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
Kishimoto, Taishiro; Watanabe, Koichiro; Uchida, Hiroyuki; Mimura, Masaru; Kane, John M; Correll, Christoph U
Background Anti-psychotics, prescribed to people with dementia, are associated with approximately 1,800 excess annual deaths in the UK. A key public health objective is to limit such prescribing of anti-psychotics. Methods This project was conducted within primary care in Medway Primary Care Trust (PCT) in the UK. There were 2 stages for the intervention. First, primary care information systems including the dementia register were searched by a pharmacy technician to identify people with dementia prescribed anti-psychotics. Second, a trained specialist pharmacist conducted targeted clinical medication reviews in people with dementia initiated on anti-psychotics by primary care, identified by the data search. Results Data were collected from 59 practices. One hundred and sixty-one (15.3%) of 1051 people on the dementia register were receiving low-dose anti-psychotics. People with dementia living in residential homes were nearly 3.5 times more likely to receive an anti-psychotic [25.5% of care home residents (118/462) vs. 7.3% of people living at home (43/589)] than people living in their own homes (p?0.0001; Fisher’s exact test). In 26 practices there was no-one on the dementia register receiving low-dose anti-psychotics. Of the 161 people with dementia prescribed low-dose anti-psychotics, 91 were receiving on-going treatment from local secondary care mental health services or Learning Disability Teams. Of the remaining 70 patients the anti-psychotic was either withdrawn, or the dosage was reduced, in 43 instances (61.4%) following the pharmacy-led medication review. Conclusions In total 15.3% of people on the dementia register were receiving a low-dose anti-psychotic. However, such data, including the recent national audit may under-estimate the usage of anti-psychotics in people with dementia. Anti-psychotics were used more commonly within care home settings. The pharmacist-led medication review successfully limited the prescribing of anti-psychotics to people with dementia.
Background Prescribing of antipsychotics (AP) to young people has increased in the last decade internationally. We aimed to characterize AP prescribing in a population of low-income youth in Nova Scotia, Canada. Methods We conducted a population database study of AP prescription claims and health services utilization by young people aged 25 years and younger receiving drug benefits through the publicly funded Pharmacare program between October 1, 2000 to September 30, 2007. Results Four percent (1715/43888) of youth receiving Pharmacare benefits filled AP prescriptions. The use of second generation antipsychotics (SGAs) significantly increased (p?0.0001) in all age groups except 0-5 year olds, whereas first generation antipsychotic use significantly decreased. Pharmacare beneficiaries aged 21-25 years represented 45.2% of AP users. The majority (66%) of youth filling AP prescriptions had 2 or more psychiatric diagnoses. Most youth (76%) filled prescriptions for only one type of AP during the study period. Psychotic disorders were the most common indication for AP use except with risperidone, in which ADHD was the most likely reason for use. Co-prescribing of psychotropics was prevalent with antidepressants and mood stabilizers prescribed in 42% and 27% of AP users, respectively. General practitioners (GPs) prescribed incident APs most often (72%) followed by psychiatrists (16%). The age- and gender-adjusted rate of death was higher in AP users as compared to the age-matched general population of Nova Scotia. Conclusions SGA use increased significantly over seven years in a cohort of 0 to 25 years olds receiving Pharmacare benefits. Off-label use of APs was prevalent with ADHD and other non-psychotic disorders being common reasons for AP use. GPs initiated most AP prescriptions. Co-prescribing of other psychotropics, especially antidepressants and mood stabilizers, was prevalent even in younger age strata. This study raises further questions about AP prescribing in those 25 years of age and under, especially given the range of diagnoses and psychotropic co-prescribing.
|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…
Paton, C.; Flynn, A.; Shingleton-Smith, A.; McIntyre, S.; Bhaumik, S.; Rasmussen, J.; Hardy, S.; Barnes, T.
The Food and Drug Administration has approved the use of antipsychotic medications in some children and adolescents with severe emotional and behavioral disorders. However, recent national data show a dramatic rise in off-label and Food and Drug Administration–approved uses of these medications. Of particular note is a twofold to fivefold increase in the use of antipsychotic medications in preschool children, despite little information on their long-term effects. This article describes the trend in pediatric antipsychotic medication use, possible explanations for the increase, implications for children’s health, and recommendations for pediatric providers who work with parents of children and adolescents who seek or receive antipsychotic medication treatments.
Harrison, Joyce Nolan; Cluxton-Keller, Fallon; Gross, Deborah
The aim of this review is to provide information for interpreting outcome results from monitoring of antipsychotics in biological samples. A brief overview of the working mechanisms, pharmacological effects, drug interactions, and analytical methods of classical and atypical antipsychotics is given. Nineteen antipsychotics were selected based on their importance in the worldwide market as follows: amisulpride, aripiprazole, asenapine, bromperidol, clozapine, flupenthixol, haloperidol, iloperidone, lurasidone, olanzapine, paliperidone, perphenazine, pimozide, pipamperone, quetiapine, risperidone, sertindole, sulpiride, and zuclopenthixol. A straightforward relationship between administered dose, plasma or serum concentration, clinical outcome, or adverse effects is often lacking. Nowadays, focus lies on therapeutic drug monitoring and individualized therapy to find adequate treatment, to explain treatment failure or nonresponse, and to check patient compliance. However, extensive research in this field is still mandatory. PMID:23149440
Patteet, Lisbeth; Morrens, Manuel; Maudens, Kristof E; Niemegeers, Peter; Sabbe, Bernard; Neels, Hugo
Objectives. This study evaluated how clinicians monitored glucose, lipids, body mass index (BMI), and blood pressure (BP) of patients being treated with second-generation antipsychotics (SGAs) before and after the publication of the American Diabetes Association (ADA) and American Psychiatric Association (APA) Consensus Statement concerning antipsychotic drugs and obesity and diabetes in February, 2004. Methods. A retrospective analysis of GE Centricity electronic health records for the 2001-2008 period was conducted. SGA-naïve patients receiving monotherapy with any SGA (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone) were identified. Two scenarios were examined: The "Any" monitoring scenario was defined as at least one instance of monitoring of a parameter at any time point during the observation period (from 30 days before beginning the SGA until 395 days after beginning the SGA); the "Full" monitoring scenario was defined as a situation in which the number of times a parameter was monitored during the observation period was equal to the yearly frequency recommended by ADA/APA. Pre- and post-consensus statement monitoring rates were computed and monitoring trends were evaluated by quarterly time intervals using segmented time-series design. Results. The final sample consisted of 24,826 patients, with mean age of 47.9 years, 61% of whom were female. Pre- and post- consensus statement monitoring compared as following: "Any" scenario: BP (92% [pre] vs. 94% [post]), BMI (66% vs. 77%), glucose (60% vs. 65%), lipids (36% vs. 41%); "Full" scenario; BP (72% vs. 75%), BMI (23% vs. 27%), glucose (23% vs. 27%), lipids (17% vs. 20%). Regression analyses found the following per quarter increases in the post-con- sensus statement period for the "Any" scenario: glucose (1.4%, p = 0.003), lipids (1.0%, p = 0.008), BP (0.6%, p = 0.006) and the following per quarter increases for the "Full" scenario: glucose (1.0%, p = 0.002), lipids (1.2%, p < 0.001) and BP (1.3%, p = 0.004). Conclusions. The publication of the Consensus Statement alone did not make a clinically meaningful difference to monitoring rates. (Journal of Psychiatric Practice 2013;19:360-374). PMID:24042242
Dhamane, Amol D; Martin, Bradley C; Brixner, Diana I; Hudson, Teresa J; Said, Qayyim
Aims To estimate changes in the frequency of use of various antipsychotic drugs in the UK from 1991 to 2000 and to relate these changes to patients' characteristics. Methods We conducted a population-based observational study using data from general practices that contribute information to the General Practice Research Database (GPRD). The study population comprised men and women 10–99 years old. We estimated annual use, first-time use, duration of use and, in a sample of 200 patients, indications for use of various antipsychotic drugs, and we observed how these measures had changed over the past decade. Results The annual use of antipsychotic drugs increased from 10.5 per thousand in 1991 to 12.2 per thousand in 2000, an overall increase of 16%. The increase was greater in men (25.2%) than women (2.7%). At the same time, the rate of new use of antipsychotic drugs was stable in men and decreased by 21% in women. The difference between patterns of annual use and rates of new use is attributable to the increasing average annual duration of treatment in both men and women during the past decade. Thioridazine, which the UK Committee on the Safety of Medicines (CSM) recently recommended should be used only for second-line treatment of schizophrenia in adults, was the most commonly prescribed antipsychotic throughout the study period. Its use increased as a proportion of all antipsychotic drug use from 1991 to 2000 in men and women aged 10–69 years, but decreased in older users. More than half of all first-time use of antipsychotic drugs in the sample of patients we evaluated was for treatment of depression, anxiety states, and panic disorders, while less than 10% was for treatment of schizophrenia and other psychoses. Conclusion The use of antipsychotic drugs has increased in the UK during the past decade, primarily due to increased average annual duration of use rather than higher rates of new use. Most antipsychotic drug use appears to have been prescribed to treat nonpsychotic disorders. It will be of interest to see whether the use of thioridazine, which was the most widely prescribed antipsychotic during 1991–2000, decreases during the next decade in response to the recent CSM recommendation.
Kaye, James A; Bradbury, Brian D; Jick, Hershel
Background Antipsychotic drugs are widely used for the treatment of Behavioral and Psychological Symptoms of Dementia (BPSD), despite their limited efficacy and concerns about safety. The aim of this study was to describe antipsychotic drug therapy among people with dementia living in specialized care units in northern Sweden. Methods This study was conducted in 40 specialized care units in northern Sweden, with a total study population of 344 people with dementia. The study population was described in regard to antipsychotic drug use, ADL function, cognitive function and BPSD, using the Multi-Dimensional Dementia Assessment Scale (MDDAS). These data were collected at baseline and six months later. Detailed data about antipsychotic prescribing were collected from prescription records. Results This study showed that 132 persons (38%) in the study population used antipsychotic drugs at the start of the study. Of these, 52/132 (39%) had prescriptions that followed national guidelines with regard to dose and substance. After six months, there were 111 of 132 persons left because of deaths and dropouts. Of these 111 people, 80 (72%) were still being treated with antipsychotics, 63/111 (57%) with the same dose. People who exhibited aggressive behavior (OR: 1.980, CI: 1.515-2.588), or passiveness (OR: 1.548, CI: 1.150-2.083), or had mild cognitive impairment (OR: 2.284 CI: 1.046-4.988), were at increased risk of being prescribed antipsychotics. Conclusion The prevalence of antipsychotic drug use among people with dementia living in specialized care units was high and inappropriate long-term use of antipsychotic drugs was common.
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 taking 2 or more antipsychotics at once. Predictors of multiple antipsychotic use included gender, residence, psychiatric diagnosis and previous hospitalizations. Implications of medication prescriptions to this vulnerable population are discussed. PMID:22093645
Lunsky, Yona; Elserafi, Jonny
Women who are pregnant and who have a history of psychosis are commonly managed with antipsychotic medications. The evidence regarding the use of antipsychotics in pregnancy has been insufficient to provide adequate support for this practice and is a concern for clinicians and women alike. This review presents literature surrounding the use of antipsychotic medications in pregnancy, providing an overview of the historical and contemporary perspectives which influence clinicians prescribing practices. Data were sourced from Medline, CINAHL, PsycINFo, using the terms antipsychotics with pregnancy and psychosis or schizophrenia. This was expanded to include the most common atypical antipsychotics: olanzapine, risperidone, clozapine, quetiapine, ziprasidone and aripiprazole. Literature was found reporting the use of antipsychotic medications in pregnancy since the introduction of antipsychotics in the 1950s, comprising mainly of authors' reviews of the literature, case studies, retrospective reports, drug company registries and more recently a prospective comparative study. This review identifies that the literature provides no clear answer for clinicians as to the risk associated with the use of antipsychotics in pregnancy. To this effect, recently in Australia, the National Register of Antipsychotic Medications in Pregnancy was established to prospectively collect information regarding outcomes for mother and baby, when antipsychotic medications have been used during pregnancy. PMID:20465753
McCauley-Elsom, K; Gurvich, C; Elsom, S J; Kulkarni, J
|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…
Lunsky, Yona; Elserafi, Jonny
Findings from 2 pivotal government-funded studies of comparative antipsychotic effectiveness undermine assumptions about the marked superiority of the more expensive second-generation “atypical” medications in comparison to the less expensive first-generation “typical” drugs. Because this assumption was the basis for the almost universal recommendation that these newer antipsychotics be used preferentially resulting in a 10-fold increase in state governmental expenditures on this class of medications over the past decade, a reassessment of policy is called for. To address the issue, the Medical Directors Council of the National Association of State Mental Health Program Directors critically reviewed findings of these studies in the context of other data and considered policy implications in the light of the obligations of state government to make available best possible and individually optimized treatment that is cost-effective. The Medical Directors Council unanimously adopted a set of recommendations to promote appropriate access, efficient utilization, and best practice use. We present our policy statement, in which we provide a succinct background, articulate general principles, and describe a set of 4 broad recommendations. We then summarize our understanding of the current state of knowledge about comparative antipsychotic effectiveness, best antipsychotic practice, and considerations for state policy that represent the basis of our position statement.
Parks, Joseph; Radke, Alan; Parker, George; Foti, May-Ellen; Eilers, Robert; Diamond, Mary; Svendsen, Dale; Tandon, Rajiv
Louisiana physicians often face difficult predicaments in treating patients with chronic pain complaints. On the one hand, there is a greater appreciation for the debilitating impact of chronic pain on quality of life and better recognition that chronic pain is a disease in its own right deserving treatment. On the other hand, we regularly learn of arrests of physicians for prescribing these medications and read reports of exploding pain medication abuse. This article dispenses common sense advice for the Louisiana physician in approaching chronic pain issues such as defining your treatment population, obtaining independent corroborating records, prescribing extended-release pain medications when possible, considering adjunctive treatments to reduce total opiate use, collaborating with colleagues regularly, utilizing treatment agreements, employing sensible verification methods of proper medication use, opening the doctor-patient relationship to include concerned family or friends, using psycho-social indicators of good functioning, and reappraising the success of treatment at appropriate intervals. By employing these common-sense approaches Louisiana physicians can approach pain management prescribing with more assurance and confidence. PMID:21294488
Potash, Mordecai N
Conventional antipsychotic medication is commonly prescribed to patients with autistic spectrum disorder. However, a high incidence of severe adverse reactions highlights the need to find more favourable treatments. Atypical antipsychotics may combine efficacy in ameliorating some autistic symptoms with a lower incidence of some adverse reactions. This article reviews the use of atypical antipsychotics in autistic disorder, with particular focus
L. Barnard; A. H. Young; J. Pearson; J. Geddes; G. OBrien
This study explored the demographic and diagnostic features of children who were currently receiving antipsychotics compared to children who were receiving other psychotropics in a cohort of children with and without elevated symptoms of mania (ESM). Participants were recruited from 10 child outpatient mental health clinics associated with four universities. Guardians with children between 6-12 years who presented for new clinical evaluations completed the Parent General Behavior Inventory-10 Item Mania Scale (PGBI-10M). All children who scored ?12 on the PGBI-10M and a select demographically matched comparison group of patients who scored ?11 were invited to participate. Children were divided into two groups: those receiving at least one antipsychotic medication and those receiving other psychotropic medications. The groups were compared on demographics, diagnoses, psychiatric symptoms, functioning, and past hospitalizations. Of the 707 children enrolled in the Longitudinal Assessment of Manic Symptoms (LAMS) study, 443 (63%) were prescribed psychotropic medication at baseline: 157 (35%) were receiving an antipsychotic and 286 (65%) were prescribed other agents. Multivariate results indicated that being prescribed antipsychotics was related to being white, previous hospitalization, having a psychotic or bipolar 1 disorder and the site where the child was receiving services (p<0.001). In this sample, it is relatively common for a child to be prescribed an antipsychotic medication. However, the only diagnoses associated with a greater likelihood of being treated with an antipsychotic were psychotic disorders or unmodified DSM-IV bipolar 1 disorder. PMID:21851189
Findling, Robert L; Horwitz, Sarah McCue; Birmaher, Boris; Kowatch, Robert A; Fristad, Mary A; Youngstrom, Eric A; Frazier, Thomas W; Axelson, David; Ryan, Neal; Demeter, Christine A; Depew, Judith; Fields, Benjamin; Gill, Mary Kay; Deyling, Elizabeth A; Rowles, Brieana M; Arnold, L Eugene
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 (?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
Weight gain is a frequent adverse effect of many second-generation antipsychotic (SGA) drugs. Although a number of candidate gene studies have focused on SGA-related weight gain, a clinical benefit for pharmacotherapy has not been achieved as yet. Genome-wide association studies offer great potential of identifying novel candidate genes and help to complete the search for relevant polygenetic risk factors. A polymorphism near the human melanocortin 4 receptor gene (MC4R) was associated with overweight and body mass index in recent studies. Owing to the central role of the MC4R receptor in energy homeostasis, we investigated the influence of the rs17782313 polymorphism on SGA-related weight gain. Three hundred forty-five white inpatients receiving different atypical antipsychotics (clozapine, olanzapine, risperidone, paliperidone, quetiapine, or amisulpride) were included in a naturalistic design. After 4 weeks of treatment, patients homozygous for the rs17782313 C-allele had a significantly higher risk of weight gain and body mass index increase, with a dose effect of the C-allele. In a subpopulation without additional weight gain-inducing comedication, the 106 TT-allele carriers gained on average 1.09% of their baseline weight within the 4 weeks of treatment, whereas the 57 CT-allele carriers and the 9 CC-allele carriers gained 3.28% and 5.47% (P = 0.003). Our findings indicate that the rs17782313 polymorphism could increase the amount of SGA-related weight gain and may influence MC4R expression, which could result in an imbalance of energy homeostasis. Nevertheless, further studies are needed to elucidate the role and mechanism of this polymorphism. PMID:23277235
Czerwensky, Fabian; Leucht, Stefan; Steimer, Werner
Background: Respiratory infection with Pseudomonas aeruginosa is very common in patients with cystic fibrosis (CF) but antimicrobial resistance rates of CF isolates across the UK are largely unknown.Methods: The susceptibility of 417 CF patient isolates of P aeruginosa from 17 hospitals to six commonly prescribed antibiotics were examined. Isolates were tested by an agar break point dilution method and E-tests
T L Pitt; M Sparrow; M Warner; M Stefanidou
Objective To determine the sensitivity of 4 strains of Oxalobacter formigenes (OxF) found in humans, HC1, Va3, CC13, and OxK, to varying concentrations of commonly-prescribed antibiotics. OxF gut colonization has been associated with a decreased risk of forming recurrent calcium oxalate kidney stones. Methods For each strain and each antibiotic concentration, 100 ?L of an overnight culture and 100 ?L of the appropriate antibiotic were added to a 7 mL vial of oxalate culture media containing 20 mM oxalate. On the fourth day, vials were visually examined for growth, and a calcium oxalate precipitation test was performed to determine whether OxF grew in the presence of the antibiotic. Results All 4 OxF strains were resistant to amoxicillin, amoxicillin/clavulanate, ceftriaxone, cephalexin, and vancomycin while they were all sensitive to azithromycin, ciprofloxacin, clarithromycin, clindamycin, doxycycline, gentamicin, levofloxacin, metronidazole, and tetracycline. One strain, CC13, was resistant to nitrofurantoin while the others were sensitive. Differences in minimum inhibitory concentration between strains were demonstrated. Conclusions Four human strains of OxF are sensitive to a number of antibiotics commonly utilized in clinical practice; however, minimum inhibitory concentrations differ between strains.
Lange, Jessica N.; Wood, Kyle D.; Wong, Hayes; Otto, Richard; Mufarrij, Patrick W.; Knight, John; Akpinar, Haluk; Holmes, Ross P.; Assimos, Dean G.
Objective This study examined a cohort of Medicaid patients with new prescriptions for atypical antipsychotic medication to determine the prevalence of sub-therapeutic atypical antipsychotic medication use and to identify patient and prescribing provider characteristics associated with its occurrence. Method This observational cohort study examined Medicaid administrative claims data for patients age 20–64 with a new prescription for an atypical antipsychotic medication (clozapine, olanzapine, quetiapine, risperidone, ziprasidone) between 1/2004 and 12/2004. Patient characteristics, prescribing provider characteristics, length of therapy, and dosing were examined. A logistic regression assessed the probability of sub-therapeutic dosing. Results Among 830 individuals starting an atypical antipsychotic, only 15% had a documented diagnosis of schizophrenia, sub-therapeutic dosing was common (up to 86% of patients taking quetiapine), and 40% of the sample continued less than 30 days with the indexed prescription. A logistic model indicated that a general practitioner as prescribing provider, length of therapy less than 30 days, and prescription of quetiapine were significantly associated with a sub-therapeutic dose. Conclusions These results suggest there is extensive use of expensive atypical anti-psychotic medications for off-label purposes such as sedation or for other practice patterns that should be explored further. Approaches that minimize off-label atypical antipsychotic use could be of considerable value to Medicaid programs. In addition, theses findings support the need for the introduction or increased use of utilization monitoring, and the implementation of medication practice guidelines as appropriate decision support for prescribing providers.
Hartung, Daniel; Wisdom, Jennifer P.; Pollack, David A.; Hamer, Ann; Haxby, Dean; Middleton, Luke; McFarland, Bentson
Objectives: Anecdotal evidence suggests that second-generation antipsychotic agents are increasingly used to treat sleep problems. This study sought to quantify the proportion of new prescriptions for second-generation antipsychotic agents started for sleep/sedation and the correlates of such use. Design: A cross-sectional survey of provider decision making at the time second-generation antipsychotic agents were prescribed, documenting the reasons for the medication, patient demographics, psychiatric and medical diagnoses, patient health characteristics, and provider background. Setting: A single Veterans Affairs Medical Center over a 20-month period. Participants: Prescribers of second-generation antipsychotic agents. Interventions: N/A. Results: Seven hundred seven (32.2%) of 2,613 surveys indicated sleep/sedation was at least one reason for using a second-generation anti-psychotic agent, whereas for 266 (12.1%) it was the only reason. Quetiapine was most frequently prescribed overall as well as for sleep/sedation (47.0% and 73.6% respectively). Second-generation antipsychotic agent use for sleep/sedation was unrelated to sociodemographic characteristics, least likely in patients with schizophrenia or bipolar disorder, and most likely as a newly started second-generation antipsychotic agent. Conclusion: Sleep/sedation is a common reason given for new prescriptions of second-generation antipsychotic agents. Quetiapine is most frequently used for this purpose. A greater understanding of why providers use second-generation antipsychotic agents rather than safer and less costly alternatives for sleep problems may advance the development of interventions to reduce adverse effects. Citation: Hermes EDA; Sernyak M; Rosenheck R. Use of second-generation antipsychotic agents for sleep and sedation: a provider survey. SLEEP 2013;36(4):597-600.
Hermes, Eric D. A.; Sernyak, Michael; Rosenheck, Robert
This study sought to determine whether the presence of in vitro anticholinergic activity (AA) among different drugs is associated with reporting of neuropsychiatric adverse events (NPAEs) and whether age affects this relationship. Retrospective case/noncase analyses using Australia's spontaneous Adverse Drug Reaction System (ADRS) database containing 150 475 reports determined crude and adjusted reporting odds ratios (RORs) for NPAEs for 23 drugs with various reported in vitro AA. Covariates were age (treated as a dichotomous variable [> or =65 years]), gender, and concomitant use of antipsychotics, benzodiazepines, tricyclic antidepressants, and drugs with recognized inherent anticholinergic properties (anticholinergic drugs). The interaction effect between these covariates and each drug exposure category was examined. Age (> or =65 years) has a significant association with greater odds relative to younger age for reporting NPAEs. Drugs with reported significant AA in vitro were not always associated with RORs greater than 1 for reporting NPAEs, highlighting a dissonance between the in vitro AA index and ADRS observations. Significant interactions were observed between age (> or =65 years) and exposure to cimetidine, anticholinergic drugs, antipsychotics, and tricyclic antidepressants in modifying odds for reporting NPAEs, reinforcing the need for cautious use and monitoring of drugs with AA in older people. PMID:19783711
Nishtala, Prasad S; Fois, Romano A; McLachlan, Andrew J; Bell, J Simon; Kelly, Patrick J; Chen, Timothy F
Background Second generation antipsychotics (SGAs) are thought to have a lower likelihood of inducing extrapyramidal symptoms (EPS) than first generation antipsychotics (FGAs). Clinical observations suggest that younger patients may be more sensitive to SGA-associated EPS than adults and require therapy with anticholinergic agents, which are known to impair cognitive performance. The scope of anticholinergic use in this patient population and differences in utilization across SGAs (as well as FGAs) has not been extensively studied. Objective The primary objective of this study was to determine the proportion of patients five to 18 years of age who received anticholinergic therapy during the initial stages of antipsychotic treatment. A secondary objective was to compare anticholinergic use across patients receiving aripiprazole, risperidone, and quetiapine, SGAs previously identified to be the most commonly prescribed at the academic institution studied. Methods Patients five to 18 years of age initiating a trial of an antipsychotic between January 1, 2005 and September 1, 2008 were identified in a retrospective review of prescription and medical records. Demographic characteristics, antipsychotic and anticholinergic utilization, indications, diagnoses, and concomitant medications and doses were collected from the electronic medical record. For patients who received more than one therapeutic course of an antipsychotic during the identified timeframe, only the first course identified in the medical record was used for analyses. Anticholinergic utilization at antipsychotic initiation and after 30 days was assessed. Variables associated with anticholinergic use and differences across agents were identified. Results A total of 235 antipsychotic treatment courses were identified. Of these, 152 patients met our inclusion criteria and represented the first documented use of an antipsychotic at the present institution. Anticholinergic use at any time during the first 30 days of treatment was identified in 32 patients (21%) while EPS was documented for 12 patients (7.8%). FGA or polypharmacy defined as simultaneous use of ?1 scheduled antipsychotic versus SGA (OR=18.98; 95% CI:4.74 – 75.95) was the primary characteristic significantly associated with anticholinergic use 30 days after initiation. Risperidone, quetiapine, and aripiprazole were the three most commonly prescribed antipsychotics. Of these SGAs, anticholinergic use was most frequently prescribed with risperidone treatment (p=0.03). Conclusion Anticholinergic use exceeded the incidence of EPS as documented in the electronic medical record (21% vs 8%) and differed across individual medications as well as antipsychotic class. Use of an FGA or polypharmacy was a key predictor of anticholinergic use.
Hong, Irene S.; Bishop, Jeffrey R.
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.
Objective Osteoporosis is increasingly common worldwide and there is growing concern that the long-term use of antipsychotic medications increases the risk of this disorder. In this review we consider whether antipsychotics may contribute to the development of osteoporosis through reductions in bone mineral density (BMD), discuss the possible mechanisms involved and consider the clinical implications of such a relationship. Methods We searched the literature for studies in this area published between 1966 and 2010 using the Medline and PubMed databases and the following search terms: (schizophrenia OR antipsychotic OR neuroleptic) AND (osteoporosis OR hyperprolactinaemia OR bone mineral density). Results The available data indicates that statistically significant reductions in bone mineral density are frequently seen in patients prescribed antipsychotic medications and suggests that there is a higher incidence of clinically significant reductions compared with the normal population. Conclusions Clinicians should be aware for the potential negative effects of antipsychotic medications on bone mineral density, particularly in patients with additional risk factors for osteoporosis. Recommendations regarding routine monitoring of bone mineral density for patients prescribed antipsychotic medications cannot be made on the basis of existing evidence and more research is required. Is antipsychotic treatment linked to low bone mineral density and osteoporosis? A review of the evidence and the clinical implications
Crews, Matthieu P K; Howes, Oliver D
Scientific research aiming at discovering new generations of effective medications is a common practice in medicine, and psychiatric research is no exception. Antipsychotics are used to treat chronic mental illnesses such as schizophrenia. The new generation of antipsychotics (atypicals) gradually reveal their advantages in comparison to the older generation of antipsychotics (conventional, typicals) and are increasingly applied to the everyday practice. Although there are no differences in the therapeutic effectiveness between the two groups mentioned, atypical antipsychotics have become the drugs of choice. A certain number of women in their reproductive age suffer from schizophrenia and other mental illnesses which demand antipsychotic treatment. Atypical antipsychotics have been available on the market since the mid 90's so the experience in the application of these medicaments in treating pregnant women is relatively modest. This study will present our own experience in the treatment of a pregnant woman suffering from schizophrenia, who was treated with ziprasidone for the duration of her pregnancy. The psychotic symptoms remained in remission throughout the whole pregnancy period, during labour and after the birth. The pregnancy course remained normal all through to the birth, which was carried out naturally and normally. A healthy baby was born within the term expected. PMID:19794358
Ruzi?, Klementina; Dadi?-Hero, Elizabeta; Knez, Rajna; Medved, Paola; Petri?, Daniela
Recent studies have shown a strong link between Toxoplasma gondii infection and psychiatric disorders, especially schizophrenia and bipolar disorders (odd ratio ?2.7 for each disorder). Antipsychotic drugs and mood stabilizers may have anti-toxoplasmic activity that potentially may be associated with better effectiveness in these disorders, but previous results have been few in number and conflicting. We therefore sought to determine which daily prescribed antipsychotics and mood stabilizer have the best anti-toxoplasmic activity during the development phase of the parasite. In the present study, we examined the effects of commonly used antipsychotic drugs (amisulpride, cyamemazine, fluphenazine, haloperidol, levomepromazine, loxapine, olanzapine, risperidone and tiapride) and one mood-stabilizing agent (valproate) on toxoplasmic activity. We replicated that fluphenazine has a high anti-toxoplasmic activity, but it does not seem to be a phenothiazine-specific class effect: indeed, we found that another first-generation antipsychotic, zuclopenthixol, has a high anti-toxoplasmic activity. Valproate, tiapride and amisulpride have no anti-toxoplasmic activity on parasite growth, and the other antipsychotic drugs showed low or intermediate anti-toxoplasmic activity. As it is not possible to know the intracellular concentrations of antipsychotics in the brain, further clinical studies are warranted to determine whether these in vitro findings have potential implications in treatment of toxo-positive patients with schizophrenia. These findings may be potentially relevant for the choice of the first-line antipsychotic drug or mood stabilizer in previously infected patients. PMID:23771405
Fond, Guillaume; Macgregor, Alexandra; Tamouza, Ryad; Hamdani, Nora; Meary, Alexandre; Leboyer, Marion; Dubremetz, Jean-Francois
inflation, increase in utilization, and the shift from older to newer thera- pies. Pure price inflation is further discussed in an annual employer health benefits survey reported by the American Association of Retired Persons3 in which they compare changes in the manufacturer prices for the most commonly used brand-name prescription drugs in 2005 with general infla- tion. The cumulative comparison
C. Daniel Mullins; Francis B. Palumbo; Mojdeh Saba
Background Antipsychotic medications are commonly prescribed to nursing home residents despite their well-established adverse event profiles. Because little is known about their use in Veterans Administration(VA) nursing homes (i.e., Community Living Centers(CLCs)), we assessed the prevalence and risk factors for their use in older residents of VA CLCs. Methods This cross-sectional study included 3,692 Veterans ?age 65 who were admitted between January 2004-June 2005 to one of 133 VA CLCs and had a stay of ?90 days. We used VA Pharmacy Benefits Management data to examine antipsychotic use and VA Medical SAS datasets and the Minimum Data Set to identify evidence-based indications for antipsychotic use (e.g., schizophrenia, dementia with psychosis). We used multivariable logistic regression with generalized estimating equations to identify factors independently associated with antipsychotic use. Results Overall, 948/3,692(25.7%) residents used an antipsychotic, of which 59.3% had an evidence-based indication for use. Residents with aggressive behavior (odds ratio[OR]=2.74, 95% confidence interval[CI]=2.04-3.67) and polypharmacy (9+ drugs; OR=1.84, 95%CI=1.41-2.40) were more likely to receive antipsychotics, as were users of antidepressants (OR=1.37, 95%CI=1.14-1.66), anxiolytic/hypnotics (OR=2.30, 95%CI=1.64-3.23) or drugs for dementia (OR=1.52, 95%CI=1.21-1.92). Those residing in Alzheimer's/dementia special care units were also more likely to use an antipsychotic (OR=1.66, 95%CI=1.26-2.21). Veterans with dementia but no documented psychosis were as likely as those with an evidence-based indication to receive an antipsychotic (OR=1.10, 95%CI=0.82-1.47). Conclusions Antipsychotic use is common in older VA CLC residents, including those without a documented evidence-based indication for use. Further quality improvement efforts are needed to reduce potentially inappropriate antipsychotic prescribing.
Gellad, WF; Aspinall, SL; Handler, SM; Stone, RA; Castle, N; Semla, TP; Good, CB; Fine, MJ; Dysken, M; Hanlon, JT
|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.…
Ansbach, Robert K.; Dybus, Karen; Bergeson, Rachel
Prescription of atypical antipsychotics has increased in recent years. There have also been changes in the guidance on using older drugs, particularly the restriction in the use of thioridazine. We analysed deaths due to poisoning involving antipsychotics in England and Wales, 1993-2002, by age, sex, intent, and agents involved. We also studied antipsychotic prescribing in the community and poisoning deaths
C. Griffiths; R. J. Flanagan
Objectives To document the extent and appropriateness of use of antipsychotics and benzodiazepines among nursing home residents using a nationally representative survey. Methods Cross-sectional analysis of the 2004 National Nursing Home Survey. Bivariate and multivariate analyses examined relationships between resident and facility characteristics and antipsychotic and benzodiazepine use by appropriateness classification among residents aged 60 years and older (N = 12,090). Resident diagnoses and information about behavioral problems were used to categorize antipsychotic and benzodiazepine use as appropriate, potentially appropriate, or having no appropriate indication. Results More than one quarter (26%) of nursing home residents used an antipsychotic medication, 40% of whom had no appropriate indication for such use. Among the 13% of residents who took benzodiazepines, 42% had no appropriate indication. In adjusted analyses, the odds of residents taking an antipsychotic without an appropriate indication were highest for residents with diagnoses of depression (odds ratio [OR] = 1.31; 95% confidence interval [CI]: 1.12–1.53), dementia (OR = 1.82; 95% CI: 1.52–2.18), and with behavioral symptoms (OR = 1.97, 95% CI: 1.56–2.50). The odds of potentially inappropriate antipsychotic use increased as the percentage of Medicaid residents in a facility increased (OR = 1.08, 95% CI: 1.02–1.15) and decreased as the percentage of Medicare residents increased (OR = 0.46, 95% CI: 0.25–0.83). The odds of taking a benzodiazepine without an appropriate indication were highest among residents who were female (OR = 1.44; 95% CI: 1.18–1.75), white (OR = 1.95; 95% CI: 1.47–2.60), and had behavioral symptoms (OR = 1.69; 95% CI: 1.41–2.01). Conclusion Antipsychotics and benzodiazepines seem to be commonly prescribed to residents lacking an appropriate indication for their use.
