ohno, Yukihiro
Antipsychotics are often used in conjunction with anti-Alzheimer drugs to treat the behavioral and psychological symptoms of dementia (BPSD). Here, we examined the effects of cholinesterase inhibitors (ChEIs), donepezil and galantamine, on antipsychotic-induced extrapyramidal side effects (EPS) in mice. The effects of serotonergic agents on the EPS drug interaction were also evaluated. Donepezil (0.3-3 mg/kg) did not induce EPS signs by itself; however, it significantly potentiated bradykinesia induction with a low dose of haloperidol (0.5 mg/kg) in dose-dependent and synergistic manners. Galantamine (0.3-3 mg/kg) elicited mild bradykinesia at a high dose and dose-dependently augmented haloperidol-induced bradykinesia. The EPS potentiation by galantamine was blocked by trihexyphenidyl (a muscarinic antagonist), but not by mecamylamine (a nicotinic antagonist). In addition, the bradykinesia potentiation by galantamine was significantly reduced by (±)-8-hydroxy-2-(di-n-propylamino)-tetralin (a 5-HT1A agonist), ritanserin (a 5-HT2 antagonist), and SB-258585 (a 5-HT6 antagonist). The present results give us a caution for the antipsychotics and ChEIs interaction in inducing EPS in the treatment of BPSD. In addition, second generation antipsychotics, which can stimulate 5-HT1A receptors or antagonize 5-HT2 and 5-HT6 receptors, seem to be favorable as an adjunctive therapy for BPSD. PMID:25850380
Keiko Ohoyama; Satoshi Yamamura; Tatsuya Hamaguchi; Masanori Nakagawa; Eishi Motomura; Takashi Shiroyama; Hisashi Tanii; Motohiro Okada
To clarify the mechanisms of action of blonanserin, an atypical antipsychotic drug, we studied the effects of systemic administration of blonanserin and risperidone on extracellular levels of norepinephrine, dopamine, serotonin, GABA and glutamate in the medial prefrontal cortex using microdialysis, and neuronal firing in the ventral tegmental area, locus coeruleus, dorsal raphe nucleus and mediodorsal thalamic nucleus using radiotelemetry. The
Ke, Yonggang; Ong, Luvena L.; Sun, Wei; Song, Jie; Dong, Mingdong; Shih, William M.; Yin, Peng
We describe a general framework for constructing two-dimensional crystals with prescribed depth and sophisticated three-dimensional features. These crystals may serve as scaffolds for the precise spatial arrangements of functional materials for diverse applications. The crystals are self-assembled from single-stranded DNA components called DNA bricks. We demonstrate the experimental construction of DNA brick crystals that can grow to micron-size in the lateral dimensions with precisely controlled depth up to 80 nanometers. They can be designed to display user-specified sophisticated three-dimensional nanoscale features, such as continuous or discontinuous cavities and channels, and to pack DNA helices at parallel and perpendicular angles relative to the plane of the crystals. PMID:25343605
Dang, Ruili; Jiang, Pei; Cai, Hualin; Li, Huande; Guo, Ren; Wu, Yanqin; Zhang, Lihong; Zhu, Wenye; He, Xin; Liu, Yiping; Xu, Ping
Metabolic syndrome is a major concern in psychotic patients receiving atypical antipsychotics. Recent evidence suggests that sterol regulatory element-binding proteins (SREBPs) and insulin-induced genes (INSIGs) are implicated in the antipsychotic-induced metabolic side-effects. Vitamin D (VD) deficiency, a highly prevalent phenomenon among patients with psychosis, might also predispose individuals to metabolic syndrome Considering that VD has modulating effects on the INSIG/SREBP pathway, it is possible that VD may have a role in the antipsychotic-induced metabolic disturbances involving its effects on the INSIG/SREBP system. Thus, the present study aimed to evaluate the effects of VD deficiency and VD supplementation on antipsychotic-induced metabolic changes in rats. After 4-week administration, clozapine (10mg/kg/d) and risperidone (1mg/kg/d) both caused glucose intolerance and insulin resistance in VD deficient rats, but not in rats with sufficient VD status. Antipsychotic treatments, especially clozapine, elevated serum lipid levels, which were most apparent in VD deficient rats, but alleviated in VD-supplemented rats. Additionally, antipsychotic treatments down-regulated INSIGs and up-regulated SREBPs expression in VD deficient rats, and these effects were attenuated when VD status was more sufficient. Collectively, this study disclose the novel findings that antipsychotic-induced metabolic disturbances is exacerbated by VD deficiency and can be alleviated by VD supplementation, providing new evidence for the promising role of VD in prevention and treatment of metabolic disorders caused by antipsychotic medications. Furthermore, our data also suggest the involvement of INSIG/SREBP pathway in the antipsychotic-induced hyperlipidemia and beneficial effects of VD on lipid profile. PMID:26003080
Randell, Michael D; Duffy, Phillip J
Complications resulting from the use of compounded medications have become a troubling trend nationwide. There is a significant potential for patients to suffer serious harm from the use of substandard medications prepared by compounding pharmacies, and the reality of this problem has been demonstrated in several well-publicized incidences of serious medical complications, including patient deaths, that directly resulted from the use of medications prepared at compounding pharmacies. Unlike US Food and Drug Administration (FDA)-approved drugs, compounded products are not required to meet evidentiary standards for establishing safety and efficacy. Moreover, these products are not held to Good Manufacturing Practices, which require regular inspections, quality control testing, and rejection of material not meeting specifications. Physicians, as well as other prescribers, need to be aware that when a patient suffers harm from using a compounded medication, those injured patients may bring negligence and malpractice claims, not only against the pharmacy and the pharmacist responsible for preparing the medication, but also against the prescribing physician and the physician’s practice. Consequently, the best way for physicians to manage professional risk and avoid both litigation and potential negative patient outcomes related to compounded pharmaceuticals is to not use these products if there is an FDA-approved product available. However, if the use of a compounded medication is medically necessary, then physicians should adhere to the FDA guidance concerning traditional compounding. Moreover, it would be prudent for any physician who intends to either resell or participate in the distribution of compounded products beyond the direct treatment of their patients to consider obtaining the appropriate insurance coverage for this activity. PMID:25276868
Context: Drug-drug interactions(DDIs) are significant but avoidable causes of iatrogenic morbidity and hospital admission. Aim: To detect potential drug-drug interactions among medications received by hypertensive patients. Materials and Methods: Patients of both sex and all adult age groups, who were attending medicine out -patient department (OPD) of a tertiary care teaching rural hospital since last six months and were being prescribed antihypertensive drug/s for essential hypertension, were selected for the study. Hypertensive patient with co-morbities diabetes mellitus, ischemic heart diseases, congestive heart failure, and chronic renal diseases were also included in the study. Potential drug drug interactions were checked with medscape drug interaction software. Results: With the help of medscape drug interaction software, 71.50% prescriptions were identified having atleast one drug-drug interaction. Total 918 DDIs were found in between 58 drug pairs. 55.23% DDIs were pharmacodynamic, 4.79% pharmacokinetic type of DDIs. 32.24% DDIs were found affecting serum potassium level. 95.42% DDIs were found significant type of DDIs. Drug drug interaction between atenolol & amlodipine was the most common DDI (136) followed by metoprolol and amlodine (88) in this study. Atenolol and amlodipine ( 25.92%) was the most common drugs to cause DDIs in our study. Conclusion: We detected a significant number of drug drug interaction in hypertensive patients. These interactions were between antihypertensive agents or between hypertensive and drug for co-morbid condition. PMID:25584241
Riordan, Henry J.; Antonini, Paola; Murphy, Michael F.
Background Metabolic syndrome is a leading cause of morbidity and mortality in patients with schizophrenia, with a prevalence rate double that of nonpsychiatric populations. Given the amount of evidence suggesting a link between atypical antipsychotic medications and metabolic syndrome, several agencies have recommended regular clinical monitoring of weight, symptoms of hyperglycemia, and glucose in chronically medicated patients with schizophrenia. Objectives To summarize the current literature on atypical antipsychotic-induced metabolic syndrome in patients with schizophrenia, outline some of the molecular mechanisms behind this syndrome, identify demographic and disease-related risk factors, and describe cost-effective methods for surveillance. Discussion The differential prevalence of metabolic syndrome associated with various atypical antipsychotic medications has been evidenced across numerous studies, with higher effects seen for certain antipsychotic medications on weight gain, waist circumference, fasting triglyceride level, and glucose levels. Given the association of these symptoms, all atypical antipsychotic medications currently include a warning about the risk of hyperglycemia and diabetes, as well as suggestions for regular monitoring. Despite this, very little data are available to support adherence to these monitoring recommendations. Lack of awareness and resources, diffusion of responsibility, policy implementation, and organizational structure have all been implicated. Conclusion The treatment of schizophrenia involves a balance in terms of risks and benefits. Failing to treat because of risk for complications from metabolic syndrome may place the patient at a higher risk for more serious health outcomes. Supporting programs aimed at increasing monitoring of simple laboratory and clinical measures associated with metabolic syndrome may decrease important risk factors, improve patients' quality of life, and reduce healthcare costs. PMID:25126357
Anderson, Paul M; Pinault, Didier; O'Brien, Terence J; Jones, Nigel C
Noncompetitive N-methyl-d-aspartate receptor (NMDAr) antagonists can elicit many of the symptoms observed in schizophrenia in healthy humans, and induce a behavioural phenotype in animals relevant to psychosis. These compounds also elevate the power and synchrony of gamma (?) frequency (30-80 Hz) neural oscillations. Acute doses of antipsychotic medications have been shown to reduce ongoing ? power and to inhibit NMDAr antagonist-mediated psychosis-like behaviour in rodents. This study aimed to investigate how a chronic antipsychotic dosing regimen affects ongoing cortical ? oscillations, and the electrophysiological and behavioural responses induced by the NMDAr antagonist ketamine. Male Wistar rats were chronically treated with haloperidol (0.25 mg/kg/d), clozapine (5 mg/kg/d), LY379268 (0.3 mg/kg/d) or vehicle for 28 d, delivered by subcutaneous (s.c.) osmotic pumps. Weekly electrocorticogram (ECoG) recordings were acquired. On day 26, ketamine (5 mg/kg, s.c.) was administered, and ECoG and locomotor activity were simultaneously measured. These results were compared with data generated previously following acute treatment with these antipsychotics. Sustained and significant decreases in ongoing ? power were observed during chronic administration of haloperidol (64%) or clozapine (43%), but not of LY379268 (2% increase), compared with vehicle. Acute ketamine injection concurrently increased ? power and locomotor activity in vehicle-treated rats, and these effects were attenuated in rats chronically treated with all three antipsychotics. The ability of haloperidol or clozapine to inhibit ketamine-induced elevation in ? power was not observed following acute administration of these drugs. These results indicate that modulation of ? power may be a useful biomarker of chronic antipsychotic efficacy. PMID:24964190
Linck, Viviane M; Ganzella, Marcelo; Herrmann, Ana P; Okunji, Christopher O; Souza, Diogo O; Antonelli, Marta C; Elisabetsky, Elaine
Alstonine is the major component of plant based remedies that traditional psychiatrists use in Nigeria. Alstonine is an indole alkaloid that has an antipsychotic experimental profile comparable with that of clozapine and is compatible with the alleged effects in mental patients. Representing a desirable innovation in the pharmacodynamics of antipsychotic medications, the evidence indicates that alstonine does not bind to D2 dopamine receptors (D2R) and differentially regulates dopamine in the cortical and limbic areas. The purpose of this study was to further investigate the effects of alstonine on D2R binding in specific brain regions using quantitative autoradiography (QAR) and its effects on dopamine (DA) uptake in mouse striatal synaptosomes. The effects of alstonine on D2R binding were determined in the nucleus accumbens and caudate-putamen using QAR in mice treated with alstonine doses that have antipsychotic effects. The effects of alstonine [3H]DA uptake were assessed in synaptosomes prepared from striatal tissue obtained from mice treated acutely or for 7 days with alstonine. Alstonine did not change the D2R binding densities in the studied regions. DA uptake was increased after acute (but not after 7 days) treatment with alstonine. Consistent with the alstonine behavioral profile, these results indicate that alstonine indirectly modulates DA receptors, specifically by modulating DA uptake. This unique mechanism for DA transmission modulation contributes to the antipsychotic-like effects of alstonine and is compatible with its behavioral profile in mice and alleged effects in patients. These results may represent an innovation in the antipsychotic development field. PMID:25636871
Pacher, Pal; Kecskemeti, Valeria
The cardiovascular toxicity of older generation of tricyclic antidepressants (e.g. imipramine, desipramine, amitriptyline, clomipramine) and neuroleptics (e.g. haloperidol, droperidol, thioridazine, pimozide) is well established. These drugs inhibit cardiovascular Na(+), Ca(2+) and K(+) channels often leading to life-threatening arrhythmia. To overcome the toxicity of old generation of antidepressants and antipsychotics, selective serotonin reuptake inhibitor antidepressants (SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, venlafaxin) and several new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) were introduced during the past decade. Although these new compounds are not more effective in treating psychiatric disorders than older medications, they gained incredible popularity since they have been reported to have fewer and more benign side effect profile (including cardiovascular) than predecessors. Surprisingly, an increasing number of case reports have demonstrated that the use of SSRIs and new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) is associated with cases of arrhythmias, prolonged QTc interval on electrocardiogram (ECG) and orthostatic hypotension in patients lacking cardiovascular disorders, raising new concerns about the putative cardiovascular safety of these compounds. In agreement with these clinical reports these new compounds indeed show marked cardiovascular depressant effects in different mammalian and human cardiovascular preparations by inhibiting cardiac and vascular Na(+), Ca(2+) and K(+) channels. Taken together, these results suggest that the new generation of antidepressants and antipsychotics also have clinically important cardiac as well as vascular effects. Clinicians should be more vigilant about these potential adverse reactions and ECG control may be suggested during therapy, especially in patients with cardiovascular disorders. The primary goal of this review is to shed light on the recently observed clinically important cardiovascular effects of new antidepressants and antipsychotics and discuss the mechanism beyond this phenomenon. PMID:15320756
Pacher, Pal; Kecskemeti, Valeria
The cardiovascular toxicity of older generation of tricyclic antidepressants (e.g. imipramine, desipramine, amitriptyline, clomipramine) and neuroleptics (e.g. haloperidol, droperidol, thioridazine, pimozide) is well established. These drugs inhibit cardiovascular Na+, Ca2+ and K+ channels often leading to life-threatening arrhythmia. To overcome the toxicity of old generation of antidepressants and antipsychotics, selective serotonin reuptake inhibitor antidepressants (SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, venlafaxin) and several new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) were introduced during the past decade. Although these new compounds are not more effective in treating psychiatric disorders than older medications, they gained incredible popularity since they have been reported to have fewer and more benign side effect profile (including cardiovascular) than predecessors. Surprisingly, an increasing number of case reports have demonstrated that the use of SSRIs and new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) is associated with cases of arrhythmias, prolonged QTc interval on electrocardiogram (ECG) and orthostatic hypotension in patients lacking cardiovascular disorders, raising new concerns about the putative cardiovascular safety of these compounds. In agreement with these clinical reports these new compounds indeed show marked cardiovascular depressant effects in different mammalian and human cardiovascular preparations by inhibiting cardiac and vascular Na+, Ca2+ and K+ channels. Taken together, these results suggest that the new generation of antidepressants and antipsychotics also have clinically important cardiac as well as vascular effects. Clinicians should be more vigilant about these potential adverse reactions and ECG control may be suggested during therapy, especially in patients with cardiovascular disorders. The primary goal of this review is to shed light on the recently observed clinically important cardiovascular effects of new antidepressants and antipsychotics and discuss the mechanism beyond this phenomenon. PMID:15320756
, generator matrix of C Â· dual distance d= minimum distance of C . Â p.5/22 #12;Coding Theory Search for code C with prescribed: . Â p.6/22 #12;Coding Theory Search for code C with prescribed: Â· field size q . Â p.6/22 #12;Coding Theory Search for code C with prescribed: Â· field size q Â· length n . Â p.6/22 #12
Objective To describe, explore, and compare organisational routines for repeat prescribing in general practice to identify contributors and barriers to safety and quality. Design Ethnographic case study. Setting Four urban UK general practices with diverse organisational characteristics using electronic patient records that supported semi-automation of repeat prescribing. Participants 395 hours of ethnographic observation of staff (25 doctors, 16 nurses, 4 healthcare assistants, 6 managers, and 56 reception or administrative staff), and 28 documents and other artefacts relating to repeat prescribing locally and nationally. Main outcome measures Potential threats to patient safety and characteristics of good practice. Methods Observation of how doctors, receptionists, and other administrative staff contributed to, and collaborated on, the repeat prescribing routine. Analysis included mapping prescribing routines, building a rich description of organisational practices, and drawing these together through narrative synthesis. This was informed by a sociological model of how organisational routines shape and are shaped by information and communications technologies. Results Repeat prescribing was a complex, technology-supported social practice requiring collaboration between clinical and administrative staff, with important implications for patient safety. More than half of requests for repeat prescriptions were classed as “exceptions” by receptionists (most commonly because the drug, dose, or timing differed from what was on the electronic repeat list). They managed these exceptions by making situated judgments that enabled them (sometimes but not always) to bridge the gap between the idealised assumptions about tasks, roles, and interactions that were built into the electronic patient record and formal protocols, and the actual repeat prescribing routine as it played out in practice. This work was creative and demanded both explicit and tacit knowledge. Clinicians were often unaware of this input and it did not feature in policy documents or previous research. Yet it was sometimes critical to getting the job done and contributed in subtle ways to safeguarding patients. Conclusion Receptionists and administrative staff make important “hidden” contributions to quality and safety in repeat prescribing in general practice, regarding themselves accountable to patients for these contributions. Studying technology-supported work routines that seem mundane, standardised, and automated, but which in reality require a high degree of local tailoring and judgment from frontline staff, opens up a new agenda for the study of patient safety. PMID:22053317
To determine the medication prescribing patterns in hospitalized patients with chronic kidney disease (CKD) in a Malaysian hospital, we prospectively studied a cohort of 600 patients in two phases with 300 patients in each phase. The first phase was carried out from the beginning of February to the end of May 2007, and the second phase was from the beginning of March to the end of June 2008. Patients with CKD who had an estimated creatinine clearance ? 50 mL/min and were older than 18 years were included. A data collection form was used to collect data from the patients' medical records and chart review. All systemic medications prescribed during hospitalization were included. The patients were prescribed 5795 medications. During the first phase, the patients were prescribed 2814 medication orders of 176 different medications. The prescriptions were 2981 of 158 medications during the second phase. The mean number of medications in the first and second phases was 9.38 ± 3.63 and 9.94 ± 3.78 respectively (P-value = 0.066). The top five used medications were calcium carbonate, folic acid/vitamin B complex, metoprolol, lovastatin, and ferrous sulfate. The most commonly used medication classes were mineral supplements, vitamins, antianemic preparations, antibacterials, and beta-blocking agents. This study provides an overview of prescription practice in a cohort of hospitalized CKD patients and indicates possible areas of improvement in prescription practice. PMID:22382249
Sun, Xiaoyun; Jackson, Sukhan; Carmichael, Gordon A; Sleigh, Adrian C
In 2003, China introduced a new community-based rural health insurance called the New Cooperative Medical Scheme (NCMS). In 2005, to assess the NCMS effects on village doctors' prescribing behaviour, we compared an NCMS county and a non-NCMS county in Shandong Province. We collected information from a representative total of 2271 patient visits in 30 village health stations (15 per county). The average number of drugs prescribed (4.6 in the NCMS county vs. 3.1 in the non-NCMS county) and use of antibiotics (72.4% vs. 59.3%) and injections (65.1% vs. 56.3%) were high in both counties, and higher in the NCMS county. Within NCMS villages, prescribing for insured vs. uninsured patients showed a similar pattern with more drugs, antibiotics and injections for those insured. Overall, for NCMS patients, the prescription excess was about equal in value to their 20% fee discount. We conclude that over-prescribing is common in villages and worse with NCMS health insurance, raising concerns for health service quality and drug-use safety. We propose that the NCMS should be redesigned with incentives for service quality improvement. A stricter regulatory environment for doctors' prescriptions is needed in rural China to counter irrational drug use. PMID:19342138
Nguyen, Ha T.; Grzywacz, Joseph G.; Quandt, Sara A.; Neiberg, Rebecca H.; Lang, Wei; Altizer, Kathryn; Stoller, Eleanor P.; Bell, Ronny A.; Arcury, Thomas A.