Stevenson, David G.; Decker, Sandra L.; Dwyer, Lisa L.; Huskamp, Haiden A.; Grabowski, David C.; Metzger, Eran D.; Mitchell, Susan L.
Second generation antipsychotics (SGAs) have been linked to metabolic and bone disorders in clinical studies, but the mechanisms of these side effects remain unclear. Additionally, no studies have examined whether SGAs cause bone loss in mice. Using in vivo and in vitro modeling we examined the effects of risperidone, the most commonly prescribed SGA, on bone in C57BL6\\/J (B6) mice.
Katherine J. Motyl; Ingrid Dick-de-Paula; Ann E. Maloney; Sutada Lotinun; Sheila Bornstein; Francisco J. A. de Paula; Roland Baron; Karen L. Houseknecht; Clifford J. Rosen
RATIONALE: Autism spectrum disorders (ASDs) affect 1 % of children, having significant impact on health and social outcomes. Psychotropic medication use by individuals with ASD in the USA increased over time, and polypharmacy occurred in >50 % of those prescribed. In the UK, no psychotropic drugs are approved in ASDs, and little is known about patterns of pharmacological treatment in the ASD population and associated co-morbidities. METHODS: We used The Health Improvement Network, a nationally representative primary care database, to assess the prevalence of ASD diagnoses, psychotropic drug prescribing and neuropsychiatric co-morbidities of 0-24 year olds between 1992 and 2008. RESULTS: ASD prevalence increased 65-fold from 0.01 % (1992) to 0.50 % (2008). Psychotropic drugs were prescribed to 29 % (1,619/5,651) of the ASD cohort; the most prescribed drugs were sleep medication (9.7 % of prescribed patients), psychostimulants (7.9 %) and antipsychotics (7.3 %). More patients were given psychostimulants and sleep medications over time from 1.5-6.3 % and 2.2-5.9 % respectively. Thirty-seven per cent of the cohort had ?1 record of a neuropsychiatric co-morbidity, the most common being developmental difficulties and learning disabilities (12.6 %), behavioural, conduct and personality disorders (11.1 %) and attention deficit hyperactivity disorder (7.5 %). CONCLUSIONS: British physicians are more conservative in prescribing practice than American colleagues. However, use of psychostimulants and antipsychotics is much higher in those with ASD than in the general population. Polypharmacy was seen in 34 % of prescribed patients in 2008. Additional studies examining use, efficacy, and long-term safety of antipsychotics and psychostimulants in autistic individuals are warranted. PMID:23681164
Murray, Macey L; Hsia, Yingfen; Glaser, Karen; Simonoff, Emily; Murphy, Declan G M; Asherson, Philip J; Eklund, Hanna; Wong, Ian C K
Antipsychotic-induced weight gain has emerged as a serious complication in the treatment of patients with atypical antipsychotic drugs. The cannabinoid receptor 1 (CNR1) is expressed centrally in the hypothalamic region and associated with appetite and satiety, as well as peripherally. An antagonist of CNR1 (rimonabant) has been effective in causing weight loss in obese patients indicating that CNR1 might be important in antipsychotic-induced weight gain. Twenty tag SNPs were analyzed in 183 patients who underwent treatment (with either clozapine, olanzapine, haloperidol, or risperidone) for chronic schizophrenia were evaluated for antipsychotic-induced weight gain for up to 14 weeks. The polymorphism rs806378 was nominally associated with weight gain in patients of European ancestry treated with clozapine or olanzapine. ‘T' allele carriers (CT+TT) gained more weight (5.96%), than the CC carriers (2.76%, p=0.008, FDR q-value=0.12). This translated into approximately 2.2?kg more weight gain in patients carrying the T allele than the patients homozygous for the CC genotype (CC vs CT+TT, 2.21±4.51 vs 4.33±3.89?kg; p=0.022). This was reflected in the allelic analysis (C vs T allele, 3.84 vs 5.83%, p=0.035). We conducted electrophoretic mobility shift assays which showed that the presence of the T allele created a binding site for arylhydrocarbon receptor translocator (ARNT), a member of the basic helix–loop–helix/Per–Arnt–Sim protein family. In this study, we provide evidence that the CNR1 gene may be associated with antipsychotic-induced weight gain in chronic schizophrenia patients. However, these observations were made in a relatively small patient population; therefore these results need to be replicated in larger sample sets.
Tiwari, Arun K; Zai, Clement C; Likhodi, Olga; Lisker, Annika; Singh, Deepika; Souza, Renan P; Batra, Poonam; Zaidi, Syed H E; Chen, Sheng; Liu, Fang; Puls, Imke; Meltzer, Herbert Y; Lieberman, Jeffrey A; Kennedy, James L; Muller, Daniel J
Suicide rates in the elderly have declined in many countries in recent years. This decline has been reported to be associated with increased prescribing of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), antipsychotics and antimanic drugs and reduced prescribing of barbiturates, hypnotics and sedatives. This study examined the relationship between prescribing patterns of individual psychotropic drugs and suicide rates by specific methods of elderly suicides. There was a negative correlation between the prescription of tricyclic antidepressants, selective serotonin reuptake inhibitors, antipsychotics, antimanic drugs and non-opiate analgesics and a decline in elderly suicide rates due to poisoning by solid and liquid substances, hanging, strangulation and suffocation, drowning, firearms and explosives, and jumping from high places. There was a positive correlation between the prescription of barbiturates, hypnotics and sedatives and elderly suicide rates due to poisoning by solid and liquid substances, hanging, strangulation and suffocation, drowning, firearms and explosives, and jumping from high places. This study demonstrated that changes in prescribing patterns of individual psychotropic drugs do influence elderly suicide rates of the commonly used methods of suicide and suggest that this may be due to more accurate diagnostic-specific prescribing of psychotropic drugs. PMID:15895636
Shah, Ajit; Lodhi, Lubbaba
Objective This randomized trial addressed risks and benefits of staying on antipsychotic polypharmacy versus switching to monotherapy. Method Adult outpatients with schizophrenia taking two antipsychotics (127 participants across 19 sites) were randomly assigned to Stay on Polypharmacy or Switch to Monotherapy by discontinuing one antipsychotic. The trial lasted for 6 months, with a 6-month naturalistic follow-up. Kaplan-Meier and Cox regression analyses examined time to discontinuation of assigned antipsychotic treatment, and random regression models examined additional outcomes through time. Results Individuals assigned to Switch to Monotherapy had shorter times to all-cause treatment discontinuation than those assigned to Stay (p <.05). By month 6, 86% (n=48) of those assigned to Stay on Polypharmacy were still taking both medications whereas 69% (n=40) of those assigned to Switch to Monotherapy were still taking that monotherapy. Most monotherapy discontinuations entailed returning to the original polypharmacy. Groups did not differ with respect to psychiatric symptomatology or hospitalizations. The monotherapy group lost weight whereas the polypharmacy group gained weight. Conclusions Discontinuing one of two antipsychotics was followed by treatment discontinuation more often and more quickly than when both antipsychotics were continued. However, two thirds of participants successfully switched, groups did not differ with respect to symptom control, and switching to monotherapy resulted in weight loss. This supports the reasonableness of prescribing guidelines encouraging trials of antipsychotic monotherapy for individuals receiving antipsychotic polypharmacy, with the caveat that individuals should be free to return to polypharmacy if an adequate trial on antipsychotic monotherapy proves unsatisfactory.
Essock, Susan M.; Schooler, Nina R.; Stroup, T. Scott; McEvoy, Joseph P.; Rojas, Ingrid; Jackson, Carlos; Covell, Nancy H
Antipsychotic medications are widely used to treat several psychiatric disorders and are commonly categorized into two classes. First-generation antipsychotics (FGAs), also known as typical antipsychotics, were developed in the 1950s. Although they are us...
The advent of atypical antipsychotics greatly changed the treatment pattern for mental illnesses worldwide. This study was designed to determine the trend in prevalence, prescribing pattern, and cost of antipsychotic agents in Taiwan from 1997 to 2001. Data were obtained from claims completed for a random sample of 200,000 people registered with the National Health Insurance program. The antipsychotics monitored included all group N05A drugs in the Anatomical Therapeutic Chemical classification system (version 2000). Conventional and atypical antipsychotics were handled separately. Of the 195,971 eligible registrants, 37,441 (19.1%) received any kind of antipsychotic during this 5-year period, but only 713 (0.4%) used atypical antipsychotics. The prevalence of conventional antipsychotic use during each successive year of this study was 5.2%, 5.7%, 6.6%, 6.2%, and 6.1% and 0.1%, 0.1%, 0.1%, 0.2%, and 0.3% for atypical agents. Although far fewer registrants used them, atypicals comprised 19.1% of all prescribed amounts measured in defined daily doses and 56.1% of the cost for all antipsychotics in 2001. During the 5-year study period, atypical antipsychotics were prescribed for 405 (57%) patients with schizophrenia, 132 (19%) with affective disorder, 128 (18%) with other psychiatric disorders, and 48 (7%) with a nonpsychiatric disorder. With the loosening of reimbursement restrictions in 2002, continued growth of atypical antipsychotic use in Taiwan might be expected. PMID:15058752
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.
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
Tejal K. Gandhi; Saul N. Weingart; Andrew C. Seger; Joshua Borus; Elisabeth Burdick; Eric G. Poon; Lucian L. Leape; David W. Bates
Recent UK guidelines support the prescription of injectable heroin and methadone for opiate dependence, but many doctors disagree. Heroin has been prescribed in England for almost a hundred years, and the "British system" was once the subject of international curiosity. Since 1965, a prescriber licensing system has led to a great reduction in the proportion of opiate addicts treated with heroin. Recent trials in Switzerland and the Netherlands have prompted a review of British practice. It will probably remain somewhat different from continental practice, particularly with respect to long-term supervised injecting, but without adequate funding it may disappear altogether. PMID:16188711
Despite evidence from a variety of experimental approaches implicating the neuropeptide neurotensin in both the mechanism of action of antipsychotic drugs and the pathophysiology of schizophrenia, there has been some debate as to whether a peripherally administered neurotensin receptor agonist represents a sound strategy for the development of a novel class of antipsychotic drugs. PMID:11786316
Kinkead, Becky; Nemeroff, Charles B
In his everyday work the family physician sees many patients whose problems have been diagnosed but for whom postponement of an active treatment plan is indicated. The physician must therefore prescribe procrastination in a carefully planned way. I describe some ideas and practical methods for doing this. PMID:529244
Thomson, G H
In his everyday work the family physician sees many patients whose problems have been diagnosed but for whom postponement of an active treatment plan is indicated. The physician must therefore prescribe procrastination in a carefully planned way. I describe some ideas and practical methods for doing this.
Thomson, George H.
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.
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 Scale (AIMS), and Dyskinesia Identification System Condensed User Scale (DISCUS) are reviewed. Symptom
Johnny L. Matson; Sara Mahan
Atypical antipsychotics are increasingly popular and increasingly prescribed. In some countries, they can even be obtained over-the-counter, without a prescription, making their abuse quite easy. Although atypical antipsychotics are thought to be safer than typical antipsychotics, they still have severe side effects. Intoxications are not rare and some of them have a fatal outcome. Drug interactions involving atypical antipsychotics complicate patient management in clinical settings and the determination of the cause of death in fatalities. In view of the above, analytical strategies that can efficiently isolate atypical antipsychotics from a variety of biological samples and quantify them accurately, sensitively and reliably, are of utmost importance both for the clinical, as well as for the forensic toxicologist. In this review, we will present and discuss novel analytical strategies that have been developed from 2004 to the present day for the determination of atypical antipsychotics in various biological samples. PMID:22533569
Fragou, Domniki; Dotsika, Spyridoula; Sarafidou, Parthena; Samanidou, Victoria; Njau, Samuel; Kovatsi, Leda
The definition and assessment of adherence vary considerably across studies. Increasing consensus regarding these issues is necessary to improve our understanding of adherence and the development of more effective treatments. We review the adherence literature over the past 3 decades to explore the definitions and assessment of adherence to oral antipsychotics in schizophrenia patients. A total of 161 articles were identified through MEDLINE and PsycINFO searches. The most common method used to assess adherence was the report of the patient. Subjective and indirect methods including self-report, provider report, significant other report, and chart review were the only methods used to assess adherence in over 77% (124/161) of studies reviewed. Direct or objective measures including pill count, blood or urine analysis, electronic monitoring, and electronic refill records were used in less than 23% (37/161) of studies. Even in studies utilizing the same methodology to assess adherence, definitions of an adherent subject varied broadly from agreeing to take any medication to taking at least 90% of medication as prescribed. We make suggestions for consensus development, including the use of recommended terminology for different subject samples, the increased use of objective or direct measures, and the inclusion in all studies of an estimate of the percentage of medication taken as prescribed in an effort to increase comparability among studies. The suggestions are designed to advance the field with respect to both understanding predictors of adherence and developing interventions to improve adherence to oral antipsychotic medications.
Velligan, Dawn I.; Lam, Yui-Wing Francis; Glahn, David C.; Barrett, Jennifer A.; Maples, Natalie J.; Ereshefsky, Larry; Miller, Alexander L.
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.
Tully, Mary P
Background\\/Aims: To evaluate whether dementia patients prescribed antipsychotic drugs have a higher mortality compared to unexposed patients, and to investigate whether there are differences in mortality associated with exposure to conventional versus atypical antipsychotic drugs. Methods: Retrospective population cohort study with information gathered from the Italian Health Information System. All 4,369 residents of Milan (Italy) aged 60 years or older
Massimo Musicco; Katie Palmer; Antonio Russo; Carlo Caltagirone; Fulvio Adorni; Carla Pettenati; Luigi Bisanti
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.
Vasilyeva, Irina; Biscontri, Robert G.; Enns, Murray W.; Metge, Colleen J.; Alessi-Severini, Silvia
BACKGROUND. Elderly people are prescribed more drugs than younger people. The consequences of excessive or unwise prescribing, such as drug interactions, are well known. AIM. A longitudinal study was undertaken to examine levels and patterns of prescribed drug use among a group of elderly people. METHOD. Use of prescribed drugs by a sample of elderly people in Nottingham aged 65 years and over was assessed on two occasions four years apart, in 1985 and 1989. RESULTS. Complete drug data were available for 1003 respondents in 1985 and 662 respondents in 1989 (with attrition due mainly to mortality). Drug use increased significantly with age. Women took significantly more drugs than men. Approximately half of respondents were taking at least two drugs. The overall number of drugs per person being taken in 1989 was significantly greater than in 1985. This difference remained significant when age and mortality were controlled, suggesting that changes in drug use over time within this sample may reflect genuine changes in prescribing practice (rather than simply the effects of ageing). The most commonly prescribed drug classes on each occasion were drugs for the cardiovascular system, central nervous system, musculoskeletal system, gastrointestinal tract and respiratory system. The subgroups of drugs most commonly reported at each interview were diuretics, hypnotics and anxiolytics, analgesics and non-steroidal anti-inflammatory drugs. Drugs within the category 'hypnotics and anxiolytics' showed clear and differential trends over time, with the use of anxiolytics falling, while the use of hypnotics increased. Among those respondents admitted to residential care during the course of the study higher levels of psychotropic drug use, and an increase in antipsychotic medication, were observed. CONCLUSION. It is important that the drug regimens of elderly people are frequently reviewed to ensure that only the minimum number of effective drugs, in the simplest regimen, are prescribed.
Rumble, R H; Morgan, K
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.
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
There is currently considerable uncertainty regarding prescribing practices for pregnant women with severe and persistent psychiatric disorders. The physician and the mother have to balance the risks of untreated psychiatric illness against the potential fetal toxicity associated with pharmacological exposure. This is especially true for women taking atypical antipsychotics. Although these drugs have limited evidence for teratological risk, there are reports of altered fetal growth, both increased and decreased, with maternal atypical antipsychotic use. These effects may be mediated through changes in the maternal metabolism which in turn impacts placental function. However, the presence of receptors targeted by atypical antipsychotics in cell lineages present in the placenta suggests that these drugs can also have direct effects on placental function and development. The signaling pathways involved in linking the effects of atypical antipsychotics to placental dysfunction, ultimately resulting in altered fetal growth, remain elusive. This paper focuses on some possible pathways which may link atypical antipsychotics to placental dysfunction. PMID:22848828
Raha, Sandeep; Taylor, Valerie H; Holloway, Alison C
There is currently considerable uncertainty regarding prescribing practices for pregnant women with severe and persistent psychiatric disorders. The physician and the mother have to balance the risks of untreated psychiatric illness against the potential fetal toxicity associated with pharmacological exposure. This is especially true for women taking atypical antipsychotics. Although these drugs have limited evidence for teratological risk, there are reports of altered fetal growth, both increased and decreased, with maternal atypical antipsychotic use. These effects may be mediated through changes in the maternal metabolism which in turn impacts placental function. However, the presence of receptors targeted by atypical antipsychotics in cell lineages present in the placenta suggests that these drugs can also have direct effects on placental function and development. The signaling pathways involved in linking the effects of atypical antipsychotics to placental dysfunction, ultimately resulting in altered fetal growth, remain elusive. This paper focuses on some possible pathways which may link atypical antipsychotics to placental dysfunction.
Raha, Sandeep; Taylor, Valerie H.; Holloway, Alison C.
In elderly persons, antipsychotic drugs are clinically prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications (schizophrenia and bipolar disorder). The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia. In April 2005, the FDA, based on a meta-analysis of 17 double-blind randomized placebo-controlled trials among elderly
Dilip V Jeste; Dan Blazer; Daniel Casey; Thomas Meeks; Carl Salzman; Lon Schneider; Pierre Tariot; Kristine Yaffe
The incidence of schizophrenia in the general population ranges from about 1% to 2%. Schizophrenia affects men and women equally, occurring in all cultures and socioeconomic classes. The peak age of onset in women is 25 to 35 years, which are also the peak childbearing years, and women with psychotic illnesses are likely to have more unplanned pregnancies than women without a psychotic illness. Not only are antipsychotic medications prescribed for schizophrenia, but, especially since the introduction of the second-generation (atypical) antipsychotics, these drugs are also used to treat other psychiatric illnesses such as bipolar disorder. As a result, there is an increase in the number of women requiring antipsychotic drug therapy who are likely to become pregnant. It is important to evaluate the safety of these drugs in pregnancy, as most women with a serious psychiatric illness cannot stop taking their medication, as this would interfere with their activities of daily living, especially taking care of an infant. In this review, we describe available up-to-date, evidence-based information regarding the safety of antipsychotic drugs that are currently used in pregnancy. These include first-generation (conventional) antipsychotics (eg, promethazine, chlorpromazine, prochlorperazine, haloperidol, perphenazine, trifluoperazine, loxapine, thioridazine, flupenthixol, fluphenazine) and second-generation antipsychotics (eg, clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone). To date, no definitive association has been found between use of antipsychotics during pregnancy and an increased risk of birth defects or other adverse outcomes. However, there is a paucity of information, with a lack of large, well designed, prospective comparative studies. The information presented here should therefore not be interpreted as conclusive with regard to the safety of these drugs, as more research is needed. Women who require treatment should always discuss the risks and benefits of pharmacotherapy with their physician and, if it is felt that treatment should be continued during pregnancy, the evidenced-based information presented here will be of help in this important decision. PMID:19461391
Einarson, Adrienne; Boskovic, Rada
Individuals with intellectual disability frequently use antipsychotics for many years. This may have detrimental health effects, including neurological symptoms and metabolic and hormonal dysregulation, the latter possibly affecting bone metabolism. There is large variability in the degree in which antipsychotic agents lead to these health problems. In the current study we investigated potential determinants of physical symptoms and biological parameters known to be associated with use of antipsychotics in a convenience sample of 99 individuals with intellectual disability who had used antipsychotics for more than one year for behavioural symptoms. We focused on extrapyramidal symptoms; on overweight and presence of components of the metabolic syndrome; and on elevated plasma prolactin and bone turnover parameters. As predictor variables, we used patient (sex, age, genetic polymorphisms, and severity of intellectual disability) and medication use (type and dosage) characteristics. We found extrapyramidal symptoms to be present in 53%, overweight or obesity in 46%, and the metabolic syndrome in 11% of participants. Hyperprolactineaemia and one or more elevated bone turnover markers were present in 17% and 25%, respectively. Higher age and more severe intellectual disability were associated with dyskinesia and a higher dosage of the antipsychotic drug was associated with parkinsonism. Less severe intellectual disability was related to higher Body Mass Index. Use of atypical antipsychotics was associated with higher diastolic blood pressure and elevated fasting glucose. Clinicians who prescribe antipsychotics in individuals with intellectual disability should carefully balance the potential benefits of prolonged treatment against the risk of health hazards associated with the use of antipsychotics. PMID:23792429
de Kuijper, Gerda; Mulder, Hans; Evenhuis, Heleen; Scholte, Frans; Visser, Frank; Hoekstra, Pieter J
Chronic illness can result in chronicity of clinical practice. As we have moved away from prescribing classical antipsychotics and tricyclic antidepressants, issues remain with the use of atypical antipsychotics and second-generation antidepressants that need to be addressed, namely, iatrogenic discontinuation syndromes and supersensitivity psychiatric symptoms. An optimal maintenance drug treatment consists of regular attempts to reduce the dose by finding
Guy Chouinard; Virginie-Anne Chouinard
Background Antipsychotic are the cornerstone in the treatment of schizophrenia. They also have a number of side-effects. Constipation is thought to be common, and a potential serious side-effect, which has received little attention in recent literature. Method We performed a retrospective study in consecutively admitted patients, between 2007 and 2009 and treated with antipsychotic medication, linking different electronic patient data to evaluate the prevalence and severity of constipation in patients with schizophrenia under routine treatment conditions. Results Over a period of 22 months 36.3% of patients (99) received at least once a pharmacological treatment for constipation. On average medication for constipation was prescribed for 273 days. Severe cases (N = 50), non-responsive to initial treatment, got a plain x-ray of the abdomen. In 68.4% fecal impaction was found. Conclusion A high prevalence of constipation, often severe and needing medical interventions, was confirmed during the study period. Early detection, monitoring over treatment and early intervention of constipation could prevent serious consequences such as ileus.
Background Care home residents are vulnerable to the adverse effects of prescribing but there is limited monitoring in the UK. Aim To compare prescribing quality in care homes in England and Wales with the community and with US nursing homes. Design and setting Cross-sectional analysis of a UK primary care database and comparison with the US National Nursing Home Survey including 326 general practices in 2008–2009 in England and Wales, with 10 387 care home and 403 259 community residents aged 65 to 104 years. Method Comparison of age- and sex-standardised use of ‘concern’ and common drug groups in the last 90 days and potentially inappropriate prescribing based on a consensus list of medications best avoided in older people (Beers criteria). Results Compared to the community, care home residents were more likely to receive ‘concern’ drugs, including benzodiazepines (relative risk (RR) = 2.05, 95% confidence interval (CI) = 1.90 to 2.22), anticholinergic antihistamines (RR = 2.78, 95% CI = 2.38 to 3.23), loop diuretics (RR = 1.47, 95% CI = 1.41 to 1.53), and antipsychotics (RR = 22.7, 95% CI = 20.6 to 24.9). Use of several common drug groups, including laxatives, antidepressants, and antibiotics, was higher, but use of cardiovascular medication was lower. Thirty-three per cent (95% CI = 31.7% to 34.3%) of care home residents in England and Wales received potentially inappropriate medication, compared to 21.4% (95% CI = 20.9% to 21.8%) in the community. The potentially inappropriate prescribing rate in US nursing homes was similar to England and Wales. Conclusion Care home prescribing has the potential for improvement. High use of anticholinergic and psychotropic medication may contribute to functional and cognitive decline. The targeting and effectiveness of medication reviews in care homes needs to be improved.
Shah, Sunil M; Carey, Iain M; Harris, Tess; DeWilde, Stephen; Cook, Derek G
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
Erickson, Steven K; Ciccone, J Richard; Schwarzkopf, Steven B; Lamberti, J Steven; Vitacco, Michael J
The highly efficacious actions of N -desmethylclozapine at muscarinic receptors are unique and not a common property of either typical or atypical antipsychotic drugs: is M 1 agonism a pre-requisite for mimicking clozapine’s actions?
Rationale: Recent studies have suggested that the salutary actions of clozapine in schizophrenia may be due to selective activation of M1 muscarinic receptors by clozapine and\\/or its major active metabolite N-desmethyl- clozapine. Objective: We systematically tested this hy- pothesis by screening a large number of psychoactive compounds, including many atypical antipsychotic drugs, for agonist activity at cloned, human M1 ,M
Marilyn A. Davies; Beth Ann Compton-Toth; Sandra J. Hufeisen; Herbert Y. Meltzer; Bryan L. Roth
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.…
Scheifes, A.; Stolker, J. J.; Egberts, A. C. G.; Nijman, H. L. I.; Heerdink, E. R.
Antipsychotic medications are important for the successful management of schizophrenia. Continuous treatment with medication is superior in relapse prevention and non-adherence to antipsychotic medication is associated with a poor clinical outcome. Long-acting injectable antipsychotics (LAIs) that can guarantee adherence to a treatment regimen could be a useful treatment option. With the introduction of second-generation atypical antipsychotics-long acting injection (SGA-LAI), the risks for extrapyramidal adverse events are decreased. The indications for SGA-LAI have been extended from chronic, stabilized patients to acute psychotic patients. Some studies investigated the use of LAI in first-episode schizophrenia patients and raised the possibility of prescribing LAI as a treatment option. However, there is still limited research using LAI in first-episode schizophrenia. More well-designed, randomized, controlled clinical trials using SGA-LAIs in first episode schizophrenia are needed. Additionally, studies on side effects of SGA-LAI in long-term use are required prior to recommending LAI for patients with first episode schizophrenia.
Data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) was used with the objective of evaluating factors associated with antipsychotic dose changes. CATIE was a randomized, comparative effectiveness trial for patients with schizophrenia in which a clinician prescribed a double-blind, flexible dose of 1 of 5 antipsychotic medications. The mean number of capsules prescribed monthly was evaluated to identify the period following up-titration with the least sample attrition in which dose changes were likely in response to clinical factors. Demographic, efficacy and tolerability variables were evaluated in two regression models predicting a one capsule dose decrease or increase. The mean dose increased to 2.7 capsules over the first 3 months. The post-titration plateau was identified as between 3 and 6 months. Factors associated with dose increases included the Clinical Global Impression Scale at 6 months and change in the Positive and Negative Syndrome Scale between 3 and 6 months. Decreased dosing was associated only with lower patient rated 6-month global impression of health. Neither tolerability measures, nor body weight were significantly associated with dose changes. In conclusion, dose changes were weakly associated with measures of current or changing clinical status and not affected by measures of side effects.
Hermes, Eric; Rosenheck, Robert
Background: Community treatment orders (CTOs) are increasingly being used, despite a weak evidence base, and problems continue regarding Second Opinion Appointed Doctor (SOAD) certification of medication. Aims: The aim of the current study was to describe current CTO usage regarding patient characteristics, prescribed medication and CTO conditions. Method: A 1-year prospective cohort study with consecutive sampling was conducted for all patients whose CTO was registered in a large mental health trust. Only the first CTO for each patient was included. Measures included sociodemographic variables, psychiatric diagnosis, CTO date of initiation and conditions, psychotropic medication and date of SOAD certification for medication. This study was conducted in the first year of CTO legislation in England and Wales. Results: A total of195 patients were sampled (mean age 40.6 years, 65% male, 52% black ethnic origin). There was significant geographical variability in rates of CTO use (?2 = 11.3, p = 0.012). A total of 53% had their place of residence specified as a condition and 29% were required to allow access into their homes. Of those with schizophrenia, 64% were prescribed an antipsychotic long-acting injection (LAI). Of the total group, 7% received high-dose antipsychotics, 10% were prescribed two antipsychotics and only 15% received SOAD certification in time. Conclusions: There was geographical and ethnic variation in CTO use but higher rates of hospital detention in minority ethnic groups may be contributory. Most patients were prescribed antipsychotic LAIs and CTO conditions may not follow the least restrictive principle.
Patel, Maxine X.; Matonhodze, Jane; Baig, Mirza K.; Gilleen, James; Boydell, Jane; Holloway, Frank; Taylor, David; Szmukler, George; Lambert, Tim; David, Anthony S.
The introduction of atypical antipsychotic drugs (AAPDs), or second-generation antipsychotics, with clozapine as the prototype, has largely changed the clinicians' attitudes toward the treatment of mental illnesses including, but not limited to schizophrenia. Initially, there was optimism that AAPDs would be superior over typical antipsychotic drugs (TAPDs), or first-generation antipsychotic drugs, in terms of efficacy in various phenomenological aspects, including cognitive impairment, and less likelihood of causing adverse events. However, these views have been partly challenged by results from recent meta-analysis studies. Specifically, cardio-metabolic side effects of AAPDs, in spite of a relative paucity of extrapyramidal symptoms, may sometimes limit the use of these agents. Accordingly, attempts have been made to develop newer compounds, e.g., lurasidone, with the aim of increasing efficacy and tolerability. Further investigations are warranted to determine if a larger proportion of patients will be benefitted by treatment with AAPDs compared to TAPDs in terms of remission and recovery.
A hazardous fuel reduction project planned for Dry Armells Creek within the Missouri Breaks National Monument, Montana was modified to test the effects of prescribed fire on various ecological processes within the dry, prairie savanna forest types common ...
C. Wood C. B. Marlow J. Walker R. Tucker V. Shea
Obesity is one of the most common physical health problems among patients with severe and persistent mental illnesses, such as schizophrenia. Multifactorial in origin, obesity can be attributed to an unhealthy lifestyle as well as the effects of psychotropic medications such as second-generation antipsychotics. Excess body weight increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, hypertension, and gallbladder disease. A PubMed search revealed 403 English-language citations to the query "schizophrenia" AND "obesity" and 469 citations to the query "obesity" AND "antipsychotics." The evidence is that different antipsychotics have different propensities for weight gain, and that children, adolescents, and fi rst-episode patients are at higher risk for weight gain associated with antipsychotic treatment. Monitoring body weight early in treatment will help predict those at high risk for substantial weight gain. Switching antipsychotic medication may or may not be clinically feasible, but can lead to a reduction in body weight. Lifestyle therapies and other nonpharmacological interventions have been shown to be effective in controlled clinical trials, but the evidence base for adjunctive medication strategies such as with orlistat, sibutramine, amantadine, nizatidine, metformin, topiramate, and others, is conflicting. At the very least, a "small-steps approach" to managing weight should be offered to all patients who are overweight or obese. PMID:18654065
Citrome, Leslie; Vreeland, Betty
Weight gain is a common complication of antipsychotic treatment. Its consequences include decreased self-esteem, reduced quality of life, reduced adherence with medication and increased morbidity and mortality. Most studies that assess weight change are short term. Among the atypicals mean weight gain is greatest with olanzapine and clozapine and least with aripiprazole and ziprasidone. Mean weight change obscures the marked
The quinidine-like effects of some antidepressant drugs (particularly tricyclic antidepressants) and many antipsychotic drugs (particularly the phenothiazines) confound treatment of psychosis and depression in patients with major mental illness. This is especially true among elderly patients with existing risk factors for corrected QT (QTc) interval prolongation. We used PubMed, previously reported review articles and the extensive personal files of the authors to identify cases of subjects aged>or=60 years who developed QTc interval prolongation, polymorphic ventricular tachycardia (PVT)/torsade de pointes (TdP) and/or sudden cardiac death while taking antipsychotic or antidepressant drugs or a combination of these medications. We identified 37 patients who had taken, in total, 46 antipsychotic or antidepressant drugs. Our most striking finding was that almost four-fifths of our cases involved women. When the 14 critically ill subjects receiving haloperidol intravenously were excluded, 91.3% of our subjects were women. Almost three-quarters of our study subjects had cardiovascular disease. Intravenous administration of haloperidol in the critically ill and profoundly agitated elderly warrants particular comment. Of the 14 subjects in this category identified, six were men and eight were women. In 13 cases, the drug dose far exceeded the 2 mg necessary to produce an antipsychotic effect. These clinicians were using an agent to achieve sedation that usually requires very high doses in the critically ill and profoundly agitated elderly to achieve this effect. Inclusion criteria for our literature review required antipsychotic and/or antidepressant drug-induced QTc interval prolongation. Even so, our finding that 31 of our 37 subjects developed PVT is sobering. However, the reader should not conclude that drug-induced QTc interval prolongation is highly predictive of PVT or its TdP subtype. All of our study subjects had at least two risk factors for TdP, with age and sex being the most common. We included the rare case of a patient with congenital long QT syndrome who developed further lengthening of the QTc interval and TdP when prescribed an antidepressant drug well known to produce QTc interval prolongation. We conclude with recommendations for clinicians not expert in the specialty of cardiology to deal with the many questions raised in this review. Specifically, such clinicians treating elderly patients with antipsychotic and antidepressant drugs that may prolong the QTc interval should aggressively obtain a baseline ECG for elderly female patients with additional risk factors such as personal or family history of pre-syncope or syncope, electrolyte disturbances or cardiovascular disease. Elderly male patients are also subject to QTc interval prolongation when such risk factors are present. It is important that the clinicians themselves inspect ECGs. If the QT interval is more than half the RR interval, QTc interval prolongation is likely to be present. In such cases, a cardiology colleague interested in QTc interval issues and TdP should be asked to review the ECG. Finally, nothing in our recommendations replaces meticulous attention to US FDA guidelines in the package insert of each drug. PMID:19929028
Vieweg, W Victor R; Wood, Mark A; Fernandez, Antony; Beatty-Brooks, Mary; Hasnain, Mehrul; Pandurangi, Anand K
Sexual dysfunction is a common condition in patients taking antipsychotics, and is the most bothersome symptom and adverse drug effect, resulting in a negative effect on treatment compliance. It is known that hyperprolactinemia is a major cause of sexual dysfunction. Based on the blockade of dopamine D2 receptors, haloperidol, risperidone, and amisulpride are classed as prolactin-elevating antipsychotics, while olanzapine, clozapine, quetiapine, ziprasidone, and aripiprazole are classed as prolactin-sparing drugs. Risperidone and the other typical antipsychotics are associated with a high rate of sexual dysfunction as compared to olanzapine, clozapine, quetiapine, and aripiprazole. With regard to treatment in patients suffering from sexual dysfunction, sildenafil was associated with significantly more erections sufficient for penetration as compared to a placebo. Subsequent studies are needed in order to provide physicians with a better understanding of this problem, thereby leading toward efficacious and safe solutions. PMID:23596605
Park, Yeon Won; Kim, Yooseok; Lee, Jun Ho
Newer atypical antipsychotics demonstrate superior effectiveness, with a diminished incidence of extrapyramidal side effects compared with older typical antipsychotics, but they have been associated with the development of obesity and new-onset diabetes. A small number of reports documenting modest hypertriglyceridemia related to newer antipsychotics have implicated fluperlapine, clozapine, and, most recently, olanzapine. This study summarizes the results of 14 cases of severe hypertriglyceridemia (>600 mg/dL) associated with olanzapine and quetiapine therapy occurring among inpatients at Oregon State Hospital, including 7 patients whose serum triglyceride levels exceeded 1,000 mg/ dL. Four of these patients also developed new-onset diabetes. Nine cases occurred during the first 8 months of treatment, with three cases identified within 3 months of commencing olanzapine or quetiapine therapy. Weight gain in olanzapine and quetiapine groups was modest (12.3 lb and 8.5 lb, respectively) and did not correlate with the severity of hypertriglyceridemia. Biochemical causes for severe hypertriglyceridemia associated with novel antipsychotics are unclear, but clinical monitoring of serum lipids must be added to the concerns about the metabolic consequences of therapy with certain newer antipsychotic agents. PMID:11476120
Meyer, J M
Background Since the introduction of antipsychotics, especially the so called atypicals, the treatment of schizophrenia has shown important improvements. At the present time, it is preferred to label clozapine and other antipsychotics sharing similar profiles as second-generation antipsychotics (SGAs). These medications have been proposed by some experts as a first line treatment for schizophrenia. It is critical to have reliable data about antipsychotic prescription in Mexico and to create management guidelines based on expert meetings and not only on studies carried out by the pharmaceutical industry. Only this approach will help to make the right decisions for the treatment of schizophrenia. Methods A translated version of Rabinowitz's survey was used to evaluate antipsychotic prescription preferences and patterns in Mexican psychiatrists. The survey questionnaire was sent by mail to 200 psychiatrists from public institutions and private practice in Mexico City and Guadalajara, Mexico. Results Recommendations for antipsychotics daily doses at different stages of the treatment of schizophrenia varied widely. Haloperidol was considered as the first choice for the treatment of positive symptoms. On the contrary, risperidone was the first option for negative symptoms. For a patient with a high susceptibility for developing extrapyramidal symptoms (EPS), risperidone was the first choice. It was also considered that SGAs had advantages over typical antipsychotics in the management of negative symptoms, cognitive impairment and fewer EPS. Besides, there was a clear tendency for prescribing typical antipsychotics at higher doses than recommended and inadequate doses for the atypical ones. Conclusions Some of the obstacles for the prescription of SGAs include their high cost, deficient knowledge about their indications and dosage, the perception of their being less efficient for the treatment of positive symptoms and the resistance of some Mexican physicians to change their prescription pattern. It is necessary to reach a consensus, in order to establish and standardize the treatment of schizophrenia, based on the information reported in clinical trials and prevailing economic conditions in Mexico.