Objectives To examine the association of cognitive function with use of non-prescribed therapies for managing acute and chronic conditions, and to determine whether use of non-prescribed therapies changes over time in relation to baseline cognitive function. Methods 200 community-dwelling adults aged 65 and older were recruited from three counties in south central North Carolina. Repeated measures of daily symptoms and treatment were collected on three consecutive days at intervals of at least one month. The Mini-Mental State Examination (MMSE), the primary cognitive measure, was collected as part of the baseline survey. Data were collected on the daily use of common non-prescribed therapies (use of prayer, ignore symptoms, over-the-counter remedies, food and beverage therapies, home remedies, and vitamin, herb, or supplements) on each of the three days of the follow-up interviews for up to six consecutive months. Results Older adults with poorer cognitive function were more likely to pray and ignore symptoms on days that they experienced acute symptoms. Poorer cognitive function was associated with increased use of home remedies for treating symptoms related to existing chronic conditions. Conclusions Cognitive function may play a role in why older patients use some non-prescribed therapies in response to acute and chronic conditions. PMID:22304694
Barnett, Erin R; Bernardy, Nancy C; Jenkyn, Aaron B; Parker, Louise E; Lund, Brian C; Alexander, Bruce; Friedman, Matthew J
Evidence-based psychotherapies (EBP) for Posttraumatic Stress Disorder are not utilized to their full extent within the Department of Veterans Affairs (VA). VA provides care to many persons with PTSD and has been in the forefront of clinical practice guidelines and EBP training and dissemination. Yet VA continues to find EBP implementation difficult. Veterans with PTSD often initially present to prescribing clinicians, who then help make care decisions. It is therefore critical that these clinicians correctly screen and triage appropriate mental health care. The purpose of this study was to assess VA prescribing clinicians' knowledge, perceptions, and referral behaviors related to EBPs for PTSD and to identify facilitators and barriers to implementing EBPs within VA. We conducted qualitative interviews with 26 VA prescribing clinicians. Limited access to EBPs was the most commonly noted barrier. The clinicians we interviewed also held specific beliefs and behaviors that may delay or deter EBPs. Strategies to improve utilization also emerged. Findings suggest the need for increased access to EBPs, training to optimize the role of prescribing clinicians in helping Veterans with PTSD make appropriate care decisions, and specific organizational changes to facilitate access and effective referral systems for EBPs. PMID:25431445
Barnett, Erin R.; Bernardy, Nancy C.; Jenkyn, Aaron B.; Parker, Louise E.; Lund, Brian C.; Alexander, Bruce; Friedman, Matthew J.
Evidence-based psychotherapies (EBP) for Posttraumatic Stress Disorder are not utilized to their full extent within the Department of Veterans Affairs (VA). VA provides care to many persons with PTSD and has been in the forefront of clinical practice guidelines and EBP training and dissemination. Yet VA continues to find EBP implementation difficult. Veterans with PTSD often initially present to prescribing clinicians, who then help make care decisions. It is therefore critical that these clinicians correctly screen and triage appropriate mental health care. The purpose of this study was to assess VA prescribing clinicians’ knowledge, perceptions, and referral behaviors related to EBPs for PTSD and to identify facilitators and barriers to implementing EBPs within VA. We conducted qualitative interviews with 26 VA prescribing clinicians. Limited access to EBPs was the most commonly noted barrier. The clinicians we interviewed also held specific beliefs and behaviors that may delay or deter EBPs. Strategies to improve utilization also emerged. Findings suggest the need for increased access to EBPs, training to optimize the role of prescribing clinicians in helping Veterans with PTSD make appropriate care decisions, and specific organizational changes to facilitate access and effective referral systems for EBPs. PMID:25431445
Anderson, L.S.; Athay, R.G. (Ritter Observatory, Toledo, OH (USA) High Altitude Observatory, Boulder, CO (USA))
Computed model solar chromospheres for prescribed departures from radiative equilibrium are specified in terms of the local mechanical (nonradiative) heat input. The computations are fully non-LTE and include millions of spectral lines. From the variety of models considered, the requirements on the heat input for a positive temperature gradient, dT/dh, in different layers of the chromosphere are discussed. The derived radiative cooling function for different models show that the cooling function is model-dependent. By comparing the computed models with the Vernazza, Avrett, and Loeser (1981) models, it is shown that the VAL-C model is characterized by a total heat flux 1.4 x 10 to the 7th ergs/sq cm/per sec, most of which is dissipated near the base of the temperature plateau. Half of the radiation loss is provided by Fe II, with Ca II, Mg II, and H playing important, but secondary, roles. CO molecules and H(-) are of lesser importance even near the temperature minimum, except in cases of minimal heating. 15 refs.
Anderson, Lawrence S.; Athay, R. Grant
Computed model solar chromospheres for prescribed departures from radiative equilibrium are specified in terms of the local mechanical (nonradiative) heat input. The computations are fully non-LTE and include millions of spectral lines. From the variety of models considered, the requirements on the heat input for a positive temperature gradient, dT/dh, in different layers of the chromosphere are discussed. The derived radiative cooling function for different models show that the cooling function is model-dependent. By comparing the computed models with the Vernazza, Avrett, and Loeser (1981) models, it is shown that the VAL-C model is characterized by a total heat flux 1.4 x 10 to the 7th ergs/sq cm/per sec, most of which is dissipated near the base of the temperature plateau. Half of the radiation loss is provided by Fe II, with Ca II, Mg II, and H playing important, but secondary, roles. CO molecules and H(-) are of lesser importance even near the temperature minimum, except in cases of minimal heating.
Robinson, M. S.; Anthony, T. R.; Littau, S. R.; Herckes, P.; Nelson, X.; Poplin, G. S.; Burgess, J. L.
Wildland firefighters are exposed to particulate matter and gases containing polycyclic aromatic hydrocarbons (PAHs), many of which are known carcinogens. Our objective was to evaluate the extent of firefighter exposure to particulate and PAHs during prescribed pile burns of mainly ponderosa pine slash and determine whether these exposures were correlated with changes in urinary 1-hydroxypyrene (1-HP), a PAH metabolite. Personal and area sampling for particulate and PAH exposures were conducted on the White Mountain Apache Tribe reservation, working with 21 Bureau of Indian Affairs/Fort Apache Agency wildland firefighters during the fall of 2006. Urine samples were collected pre- and post-exposure and pulmonary function was measured. Personal PAH exposures were detectable for only 3 of 16 PAHs analyzed: naphthalene, phenanthrene, and fluorene, all of which were identified only in vapor-phase samples. Condensed-phase PAHs were detected in PM2.5 area samples (20 of 21 PAHs analyzed were detected, all but naphthalene) at concentrations below 1 ?g m?3. The total PAH/PM2.5 mass fractions were roughly a factor of two higher during smoldering (1.06 ± 0.15) than ignition (0.55 ± 0.04 ?g mg?1). There were no significant changes in urinary 1-HP or pulmonary function following exposure to pile burning. In summary, PAH exposures were low in pile burns, and urinary testing for a PAH metabolite failed to show a significant difference between baseline and post-exposure measurements. PMID:18515848
Wang, Kai; Liu, Sheng; Chen, Fei; Qin, Zong; Liu, Zongyuan; Luo, Xiaobing
Freeform lenses are playing a more and more important role in LED secondary optics design. In this study, based on the new light energy mapping relationship, edge ray principle, Snell's law and error control of surface construction, a modified discontinuous freeform lens design method was presented for rectangularly prescribed illumination, with the advantages of a flexible energy mapping relationship, accurate light irradiation control and easier to manufacture. A polymethyl methacrylate (PMMA) discontinuous freeform lens was designed as an example for LED tunnel illumination according to this method. The numerical simulation results demonstrated that the light pattern of the lens was in good agreement with the expected illumination performance when using a point source. Tolerance analyses were also conducted. An extended light source had little effect on the light output efficiency (LOE) of the lens but significantly decreased the effective illumination area. Installation errors had more effect on the uniformity and shape of the light pattern than the LOE of the lens. The tolerances of vertical, horizontal and rotational deviation of this lens were 0.4 mm, 0.4 mm and 2°, respectively.
Whitmire, Alexandra; Johnston, Smith; Lockley, Steven
The NASA Fatigue Management Team is developing recommendations for managing fatigue during travel and for shift work operations, as Clinical Practice Guidelines for the Management of Circadian Desynchrony in ISS Operations. The Guidelines provide the International Space Station (ISS ) flight surgeons and other operational clinicians with evidence-based recommendations for mitigating fatigue and other factors related to sleep loss and circadian desynchronization. As much international travel is involved both before and after flight, the guidelines provide recommendations for: pre-flight training, in-flight operations, and post-flight rehabilitation. The objective of is to standardize the process by which care is provided to crewmembers, ground controllers, and other support personnel such as trainers, when overseas travel or schedule shifting is required. Proper scheduling of countermeasures - light, darkness, melatonin, diet, exercise, and medications - is the cornerstone for facilitating circadian adaptation, improving sleep, enhancing alertness, and optimizing performance. The Guidelines provide, among other things, prescribed travel schedules that outline the specific implementation of these mitigation strategies. Each travel schedule offers evidence based protocols for properly using the NASA identified countermeasures for fatigue. This presentation will describe the travel implementation schedules and how these can be used to alleviate the effects of jet lag and/or schedule shifts.
Sun, FangFang; Stock, Eileen M.; Copeland, Laurel A.; Zeber, John E.; Ahmedani, Brian K.; Morissette, Sandra B.