Apiquian, Rogelio; Fresan, Ana; de la Fuente-Sandoval, Camilo; Ulloa, Rosa-Elena; Nicolini, Humberto
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…
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…
Noggle, Chad A.; Dean, Raymond S.
Antipsychotic medicines are the cornerstone pharmacotherapy for patients with psychotic disorders. Early and continuous management of psychoses improves the quality of life, decreases hospitalization and reduces medical costs. However, many psychotic patients are not fully compliant with treatment, and thus they more often experience a relapsing course with a suboptimal clinical outcome. Long-term parenteral antipsychotic agents may improve compliance by offering clear evidence of medication non-compliance and documented drug administration monitoring. Using injection therapy might be especially beneficial to poorly compliant individuals with their first-psychotic episode and those with severe psychopathology or comorbid substance abuse. The availability of five different antipsychotic drug depot medications offers diverse treatment options which can be individualized for each case. PMID:22250654
Baweja, Raman; Sedky, Karim; Lippmann, Steven
This article briefly reviews the novel atypical second-generation antipsychotic drugs iloperidone (Fanapt®), asenapine (Saphris®), and lurasidone (Latuda®), all of which have been approved by the U.S. Food and Drug Administration since 2009. Each is indicated for the treatment of schizophrenia, and asenapine has an additional indication for bipolar disorder. Very little information is available on their use in other disorders, pediatric and geriatric patients, and during pregnancy and breastfeeding. Their overall efficacy is no different than other antipsychotic drugs, but they do have different side effect profiles. Because of their unique pharmacologies and different tolerability profiles, they may be a more effective alternative for patients who do not respond to or cannot tolerate other antipsychotic drugs. PMID:21446639
Howland, Robert H
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 vitamin B6 (the first choice over-the-counter treatment for many women with PMS) have been made. This study investigates the annual rates of diagnoses and prescribing patterns for premenstrual syndrome (1993-1998) within a computerised general practitioner database. METHODS: Retrospective survey of prescribing data for premenstrual syndrome between 1993-1998 using the General Practice Research Database for the West Midlands Region which contains information on 282,600 female patients RESULTS: Overall the proportion of women with a prescription-linked diagnosis of premenstrual syndrome has halved over the five years. Progestogens including progesterone were the most commonly recorded treatment for premenstrual syndrome during the whole study period accounting for over 40% of all prescriptions. Selective serotonin-reuptake inhibitors accounted for only 2% of the prescriptions in 1993 but rose to over 16% by 1998, becoming the second most commonly recorded treatment. Vitamin B6 accounted for 22% of the prescriptions in 1993 but dropped markedly between 1997 and 1998 to 11%. CONCLUSIONS: This study shows a yearly decrease in the number of prescriptions linked to diagnoses for premenstrual syndrome. Progestogens including progesterone, is the most widely prescribed treatment for premenstrual syndrome despite the lack of evidence demonstrating their efficacy. PMID:12086594
Wyatt, Katrina M; Dimmock, Paul W; Frischer, Martin; Jones, Paul W; O'Brien, Shaugn PM
... FULL PRESCRIBING INFORMATION: CONTENTS* ... had a treatment-emergent blood glucose level of ... a 25% reduction in cholesterol content of the ... More results from www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials
Text Version... HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all ... Diary cards and CRFs did not record solicited local reactions ... More results from www.fda.gov/downloads/biologicsbloodvaccines/allergenics
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.
Aakre, Jennifer M; Medoff, Deborah R; Dixon, Lisa B; Kreyenbuhl, Julie A
BACKGROUND: To reduce the prevalence of antibioticresistant bacteria in the community, physicians must optimize their use of antibiotics.\\u000a However, optimal use from the perspective of the community (reserving newer agents for future use) is not always consistent\\u000a with optimal use from the perspective of the individual patient (prescribing newer, broader agents).\\u000a \\u000a \\u000a OBJECTIVES: To identify preferred patterns of antibiotic prescribing for
Joshua P. Metlay; Judy A. Shea; Linda B. Crossette; David A. Asch
Pediatric behavioral and affective disorders often require antipsychotic therapy, in combination with psychotherapeutic interventions, for their treatment and stabilization. Although pharmacotherapy can include either typical or atypical antipsychotics, the latter are generally preferred because of their apparently lower risk of adverse effects. Recent controlled trials have demonstrated the efficacy of some of these agents (including aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone) in adolescent schizophrenia and children or adolescent bipolar mania, or to treat severe aggression and self-injury in the context of autism in children and adolescents. Although few studies have systematically monitored their short- and, more importantly, long-term safety, current evidence indicates that sedation, hyperprolactinemia, and metabolic abnormalities such as excess weight gain, diabetes, and related cardiovascular effects were clinically relevant adverse effects in young patients, with the individual agents differing in their propensity to induce these effects. When prescribing antipsychotics for children and adolescents, physicians should therefore be aware of the specific adverse effect profiles and patients should be closely monitored for the short- and long-term development of adverse events. In pediatric patients, the starting dose, titration plan, and maintenance dose of antipsychotics must be based on their pharmacokinetics and metabolism, as in adults. Because there are significant individual differences in drug and active metabolite(s) pharmacokinetics and metabolism, which may be further affected by a number of confounding factors (including demographic variables, phenotype and drug interactions), therapeutic drug monitoring may be a valid tool for individualizing dosage, but its interpretation should also take account of changes in pharmacodynamic sensitivity with the development during childhood and adolescence. PMID:23588704
Objective Treatment with atypical antipsychotics may prolong the rate-corrected Q–T interval (QTc) on electrocardiogram and increase\\u000a the risk of dangerous ventricular arrhythmias. Polytherapy with atypical antipsychotics is becoming common, but the effect\\u000a of this practice on the QTc has not been explored in detail.\\u000a \\u000a \\u000a \\u000a Methods Among 364 adults treated with atypical antipsychotics randomly selected from consecutive admissions to a single hospital,\\u000a electrocardiograms
Christoph U. Correll; Anne M. Frederickson; Vicki Figen; Elizabeth J. Ginn-Scott; Rudy A. Pantaleon Moya; John M. Kane; Peter Manu
This study examined the impact of race and arrest history on the likelihood of being prescribed, and maintaining an atypical antipsychotic prescription for 90 or more days among patients with schizophrenia in the community. Participants were 224 adults with schizophrenia-spectrum disorders receiving services in public-sector mental health systems in North Carolina. The data used for this report were from a
Richard A. Van Dorn; Jeffrey W. Swanson; Marvin S. Swartz; Eric B. Elbogen
The introduction of atypical antipsychotic drugs (AAPDs), or second-generation antipsychotics, with clozapine as the prototype, has largely changed the clinicians' attitudes toward the treatment of mental illnesses including, but not limited to schizophrenia. Initially, there was optimism that AAPDs would be superior over typical antipsychotic drugs (TAPDs), or first-generation antipsychotic drugs, in terms of efficacy in various phenomenological aspects, including cognitive impairment, and less likelihood of causing adverse events. However, these views have been partly challenged by results from recent meta-analysis studies. Specifically, cardio-metabolic side effects of AAPDs, in spite of a relative paucity of extrapyramidal symptoms, may sometimes limit the use of these agents. Accordingly, attempts have been made to develop newer compounds, e.g., lurasidone, with the aim of increasing efficacy and tolerability. Further investigations are warranted to determine if a larger proportion of patients will be benefitted by treatment with AAPDs compared to TAPDs in terms of remission and recovery. PMID:23986702
IMPORTANCE The increased prescribing of antipsychotics for children and youth has heightened concerns that this practice increases the risk of type 2 diabetes mellitus. OBJECTIVE To compare the risk of type 2 diabetes in children and youth 6 to 24 years of age for recent initiators of antipsychotic drugs vs propensity score-matched controls who had recently initiated another psychotropic medication. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of the Tennessee Medicaid program with 28?858 recent initiators of antipsychotic drugs and 14?429 matched controls. The cohort excluded patients who previously received a diagnosis of diabetes, schizophrenia, or some other condition for which antipsychotics are the only generally recognized therapy. MAIN OUTCOMES AND MEASURES Newly diagnosed diabetes during follow-up, as identified from diagnoses and diabetes medication prescriptions. RESULTS Users of antipsychotics had a 3-fold increased risk for type 2 diabetes (HR?=?3.03 [95% CI?=?1.73-5.32]), which was apparent within the first year of follow-up (HR?=?2.49 [95% CI?=?1.27-4.88]). The risk increased with cumulative dose during follow-up, with HRs of 2.13 (95% CI?=?1.06-4.27), 3.42 (95% CI?=?1.88-6.24), and 5.43 (95% CI?=?2.34-12.61) for respective cumulative doses (gram equivalents of chlorpromazine) of more than 5 g, 5 to 99 g, and 100 g or more (P?.04). The risk remained elevated for up to 1 year following discontinuation of antipsychotic use (HR?=?2.57 [95% CI?=?1.34-4.91]). When the cohort was restricted to children 6 to 17 years of age, antipsychotic users had more than a 3-fold increased risk of type 2 diabetes (HR?=?3.14 [95% CI?=?1.50-6.56]), and the risk increased significantly with increasing cumulative dose (P?.03). The risk was increased for use restricted to atypical antipsychotics (HR?=?2.89 [95% CI?=?1.64-5.10]) or to risperidone (HR?=?2.20 [95% CI?=?1.14-4.26]). CONCLUSIONS AND RELEVANCE Children and youth prescribed antipsychotics had an increased risk of type 2 diabetes that increased with cumulative dose. PMID:23965896
Bobo, William V; Cooper, William O; Stein, C Michael; Olfson, Mark; Graham, David; Daugherty, James; Fuchs, D Catherine; Ray, Wayne A
Inappropriate and widespread prescribing of antipsychotics in LTCF is of concern. This study aimed to explore the association of resident and room characteristics with antipsychotic use in this setting. This is cross-sectional secondary analysis of the baseline data of 280 residents ? 65 years old, from a prospective, observational, LTCF multi-site (n=7) cohort study on delirium. Demographic data included age, sex and length of stay. Resident characteristics assessed were presence of dementia, disruptive behavior, delirium and use of restraints. Room characteristics assessed were single room, clock/calendar, and telephone. Separate logistic regression models were used to explore the association of resident and room characteristics with antipsychotic use, adjusting for demographic variables. Mean age was 84.9 ± 7.0 years (± S.D.) with 56% female. The mean prevalence of antipsychotics use was 31.1% (range: 25.6-50.0%). The regression model of resident characteristics revealed a significant association between disruptive behavior (OR=1.18, 95% CI=1.12-1.25) and antipsychotic use. The model of room characteristics revealed a significant association between absence of a clock or calendar (OR=1.93, 95% CI=1.04-3.56) and absence of a telephone (OR=2.79, 95% CI=1.48-5.25). Our results suggest that behavior problems are associated with a higher likelihood of antipsychotic use. Absence of a clock/calendar and of a telephone was related to antipsychotic use. Further research is needed to confirm these findings. PMID:21824669
Monette, Johanne; Alessa, Waleed; McCusker, Jane; Cole, Martin; Voyer, Philippe; Champoux, Nathalie; Ciampi, Antonio; Sourial, Nadia; Monette, Michele; Belzile, Eric
Prescribing errors are particularly important in paediatrics where dose calculations are complicated and small errors can cause significant harm. Unfortunately, there is no generally agreed definition of what constitutes an error, so studies often use differing criteria. In addition to this, obtaining statistics on rates of error is problematic as staff may be reluctant to report errors or may not include errors that were corrected before any harm occurred. Prescribing errors can be reduced by improving training, using computerised systems and involving pharmacists in checking drug charts. PMID:21109509
OBJECTIVE: To estimate the prevalence of questionable and rational high-risk prescribing among elderly people of the three drug groups most commonly implicated in drug-related illness: cardiovascular drugs, psychotropic drugs and nonsteroidal anti-inflammatory drugs (NSAIDs). DESIGN: Retrospective prevalence study; all prescription and billing records for the period Jan. 1 to Dec. 31, 1990, for the study sample were retrieved from the relevant provincial databases of the Régie de l'assurance-maladie du Québec. SETTING: Quebec. PARTICIPANTS: Regionally stratified random sample of 63,268 elderly medicare registrants who made at least one visit to physician in 1990 and were not living in a health care institution for the entire year. MAIN OUTCOME MEASURE: Prescription information was examined for three types of high-risk prescribing: rational and questionable drug combinations, excessive treatment duration and drugs relatively contraindicated for use in elderly people. RESULTS: Overall, 52.6% of the patients experienced one or more events of high-risk prescribing, and 45.6% experienced at least one that was questionable. High-risk prescribing was most prevalent for psychotropic drugs, and questionable prescribing was more frequent than rational prescribing in this drug group. An estimated 30.8% of the total elderly population in Quebec received benzodiazepines for more than 30 consecutive days, 12.9% received a long-acting benzodiazepine, and 13.0% received a questionable high-risk psychotropic drug combination. The prevalence of high-risk prescribing was higher among the women than among the men and increased with age until 75 to 84 years. There were significant unexplained differences between regions in the regional prevalence of high-risk prescribing, particularly of psychotropic drugs. CONCLUSION: The prevalence of questionable high-risk prescribing, especially of psychotropic drugs, is substantial among elderly people. This may be a potentially important and avoidable risk factor for drug-related illness in elderly people.
Tamblyn, R M; McLeod, P J; Abrahamowicz, M; Monette, J; Gayton, D C; Berkson, L; Dauphinee, W D; Grad, R M; Huang, A R; Isaac, L M
Lurasidone is a new atypical antipsychotic that has demonstrated positive effects on psychosis, mood, and cognition. This improved efficacy and safety profile for the treatment of schizophrenia. Its overall tolerability profile seems to be comparable to the other atypical antipsychotics. Perhaps its more potent blockade on the 5HT7 receptor will give it more of an advantage in treating the negative symptoms as well as improve cognitive and depressive symptoms associated with schizophrenia. Additionally, it does not appear to have any significant adverse impact on the metabolic profile, such as weight, glucose, or lipid metabolism. Lurasidone is also associated with good cardiovascular tolerability without widening of the QT interval. The use of this medication may be of particular interest in patients presenting with endocrine or cardiovascular abnormalities. The average price for a 30-day supply of lurasidone is $475.98. PMID:22545643
Nolan, Shambria F; Roman, Marian W
\\u000a Development of effective screening strategies for improved antipsychotic drugs (APDs) rely primarily on the actual hypotheses\\u000a for mechanism of action of these compounds. In the early times of the dopamine (DA) hypothesis of schizophrenia animal models\\u000a were designed to detect compounds which blocked the behavioural effects of high doses of dopaminergic drugs (e.g. amphetamine-,\\u000a apomorphine-and methylphenidate-induced stereotyped behaviour). Whenin vitroreceptor
Studies of novel antipsychotics in healthy volunteers are traditionally concerned with kinetics and tolerability, but useful information may also be obtained from biomarkers of clinical endpoints. A useful biomarker should meet the following requirements: a consistent response across studies and antipsychotics; a clear response of the biomarker to a therapeutic dose; a dose–response relationship; a plausible relationship between biomarker, pharmacology and pathogenesis. In the current review, all individual tests found in studies of neuroleptics in healthy volunteers since 1966 were progressively evaluated for compliance with these requirements. A MedLine search yielded 65 different studies, investigating the effects of 23 different neuroleptics on 101 different (variants of) neuropsychological tests, which could be clustered into seven neuropsychological domains. Subjective and objective measures of alertness, and of visual-visuomotor-auditory and motor skills were most sensitive to antipsychotics, although over half of all the studies failed to show statistically significant differences from placebo. The most consistent effects were observed using prolactin response and saccadic eye movements, where 96% and 83% of all studies resp. showed statistically significant effects. The prolactin inducing dose equivalencies relative to haloperidol of 19 different antipsychotic agents correlated with the lowest recommended daily maintenance dose (r2 = 0.52). This relationship could reflect the clinical practice of aiming for maximum tolerated levels, or it could represent a common basis behind prolactin release and antipsychotic activity (probably D2-receptor antagonism). The number of tests used in human psychopharmacology appears to be excessive. Future studies should look for the most specific and sensitive test within each of the domains that are most susceptible to neuroleptics.
de Visser, S J; van der Post, J; Pieters, M S M; Cohen, A F; van Gerven, J M A
Prescribing of medicines is the key clinical activity in the working life of most doctors. In recent years, a broad consensus regarding the necessary competencies has been achieved. Each of these is a complex mix of knowledge, judgement and skills. Surveys of those on the threshold of their medical careers have revealed widespread lack of confidence in writing prescriptions. A valid and reliable assessment of prescribing competence, separate from an overall assessment of medical knowledge and skill, would have many benefits for clinical governance and patient safety, and would provide a measure of the success of training programmes in therapeutics. Delivering such an assessment presents many challenges, not least of which are the difficulty in identifying a surrogate marker for competent prescribing in clinical practice and the challenge of ensuring that competence assessed in a controlled environment predicts performance in clinical practice. This review makes the case for an on-line OSCE as the most valid form of assessment and sets out the requirements for its development, scope, composition and delivery. It describes an on-going attempt to develop a national assessment of prescribing skills towards the end of undergraduate medical training in the UK.
Mucklow, John; Bollington, Lynne; Maxwell, Simon
|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…
Antipsychotic medication has been enormously helpful in the treatment of psychotic symptoms during the past several decades.\\u000a Unfortunately, several important side effects that can cause significant morbidity and mortality. The two most common are\\u000a abnormal involuntary movements (tardive dyskinesia) and weight gain progressing through diabetes to metabolic syndrome. A\\u000a more rare and life-threatening adverse effect is clozapine-induced agranulocytosis (CIA), which
Nabilah I. Chowdhury; Gary Remington; James L. Kennedy
The post mortem redistribution of ten commonly prescribed antipsychotic drugs (APs) was investigated. Femoral blood was collected from 273 cases at admission to mortuary (AD) and at post-mortem (PM). The PM samples were collected at various times up to nine days after admission and the sample pairs analysed using LC-MS/MS. The drugs included in this study were 9OH-risperidone (paliperidone), amisulpride, chlorpromazine, clozapine, haloperidol, olanzapine, promethazine, quetiapine, risperidone, and zuclopenthixol. Haloperidol, quetiapine and risperidone showed minimal changes between AD and PM specimens, whereas the majority of drugs showed significant changes between the sample pairs collected at different time points post mortem (p<0.01) in addition to an average concentration change greater than the uncertainty of measurement of the applied method. Average increases in blood concentrations after admission to the mortuary ranged up to 112% (chlorpromazine and olanzapine) but also decreases up to -43% (9OH-risperidone) were seen. There were large standard deviations between sample pairs and substantial day-to-day unpredictable changes that highlight the difficulty in the interpretation of drug concentrations post-mortem. Based on the presented data, we recommend that specimens for toxicological analysis should to be taken as soon as possible after admission of a deceased person to the mortuary in order to minimise the effects of the PM interval on the drug concentration in blood. PMID:22748972
Saar, Eva; Beyer, Jochen; Gerostamoulos, Dimitri; Drummer, Olaf H
With the recent Center for Medicare and Medicaid Services and stimulus package incentives for health information technology, many clinicians are expected to adopt or enhance their use of e-prescribing systems. E-prescribing has nearly eradicated medication errors resulting from prescriber handwriting interpretations, yet several other patient-care and workflow benefits still remain a promise. As prescribers select or update their e-prescribing systems (whether stand-alone or integrated with electronic health records), close attention is needed to the e-prescribing application features and level of clinical decision support to avoid clinical blind spots, including incomplete or inaccurate patient medication lists, poor drop-down menu or screen design, and lack of clinically relevant and actionable drug interaction and drug allergy alerts. This article presents three case studies that highlight common e-prescribing problems involving diabetes patients.
Smith, Marie; Dang, Devra; Lee, Jennifer
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
Bernardo, Miquel; Vieta, Eduard; Saiz Ruiz, Jerónimo; Rico-Villademoros, Fernando; Alamo, Cecilio; Bobes, Julio
Since 2003, the U.S. Food and Drug Administration as well as the American Diabetes Association, the American Psychiatric Association, and others have called for routine monitoring of cardiometabolic risk factors for patients of all ages prescribed second-generation antipsychotic medications. This survey of major public and private mental health treatment systems in 2010 found that adherence to such guidelines was limited. The authors describe some of the impediments to widespread monitoring of cardiometabolic risk factors among psychiatric patients taking second-generation antipsychotics and advocate for a nationwide commitment to providing the organizational and financial supports necessary to ensure systematic screening of cardiometabolic health among such patients. PMID:22388526
Jerrell, Jeanette M; McIntyre, Roger S; Black, George B
Background Patients with intellectual disabilities may be treated with antipsychotic medications for a variety of diagnoses. Use of this category of medication can increase prolactin levels and place the patient at risk for sexual dysfunction and lower bone mineral density. The proposed mechanism of action is affinity for the dopamine receptor. Use of bromocriptine, a dopamine receptor antagonist, was proposed to attenuate hyperprolactinemia. Objectives The objectives of this study were to (1) review serum prolactin (PRL) elevations associated with the use of antipsychotic (AP) medications in an intellectually disabled adult population and (2) determine if any association existed between the level of elevation and AP used. Patients and Methods Medical records for adult patients at two Oklahoma facilities for the intellectually disabled were reviewed to evaluate prolactin levels for individuals prescribed antipsychotics. A linear regression model was used to evaluate the relationship between prolactin levels with intellectual disability level, bromocriptine use, demographics, and antipsychotic. Results 73 (n = 53 males, n = 20 females) patients met criteria. The average age was 41.2 years. Nearly 70% of the patients had severe to profound levels of disability. 77% were prescribed second generation antipsychotics; 19% received first generation agents. Two variables, gender and bromocriptine use, were found to be significant predictors of prolactin levels. Mean prolactin level for females was 44 ng/mL (normal range: 4-30 ng/mL, males = 4-23 ng/mL). Patients who did not receive bromocriptine had mean levels of 23 ng/mL. No significant difference in prolactin levels was found for type of AP. Conclusions Mean prolactin levels for females were significantly higher than for males. Both sexes were found to have higher-than-normal levels. Use of bromocriptine was associated with higher prolactin levels. In this population of patients, the type of AP used had no significance on prolactin levels.
Lambert, Tammy L; Farmer, Kevin C; Brahm, Nancy C
Objectives The purpose of this study is to examine the use of prescribed psychoactive medications in a prospective cohort of children shortly after they entered foster homes; and to identify demographics, maltreatment history, psychiatric diagnoses including ADHD comorbidity, and level of aggression that contribute to prescribed use of stimulant and atypical antipsychotic medication over time. Methods The sample included N?=?252 children (nested in 95 sibling groups) followed for three years up to 4 yearly waves. Results Nearly all (89%) met criteria for at least one of eight psychiatric diagnoses and 31% (75/252) used one or more prescribed psychoactive medications. Over half (55%) were diagnosed with Attention Deficit Hyperactivity Disorder (ADHD); of these 38% used stimulants and 36% used atypical antipsychotics. Of the 75 medicated children, 19% received ?3 different classes of drugs over the course of the study. Stimulants (69%) and atypical antipsychotics (65%) were the most frequently used drugs among medicated children. Adjusted odds ratios (AOR) showed that male gender (AOR?=?3.2; 95% CI?=?1.5–9.3), African American vs Latino ethnicity (AOR?=?5.4; 95% CI?=?2.1–14.2), ADHD regardless of Oppositional Defiant (ODD) or Conduct (CD) comorbidity (AOR?=?6.0, 95% CI?=?1.3–27.5), ODD or CD (AOR?=?11.1, 95% CI?=?2.1–58.6), and Separation Anxiety (AOR?=?2.0, 95% CI?=?1.0–4.0) psychiatric disorders were associated with the use of prescribed stimulants; while male gender (AOR?=?3.8, 95% CI?=?1.5–9.3), African American vs Latino (AOR?=?5.1, 95% CI?=?1.2–9.2) or Mixed/Other ethnicity (AOR?=?3.3, 95% CI?=?1.9–13.7), ADHD regardless of ODD or CD comorbidity (AOR?=?5.8, 95% CI?=?1.2–28.7), ODD or CD (AOR?=?13.9, 95% CI?=?3.3–58.5), Major Depression/Dysthymia (AOR?=?2.8, 95% CI?=?1.1–6.7) psychiatric disorders, and history of sexual abuse (AOR?=?4.6, 95% CI?=?1.3–18.4) were associated with the use of prescribed atypical antipsychotics. Conclusion The aggressive use of atypical antipsychotics, which has unknown metabolic risks, suggests that the efficacy and safety of such treatment strategies for psychiatrically ill children in foster care should be monitored.
Linares, L. Oriana; Martinez-Martin, Nuria; Castellanos, F. Xavier
Recently, there has been increased concern about the occurrence of diabetes associated with the use of atypical antipsychotic (AAP) drugs. The relationship between diabetes, schizophrenia, and antipsychotic drugs is complex and intriguing, as untreated patients with schizophrenia are known to suffer from diabetes more often than the general population. Thirty individual case reports of clozapine-, 26 cases of olanzapine- and
Jambur Ananth; Ravi Venkatesh; Karl Burgoyne; Sarath Gunatilake
Delirium is characterized by disturbances of consciousness, attention, cognition, perception, emotions, sleep, and psychomotor activity. Management of delirium involves ensuring safety, improving functioning, identifying and treating the illness underlying the delirium, and use of antipsychotics or benzodiazepines to control behavioural symptoms and prevent mortality. Haloperidol continues to be the most commonly used antipsychotic in delirium. However, in recent times data have emerged which suggest that atypical antipsychotics may be as efficacious as haloperidol in the treatment of delirium. This review intends to review the data with respect to usefulness of atypical antipsychotics in the treatment of delirium. Besides atypical antipsychotics, data with respect to another group of medications - cholinesterase inhibitors are also reviewed. Electronic and manual searches were conducted to identify all the relevant studies and case reports/case series. Evidence suggests that risperidone, olanzapine and quetiapine are as efficacious as haloperidol in the treatment of delirium but have lesser side effects. Data for other atypical antipsychotics are scarce. The data on cholinesterase inhibitors for treatment and prevention of delirium are beginning to accumulate, but do not seem to be convincing. Our review suggests that risperidone, olanzapine and quetiapine are good alternatives to haloperidol in the treatment of delirium. PMID:21394715
Grover, S; Mattoo, S K; Gupta, N
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
Greene, Jeremy A
Medications are commonly prescribed to psychiatric inpatients on a PRN (pro re nata\\/as required) basis, allowing drugs to be administered on patient request or at nurses' discretion for psychiatric symptoms, treatment side effects or physical complaints. However, there has been no formal study of the pharmacokinetic implications of PRN prescribing. The objective of the study was to determine the prevalence
Simon J. C. Davies; Martin S. Lennard; Parviz Ghahramani; Peter Pratt; Andrea Robertson; John Potokar
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
Harding, Rosie; Peel, Elizabeth
For those facing progressive life limiting disease, symptoms across a range of systems can be problematic. Clinicians may find themselves prescribing from several classes of drugs to alleviate distressing problems and to maximise quality of life for patients. Many drugs used for symptom control in palliative care give rise to neuropsychiatric side effects as they affect the central nervous system either directly or indirectly. The common unwanted effects of these drugs are well known, but there are some important neuropsychiatric effects that physicians are less aware of. If unrecognised, these effects can generate considerable distress and unnecessary harm to patients. We aim to highlight some of the adverse neuropsychiatric effects which occur with commonly used drugs in palliative care. Antiemetics such as metoclopramide and haloperidol can cause significant levels of neuropsychiatric toxicity, as can opiates, antidepressants, anxiolytics and antipsychotics. The syndromes or entities that will be considered are delirium, drug induced parkinsonism, akathisia, serotonin syndrome and neuroleptic malignant syndrome. The intention is to alert clinicians to the iatrogenic complications which may ensue on prescribing drugs commonly used in the palliative care setting. PMID:18372482
Jackson, N; Doherty, J; Coulter, S
Background Information about antibiotic prescribing practice in primary care is not available for Ireland, unlike other European countries. The study aimed to ascertain the types of antibiotics and the corresponding conditions seen in primary care and whether general practitioners (GPs) felt that an antibiotic was necessary at the time of consultation. This information will be vital to inform future initiatives in prudent antibiotic prescribing in primary care. Methods Participating GPs gathered data on all antibiotics prescribed by them in 100 consecutive patients’ consultations as well as data on the conditions being treated and whether they felt the antibiotic was necessary. Results 171 GPs collected data on 16,899 consultations. An antibiotic was prescribed at 20.16% of these consultations. The majority were prescribed for symptoms or diagnoses associated with the respiratory system; the highest rate of prescribing in these consultations were for patients aged 15–64?years (62.23%). There is a high rate of 2nd and 3rd line agents being used for common ailments such as otitis media and tonsillitis. Amoxicillin, which is recommended as 1st line in most common infections, was twice as likely to be prescribed if the prescription was for deferred used or deemed unnecessary by the GP. Conclusion The study demonstrates that potentially inappropriate prescribing is occurring in the adult population and the high rate of broad-spectrum antimicrobial agents is a major concern. This study also indicates that amoxicillin may be being used for its placebo effect rather than specifically for treatment of a definite bacterial infection.
Obesity and metabolic side effects such as diabetes mellitus are major concerns in public health. Mentally ill people are a high risk subgroup for obesity and metabolic syndrome because of behavior, non treatment, and medication side effects. In this research, I conducted a retrospective chart review to compare the weight and body mass index of consumers who were prescribed antipsychotic
Orthostatic hypotension is a common adverse effect of antipsychotics that may delay or prevent titration to a dose necessary to control psychotic symptoms. Complications of orthostatic hypotension include syncope, transient ischaemic attack, stroke, myocardial infarction and death. The risk of orthostatic hypotension associated with antipsychotic therapy is increased in patients with disorders of the autonomic nervous system, fluid imbalance and those taking concomitant drug therapy that affects haemodynamic tone. Prospective monitoring for changes in postural blood pressure is important because patients with psychotic disorders often do not articulate symptoms of orthostasis and the subjective report of dizziness does not correlate well with orthostatic blood pressure changes. Nonpharmacological strategies and patient education, most notably, slowly rising from the supine position, are crucial first steps in the prevention and treatment of both symptomatic and asymptomatic orthostatic hypotension. Pharmacological treatment is only recommended when symptomatic orthostatic hypotension persists despite proper nonpharmacological therapy and there is a compelling indication for antipsychotic treatment. Fludrocortisone is a reasonable first choice for symptomatic orthostatic hypotension. Other agents including desmopressin and midodrine may be considered in patients who do not respond favourably to a trial of fludrocortisone, but safety concerns and lack of evidence limit the utility of these agents. PMID:21790209
Gugger, James J
Objective: To systematically review the efficacy and tolerability data of antipsychotics in children and adolescents with schizophrenia. Materials and Methods: Pubmed, Google scholar and Psych Info were searched to identify studies published in peer-reviewed English language journals. All studies evaluating the efficacy of antipsychotics in children and adolescents with schizophrenia and having 3 or more participants were included. Of the studies identified, only randomized controlled trials were included in the meta-analysis. Data was analysed using effect size calculation as per Cohen's d. Fifty published studies were identified which reported use of antipsychotics in children and adolescents with schizophrenia. Of these, 15 randomized controlled studies were included in meta-analysis. Results: Evidence suggests that both first generation antipsychotics (FGA) and second generation antipsychotics (SGAs) are better than placebo (effect size [ES] 2.948, confidence interval [CI] 1.368 to 4.528, sample size 31; and ES 0.454, CI 0.414 to 0.542, sample size 1308 respectively). However, FGAs seemed to be inferior to SGAs (ES -0.363, CI -0.562 to -0.163, sample size of 243) and clozapine is superior to all other antipsychotics (ES 0.848, CI 0.748 to 0.948, and sample size 85) in treatment of schizophrenia in children and adolescents. The extrapyramidal side effects are more common with FGAs while metabolic adverse effects are more common with SGAs. Conclusion: FGAs and SGAs are effective in the treatment of children and adolescents with schizophrenia. Clozapine apparently is the most effective antipsychotic in this condition.