Purpose To investigate patterns in pharmacological treatment for patients with schizophrenia, we examined antipsychotic polypharmacy across multiple outpatient healthcare settings and their association with hospital admission. Methods This multi-system study utilized data on patients diagnosed with schizophrenia, including 119,662 Veterans in the Department of Veterans Affairs (VA) healthcare system, 553 and 4,887 patients in two private, integrated health systems (HMO), and outpatients (17,596,617 visits in 1-week look-back) from a nationally representative sample of U.S. residents seeking care outside federal systems (National Ambulatory Medical Care Survey, NAMCS). Antipsychotic polypharmacy was defined as the use of more than one antipsychotic agent during the covered period (week, year). The prevalence and trend of antipsychotic polypharmacy was assessed in each system (2002-2009 or 2005-2009) and their association with one-year hospital admission using multivariable logistic regression. Results Annual antipsychotic treatment in the VA ranged 74-78% each year, with the lowest rates observed in the HMO (49-67% site 1, 22-41% site 2) per pharmacy fill data; NAMCS ranged 69-84% per clinician-reported prescriptions. Polypharmacy rates depended on the defined covered period. The VA had lower polypharmacy rates when data were restricted to the one-week covered period used in non-federal systems (20-22% vs. 19-31% NAMCS). In each system, polypharmacy was associated with increased odds of admission (odds ratio ranging 1.4-2.4). Conclusions The unadjusted longitudinal trends suggest tremendous system variations in antipsychotic use among patients with schizophrenia. Cross-system comparisons are inherently subject to uncertainty due to variation in the amount and type of data collected. Given the current debate over healthcare access and costs, electronic systems to signal polypharmacy could assist in identifying patients requiring more complex clinical and pharmacy management, individuals at substantially higher risk for adverse events. Such enhanced sentinel detection and follow-up care could ultimately lead to improved clinical practice and fiscal well-being. PMID:24733136
be unsuccessful if the trade-off between adequate fire severity and mitigation of fire risk is too conservativeUSE OF PRESCRIBED FIRE IN ECOLOGICAL RESTORATION: LESSONS FROM CHITTENDEN MEADOW, SKAGIT VALLEY of Research Project: Use of Prescribed Fire in Ecological Restoration: Lessons from Chittenden Meadow, Skagit
Denig, P; Witteman, C; Schouten, H
Background: This study describes cognitive processes of doctors who are deciding on the treatment for a patient. This helps to uncover how prescribing decisions could benefit from (computerised) support. Methods: While thinking aloud, 61 general practitioners made prescribing decisions for five patients with urinary tract infections or stomach complaints. The resulting 305 transcripts were analysed to determine the scope and nature of the decision processes. Differences in the process were related to case or doctor characteristics, and to differences in the quality of prescribing behaviour. Results: The decision processes were not extensive, particularly for patients with a urinary tract infection. The doctors did not actively consider all possible relevant information. Considerations referring to core aspects of the treatment were made in 159 cases (52%) and to contextual aspects in 111 cases (36%). Habitual behaviour, defined as making a treatment decision without any specific contemplation, was observed in 118 cases (40%) and resulted in prescribing first choice as well as second choice drugs. For stomach complaints, second choice drugs were often prescribed after considering other treatments or in view of specific circumstances. Experience of the doctor was not related to the type of decision process. Conclusions: The processes observed deviate from the decision theoretic norm of thoroughly evaluating all possible options, but these deviations do not always result in suboptimal prescribing. Decision support is useful for bringing pertinent information and first choice treatments to the prescriber's attention. In particular, information about relevant contraindications, interactions, and costs could improve the quality of prescribing. PMID:12448805
Broglio, Kathleen; Cole, B Eliot
Millions of Americans have chronic pain for which chronic opioid therapy may be warranted. In light of recent abuse of these medications, clinicians must exercise caution and develop uniform approaches to prescribing. It is possible to assess for opioid risk and safely prescribe opioids. PMID:24784857
This report summarizes reported data on air emissions from prescribed burning, which is defined as the skillful application of fire in forest and range management under conditions that will confine the fire to a predetermined area and accomplish certain planned benefits. Prescrib...
Sweileh, Waleed M.; Odeh, Jihad Bani; Shraim, Naser Y.; Zyoud, Sa’ed H.; Sawalha, Ansam F.; Al-Jabi, Samah W.
Objective The present study was carried out to investigate and compare the three methods for calculating total antipsychotic dose among outpatients with schizophrenia attending primary psychiatric health care centers. The three methods were: Defined Daily Doses (DDDs), chlorpromazine equivalents (CPZeq) and percentages of the British National Formulary (BNF) maximum. Methodology Antipsychotic drug dosing data for 250 patients with schizophrenia were investigated by calculating Spearman’s rank correlation coefficients. Factors associated with antipsychotic dose, expressed as DDDs, CPZeq and percentages of the BNF maximum recommended daily dose, were investigated by means of linear regression analysis. Results Spearman’s correlation showed that there is a significant relationship between all pairs of the three dosing methods. In all three methods, coherence was strongest when dealing with first generation antipsychotics (FGA). Linear regression analyses showed a high degree of coherence between antipsychotic doses expressed as DDDs, CPZeq and percentages of the BNF maximum recommended daily dose. Conclusion All three tested methods are reliable and coherent for calculating antipsychotic dosing. PMID:24648824
Kato, Yutaka; Muramatsu, Taro; Kato, Motoichiro; Shibukawa, Yoshiyuki; Shintani, Masuro; Mimura, Masaru
Introduction Patients with schizophrenia commonly exhibit deficits of non-verbal communication in social contexts, which may be related to cognitive dysfunction that impairs recognition of biological motion. Although perception of biological motion is known to be mediated by the mirror neuron system, there have been few empirical studies of this system in patients with schizophrenia. Methods Using magnetoencephalography, we examined whether antipsychotic-free schizophrenia patients displayed mirror neuron system dysfunction during observation of biological motion (jaw movement of another individual). Results Compared with normal controls, the patients with schizophrenia had fewer components of both the waveform and equivalent current dipole, suggesting aberrant brain activity resulting from dysfunction of the right inferior parietal cortex. They also lacked the changes of alpha band and gamma band oscillation seen in normal controls, and had weaker phase-locking factors and gamma-synchronization predominantly in right parietal cortex. Conclusions Our findings demonstrate that untreated patients with schizophrenia exhibit aberrant mirror neuron system function based on the right inferior parietal cortex, which is characterized by dysfunction of gamma-synchronization in the right parietal lobe during observation of biological motion. PMID:22132217
Herrold, Amy A.; Pape, Theresa Louise-Bender; Guernon, Ann; Mallinson, Trudy; Collins, Eileen; Jordan, Neil
Background. Despite a lack of clear evidence, multiple neurostimulants are commonly provided after severe brain injury (BI). The purpose of this study is to determine if the number of neurostimulants received during rehabilitation was associated with recovery of full consciousness or improved neurobehavioral function after severe BI. Method. Data from 115 participants were extracted from a neurobehavioral observational study database for this exploratory, retrospective analysis. Univariate optimal data analysis was conducted to determine if the number of neurostimulants influenced classification of four outcomes: recovery of full consciousness during rehabilitation, recovery of full consciousness within one year of injury, and meaningful neurobehavioral improvement during rehabilitation defined as either at least a 4.7 unit (minimal detectable change) or 2.58 unit (minimal clinically important difference) gain on the Disorders of Consciousness Scale-25 (DOCS-25). Results. Number of neurostimulants was not significantly (P > 0.05) associated with recovery of full consciousness during rehabilitation, within one year of injury, or meaningful neurobehavioral improvement using the DOCS-25. Conclusions. Receiving multiple neurostimulants during rehabilitation may not influence recovery of full consciousness or meaningful neurobehavioral improvement. Given costs associated with additional medication, future research is needed to guide physicians about the merits of prescribing multiple neurostimulants during rehabilitation after severe BI. PMID:25587576
Kumbar, Shivaprasad Kalakappa
Background: Prescription is document through which doctor, patient and pharmacist are communicated. Many a times if these documents are not properly written or misinterpreted it can affect management of patients. WHO established prescribing indicators to analyse prescription and promoted rational use of drugs and better management of patients. Aim: To study the prescription pattern according to WHO prescribing indicators among private hospitals. Settings and Design: The observational, prospective study carried out at different private hospitals at metro city in Western India to study the prescription pattern among private hospital. Materials and Methods: Study was conducted at different private hospitals of metro city. A total of 250 prescriptions of outdoor patients from various departments of private hospitals were collected for a period of three months (August to October) 2012 and evaluated. Statistical analysis: The study was analysed using Z-test. Results: Patient details like age and gender was not written in all (100%) prescriptions. It was noticed that dose, direction of drug and duration of treatment was not completely written in 90%, 74% and 80% of prescriptions respectively. Abbreviations were used in all (100%) prescriptions. Doctor’s medical registration number was mentioned in 0% prescriptions. Total 869 drugs were prescribed in 250 prescriptions. Average number of drug prescribed was 3.38±1.79 (Mean±SD). It was reported that Group II (3 to 4 encoutner) was significantly higher as compared to Group I (less than or equal to 2 encoutner) and Group III( more than four encounter). It was significantly (p<0.05) prescribed brand name prescriptions (93.33%) as compared to generic name prescriptions (6.7%). Percentage of encounter with antibiotics and injections was 54% and 18% respectively. Approximately 70% drugs were prescribed according to Essential Medicine List (EML) of State. Antibiotics accounted 30% of prescribed drugs which was significantly higher as compared to other group of prescribed drugs. Conclusion: Our study revealed that prescription errors were most commonly observed at private hospitals and antibiotics was commonly prescribed in private sector. Therefore, strict policy to good prescribing practice and strict antibiotic policy in outdoor patients are required to promote rational use of drugs. PMID:25954629
Green, Carla A; Janoff, Shannon L; Yarborough, Bobbi Jo H; Yarborough, Micah T
People taking antipsychotic medications are at increased risk for obesity, diabetes, and early mortality. Few weight loss interventions have targeted this population. Thirty-six individuals were randomized to an evidence-based 12-week weight loss intervention (PREMIER with DASH diet, n = 18) or to usual care (n = 18) in this feasibility trial. Average attendance was 8.6 of 12 sessions. Intent-to-treat analyses of covariance, adjusted for baseline weight, showed significant changes in weight: Mean weight in intervention participants declined from 213.3 to 206.6 pounds, while control participants' weight was unchanged. It is possible to recruit, assess, intervene with, and retain participants taking antipsychotic medications in a dietary and exercise lifestyle change trial. Participants reported high levels of satisfaction with the intervention. PMID:24566560
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Titier, Karine; Girodet, Pierre-Olivier; Verdoux, Hélène; Molimard, Mathieu; Bégaud, Bernard; Haverkamp, Wilhelm; Lader, Malcolm; Moore, Nicholas
Syncope and sudden death are features of schizophrenia that can be attributed to ischaemic heart disease, the use of antipsychotics (because of proarrhythmia or other reasons such as pharyngeal dyskinesia) or the psychiatric disease itself. Cases have been described with most antipsychotics and have led to the withdrawal, temporary suspension from the market or restricted use of antipsychotics, such as sultopride, droperidol, sertindole or thioridazine. Reviewing the available data shows that all antipsychotics tested affect the cardiac potassium channel, with the concentration that produces 50% inhibition (IC50) ranging from 1 nmol/L (haloperidol) to 6 micromol/L (olanzapine). Experimental in vitro or in vivo electrophysiological studies have shown a dose-dependent increase in the duration of the action potential with various degrees of indicators of serious arrhythmogenicity. However, this does not always translate clinically into an increased duration of the QT interval or increased risk of torsade de pointes or sudden death in clinical trials or pharmacoepidemiological studies. In turn, QT prolongation in clinical trials does not always translate to an increased risk of torsade de pointes or sudden death. The reasons for these apparent discrepancies are unclear and could be related to insufficiently powered field studies, low plasma and tissue drug concentrations with reference to in vitro data or drug effects on other receptors or ion channels that have a protective effect. Alternatively, risks that were not apparent from preclinical or clinical data could be related to the use of the drug in high-risk patients, metabolic interactions or other factors that would only be encountered in large postmarketing populations. The assessment of cardiovascular safety, both preclinical and during premarketing clinical trials, needs to be supported by appropriately powered pharmacoepidemiology studies. PMID:15649104
Caccia, Silvio; Invernizzi, Roberto William; Nobili, Alessandro; Pasina, Luca
Cariprazine is a potential antipsychotic awaiting approval from the US Food and Drug Administration. It is a dopamine D2- and D3-receptor partial agonist, with higher affinity for D3 receptors, as opposed to the D2 antagonism of most older antipsychotic agents. Like most lipophilic antipsychotics, it undergoes extensive hepatic metabolism by cytochrome P450 (CYP), mainly the highly variable 3A4, with the formation of active metabolites. However, the parent compound – particularly its active didesmethyl derivative – is cleared very slowly, with elimination half-lives in schizophrenic patients ranging from 2–5 days for cariprazine to 2–3 weeks for didesmethyl-cariprazine. Exposure to the latter was several times that for cariprazine, although didesmethyl-cariprazine did not reach steady state within the 3 weeks of 12.5 mg/day dosing. Preliminary information on its therapeutic role comes from press releases and a few abstracts presented at scientific meetings. In short-term controlled trials, it was more effective than placebo in reducing positive and negative symptoms of schizophrenia, with an effective dose range of 1.5–12 mg/day. Although cariprazine was associated with a higher incidence of akathisia and extrapyramidal side effects than placebo, it did not cause weight gain, metabolic abnormalities, prolactin increase, or corrected QT prolongation. Similarly, cariprazine’s efficacy and tolerability for the treatment of bipolar disorder (manic/mixed and depressive episodes) was established in the dose range of 3–12 mg/day, although again no long-term data are available. Well-designed clinical trials, mainly direct “head-to-head” comparisons with other second-generation antipsychotic agents, are needed to define the therapeutic role and safety profile of cariprazine in schizophrenia and bipolar mania. PMID:23966785
Gahr, Maximilian; Kölle, Markus A; Schönfeldt-Lecuona, Carlos; Lepping, Peter; Freudenmann, Roland W
Paliperidone (9-hydroxy-risperidone), the active metabolite of risperidone, was approved for treating schizophrenia worldwide in 2006 as paliperidone extended-release (PER), and became the first second-generation antipsychotic specifically licensed for treating schizoaffective disorder in 2009. However, at the same time, its comparatively high cost gave rise to concerns about the cost-effectiveness of PER as compared with its precursor, risperidone. This paper reviews the existing knowledge of the pharmacology, kinetics, efficacy, tolerability, and fields of application of PER, and compares PER with risperidone in order to determine whether it has a place in antipsychotic therapy. An independent assessment of all relevant publications on PER published until July 2010 was undertaken. PER has a unique pharmacological profile, including single dosing, predominantly renal excretion, low drug–drug interaction risk, and differs from risperidone in terms of mode of action and pharmacokinetics. High-level evidence suggests that PER is efficacious and safe in schizophrenia, schizoaffective disorder, and acute manic episodes. There is a striking lack of published head-to-head comparisons between PER and risperidone, irrespective of indication. Low-level evidence shows a lower risk for hyperprolactinemia and higher patient satisfaction with PER than with risperidone. PER adds to the still limited arsenal of second-generation antipsychotics. In the absence of direct comparisons with risperidone, it remains difficult to come to a final verdict on the potential additional therapeutic benefits of PER which would justify its substantially higher costs as compared with risperidone. However, in terms of pharmacology, the available evidence cautiously suggests a place for PER in modern antipsychotic therapy. PMID:21448450
Shin, Hyewon; Song, Jin-Ho
Microglial dysfunction and neuroinflammation are thought to contribute to the pathogenesis of schizophrenia. Some antipsychotic drugs have anti-inflammatory activity and can reduce the secretion of pro-inflammatory cytokines and reactive oxygen species from activated microglial cells. Voltage-gated proton channels on the microglial cells participate in the generation of reactive oxygen species and neuronal toxicity by supporting NADPH oxidase activity. In the present study, we examined the effects of two typical antipsychotics, chlorpromazine and haloperidol, on proton currents in microglial BV2 cells using the whole-cell patch clamp method. Chlorpromazine and haloperidol potently inhibited proton currents with IC50 values of 2.2 ?M and 8.4 ?M, respectively. Chlorpromazine and haloperidol are weak bases that can increase the intracellular pH, whereby they reduce the proton gradient and affect channel gating. Although the drugs caused a marginal positive shift of the activation voltage, they did not change the reversal potential. This suggested that proton current inhibition was not due to an alteration of the intracellular pH. Chlorpromazine and haloperidol are strong blockers of dopamine receptors. While dopamine itself did not affect proton currents, it also did not alter proton current inhibition by the two antipsychotics, indicating dopamine receptors are not likely to mediate the proton current inhibition. Given that proton channels are important for the production of reactive oxygen species and possibly pro-inflammatory cytokines, the anti-inflammatory and antipsychotic activities of chlorpromazine and haloperidol may be partly derived from their ability to inhibit microglial proton currents. PMID:24990667
Barbui, Corrado; Signoretti, Alessandra; Mulè, Serena; Boso, Marianna; Cipriani, Andrea
In patients with schizophrenia who do not have an optimal response to clozapine, it remains unclear if there is an evidence base to support a second antipsychotic in combination with clozapine. The present systematic review was therefore carried out to determine the efficacy of various clozapine combination strategies with antipsychotics. Relevant studies were located by searching the Cochrane Schizophrenia Group Trials Register, Medline, and Embase (up to November 2007). Only studies randomly allocating patients to clozapine plus another antipsychotic vs clozapine monotherapy were included. The search yielded 21 studies suitable for reanalysis. In 3 trials, clozapine was combined with a phenothiazine, in 8 trials with a benzamide, and in the remaining trials with risperidone. While the majority of randomized trials were not double blind, 6 studies were double-blind placebo-controlled trials. A total of 14 randomized open studies significantly favored clozapine combination strategy in terms of mean difference (random effect standardized mean difference [SMD] = ?0.80, 95% confidence interval [CI] = ?1.14 to ?0.46); however, data extracted from 6 randomized double-blind studies did not show a statistically significant positive effect of this combination strategy in terms of mean difference (SMD = ?0.12, 95% CI = ?0.57 to 0.32). In terms of percentage of patients failing to show an improvement, a total of 10 randomized open studies significantly favored clozapine combination strategy (random effect relative risk [RR] = 0.64, 95% CI = 0.42 to 0.97), but data extracted from 6 randomized double-blind studies did not show a statistically significant positive effect of this combination strategy (RR = 0.91, 95% CI = 0.75 to 1.11). We conclude that the evidence base supporting a second antipsychotic in addition to clozapine in partially responsive patients with schizophrenia is weak. This weak evidence indicates modest to absent benefit. PMID:18436527
Benedetto Vitiello; Christoph Correll; Barbara van Zwieten-Boot; Alessandro Zuddas; Mara Parellada; Celso Arango
Second-generation antipsychotics (SGA) are increasingly used to treat children and adolescents. The European College of Neuro-psychopharmacology convened an expert panel to review relevant efficacy and safety data, and identify needs for further research. Controlled studies support the short-term efficacy of several SGA for treating psychosis, mania, and aggression within certain diagnostic categories. Except for clozapine, no clinically significant superiority in
Marsha E Stockton; Kurt Rasmussen
This study examined the effects of the novel atypical antipsychotic olanzapine (LY170053) on the activity of substantia nigra pars compacta (A9) and ventral tegmental area (A10) dopamine cells in anesthetized rats. Acute administration of olanzapine (10, 20 mg\\/kg sc) increased the number of spontaneously active A10, but not A9, dopamine cells. Chronic administration of olanzapine (10, 20 mg\\/kg\\/day × 21
Hideki Hattori; Masae Iwai; Tadashi Ogawa; Yoko Mizutani; Akira Ishii; Osamu Suzuki; Hiroshi Seno
Blonanserin is a novel antipsychotic agent having dopamine D2 and serotonin 5-HT2A receptor antagonist properties. In this communication, a simple method for analysis of blonanserin in human plasma by gas\\u000a chromatography-mass spectrometry (GC-MS) using hexobarbital as internal standard (IS) is presented. One milliliter of plasma\\u000a containing blonanserin and 50 ng of IS was mixed well with 0.5 ml of 0.1
S. Takahashi; K. Sonehara; K. Takagi; T. Miwa; K. Horikomi; N. Mita; H. Nagase; K. Iizuka; K. Sakai
Rationale: MS-377 ((R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]methyl-2-pyrrolidinone l-tartrate) was discovered as a new chemical entity with affinity for ? receptors and without affinities for dopamine receptors. Objective: In the present study, we examined the antipsychotic profile of MS-377 in several in vitro and in vivo experiments. Methods: As in vitro assays, radioligand binding assays for ?1, ?2, D2 and 5-HT2 receptors were performed. As
Nowak, D A; Connemann, B J; Alan, M; Spitzer, M
Background Antipsychotic treatment in schizophrenia is frequently associated with extrapyramidal side effects. Objective behavioural measures to evaluate the severity of extrapyramidal side effects in the clinical setting do not exist. Objectives This study was designed to investigate grasping movements in five drug naive and 13 medicated subjects with schizophrenia and to compare their performance with that of 18 healthy control subjects. Deficits of grip force performance were correlated with clinical scores of both parkinson?like motor disability and psychiatric symptom severity Methods Participants performed vertical arm movements with a handheld instrumented object and caught a weight that was dropped into a handheld cup either expectedly from the opposite hand or unexpectedly from the experimenter's hand. The scaling of grip force and the temporospatial coupling between grip and load force profiles was analysed. The psychiatric symptom severity was assessed by the positive and negative symptom score of schizophrenia and the brief psychiatric rating scale. Extrapyramidal symptoms were assessed by the unified Parkinson's disease rating scale. Results Drug naive subjects with schizophrenia performed similar to healthy controls. In contrast, medicated subjects with schizophrenia exhibited excessive grip force scaling and impaired coupling between grip and load force profiles. These performance deficits were strongly correlated with the severity of both extrapyramidal side effects related to antipsychotic therapy and negative symptoms related to the underlying pathology. Conclusions These data provide preliminary evidence that deficits of sensorimotor performance in schizophrenia are, at least in part, related to the side effects of antipsychotic treatment. The investigation of grasping movements may provide a sensitive measure to objectively evaluate extrapyramidal side effects related to antipsychotic therapy. PMID:16614027
A. Schotte; P. F. M. Janssen; W. Gommeren; W. H. M. L. Luyten; P. Gompel; A. S. Lesage; K. Loore; J. E. Leysen
Risperidone and its active metabolite 9-OH-risperidone were compared to reference antipsychotic drugs (haloperidol, pipamperone, fluspirilene, clozapine, zotepine) and compounds under development (olanzapine, seroquel, sertindole, ORG-5222, ziprasidone) for in vitro binding to neurotransmitter receptors in brain tissue and on membranes of recombinant cells expressing cloned human receptors and for in vivo occupancy of neurotransmitter receptors in rat and guinea-pig brain following
Tuplin, Erin W; Stocco, Marlaina R; Holahan, Matthew R
The noncompetitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5-10-imine maleate (MK-801) has been shown to increase the probability of operant responding during extinction and reduce infralimbic prefrontal cortical activation, possibly modeling the cognitive dysfunction symptomology, and underlying cause, in patients with schizophrenia. The present study sought to determine if typical and/or atypical antipsychotics would attenuate the MK-801-induced behavioral perseveration and whether this would be associated with concomitant changes in phosphorylated ERK1/2 (pERK1/2) labeling in the infralimbic cortex (IL). Male, Long Evans rats were pretreated with the typical antipsychotic, Flupenthixol (0, 0.125, 0.25 or 0.5 mg/kg) or the atypical antipsychotic, aripiprazole (0, 0.3, 1.0, 3.0 mg/kg), then given 0.1 mg/kg MK-801 followed by a 60-min appetitive operant extinction session. Flupenthixol produced a dose-dependent decrease in MK-801-induced bar pressing behavior and locomotor activity and a dose-dependent increase in IL pERK1/2 labeling. Aripiprazole produced a U-shaped dose-response curve on MK-801-induced bar pressing behavior, a dose-dependent decrease in locomotor activity but no changes in IL pERK1/2 labeling. The attenuation of the MK-801-induced behavioral (bar pressing, locomotion) profile by Flupenthixol indicates a clear dopaminergic contribution to this behavior. The behavioral effect of aripiprazole may be due to its a) binding to presynaptic dopamine receptors at the midrange dose decreasing dopamine output and b) binding to postsynaptic dopamine receptors at the higher dose increasing dopamine tone. While both classes of antipsychotics can normalize perseverative behavioral symptoms, the underlying prefrontal cortical dysregulation seems to persist. (PsycINFO Database Record PMID:26052791
Russell, R.E.; Royle, J.A.; Saab, V.A.; Lehmkuhl, J.F.; Block, W.M.; Sauer, J.R.
Prescribed fire is a management tool used to reduce fuel loads on public lands in forested areas in the western United States. Identifying the impacts of prescribed fire on bird communities in ponderosa pine (Pinus ponderosa) forests is necessary for providing land management agencies with information regarding the effects of fuel reduction on sensitive, threatened, and migratory bird species. Recent developments in occupancy modeling have established a framework for quantifying the impacts of management practices on wildlife community dynamics. We describe a Bayesian hierarchical model of multi-species occupancy accounting for detection probability, and we demonstrate the model's usefulness for identifying effects of habitat disturbances on wildlife communities. Advantages to using the model include the ability to estimate the effects of environmental impacts on rare or elusive species, the intuitive nature of the modeling, the incorporation of detection probability, the estimation of parameter uncertainty, the flexibility of the model to suit a variety of experimental designs, and the composite estimate of the response that applies to the collection of observed species as opposed to merely a small subset of common species. Our modeling of the impacts of prescribed fire on avian communities in a ponderosa pine forest in Washington indicate that prescribed fire treatments result in increased occupancy rates for several bark-insectivore, cavity-nesting species including a management species of interest, Black-backed Woodpeckers (Picoides arcticus). Three aerial insectivore species, and the ground insectivore, American Robin (Turdus migratorius), also responded positively to prescribed fire, whereas three foliage insectivores and two seed specialists, Clark's Nutcracker (Nucifraga columbiana) and the Pine Siskin (Carduelis pinus), declined following treatments. Land management agencies interested in determining the effects of habitat manipulations on wildlife communities can use these methods to provide guidance for future management activities. ?? 2009 by the Ecological Society of America.
Russell, Robin E; Royle, J Andrew; Saab, Victoria A; Lehmkuhl, John F; Block, William M; Sauer, John R
Prescribed fire is a management tool used to reduce fuel loads on public lands in forested areas in the western United States. Identifying the impacts of prescribed fire on bird communities in ponderosa pine (Pinus ponderosa) forests is necessary for providing land management agencies with information regarding the effects of fuel reduction on sensitive, threatened, and migratory bird species. Recent developments in occupancy modeling have established a framework for quantifying the impacts of management practices on wildlife community dynamics. We describe a Bayesian hierarchical model of multi-species occupancy accounting for detection probability, and we demonstrate the model's usefulness for identifying effects of habitat disturbances on wildlife communities. Advantages to using the model include the ability to estimate the effects of environmental impacts on rare or elusive species, the intuitive nature of the modeling, the incorporation of detection probability, the estimation of parameter uncertainty, the flexibility of the model to suit a variety of experimental designs, and the composite estimate of the response that applies to the collection of observed species as opposed to merely a small subset of common species. Our modeling of the impacts of prescribed fire on avian communities in a ponderosa pine forest in Washington indicate that prescribed fire treatments result in increased occupancy rates for several bark-insectivore, cavity-nesting species including a management species of interest, Black-backed Woodpeckers (Picoides arcticus). Three aerial insectivore species, and the ground insectivore, American Robin (Turdus migratorius), also responded positively to prescribed fire, whereas three foliage insectivores and two seed specialists, Clark's Nutcracker (Nucifraga columbiana) and the Pine Siskin (Carduelis pinus), declined following treatments. Land management agencies interested in determining the effects of habitat manipulations on wildlife communities can use these methods to provide guidance for future management activities. PMID:19688932
Koponen, Marjaana; Taipale, Heidi; Tanskanen, Antti; Tolppanen, Anna-Maija; Tiihonen, Jari; Ahonen, Riitta; Hartikainen, Sirpa
Antipsychotics are recommended only for short-term treatment of severe behavioral and psychological symptoms of dementia. Our objective was to study the duration of antipsychotic use and factors associated with long-term use (365 days or over) among community-dwelling persons with Alzheimer?s disease (AD) during a 7-year follow-up. This was a nationwide register-based cohort study including all community-dwelling residents in Finland diagnosed with AD in 2005 (n=7217). The follow-up for antipsychotic use started 3 years before the diagnosis of AD and we applied a 7-year washout period to ascertain truly incident antipsychotic use. Follow-up ended on institutionalization, death or at the end of study period (December 31, 2009). Duration of antipsychotic use was modeled from individual purchase histories recorded in the Finnish Prescription Register. During the 7-year follow-up, 34% (2287/6740) of persons initiated antipsychotic use. Median duration of the first antipsychotic use period was 219 (interquartile range 85-583) days. Of those who discontinued antipsychotic use (n=1303), 44% restarted use later. Among users with at least one year of follow-up time after initiating antipsychotic use, prevalence of long-term use was 57% (893/1563). Long-term use was associated with initiation of use after AD diagnosis and choice of antipsychotic. Duration of use was more likely to be shorter among haloperidol users and longer among quetiapine users compared with risperidone users. In conclusion, long-term use of antipsychotics is frequent among community-dwelling persons with AD. Duration of use is not in line with the guidelines recommending time-limited use of antipsychotics. PMID:26233607
Schneider, Carolina; Taylor, David; Zalsman, Gil; Frangou, Sophia; Kyriakopoulos, Marinos
Antipsychotic medications (APs) are a well-established pharmacological treatment in adults with serious mental health problems. However, many adult mental health disorders have their origins and onset in childhood or adolescence. The understanding that neuropsychiatric conditions of childhood are in part biologically determined, led to an increase in the number of clinical trials supporting evidence on the efficacy of antipsychotic agents as first-line treatment for childhood psychotic disorders and therapeutic augmentation of nonpsychotic conditions. In recent years the use of antipsychotics in children and adolescents for neurodevelopmental, behavioural and psychiatric disorders has significantly increased while the age of prescription has decreased. These trends have not been matched by advances in the understanding of APs' safety profile in this group of patients. It is therefore crucial that current and future practice is informed by up-to-date synthesis of the evidence and clinical guidelines about the use and monitoring of these treatments in paediatric populations, since the effectiveness of early therapeutic interventions in children can affect positively the long-term outcome. PMID:24902872
Cuerda, C; Velasco, C; Merchán-Naranjo, J; García-Peris, P; Arango, C
Second-generation antipsychotics (SGA) are associated with weight gain and metabolic alterations including hyperglycemia, dyslipidemia, hypertension and metabolic syndrome. These metabolic side effects increase cardiovascular risk and are related to medication non-compliance. Patients without previous exposure to these or other antipsychotic drugs (naive patients) seem to be more prone to develop these metabolic abnormalities. The mechanisms behind weight gain can be an increase in food intake and/or a decrease in energy expenditure. This review comprehensively examines the current knowledge on the impact of these drugs on food intake and energy expenditure. The influence of these drugs on appetite and food intake (total caloric intake and food sources) is reviewed as well as the evidence of abnormal eating behaviors. The studies evaluating the effect on resting energy expenditure are critically examined, taking into account the influence of body composition and previous exposure to antipsychotics (naive vs non-naive patients). Finally, the influence of these drugs on physical activity is also discussed. The knowledge of the mechanisms of weight gain in patients starting these drugs may be useful to further prompt research in this field and ameliorate the metabolic side effects associated with these treatments. PMID:24327118
Shen, Winston W.; Pae, Chi-Un; Moreno, Raquel; Rubio, Gabriel; Molina, Juan D.; Noriega, Concha; Pérez-Nieto, Miguel A.; Huelves, Lorena; Álamo, Cecilio
Objective We have carried out a bibliometric study on the scientific publications in relation to atypical or second-generation antipsychotic drugs (SGAs) in South Korea. Methods With the EMBASE and MEDLINE databases, we selected those publications made in South Korea whose title included the descriptors atypic* (atypical*) antipsychotic*, second-generation antipsychotic*, clozapine, risperidone, olanzapine, ziprasidone, quetiapine, sertindole, aripiprazole, paliperidone, amisulpride, zotepine, asenapine, iloperidone, lurasidone, perospirone and blonanserin. We applied some bibliometric indicators of paper production and dispersion with Price's law and Bradford's law, respectively. We also calculated the participation index (PI) of the different countries, and correlated the bibliometric data with some social and health data from Korea (such as total per capita expenditure on health and gross domestic expenditure on research and development). Results We collected 326 original papers published between 1993 and 2011. Our results state fulfilment of fulfilled Price's law, with scientific production on SGAs showing exponential growth (correlation coefficient r=0.8978, as against an r=0.8149 after linear adjustment). The most widely studied drugs were risperidone (91 papers), aripiprazole (77), olanzapine (53), and clozapine (43). Division into Bradford zones yielded a nucleus occupied by the Progress in Neuro-Psychopharmacology and Biological Psychiatry (36 articles). A total of 86 different journals were published, with 4 of the first 10 used journals having an impact factor being greater than 4. Conclusion The publications on SGAs in South Korea have undergone exponential growth over the studied period, without evidence of reaching a saturation point. PMID:23482954
Knapp, M; Ilson, S; David, A
Depot treatment of schizophrenia - to date restricted to conventional antipsychotic medications - remains widespread. Whilst there have been numerous studies of clinical effectiveness, and systematic reviews of the accumulated evidence, little appears to be known about the cost-effectiveness of depot treatment. A systematic review was conducted of the international literature in an attempt to find, appraise and summarize the economic evaluative evidence. Very few studies of relevance or quality could be found. Most of the papers purporting to examine the economic consequences of depot treatment were methodologically weak. There were no randomized controlled trials of depot vs. oral antipsychotics, the few mirror-image studies were uncontrolled and a single naturalistic observational study measured costs only narrowly. Two modelling studies - which have a number of limitations because of their partial reliance on expert opinion rather than observational data - suggest that depot treatment may lower costs and improve cost-effectiveness. Overall, however, it is not possible to draw conclusions as to the cost-effectiveness of depot conventional antipsychotic treatment for schizophrenia. PMID:11981355
Farde, L.; Wiesel, F.A.; Halldin, C.; Sedvall, G.