Sarkar, Siddharth; Grover, Sandeep
Prescribed burning has become an increasingly common management tool to modify habitats for many species in the southeastern United States. On military installations in the southeast, prescribed burning is used frequently on a landscape scale to control m...
D. S. Maas R. L. Musson T. J. Hayden
Antipsychotics are an important class of drugs for the management of schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors are present throughout the brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements of the face and limbs for which there is little treatment. In this study, we investigated whether nicotine administration could reduce tardive dyskinesia because nicotine attenuates other drug-induced abnormal movements. We used a well established model of tardive dyskinesia in which rats injected with the commonly used antipsychotic haloperidol develop vacuous chewing movements (VCMs) that resemble human orofacial dyskinesias. Rats were first administered nicotine (minipump; 2 mg/kg per day). Two weeks later, they were given haloperidol (1 mg/kg s.c.) once daily. Nicotine treatment reduced haloperidol-induced VCMs by ?20% after 5 weeks, with a significant ?60% decline after 13 weeks. There was no worsening of haloperidol-induced catalepsy. To understand the molecular basis for this improvement, we measured the striatal dopamine transporter and nicotinic acetylcholine receptors (nAChRs). Both haloperidol and nicotine treatment decreased the transporter and ?6?2* nAChRs (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex) when given alone, with no further decline with combined drug treatment. By contrast, nicotine alone increased, while haloperidol reduced ?4?2* nAChRs in both vehicle and haloperidol-treated rats. These data suggest that molecular mechanisms other than those directly linked to the transporter and nAChRs underlie the nicotine-mediated improvement in haloperidol-induced VCMs in rats. The present results are the first to suggest that nicotine may be useful for improving the tardive dyskinesia associated with antipsychotic use.
Bordia, Tanuja; McIntosh, J. Michael
An outline of the pharmacology of important components of extemporaneous prescriptions will be undertaken over four issues of the journal. Substances such as dithranol, salicylic acid and coal tar will be examined in some depth with regard to their mode of action, uses and side effects. In addition, examples of extemporaneous formulations containing these substances will be provided along with advice regarding their use. Substances such as sulphur, calamine, podophyllin and menthol will also be reviewed using the same format but in less detail. The articles are designed to provide practical knowledge in the area of extemporaneous prescribing. Complicated areas of pharmaceutical chemistry, unless relevant to the clinical setting, will not be discussed. PMID:7702499
Artemi, P; Land, W A
Treatment with several antipsychotic drugs can result in weight gain, which may lead to further morbidity such as type 2 diabetes and cardiovascular disease via the development of metabolic syndrome. These important and problematic metabolic consequences of antipsychotic drug treatment probably reflect a pharmacological disruption of the mechanisms involved in control of food intake and body weight. The extent of weight gain following antipsychotic drug treatment shows substantial variability between individuals, due in part to genetic factors. Common functional polymorphisms in many candidate genes implicated in the control of body weight and various aspects of energy and lipid metabolism have been investigated for association with weight gain in subjects receiving antipsychotic drug treatment, and with metabolic pathology in chronic schizophrenia. Perhaps the strongest and most replicated findings are the associations with promoter polymorphisms in the 5-HT2C receptor and leptin genes, although many other possible genetic risk factors, including polymorphisms in the fat mass and obesity associated (FTO) gene and genes for the alpha2A adrenoceptor and melanocortin4 receptor, have been reported. Genome-wide association studies (GWAS) have also addressed antipsychotic-induced weight gain and other indicators of metabolic disturbances. However there is as yet little consistency between these studies or between GWAS and classical candidate gene approaches. Identifying common genetic factors associated with drug-induced weight gain and its metabolic consequences may provide opportunities for personalized medicine in the predictive assessment of metabolic risk as well as indicating underlying physiological mechanisms. PMID:23431082
Reynolds, Gavin P
Chronically elevated levels of corticotropin-releasing factor (CRF) in transgenic mice overexpressing CRF in the brain (CRF-OE) appear to be associated with alterations commonly associated with major depressive disorder, as well as with sensorimotor gating deficits commonly associated with schizophrenia. In the present study, we tested the hypothesis that antipsychotics may be effective in normalizing prepulse inhibition (PPI) of acoustic startle in CRF-OE mice, which display impaired sensorimotor gating compared to wild-type (WT) mice. The typical antipsychotic haloperidol and atypical antipsychotic risperidone improved PPI in the CRF-OE mice, but were ineffective in WT mice. The atypical antipsychotic clozapine did not influence PPI in CRF-OE mice, but reduced gating in WT mice. This effect of clozapine in the CRF-OE mice may thus be regarded as a relative improvement, consistent with the observed effect of haloperidol and risperidone. As expected, the anxiolytic, nonantipsychotic chlordiazepoxide was devoid of any effect. All four compounds dose-dependently reduced the acoustic startle response irrespective of genotype. These results indicate that antipsychotic drugs are effective in improving startle gating deficits in the CRF-OE mice. Hence, the CRF-OE mouse model may represent an animal model for certain aspects of psychotic depression, and could be a valuable tool for research addressing the impact of chronically elevated levels of CRF on information processing. PMID:12865891
Dirks, Anneloes; Groenink, Lucianne; Westphal, Koen G C; Olivier, Jocelien D A; Verdouw, P Monika; van der Gugten, Jan; Geyer, Mark A; Olivier, Berend
We examined the trends in prescribing psychotropic drugs to children and adolescents within an inpatients adolescent psychiatric ward in Israel. Data of 414 subjects, ranging from 12- to 22-year-old, covering the years 1997, 2002 and 2007, was examined retrospectively. Analyzed variables included the number and type of drug prescriptions per patient at discharge, the subjects' age at discharge and the number of diagnoses per patient at discharge. Analysis of variance (ANOVA) with repeated measures was used to evaluate changes between the three calendar years, along the 10-year study period, while Pearson ?(2) test was performed for categorical variables. Over the study period the mean age at discharge decreased significantly, by about a year and a half, the mean number of diagnoses increased significantly, from 1.6 to 2.4 diagnoses per patient and the total number of drugs prescribed at discharge increased significantly from 1.48 to 1.93 per patient. Overall, the number of patients who were prescribed mood stabilizers increased by 14%, those who were prescribed antidepressants increased by almost 24%, almost 16% in antipsychotics prescriptions and 51.5% in prescriptions of atypical antipsychotics. Typical antipsychotic prescriptions decreased by 35.5% and accordingly, the number of patients who were prescribed agents for the treatment of extra-pyramidal side effects decreased by almost 24%. Due to a low number of inpatients with attention deficit and hyperactivity disorder (ADHD), no significant statistical conclusion could be drawn regarding trends in psychostimulant prescriptions. Our findings agree with other published studies from the last two decades. The growing use of psychotropic agents in children and adolescents merit a continuous concern with regard to their effects on the developing brain and impact on quality of life and to authorizing these drugs for use in specific young age subgroups. PMID:21276716
Gilat, Y; Ben-Dor, D H; Magen, A; Wolovick, L; Vekslerchik, M; Weizman, A; Zalsman, G
Schizophrenia is associated with progressive brain changes, including progressive brain tissue decreases and lateral ventricular volume increases for up to at least 20 years after disease onset. In view of the fact that the vast majority of such patients are treated with antipsychotic medication and that recent non-human mammalian studies have reported an association between antipsychotic medication and brain tissue changes, the important question arises as to whether the brain changes seen in schizophrenia are associated with antipsychotic medication. The reviewed article presents structural magnetic resonance neuroimaging data relating to 211 patients with schizophrenia from the Iowa Longitudinal Study, which demonstrates that greater intensity of antipsychotic treatment was associated with indicators of generalized and specific brain tissue changes, after controlling for the effects of illness duration, illness severity and substance abuse. The study and its implications are discussed in the context of the current state of knowledge regarding the pathophysiology of schizophrenia. PMID:21721911
Puri, Basant K
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
Alessi-Severini, Silvia; 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.
Dahl, Matthew; Schultz, Jennifer; Metge, Colleen; Raymond, Colette
Objective To report the frequency, types, and causes of errors associated with outpatient computer-generated prescriptions, and to develop a framework to classify these errors to determine which strategies have greatest potential for preventing them. Materials and methods This is a retrospective cohort study of 3850 computer-generated prescriptions received by a commercial outpatient pharmacy chain across three states over 4?weeks in 2008. A clinician panel reviewed the prescriptions using a previously described method to identify and classify medication errors. Primary outcomes were the incidence of medication errors; potential adverse drug events, defined as errors with potential for harm; and rate of prescribing errors by error type and by prescribing system. Results Of 3850 prescriptions, 452 (11.7%) contained 466 total errors, of which 163 (35.0%) were considered potential adverse drug events. Error rates varied by computerized prescribing system, from 5.1% to 37.5%. The most common error was omitted information (60.7% of all errors). Discussion About one in 10 computer-generated prescriptions included at least one error, of which a third had potential for harm. This is consistent with the literature on manual handwritten prescription error rates. The number, type, and severity of errors varied by computerized prescribing system, suggesting that some systems may be better at preventing errors than others. Conclusions Implementing a computerized prescribing system without comprehensive functionality and processes in place to ensure meaningful system use does not decrease medication errors. The authors offer targeted recommendations on improving computerized prescribing systems to prevent errors.
Rothschild, Jeffrey M; Salzberg, Claudia; Keohane, Carol A; Zigmont, Katherine; Devita, Jim; Gandhi, Tejal K; Dalal, Anuj K; Bates, David W; Poon, Eric G
AIMS We aimed to examine the frequency of high-dose (defined as mean chlorpromazine mg equivalent doses above 1000) antipsychotic prescriptions in schizophrenia and their clinical correlates in the context of a comparison between studies in 2001 and 2004 within six East Asian countries and territories. METHODS Prescriptions of high-dose antipsychotic for a sample of 2136 patients with schizophrenia from six countries and territories (mainland China, Hong Kong, Korea, Japan, Taiwan and Singapore) were evaluated in 2004 and compared with data obtained for 2399 patients in 2001. RESULTS Overall, the comparison between 2001 and 2004 showed a significant decrease in high-dose antipsychotic use from 17.9 to 6.5% [odds ratio (OR) 0.32, 95% confidence interval (CI) 0.26, 0.39, P < 0.001]. Patients who received high-dose antipsychotics were significantly more likely to have multiple admissions (OR 1.96, 95% CI 1.16, 3.33, P = 0.009), more positive psychotic symptoms such as delusions (OR 2.05, 95% CI 1.38, 3.05, P < 0.001) and hallucinations (OR 1.85, 95% CI 1.30, 2.64, P = 0.001), but less likely to have negative symptoms (OR 0.58, 95% CI 0.40, 0.82, P = 0.002). Multivariate regression analyses revealed that prescription of high-dose antipsychotics was also predicted by younger age (P < 0.001), time period of study (2001; P < 0.001), use of first-generation antipsychotic (P < 0.001) and depot antipsychotics (P < 0.001) as well as antipsychotic polytherapy (P < 0.001). CONCLUSIONS We identified the clinical profile and treatment characteristics of patients who are at risk of receiving high antipsychotic doses. These findings should provide impetus for clinicians to constantly monitor the drug regimes and to foster rational, evidence-based prescribing practices.
Sim, Kang; Su, Hsin Chuan; Fujii, Senta; Yang, Shu-yu; Chong, Mian-Yoon; Ungvari, Gabor; Si, Tianmei; He, Yan Ling; Chung, Eun Kee; Chan, Yiong Huak; Shinfuku, Naotaka; Kua, Ee Heok; Tan, Chay Hoon; Sartorius, Norman
Recognition and treatment of the side effects of psychotropic medication as regards sexual function are topics of increasing clinical concern. However, treatment-induced sexual dysfunction is not regularly queried in patients. In this article, we discuss the association between antipsychotic use and sexual dysfunction and how antipsychotics differ in their side-effect profiles. We also investigate possible reasons for under-reporting of sexual
Sutha Murthy; Kevan R. Wylie
Antipsychotic medications are widely used to manage psychotic and behavioral disorders in older adults, including primary\\u000a psychotic disorders such as schizophrenia, and psychosis and behavioral disturbances associated with dementia. These two broad\\u000a diagnostic indications are associated with contrasting recommended treatment durations, with the former requiring indefinite\\u000a treatment across the life span. Antipsychotic drug dosing for schizophrenia is based primarily on
Chloe Leon; Philip Gerretsen; Hiroyuki Uchida; Takefumi Suzuki; Tarek Rajji; David C. Mamo
In the remitted phase of bipolar I disorder, sexual dysfunction is commonly due to drugs used in the treatment rather than the disease itself. There are very few studies, especially in the Indian population, addressing the frequency of sexual dysfunction due to antipsychotics in bipolar I disorder. Hence this study was done to determine the sexual dysfunction due to antipsychotics and to compare the same among typical and atypical antipsychotics. A cross sectional study with 108 male patients of remitted bipolar I disorder (DSM-IV), chosen by purposive sampling technique was done. Psychopathology was assessed using the Brief Psychiatric Rating Scale, Structured Interview Guide for the Hamilton Depression Rating Scale and Young Mania Rating Scale. Sexual side effects due to antipsychotics were assessed using the Udvalg for Kliniske ndersogelser (UKU) side effect rating scale. The total sample size was divided into two groups of those on typical antipsychotics (n = 53) and atypical antipsychotics (n = 55). The two groups were compared for sexual dysfunction using Chi-square test. Results showed dysfunction in at least one phase of the sexual response cycle, comprising of desire, arousal and orgasm, was present in 66% of the sample population. Erectile dysfunction was present in 42% of the sample population and it was the most common type of sexual dysfunction reported. It was also significantly different across the two groups (p = 0.025). There was no significant difference in other aspects of sexual dysfunction across the two groups. In conclusion patients of Bipolar I disorder experience sexual side effects of antipsychotics frequently. Erectile dysfunction is the most common sexual dysfunction among men and this is significantly higher with typical than atypical antipsychotics.
Nagaraj, Anil Kumar M.; Nizamie, Haque S.; Akhtar, Sayeed; Sinha, Baxi Neeraj P.; Goyal, Nishant
Objective: To test the hypothesis that the prescribing behaviour of doctors would improve after having experience with a computerised rule based prescribing system. Design: A prospective observational study of changes in prescribing habits resulting from the use of a computerised prescribing system in (1) a cohort of experienced users compared with a new cohort, and (2) a single cohort at the beginning and after 3 weeks of computer aided prescribing. Setting: 64 bed renal unit in a teaching hospital. Intervention: Routine use of a computerised prescribing system by doctors and nurses on a renal unit from 1 July to 31 August 2001. Main outcome measures: Number of warning messages generated by the system; proportion of warning messages overridden; comparison between doctors of different grades; comparison by doctors' familiarity with the system. Results: A total of 51 612 records relating to 5995 prescriptions made by 103 users, of whom 42 were doctors, were analysed. The prescriptions generated 15 853 messages, of which 6592 were warning messages indicating prescribing errors or problems. Doctors new to the system generated fewer warning messages after using the system for 3 weeks (0.81 warning messages per prescription v 0.42 after 3 weeks, p = 0.03). Doctors with more experience of the system were less likely to generate a warning message (Spearman's ? = –0.90, p = 0.04) but were more likely to disregard one (Spearman's ? = –1, p<0.01). Senior doctors were more likely than junior doctors to ignore a warning message. Conclusions: Doctors are influenced by the experience of using a computerised prescribing system. When judged by the number of warning messages generated per prescription, their prescribing improves with time and number of prescriptions written. Consultants and registrars are more likely to use their clinical judgement to override warning messages regarding prescribed drugs.
Anton, C; Nightingale, P; Adu, D; Lipkin, G; Ferner, R
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.
Forestry, Florida D.; Smokeybear.com
|This book presents a wide-ranging analysis of what can be done to reduce the misuse of psychoactive drugs without compromising appreciation for their therapeutic value. Emphasis is placed on the need to give physicians guidelines for deciding to whom to prescribe, what to prescribe, how much, and for how long. Chapter 1 provides an introduction…
Ghodse, Hamid, Ed.; Khan, Inayat, Ed.
Clinical and psychosocial deterioration associated with schizophrenia occurs within the first few years following the onset of the illness. Therefore, to improve the long-term prognosis, it is important to provide schizophrenia patients with intensive treatment following their first episode. Relapse is highly associated with partial medication adherence or nonadherence in patients with first-episode schizophrenia. Recent studies suggest that long-acting injectable (LAI) antipsychotics compared with oral antipsychotics are more effective for medication adherence and relapse prevention. Moreover, some clinical guidelines for the treatment of schizophrenia suggested that LAI antipsychotics should be considered when patients are nonadherent “at any stage.” Decreased compliance is a common cause of relapse during the initial stages of the disease. Therefore, LAI antipsychotics should be highly considered when treating patients with first-episode schizophrenia. In the present paper, clinical trial data and current guidelines on the use of LAI antipsychotics for first-episode schizophrenia are discussed as well as the pros and cons of this treatment option.
Kim, Borah; Lee, Sang-Hyuk; Yang, Yen Kuang; Park, Jong-Il; Chung, Young-Chul
Antipsychotics have provided a great improvement in the management of people with schizophrenia. The first generation antipsychotics could establish the possibility of managing many psychotic subjects in an outpatient setting. With the advent of the second (SGA) and third generation antipsychotics (TGA), other psychiatric disorders such as bipolar depression, bipolar mania, autism, and major depressive disorder have now been approved for the use of these drugs for their treatment. Also, the administration of more specific assessment tools has allowed for better delineation of the repercussions of these drugs on symptoms and the quality of life of patients who use antipsychotic agents. In general, the SGA share similar mechanisms of action to achieve these results: dopamine-2 receptor antagonism plus serotonin-2A receptor antagonism. The TGA (eg, aripiprazole) have partial agonist activity at the dopamine-2 receptor site, and are also called dopaminergic stabilizers. The pharmacological profile of SGA and TGA may provide better efficacy against negative symptoms, and are less likely to produce extrapyramidal symptoms; however, the SGA and TGA are associated with many other adverse events. The clinician has to balance the risks and benefits of these medications when choosing an antipsychotic for an individual patient.
de Araujo, Arao Nogueira; de Sena, Eduardo Ponde; de Oliveira, Irismar Reis; Juruena, Mario F
A small reduction in prescribing costs is reported from a general practice that has been using a computer for repeat prescribing for three years. The possible reasons for this are discussed. The information available from the Prescription Pricing Authority (PPA) and from practice workload measurements was found to be inconclusive. An elaboration of the computer-controlled system of repeat prescribing to provide a detailed cost analysis of this aspect of prescribing was devised, and the first results are presented. It is calculated that 27 per cent of prescriptions in the practice are produced from electronic records and that the average cost of these is not significantly greater than for prescriptions issued in other situations.
In this article, it is aimed to review the efficacies of mood stabilizers and atypical antipsychotics, which are used commonly in psychopharmacological treatments of bipolar and borderline personality disorders. In this context, common phenomenology between borderline personality and bipolar disorders and differential features of clinical diagnosis will be reviewed in line with the literature. Both disorders can demonstrate common features in the diagnostic aspect, and can overlap phenomenologically. Concomitance rate of both disorders is quite high. In order to differentiate these two disorders from each other, quality of mood fluctuations, impulsivity types and linear progression of disorders should be carefully considered. There are various studies in mood stabilizer use, like lithium, carbamazepine, oxcarbazepine, sodium valproate and lamotrigine, in the treatment of borderline personality disorder. Moreover, there are also studies, which have revealed efficacies of risperidone, olanzapine and quetiapine as atypical antipsychotics. It is not easy to differentiate borderline personality disorder from the bipolar disorders. An intensively careful evaluation should be performed. This differentiation may be helpful also for the treatment. There are many studies about efficacy of valproate and lamotrigine in treatment of borderline personality disorder. However, findings related to other mood stabilizers are inadequate. Olanzapine and quetiapine are reported to be more effective among atypical antipsychotics. No drug is approved for the treatment of borderline personality disorder by the entitled authorities, yet. Psychotherapeutic approaches have preserved their significant places in treatment of borderline personality disorder. Moreover, symptom based approach is recommended in use of mood stabilizers and atypical antipsychotics.
Belli, Hasan; Ural, Cenk; Akbudak, Mahir
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
Eleanor Bradley; Brian Hynam; Peter Nolan
Adverse drug reactions (ADRs) are a major concern in pharmacotherapy and are more common among women. Immortalized human lymphoblastoid cell lines (LCLs) are emerging as a novel tool for studying interindividual variability in drug response, including ADRs. In the present study, we compared sensitivities of LCLs from unrelated healthy male and female donors to growth inhibition by a panel of common drugs. We observed large interindividual drug sensitivity variations with similar mean sensitivities recorded for LCLs from male and female donors for most tested drugs. A notable exception was observed for the typical antipsychotic haloperidol and the atypical antipsychotic risperidone, which exhibited, on average, more robust in vitro growth inhibition in male as compared with female LCLs. An opposite finding was observed for the antidepressant paroxetine, which was more potent for inhibiting the growth of female as compared with male LCLs. These observations are discussed in the context of the higher incidence of dystonia reported for male schizophrenia patients treated with haloperidol and the higher efficacy of paroxetine in female major depression patients. PMID:22760742
Morag, Ayelet; Oved, Keren; Gurwitz, David
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
Sheena Derry; R Andrew Moore
This review describes the animal behavior models that provide insight into the mechanisms underlying the critical differences between the actions of typical vs. atypical antipsychotic drugs. Although many of these models are capable of differentiating between antipsychotic and other psychotropic drugs, only a few seem to be able to differentiate between typical and atypical antipsychotics, such as the paw test
Mark A. Geyer; Bart Ellenbroek
The reintroduction of clozapine, the prototype of atypical antipsychotics, in the late 1980s has led to significant advances in the pharmacological management of schizophrenia. Since then, there has been a rapid development of novel “atypical” antipsychotic agents that have been pharmacologically modeled, to a certain extent, after their predecessor clozapine. As with all antipsychotics, there is variability among individuals in
Mario Masellis; Vincenzo S Basile; Vural Özdemir; Herbert Y Meltzer; Fabio M Macciardi; James L Kennedy
Objective. To design, implement, and evaluate an interprofessional learning workshop on pediatric prescribing. Design. An interactive workshop on pediatric prescribing was designed and delivered by pediatricians and pharmacists to fourth-year medical and pharmacy students on 3 university campus settings. Students were assigned to either interprofessional workshop groups (pharmacy and medical students) or non-interprofessional workshop groups (medical students only). Assessment. Two hundred thirty students completed the workshops and 92% returned both the pre- and post-workshop questionnaires. Attitudes toward interprofessional learning significantly improved among students in the interprofessional workshop groups (p< 0.001) and confidence in prescribing for pediatric patients significantly improved among all students (p< 0.001). Conclusions. The workshop improved medical and pharmacy students’ knowledge and confidence in pediatric prescribing and significantly improved their attitudes toward working and learning with other professionals.
Yuen, Sebastian; Hunt, Linda; Emond, Alan
Text Version... HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use CERVARIX safely and effectively ... More results from www.fda.gov/downloads/biologicsbloodvaccines/vaccines
The aim of the present study was to develop recommendations for antenatal care and monitoring for women with bipolar disorder and schizophrenia who are on lithium carbonate, antipsychotic or anti-epileptic medication during pregnancy. A literature search and review of original research, published reviews and guidelines was undertaken for mood stabilizers and antipsychotics in pregnancy and for the management of bipolar disorder and schizophrenia in pregnancy. This information was summarized, condensed and then reviewed by representatives of psychiatry, pharmacy, paediatrics and obstetrics to produce an information booklet and subsequently monitoring recommendations and tables. A model of antenatal monitoring and care for women with schizophrenia, bipolar disorder and related disorders who are maintained on psychotropic medication was developed. This included an online and published booklet for clinicians summarizing psychotropic medication in pregnancy, and lactation and monitoring tables that could be part of patient case files. These were to assist in reminding and educating staff on the need for additional monitoring and assessment above standard antenatal care for women on mood stabilizers and antipsychotic medication. Women with bipolar disorder and schizophrenia have an increased risk of complications in pregnancy from their illness and from the medications they are prescribed. A summary of the risks and a model of suggested additional monitoring during pregnancy have been developed in consultation across a number of clinical disciplines. PMID:20113298
Galbally, Megan; Snellen, Martien; Walker, Susan; Permezel, Michael
Objective—To develop a practitioner led definition of a prescribing error for use in quantitative studies of their incidence.Design—Two stage Delphi technique.Subjects—A panel of 34 UK judges, which included physicians, surgeons, pharmacists, nurses and risk managers.Main outcome measures—The extent to which judges agreed with a general definition of a prescribing error, and the extent to which they agreed that each of
B Dean; N Barber; M Schachter
Background:UnlikemedicinesprescribedforFoodand DrugAdministration-approvedindications,off-labeluses may lack rigorous scientific scrutiny. Despite concerns aboutpatientsafetyandcoststothehealthcaresystem,little is known about the frequency of off-label drug use or the degree of scientific evidence supporting this practice. Methods: We used nationally representative data from the 2001 IMS Health National Disease and Therapeutic Index (NDTI) to define prescribing patterns by diagno- sis for 160 commonly prescribed drugs. Each reported drug-diagnosis
David C. Radley; Stan N. Finkelstein; Randall S. Stafford
AIMS: Explore and compare junior doctors' perceptions of their self-efficacy in prescribing, their prescribing errors and the possible causes of those errors. METHODS: A cross-sectional questionnaire study was distributed to foundation doctors throughout Scotland, based on Bandura's Social Cognitive Theory and Human Error Theory (HET). RESULTS: 548 questionnaires were completed (35.0% of the national cohort). F1s estimated a higher daytime error rate (median 6.7 (IQR 2-12.4)) than F2s (4.0 IQR (0-10) (p=0.002)), calculated based on the total number of medicines prescribed. The majority of self-reported errors (250; 49.2%) resulted from unintentional actions. Interruptions and pressure from other staff were commonly cited causes of errors. F1s were more likely to report insufficient prescribing skills as a potential cause of error than F2s (p= 0.002). The prescribers did not believe that the outcomes of their errors were serious. F2s reported higher self-efficacy scores than F1s in most aspects of prescribing (p<0.001). CONCLUSION: Foundation doctors were aware of their prescribing errors, yet were confident in their prescribing skills and apparently complacent about the potential consequences of prescribing errors. Error causation is multi-factorial often due to environmental factors, but with lack of knowledge also contributing. Thereforeinterventions are needed at all levels, including environmental changes, improving knowledge, providing feedback and changing attitudes towards the role of prescribing as a major influence on patient outcome. PMID:23627415
Ryan, Cristín; Ross, Sarah; Davey, Peter; Duncan, Eilidh M; Fielding, Shona; Francis, Jill J; Johnston, Marie; Ker, Jean; Lee, Amanda Jane; Macleod, Mary Joan; Maxwell, Simon; McKay, Gerard; McLay, James; Webb, David J; Bond, Christine
Aim To compare the blood lactate levels between patients with psychotic disorder receiving first- and those receiving second-generation antipsychotics. Methods The study was conducted at the psychiatric inpatient and outpatient clinics of the Split Clinical Hospital from June 6, 2008 to October 10, 2009. Sixty patients with psychotic disorder who were assigned to 6-month treatment were divided in two groups: 30 received haloperidol (first generation antipsychotic) and 30 received olanzapine (second generation antipsychotic). Blood lactate levels, other metabolic parameters, and scores on the extrapyramidal symptom rating scale were assessed. Results Patients receiving haloperidol had significantly higher blood lactate levels than patients receiving olanzapine (P?0.001). They also more frequently had parkinsonism, which was significantly correlated with both haloperidol treatment at 1 month (P?0.001) and 6 months (P?=?0.016) and olanzapine treatment at baseline (P?=?0.016), 3 months (P?=?0.019), and 6 months (P?=?0.021). Also, patients receiving haloperidol had significant correlation between blood lactate and dystonia at 1 month (P?0.001) and 6 months (P?=?0.012) and tardive dyskinesia at 1 month (P?=?0.032). There was a significant difference between the treatment groups in lactate levels at all points from baseline to month 6 (P?0.001). Conclusion It is important to be aware of the potential effect of haloperidol treatment on increase in blood lactate levels and occurrence of extrapyramidal side effects. Therefore, alternative antipsychotics should be prescribed with lower risk of adverse side effects. Trial identification number NCT01139463
Glavina, Trpimir; Mrass, Damir; Dodig, Tajana; Glavina, Gordana; Pranic, Shelly; Uglesic, Boran
Behavioral models of antipsychotic drug (APD) action in the rat are widely used for the screening and developing APDs. Valid models are not only required to be selective and specific for APDs, but also to be able to dissociate between typical and atypical APDs. In recent years, newer models have been developed that are claimed to model processes impaired in
Ina Weiner; Inna Gaisler; Daniela Schiller; Amit Green; Lee Zuckerman; Daphna Joel
There is growing acceptance that pregnancy itself is not a protective factor against mental disorders. Indeed, some mental disorders such as psychotic and bipolar disorders may become worse during pregnancy and the immediate postpartum period. In pregnant women with a mental disorder that can be treated with antipsychotics, the known risks -teratogenic, obstetric, neonatal and those affecting the mother- indicate that, in general, the risk of the non-treated disorder is higher than that resulting from the use of antipsychotics and that the reduction in psychoticism improves the overall prognosis of these women. All the antipsychotics marketed in Spain are included in category C of the US Food and Drug Administration, with the exception of clozapine and piperazine, which are included in category B. The use of all of these drugs should be avoided during breast feeding as far as possible. The most reliable current recommendations indicate that optimal control of severe mental disorders should be maintained during pregnancy, the postpartum and subsequent periods. These recommendations also indicate that women with mental disorders must be considered as high risk and that both these women and their pregnancies should be constantly monitored. The currently available scientific information does not allow more than relatively secure individually-tailored recommendations to be made. When taking the decision of whether or not to treat with antipsychotics, the use of a risk-benefit relationship is crucial, with the participation of the woman's partner or legal representative, other physicians and even the clinical pharmacist if necessary. PMID:23034313
Guillén, José Manuel Bertolín; Company, Enrique Soler
Abstract Objective To measure physicians’ experiences with opioid-related adverse events and their perceived level of confidence in their opioid prescribing skills and practices. Design Mailed survey. Setting The province of Ontario. Participants A total of 1000 primary care physicians randomly selected from the College of Physicians and Surgeons of Ontario registration database. Main outcome measures Opioid-related adverse events and concerns (eg, number of patients, type of opioid, cause of the event or concern); physicians’ confidence, comfort, and satisfaction with opioid prescribing; physicians’ opinions on strategies to optimize their prescribing; and physicians’ perspectives of their interactions with pharmacists and nurses. Results The response rate was close to 66%, for a total of 658 participants. Almost all respondents reported prescribing opioids for chronic pain in the past 3 months. Eighty-six percent of respondents reported being confident in their prescribing of opioids, but 42% of respondents indicated that at least 1 patient had experienced an adverse event related to opioids in the past year, usually involving oxycodone, and 16.3% of respondents did not know if their patients had experienced any opioid-related adverse events. The most commonly cited factors leading to adverse events were that the patient took more than prescribed, the prescribed dose was too high, or the patient took alcohol or sedating drugs with the opioids. Most physicians had concerns about the opioid use of 1 or more of their patients; concerns included running out of opioids early, minimal access to pain and addiction treatment, and addiction and overdose. The reported number of physicians’ patients taking opioids was positively associated with their confidence and comfort levels in opioid prescribing and negatively associated with their belief that many patients become addicted to opioids. Conclusion Most physicians have encountered opioid-related adverse events. Comprehensive strategies are required to promote safe prescribing of opioids, including guidelines and comprehensive office-system materials.