Using positron emission tomography and the carbon 11-labeled ligand raclopride, central D2-dopamine receptor occupancy in the putamen was determined in psychiatric patients treated with clinical doses of psychoactive drugs. Receptor occupancy in drug-treated patients was defined as the percent reduction of specific carbon 11-raclopride binding in relation to the expected binding in the absence of drug treatment. Clinical treatment of schizophrenic patients with 11 chemically distinct antipsychotic drugs (including both classic and atypical neuroleptics such as clozapine) resulted in a 65% to 85% occupancy of D2-dopamine receptors. In a depressed patient treated with the tricyclic antidepressant nortriptyline, no occupancy was found. The time course for receptor occupancy and drug levels was followed after withdrawal of sulpiride or haloperidol. D2-dopamine receptor occupancy remained above 65% for many hours despite a substantial reduction of serum drug concentrations. In a sulpiride-treated patient, the dosage was reduced in four steps over a nine-week period and a curvilinear relationship was demonstrated between central D2-dopamine receptor occupancy and serum drug concentrations. The results demonstrate that clinical doses of all the currently used classes of antipsychotic drugs cause a substantial blockade of central D2-dopamine receptors in humans. This effect appears to be selective for the antipsychotics, since it was not induced by the antidepressant nortriptyline.
Balzan, Ryan P.; Galletly, Cherrie
Background: Psychotherapies for psychosis typically aim to develop an awareness of the implausible content of a delusion or target the underlying cognitive biases (i.e., problematic thinking styles, such as hasty decisions and illusory control) that foster and maintain delusional beliefs. A recently designed individual-based treatment entitled metacognitive therapy (MCT+) combines these two approaches. Emerging evidence suggests individualized MCT+, when used concurrently with antipsychotic medication, may be an effective psychological treatment for reducing delusional symptoms. However, it remains to be tested whether MCT+ can be effective in patients with active delusions who are not currently receiving psychotropic drugs. Method: We present two cases (one patient with schizophrenia and the other with delusional disorder) experiencing active delusions who underwent 4-weeks of intensive MCT+, without concurrent antipsychotic medication (minimum 6-months unmedicated). Baseline and 6-week follow-up data are presented on a variety of measures assessing delusion symptom severity (i.e., PANSS, PSYRATS, SAPS), clinical insight, and cognitive bias propensity. Results: After 4-weeks of MCT+, both patients showed substantial reduction in delusional symptoms, reported improved clinical insight, and were less prone to making illusory correlations. Conclusions: The presented case studies provide preliminary evidence for the feasibility of MCT+ in treating patients not taking, or resistant to, antipsychotic medication. PMID:26217283
Sendt, Kyra-Verena; Tracy, Derek Kenneth; Bhattacharyya, Sagnik
Adherence to antipsychotics improves outcome in schizophrenia. There is a lack of consensus on which factors most influence adherence behaviour and methodological issues hinder interpretation of existing evidence. A rigorous systematic search designed to identify robustly implicated factors emerging from methodologically rigorous studies narrowed our search to 13 observational studies (total N=6235) relating to adherence, antipsychotics and schizophrenia. Studies varied significantly, with reported adherence rates ranging from 47.2% to 95%. Positive attitude to medication and illness insight were the only factors consistently associated with better adherence, while contradictory results were found for socio-demographic characteristics, symptom severity and side effects. Only distinct aspects of the therapeutic relationship and social support in younger patients were related to good adherence. Antipsychotic type or formulation and neurocognitive functioning did not appear to impact medication adherence. Despite greater methodological rigour in determining studies to include in the present systematic review, it remains difficult to guide clinicians in this vital area and most of the work discussed contained small sample sizes. Future research in this field should therefore prioritise prospective study designs over longer periods and larger samples in naturalistic settings, providing a more appropriate and clinically meaningful framework than widely used cross-sectional designs. PMID:25466227
Erzengin, Mahmut; Bilen, Cigdem; Ergun, Adem; Gencer, Nahit
The antipsychotic drugs currently used to treat schizophrenia can be divided into two distinct classes, typical and atypical antipsychotics. Many drug molecules are enzyme inhibitors that bind reversibly or irreversibly to their target through intermolecular interactions. That's why enzyme inhibition studies are an important issue for drug design and biochemical applications. In this study, in vitro inhibition effect of some antipsychotic drugs on the purified carbonic anhydrase (CA) I and II isoenzymes were investigated by using CO2 as a substrate. CA I and II were purified from human erythrocytes by a simple one step procedure using Sepharose 4B-L-tyrosine-sulfonamide affinity column. The results showed that all the drugs inhibited the cytosolic carbonic anhydrases enzyme activity in a concentration-dependent fashion. Among the studied drugs, aripiprazole and pramipexole were found to be the most active one for hCA I (IC50: 3.64 and 5.37??M) and hCA II (IC50: 4.16 and 4.81??M) activity, respectively. PMID:24289818
When “antipsychotic” drugs were introduced into psychiatry in the 1950s, they were thought to work by inducing a state of neurological suppression, which reduced behavioral disturbance as well as psychotic symptoms. This view was reflected in the name “neuroleptic.” Within a few years, however, the idea that the drugs were a disease-specific treatment for schizophrenia or psychosis, and that they worked by modifying the underlying pathology of the condition, replaced this earlier view, and they became known as “antipsychotics.” This transformation of views about the drugs’ mode of action occurred with little debate or empirical evaluation in the psychiatric literature and obscured earlier evidence about the nature of these drugs. Drug advertisements in the British Journal of Psychiatry reflect the same changes, although the nondisease-specific view persisted for longer. It is suggested that professional interests rather than scientific merit facilitated the rise of the disease-specific view of drug action. The increasing popularity of atypical antipsychotics makes it important to examine the origins of the assumptions on which modern drug treatment is based. PMID:23323530
Larsson, Markus K; Schwieler, Lilly; Goiny, Michel; Erhardt, Sophie; Engberg, Göran
Schizophrenia is associated with activation of the brain immune system as reflected by increased brain levels of kynurenic acid (KYNA) and proinflammatory cytokines. Although antipsychotic drugs have been used for decades in the treatment of the disease, potential effects of these drugs on brain immune signaling are not fully known. The aim of the present study is to investigate the effects of chronic treatment with antipsychotic drugs on brain levels of cytokines and KYNA. Rats were treated daily by intraperitoneally administered haloperidol (1.5 mg/kg, n = 6), olanzapine (2 mg/kg, n = 6), and clozapine (20 mg/kg, n = 6) or saline (n = 6) for 30 days. Clozapine, but not haloperidol or olanzapine-treated rats displayed significantly lower cerebrospinal fluid (CSF) levels of interleukin-8 compared to controls. Whole brain levels of KYNA were not changed in any group. Our data suggest that the superior therapeutic effect of clozapine may be a result of its presently shown immunosuppressive action. Further, our data do not support the possibility that elevated brain KYNA found in patients with schizophrenia is a result of antipsychotic treatment.
Although the Common Core standards do not prescribe pedagogy or forbid playful learning, kindergarten teachers will find it challenging to maintain a playful classroom under this reform. Kindergarten teachers have to cover a more rigorous and accelerated curriculum now, and they are doing so in a context that rewards procedural teaching.
Goswami, Nimit; Gandhi, Anuradha; Patel, Prakruti; Dikshit, Ramkumar
Background: Fixed Dose Combinations (FDCs) improve patient compliance and decrease pill burden. However, irrational prescribing of FDCs is a major health concern. As resident doctors are primarily involved in patient management at tertiary care hospitals, knowledge about prescribing FDCs is of paramount importance. Objective: To evaluate knowledge, attitude and practice, regarding use of FDCs by resident doctors at a tertiary care teaching hospital. Materials and Methods: The study was carried out among resident doctors working at Civil Hospital, Ahmedabad, a tertiary care teaching hospital. One hundred resident doctors from the departments of medicine, obstetrics and gynaecology, surgery, paediatrics, skin and psychiatry, who gave their informed consent, were enrolled. A prevalidated questionnaire regarding knowledge, attitude and prescribing practice of fixed dose combinations was filled up. Data was analyzed with suitable statistical tests. Results: Out of the 100 residents recruited for the study, 34, 33 and 33 residents were selected from the 1st, 2nd and 3rd year respectively. The resident doctors were not aware about all of the advantages and disadvantages of FDCs. On an average, only 31% of the residents (lowest 16% among 1st year residents) had knowledge about the Essential Medicine List (EML). Knowledge about rationality of given FDCs was lacking in 81% of the residents. Only 47% could name a single banned FDC in India. Common sources of information about FDCs were medical representatives, colleagues/peers, the Monthly Index of Medical Specialities (MIMS) and Continuous Medical Education (CMEs). A majority of residents (96%) agreed that FDCs should be allowed to be marketed. The residents opined that most commonly prescribed FDCs were of antimicrobial drugs, amongst which amoxicillin + clavulanic acid was the most frequent. Conclusion: There is need to improve knowledge about rationality, EML, usage and banned FDCs in post graduate medical students to promote the rational use of drugs. PMID:23833738
Mollahaliloglu, Salih; Alkan, Ali; Donertas, Basak; Ozgulcu, Senay; Akici, Ahmet
In this study, it was aimed to investigate the utilization of antibiotics at various health care facilities. Photocopies of 1250 prescriptions which were containing antibiotics and written out in primary health care facilities (PHCFs), public hospitals (PHs), private hospitals and university hospitals in 10 provinces across Turkey, were evaluated by some drug use indicators. The number of drugs per prescription was 3.23 ± 0.92 and it was highest in PHCFs (3.34 ± 0.84), (p < 0.05). The cost per prescription was 33.3 $, being highest in PHs while being lowest in PHCFs (38.6 $ and 28.2 $ respectively). Antibiotic cost per prescription was 16.7 $ and it was also highest and lowest in PHs and PHCFs respectively (p < 0.05). The most commonly prescribed group of antibiotics was “beta-lactam antibacterials, penicillins” (29.2%) while amoxicillin/clavulanic acid was the most commonly prescribed antibiotic (18.1%). Sixty-one percent of the antibiotics prescribed for acute infections was generics; among facilities being highest in PHCFs (66.5%) and among diagnosis being highest in acute pharyngitis. In general, the duration of antibiotic therapy was approximately 7 days for acute infections. Although much more drugs were prescribed in PHCFs than others, it was found to be in an inverse proportion with both the total cost of prescriptions and the cost of antibiotics. Broad-spectrum antibiotics, beta-lactamase combinations in particular, were considered to be more preferable in all health care facilities is also notable. These results do serve as a guide to achieve the rational use of antibiotics on the basis of health care facilities and indications. PMID:23960845
Stevenson, David G.; O’Malley, A. James; Dusetzina, Stacie B.; Mitchell, Susan L.; Zarowitz, Barbara J.; Chernew, Michael E.; Newhouse, Joseph P.; Huskamp, Haiden A.
Objectives In 2006, Medicare Part D transitioned prescription drug coverage for dual-eligible nursing home residents from Medicaid to Medicare and randomly assigned them to Part D prescription drug plans (PDPs). Because PDPs may differ in coverage, residents’ assigned plans may be relatively more or less restrictive for drugs they take. Taking advantage of the fact that randomization mitigates potential selection bias common in observational studies, this study seeks to assess the impact of PDP coverageon resident outcomes for three medication classes – antidepressants, antipsychotics, and cholinesterase inhibitors. Design, Setting, Participants Using Medicare claims, Minimum Data Set assessments, pharmacy claims, and PDP formulary information, we estimate the impact of coverage restrictions – including non-coverage and coverage with restrictions – on the following outcomes for dual-eligible nursing home residents randomized to PDPs in 2006–2008: depression; hallucinations/delusions; aggressive behaviors; cognitive performance; and activities of daily living. We further adjust for baseline health status to address any residual imbalances in the comparison groups. Results Across 5 outcomes in each of three medication classes of interest, PDP coverage restrictions impacted one resident health outcome: for cholinesterase inhibitor users, coverage restrictions were associated with a 0.04 point lower depression rating score relative to residents facing no restrictions. However, this result was not statistically significant after adjusting for multiple comparisons. Conclusion Our findings suggest that exogenous changes in coverage for three commonly-used medication classes had no detectable impact on nursing home resident health outcomes in 2006–2008. There are several possible explanations for this lack of association, including the role of policy protections for dual-eligible nursing home residents and the possibility that suitable clinical alternatives were identified or previously used medications offered little clinical benefit. PMID:25123044
Part of a special section on the state of industrial minerals in 1997. The state of the common clay industry worldwide for 1997 is discussed. Sales of common clay in the U.S. increased from 26.2 Mt in 1996 to an estimated 26.5 Mt in 1997. The amount of common clay and shale used to produce structural clay products in 1997 was estimated at 13.8 Mt.
Gao, Keming; Yuan, Chengmei; Wu, Renrong; Chen, Jun; Wang, Zuowei; Fang, Yiru; Calabrese, Joseph R
English-language literature cited in MEDLINE from January, 1980 to October 30, 2014 was searched by using terms of antipsychotic, generic and brand names of atypical antipsychotics, "bipolar depression/bipolar disorder", "placebo", and "trial". The parameters of response (?50% improvement on MADRS, Montgomery-Asberg Depression Rating Scale total score), remission (either ?12 or 8 on MADRS total score at endpoint), discontinuation due to adverse events (DAEs), somnolence, ?7% weight gain, overall extrapyramidal side-effects (EPSs), and akathisia, were extracted from originally published primary outcome papers. The number needed to treat to benefit (NNT) for response and remission or harm (NNH) for DAEs or other side effects relative to placebo were estimated and presented with the estimate and 95% confidence interval. Olanzapine monotherapy, olanzapine-fluoxetine combination (OFC), quetiapine-IR monotherapy, quetiapine-XR monotherapy, lurasidone monotherapy, and lurasidone adjunctive therapy were superior to placebo with NNTs for responses of 11-12, 4, 7-8, 4, 4-5, and 7, and NNTs for remission of 11-12, 4, 5-11, 7, 6-7, and 6, respectively. There was no significant difference between OFC and lamotrigine, and between aripiprazole or ziprasidone and placebo in response and remission. Olanzapine monotherapy, quetiapine-IR, quetiapine-XR, aripiprazole, and ziprasidone 120-160 mg/day had significantly increased risk for DAEs with NNHs of 24, 8-14, 9, 12, and 10, respectively. For somnolence, quetiapine-XR had the smallest NNH of 4. For ?7% weight gain, olanzapine monotherapy and OFC had the smallest NNHs with both of 5. For akathisia, aripiprazole had the smallest NNH of 5. These findings suggest that among the FDA-approved agents including OFC, quetiapine-IR and -XR, lurasidone monotherapy and adjunctive therapy to a mood stabilizer, the differences in the NNTs for response and remission are small, but the differences in NNHs for DAEs and common side-effects are large. Therefore, the selection of an FDA-approved atypical antipsychotic for bipolar depression should be based upon safety and tolerability. PMID:26024955
Thurber’s needlegrass (Achnatherum thurberianum (Piper) Barkworth) is an important component of many sagebrush communities in the Intermountain West. Prescribed fall burning is often implemented in sagebrush plant communities to mimic historic wildfires, improve wildlife habitat, and increase lives...