Wenghofer, Elizabeth Francis; Wilson, Lynn; Kahan, Meldon; Sheehan, Carolynn; Srivastava, Anita; Rubin, Ava; Brathwaite, Joanne
Medication errors are probably the most prevalent form of medical error, and prescribing errors are the most important source of medication errors. In this article we suggest interventions are needed at three levels to improve prescribing: (1) improve the training, and test the competence, of prescribers; (2) control the environment in which prescribers perform in order to standardise it, have
N Barber; M Rawlins; B Dean Franklin
Medications are being used with greater frequency to address pediatric mental health problems, and in recent years atypical antipsychotic (AAP) prescriptions have increased more than any other class. Acute care practitioners must be aware of the pharmacology of AAPs and the conditions, on- and off-label, for which they are prescribed. This involves identifying and managing side effects that manifest both mentally and physically. Although "atypicality" confers a lower risk of movement side effects compared to conventional agents, children are more sensitive than adults to extrapyramidal reactions. Like adults, they also may present with toxic sedation, confusion, cardiovascular dysfunction, and metabolic derangements. Evaluation and management of these toxicities requires an index of suspicion, a careful symptom and medication history, physical examination, and targeted interventions. This review is designed to orient the emergency practitioner to the challenging task of recognizing and treating adverse effects related to acute and chronic atypical antipsychotic exposure in children. PMID:23471213
Rasimas, J J; Liebelt, Erica L
Astrocytes express dopamine receptors and respond to dopamine stimulation. However, the role of astrocytes in psychiatric disorders and the effects of antipsychotics on astroglial cells have only been investigated recently. S100B is a glial-derived protein, commonly used as a marker of astroglial activation in psychiatric disorders, particularly schizophrenia. We investigated S100B secretion in three different rat brain preparations (fresh hippocampal slices, C6 glioma cells and primary astrocyte cultures) exposed to apomorphine and antipsychotics (haloperidol and risperidone), aiming to evaluate, ex vivo and in vitro, whether dopamine activation and dopaminergic antagonists modulate astroglial activation, as measured by changes in the extracellular levels of S100B. The serum S100B elevation observed in schizophrenic patients is not reflected by the in vitro decrease of S100B secretion that we observed in hippocampal slices, cortical astrocytes and C6 glioma cells treated with apomorphine, which mimics dopaminergic hyperactivation. This decrease in S100B secretion can be explained by a stimulation of D2 receptors negatively coupled to adenyl cyclase. Antipsychotic medications and antioxidant supplementation were able to prevent the decline in S100B secretion. Findings reinforce the benefits of antioxidant therapy in psychiatric disorders. Based on our results, in hippocampal slices exposed to apomorphine, it may be suggested that antipsychotics could help to normalize S100B secretion by astrocytes. PMID:21513766
Nardin, Patrícia; Tramontina, Ana Carolina; Quincozes-Santos, André; Tortorelli, Lucas S; Lunardi, Paula; Klein, Paulo R; Wartchow, Krista M; Bobermin, Larissa D; Gottfried, Carmem; Elisabetsky, Elaine; Gonçalves, Carlos-Alberto
Results Antibiotics were prescribed to 63% of patients with an ARTI, ranging from 46% of patients with the common cold or nonspecific URTIs to 69% of patients with acute sinusitis. Broad-spectrum agents were chosen in 54% of patients prescribed an antibiotic, including 51% of patients with the common cold and nonspecific URTIs, 53% with acute sinusitis, 62% with acute bronchitis,
Michael A. Steinman; C. Seth Landefeld; Ralph Gonzales
Text Version... includes psychological, educational and social interventions. ... pneumonia is a common cause of morbidity ... they were not necessarily caused by it. ... More results from www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials
Doctors should pay greater attention to managing the risk-benefit relationship to improve care of patients over 65, urge Jerry Avorn and William Shrank (doi: 10.1136\\/bmj.39520.671053.94). The challenge of safer prescribing, says Anne Spinewine, lies in shared decision making
OBJECTIVE Concerns over rising drug costs, pharmaceutical advertising and potential conflicts of interest have focused attention on physician prescribing behavior. We examine how broadly physicians prescribe within the ten most prevalent therapeutic classes, the factors affecting their choices, and its impact on patient-level outcomes. STUDY DESIGN Retrospective study from 2005 to 2007 examining prescribers with at least five initial prescriptions within a class from 2005–2007. Medical and pharmacy claims are linked to prescriber information from 146 different health plans, reflecting 1,975 to 8,923 unique providers per drug class. METHODS Primary outcomes are the number of distinct drugs in a class initially prescribed by a physician over 1- and 3-year periods, medication possession ratio, and out of pocket costs. RESULTS In 8 of 10 therapeutic classes, the median physician prescribes at least 3 different drugs and less than one in six physicians prescribes only brand drugs. Physicians prescribing only one or two drugs in a class are more likely to prescribe the most advertised drug. Physicians who prescribe fewer drugs are less likely to see patients with other comorbid conditions and varied formulary designs. Prescribing fewer drugs is associated with lower rates of medication adherence and higher out-of-pocket costs for drugs, but the effects are small and inconsistent across classes. CONCLUSIONS Physicians prescribe more broadly than commonly perceived. Though narrow prescribers are more likely to prescribe highly advertised drugs, few physicians prescribe these drugs exclusively. Narrow prescribing has modest effects on medication adherence and out of pocket costs in some classes.
Joyce, Geoffrey F.; Carrera, Mariana; Goldman, Dana P.; Sood, Neeraj
Diabetes mellitus occurs in schizophrenia patients at higher rates than in the general population. Reasons for this elevated risk are poorly understood and have not been examined prospectively in antipsychotic-naïve, first-episode patients. This study aims to determine which antipsychotics are associated with diabetes development in antipsychotic-naïve schizophrenia patients. All antipsychotic-naïve patients diagnosed with schizophrenia in Denmark between 01 January 1997 and 31 December 2004, followed until 31 December 2007, allowing for ?3 years follow-up, unless death or diabetes onset occurred. Risk factors for the time to diabetes onset were assessed, including antipsychotics taken for at least 180 defined daily doses in the first year after first antipsychotic prescription (‘initial treatment'). Risk factors for diabetes incidence were assessed, including antipsychotic use within 3 months before diabetes onset or study end (‘current treatment'). Of 7139 patients, followed for 6.6 years (47?297 patient years), 307 developed diabetes (annual incidence rate: 0.65%). Time to diabetes onset was significantly shorter in patients with higher age (hazard ratio (HR): 1.03, confidence interval (CI): 1.02–1.03) and those with ‘initial' treatment of olanzapine (HR: 1.41, CI: 1.09–1.83), mid-potency first-generation antipsychotics (FGAs) (HR: 1.60, CI: 1.07–2.39), antihypertensive (HR: 1.87, CI: 1.13–3.09), or lipid-lowering drugs (HR: 4.67, CI: 2.19–10.00). Significant factors associated with diabetes within 3 month of its development included treatment with low-potency FGAs (odds ratio (OR): 1.52, CI: 1.14–2.02), olanzapine (OR: 1.44, CI: 1.98–1.91), and clozapine (OR: 1.67, CI: 1.14–2.46), whereas aripiprazole was associated with lower diabetes risk (OR: 0.51, CI: 0.33–0.80). In addition to general diabetes risk factors, such as age, hypertension, and dyslipidemia, diabetes is promoted in schizophrenia patients by initial and current treatment with olanzapine and mid-potency FGAs, as well as by current treatment with or low-potency first-generation antipsychotics and clozapine, whereas current aripiprazole treatment reduced diabetes risk. Patients discontinuing olanzapine or mid-potency FGA had no increased risk of diabetes compared with patient not treated with the drugs at anytime.
Nielsen, Jimmi; Skadhede, S?ren; Correll, Christoph U
Objective This study compared the efficacy and tolerability of aripiprazole with that of other atypical antipsychotics by examining patients with pediatric bipolar disorder (PBD) at a child and adolescent psychiatric clinic in a university hospital in Korea. Methods We reviewed the medical records of 127 pediatric patients with bipolar disorder aged 4-18 years treated at Department of Child and Adolescent Psychiatric, Yonsei University Severance Hospital between January 2010 and October 2011 to collect demographic and clinical data. Using the Clinical Global Impression (CGI) scales, we evaluated levels of severity of and improvements in symptoms at the first, second, third, fourth, and fifth hospital visits. Results The mean age of patients was 12.29±3.47 years. The sample included 91 (71.7%) male and 36 (28.3%) female patients. Aripiprazole was prescribed to 62 (48.8%) patients, risperidone to 52 (40.9%), quetiapine to 11 (8.7%), and paliperidone to two (1.6%). Patients treated with aripiprazole had lower CGI-Severity (CGI-S) scores than did patients treated with other atypical antipsychotics at the second and third visits. The CGI-Improvement (CGI-I) scores of patients treated with aripiprazole were lower at the second visit. Treatment with atypical antipsychotics was well tolerated, and no serious or fatal side effects were observed. Conclusion The present retrospective chart review suggests that atypical antipsychotics may be effective and safe for the treatment of patients with PBD. In particular, treatment with aripiprazole may be more effective than treatment with other atypical antipsychotics in the early phase. These results should be verified in future multi-center controlled studies.
Oh, Jooyoung; Chang, Jhin Goo; Lee, Seul Bi; Song, Dong-Ho
Typical antipsychotics exert their effect by blocking post-synaptic dopaminergic receptors; blockade of the mesolimbic and mesocortical pathways are therapeutic and help reduce positive psychotic symptoms but blockade of the nigro-striatal pathway produces extrapyramidal side effects (EPSE). Post clozapine, the Food and Drug Administration (FDA) has approved the use of four newer atypical antipsychotics; risperidone, olanzapine, quetiapine and ziprasidone for the treatment of schizophrenia. Because of their dual serotonin and dopamine receptor blocking abilities, atypical antipsychotics have greater efficacy (especially for negative symptoms) and fewer EPSE when compared to the typical antipsychotics. Given the lack of studies directly comparing these agents, we used the Physician Desk Reference (PDR) to calculate the treatment emergent placebo adjusted side effects for these atypical antipsychotics. The results are then presented in an easy to read table. To the best of our knowledge, this is the first comparison study involving these four newer antipsychotic agents. PMID:12665274
Alao, Adekola O; Malhotra, Kamna; Dewan, Mantosh J
Novel antipsychotics (clozapine, risperidone, olanzapine, quetiapine) are effective in treating psychotic symptoms, also in neurological disease. Hyperprolactinemia is a side effect related to antipsychotics that can cause galactorrhea, gynecomastia, amenorrhea, anovulation, impaired spermatogenesis, decreased libido and sexual arousal, impotence, and anorgasmia, consequent to removal of tonic dopaminergic inhibition of prolactin secretion via hypothalamic dopaminergic receptor blockade in the tuberoinfundibolar tract. Hyperprolactinemia occurs more frequently during treatment with risperidone and olanzapine compared with clozapine and quetiapine. The therapeutic algorithm to antipsychotic-relatedhyperprolactinemia is the following: reduction in antipsychotic dose, addition of cabergoline, bromocriptine, amantadine, and/or switch to another antipsychotic. We propose switching to quetiapine in symptomatic hyperprolactinemia related to antipsychotics and describe five cases. PMID:12522680
Keller, R; Mongini, F
There are multiple benefits of appropriate antimicrobial prescribing: it has a direct impact on clinical outcomes, avoids adverse effects, is cost effective and, perhaps most importantly, it helps to prevent the emergence of resistance. However, any physician can prescribe antibiotics, which is not the case with other clinically relevant drugs. There is great variability in the prescribing physician's (PP) training, motivation, workload and setting, including accessibility to infectious diseases consultants and/or diagnostic techniques, and therefore there is a high risk of inappropriate prescription. Many antibiotic prescribing errors occur around the selection and duration of treatment. This includes a low threshold for the indication of antibiotics, delayed initiation of treatment when indicated, limited knowledge of local antimicrobial resistance patterns by the PPs, errors in the final choice of dose, route or drug and a lack of de-escalation. Similarly, the prescription of prophylactic antibiotics to prevent surgical site infections, despite being commonly accepted, is suboptimal. Factors that may explain suboptimal use are related to the absence of well-defined protocols, poor knowledge of prophylactic protocols, miscommunication or disagreement between physicians, logistical problems, and a lack of audits. A proper understanding of the prescribing process can guide interventions to improve the PP's practices. Some of the potential interventions included in a stewardship program are education in antimicrobial prescribing, information on the local resistance patterns and accessibility to a qualified infectious diseases consultant. PMID:24129284
Calbo, Esther; Alvarez-Rocha, Luis; Gudiol, Francisco; Pasquau, Juan
\\u000a Schizophrenia patients have high prevalence of cardiovascular (CV) disease risk factors and high CV mortality, with increasing\\u000a concern over the contribution of antipsychotic medications to cardiometabolic risk. The design of the NIMH-sponsored Clinical\\u000a Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial was driven by a need to understand the efficacy\\u000a and safety differences between atypical antipsychotics, and between atypical and
Jonathan M. Meyer
Alterations in plasma leptin have been reported in schizophrenia patients treated with antipsychotics, suggesting the hypothesis that impairments in leptin secretion or signaling might play a role in antipsychotic-induced weight gain. Plasma leptin was measured in 72 schizophrenia patients chronically treated with olanzapine (n=27), risperidone (n=24) or typical antipsychotics (n=21) and 124 healthy adult control subjects. ANCOVA was used to
Dan W Haupt; Angela Luber; Justin Maeda; Angela K Melson; Julie A Schweiger; John W Newcomer
|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…
Willett, Gilbert M.; Hyde, Jennifer E.; Uhrlaub, Michael B.; Wendel, Cara L.; Karst, Gregory M.
This study examined associations between medications prescribed to control children's problem behaviors and levels of, and diurnal variation in, salivary cortisol (C), testosterone (T), and dehydroepiandrosterone (DHEA). Saliva was collected in the morning, midday, and afternoon from 432 children ages 6-13 years. Relative to a no-medication comparison group, children taking (1) antipsychotics had higher DHEA levels and flat C diurnal rhythms, (2) Ritalin or Adderall had flat T diurnal rhythms, (3) Concerta had higher T and DHEA levels, (4) antidepressants had flat DHEA diurnal rhythms, and (5) hypotensives had flat DHEA diurnal rhythms and higher T levels. Medications prescribed to control children's problem behaviors should be monitored in studies of the endocrine correlates and consequences of developmental psychopathology. PMID:17517013
Hibel, Leah C; Granger, Douglas A; Cicchetti, Dante; Rogosch, Fred
The purpose of this study was to investigate the potency of atypical antipsychotics (clozapine, olanzapine, amisulpride, quetiapine, aripiprazole, risperidone) to reduce immobility time and to increase the fighting power, and the number of fights in an automated version of the tail suspension test in C57BL/6J mice. Antidepressant drugs, citalopram and imipramine were tested for comparison. Olanzapine (0.125-5 mg/kg), amisulpride (0.5-2 mg/kg), quetiapine (0.25-2 mg/kg), aripiprazole (0.25-1 mg/kg), and risperidone (0.005-0.05 mg/kg) did not produce any antidepressant-like effect. Only clozapine (0.156-2.5 mg/kg), administered at a dose of 0.312 mg/kg, significantly increased the number of fight episodes. As expected, citalopram (20-40 mg/kg) and imipramine (10-30 mg/kg) dose dependently produced antidepressant-like activity in the same procedure. The effect of antipsychotics on spontaneous locomotor activity and MK-801-induced or d-amphetamine-induced hyperactivity, were also tested in CD-1 mice to confirm the active doses of these drugs in tests commonly used to predict antipsychotic-like activity. Careful screening of potential antipsychotics for their antidepressant effects is considered to be an important part of modern drug development. Our data suggest that the tail suspension test in mice may be relatively insensitive to antidepressant-like activity of atypical antipsychotic drugs with antidepressant properties confirmed by clinical trials. PMID:21127415
Weso?owska, Anna; Partyka, Anna; Jastrz?bska-Wi?sek, Magdalena; Kolarz, Adam; Mierzejewski, Pawe?; Bie?kowski, Przemys?aw; Ko?aczkowski, Marcin
The search for the underlying pathophysiology of schizophrenia has been an active avenue of investigation since the disease was first recognized more than 100 years ago. Although a great deal of the research has been driven by the known pharmacology of effective antipsychotic drugs, i.e., overactivity of the dopamine system, recent advances in neurobiology provide evidence that reduced synaptic connectivity/neurotransmission may play a substantial role in this disorder. One neuropeptide long posited to play a role in the biology of schizophrenia is neurotensin (NT). Central nervous system administration of NT has been shown to produce a wide variety of effects. Because of its close association with the dopamine (DA) system, the role of the NT system in clinical disorders hypothesized to involve DA circuits such as schizophrenia, Parkinson's disease, and drug abuse has been closely scrutinized. In addition, NT neurotransmission has been implicated in regulation of the stress response, stress-induced gastric ulcers, temperature regulation, food consumption, and analgesia. NT also acts as a growth factor in a variety of human cancer cell lines derived from lung, colon, prostate, and pancreas. This review first provides a background of the NT system. Second, data indicating that NT may mediate the effects of antipsychotic drugs are summarized. Third, data implicating NT in the pathophysiology of schizophrenia are described. Finally, evidence suggesting the use of NTergic compounds as novel antipsychotic drugs are presented. PMID:15006494
Kinkead, Becky; Nemeroff, Charles B
There is neurobiologically based, theoretical support for the use of antipsychotic medications in the treatment of anxiety, and two first-generation neuroleptics are approved by the United States Food and Drug Administration for the treatment of nonpsychotic anxiety. However, neuroleptics are associated with a large side effect burden, which has limited their utility in the treatment of nonpsychotic disorders. Because of their somewhat improved safety profile, atypical antipsychotics are increasingly used for the treatment of nonpsychotic anxiety. The published literature describing the efficacy of atypical antipsychotics in randomized, controlled trials involving patients with anxiety disorders is briefly reviewed, and the safety of atypical antipsychotics in nonpsychotic disorders is discussed. There is moderately strong controlled evidence supporting the use of some atypical antipsychotics, either as adjunctive treatment or monotherapy, in the treatment of nonpsychotic anxiety; however, the side effect burden of some atypical antipsychotics probably outweighs their benefits for most patients with anxiety disorders. The evidence to date does not warrant the use of atypical antipsychotics as first-line monotherapy or as first- or second-line adjunctive therapy in the treatment of anxiety disorders. Rigorous, independently funded, long-term studies are needed to support the off-label use of atypical antipsychotics in the treatment of anxiety disorders. Nevertheless, some patients with highly refractory anxiety disorders may benefit from the judicious and carefully monitored use of adjunctive atypical antipsychotics. A careful risk-benefit assessment must be undertaken by the physician, on a case-by-case basis, with appropriate informed consent.
... ziprasidone (Geodon). All of tvhe atypical antipsychotics are approved for the treatment of schizophrenia. None, however ... More results from www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders
Case reports indicate that antipsychotics can cause priapism, a persistent penile erection possibly leading to erectile dysfunction. The mechanism of antipsychotic-induced priapism is thought to be related to blockade of alpha1 adrenergic receptors, but clinical data supporting this hypothesis are lacking. The aim of this study was to investigate if the presence of safety signals for antipsychotics and priapism is associated with their alpha1 affinity. Spontaneous reports of adverse drug reactions contained in the US Adverse Event Reporting System database were used to calculate reporting odds ratios (RORs) of priapism for antipsychotics. In total, 426 cases of priapism with 144 of them attributed to antipsychotics were identified. For antipsychotics with high alpha1 affinity, the adjusted ROR was markedly elevated (ROR = 9.9; 95% CI, 7.9-12.4), whereas a weaker signal was observed for antipsychotics with low/medium alpha1 affinity (ROR = 3.6; 95% CI, 2.4-5.2). Signals were present for chlorpromazine, quetiapine, risperidone, ziprasidone, and aripiprazole. After restricting the analysis to cases with medical intervention or disability, the safety signal remained evident only for antipsychotics with high but not for those with low/medium affinity. The observed pattern of signals indicates a relationship between alpha1 affinities of antipsychotics and the occurrence of priapism. PMID:20075651
Andersohn, Frank; Schmedt, Niklas; Weinmann, Stefan; Willich, Stefan N; Garbe, Edeltraut
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
Nikki J. Radke; David B. Wester; Gad Perry; Sandra Rideout-Hanzak
The prescribing of psychotropic drugs was studied in a Scottish general practice of five doctors and 8,300 patients; one third of the patients were aged 12 years or less. In 1971, 336 prescriptions for psychotropic drugs were issued to 172 children and 2,583 to the adults. Most children were given only one prescription, but some needed up to ten in one year. The drugs consisted of sedatives (43 per cent), tranquillisers (41 per cent), and hypnotics (17 per cent). Most were given for behaviour disorders and enuresis. The analysis of drugs given by each doctor showed that one had given about one third of the total. This demonstration of comparative over-prescribing was useful in discussing self-audit.
Bain, D. J. G.
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.
Fernández, Cristina; Vega, José A.; Fonturbel, Teresa
Background Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG) is a common side effect of the atypical antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI). However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs. We explored these potential associations by genotyping GHRL alleles in SZ patients and controls. We also examined the relation between these SNPs and changes in metabolic indices during AAP treatment in SZ subgroups distinguished by high or low therapeutic response. Methods Four SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C) were genotyped in 634 schizophrenia patients and 606 control subjects. Results There were no significant differences in allele frequencies, genotype distributions, or the distributions of two SNP haplotypes between SZ patients and healthy controls (P > 0.05). There was also no significant difference in symptom reduction between genotypes after 8 weeks of AAP treatment as measured by positive and negative symptom scale scores (PANSS). However, the -604 G/A polymorphism was associated with a greater BMI increase in response to AAP administration in both APP responders and non-responders as distinguished by PANSS score reduction (P < 0.001). There were also significant differences in WG when the responder group was further subdivided according to the specific AAP prescribed (P < 0.05). Conclusions These four GHRL gene SNPs were not associated with SZ in this Chinese Han population. The -604 G/A polymorphism was associated with significant BW and BMI increases during AAP treatment. Patients exhibiting higher WG showed greater improvements in positive and negative symptoms than patients exhibiting lower weight gain or weight loss.
In paediatrics, antibiotics are among the most commonly prescribed drugs. Because of an overall rise in health care costs,\\u000a lack of uniformity in drug prescribing and the emergence of antibiotic resistance, monitoring and control of antibiotic use\\u000a is of growing concern and strict antibiotic policies are warranted. Before such a policy can be implemented, detailed knowledge\\u000a of antibiotic prescribing patterns
M. A. van Houten; M. Laseur; J. L. L. Kimpen
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
Kapetanovic, Suad; 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
This paper reports a pilot study exploring mental health nurse prescribers' perceptions of barriers to prescribing independently but also includes perceptions of barriers to supplementary prescribing. Current prescribing practice as experienced by mental health nurses suggests a need to identify and highlight these barriers. A mixed methodology explanatory sequential study was carried out over 3 months in Scotland in 2008 as part of a Master's degree. A questionnaire was completed by 33 mental health nurse prescribers. A focus group was conducted with 12 mental health nurse prescribers. Participants' views exposed a number of barriers to prescribing previously unidentified in a review of the relevant literature, and concurred with some previously documented barriers. Sixty per cent of mental health nurse prescribers in the study were not prescribing. Barriers identified in the study included concern about how prescribing impacts on the therapeutic relationship, role conflict, lack of support, inappropriateness of prescriber training, remuneration, qualifying to prescribing time, supervision, prescribing policies, clinical governance and nurse management. Nurse prescribing involves increased accountability and responsibility which is not currently recognized in job status or pay banding. Mental health nurse prescribing has the potential to enhance service provision, but until barriers to prescribing have been identified and addressed as part of the process of organizational change, nurse prescribing cannot achieve its maximum potential. PMID:22295995
Ross, J D; Kettles, A M
Antibiotic resistance is increasingly affecting the management of infectious diseases. The prescribing clinician is not only important to the development of the problem but also central to its solution. This article addresses the current weaknesses in the information systems and the evidence base that support prescribing. Remedies necessary for improvements in prudent prescribing include better guidance in managing specific diseases
Roger G. Finch
With the expansion of nurse prescribing to include the whole British National Formulary, it is essential that all prescribing nurses can accurately calculate and check medication doses. A more uniform approach to professional education for nurse prescribers is needed. This process would be assisted by dissemination of existing good practice and adjustments to the current national standards of assessment. PMID:17436893
Warburton, Paul; Kahn, Peter
Many psychotropics prescribed to children are unlicensed or off-label. This article uses the two most prescribed psychotropics (MPH and SSRIs) to illustrate various concerns about their impact on youth. Many mental illnesses begin in childhood or early adulthood, warranting a treatment of some kind. However, commentators have argued that prescribing is influenced by five myths: (1) children are little adults;
Shaheen E Lakhan; Gareth E Hagger-Johnson
This study assessed the association between second-generation antipsychotic medications and risk of pneumonia requiring hospitalization in patients with schizophrenia because the evidence is limited in the population. We enrolled a nationwide cohort of 33,024 inpatients with schizophrenia ranged in age from 18 to 65 years, who were derived from the National Health Insurance Research Database in Taiwan from 2000 to 2008. Cases (n = 1741) were defined as patients who developed pneumonia after their first psychiatric admissions. Risk set sampling was used to match each case with 4 controls by age, sex, and the year of the first admission based on nested case-control study. Antipsychotic exposure was categorized by type, duration, and daily dose, and the association between exposure and pneumonia was assessed using conditional logistic regression. We found that current use of clozapine (adjusted risk ratio = 3.18, 95% CI: 2.62-3.86, P < .001) was associated with a dose-dependent increase in the risk. Although quetiapine, olanzapine, zotepine, and risperidone were associated with increased risk, there was no clear dose-dependent relationship. Amisulpride was associated with a low risk of pneumonia. The use of clozapine combined with another drug (olanzapine, quetiapine, zotepine, risperidone, or amisulpride), as assessed separately, was associated with increased risk for pneumonia. In addition, with the exception of amisulpride, each drug was associated with increased risk for pneumonia at the beginning of treatment. Clinicians who prescribe clozapine to patients with schizophrenia should closely monitor them for pneumonia, particularly at the start of therapy and when clozapine is combined with other antipsychotics. PMID:22282455
Kuo, Chian-Jue; Yang, Shu-Yu; Liao, Ya-Tang; Chen, Wei J; Lee, Wen-Chung; Shau, Wen-Yi; Chang, Yao-Tung; Tsai, Shang-Ying; Chen, Chiao-Chicy
More than 50 years after the introduction of modern pharmacotherapies for schizophrenia, there remains a tremendous need for therapeutic advances. A second generation of antipsychotic drugs, introduced over the past 15 years, has provided uncertain advantages over the first-generation drugs. This paper reviews the designs of studies that evaluate the effectiveness of putative antipsychotic drugs. Data from the trials needed
Wayne M. Alves; Robert M. Hamer; Jeffrey A. Lieberman; T. Scott Stroup
Previously, clinicians worked with antipsychotic drugs that almost invariably caused extrapyramidal side effects (EPS) at the dose at which they were clinically effective. By definition, all newer generation atypical antipsychotic agents are significantly better than conventional agents with regard to EPS; i.e., they are clinically effective at doses at which they do not cause EPS. This EPS advantage of atypical
|The behavior disorders of 54 Japanese individuals with mental retardation receiving antipsychotic medication were compared to 52 subjects receiving anticonvulsants and 202 subjects without medication. Results found the problem behaviors of subjects receiving antipsychotic drugs were more severe and severity of disability was associated with…
BACKGROUND: Men and women with schizophrenia suffer not only from their illness but also from the side effects of their medications. OBJECTIVE: To review the toll of antipsychotic side effects specifically on women. STUDY DESIGN: A review of the literature in the PubMed database since 1990 using search terms: sex difference, antipsychotics, schizophrenia, pharmacokinetics, pharmacodynamics, and pharmacogenomics and retrieving additional
Mary V. Seeman
Standards developed from the Royal College of Psychiatrists'consensus statement on the use of high- dose antipsychotics were audited. The baseline survey and two completed audit cycles are described showing improvement in the monitoring and management of out-patients on higher dose depot antipsychotics. Initially the main problem was poor attendance at hospital appointments. Practice was changed by (a) medical staff becoming
John R. Taylor; Ian B. Cookson
Neuropathic pain affects between 5% and 10% of the US population and can be refractory to treatment. Opioids may be recommended as a second-line pharmacotherapy but have risks including overdose and death. Cannabis has been shown to be effective for treating nerve pain without the risk of fatal poisoning. The author suggests that physicians who treat neuropathic pain with opioids should evaluate their patients for a trial of cannabis and prescribe it when appropriate prior to using opioids. This harm reduction strategy may reduce the morbidity and mortality rates associated with prescription pain medications.
When Department of Health and Human Services (HHS) Secretary Michael Leavitt called on Medicare, Medicaid, and large private health care payers in November to require physicians to ditch the pen-and-pad route and write their prescriptions electronically, it should have come as no surprise. Leavitt has been preaching the gospel of harnessing health information technology, including e-prescribing, for years now as a way to reduce increasing numbers of medical errors and to ensure that patients receive correct medications and dosages. But what he wrote on his official blog on the HHS Web site caused a flurry of news coverage and renewed interest from Congress. PMID:18488796
Thinning and prescribed burning are common management practices for reducing fuel buildup in ponderosa pine forests. However, it is not well understood if their combined use is required to lower wildfire risk and to help restore natural ecological function. We compared 16 treatment combinations of thinning, prescribed fire, and slash retention for two decades across a site quality gradient of
Matt D. Busse; P. H. Cochran; William E. Hopkins; William H. Johnson; Gregg M. Riegel; Gary O. Fiddler; Alice W. Ratcliff; Carol J. Shestak
Schoch, P. and Binkley, D., 1986. Prescribed burning increased nitrogen availability in a mature loblolly pine stand. For. Ecol. Manage., 14: 13--22. Prescribed burning is a common management practice in loblolly pine (Pinus taeda L.) ecosystems. Several studies have examined the volatilization losses of nitrogen (N), but little information is available on subsequent availability of N. We examined the effects
PETER SCHOCH; D BINKLEY
Objectives To evaluate the prescribing patterns of compound mixtures of cough and cold liquid medications, known as mezclitas, which are prescribed to patients with respiratory illnesses in Puerto Rico. Secondary objectives include assessing the potential safety of these mixtures and patients’ perception of them. Methods Using a cross sectional study approach, a convenience sample was obtained from five pharmacies in Puerto Rico, from October 2008 to October 2009. Patients were asked to complete a 9-item questionnaire of demographic information, in addition to their mezclita prescription data. Results The mean age of patients was 43 years with a range of less than 12 months to 101 years. For children ? four years of age, 71% were prescribed cough and cold medications. Sixty-four percent of the prescriptions were given to females. The most prevalent ingredient employed was guaifenesin, which appeared in about 77% of the mezclitas. ‘Common cold’ was the principal diagnosis for 62% of the prescriptions, of which 75% of these prescriptions contained a corticosteroid and 17% contained a beta2 agonist bronchodilator. The top medical prescribing specialty was general medicine (51%). Thirty-eight percent of hypertensive patients were prescribed a decongestant. The majority of diabetic patients (60%) were dispensed a corticosteroid. Most (74%) patients reported that they had a rapid and good response to their mezclita. Conclusion Mezclitas were most commonly prescribed for acute symptoms of upper respiratory illness by general physicians, despite possible side effects. This study suggests that the prescription patterns of mezclitas do not always consider evidence-based medicine treatment guidelines.
Quevedo, Juan; Marsh, Wallace; Yulfo, Jessica; Alvarez, Olga; Felici, Marcos; Rojas, Maria E
The atypical antipsychotic drugs are considered a first-line treatment for mania in bipolar disorder with many having a proven superiority to the classical mood stabilisers. This review addresses the pharmacological mechanisms underlying this therapeutic efficacy, as well as those mechanisms considered responsible for the adverse effects of antipsychotic drugs, with a particular focus on the recently introduced asenapine. The high efficacy in bipolar mania of haloperidol, a relatively selective dopamine D2-like receptor antagonist, indicates that the one common receptor mechanism underlying antipsychotic effects on mania is antagonism at the D2 receptor. Serotonin receptors are implicated in antidepressant response, and relief of depressed mood in mixed states is likely to involve drug effects at one, or more likely several interacting, serotonin receptors. Asenapine shows a unique breadth of action at these sites, with potential effects at clinical doses at 5HT1A, 1B, 2A, 2C, 6 and 7 receptors. Antagonism at alpha2 adrenoceptors may also be involved. Adverse effects include those classically associated with dopamine D2 receptor blockade, the extrapyramidal side effects (EPS), and which are relatively diminished in the atypical (in comparison with the conventional) antipsychotics. A variety of protective mechanisms against EPS associated with different drugs include low D2 affinity, D2 partial agonism, high 5-HT2A and 2C antagonism. Similar effects at the D2 and 5-HT2C receptors may underlie the low propensity for hyperprolactinaemia of the atypicals, although the strong prolactin-elevating effect of risperidone reflects its relatively high blood/brain concentration ratio, a consequence of it being a substrate for the p-glycoprotein pump. Weight gain is a further concern of antipsychotic treatment of bipolar disorder which is particularly severe with olanzapine. Histamine H1, alpha1 adrenergic and particularly 5-HT2C receptors are implicated in this effect, although the lower propensity for weight gain shown by asenapine which, like olanzapine, binds to these receptors, indicates that other protective receptor mechanisms, or subtle differences in the 5-HT2C receptor-mediated effects, may be important. Of other peripheral and central effects, the pharmacological basis of sedation (H1 receptors) and postural hypotension (alpha1 adrenoceptors) are rather better understood. The relative benefits of atypical antipsychotics like asenapine can be understood from their receptor pharmacology, and this understanding is key to the future development of improved treatment for bipolar disorder.
The mammalian hippocampus continues to generate new neurons throughout life. The function of adult-generated neurons remains controversial, but adult neurogenesis in the hippocampus is related to depression. Studies show that neurogenesis in the hippocampus is regulated by antidepressants in both humans and rodents, but no studies have examined the effects of age, sex, or antipsychotic exposure on the relationship between depression, antidepressant exposure, and hippocampal neurogenesis in humans. Hippocampal sections were obtained from the Stanley Medical Research Institute and were immunohistochemically labeled for the immature neuron marker doublecortin and the cell cycle arrest marker p21. We compared the number of cells in the granule cell layer and subgranular zone that expressed these proteins in brains from control subjects (n=12), patients with major depressive disorder (MDD) without psychotic symptoms (n=12), and patients with MDD and psychotic symptoms (n=12). We show here that the density of doublecortin/NeuN expression was increased in MDD patients compared with controls and MDD patients with psychosis, with the effect greater in women. Further, we show that older depressed patients without psychosis had higher levels of p21/NeuN expression and that depressed individuals prescribed antidepressants had higher levels of p21/NeuN expression, but only in older women. We show for the first time that changes in neurogenesis due to prescribed antidepressants or depression are dependent on age, sex, and the presence of antipsychotics or psychotic symptoms. PMID:23778854
Epp, Jonathan R; Beasley, Clare L; Galea, Liisa Am
Williams syndrome (WS) is a neurodevelopmental genetic disorder characterized in part by anxiety and behavioral difficulties. We examine the effectiveness and adverse effects of antidepressant, anxiolytic, and antipsychotic medications in individuals with WS. A total of 513 parents/caregivers completed a survey of psychotropic medication usage regarding their child or adult with WS. Twenty-four percent (24%) of the individuals had been prescribed an SSRI medication, while 12% had been prescribed another type of antidepressant or anxiolytic. Overall, 81% of respondents indicated that SSRI medications were either "Helpful" or "Somewhat Helpful", with paroxetine reported to be the least helpful. Sixty-four percent (64%) of survey participants reported that non-SSRI antidepressants and anxiolytics were either "Helpful" or "Somewhat Helpful" in treating symptoms of anxiety. Side effects for the antidepressants and anxiolytics were typically neurological in nature. Ten percent (10%) of the survey participants reported taking an antipsychotic medication, with risperidone and quetiapine described as more helpful than aripiprazole. Medication effectiveness may be related to the impact on serotonin levels. These findings call for further studies of medication usage in WS in order to improve their quality of life. PMID:22776821
Martens, Marilee A; Seyfer, Daisha L; Andridge, Rebecca R; Foster, Jessica E A; Chowdhury, Monali; McClure, Kelsey E; Coury, Daniel L
Background Channeling occurs when a medication and its potential comparators are selectively prescribed based on differences in underlying patient characteristics. Drug safety advisories can provide new information regarding the relative safety or effectiveness of a drug product which might increase selective prescribing. In particular, when reported adverse effects vary among drugs within a therapeutic class, clinicians may channel patients toward or away from a drug based on the patient's underlying risk for an adverse outcome. If channeling is not identified and appropriately managed it might lead to confounding in observational comparative effectiveness studies. Objective To demonstrate channeling among new users of second generation antipsychotics following a Food and Drug Administration safety advisory and to evaluate the impact of channeling on cardiovascular risk estimates over time. Data Source Florida Medicaid data from 2001–2006. Study Design Retrospective cohort of adults initiating second generation antipsychotics. We used propensity scores to match olanzapine initiators with other second generation antipsychotic initiators. To evaluate channeling away from olanzapine following an FDA safety advisory, we estimated calendar time-specific propensity scores. We compare the performance of these calendar time-specific propensity scores with conventionally-estimated propensity scores on estimates of cardiovascular risk. Principal Findings Increased channeling away from olanzapine was evident for some, but not all, cardiovascular risk factors and corresponded with the timing of the FDA advisory. Covariate balance was optimized within period and across all periods when using the calendar time-specific propensity score. Hazard ratio estimates for cardiovascular outcomes did not differ across models (Conventional PS: 0.97, 95%CI: 0.81–3.18 versus calendar time-specific PS: 0.93, 95%CI: 0.77–3.04). Conclusions Changes in channeling over time was evident for several covariates but had limited impact on cardiovascular risk estimates, possibly due to unmeasured confounding. Although calendar time-specific propensity scores appear to improve covariate balance, the impact on comparative effectiveness results is limited in this setting.