Yahalom, Zohar; Shani, Segev
The regulation of pharmaceuticals is becoming more complex in recent years. Current regulation is no longer limited to deciding whether a specific drug would be allowed to be placed on the market. Today, a significant part of the regulatory process is focused on setting the terms for utilization of each drug, regarding the target population, dosages, mode of administration, etc. These terms have enormous implications on both pharmaceutical companies and caregivers. In Israel, the only publicly available source of information on terms of registration is the prescribing information ("physician leaflet"). The prescribing information contains instructions for use, as well as a Lot of safety information regarding the product. Therefore, the wording of the prescribing information may have serious regulatory and legal implications on caregivers. The objective of this article is to describe the relevant laws and regulations requiring its publication, while discussing the practical issues and implications of the use of prescribing information by physicians in Israel. PMID:25563030
Liu, Heng; Li, Sheng-Gang; Sun, Ye-Guo; Wang, Hong-Xing
In this paper the synchronization for two different fractional-order chaotic systems, capable of guaranteeing synchronization error with prescribed performance, is investigated by means of the fractional-order control method. By prescribed performance synchronization we mean that the synchronization error converges to zero asymptotically, with convergence rate being no less than a certain prescribed function. A fractional-order synchronization controller and an adaptive fractional-order synchronization controller, which can guarantee the prescribed performance of the synchronization error, are proposed for fractional-order chaotic systems with and without disturbances, respectively. Finally, our simulation studies verify and clarify the proposed method. Project supported by the National Natural Science Foundation of China (Grant Nos. 11401243 and 61403157), the Fundamental Research Funds for the Central Universities of China (Grant No. GK201504002), and the Natural Science Foundation for the Higher Education Institutions of Anhui Province of China (Grant No. KJ2015A256).
Choudhry, A J; Mubasher, M
Two hundred sixty-two randomly sampled general physicians of Lahore were interviewed to study the current practices and factors affecting the management of acute watery diarrhoea (AWD) in children below 5 years of age. Among the physicians, 19% prescribed ORS alone, 61% ORS with some drug, 15% drugs alone and 5% increased fluid intake only. Physicians in government sector, recent graduates and those trained in a paediatrics unit prescribed more on the WHO guidelines (p<0.05). Attending a diarrhoea training unit (DTU) course, reading WHO guidelines for management of diarrhoea and total number of patients seen daily had no significant effect on prescribing practices. Two hundred fifty-five (97%) physicians thought that majority of other physicians prescribed drugs for the management of acute watery diarrhoea to satisfy the mothers of the children, their belief in the effectiveness of drugs and competition in practice. PMID:9056735
...will stop paying the annuity. (c) Acceptable reasons for failure to follow prescribed treatment. The following are examples...4) The treatment because of its magnitude (e.g., open heart surgery), unusual nature (e.g., organ...
...will stop paying the annuity. (c) Acceptable reasons for failure to follow prescribed treatment. The following are examples...4) The treatment because of its magnitude (e.g., open heart surgery), unusual nature (e.g., organ...
Hasty, Michael; Schrager, Jason; Wrenn, Keith
The purpose of this study was to compare physicians' perceptions about managed care restrictions on drug prescribing with objective measures of the restrictions' effects. When asked a general question, 17 emergency medicine physicians in one urban, university hospital answered that they had to prescribe an antibiotic that was not their first choice because of managed care restrictions 32% of the time. The actual frequency of prescribing other than first-choice antibiotics, which was determined by asking the same physicians about the prescription of specific antibiotics for specific patients seen recently in the emergency department, was 6% (p < .0001). We conclude that emercency medicine physicians treating patients in one managed care system significantly overstimated the restrictions imposed by managed care formularies on their antibiotic prescribing practices. Additional studies are warranted to measure the extent of this bias. PMID:10632821
...will stop paying the annuity. (c) Acceptable reasons for failure to follow prescribed treatment. The following are examples...4) The treatment because of its magnitude (e.g., open heart surgery), unusual nature (e.g., organ...
Webster, Lynn R; Reisfield, Gary M; Dasgupta, Nabarun
The provision of long-term opioid analgesic therapy for chronic pain requires a careful risk/benefit analysis followed by clinical safety measures to identify and reduce misuse, abuse, and addiction and their associated morbidity and mortality. Multiple data sources show that benzodiazepines, prescribed for comorbid insomnia, anxiety, and mood disorders, heighten the risk of respiratory depression and other adverse outcomes when combined with opioid therapy. Evidence is presented for hazards associated with coadministration of opioids and benzodiazepines and the need for caution when initiating opioid therapy for chronic pain. Clinical recommendations follow, as drawn from 2 previously published literature reviews, one of which proffers 8 principles for safer opioid prescribing; the other review presents risks associated with benzodiazepines, suggests alternatives for co-prescribing benzodiazepines and opioids, and outlines recommendations regarding co-prescribing if alternative therapies are ineffective. PMID:25526233
Kranjec, Alexander; Cardillo, Eileen R; Schmidt, Gwenda L; Chatterjee, Anjan
Prepositions combine with nouns flexibly when describing concrete locative relations (e.g. at/on/in the school) but are rigidly prescribed when paired with abstract concepts (e.g. at risk; on Wednesday; in trouble). In the former case they do linguistic work based on their discrete semantic qualities, and in the latter they appear to serve a primarily grammatical function. We used the abstract concept of time as a test case to see if specific grammatically prescribed prepositions retain semantic content. Using ambiguous questions designed to interrogate one's meaningful representation of temporal relations, we found that the semantics of prescribed prepositions modulate how we think about time. Although prescribed preposition use is unlikely to be based on a core representational organization shared between space and time, results demonstrate that the semantics of particular locative prepositions do constrain how we think about paired temporal concepts. PMID:19846070
Poetker, David M; Smith, Timothy L
As otolaryngologists, we prescribe many medications to our patients. The objective of this article is to review the potential side effects and medicolegal risks of the common medications used to treat chronic rhinosinusitis. The authors evaluate some of the common side effects as well as the published literature on the lawsuits associated with those medications. Finally, the authors review the informed consent discussion and opportunities to improve patient care and decrease the risk of litigation. PMID:26117297
The purpose of this work is to construct asymptotically flat, time symmetric initial data with an apparent horizon of prescribed intrinsic geometry. To do this, we use the parabolic partial differential equation for prescribing scalar curvature. In this equation the horizon geometry is contained within the freely specifiable part of the metric. This contrasts with the conformal method in which the geometry of the horizon can only be specified up to a conformal factor.
Freeman, J K; Barnes, J H; Summers, K H; Szeinbach, S L
The authors asked general and family practitioners to rate the importance of several items relating to the prescribing of drug products for patients with panic disorder. Physicians preferred to use benzodiazepines alone and in combination with antidepressants for treatment, regardless of the presence or absence of phobic avoidance. Adverse drug events, efficacy, and patient characteristics were found to be important considerations when physicians prescribe medication. Educational and promotional strategies for pharmaceutical manufacturers and marketers are discussed. PMID:10126028
Weinger, M.B.; Gregg, W.M.; Johnson, K.B.
Summary Objective This study explores alternative approaches to the display of drug alerts, and examines whether and how human-factors based interface design can be used to improve the prescriber’s perception about drug alert presentation, signal detection from noisy alert data, and their comprehension of clinical decision support during electronic prescribing. Methods We reviewed issues with presenting multiple drug alerts in electronic prescribing systems. User-centered design, consisting of iterative usability and prototype testing was applied. After an iterative design phase, we proposed several novel drug alert presentation interfaces; expert evaluation and formal usability testing were applied to access physician prescribers’ perceptions of the tools. We mapped drug alert attributes to different interface constructs. We examined four different interfaces for presenting multiple drug alerts. Results A TreeDashboard View was better perceived than a text-based ScrollText View with respect to the ability to detect critical information, the ability to accomplish tasks, and the perceptional efficacy of finding information. Conclusion A robust model for studying multiple drug-alert presentations was developed. Several drug alert presentation interfaces were proposed. The TreeDashboard View was better perceived than the text-based ScrollText View in delivering multiple drug alerts during a simulation of electronic prescribing. PMID:25024753
Kim, Sun H.; Reaven, Gerald; Lindley, Steven
C-reactive protein (CRP) is an inflammatory marker associated with obesity, insulin resistance, and cardiovascular disease. A recent study found CRP to be higher in individuals treated with certain antipsychotic medications such as olanzapine; however, it is unclear whether this is associated directly with drug intake or indirectly with drug-associated weight gain and insulin resistance. The objective of this study was to explore potential predictors of CRP including insulin resistance, components of the metabolic syndrome, psychiatric diagnosis, and antipsychotic medication in patients treated with antipsychotics. Sixty-four outpatients without diabetes being treated with a single second generation antipsychotic medication had direct measurements of insulin resistance at the end of a 180-minute infusion of glucose, insulin and octreotide (insulin suppression test) as well as components of the metabolic syndrome. Insulin resistance was the strongest predictor of CRP (r=0.52, p<0.001). When adjusted for insulin resistance, there was no significant relationship between CRP and any of the components of the metabolic syndrome criteria, specific drug treatment or psychiatric diagnoses. In conclusion, insulin resistance is strongly associated with CRP levels and likely contributes to previous associations between CRP and certain antipsychotic treatments. PMID:20861740
... Apr 9;9(4):e91755. Doi:10.1371/journal.pone.0091755. PMID: 24717837 The mission of the NIAMS, a part of the U.S. Department of Health and Human Services' National Institutes of Health, is to support research into the ...
Shehzad, Sabir Ali; Alsaedi, Ahmad; Hayat, Tasawar
This paper investigates the steady hydromagnetic three-dimensional boundary layer flow of Maxwell fluid over a bidirectional stretching surface. Both cases of prescribed surface temperature (PST) and prescribed surface heat flux (PHF) are considered. Computations are made for the velocities and temperatures. Results are plotted and analyzed for PST and PHF cases. Convergence analysis is presented for the velocities and temperatures. Comparison of PST and PHF cases is given and examined. PMID:23874523
Zhang, Y.; Obrist, D.; Zielinska, B.; Gerler, A.
Biomass burning is an important emission source of pollutants to the atmosphere, but few studies have focused on the chemical composition of emissions from prescribed burning activities. Here we present results from a sampling campaign to quantify particulate-phase emissions from various types of prescribed fires including carbon species (Elemental Carbon: EC; Organic Carbon: OC; and Total Carbon: TC); polar organic compounds (12 different compounds and four functional classes); water-soluble potassium (K+); and mercury (Hg). We measured emissions from the following types of prescribed biomass burning in the Lake Tahoe basin located on the California/Nevada border: (i) log piles stacked and dried in the field; (ii) log piles along with green understory vegetation; and (iii) understory green vegetation and surface litter; further emissions were collected from burns conducted in a wood stove: (iv) dried wooden logs; (v) green foliage of understory vegetation collected from the field; and (vi) surface organic litter collected from the field; finally, samples were also taken from (vii) ambient air in residential areas during peak domestic wood combustion season. Results show that OC/EC ratios of prescribed burns in the field ranged from 4 to 10, but lower values (around 1) were observed in controlled stove fires. These results are consistent with an excess of OC emissions over EC found in wildfires. OC/EC ratios, however, showed clear separations between controlled wood stove combustion (higher EC) and prescribed burns in the field (lower EC). We attribute this difference to a higher combustion temperatures and dominance of flaming combustion in wood stove fires. OC positively and linearly correlated to the sum of polar organic compounds across all burn types (r2 of 0.82). The most prevalent group of polar compounds emitted during prescribed fires was resin acids (dehydroabietic, pimaric, and abietic acids), followed by levoglucosan plus mannositol. Negligible contributions were observed for inositols, arabitols, and lignin derivates. Although some of these polar compound classes are linked to specific woody or green tissues, we found no significant differences of emission ratios between different types of fires. Water-soluble K+, a common tracer for biomass combustion, showed a clear separation between understory burns (low K+) and wooden pile burns (10 to 20 times higher), suggesting that K+ can potentially be used for differentiating between green versus dry, wooden biomass combustion. Finally, Hg emissions were very low across all fire emissions collected, but were enhanced in urban air sampling which might allow for differentiating sources from biomass combustion from other urban sources.
Mathew, Paul G.; Pavlovic, Jelena M.; Lettich, Alyssa; Wells, Rebecca E.; Robertson, Carrie E.; Mullin, Kathleen; Charleston, Larry; Dodick, David W.; Schwedt, Todd J.