Dusetzina, Stacie B.; Mack, Christina D.; Sturmer, Til
The goal of this study was to assess in human liver microsomes the inhibitory capacity of commonly used antipsychotics on the most prominent CYP450 drug metabolizing enzymes (CYP1A2, CYP2C9, CYP2D6, and CYP3A). Chlorpromazine was the only antipsychotic that inhibited CYP1A2 activity (IC50 = 9.5? ? M), whilst levomepromazine, chlorpromazine, and thioridazine significantly decreased CYP2D6-mediated formation of 1'-hydroxybufuralol (IC50 range, 3.5-25.5? ? M). Olanzapine inhibited CYP3A-catalyzed production of 1', and 4'-hydroxymidazolam (IC50 = 14.65 and 42.20? ? M, resp.). In contrast, risperidone (IC50 = 20.7? ? M) and levomepromazine (IC50 = 30? ? M) showed selectivity towards the inhibition of midazolam 1'-hydroxylation reaction, and haloperidol did so towards 4'-hydroxylation (IC50 of 2.76? ? M). Thioridazine displayed a Ki of 1.75? ? M and an inhibitory potency of 1.57 on CYP2D6, suggesting a potential to induce in vivo interactions. However, with this exception, and given the observed Ki values, the potential of the assayed antipsychotics to produce clinically significant inhibitions of CYP450 isoforms in vivo seems limited. PMID:23476805
Gervasini, Guillermo; Caballero, Maria J; Carrillo, Juan A; Benitez, Julio
The goal of this study was to assess in human liver microsomes the inhibitory capacity of commonly used antipsychotics on the most prominent CYP450 drug metabolizing enzymes (CYP1A2, CYP2C9, CYP2D6, and CYP3A). Chlorpromazine was the only antipsychotic that inhibited CYP1A2 activity (IC50 = 9.5??M), whilst levomepromazine, chlorpromazine, and thioridazine significantly decreased CYP2D6-mediated formation of 1?-hydroxybufuralol (IC50 range, 3.5–25.5??M). Olanzapine inhibited CYP3A-catalyzed production of 1?, and 4?-hydroxymidazolam (IC50 = 14.65 and 42.20??M, resp.). In contrast, risperidone (IC50 = 20.7??M) and levomepromazine (IC50 = 30??M) showed selectivity towards the inhibition of midazolam 1?-hydroxylation reaction, and haloperidol did so towards 4?-hydroxylation (IC50 of 2.76??M). Thioridazine displayed a Ki of 1.75??M and an inhibitory potency of 1.57 on CYP2D6, suggesting a potential to induce in vivo interactions. However, with this exception, and given the observed Ki values, the potential of the assayed antipsychotics to produce clinically significant inhibitions of CYP450 isoforms in vivo seems limited.
Gervasini, Guillermo; Caballero, Maria J.; Carrillo, Juan A.; Benitez, Julio
Olanzapine (OLZ), risperidone (RPD) and quetiapine (QTP) are atypical antipsychotic drugs and are commonly used for the treatments of schizophrenia and bipolar disorders. However, recent reports indicated that these drugs could exhibit toxic effects on nervous and cardiovascular systems. To our best knowledge, there are scarce data considering the genotoxic damage potentials of OLZ, RPD and QTP on human lymphocyte culture system. Therefore, in this study, the genotoxic potentials of OLZ, RPD and QTP (0-400 mg/L) have been evaluated in human whole blood cultures (WBCs; n = 4). The single cell gel electrophoresis (SCGE) and micronucleus (MN) assays were applied to estimate the DNA damage. The results of the present study indicated that the tested antipsychotic drug did not induce genotoxicity. In fact, the mean values of the total scores of cells showing DNA damage (for SCGE assay) and MN/1000 cell were not found significantly different from the control values (p > 0.05). However, the application of the highest drug concentrations (250 mg/L and above) caused the sterility in lymphocyte cultures. It is concluded that the tested three different atypical antipsychotic drugs can be used safely, but it is necessary to consider the cytotoxic effects that are likely to appear depending on the doses exposed. PMID:21937534
Togar, Basak; Turkez, Hasan; Tatar, Abdulgani; Kirkpinar, Ismet; Hacimuftuoglu, Ahmet; Geyikoglu, Fatime; Keles, M Sait; Dirican, Ebubekir
In this article we examine the two major classes of side effects with atypical antipsychotics: extrapyramidal symptoms (EPS) and the metabolic syndrome (the triad of diabetes, dyslipidemia, and hypertension, with associated obesity). We conclude that atypical antipsychotics continue to have notable risks of EPS, particularly akathisia, and that these agents also appear to increase the risk of the metabolic syndrome, though this effect seems most marked with clozapine and olanzapine. Novel conclusions based on this review are as follows: we provide a classification scheme based on low versus high D2 binding affinity (which is, to our knowledge, a new means of classifying atypical antipsychotics); we emphasize that the akathisia risk is likely equal among agents and that tardive dyskinesia is an early, and not late, risk in treatment (a common misconception); we make the methodological point that in randomized clinical trials, there is a high risk of false-negatives regarding side effects; we raise the issue of confounding bias in epidemiological studies of metabolic syndrome; and we stress the need to compare side effects in the same studies and not different studies. Future prospective observational cohort studies must target side effects and be designed to collect and analyze data on confounding factors. PMID:16787887
Shirzadi, Arshia A; Ghaemi, S Nassir
Prescribed burning is a commonly advocated and historical practice for control of woody species encroachment into grasslands on all continents. However, desert grasslands of the southwestern United States often lack needed herbaceous fuel loads for effective prescriptions, dominant perennial gramin...
Second-generation antipsychotics have attracted practitioners’ and policy-makers’ attention, because of concerns over their health effects and costs. Comparative effectiveness data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)—a high-profile National Institutes of Health (NIH)–funded study—have been used to argue for restricting coverage for these costly drugs. But concerns about the design of CATIE and its associated cost-effectiveness analysis and uncertainty about the precision of these findings raise questions about this interpretation. Our work suggests that additional research to increase the precision of comparisons of the effectiveness of antipsychotics would be well worth the cost.
Meltzer, David O.; Basu, Anirban; Meltzer, Herbert Y.
Background: Hypertension is an increasingly common problem in adolescents yet current medical management of primary hypertension in adolescents has not been well-described. Methods: We identified adolescents with primary hypertension by International Classification of Diseases, Ninth Revision codes and looked at prescription patterns chronologically for antihypertensive drug class prescribed and the specialty of prescribing physician. We also examined patient demographics and presence of obesity-related comorbidities. Results: During 2003–2008, there were 4296 adolescents with primary hypertension (HTN); 66% were boys; 73% were aged 11 to 14 years; 53% were black, 41% white, and 4% Hispanic; and 48% had obesity-related comorbidity. Twenty-three percent (977) received antihypertensive prescription. White subjects (odds ratio [OR]: 1.61; confidence interval [CI]: 1.39–1.88), older adolescents (?15 years, OR: 2.11; CI: 1.79–2.48), and those with comorbidity (OR: 1.57; CI: 1.36–1.82) were more likely to receive antihypertensive prescriptions controlling for gender and years of Medicaid eligibility in logistic regression. Angiotensin converting enzyme inhibitors were the most frequently prescribed monotherapy. Nearly two-thirds of adolescents received prescriptions from adult primary care physicians (PCPs) only. More than one-quarter of adolescents who received a prescription received combination therapy, which was most often prescribed by adult PCPs. Conclusions: Adult PCPs were the leading prescribers of antihypertensives for adolescents with primary HTN. Race differences exist in physicians’ prescribing of antihypertensives to adolescents with primary HTN. The choice of antihypertensives by physicians of different specialties warrants additional study to understand the underlying rationale for treatment decisions and to determine treatment effectiveness.
Cohn, Lisa; Rocchini, Albert; Kershaw, David; Freed, Gary; Ascione, Frank; Clark, Sarah
Concern about controlled substance diversion and overview of prescribers by legal and regulatory officials is growing. The article is designed to increase health professionals' awareness of the methods of diversion and to provide guidance on how diversion can be foiled. This paper also should help healthcare practitioners to better understand the regulations governing prescribing of controlled substances. Examples of unlawful prescribing of controlled substances are presented. Some behaviors of persons illegitimately seeking controlled substances from prescribers are described. Strategies to lessen the possibility of prescriptions being altered are discussed. Federal and state laws and regulations pertaining to controlled substances are described. PMID:14640336
Gibbs, Landon S; Haddox, J David
ObjectiveTo evaluate prescribing errors made during induction training and evaluate these for any common themes.MethodsFour basic questions requiring five or six drugs to be prescribed were administered at the end of the Child Health Induction session for junior doctors. These focused on commonly used medications including analgesics and antibiotics. The doctors were given the BNF for Children (BNFC) and were
C D Nagaraj; R J McArtney; D Tuthill
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
Kay, C R
Clozapine is often referred to as the gold standard for the treatment of schizophrenia and yet has also been described as the most underutilized treatment for schizophrenia supported by solid evidence-based medicine. In 2008, it was used to treat only 4.4% of patients with schizophrenia in the U.S., which is ~10-20% of those with approved indications for clozapine for which there is no alternative of equal efficacy. Its use is much higher in Scandinavian countries and China. The primary indications for clozapine are: 1) treatment-resistant schizophrenia or schizoaffective disorder, defined as persistent moderate to severe delusions or hallucinations despite two or more clinical trials with other antipsychotic drugs; and, 2) patients with schizophrenia or schizoaffective disorder who are at high risk for suicide. Concerns over a number of safety considerations are responsible for much of the underutilization of clozapine: 1) agranulocytosis; 2) metabolic side effects; and, 3) myocarditis. These side effects can be detected, prevented, minimized and treated, but there will be a very small number of fatalities. Nevertheless, clozapine has been found in two large epidemiologic studies to have the lowest mortality of any antipsychotic drug, mainly due to its very large effect to reduce the risk for suicide. Other reasons for limited use of clozapine include the extra effort entailed in monitoring white blood cell counts to detect granulocytopenia or agranulocytosis and, possibly, minimal efforts to market it now that it is largely generic. Awareness of the benefits and risks of clozapine is essential for increasing the use of this lifesaving agent. PMID:23006238
Meltzer, Herbert Y
BACKGROUND A diagnosis of schizophrenia requires development of a pharmacotherapy regimen that balances many factors in the therapeutic decision-making process. Patient age and the presence or absence of comorbid chemical dependency represent two factors. Comorbid chemical dependency can have a profound impact on the successful treatment of schizophrenia, making patients with dual diagnoses of schizophrenia and chemical dependence a uniquely challenging population. There is little information regarding treatment of schizophrenia and chemical dependence in the pediatric population. Existing data from pediatric and adult populations may facilitate a well-guided and knowledgeable approach to treating pediatric dual diagnosis patients. METHODS A review of the literature for medication trials evaluating antipsychotic medication used to treat schizophrenia in childhood and adolescence as well as antipsychotic use in the treatment of the dual diagnoses of schizophrenia and chemical dependence was done. Databases for Ovid MEDLINE, PubMed, and PsycInfo were searched using the terms “addiction,” “adolescence,” “childhood,” “dual diagnosis,” “schizophrenia,” and “substance abuse.” Results were limited to English-language articles. RESULTS Seven articles were identified related to psychotic disorders and substance abuse in pediatric populations. Psychosis measurement instruments included the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression. Mean improvements were insignificant in most cases. Medication trials included clozapine, olanzapine, risperidone, and molindone. Trial safety concerns included metabolic effects, increased prolactin levels, and akathisia. One study with random assignment to olanzapine was discontinued early because of substantial weight gain without evidence of superior efficacy. Clozapine treatment was associated with more adverse drug events. CONCLUSION There is a great need for more research and use of available data to develop safe and effective treatment guidelines for childhood and adolescent dual diagnosis patients. When appropriate decisions are made regarding treatment of patients with comorbid schizophrenia and chemical dependence, both conditions may benefit with increased remission.
Price, Scott A.; Brahm, Nancy C.
Aim This study evaluated the impact of 6789 SNPs on treatment response to antipsychotics in Caucasian patients from the CATIE study. Materials & methods An Illumina (CA, USA) BeadChip was designed that targeted genes potentially impacting disease risk, disease presentation or antipsychotic response. SNPs tagged regions of linkage disequilibrium or functional variants not detectable using previous genotypes for CATIE. Change in Positive and Negative Syndrome scale total score was modeled using a mixed model repeated measures method that assumed a 30-day lag period. Genetic association analysis was performed using linear regression. Results Association analysis identified 20 SNPs with p-values of ?5 × 10?4. Many of these are in genes previously implicated in schizophrenia and other neuropsychiatric diseases. Conclusion The targeted approach identified SNPs possibly influencing response to antipsychotic drugs in Caucasian patients suffering from schizophrenia. The findings support a biological link between disease risk and presentation and antipsychotic response.
Liu, Qian; Jamba, Maidar; Patrick, Calvin; Padmanabhan, Saranya; Brennan, Mark D
The first- and second-generation antipsychotic drugs have become mainstay drug treatment for schizophrenia. However, patients\\u000a who receive antipsychotic drugs differ with respect to treatment response and drug-induced adverse events. The biological\\u000a predictors of treatment response are being researched worldwide, with emphasis on molecular genetic predictors of treatment\\u000a response. Because of the rapid and exciting developments in the field, we reviewed
Charles U. Nnadi; Anil K. Malhotra
Influencing clinicians' prescribing behaviour is important because inappropriate use and overuse of antibiotics are major drivers of antibiotic resistance. A systematic review of interventions for promoting prudent prescribing of antibiotics by general practitioners suggests that multifaceted interventions will maximize acceptability. This article reports how this type of approach has been used successfully in Derbyshire, UK over the last 4 years. The range of interventions that have been used includes educational meetings (both open group events and others targeted at higher prescribers in the surgery) using a supportive and guiding ethos; the provision of support materials aimed at empowering avoidance or delayed antibiotic prescribing, where appropriate, and improving patients' knowledge and confidence in self-management; and the production of different treatment guidelines incorporating key messages with evidence, indicating where antibiotics are unlikely to be of benefit. Education on antibiotics in schools was a novel approach, which was developed in North Derbyshire to increase public awareness of the appropriate treatment for common illnesses without using antibiotics. PMID:24030546
Harris, Diane J
Priapism is a rare but important side effect of antipsychotic drugs which may evolve into a urological emergency. Most antipsychotic drugs are alpha-1 adrenergic antagonists, which is thought to be the principal mechanism involved in antipsychotic-induced priapism. Other aetiologies exist, however. A case is presented with multiple episodes of priapism during the use of several different antipsychotic drugs. The case is representative of many patients treated with antipsychotic drugs, as there were hyperprolactinemia, and illicit drug use, which are known causes of priapism. Moreover, the patient used combinations of antipsychotic drugs. The case thus illustrates the etiological complexity which could delay a diagnosis of antipsychotic-induced priapism, and the problem of establishing a link between priapism and one particular ingredient of a drug combination. The case presents how a treatment regimen was finally established balancing antipsychotic efficacy to acceptable side effects and offers guidance to physicians regarding how antipsychotic-induced priapism may be resolved.
Sinkeviciute, Igne; Kroken, Rune A.; Johnsen, Erik
Irrational prescribing is a global problem. Rational prescribing cannot be defined without a method of measurement and a reference standard. The former is now available but the latter needs further development. Proven effective interventions to promote rational prescribing in developed countries are treatment protocols based on wide consultation and consensus, properly introduced and with a possibility of feedback; face-to-face education focussed on a particular prescribing problem in selected individuals; structured order forms; and focussed educational campaigns. Essential drugs lists are probably effective when based on consensus and used within a comprehensive educational programme. Printed materials alone are not effective. In most cases the usefulness of such strategies in developing countries has not been proven and should be studied. Medical education in clinical pharmacology and pharmacotherapy should be based on the practical needs of future prescribes, should include the principles of rational therapeutics and problem solving, and should immunize the students against the influences they are likely to encounter in their professional life, such as patient pressure, drug promotion and irrational prescribing by peers. Within the scope of a national formulary, specialist departments in teaching hospitals should define prescribing policies as the basis for prescribing, teaching, examinations and medical audit.
Hogerzeil, H V
Background There are claims that second-generation antipsychotics produce fewer extrapyramidal side-effects (EPS) compared with first-generation drugs. Aims To compare the incidence of treatment-emergent EPS between second-generation antipsychotics and perphenazine in people with schizophrenia. Method Incidence analyses integrated data from standardised rating scales and documented use of concomitant medication or treatment discontinuation for EPS events. Mixed model analyses of change in rating scales from baseline were also conducted. Results There were no significant differences in incidence or change in rating scales for parkinsonism, dystonia, akathisia or tardive dyskinesia when comparing second-generation antipsychotics with perphenazine or comparing between second-generation antipsychotics. Secondary analyses revealed greater rates of concomitant antiparkinsonism medication among individuals on risperidone and lower rates among individuals on quetiapine, and lower rates of discontinuation because of parkinsonism among people on quetiapine and ziprasidone. There was a trend for a greater likelihood of concomitant medication for akathisia among individuals on risperidone and perphenazine. Conclusions The incidence of treatment-emergent EPS and change in EPS ratings indicated that there are no significant differences between second-generation antipsychotics and perphenazine or between second-generation antipsychotics in people with schizophrenia.
Miller, Del D.; Caroff, Stanley N.; Davis, Sonia M.; Rosenheck, Robert A.; McEvoy, Joseph P.; Saltz, Bruce L.; Riggio, Silvana; Chakos, Miranda H.; Swartz, Marvin S.; Keefe, Richard S. E.; Stroup, T. Scott; Lieberman, Jeffrey A.
Viewed in the context of ever-expanding conceptual boundaries for the diagnosis of bipolar disorder including the spectrum concept of DSM-IV, or even beyond (Akiskal and Pinto, 1999), it becomes obvious that lithium is the treatment of choice in a minority? of patients only (Bowden et al, 2000). This article reviews what additional benefit atypical antipsychotics may provide in patients with bipolar disorder. Due both to tradition and to the regulatory requirements in the USA (FDA) and European Union (EMEA), the main target of clinical trials with atypical antipsychotics has been typical manic disorder. More recently, a significant subgroup of atypical patients, e.g., with mixed states, marked psychosis, or rapid cycling, have participated in these studies to allow an estimation of the value of atypical antipsychotics in these conditions. For the purposes of filing applications for registration with the regulatory agencies, the existing evidence is probably weak, however; from a clinical perspective, it is important that most atypical antipsychotics have also been tested in combination treatments. Finally, first data are now available on long-term prophylactic efficacy of atypical antipsychotics. These combined efficacy data definitely support the use of atypical antipsychotics in bipolar disorder, and it is now the time to collect more experience with these substances in severely ill patients in clinical settings.
Grunze, H.; Moller, H.J.
Until recently, prescribers had to deal with generics, considered to be simple molecules that are easy to copy. But as discussed in this paper, the biodisponibility of generics remains a source of uncertainty. And now there are biosimilars, limited for the time being in the cancer setting to granulocyte-colony stimulating factors (G-CSFs) and epoetins. Soon there will be biosimilar monoclonal antibodies with anticancer activity. Prescribers will ask, as they did for generics, if such drugs have the same activity as originators, if their safety profile is the same, if quality of the production process is guaranteed. Prescribers will want to know if their patients are indeed receiving the prescribed product, and not another. Finally prescribers will want to check that the lower cost of biosimilars will allow them to adhere to international guidelines. This should benefit patients and the community. PMID:22258706
Aapro, M S
This study aims to estimate the prevalence of and temporal trends in prenatal antipsychotic medication use within a cohort of pregnant women in the U.S. We identified live born deliveries to women aged 15-45 years in 2001-2007 from 11 U.S. health plans participating in the Medication Exposure in Pregnancy Risk Evaluation Program. We ascertained prenatal exposure to antipsychotics from health plan pharmacy dispensing files, gestational age from linked infant birth certificate files, and ICD-9-CM diagnosis codes from health plan claims files. We calculated the prevalence of prenatal use of atypical and typical antipsychotics according to year of delivery, trimester of pregnancy, and mental health diagnosis. Among 585,615 qualifying deliveries, 4,223 (0.72%) were to women who received an atypical antipsychotic and 548 (0.09%) were to women receiving a typical antipsychotic any time from 60 days before pregnancy through delivery. There was a 2.5-fold increase in atypical antipsychotic use during the study period, from 0.33% (95% confidence interval: 0.29%, 0.37%) in 2001 to 0.82% (0.76%, 0.88%) in 2007, while the use of typical antipsychotics remained stable. Depression was the most common mental health diagnosis among deliveries to women with atypical antipsychotic use (63%), followed by bipolar disorder (43%) and schizophrenia (13%). The number and proportion of pregnancies exposed to atypical antipsychotics has increased dramatically in recent years. Studies are needed to examine the comparative safety and effectiveness of these medications relative to other therapeutic options in pregnancy. PMID:23389622
Toh, Sengwee; Li, Qian; Cheetham, T Craig; Cooper, William O; Davis, Robert L; Dublin, Sascha; Hammad, Tarek A; Li, De-Kun; Pawloski, Pamala A; Pinheiro, Simone P; Raebel, Marsha A; Scott, Pamela E; Smith, David H; Bobo, William V; Lawrence, Jean M; Dashevsky, Inna; Haffenreffer, Katherine; Avalos, Lyndsay A; Andrade, Susan E
\\u000a Antipsychotic innovation can be divided into three eras. The first era began with the serendipitous discovery of the classical\\u000a antipsychotic neuroleptics, later found to mediate their therapeutic actions by blocking D2 dopamine receptors, particularly\\u000a in the mesolimbic dopamine pathway . From the late 1950s through the 1980s, a large number of effective compounds sharing this mechanism of action were thus
Stephen M. Stahl; Darius K. Shayegan
We studied national prescribing practices for psychotropic drugs in adolescent psychiatric outpatient care in Finland in the cross-sectional survey study in 1999. A questionnaire was sent to the adolescent psychiatrists employed in the community outpatient clinics covering all Finland. The response rate was 81% (n=34). On average, the respondents reported that 33% of their outpatients were treated with drugs. Selective serotonin reuptake inhibitors (SSRIs) were the drug of choice in the treatment of depression and obsessive-compulsive disorder (OCD). Atypical antipsychotics played an important role in the treatment of psychotic adolescents. Adolescent psychopharmacology is an important and developing part of treatment of mentally disordered young people, on the understanding that drug therapies are adjunct to other treatment interventions. PMID:14630545
Haapasalo-Pesu, Kirsi-Maria; Saarijärvi, Simo; Sorvaniemi, Marko
Patients within satellite haemodialysis units do not always have access to a medical practitioner. This may cause problems when prescriptions are required. Amendments to UK law to allow the introduction of supplementary prescribing came into force in 2003 allowing nurses with the appropriate experience, training and qualification to prescribe for their patients. Within a 14-station satellite unit a prescribing partnership has been successfully established. Clinical Management Plans have been implemented for haemodialysis patients. These include areas such as dialysis adequacy, access management, anti-coagulation, anaemia management, MRSA treatment and prophylaxis, antihypertensive therapy, calcium and phosphate control and exit site or line infection. 100% of patients within the unit have consented to the nurse prescribing for them under the Clinical Management Plan. Supplementary prescribing enhances nursing practice by empowering those who are best placed to make decisions regarding care and treatment for their patients. Patients appear confident in the ability of the nurse within the haemodialysis unit to prescribe competently. Nurse prescribing is of benefit to patient care, meeting the demands of an expanding patient population. It is recognition of the skill and experience required of haemodialysis nurses. PMID:16363416
One year after implementation of a 2005 Washington State law that granted Certified Registered Nurse Anesthetists (CRNAs) authority to prescribe schedule II through IV controlled substances, only 30% of CRNAs held prescriptive authority. The purpose of this study was to describe Washington State CRNA prescribing practices and workforce and practice characteristics. A questionnaire was mailed in 2006 to CRNAs licensed in Washington with addresses in Washington, Oregon, and Idaho. A typical respondent was 51 years old, white, and equally likely to be male or female, with 19 years of experience. More than half (52.2%) of the CRNAs were employed by hospitals, and 22% were in solo practice. Forty-one percent of the sample had prescriptive authority; however, 11% had prescriptive authority without Drug Enforcement Administration (DEA) registration. Respondents without prescriptive authority used the Nurse Practice Act provision to "select, order and administer" as the foundation for practice. Of CRNAs with prescriptive authority, 94.7% prescribed anesthetics, 60% prescribed nonsteroidal anti-inflammatory medications, and just 53.3% prescribed narcotic analgesics. Professional and policy controversies about autonomous prescribing for CRNAs are discussed. Further research is needed to determine the factors that limit CRNA prescribing and the transition to a new scope of practice. PMID:21473223
Kaplan, Louise; Brown, Marie-Annette; Simonson, Dan
|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…
Shea, Michael; Fields, Karl B.
Objective: To determine if care concordant with 2009 Schizophrenia Patient Outcomes Research Team (PORT) pharmacological recommendations for schizophrenia is associated with decreased mortality. Methods: We conducted a retrospective cohort study of adult Maryland Medicaid beneficiaries with schizophrenia and any antipsychotic use from 1994 to 2004 (N = 2132). We used Medicaid pharmacy data to measure annual and average antipsychotic continuity, to calculate chlorpromazine (CPZ) dosing equivalents, and to examine anti-Parkinson medication use. Cox proportional hazards regression models were used to examine the relationship between antipsychotic continuity, antipsychotic dosing, and anti-Parkinson medication use and mortality. Results: Annual antipsychotic continuity was associated with decreased mortality. Among patients with annual continuity greater than or equal to 90%, the hazard ratio [HR] for mortality was 0.75 (95% confidence interval [CI] 0.57-0.99) compared with patients with annual medication possession ratios (MPRs) of less than 10%. The HRs for mortality associated with continuous annual and average antipsychotic continuity were 0.75 (95% CI 0.58-0.98) and 0.84 (95% CI 0.58-1.21), respectively. Among users of first-generation antipsychotics, doses greater than or equal to 1500 CPZ dosing equivalents were associated with increased risk of mortality (HR 1.88, 95% CI 1.10-3.21), and use of anti-Parkinson medication was associated with decreased risk of mortality (HR 0.72, 95% CI 0.55-0.95). Mental health visits were also associated with decreased mortality (HR 0.96, 95% CI 0.93-0.98). Conclusions: Adherence to PORT pharmacological guidelines is associated with reduced mortality among patients with schizophrenia. Adoption of outcomes monitoring systems and innovative service delivery programs to improve adherence to the PORT guidelines should be considered. PMID:23112292
Cullen, Bernadette A; McGinty, Emma E; Zhang, Yiyi; Dosreis, Susan C; Steinwachs, Donald M; Guallar, Eliseo; Daumit, Gail L
Novel antipsychotics represent a significant advance in the treatment of schizophrenia after many years of few developments. The conventional antipsychotics are potent D2 antagonists, but fail to achieve a response in about 30% of cases. They are also associated with a high rate of extrapyramidal side effects. The greater and broader spectrum of efficacy combined with the reduced short- and long-term side effects of the new drugs such as quetiapine, risperidone, olanzapine and ziprasidone, contribute to a fresh optimism for the pharmacotherapy of schizophrenia. These novel agents are now driving further advances in schizophrenia research through a growing understanding of their pharmacological and clinical profiles. Clozapine, the first novel antipsychotic, has relatively low activity at D2 receptors, a high affinity for D4 receptors and a greater 5-HT2 (serotonin) than D2 antagonism. Hence, clozapine and other novel antipsychotics can be classified as such by this latter characteristic. However, some of these drugs have D2 occupancy greater than 60% (the clinical response threshold), while others have a lower D2 occupancy. The novel antipsychotics according have also been classified according to their activity on different neurotransmitter systems. While more effective, novel antipsychotics are not a panacea; they have limitations and side effects. In clinical practice, the American Psychiatric Association recommends either a conventional or novel antipsychotic for initial treatment of schizophrenia, whereas Canadian guidelines recommend novel agents. These agents should also be considered for treatment of refractory schizophrenia. Patients whose schizophrenia does not respond to one of these agents may respond to another. Future research should involve longer clinical trials, given the long periods needed to establish efficacy, and should address many remaining questions about the novel agents.
Remington, G; Chong, S A
Using fiscal and administrative data routinely collected by the Tennessee Medicaid program, we conducted epidemiologic analyses of physicians' prescribing of selected antibiotics in office practice. This research has defined several subgroups of physicians who regularly malprescribed chloramphenicol or tetracyclines (to children less than 8 years old). After special educational mailings to all physicians, prescribing of these antimicrobial drugs diminished. Similar analyses could enable the profession to design specific remedial educational interventions, target them at physicians needing contemporary information, and assess their impact by monitoring subsequent prescribing. Such a program might diminish inappropriate drug use, reduce adverse drug reactions, help contain medical care costs, and produce better educated physicians. PMID:717958
Schaffner, W; Ray, W A; Federspiel, C F
CONTEXT: Prescribing errors involving medication dose formulations have been reported to occur frequently in hospitals. No systematic\\u000a evaluations of the characteristics of errors related to medication dosage formulation have been performed.\\u000a \\u000a \\u000a OBJECTIVE: To quantify the characteristics, frequency, and potential adverse patient effects of prescribing errors involving medication\\u000a dosage forms.\\u000a \\u000a \\u000a \\u000a \\u000a DESIGN: Evaluation of all detected medication prescribing errors involving or related
Timothy S. Lesar
Electronic prescribing offers the prospect of safer medication management, but fulfillment of that promise depends on ready access to personal health information from many sources, thus raising new concerns about information privacy and security. Federal privacy regulations under the Health Insurance Portability and Accountability Act of 1996 (HIPAA) limit the sharing of health information by providers, and particularly may discourage information sharing over distributed computer networks. This analysis finds that although HIPAA has only a limited effect on current e-prescribing practices, future electronic prescribing systems will likely fall short of their potential benefits, absent policy refinements designed to encourage clinically appropriate, networked sharing of patient health information. PMID:15835603
Greenberg, Michael D; Ridgely, M Susan; Bell, Douglas S
Objective The rate-corrected electrocardiographic QT (QTc) interval may significantly increase in patients with schizophrenia taking\\u000a antipsychotics. The objective of this naturalistic study was to assess the prevalence of prolonged QTc interval in a large\\u000a population of inpatients with chronic schizophrenia and to explore QTc relationship with demographic variables and prescribed\\u000a treatments.\\u000a \\u000a \\u000a \\u000a \\u000a Materials and methods Electrocardiograms were obtained from age- and sex-matched 456
Fu De Yang; Xiang Qun Wang; Xiu Ping Liu; Ke Xin Zhao; Wei Hong Fu; Xue Ru Hao; Xing Li Zhang; Guo Shu Huang; Sheng Cai Qu; Jing Shen Bai; Xu Feng Huang; Thomas R. Kosten; Xiang Yang Zhang
The effect of atypical antipsychotic solian (amisulpride), binding predominantly to dopamine D2/D3-receptors, on the immune reactivity has been studied in mice of the CBA strain with different psychoemotional states (aggressive and submissive behavior). In addition, the effect of solian on the expression of various CD-markers of lymphocytes in has been analyzed in vitro for patients with schizophrenia diagnosis. Chronic (10 days) administration of solian in mice at a dose of 5.0 mg/kg resulted in a significant suppression of the immune response to T-dependent antigen (sheep red blood cells). This effect was manifested in animals with both psychoemotional states, but was more expressed in aggressive animals. In the in vitro system, solian produced opposite effects on the expression of surface CD receptors in lymphocytes of patients with schizophrenia. It is suggested that solian does not only affects immune function through D2 receptors of the brain, but also directly influences immunocompetent cells. PMID:23901463
Idova, G V; Al'perina, E L; Lobacheva, O A; Zhukova, E N; Che?do, M A; Meniavtseva, T A; Vetlugina, T P
Background Improving neurocognitive abilities is a treatment priority in schizophrenia, however, pharmacological efforts to enhance deficits after illness onset have resulted in quite modest results that are of questionable clinical meaningfulness. Individuals at clinical risk for psychosis demonstrate neurocognitive impairments intermediate to the level of deficits observed in schizophrenia and normative performance, suggesting that a similar magnitude of improvement might result in more clinically meaningful change. In this study, we examined neurocognitive changes after six months of treatment in adolescents with clinical signs of risk for psychosis. Methods Adolescents who were referred to the Recognition and Prevention program, which is focused on treatment and research for individuals at a clinical high risk for psychosis, were followed in a naturalistic treatment design. At study entry and approximately six months after starting treatment, we examined neuropsychological functioning and clinical symptoms for patients who remained off medications (OFF; N=27), started selective serotonin reuptake inhibitor antidepressant medication (AD; N=15), or started a second-generation antipsychotic medication (AP; N=11) within three months of study entry. We also included a locally recruited healthy comparison group (HC; N=17). Results The clinical groups were not significantly different on baseline demographic, neurocognitive, or clinical symptom measures. Linear mixed models were used to examine cognitive changes, with time between assessments, depressive symptom severity, and attenuated positive symptom severity as random effects. Group by time effects were observed in sustained attention and verbal learning, with the AD group showing a more favorable response than the AP group. The AD group’s improvements were not significantly different from the HC or OFF group. Conclusion Early intervention for those at clinical high risk for psychosis may result in neurocognitive improvements. These improvements were observed for those prescribed antidepressant, but not antipsychotic medications even though the groups did not differ in clinical symptom severity or treatment response.
Bowie, Christopher R.; McLaughlin, Danielle; Carrion, Ricardo E.; Auther, Andrea M.; Cornblatt, Barbara A.