Background Optimizing patient satisfaction with their medical care and maximizing patient adherence with treatment plans requires an understanding of patient preferences regarding education and their role in decision making when treatments are prescribed. Objective To assess the congruence between patient expectations and actual practice regarding education and decision making at the time a triptan is prescribed. Methods This multicenter cross-sectional survey was performed by headache fellow members of the American Headache Society Headache Fellows Research Consortium at their respective tertiary care headache clinics. Migraine patients who were new patients to the headache clinic and who were current triptan users (use within prior 3 months and for ?1 year) or past triptan users (no use within 6 months; prior use within 2 years) completed questionnaires that assessed the education they received and their role in decision making at the time a triptan was first prescribed as well as their desire for education and participation in decision making when a triptan is prescribed. Results Consistent with patient preference, most participants received the majority of their education about the triptan from the prescriber's office (70.2%). In descending rank order, participants most desired to be informed about how to decide if a triptan should be taken, when during the course of migraine a triptan should be taken, possible side effects, cost, and how to obtain refills. Regarding side effects, most participants preferred to receive education about the most common side effects of a triptan rather than addressing all possible side effects. Regarding triptan dosing, participants desired to be informed in descending order of importance about taking other medications with triptans, how many doses can be taken for each migraine, how many doses can be taken each week/month, what to do if the triptan does not work, and the triptan mechanism of action. The vast majority of participants (92%) preferred that the decision to prescribe a triptan be a joint decision between the patient and the provider. In actual practice, participants were not as involved in decision making as they would like to be, with patients reporting that the prescriber was the sole decision maker 55.1% of the time. Participants had confidence in their providers (87.7%) and generally felt they did a good job educating them about the triptan (71.1%). Conclusions Based on this study, it is clear that patients prefer the shared model approach to medical decision making in regards to the prescription of triptans. The majority of patients received education that was generally consistent with their desires. Patients preferred that the prescribing provider be the primary source of information. The most desired educational topics included when/if a triptan should be taken, the number of times a triptan can be taken for a single migraine, co-administration with other acute medications, and the most common side effects. Focusing on these topics should enhance patient satisfaction and may improve compliance. PMID:24512184
Upadhyaya, Prerna; Seth, Vikas; Sharma, Monika; Ahmed, Mushtaq; Moghe, Vijay Vasant; Khan, Zafar Yab; Gupta, Vinay Kumar; Jain, Shipra Vikram; Soni, Utkarsh; Bhatia, Manohar; Abhijit, Kumar; Goyal, Jaswant
Objectives The study aimed to review the prescribing knowledge of first-year postgraduate doctors in a medical college in India, using the principles of good prescribing, to suggest strategies to improve rational prescribing, and to recommend what curriculum planners can do to accomplish this objective. Methods Fifty first-year postgraduate doctors were asked to fill in a structured questionnaire that sought information regarding their undergraduate training in clinical pharmacology and therapeutics, prescribing habits, and commonly consulted drug information sources. Also, the questionnaire assessed any perceived deficiencies in their undergraduate clinical pharmacology teaching and sought feedback regarding improvement in the teaching. Results Eighty-eight percent of residents said that they were taught prescription writing in undergraduate pharmacology teaching; 48% of residents rated their prescribing knowledge at graduation as average, 28% good, 4% excellent, 14% poor, and 4% very poor; 58% felt that their undergraduate training did not prepare them to prescribe safely, and 62% felt that their training did not prepare them to prescribe rationally. Fifty-eight percent of residents felt that they had some specific problems with writing a prescription during their internship training, while 92% thought that undergraduate teaching should be improved. Their suggestions for improving teaching methods were recorded. Conclusions This study concludes that efforts are needed to develop a curriculum that encompasses important aspects of clinical pharmacology and therapeutics along with incorporation of the useful suggestions given by the residents. PMID:23762001
Koley, Munmun; Saha, Subhranil; Ghosh, Shubhamoy; Nag, Goutam; Kundu, Monojit; Mondal, Ramkumar; Purkait, Rajib; Patra, Supratim
A preliminary version of the homeopathic prescribing and patient care indicators was available. The instrument was modified further in this study with an intention to address formally its validity and reliability, audit prescriptions, identify areas of sub-optimal prescribing, and highlight target areas for improving the quality of practices. A cross-sectional study with record analysis was conducted on systematically sampled 377 patients of Mahesh Bhattacharyya Homeopathic Medical College and Hospital (MBHMC and H), Howrah, West Bengal, India. The outcome measures were homeopathic prescribing indicators (6 items) and patient care indicators (5 items). Individualized homeopathic prescriptions predominated in the encounters. Areas demanding immediate attention were extremely poor labeling of drugs dispensed from the hospital pharmacy, improper record of case history and disease diagnosis, ongoing therapies, and investigational findings in the prescriptions. Internal consistency of the overall instrument was estimated to be good (Cronbach's alpha: Prescribing indicators 0.752 and patient care indicators 0.791). The prescribing indicators, except items 1 and 3, reflected acceptable item-corrected total correlations - Pearson's r from 0.58 (95% CI: 0.52-0.65) to 0.74 (95% CI: 0.69-0.78). The patient care indicators, except item 2, showed acceptable correlations - Pearson's r from 0.40 (95% CI: 0.31-0.48) to 0.82 (95% CI: 0.78-0.85). The instrument also showed high discriminant validity (prescribing indicators P < 0.0001 and patient care indicators P < 0.0001). Improper prescribing practice was quite rampant and corrective measures are warranted. The developed indicators appeared to be validated and reliable; however, they are amendable for further development. PMID:25379474
Allison, Laura; Moncrieff, Joanna
This paper examines factors involved in the theory and practice of emergency sedation for behavioural disturbance in psychiatry in the mid-twentieth century, and the emergence of the concept of 'rapid tranquillisation'. The practice received little attention until the arrival of antipsychotic drugs, which replaced older sedatives and became the agents most strongly associated with the treatment of aggression and challenging behaviour. Emergency sedation was subsequently portrayed in psychiatric literature and advertising as a therapeutic and diagnosis-driven endeavour, and the concept of rapid tranquillisation emerged in this context in the 1970s. Use of non-antipsychotic sedatives, like the benzodiazepines, is barely visible in contemporary sources, and the research suggests that antipsychotics became the mainstay of rapid tranquillisation strategies because of beliefs about their specific therapeutic properties in psychosis and schizophrenia, and not because of demonstrated superiority over other agents. PMID:24594821
López-Muñoz, Francisco; Sim, Kang; Shen, Winston Wu; Huelves, Lorena; Moreno, Raquel; Molina, Juan de Dios; Rubio, Gabriel; Noriega, Concha; Ángel Miguel, Pérez-Nieto; Álamo, Cecilio
INTRODUCTION A bibliometric study was carried out to ascertain the volume and impact of scientific literature published on second-generation antipsychotic drugs (SGAs) in Singapore from 1997 to 2011. METHODS A search of the EMBASE and MEDLINE databases was performed to identify articles originating from Singapore that included the descriptors ‘atypic* antipsychotic*’, ‘second-generation antipsychotic*’, ‘clozapine’, ‘risperidone’, ‘olanzapine’, ‘ziprasidone’, ‘quetiapine’, ‘sertindole’, ‘aripiprazole’, ‘paliperidone’, ‘amisulpride’, ‘zotepine’, ‘asenapine’, ‘iloperidone’, ‘lurasidone’, ‘perospirone’ and ‘blonanserin’ in the article titles. Certain bibliometric indicators of production and dispersion (e.g. Price's Law on the increase of scientific literature, and Bradford's Law) were applied, and the participation index of various countries was calculated. The bibliometric data was also correlated with some social and health data from Singapore, such as the total per capita expenditure on health and gross domestic expenditure on research and development. RESULTS From 1997 to 2011, a total of 51 articles on SGAs in Singapore were published. Our results suggested non-fulfilment of Price's Law (r = 0.0648 after exponential adjustment vs. r = 0.2140 after linear adjustment). The most widely studied drugs were clozapine (21 articles), risperidone (16 articles) and olanzapine (8 articles). Division into Bradford zones yielded a nucleus occupied by the Journal of Clinical Psychopharmacology (6 articles) and the Singapore Medical Journal (4 articles). The analysed material was published in a total of 30 journals, with the majority from six journals. Four of these six journals have an impact factor greater than 2. CONCLUSION Publications on SGAs in Singapore are still too few to confirm an exponential growth of scientific literature. PMID:24452974
Ascher-Svanum, Haya; Nyhuis, Allen W.; Faries, Douglas E.; Kinon, Bruce J.; Baker, Robert W.; Shekhar, Anantha
Objective: Early nonresponse to antipsychotics appears to predict subsequent nonresponse to treatment when assessed in randomized controlled trials of predominately acute inpatients treated for schizophrenia. This study assessed the predictive accuracy of early nonresponse to treatment and its clinical, functional, and economic ramifications in the naturalistic treatment of predominately chronic outpatients treated for schizophrenia. Methods: This post hoc analysis used data from a 1-year, randomized, open-label study of olanzapine, risperidone, and typical antipsychotics in the treatment of schizophrenia. If clinically warranted, patients could switch antipsychotics following 8 weeks of treatment. Patients completing 8 weeks of treatment (n?=?443 of 664 enrollees) were included. Patients with early response (?20% improvement from baseline on the Positive and Negative Syndrome Scale at 2 weeks) were compared with early nonresponders on symptom remission, functionality, perceptions of medication influence, and total health care costs at 8 weeks. Results: Early response/nonresponse at 2 weeks predicted subsequent response/nonresponse at 8 weeks with a high level of accuracy (72%) and specificity (89%). After 8 weeks, early nonresponders were less likely to achieve symptom remission (P < .001), improved less on functional domains (P < .05), perceived medication as less beneficial (P = .004), and incurred total heath care costs over twice that of early responders ($4349 vs $2102, P = .010). Conclusions: In the usual care of schizophrenia patients, early nonresponse appears to reliably predict subsequent nonresponse to continued treatment with the same medication to be associated with poorer outcomes and higher health care costs. Identifying early nonresponders may minimize prolonging exposure to suboptimal or ineffective treatment strategies. PMID:18156640
Kimura, Goji; Kadoyama, Kaori; Brown, J.B.; Nakamura, Tsutomu; Miki, Ikuya; Nisiguchi, Kohshi; Sakaeda, Toshiyuki; Okuno, Yasushi
Objective: The reports submitted to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from 1997 to 2011 were reviewed to assess serious adverse events induced by the administration of antipsychotics to children. Methods: Following pre-processing of FAERS data by elimination of duplicated records as well as adjustments to standardize drug names, reports involving haloperidol, olanzapine, quetiapine, clozapine, ziprasidone, risperidone, and aripiprazole were analyzed in children (age 0-12). Signals in the data that signified a drug-associated adverse event were detected via quantitative data mining algorithms. The algorithms applied to this study include the empirical Bayes geometric mean, the reporting odds ratio, the proportional reporting ratio, and the information component of a Bayesian confidence propagation neural network. Neuroleptic malignant syndrome (NMS), QT prolongation, leukopenia, and suicide attempt were focused on as serious adverse events. Results: In regard to NMS, the signal scores for haloperidol and aripiprazole were greater than for other antipsychotics. Significant signals of the QT prolongation adverse event were detected only for ziprasidone and risperidone. With respect to leukopenia, the association with clozapine was noteworthy. In the case of suicide attempt, signals for haloperidol, olanzapine, quetiapine, risperidone, and aripiprazole were detected. Conclusions: It was suggested that there is a level of diversity in the strength of the association between various first- and second-generation antipsychotics with associated serious adverse events, which possibly lead to fatal outcomes. We recommend that research be continued in order to gather a large variety and quantity of related information, and that both available and newly reported data be placed in the context of multiple medical viewpoints in order to lead to improved levels of care. PMID:25589889
Ahearn, Eileen P; Chen, Peijun; Hertzberg, Michael; Cornette, Michelle; Suvalsky, Lori; Cooley-Olson, Deanna; Swanlund, Jamie; Eickhoff, Jens; Becker, Tara; Krahn, Dean
Suicide attempt rates were assessed in 1306 subjects in this 6 year retrospective study of Bipolar disorder. Participants were Veterans from 5 different Veterans Administration Hospitals who met criteria for bipolar type 1 or 2 and who had at least one prescription for lithium or divalproex or both during the study period. This study focused on the impact of atypical antipsychotics on the suicide attempt rate when used in addition to or in place of lithium or divalproex. Medication exposure was calculated using computerized pharmacy records. Suicide attempts were established through chart review including emergency room records, inpatient records, and outpatient records. There were a total of 117 suicide attempts and 2 suicide completions during the study period. Most attempts (59%) occurred when patients were on no medications. Nearly 90% of subjects spent an average of 45 months during the 6 year period on none of the aforementioned medications. The lowest percentage of suicide attempts (15%) occurred while on lithium, 21% while on divalproex and 24% while on atypical antipsychotics. When total months of exposure were taken into account, the lowest attempt rate occurred on lithium plus divalproex (6.3 attempts per 10,000 months of exposure), followed by divalproex alone (7.0 attempts/10,000 months of exposure), and lithium alone (7.7 attempts per 10,000 months of exposure). Patients on atypical antipsychotics alone had an attempt rate of 26.1 attempts per 10,000 months of exposure. In this study, lithium and divalproex provided protection against suicide attempts. Results need to be replicated in future prospective studies and clearly strategies for improving medication compliance among veterans are warranted. PMID:22871534
Marino, Eva; Guijarro, Mercedes; Hernando, Carmen; Madrigal, Javier; Díez, Carmen
Prescribed burning is commonly used to prevent accumulation of biomass in fire-prone shrubland in NW Spain. However, there is a lack of knowledge about the efficacy of the technique in reducing fire hazard in these ecosystems. Fire hazard in burned shrubland areas will depend on the initial capacity of woody vegetation to recover and on the fine ground fuels existing after fire. To explore the effect that time since burning has on fire hazard, experimental tests were performed with two fuel complexes (fine ground fuels and regenerated shrubs) resulting from previous prescribed burnings conducted in a gorse shrubland (Ulex europaeus L.) one, three and five years earlier. A point-ignition source was used in burning experiments to assess ignition and initial propagation success separately for each fuel complex. The effect of wind speed was also studied for shrub fuels, and several flammability parameters were measured. Results showed that both ignition and initial propagation success of fine ground fuels mainly depended on fuel depth and were independent of time since burning, although flammability parameters indicated higher fire hazard three years after burning. In contrast, time since burning increased ignition and initial propagation success of regenerated shrub fuels, as well as the flammability parameters assessed, but wind speed had no significant effect. The combination of results of fire hazard for fine ground fuels and regenerated shrubs according to the variation in relative coverage of each fuel type after prescribed burning enabled an assessment of integrated fire hazard in treated areas. The present results suggest that prescribed burning is a very effective technique to reduce fire hazard in the study area, but that fire hazard will be significantly increased by the third year after burning. These results are valuable for fire prevention and fuel management planning in gorse shrubland areas. PMID:21112688
Aichhorn, Wolfgang; Whitworth, Alexandra B; Weiss, Elisabeth M; Marksteiner, Josef
Six second-generation antipsychotics (SGAs), aripiprazole, clozapine, olanzapine, quetiapine, risperidone and ziprasidone, are currently US FDA approved. The aim of this review is to investigate whether sex differences exist for efficacy and adverse effects of these drugs.Sex-related differences have been shown in the pharmacokinetics of cytochrome P450 (CYP), with a higher activity in females for CYP3A4 and CYP2D6. However, even if there are pharmacokinetic differences between females and males, significantly higher plasma concentrations in women have been demonstrated only for olanzapine and clozapine. To date, sex differences in adverse effects have not been well studied, but some adverse effects such as weight gain, hyperprolactinaemia and cardiac effects are reported to be particularly problematic for women. Most of the studies reviewed indicate that clozapine and olanzapine are associated with greater bodyweight gain than the other atypical antipsychotics, and that serious adverse effects such as metabolic syndrome, which includes increased visceral adiposity, hyperglycaemia, hypertension and dyslipidaemia induced by SGAs, are more frequent in females. According to most studies, the risk for cardiac adverse effects induced by SGAs is the same in male and female patients. Although women are at a lower risk of sudden cardiac death, they have a higher risk of induced long QT syndrome from antiarrhythmic and, probably, antipsychotic drugs. The propensity of sexual dysfunctions is higher with conventional antipsychotics than with SGAs. Additionally, there is some evidence that female sexual dysfunction is associated with high prolactin levels; however, whether the degree of prolactin level elevation is different between female and male patients remains controversial. There is no evidence for sex differences for any of the SGAs to cause a higher rate of extrapyramidal symptoms, acute dystonia or any other movement disturbance. Knowledge of the risks and benefits associated with the use of SGAs during pregnancy and lactation is limited, although the direction of dose adjustments during pregnancy depends on the drug and the enzyme that is responsible for its metabolism. In general, data on sex differences were mostly obtained by posthoc analysis and, therefore, the conclusions that can be drawn are limited. For a better understanding of the basic mechanisms of sex differences, future studies with a primary focus on this topic are required. Data that are more specific will help determine the extent to which these differences will have implications for clinical management. PMID:16808551
Watanabe, Junzo; Suzuki, Yutaro; Fukui, Naoki; Ono, Shin; Sugai, Takuro; Tsuneyama, Nobuto; Someya, Toshiyuki
Most antipsychotic agents can cause QT prolongation, which causes torsades de pointes. The QT interval in healthy subjects is longer during nighttime than during daytime. The QT interval of patients treated with antipsychotics may be prolonged during nighttime, and the effects of antipsychotics on the QT interval may differ between antipsychotics. This study investigated the circadian dynamics of the QT interval in patients treated with antipsychotics and healthy controls, using a 24-hour Holter electrocardiogram in a clinical setting. Sixty-six patients with a diagnosis of schizophrenia that were treated with risperidone or olanzapine and 40 healthy volunteers were enrolled. The QT intervals were corrected using the Fridericia formula (QTcF = QT / RR). Mean ± SD nighttime QTcFs were 411.6 ± 29.0, 395.9 ± 21.2, and 387.8 ± 19.0 milliseconds (ms) in the risperidone, olanzapine, and control groups, respectively. The mean daytime QTcFs were 397.7 ± 23.4, 392.4 ± 18.9, and 382.6 ± 17.3 ms, respectively. The mean nighttime QTcF of the risperidone group was significantly longer than that of the olanzapine and control groups, although there was no significant difference in the mean daytime QTcF between the risperidone and olanzapine groups. The current study used 24-hour Holter electrocardiograms to reveal significantly longer QT intervals in the risperidone group especially during nighttime. In clinical practices, evaluations of the QT interval have been conducted over short periods in the daytime, but it is believed that such methods may not be able to fully elucidate the effects of antipsychotics on the QT interval. PMID:22198445
Koola, Maju Mathew; Wehring, Heidi J.; Kelly, Deanna L.
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
Boyda, H N; Ramos-Miguel, A; Procyshyn, R M; Töpfer, E; Lant, N; Choy, H H T; Wong, R; Li, L; Pang, C C Y; Honer, W G; Barr, A M
Second generation antipsychotic (SGA) drugs are effective treatments for psychosis. Common side-effects of SGAs include metabolic dysregulation and risk of cardiometabolic disorders. Metabolic side-effects, including glucose intolerance, can be accurately modelled in rodents. The benefits of interventions used for treating metabolic side-effects of SGAs are mostly unknown. In a 9 wk longitudinal study, female rats were given daily olanzapine (10 mg/kg s.c.) or vehicle. Animals were either sedentary or allowed 1 or 3 h daily access to a running wheel, with total wheel revolutions electronically quantified to reflect exercise intensity. Glucose tolerance tests were performed once weekly to measure glycemic control. Drug levels were measured at week 4. At week 9, abdominal fat and skeletal muscle levels of Glucose Transporter 4 (GLUT4) were measured. Exercise intensity progressively increased over time in all groups given access to running wheels; however, rats treated with olanzapine consistently exercised less than those given the vehicle. Olanzapine caused acute and persistent glucose intolerance throughout the study, which was markedly, though incompletely, ameliorated by exercise. Exercise did not affect glycemic regulation in vehicle-treated rats. Olanzapine-treated rats showed greater central adiposity. Levels of GLUT4 in skeletal muscle were higher in both groups of exercising than in sedentary rats, and GLUT4 values were negatively correlated with glucose intolerance. Routine exercise reduced olanzapine-induced glucose intolerance and increased skeletal muscle levels of GLUT 4, the insulin-responsive transporter that mediates glucose uptake into cells. The current animal model is suitable for evaluating physiological pathways involved with glucose intolerance. PMID:23953063
Hollister, Emily Brooke
In the southern Great Plains, the encroachment of grassland ecosystems by mesquite (Prosopis glandulosa), is widespread, and prescribed fire is commonly used in its control. Despite this, substantial quantitative information ...
The Pharmacological Management of Oppositional Behaviour, Conduct Problems, and Aggression in Children and Adolescents With Attention-Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, and Conduct Disorder: A Systematic Review and Meta-Analysis. Part 2: Antipsychotics and Traditional Mood Stabilizers
Pringsheim, Tamara; Hirsch, Lauren; Gardner, David; Gorman, Daniel A
Objective: Attention-deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) are among the most common psychiatric diagnoses in childhood. Aggression and conduct problems are a major source of disability and a risk factor for poor long-term outcomes. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) of antipsychotics, lithium, and anticonvulsants for aggression and conduct problems in youth with ADHD, ODD, and CD. Each medication was given an overall quality of evidence rating based on the Grading of Recommendations Assessment, Development and Evaluation approach. Results: Eleven RCTs of antipsychotics and 7 RCTs of lithium and anticonvulsants were included. There is moderate-quality evidence that risperidone has a moderate-to-large effect on conduct problems and aggression in youth with subaverage IQ and ODD, CD, or disruptive behaviour disorder not otherwise specified, with and without ADHD, and high-quality evidence that risperidone has a moderate effect on disruptive and aggressive behaviour in youth with average IQ and ODD or CD, with and without ADHD. Evidence supporting the use of haloperidol, thioridazine, quetiapine, and lithium in aggressive youth with CD is of low or very-low quality, and evidence supporting the use of divalproex in aggressive youth with ODD or CD is of low quality. There is very-low-quality evidence that carbamazepine is no different from placebo for the management of aggression in youth with CD. Conclusion: With the exception of risperidone, the evidence to support the use of antipsychotics and mood stabilizers is of low quality. PMID:25886656
Zheng, Ling; Mack, Wendy J.; Dagerman, Karen S.; Hsiao, John K.; Lebowitz, Barry D.; Lyketsos, Constantine G.; Stroup, T. Scott; Sultzer, David L.; Tariot, Pierre N.; Vigen, Cheryl; Schneider, Lon S.
Objective The second-generation antipsychotics are associated with metabolic abnormalities in patients with schizophrenia. Elderly patients with Alzheimer’s disease are frequently treated with these antipsychotics but there is little data available on their metabolic effects. Methods We assessed 186 male and 235 female Alzheimer’s disease outpatients from the Clinical Antipsychotic Trials of Intervention Effectiveness–Alzheimer’s Disease (CATIE-AD) for changes in weight, waist circumference, blood pressure, fasting glucose, and lipids in relation to duration of second-generation antipsychotics (i.e., olanzapine, quetiapine, and risperidone) use throughout the 36-week trial, using logistic regression and mixed-effects models. Results Females showed significant weight gain of 0.14 lb per week of use (p = 0.006) while change was nonsignificant in males. The odds ratios of significant weight gain (i.e., ? 7% of body weight) compared to patients who did not use antipsychotics were 1.56 (95% CI 0.53 to 4.58), 2.89 (95% CI 0.97 to 8.64), and 3.38 (95% CI 1.24 to 9.23) among patients with antipsychotics use ? 12 weeks, > 12 to 24 weeks, and > 24 weeks during the trial, respectively. Olanzapine and quetiapine treatments were significantly associated with weight gain (0.12 and 0.14 pounds/week, respectively). In addition, olanzapine was significantly associated with decreases in HDL cholesterol (?0.19mG/dL/week), and increased girth (0.07 inches/week) relative to the placebo group. No treatment effects were noted for changes in blood pressure, glucose, and triglycerides. Conclusion Second-generation antipsychotics use was associated with weight gain in females, with olanzapine and quetiapine in particular, and with unfavorable change in HDL cholesterol and girth with olanzapine. The potential consequences of these effects suggest that patients with Alzheimer’s disease treated with second-generation antipsychotics should be monitored closely. PMID:19369318
M. J. Fell; N. Anjum; K. Dickinson; K. M. Marshall; L. M. Peltola; S. Vickers; S. Cheetham; J. C. Neill
Introduction Treatment with some antipsychotic drugs may result in excessive body weight gain which can have detrimental effects on patient\\u000a compliance, morbidity and mortality. The aim of the present study was to investigate the effect of atypical antipsychotic\\u000a drugs on dietary macronutrient selection, body weight, body composition and biochemical parameters related to obesity in female\\u000a rats.\\u000a \\u000a \\u000a \\u000a Materials and methods Forty pair-housed, adult
Caddye, Wendy Sarah; Clair-Jones, Anja St
There is no systematic and robust method to assess the competence of non-medical prescribers (NMPs) locally or nationally. NMPs have a responsibility to remain up to date with the knowledge and skills to enable them to prescribe competently and safely within their field of expertise. In 2012, the National Prescribing Centre developed a single competency framework for prescribers defining a set of nine dimensions within three domains that can be used to underpin personal responsibility for prescribing. The authors identified validated assessment tools using a literature search, and selected those suitable for mapping against the nine dimensions. It was hoped that trust NMPs could provide evidence of competence covering all three of the framework domains using the chosen tools. Five NMPs used the tools to create a portfolio and audited them for suitability in establishing a robust and credible evidence-led system to evaluate and accredit ongoing competence. Feedback on their ease of use and applicability was sought. Trust NMPs were then invited to a workshop where the evidence was presented and they were asked to comment on, and contribute to, finalising the tools before they were embedded within trust policy. PMID:26110857
This Web site provides comprehensive information, selected by medical doctors, about the common cold. The goal is to provide a framework for critical thinking which will allow informed decisions about medical care for the common cold. The section entitled Understanding Colds gives a detailed overview of how the cold virus invades the human body and how cold symptoms are caused. Information about preventing colds, and some of the complications that can occur are also included. The Special Features section includes one of the most interesting parts of the site -- Myths of the Common Cold. This site should be interesting to almost anyone, but perhaps more so for those of us who have recently had a cold.
Oliver-Africano, P.; Dickens, S.; Ahmed, Z.; Bouras, N.; Cooray, S.; Deb, S.; Knapp, M.; Hare, M.; Meade, M.; Reece, B.; Bhaumik, S.; Harley, D.; Piachaud, J.; Regan, A.; Ade Thomas, D.; Karatela, S.; Rao, B.; Dzendrowskyj, T.; Lenotre, L.; Watson, J.; Tyrer, P.
Background: Aggressive challenging behaviour in people with intellectual disability (ID) is frequently treated with antipsychotic drugs, despite a limited evidence base. Method: A multi-centre randomised controlled trial was undertaken to investigate the efficacy, adverse effects and costs of two commonly prescribed antipsychotic drugs…
... supported by grants from the state Attorney General Consumer and Prescriber Education Grant Program which is funded by the multi-state settlement of consumer fraud claims regarding the marketing of the prescription ...
Brodrick, A; Preece, G; Bird, H A; Wright, V
Questionnaire replies were received from 86% of all members of the British Association for Rheumatology and Rehabilitation soliciting opinions regarding influences and attitudes to prescribing. The importance and quality of information sources for new drugs were assessed and the importance of various aspects of information considered to be necessary for inclusion in a data card were investigated. The results indicated the professional journals and independent sources such as the Prescribers Journal are highly thought of by Rheumatologists and that advertisements and 'popular' journals are less likely to be important in the transmission of awareness of a new drug. The most important aspects of information considered to be necessary for inclusion in a data card or information bulletin were adverse- or side-effects. Specific details of the drug formulation or presentation are considered to be of much less importance. Rheumatologists prefer to prescribe by generic name and are likely to use two or three drugs in the treatment of a patient. PMID:6607268
Ryan, Cristín; Ross, Sarah; Davey, Peter; Duncan, Eilidh M.; Francis, Jill J.; Fielding, Shona; Johnston, Marie; Ker, Jean; Lee, Amanda Jane; MacLeod, Mary Joan; Maxwell, Simon; McKay, Gerard A.; McLay, James S.; Webb, David J.; Bond, Christine
Objectives Study objectives were to investigate the prevalence and causes of prescribing errors amongst foundation doctors (i.e. junior doctors in their first (F1) or second (F2) year of post-graduate training), describe their knowledge and experience of prescribing errors, and explore their self-efficacy (i.e. confidence) in prescribing. Method A three-part mixed-methods design was used, comprising: prospective observational study; semi-structured interviews and cross-sectional survey. All doctors prescribing in eight purposively selected hospitals in Scotland participated. All foundation doctors throughout Scotland participated in the survey. The number of prescribing errors per patient, doctor, ward and hospital, perceived causes of errors and a measure of doctors' self-efficacy were established. Results 4710 patient charts and 44,726 prescribed medicines were reviewed. There were 3364 errors, affecting 1700 (36.1%) charts (overall error rate: 7.5%; F1:7.4%; F2:8.6%; consultants:6.3%). Higher error rates were associated with : teaching hospitals (p<0.001), surgical (p?=?<0.001) or mixed wards (0.008) rather thanmedical ward, higher patient turnover wards (p<0.001), a greater number of prescribed medicines (p<0.001) and the months December and June (p<0.001). One hundred errors were discussed in 40 interviews. Error causation was multi-factorial; work environment and team factors were particularly noted. Of 548 completed questionnaires (national response rate of 35.4%), 508 (92.7% of respondents) reported errors, most of which (328 (64.6%) did not reach the patient. Pressure from other staff, workload and interruptions were cited as the main causes of errors. Foundation year 2 doctors reported greater confidence than year 1 doctors in deciding the most appropriate medication regimen. Conclusions Prescribing errors are frequent and of complex causation. Foundation doctors made more errors than other doctors, but undertook the majority of prescribing, making them a key target for intervention. Contributing causes included work environment, team, task, individual and patient factors. Further work is needed to develop and assess interventions that address these. PMID:24404122
Tarn, Derjung M.; Paterniti, Debora A.; Orosz, Deborah K.; Tseng, Chi-Hong; Wenger, Neil S.
PURPOSE Physicians prescribing new medications often do not convey important medication-related information. This study tests an intervention to improve physician-patient communication about newly prescribed medications. METHODS We conducted a controlled clinical trial of patients in 3 primary care practices, combining data from patient surveys with audio-recorded physician-patient interactions. The intervention consisted of a 1-hour physician-targeted interactive educational session encouraging communication about 5 basic elements regarding a new prescription and a patient information handout listing the 5 basic elements. Main outcome measures were the Medication Communication Index (MCI), a 5-point index assessed by qualitative analysis of audio-recorded interactions (giving points for discussion of medication name, purpose, directions for use, duration of use, and side effects), and patient ratings of physician communication about new prescriptions. RESULTS Twenty-seven physicians prescribed 113 new medications to 82 of 256 patients. The mean MCI for medications prescribed by physicians in the intervention group was 3.95 (SD = 1.02), significantly higher than that for medications prescribed by control group physicians (2.86, SD = 1.23, P <.001). This effect held regardless of medication type (chronic vs nonchronic medication). Counseling about 3 of the 5 MCI components was significantly higher for medications prescribed by physicians in the intervention group, as were patients’ ratings of new medication information transfer (P = .02). Independent of intervention or control groups, higher MCI scores were associated with better patient ratings about information about new prescriptions (P = .003). CONCLUSIONS A physician-targeted educational session improved the content of and enhanced patient ratings of physician communication about new medication prescriptions. Further work is required to assess whether improved communication stimulated by the intervention translates into better clinical outcomes. PMID:23319503
Ross, Sarah; Maxwell, Simon
Prescribing is one of the commonest tasks expected of new doctors and is a complex process involving a mixture of knowledge, judgement and skills. Preparing graduates to be prescribers is one of the greatest challenges of modern undergraduate medical education and there is some evidence to suggest that training could be improved. The aims of this article are (i) to review some of the challenges of delivering effective prescribing education, (ii) to provide a clear statement of the learning outcomes in clinical pharmacology and prescribing that should be expected of all medical graduates and (iii) to describe a curriculum that might enable students to achieve these outcomes. We build on the previous curriculum recommendations of the British Pharmacological Society and take into account those of other key bodies, notably the General Medical Council. We have also reviewed relevant evidence from the literature and set our work in the context of recent trends in medical education. We divide our recommended learning objectives into four sections: principles of clinical pharmacology, essential drugs, essential therapeutic problems and prescribing skills. Although these will not necessarily be accepted universally we believe that they will help those who design and map undergraduate curricula to explore potential gaps and identify improvements. PMID:22288524
... small black "dots" at the surface, from tiny blood vessels. Common warts are rough thick skin-colored pink or white bumps, from 1 mm to over 10 mm in size, often on the hands, face, elbows, and knees. Filiform warts are long and ...
... small black "dots" at the surface from tiny blood vessels. Common warts are rough, thick, skin-colored, pink, or white bumps from 1 mm to over 10 mm in size, often on the hands, face, elbows, and knees. Filiform warts are long and ...
The Common Chuckwalla is primarily found across the Mojave and Sonoran deserts of the United States and Mexico, at elevations ranging from sea level to 1,370 m. This large (125–180 mm) lizard is dorsoventrally flattened and has wrinkles on its belly and neck. Chuckwallas are strongly associa...
Keks, Nicholas A; Tonso, Michael; Tabone, Kelly; McHugh, Mary; Thomas, Rajan; Tune, Phil; Gelman, Mat
Objective. To evaluate dosing and time to efficacy of atypical antipsychotics in an acute inpatient unit. Methods. Admissions during 2001 were reviewed. Patients primarily treated with an atypical antipsychotic (including those simultaneously commenced on a mood stabiliser and/or antidepressant or receiving benzodiazepines) were evaluated. Non-acute patients, those without medical records or transferred to other hospitals were excluded. Medication details were noted. Results. A total of 137 patients were evaluated; 56 (41%) had received risperidone, 38 (28%) olanzapine, and 37 (27%) quetiapine. Mean doses (mg/day) at discharge were risperidone 4.1±2.3, olanzapine 22.5±10.2, quetiapine 576±472. Dose ranges (mg/day) were risperidone 0.5-12, olanzapine 5-40, quetiapine 50-1800. No differences between atypicals in time to efficacy/concomitant anticholinergics/mood stabilisers were observed. Benzodiazepine use was more frequent with risperidone and olanzapine than quetiapine. No serious side effects with any drug were noted. Quetiapine was rapidly titrated in 20 patients (up to 400 mg on Day 1). In 18 of these, acute disturbance was controlled. Two patients were switched for lack of efficacy, one due to persistent tachycardia, and five for concern about early postural hypotension. Conclusion. These data provide further evidence concerning dose and dose range of atypicals required for optimal clinical outcome. More rapid initiation with quetiapine may be of benefit to some patients in the acute inpatient setting. PMID:24940964
Preskorn, Sheldon H.
In both clinical trials and daily practice, there can be substantial inter- and ev