Background: Antipsychotic long-acting injections (LAIs) reduce covert nonadherence with medication in the clinical management of psychotic disorders. However, they are variably utilised by clinicians, especially in the long term. Factors including poor knowledge, stigma and perceived coercion can all adversely influence LAI utilisation. Previous research has emanated almost exclusively from developed countries. This study explores the knowledge and attitudes of psychiatrists and trainees in Nigeria towards LAIs. Methods: A cross-sectional study was undertaken among mental health professionals in Nigeria using a pre-existing questionnaire. Results: Participant psychiatrists (n = 128) expressed positive attitudes towards LAIs. Their knowledge concerning LAIs and its side effects was fair. The participants reported that nearly half (41.7%) of their patients with a psychotic illness were on LAIs. Those who reported a high prescribing rate for LAIs (>40%) were more likely to endorse more positive ‘patient-centred attitudes’ (p < 0.04). In contrast to previous reports, psychiatrists reported that patients were less likely to feel ashamed when on LAIs, though most endorsed the statement that force was required during LAI administration. Conclusion: The desirability of treatment by injections differs in Africa in comparison to Western cultures, possibly due to the increased potency that injections are perceived to have. This is perhaps evidenced by high rates reported for use of LAIs. Nigerian psychiatrists had positive attitudes to LAIs but their knowledge, particularly regarding side effects, was fair and needs to be improved. Providing information to patients prior to antipsychotic treatment may enhance informed consent in a country where medical paternalism is still relatively strong.
Omoaregba, Joyce O.; Okonoda, Kingsley M.; Otefe, Edebi U.; Patel, Maxine X.
Background.?There is limited knowledge of the key determinants of antimicrobial prescribing behavior (APB) in hospitals. An understanding of these determinants is required for the successful design, adoption, and implementation of quality improvement interventions in antimicrobial stewardship programs. Methods.?Qualitative semistructured interviews were conducted with doctors (n = 10), pharmacists (n = 10), and nurses and midwives (n = 19) in 4 hospitals in London. Interviews were conducted until thematic saturation was reached. Thematic analysis was applied to the data to identify the key determinants of antimicrobial prescribing behaviors. Results.?The APB of healthcare professionals is governed by a set of cultural rules. Antimicrobial prescribing is performed in an environment where the behavior of clinical leaders or seniors influences practice of junior doctors. Senior doctors consider themselves exempt from following policy and practice within a culture of perceived autonomous decision making that relies more on personal knowledge and experience than formal policy. Prescribers identify with the clinical groups in which they work and adjust their APB according to the prevailing practice within these groups. A culture of “noninterference” in the antimicrobial prescribing practice of peers prevents intervention into prescribing of colleagues. These sets of cultural rules demonstrate the existence of a “prescribing etiquette,” which dominates the APB of healthcare professionals. Prescribing etiquette creates an environment in which professional hierarchy and clinical groups act as key determinants of APB. Conclusions.?To influence the antimicrobial prescribing of individual healthcare professionals, interventions need to address prescribing etiquette and use clinical leadership within existing clinical groups to influence practice.
Charani, E.; Castro-Sanchez, E.; Sevdalis, N.; Kyratsis, Y.; Drumright, L.; Shah, N.; Holmes, A.
Objective: This study was undertaken to describe physicians' views regarding ambulatory medication prescribing safety. Methods: We conducted 17 semistructured interviews among a sample of practicing physicians from 3 integrated health delivery systems. We...
T. G. Rundall J. Hsu J. E. Lafata V. Fung K. A. Paez
The author has identified the following significant results. The effects of a prescribed burn in the Sam Houston National Forest have been detected from ERTS-1 coverage of November 27, 1972. The burn was first identified on aircraft underflight photograph...
R. B. Erb
Text Version1 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use Octagam, Immune Globulin ... More results from www.fda.gov/downloads/biologicsbloodvaccines/bloodbloodproducts
Second generation antipsychotics (SGAs) have been linked to metabolic and bone disorders in clinical studies, but the mechanisms of these side effects remain unclear. Additionally, no studies have examined whether SGAs cause bone loss in mice. Using in vivo and in vitro modeling we examined the effects of risperidone, the most commonly prescribed SGA, on bone in C57BL6/J (B6) mice. Mice were treated with risperidone orally by food supplementation at a dose of 1.25 mg/kg daily for 5 and 8 weeks, starting at 3.5 weeks of age. Risperidone reduced trabecular BV/TV, trabecular number and percent cortical area. Trabecular histomorphometry demonstrated increased resorption parameters, with no change in osteoblast number or function. Risperidone also altered adipose tissue distribution such that white adipose tissue mass was reduced and liver had significantly higher lipid infiltration. Next, in order to tightly control risperidone exposure, we administered risperidone by chronic subcutaneous infusion with osmotic minipumps (0.5 mg/kg daily for 4 weeks) in 7 week old female B6 mice. Similar trabecular and cortical bone differences were observed compared to the orally treated groups (reduced trabecular BV/TV, and connectivity density, and reduced percent cortical area) with no change in body mass, percent body fat, glucose tolerance or insulin sensitivity. Unlike in orally treated mice, risperidone infusion reduced bone formation parameters (serum P1NP, MAR and BFR/BV). Resorption parameters were elevated, but this increase did not reach statistical significance. To determine if risperidone could directly affect bone cells, primary bone marrow cells were cultured with osteoclast or osteoblast differentiation media. Risperidone was added to culture medium in clinically relevant doses of 0, 2.5 or 25 ng/ml. The number of osteoclasts was significantly increased by addition in vitro of risperidone while osteoblast differentiation was not altered. These studies indicate that risperidone treatment can have negative skeletal consequences by direct activation of osteoclast activity and by indirect non-cell autonomous mechanisms. Our findings further support the tenet that the negative side effects of SGAs on bone mass should be considered when weighing potential risks and benefits, especially in children and adolescents who have not yet reached peak bone mass.
Motyl, Katherine J.; Dick-de-Paula, Ingrid; Maloney, Ann E.; Lotinun, Sutada; Bornstein, Sheila; de Paula, Francisco J. A.; Baron, Roland; Houseknecht, Karen L.; Rosen, Clifford J.
Second generation antipsychotics (SGAs) have been linked to metabolic and bone disorders in clinical studies, but the mechanisms of these side effects remain unclear. Additionally, no studies have examined whether SGAs cause bone loss in mice. Using in vivo and in vitro modeling we examined the effects of risperidone, the most commonly prescribed SGA, on bone in C57BL6/J (B6) mice. Mice were treated with risperidone orally by food supplementation at a dose of 1.25 mg/kg daily for 5 and 8 weeks, starting at 3.5 weeks of age. Risperidone reduced trabecular BV/TV, trabecular number and percent cortical area. Trabecular histomorphometry demonstrated increased resorption parameters, with no change in osteoblast number or function. Risperidone also altered adipose tissue distribution such that white adipose tissue mass was reduced and liver had significantly higher lipid infiltration. Next, in order to tightly control risperidone exposure, we administered risperidone by chronic subcutaneous infusion with osmotic minipumps (0.5 mg/kg daily for 4 weeks) in 7 week old female B6 mice. Similar trabecular and cortical bone differences were observed compared to the orally treated groups (reduced trabecular BV/TV, and connectivity density, and reduced percent cortical area) with no change in body mass, percent body fat, glucose tolerance or insulin sensitivity. Unlike in orally treated mice, risperidone infusion reduced bone formation parameters (serum P1NP, MAR and BFR/BV). Resorption parameters were elevated, but this increase did not reach statistical significance. To determine if risperidone could directly affect bone cells, primary bone marrow cells were cultured with osteoclast or osteoblast differentiation media. Risperidone was added to culture medium in clinically relevant doses of 0, 2.5 or 25 ng/ml. The number of osteoclasts was significantly increased by addition in vitro of risperidone while osteoblast differentiation was not altered. These studies indicate that risperidone treatment can have negative skeletal consequences by direct activation of osteoclast activity and by indirect non-cell autonomous mechanisms. Our findings further support the tenet that the negative side effects of SGAs on bone mass should be considered when weighing potential risks and benefits, especially in children and adolescents who have not yet reached peak bone mass. PMID:21854880
Motyl, Katherine J; Dick-de-Paula, Ingrid; Maloney, Ann E; Lotinun, Sutada; Bornstein, Sheila; de Paula, Francisco J A; Baron, Roland; Houseknecht, Karen L; Rosen, Clifford J
... Summary – Apr. 10, 2013 Antipsychotic Medicines for Treating Schizophrenia and Bipolar Disorder: A Review of the Research ... antipsychotics-adult.cfm. Understanding Your Condition What is schizophrenia? Schizophrenia is a severe brain disorder in which ...
Understanding individual differences in the susceptibility to metabolic side effects as a response to antipsychotic therapy is essential to optimize the treatment of schizophrenia. Here we perform genomewide association studies (GWAS) to search for genetic variation affecting the susceptibility to metabolic side effects. The analysis sample consisted of 738 schizophrenia patients, successfully genotyped for 492K SNPs, from the genomic subsample of the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) study. Outcomes included twelve indicators of metabolic side effects, quantifying antipsychotic-induced change in weight, blood lipids, glucose and hemoglobin A1c, blood pressure and heart rate. Our criterion for genomewide significance was a pre-specified threshold that ensures, on average, only 10% of the significant findings are false discoveries. Twenty-one SNPs satisfied this criterion. The top finding indicated a SNP in MEIS2 mediated the effects of risperidone on hip circumference (q =.004). The same SNP was also found to mediate risperidone's effect on waist circumference (q =.055). Genomewide significant finding were also found for SNPs in PRKAR2B, GPR98, FHOD3, RNF144A, ASTN2, SOX5 and ATF7IP2, as well as several intergenic markers. PRKAR2B and MEIS2 both have previous research indicating metabolic involvement and PRKAR2B has previously been shown to mediate antipsychotic response. Although our findings require replication and functional validation, this study demonstrates the potential of GWAS to discover genes and pathways that potentially mediate adverse effects of antipsychotic medication.
Adkins, Daniel E.; Aberg, Karolina; McClay, Joseph L.; Bukszar, Jozsef; Zhao, Zhongming; Jia, Peilin; Stroup, T. Scott; Perkins, Diana; McEvoy, Joseph P.; Lieberman, Jeffrey A.; Sullivan, Patrick F.; van den Oord, Edwin J.C.G.
Importance of the field Antipsychotic drug is the mainstay of treatment for schizophrenia, and there are large inter-individual differences in clinical response and side effects. Pharmacogenetics provides a valuable tool to fulfill the promise of personalized medicine by tailoring treatment based on one’s genetic markers. Areas covered in this review This article reviews the recent progress in pharmacogenetic research of antipsychotic drugs since 2010, focusing on two areas: antipsychotic-induced weight gain and clozapine-induced agranulocytosis. Important methodological issues in this area of research are discussed. What the reader will gain Readers are expected to learn the up-to-date evidence in pharmacogenetic research, and to gain familiarity to the issues and challenges facing the field. Take home message Pharmacogenetic studies of antipsychotic drugs are promising despite of many challenges. Recent advances as reviewed in this article push the field closer to routine clinical utilization of pharmacogenetic testing. Progress in genomic technology and bioinformatics, larger sample sizes, better phenotype characterization, and careful consideration of study design issues will help to elevate antipsychotic pharmacogenetics to its next level.
Zhang, Jian-Ping; Malhotra, Anil K.
The depot antipsychotics are synthesized by esterification of the active drug to a long chain fatty acid and the resultant compound is then dissolved in a vegetable oil, with the exception of some molecules of new generation characterized by microcrystalline technologies. The absorption rate constant is slower than the elimination rate constant and therefore, the depot antipsychotics exhibit 'flip-flop' kinetics where the time to steady-state is a function of the absorption rate, and the concentration at steady-state is a function of the elimination rate The pharmacokinetics of depot antipsychotic medications are such that an intramuscular injection given at intervals of from 1 to 4 weeks will produce adequate plasma concentrations that are sufficient to prevent relapse over the dosage interval. Such medication is useful in patients who do not reliably take their oral medication. The pharmacokinetics and clinical actions of various depot formulations of antipsychotic drugs have been extensively studied. The clinical pharmacokinetics of the depot antipsychotics for which plasma level studies are available (i.e. fluphenazine enanthate and decanoate, haloperidol decanoate, bromperidol decanoate, clopenthixol decanoate, flupenthixol decanoate, perphenazine onanthat, pipotiazine undecylenate, pipotiazine palmitate, fluspirilene, Long-acting injectable risperidone, olanzapine pamoate, paliperidone palmitate, Long-acting iloperidone, Long-acting injectable aripiprazole) are reviewed. The proper study of these agents has been handicapped until recently by the necessity of accurately measuring subnanomolar concentrations in plasma. Their kinetic properties, the relationship of plasma concentrations to clinical effects, and conversion from oral to injectable therapy are discussed. PMID:23343447
Spanarello, Stefano; La Ferla, Teresa
Cognitive enhancement has become an important target for drug therapies in schizophrenia. Treatment development in this area requires assessment approaches that are sensitive to procognitive effects of antipsychotic and adjunctive treatments. Ideally, new treatments will have translational characteristics for parallel human and animal research. Previous studies of antipsychotic effects on cognition have relied primarily on paper-and-pencil neuropsychological testing. No study has directly compared neurophysiological biomarkers and neuropsychological testing as strategies for assessing cognitive effects of antipsychotic treatment early in the course of schizophrenia. Antipsychotic-naive patients with schizophrenia were tested before treatment with risperidone and again 6 weeks later. Matched healthy participants were tested over a similar time period. Test-retest reliability, effect sizes of within-subject change, and multivariate/univariate analysis of variance were used to compare 3 neurophysiological tests (visually guided saccade, memory-guided saccade, and antisaccade) with neuropsychological tests covering 4 cognitive domains (executive function, attention, memory, and manual motor function). While both measurement approaches showed robust neurocognitive impairments in patients prior to risperidone treatment, oculomotor biomarkers were more sensitive to treatment-related effects on neurocognitive function than traditional neuropsychological measures. Further, unlike the pattern of modest generalized cognitive improvement suggested by neuropsychological measures, the oculomotor findings revealed a mixed pattern of beneficial and adverse treatment-related effects. These findings warrant further investigation regarding the utility of neurophysiological biomarkers for assessing cognitive outcomes of antipsychotic treatment in clinical trials and in early-phase drug development.
Hill, S. Kristian; Reilly, James L.; Harris, Margret S. H.; Khine, Tin; Sweeney, John A.
Although antidepressant drugs do not differ much in their efficacy rates, the particular characteristics of one drug may make it a better choice in a given patient. This article provides insight into the art of prescribing antidepressants in primary care, with recommendations for prescribing for patients with chronic pain, sexual dysfunction, anxiety, chronic fatigue syndrome, fibromyalgia, severe insomnia, old age, diabetes, and heart problems. PMID:24085807
Shultz, Elizabeth; Malone, Donald A
Medication errors involving analgesics, including mistakes in prescribing, are a major contributor to suboptimal therapeutic outcomes and preventable adverse patient events. A systematic evaluation of 2,044 prevented (near-miss) analgesic prescribing errors detected in a teaching hospital was performed to better understand these errors and contributing error-prone analgesic medication characteristics. The overall detected error rate was 2.87 errors per 1,000 analgesic
Howard S. Smith; Timothy S. Lesar
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
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.
Montgomery, William; Liu, Li; Stensland, Michael D; Xue, Hai Bo; Treuer, Tamas; Ascher-Svanum, Haya
Background and objective: Risk\\/benefit profile of prescribed drug regimens is unkown. Over 60% of\\u000acommonly used medications interact on metabolic pathways (cytochrom P450 (CYP450), uridyl-glucuronyl\\u000atranferasis (UGT I, II) and P-glycoprotein (PGP) transport). Using an up-to-date knowledge on metabolic drug interactions, we aimed the study to determine the medication risk of commonly prescribed drug combinations. Design: A mathematical model was
D. Fialova; K. Vrbensky; E. Topinkova; J. Vlcek; L. W. Soerbye; C. Wagner; R. Bernabei
Trends in the prevalence of antipsychotic drug use among patients with Alzheimer's disease and other dementias including those treated with antidementia drugs in the community in the UK: a cohort study
Objective To investigate the pattern and trends of use of antipsychotics, antidepressants, hypnotics and anxiolytics in Alzheimer's disease and other dementias and in patients treated with antidementia medications. Design Cohort study with dementia patients formed in the UK Clinical Practice Research Datalink. Participants Patients with incident dementia, between 1995 and 2011 and a reference non-dementia cohort matched on age, gender and date of dementia diagnosis. Two subcohorts included new users of acetylcholinesterase inhibitors (AChEIs) and memantine. The study endpoint was use of antipsychotics, antidepressants, hypnotics and anxiolytics up to 10?years before and 4?years after dementia diagnosis, and for up to 5?years before and 1?year after first use of AChEI or memantine. Results 50?349 patients with incident dementia diagnosis and 50?349 matched controls, 10?794 first-time users of AChEI and 669 of memantine. The mean prevalence of antipsychotic use from 1995 to 2011 on diagnosis of dementia was 12.5%, decreasing from 19.9% in 1995 to 7.4% in 2011. There was an increase in antidepressant use (10.7–26.3%) and a small increase in anxiolytic use. The matched cohort showed a lower use of antipsychotics and anxiolytics but a rise in antidepressants (5.9–13.4%). Both groups showed a decrease in hypnotic use. 10.6% of AChEI and 26.3% of memantine users were prescribed antipsychotics, 34.1% and 26.3% antidepressants, 13.2% and 4.1% anxiolytics and 18.4% and 8.3% hypnotics. The slopes for monthly use of antipsychotics were positive in the year leading up to AChEI and memantine use; after treatment initiation the slope for AChEI users continued to increase but at a reduced rate whereas antipsychotic use declined for memantine users. Conclusions The marked reduction in antipsychotic use in dementia is to be welcomed while there was a steady increase in antidepressant use. There was a decline in antipsychotic use after the initiation of memantine.
Martinez, Carlos; Jones, Roy W; Rietbrock, Stephan
Rationale Rat maternal behavior, which entails complex motivational and social factors, is disrupted by the currently available typical\\u000a and atypical antipsychotics. It is thought that this disruption reflects a side effect of antipsychotics, modeling the neuroleptic-induced\\u000a negative or deficit state. Amisulpiride and aripiprazole are new atypical antipsychotics with mechanisms of action distinct\\u000a from the current typical and atypical antipsychotics. The effects
Ming Li; Radek Budin; Alison S. Fleming; Shitij Kapur
Although atypical antipsychotics differ from conventional antipsychotics in their decreased ability to cause reversible drug-induced movement disorders\\/motor side effects such as dystonia, drug- induced parkinsonism, and akathisia and potentially persistent drug-induced movement disorders\\/ motor side effects such as tardive dyskinesia, no antipsychotic agent completely eradicates this risk. Antipsychotic agents are frequently used in facilities for the elderly and in general
Bruce L. Saltz; Delbert G. Robinson; Margaret G. Woerner
... the adhesive on the tape. Over-the-counter freezing medications are available but have not been found ... physician. Treatments Your Physician May Prescribe Destruction with freezing (cryosurgery), burning (electrocautery), laser, or cantharidin, podophyllin, tretinoin, ...
Second-generation antipsychotics (SGAPs) and second-generation antidepressants (SGADs) have multiple US Food and Drug Administration-approved indications and are frequently prescribed by primary care physicians. We review the relative potential of these drugs to cause weight gain and glucose dysregulation, and offer clinical guidance to minimize and manage this risk. Among SGAPs, clozapine and olanzapine have a high risk for causing weight gain and glucose dysregulation; iloperidone, paliperidone, quetiapine, and risperidone have a medium risk; and aripiprazole, asenapine, lurasidone, and ziprasidone have a low risk. Young, drug-naïve patients are particularly vulnerable to weight gain associated with SGAPs. With the exception of clozapine, SGAPs have modest differences in their efficacy; however, their side effect profiles may influence selection. Using SGAPs with high metabolic liability conservatively and limiting their off-label use are important means to minimize risk. Patients should be screened before initiating any SGAP (or any antipsychotic medication) and monitored subsequently following standard guidelines, such as those provided by the American Diabetes Association. Healthy lifestyle counseling should be offered to all patients. Patients showing evidence of significant weight gain should be switched to an SGAP with a lower metabolic liability. Metformin may have some utility in young patients with limited exposure to antipsychotic drugs if lifestyle interventions fail and switching the SGAP is not an option. This option should be tried sooner than later for the best possible result. For SGADs, paroxetine and mirtazapine are associated with weight gain, and bupropion may cause modest weight loss. Other SGADs are mostly weight neutral, but individual variations may occur. Depression is associated with weight change and is a risk factor for glucose dysregulation. Treatment of depression improves glucose metabolism. We recommend that all patients taking SGADs be screened using anthropometric measures and metabolic assessment at baseline. Monitoring should be guided individually based on weight gain and other risk factors. PMID:22913904
Hasnain, Mehrul; Vieweg, W Victor R; Hollett, Bruce
Prescribed fire and herbicides are commonly used tools to manage introduced grasses in the Southern Plains, but their effects on livestock production are not well documented. The objectives of this experiment were to determine the effects of prescribed fire or herbicides on the production of grazin...
The objective of this review is to summarize the data about metabolic side effects of atypical antipsychotics in children.Original research articles about side effects of atypical antipsychotics used in children were reviewed. The data was obtained mainly through Medline searches, identifying articles focusing on the use of atypical antipsychotics in children. Forty studies that addressed the issue of metabolic side
Valérie J. Fedorowicz; Eric Fombonne
The exact therapeutic mechanism of action of antipsychotic drugs remains unclear. Recent evidence has shown that second-generation antipsychotic drugs (SGAs) are differentially associated with metabolic side effects compared to first-generation antipsychotic drugs (FGAs). Their proclivity to cause metabolic disturbances correlates, to some degree, with their comparative efficacy. This is particularly the case for clozapine and olanzapine. In addition, the insulin
R R Girgis; J A Javitch; J A Lieberman
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
Christine Konradi; Stephan Heckers
Treatment of schizophrenia with antipsychotic drugs is frequently sub-optimal. One reason for this may be heterogeneity between patients with schizophrenia. The objectives of this study were to identify patient, disease and treatment attributes that are important for physicians in choosing an antipsychotic drug, and to identify empirically subgroups of patients who may respond differentially to antipsychotic drugs. The survey was
C. U. Correll; F. Cañas; I. Larmo; P. Levy; J.-M. Montes; A. Fagiolini; G. Papageorgiou; A. Rossi; R. Sturlason; M. Zink
Some, but not all, antipsychotics elevate serum prolactin. Antipsychotic-induced hyperprolactinemia is thought to account for high rates of menstrual dysfunction and diminished estrogen levels in women with schizophrenia. However, few studies have directly assessed the relationships between prolactin, menstrual function, and ovarian hormone levels in this population. Sixteen premenopausal women with schizophrenia and schizoaffective disorder, eight treated with an antipsychotic
Carla M. Canuso; Jill M. Goldstein; Joanne Wojcik; Ree Dawson; Danielle Brandman; Anne Klibanski; Joseph J. Schildkraut; Alan I. Green
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
Dobrin, Irina; Dobrin, R P; Chele, Gabriela; Stef?nescu, C; Knieling, A; Chiri??, Roxana
Altered membrane phospholipid fatty acid composition is reported in schizophrenia and appears to be reduced by antipsychotic drug treatment. To determine whether antipsychotic drugs have a direct effect on brain phospholipid fatty acid composition, the effects of sub-chronic treatment with a “typical” and an “atypical” antipsychotic drug were determined in adult male Sprague–Dawley rats. Rats were treated with haloperidol (1
Beth Levant; Jennifer F. Crane; Susan E. Carlson
Chronic exposure to antipsychotic medications can persistently change brain dopamine systems. Most studies on the functional significance of these neural changes have focused on motor behavior and few have addressed how long-term antipsychotic treatment might influence dopamine-mediated reward function. We asked, therefore, whether a clinically relevant antipsychotic treatment regimen would alter the incentive motivational properties of a reward cue. We
Anne-Marie Bédard; Jérôme Maheux; Daniel Lévesque; Anne-Noël Samaha; A-N Samaha
The selection of antipsychotics as medications used primarily for treating schizophrenia and disorders similar to schizophrenia is an important aspect of the treatment of forensicpatients. This study examines the effect of antipsychotics selection (typical or atipycal) on the level of aggressiveness, side effects and the hospitalisation length. The research is conducted on 98 psychiatric patients diagnosed with schizophrenia or similar disorders (F 20-F 29) in two forensic psychiatric institutions. The patients committed aggressive criminal offence in state of insanity. The patients are currently treated in inpatient psychiatric institutions. The research was conducted by using the Aggressiveness Questionnaire (AG-87), the Simpson-Angus Scale for the assessment of extrapyramidal side effects, the Barnes Akathisia Rating Scale for the assesment of akathisia and the Abnormal Involuntary Movement Scale. The results show no significant difference between the groups of patients treated with typical and atypical antipsychotics in all the variables. PMID:21648345
Ruzi?, Klementina; Franciskovi?, Tanja; Sukovi?, Zoran; Hero, Elizabeta Dadi?; Roncevi?-Grzeta, Ika; Graovac, Mirjana; Palijan, Tija Zarkovi?
Psychotic and behavioral symptoms are common in patients with dementia. Thus, it is rational to assume that patients with dementia would gain benefit from combination therapy of an antipsychotic agent and a cognitive enhancer. Antipsychotics are not approved by the US FDA in elderly patients with dementia but their use is still prevalent in other population. In the current study, we investigate the effect of atypical antipsychotics on acetylcholine modulation by donepezil. In addition, the plasma pharmacokinetics on concurrent administration of these drugs was studied. Acetylcholine modulation was carried out in the ventral hippocampus of Sprague-Dawley rats using brain microdialysis technique. In a parallel group of animals, pharmacokinetic parameters were evaluated on administration of donepezil (5.0 mg kg(-1), ip) alone and in combination with olanzapine, clozapine, or quetiapine. Donepezil produced 348% increase in hippocampal acetylcholine levels. Coadministration of olanzapine and donepezil produced 393% increase in extracellular acetylcholine, and the effect was supported by a significantly (p < 0.05) decreased clearance of donepezil in plasma. Whereas, other plasma pharmacokinetic parameters of donepezil "AUC(0-24h), T (1/2) and T (max)" were moderately altered after this combination treatment. Concurrent administrations of clozapine or quetiapine with donepezil produced a non-significant change in acetylcholine levels in comparison to donepezil alone. The plasma pharmacokinetics of donepezil was unaltered. Results from this preclinical investigation indicate that extrapyramidal side effects may precipitate upon coadministration of donepezil with olanzapine. Care must be exercised by physicians and caregivers while administering these two drugs together. PMID:22302541
Nirogi, Ramakrishna; Bhyrapuneni, Gopinadh; Kandikere, Vishwottam; Benade, Vijay; Muddana, Nageswararao; Saralaya, Ramanatha; Irappanavar, Shantaveer; Ponnamaneni, Ranjithkumar; Mukkanti, K
Inappropriate prescribing of controlled substances, primarily opiates and benzodiazepines, is the most common complaint brought before the Oregon Board of Medical Examiners. We describe the malpractice claims experience of 120 physicians previously investigated by the Oregon board for inappropriate prescribing. These physicians were matched with a comparison group by age, specialty, and practice location. We found that a mean of one malpractice claim had been filed against each physician in our study, with the specialties of obstetrics and gynecology, neurosurgery, and orthopedics having the most claims. A significantly higher mean number of malpractice claims had been filed against 31 physicians disciplined by the board. Our study suggests a role for state regulatory boards in the malpractice area. We propose that such bodies do practice reviews based on the convergence of two events, a disciplinary action such as those described in this article and the filing of more than one malpractice claim against a physician. Further research is needed on inappropriate prescribing by physicians and its possible association with malpractice.
Bloom, J D; Williams, M H; Kofoed, L; Rhyne, C; Resnick, M
Patients with schizophrenia have a shorter life expectancy and their risk of dying from a cardiovascular disease is higher than the general population. Both facts have been attributed to the raised presence of metabolic syndrome. There is a big amount of scientific publications that deals with the relationship between schizophrenia, antipsychotic treatment, and the development of metabolic syndrome. There is also information about recommendations and clinical guides to achieve an adequate prevention, screening, and treatment of the disease. The aim of this review is to update the current information about this issue and to understand related etiologic factors, differences between antipsychotic drugs, and the current recommendations for patient's care. PMID:22841467
Aguilar, Eva; Coronas, Ramón; Caixàs, Assumpta
BACKGROUND. Ear, nose, and throat (ENT) problems are common in childhood and are important reasons to visit the general practitioner. OBJECTIVE. To examine trends in incidence rates, antibiotic prescribing, and referrals of five common ENT problems in children. DESIGN. Netherlands Information Network of General Practice (LINH), a nationally representative general practice database. Setting. A total of 50 000 children, aged
J. H. J. M. Uijen; P. J. E. Bindels; F. G. Schellevis; J. C. van der Wouden
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.
Cooper, Richard J; Lymn, Joanne; Anderson, Claire; Avery, Anthony; Bissell, Paul; Guillaume, Louise; Hutchinson, Allen; Murphy, Elizabeth; Ratcliffe, Julie; Ward, Paul
Prescribing in the perinatal period is based on a risk-benefit analysis, in the context of a limited evidence base, composed primarily of case series and reports. Mothers with depressive illness often present first in the community and effective treatment is paramount for the wellbeing of both mother and child. We aimed at investigating current prescribing practices among general practitioners (GPs) of antidepressants to mothers presenting in first trimester of pregnancy and during breastfeeding. This qualitative study was conducted by way of postal survey to 78 GPs within South Central Edinburgh catchment area. All responses were anonymous and confidential. We discovered inconsistent prescribing patterns among GPs to both pregnant and breastfeeding mothers. Only one GP suggested consulting clinical guidelines when making prescribing choices. There was no mention of the continuation of an antidepressant from pregnancy into breastfeeding as a reason of choice. Inconsistent prescribing patterns among GPs could have implications for the wellbeing of mother and child, and may be reflective of an underlying educational need among GPs. PMID:21670136
Kean, Laura Jane; Hamilton, Jane; Shah, Premal
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.
Rissmann, Robert; Dubois, Eline A; Franson, Kari L; Cohen, Adam F
The use of atypical antipsychotic medications has been reported to be increased in adolescent psychiatric outpatients and to include many patients with non-psychotic disorders. This study examined the correlates of antipsychotic usage in adolescent inpatients and compared their characteristics with a sample of adolescent inpatients who did not receive antipsychotics during their hospitalisation. A total of 159 consenting consecutive patients treated with atypical antipsychotic medications were compared with 150 patients who were admitted during the same time period and not treated with antipsychotics. The samples were compared for demographic factors, clinical diagnoses, clinical symptoms at admission and other medications received during their inpatient stay. Sex and ethnicity did not differ significantly as a function of antipsychotic mediation status. Significantly few patients with an admission diagnosis of major depression received antipsychotic medications and more patients with admission diagnosis of bipolar and/or conduct disorder were treated with antipsychotic medications. Clinical symptom differences and additional medications received were consistent with the differences in admission diagnoses. Despite the fact that significantly fewer patients with major depression received antipsychotic medications, 47% of the patients who did receive antipsychotic medications in this study had an admission diagnosis of major depression. There are several differences between these inpatient data and previous studies of outpatient claims databases, the majority of adolescent inpatient cases treated with antipsychotic medications had admission diagnoses consistent with both adult indications and previous research with adolescent patients. These data suggest an urgent need to study the safety and efficacy of atypical antipsychotic medications on aspects of depression in adolescents. PMID:17504351
Pogge, D L; Young, K; Insalaco, B; Harvey, P D
In situ radiosonde measurements were obtained during multiple prescribed fires at the Joseph W. Jones Ecological Research Center at Ichauway, Georgia in March and July of 2008. Data were obtained from prescribed fires conducted in longleaf pine ecosystems. After significant smoke generation was observed, radiosondes were launched downwind of the fire front and rose directly into the smoke plumes. Radiosondes were also launched before each burn to obtain ambient background conditions. This provided a unique dataset of smoke plume moisture to determine how moisture enhancement from fire smoke alters the dynamics of the smoke plume. Preliminary analysis of results show moisture enhancement occurred in all smoke plumes with relative humidity values increasing by 10 to 30 percent and water vapor mixing ratios increasing by 1 to 4 g kg-1. Understanding the moisture enhancement in prescribed fire smoke plumes will help determine the convective dynamics that occur in major wildland fires and convection columns.
Kiefer, C. M.; Clements, C. B.; Potter, B. E.; Strenfel, S. J.
Objectives To investigate the association between use of typical and atypical antipsychotic drugs and incidence of stroke in patients with and without dementia. Design Self controlled case series. Setting UK based electronic primary care records in the general practice research database (GPRD). Participants All patients registered in the database with a recorded incident stroke and at least one prescription for any antipsychotic drug before the end of 2002: 6790 eligible participants were identified and included in the final analysis. Main outcome measures Rate ratio for stroke in periods of time exposed to antipsychotics compared with unexposed periods. Results Use of any antipsychotic drug was associated with a rate ratio for stroke of 1.73 (95% confidence interval 1.60 to 1.87): 1.69 (1.55 to 1.84) for typical antipsychotics and 2.32 (1.73 to 3.10) for atypical antipsychotics. In patients receiving any antipsychotic drug, the rate ratios were 3.50 (2.97 to 4.12) for those with dementia and 1.41 (1.29 to 1.55) for those without dementia. Conclusions All antipsychotics are associated with an increased risk of stroke, and the risk might be higher in patients receiving atypical antipsychotics than those receiving typical antipsychotics. People with dementia seem to be at a higher risk of an associated stroke than people without dementia and use of antipsychotics should, when possible, be avoided in these patients.
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.
Maxwell, Simon; Mucklow, John
Objective: To compare physician-reported adherence of specific patients to oral second-generation antipsychotics vs. actual adherence rates determined from the patients’ pharmacy claims. Methods: Claims data from the HealthCore Integrated Research Database identified patients with schizophrenia or bipolar disorder with ?1 oral second-generation antipsychotic prescription. The prescribing physicians were identified from the pharmacy claims and asked to complete an Internet survey assessing their perception of medication adherence for 1–2 of their patients and their beliefs regarding adherence to second-generation antipsychotics in general for a 1-year period. Adherence to second-generation antipsychotics was determined for each patient by pharmacy claims for the same period. Physician survey data were merged with patient claims data via unique patient identifiers, and physician-reported adherence rates were compared with claims-based rates as measured by the medication possession ratio. Results: One hundred and fifty-three physicians responded to the survey, representing 214 patients (44 with claims for schizophrenia, 162 with bipolar disorder, 8 with claims for bipolar disorder and schizophrenia). Most physicians (60%) had no formal adherence training. More than two-thirds (68%) reported emphasising the importance of adherence and reported approximately 76% of their patients were adherent (?71% of the time). In the schizophrenia group, 16 of 17 (94%) patients with low-to-moderate (?70%) adherence levels had high (?71%) physician-estimated adherence. In the bipolar disorder group, 62 of 92 (67%) patients with low-to-moderate adherence levels had high physician-estimated adherence. Conclusions/Interpretation: These analyses suggest that, even when physicians are asked about specific patients in their practice, there is discordance between physician perceptions and adherence as measured through pharmacy claims. This disparity may delay appropriate interventions, potentially contributing to relapses.
Stephenson, J J; Tuncelli, O; Gu, T; Eisenberg, D; Panish, J; Crivera, C; Dirani, R
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
There have been continued improvements in toric soft lens design over the past three decades. Data that we have gathered from annual contact lens fitting surveys demonstrate a commensurate increase in toric lens fitting as a proportion of all soft lenses fitted. The current toric lens prescribing rate (34% of all lenses when cosmetic tints, monovision and multifocal lenses are ignored) is roughly equivalent to the rate that would be achieved if all cases of astigmatism 1.00D or more were fitted with toric lenses. Toric lenses tend to be fitted more to males and prescribed for monthly rather than daily replacement. PMID:19185528
Morgan, Philip B; Efron, Nathan
Background\\/Aim: In recent years, there has been a growing interest in developing adequate treatments for patients with a diagnosis of schizophrenia and a comorbid substance use disorder (SUD). In the present paper we aim to critically review published reports on the use of conventional and second-generation antipsychotics in the treatment of patients with schizophrenia and comorbid SUD, to provide clinicians
Luis San; Belen Arranz; Jose Martinez-Raga
The membrane transport protein P-glycoprotein (P-gp) is an interesting candidate for individual differences in response to antipsychotics. To present an overview of the current knowledge of P-gp and its interaction with second-generation antipsychotics (SGAs), an internet search for all relevant English original research articles concerning P-gp and SGAs was conducted. Several SGAs are substrates for P-gp in therapeutic concentrations. These include amisulpride, aripiprazole, olanzapine, perospirone, risperidone and paliperidone. Clozapine and quetiapine are not likely to be substrates of P-gp. However, most antipsychotics act as inhibitors of P-gp, and can therefore influence plasma and brain concentrations of other substrates. No information was available for sertindole, ziprasidone or zotepine. Research in animal models demonstrated significant differences in antipsychotic brain concentration and behavior owing to both P-gp knockout and inhibition. Results in patients are less clear, as several external factors have to be accounted for. Patients with polymorphisms which decrease P-gp functionality tend to perform better in clinical settings. There is some variability in the findings concerning adverse effects, and no definitive conclusions can be drawn at this point. PMID:21843066
Moons, Tim; de Roo, Mariska; Claes, Stephan; Dom, Geert
The advent of new antipsychotic drugs has improved the treatment of schizophrenic patients as well as those suffering from other severe psychiatric disorders. Its widespread use, however, has been associated to the development of obesity and metabolic disturbances such as diabetes mellitus, dyslipidemia and increased coronary risk. This has caused a serious concern, due to the high cardiovascular mortality that prematurely affects these patients. The etiology of these abnormalities is still a matter of debate, although it is generally believed that the new antipsychotic drugs have a control stimulating effect on appetite, and their use is associated to an increased level of cortisol and to an insulin-resistance state. In addition, there is an increase in inflammatory mediator and cytokine production, induced by the pathophysiology of the schizophrenic process itself and also caused by the direct action of the antipsychotic drugs. In spite of the mounting evidence, the metabolic management of these patients is still deficient. A close follow-up in the initial stages of the antipsychotic treatment is recommended, as well as giving advice about diet and physical exercise. Finally, when obesity or other conditions associated to metabolic syndrome appear, the recommendation is to switch to drugs with less secondary effects or to add adjuvant medications to improve the overall evolution of these patients. PMID:19399331
Rojas G, Paula; Poblete A, Catalina; Orellana G, Ximena; Rouliez A, Karen; Liberman G, Claudio
Rationale It is possible that amisulpride, with its unique receptor binding profile, is not associated with significant weight gain, a serious side effect of most “atypical” antipsychotic drugs. While most “atypicals” have a high affinity for both dopamine and serotonin receptors, amisulpride has only dopamine receptor action. Objectives To analyse the weight gain associated with amisulpride. Methods A pooled database
Stefan Leucht; Stefan Wagenpfeil; Johannes Hamann; Werner Kissling
Amisulpride clearly has the clinical profile of an atypical antipsychotic, characterised in particular by its lower propensity to induce extrapyramidal side effects as well as its greater efficacy in treating negative symptoms compared with classical neuroleptics. In addition to the clinical advantages over classical neuroleptics, it has also been demonstrated that the clinical profile of amisulpride is comparable to that
Only two tests were specific for antipsychotic potential. All effective antipsychotics blocked pharmacologically induced locomotion and affected firing in the mesolimbic DA neurons. The remaining single- (Table 1) and repeated- (Table 2) dose tests identified the atypical antipsychotics. Clozapine, thioridazine, sulpiride, tiospirone, and molindone were atypical in both types of study. Pimozide, pipamperone, aceperon, methylperon, and clotiapine were atypical in single-dose studies, clopenthixol in repeated-dose studies. Since the biochemical abnormality causing psychoses is unknown, it may be that current methods of screening for new antipsychotics are inadequate and possibly inappropriate. If a neurotransmitter other than DA is the primary cause, then totally new tests may be needed. Present tests, especially those involving behavioral paradigms, may continue to select out compounds that cause EPS side-effects. New methods such as positron emission tomography scanning and other brain-imaging techniques hold the promise of studying specific types and subtypes of receptors in the living human brain. The recent discovery of chromosomal abnormalities in psychotic illness may provide new insights into the biochemical causes of such disorders and lead to completely new compounds that will be both safer and more effective. In the meantime we plan to review the literature on the clinical use of the compounds identified as atypical in this article and to develop research protocols to assess their efficacy in treatment-resistant psychoses and intractable conditions such as tardive dyskinesia. PMID:2568176
Moore, N C; Gershon, S
This study was carried out to identify the medication prescribing errors (MPEs) pertaining to cardiovascular/antidiabetic medications in prescriptions issued to hypertensive and diabetic hypertensive patients. A retrospective, nationwide audit of prescriptions (n = 2773) issued by primary care physicians (n = 194) of 20 health centres in Bahrain was carried out. Approximately one-quarter of prescriptions ordered by two-thirds of primary care physicians had errors. No significant differences with respect to overall errors were evident in prescriptions ordered by the family physicians and general practitioners. The most common error (in 8.0% of prescriptions) was prescribing ?-blockers or diuretics (thiazide) or their combinations to patients on lipid-lowering drugs. Prescribing multiple antihypertensives, often with a similar mechanism, accounted for 2.2% errors: approximately half of these (1.45%) were two angiotensin-converting enzyme inhibitors (ACEIs) co-prescribed and/or ACEIs plus angiotensin-II receptor blockers. In 0.7% of prescriptions, ?-blockers were ordered to patients on salbutamol treatment. High-dose metformin (3 g/day) was prescribed to approximately 4% diabetic hypertensives; of these, many were elderly patients. Prescribing high-dose glibenclamide (median dose 15 mg) to the elderly accounted for 3.6% of the overall errors. Polypharmacy, such as aspirin along with an immediate-release dipyridamole, was prescribed occasionally (0.25%), particularly by the general practitioners (P = 0.0139). MPEs are common in primary care, in Bahrain. Some of these prescribing errors have the potential to harm patients. Effective measures to detect and prevent such errors are needed to improve the quality of health care. Standard treatment guidelines and educational interventions are important strategies to achieve these goals. PMID:21265878
Al Khaja, Khalid A J; Sequeira, Reginald P; Damanhori, Awatif H H
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.
Little, Paul; Watson, Louise; Morgan, Stephen; Williamson, Ian
SUMMARY G protein-coupled receptors form hetero-dimers and higher order hetero-oligomers, yet the significance of receptor heteromerization in cellular and behavioral responses is poorly understood. Atypical antipsychotic drugs, such as clozapine and risperidone all have in common a high affinity for the serotonin 5-HT2A receptor (2AR). However, closely related nonantipsychotic drugs, such as ritanserin and methysergide, while blocking 2AR function, lack comparable neuropsychological effects. Why some but not all drugs that inhibit 2AR-dependent signaling exhibit antipsychotic properties remains unresolved. We found that a heteromeric complex formed between the metabotropic glutamate 2 receptor (mGluR2) and the 2AR critically integrates the action of drugs affecting signaling and behavioral outcomes. Acting through the mGluR2/2AR heterocomplex, both glutamatergic and serotonergic drugs achieve a balance between Gi- and Gq-dependent signaling that predicts their psychoactive behavioral effects. These observations provide a novel mechanistic insight into antipsychotic action that may advance therapeutic strategies for schizophrenia.
Fribourg, Miguel; Moreno, Jose L.; Holloway, Terrell; Provasi, Davide; Baki, Lia; Mahajan, Rahul; Park, Gyu; Adney, Scott K.; Hatcher, Candice; Eltit, Jose M.; Ruta, Jeffrey D.; Albizu, Laura; Li, Zheng; Umali, Adrienne; Shim, Jihyun; Fabiato, Alexandre; MacKerell, Alexander D.; Brezina, Vladimir; Sealfon, Stuart C.; Filizola, Marta; Gonzalez-Maeso, Javier; Logothetis, Diomedes E.
CONTEXT Schizophrenic symptoms are linked to a dysfunction of dopamine neurotransmission and the brain reward system. However, it remains unclear whether antipsychotic treatment, which blocks dopamine transmission, improves, alters, or even worsens the reward-related abnormalities. OBJECTIVE To investigate changes in reward-related brain activations in schizophrenia before and after antipsychotic monotherapy with a dopamine D2/D3 antagonist. DESIGN Longitudinal cohort study. SETTING Psychiatric inpatients and outpatients in the Capital Region of Denmark. PARTICIPANTS Twenty-three antipsychotic-naive patients with first-episode schizophrenia and 24 healthy controls initially matched on age, sex, and parental socioeconomic status were examined with functional magnetic resonance imaging while playing a variant of the monetary incentive delay task. INTERVENTIONS Patients were treated for 6 weeks with the antipsychotic compound amisulpride. Controls were followed up without treatment. MAIN OUTCOME MEASURES Task-related blood oxygen level-dependent activations as measured by functional magnetic resonance imaging before and after antipsychotic treatment. RESULTS At baseline, patients, as compared with controls, demonstrated an attenuation of brain activation during reward anticipation in the ventral striatum, bilaterally. After 6 weeks of treatment, patients showed an increase in the anticipation-related functional magnetic resonance imaging signal and were no longer statistically distinguishable from healthy controls. Among the patients, there was a correlation between the improvement of positive symptoms and normalization of reward-related activation. Those who showed the greatest clinical improvement in positive symptoms also showed the greatest increase in reward-related activation after treatment. CONCLUSIONS To our knowledge, this is the first controlled, longitudinal study of reward disturbances in schizophrenic patients before and after their first antipsychotic treatment. Our results demonstrate that alterations in reward processing are fundamental to the illness and are seen prior to any treatment. Antipsychotic treatment tends to normalize the response of the reward system; this was especially seen in the patients with the most pronounced treatment effect on the positive symptoms. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01154829. PMID:22868877
Nielsen, Mette Odegaard; Rostrup, Egill; Wulff, Sanne; Bak, Nikolaj; Broberg, Brian Villumsen; Lublin, Henrik; Kapur, Shitij; Glenthoj, Birte
Antipsychotic drugs (APs) are prescribed for a wide range of psychotic illnesses. With more than 35 APs currently available worldwide, this drug class has rapidly gained importance in both clinical and forensic settings. On account of their chemical properties, many APs are present in human specimens at very low concentrations, which complicate their detection using standard gas chromatography-mass spectrometry (GC-MS) procedures that often cannot provide the required sensitivity. Recent advances in liquid chromatography-(tandem) mass spectrometry LC-MS(/MS) technology have enabled accurate detection and quantification of these compounds in various human specimens, indicated by the increasing number of published methods. Method validation has been a particular focus of analytical chemistry in recent times. Recommendations set by several guidance documents are now widely accepted by the toxicology community, as reflected by the guidelines drafted by leading toxicological societies. This review provides a critical review of single-stage and tandem LC-MS procedures for the detection and quantification of APs, with a particular emphasis on appropriate method validation. The quality of published methods is inconsistent throughout the literature. While the majority of authors incorporate some validation experiments in their respective method development, a large number of published methods lack essential components of method validation, which are considered mandatory according to the guidelines. If adapting a method for the detection of APs for use in a laboratory, analysts should ensure successful validation experiments for appropriateness and completeness have been conducted, and perform additional experiments when indicated. PMID:22573584
Saar, Eva; Beyer, Jochen; Gerostamoulos, Dimitri; Drummer, Olaf H
Use of atypical antipsychotic medications (AAMs) in the treatment of disruptive behavior (DB) in children and adolescents has increased dramatically worldwide. However, with exception of using risperidone (i.e., for the management of irritability associated with autism, manic and mixed episodes associated with bipolar I disorder, and schizophrenia) and aripiprazole (i.e., for manic and mixed episodes associated with bipolar I disorder and schizophrenia), the Food and Drug Administration (FDA) has not approved the use of AAMs in children and adolescents. Although research on use of these medications in children and adolescents has increased, mechanisms of action and long-term outcomes remain poorly understood or unknown. Particularly concerning is that use of these medications in children and adolescents may impact cognitive, social, and physical development, as side effects may interfere with activities in their educational setting, peer networks, and recreational settings. Overall, AAMs frequently are prescribed off label, control DB through sedation rather than targeting actual causes of DB, and lead to many negative side effects with unknown long-term effects. Reconsidering the use of AAMs in managing DB is encouraged strongly. PMID:21130552
McKinney, Cliff; Renk, Kimberly
Nonadherence to antipsychotic medications in serious, persistent mental illness remains a significant clinical challenge. Long-acting therapy was developed to help improve adherence to schizophrenia therapy and provide an effective means for ameliorating symptoms and preventing relapse. The Agency for Health Care Policy and Research/National Institute of Mental Health Schizophrenia Patient Outcomes Research Team recommends that antipsychotic long-acting therapy be strongly considered for patients who have difficulty adhering to an oral medication regimen or who prefer long-acting therapy. Depot conventional formulations have long been available; for clinicians and patients who would rather use an atypical antipsychotic, studies with risperidone long-acting therapy suggest that it is efficacious and well tolerated. A common concern of clinicians who elect to initiate long-acting therapy is how to introduce the possibility of changing from the current oral antipsychotic to an long-acting therapy injection. As with other aspects of patient care, having an established therapeutic relationship with the patient is advantageous for recommending changes in care, but the way in which the idea is approached may improve the likelihood of its acceptance. To help clinicians broach a recommendation of long-acting therapy with their patients, the GAIN approach was designed as a standard interview process for presenting this option. It encompasses (and is an acronym for) goal setting, action planning, initiating treatment, and nurturing motivation. This novel clinical tool is based on the principles of motivational enhancement therapy, a patient-centered approach that seeks to evoke the patient’s own motivation for change, to consolidate the decision to change, and to plan for change. This tool is also based on the Listen-Empathize-Agree-Partner, or LEAP, communication strategy. Motivational enhancement therapy, which is typically brief, has been found effective in several chronic illnesses in both outpatient and inpatient settings. GAIN may be a practical tool for aligning clinician-patient expectations and enhancing long-term maintenance of therapy.
Pharmacological treatments for serious mental illness (SMI) can cause weight gain and adverse metabolic effects. Many second generation antipsychotics and mood stabilizers appear to be particularly problematic in this regard. Several studies have investigated interventions for antipsychotic-induced, or less commonly mood stabilizer –induced, weight gain. Both lifestyle and pharmacological interventions have demonstrated effectiveness. We systematically review randomized controlled trials of pharmacological interventions for weight gain related to these medications. We conducted a meta-analysis of clinical trials for the most studied agents to estimate mean weight loss: metformin (2.93 kg, 95% C.I. 0.97–4.89, p=0.003), H2 antagonists (1.78 kg (95% C.I. ?0.50–4.06, p=0.13), topiramate (3.95 kg 95% C.I. 1.77–6.12, p=0.0004), and norepinephrine reuptake inhibitors (1.30 kg (95% C.I. ?0.06–2.66, p=0.06). Among the studied options for antipsychotic-related weight gain, metformin has the strongest evidence base and may improve vascular risk factors beyond obesity. The use of topiramate is also supported by the literature and may improve psychotic symptoms in those refractory to treatment. A marginal benefit is seen with norepinephrine reuptake inhibitors, and any vascular benefits from such weight loss may be counteracted by increases in blood pressure or heart rate. Pharmacological therapies may offer benefits as a means of supplementing the effects of lifestyle changes for weight loss. However, the existing evidence provides little evidence of specificity for pharmacological therapies to antipsychotic-induced weight gain and has not studied any connection between benefits and reduced incidence of diabetes mellitus or any vascular outcomes.
Fiedorowicz, Jess G.; Miller, Del D.; Bishop, Jeffrey R.; Calarge, Chadi A.; Ellingrod, Vicki L.; Haynes, William G.
Antipsychotic polypharmacy refers to the clinical practice of treating a patient with two or more antipsychotic drugs concurrently. There is abundant evidence in the clinical literature that treatment with antipsychotic polypharmacy is associated with an increased prevalence of drug side effects compared with monotherapy. This includes drug-induced metabolic side effects, such as glucose intolerance and insulin resistance. As these metabolic side effects have been accurately modeled in preclinical rodent paradigms using drug monotherapy, the goal of the present study was to determine the metabolic effects of antipsychotic polypharmacy using an established rodent model. In the first experiment, adult female rats were treated with clozapine (5 mg/kg), risperidone (1 mg/kg), vehicle, or clozapine + risperidone. In the second experiment, rats were treated with clozapine (5 mg/kg), haloperidol (0.1 mg/kg), vehicle, or clozapine + haloperidol. Animals were then subjected to a glucose tolerance test. Compared with vehicle-treated control animals, risperidone and haloperidol had no effect on any of the metabolic indices when administered on their own. Addition of risperidone to clozapine significantly increased fasting glucose, fasting insulin, and insulin resistance compared with the clozapine-only group. The addition of haloperidol to clozapine significantly increased fasting insulin levels, insulin resistance, and glucose intolerance compared with clozapine-only rats. These results are consistent with clinical studies and therefore indicate that animal models can successfully be used to study the metabolic side effects of antipsychotic drugs. Future studies related to understanding the physiological mechanisms involved remain a priority. PMID:23356730
Boyda, Heidi N; Procyshyn, Ric M; Tse, Lurdes; Xu, James; Jin, Chen Helen; Wong, Daniel; Pang, Catherine C Y; Honer, William G; Barr, Alasdair M
Science.gov - We Participate ... Wildfires of various sizes and intensities were more likely to occur in years with lower than ... Lightning fires were rare, however, and wildfire activity was greatest in the spring and fall. ... prescribed burning in reducing wildfire hazard and the low incidence of wildfires in the midsummer in north ...
Antibiotics represent the most widely prescribed therapeutic agents. The prevalence of drug prescription differs across age, with preschool children being most exposed to antibiotic drugs, especially in the community setting. A review with the aim to compare the profile of antibiotic drug prescription at the multinational, national and regional levels was performed. This overview of drug-utilisation studies found quantitative and
Antonio Clavenna; Maurizio Bonati
To help account for and address observed variations in medical practice, evaluations of “appropriateness” have sought to supplement incomplete evidence with professional opinion. This article contributes to an understanding and refinement of the construct of appropriateness by discussing how it has been defined and applied in studies of health care in general and prescribing in particular. We suggest that appropriateness
Stephen A. Buetow; Bonnie Sibbald; Judith A. Cantrill; Shirley Halliwell
The goal of this paper is to show from a n interactional or systemic perspective how intimacy may be damaged through traditional sex therapy approaches. This is in opposition to stated claims sex therapists, who have, since the pionem'ng work of Masters and Johnson, sought to improve intimacy Ly removing the impediment of poor sexual response. Prescribed masturbation in sex
Wildland firefighters are exposed to particulate matter and gases containing polycyclic aro- matic hydrocarbons (PAHs), many of which are known carcinogens. Our objective was to eval- uate 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
M. S. Robinson; T. R. Anthony; S. R. Littau; P. Herckes; X. Nelson; G. S. Poplin; J. L. Burgess
AIMS The question of whether new medical graduates are adequately prepared for the challenge of prescribing has been raised. Although broad outcomes for prescribing competency have been agreed, clarity is needed on the detailed outcomes expected of new graduates. This study aimed to create a consensus on the required competencies for new graduates in the area of prescribing. METHODS We used a modified Delphi approach based on the findings of a systematic review of educational interventions for improved prescribing. Panellists were asked to rank the importance of a list of 53 possible learning outcomes and to add any additional outcomes felt to be missing. RESULTS Of the 48 experts who were invited to participate, 28 agreed (58%). Forty-five learning outcomes were included from the original list of 53. A further nine outcomes were suggested by panellists, of which five were included. The wording of three outcomes was changed in line with suggestions from the panellists. Many of the agreed outcomes relate to improving patient safety through medication review, checking appropriateness of the drug for the patient, recognizing the prescriber's limitations and seeking advice when needed. Enhanced communication with the patient and healthcare team, better documentation in the notes and discharge letters were key areas featured in this Delphi exercise. DISCUSSION This study has identified 50 learning outcomes for teaching prescribing. These build on the existing British Pharmacological Society document by focusing specifically on prescribing, with greater emphasis on avoiding medication errors and better communication.
Ross, Sarah; Loke, Yoon K
Scotland has introduced a number of initiatives to enhance the prescribing of low-cost generic drugs versus originators and patent products in a class where these are seen as similar. The objective of this review is to appraise the influence of the various measures on subsequent utilization patterns and expenditure in high-volume classes to provide guidance. This review is principally a narrative review of published studies. The authors' found supply-side measures resulted in generic prices as low as 3% of pre-patent loss prices. Multiple demand-side measures resulted in high international non-proprietary name prescribing, and a considerable increase in prescribing efficiency for the proton pump inhibitors, statins, renin-angiotensin inhibitor drugs and selective serotonin reuptake inhibitors. There were no specific activities encouraging the prescription of losartan versus other angiotensin receptor blockers or risperidone versus other atypical antipsychotic drugs following generics and no change in their utilization patterns post generics. The authors can conclude multiple measures are needed to change physician prescribing habits. Authorities cannot rely on any 'spillover' effects to affect future prescribing, even in closely related classes. PMID:23977975
Godman, Brian; Bishop, Iain; Finlayson, Alexander E; Campbell, Stephen; Kwon, Hye-Young; Bennie, Marion
Objective To review the literature on educational interventions to improve prescribing and identify educational methods that improve prescribing competency in both medical and non-medical prescribers. Design A systematic review was conducted. The databases Medline, International Pharmaceutical Abstracts (IPA), EMBASE and CINAHL were searched for articles in English published between January 1990 and July 2013. Setting Primary and secondary care. Participants Medical and non-medical prescribers. Intervention Education-based interventions to aid improvement in prescribing competency. Primary outcome Improvements in prescribing competency (knows how) or performance (shows how) as defined by Miller's competency model. This was primarily demonstrated through prescribing examinations, changes in prescribing habits or adherence to guidelines. Results A total of 47 studies met the inclusion criteria and were included in the systematic review. Studies were categorised by their method of assessment, with 20 studies assessing prescribing competence and 27 assessing prescribing performance. A wide variety of educational interventions were employed, with different outcome measures and methods of assessments. In particular, six studies demonstrated that specific prescribing training using the WHO Guide to Good Prescribing increased prescribing competency in a wide variety of settings. Continuing medical education in the form of academic detailing and personalised prescriber feedback also yielded positive results. Only four studies evaluated educational interventions targeted at non-medical prescribers, highlighting that further research is needed in this area. Conclusions A broad range of educational interventions have been conducted to improve prescribing competency. The WHO Guide to Good Prescribing has the largest body of evidence to support its use and is a promising model for the design of targeted prescribing courses. There is a need for further development and evaluation of educational methods for non-medical prescribers.
Kamarudin, Gritta; Penm, Jonathan; Chaar, Betty; Moles, Rebekah
Boxed warnings, commonly referred to as "black box" warnings, are issued by the U.S. Food and Drug Administration and featured in the labeling of drugs associated with serious adverse reactions. These safety concerns are typically identified through the Adverse Event Reporting System and the Office of Surveillance and Epidemiology, which evaluates postmarket safety findings. The most common type of warning is issued when there is a potentially serious adverse effect that must be carefully weighed against the potential benefit of the drug. Warnings are also issued to draw attention to dosing, monitoring requirements, and potential drug interactions. Boxed warnings have been issued recently for oral sodium phosphate bowel preparations, fluoroquinolone antibiotics, and salmeterol. Despite these highly publicized warnings, all of these medications remain viable treatment options with appropriate patient selection. Ultimately, physicians must decide whether to prescribe drugs with boxed warnings. PMID:20112888
O'Connor, Nina R
Text Version... Autism” • In children aged 7-12 years old, concomitant use with stimulant medications were most common with aripiprazole and risperidone. ... More results from www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials
... Common Therapy for Rheumatoid Arthritis Reduces Risk of Death Taking methotrexate—a commonly prescribed anti-inflammatory medication—may reduce the risk of death among patients with rheumatoid arthritis (RA), according to ...
Massachusetts payers and providers have encouraged clinician usage of e-Prescribing technology to improve patient safety, enhance office practice efficiencies, and reduce medical costs. This report describes three early pilot e-Prescribing projects as case studies. These projects identified the e-Prescribing needs of clinicians, illustrated key issues that made implementation difficult, and clarified the impact of various types of functionality. The authors identified ten key barriers: (1) previous negative technology experiences, (2) initial and long-term cost, (3) lost productivity, (4) competing priorities, (5) change management issues, (6) interoperability limitations, (7) information technology (IT) requirements, (8) standards limitations, (9) waiting for an “all-in-one solution,” and (10) confusion about competing product offerings including hospital/Integrated Delivery System (IDN)–sponsored projects. In Massachusetts, regional projects have helped to address these barriers, and e-Prescribing activities are accelerating rapidly within the state.
Halamka, John; Aranow, Meg; Ascenzo, Carl; Bates, David W.; Berry, Kate; Debor, Greg; Fefferman, Jessica; Glaser, John; Heinold, Jerilyn; Stanley, John; Stone, Diane L.; Sullivan, Thomas E.; Tripathi, Micky; Wilkinson, Bruce
Since the development of federal standards for drug approval, the practice of medicine has historically involved the compounding of medications based on a physician's determination that a US FDA-approved product either did not exist, or could not be used for medical reasons. Today, prescriptions for non-FDA-approved compounded drugs may be driven by fanciful and largely unregulated pharmacy advertisements to physicians and patients and/or payer reimbursement policies, thus placing prescribers in the backseat for clinical decision making. This article outlines essential differences between FDA-approved drugs and compounded drugs and reasserts the primary medical role of physicians for determining what medical circumstances may necessitate treatment with non-FDA-approved products. In addition, liability concerns when prescribing non-FDA-approved drugs are discussed. While representing a US perspective, underlying principles apply globally in the setting of magistral and extemporaneous formulations produced outside national regulatory frameworks. PMID:23039281
Sellers, Sarah; Utian, Wulf H
In this noninterventional study, the implementation of 'modern' pain management in clinical practice was investigated by recording the regular prescription, administration and efficacy of analgesic drugs. This resulted in a reproducible and superficial quality control design for hospitals. One hundred and fifty surgical patients were followed during 5 days postoperatively. For every patient, pain, mood and sedation were measured using visual analogue and verbal descriptive scores; the prescription of analgesics at set times and administered doses of analgesics were also recorded. Only paracodeine and naproxen were administered regularly as prescribed, unlike paracetamol and morphine. The prescribed daily dose of morphine was only received by 4.2% of all patients. Although the postoperative pain treatment pathway was considered to be improved after better education and communication, in fact the opposite was found. This is probably caused by traditional thinking, lack of control and time pressure on the hospital staff and the subservient attitude of the patient. PMID:9485972
Boer, C; Treebus, A N; Zuurmond, W W; de Lange, J J
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,
MICHAEL S. ROBERTS; MICHELLE KING; JUUE A. STOKES; TERESA A. LYNNE; CHRISTOPHER J. BONNER; SEAN MCCARTHY; ANDREW WILSON; PAUL GLASZIOU; W. JOHN PUGH
Exercise prescription for patients with diabetes follows guidelines regarding frequency, intensity, duration, and mode of\\u000a exercise established for patients participating in a medically supervised exercise program. Physicians and health care professionals\\u000a should devise an exercise care plan that maximizes the benefits and minimizes the risks for each patient. The distinction\\u000a between prescribing exercise for patients with T1DM and patients with
Dalynn T. Badenhop
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
Dixie L. Bounds; Douglas E. Ruby
Synopsis Drug-induced movement disorders have dramatically declined with the widespread use of second generation antipsychotics but remain important in clinical practice and for understanding antipsychotic pharmacology. The diagnosis and management of dystonia, parkinsonism, akathisia, catatonia, neuroleptic malignant syndrome and tardive dyskinesia are reviewed in relation to the decreased liability of the second generation antipsychotics contrasted with evidence from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial. Data from the CATIE trial imply that advantages of second generation antipsychotics in significantly reducing extrapyramidal side effects compared with haloperidol may be diminished when compared with modest doses of lower-potency first generation drugs, that the dichotomy between first and second generation drugs may be oversimplified, and that antipsychotics could be conceptualized as a single drug class with a spectrum of risk for movement disorders depending upon receptor binding affinities and individual patient susceptibility.
Caroff, Stanley N.; Hurford, Irene; Lybrand, Janice; Campbell, E. Cabrina
This study assessed the efficacy of a weight control program for patients taking atypical antipsychotics. Thirty-one patients with schizophrenia or schizoaffective disorder participated in a 12-week weight control program that incorporated nutrition, exercise, and behavioral interventions. Changes in patients' weight and in body mass index (BMI) were recorded and compared with those of 15 patients in a control group. The intervention group had a mean weight loss of 2.7 kg (six pounds) and a mean reduction of.98 BMI points, compared with a mean weight gain of 2.9 kg (6.4 pounds) and a mean gain of 1.2 BMI points in the control group. These data suggest that the intervention was effective in this group of patients. Professionals treating persons who are taking atypical antipsychotics should encourage them to engage in weight control activities. PMID:12883145
Vreeland, Betty; Minsky, Shula; Menza, Matthew; Rigassio Radler, Diane; Roemheld-Hamm, Beatrix; Stern, Robert
Schizophrenia is an often devastating neuropsychiatric illness. Understanding the genetic variation affecting response to antipsychotics is important to develop novel diagnostic tests to match individual schizophrenic patients to the most effective and safe medication. Here we use a genomewide approach to detect genetic variation underlying individual differences in response to treatment with the antipsychotics olanzapine, quetiapine, risperidone, ziprasidone and perphenazine. Our sample consisted of 738 subjects with DSM-IV schizophrenia who took part in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Subjects were genotyped using the Affymetrix 500K genotyping platform plus a custom 164K chip to improve genomewide coverage. Treatment outcome was measured using the Positive and Negative Syndrome Scale (PANSS). Our criterion for genomewide significance was a pre-specified threshold that ensures, on average, only 10% of the significant findings are false discoveries. The top statistical result reached significance at our pre-specified threshold and involved a SNP in an intergenic region on chromosome 4p15. In addition, SNPs in ANKS1B and CNTNAP5 that mediated the effects of olanzapine and risperidone on Negative symptoms were very close to our threshold for declaring significance. The most significant SNP in CNTNAP5 is nonsynonymous, giving rise to an amino acid substitution. In addition to highlighting our top results, we provide all p-values for download as a resource for investigators with the requisite samples to carry out replication. This study demonstrates the potential of GWAS to discover novel genes that mediate effects of antipsychotics, which eventually could help to tailor drug treatment to schizophrenic patients.
McClay, Joseph L.; Adkins, Daniel E.; Aberg, Karolina; Stroup, Scott; Perkins, Diana O.; Vladimirov, Vladimir I.; Lieberman, Jeffrey A.; Sullivan, Patrick F.; van den Oord, Edwin J.C.G.
Summary. Several studies have shown an increased membrane phospholipid turnover in brain and blood cells of schizophrenic patients.\\u000a However the specificity of these findings for schizophrenia and the effects of longterm antipsychotic treatment had yet to\\u000a be demonstrated. In the present study we measured the concentrations of phospholipids in platelet membranes from 67 neuroleptic-free\\u000a schizophrenic patients compared to both healthy
A. Schmitt; A. Maras; G. Petroianu; D. F. Braus; L. Scheuer; W. F. Gattaz
Two case examples and a review of the sleep literature illustrate the potential of antipsychotic medication to trigger sleepwalking episodes in the context of schizophrenia. Causative hypotheses are briefly reviewed, as well as risk factors, differential diagnosis, and management. Sleepwalking may contribute to delusions, aggression, and accidental suicide. It is important to investigate sleep disorders in schizophrenia. They are not rare and may contribute to behavior that increases the stigma and isolation of individuals with schizophrenia. PMID:20734137
Seeman, Mary V
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.
Mailman, Richard B.; Murthy, Vishakantha
Various studies have revealed that sexual dysfunction is prevalent in schizophrenia patients treated with either first- or second-generation antipsychotics. Although sexual dysfunction may have a negative impact on adherence to treatment, no reports have studied sexual dysfunction in schizophrenia patients compared with healthy controls in Asian populations. We employed a cross-sectional, case-control survey design to collect data from 352 schizophrenic
Akira Fujii; Norio Yasui-Furukori; Norio Sugawara; Yasushi Sato; Taku Nakagami; Manabu Saito; Sunao Kaneko
Context: The health burden of antipsychotic medication is well known, but the disproportionate effect on women as compared with men is underappreciated. Objective: The goal of this article is preventive—to better inform clinicians so that the risks to women and to their offspring can be di- minished.Method:All PubMed sources in which the search term gender (or sex) was linked to
Mary V. Seeman; M. Parelman; B. Stoecker; A. Baker; D. Medeiros; D. Gaddy; D. S. Perrien; N. S. Akel; E. E. Dupont-Versteegden; R. A. Skinner; E. R. Siegel; A. Alberich-Bayarri; L. Marti-Bonmati; R. Sanz-Requena; E. Belloch; T MRI; Schizophr Bull
Background: Metabolic abnormalities, including insulin resistance and increased leptin levels, were noted in patients with schizophrenia who had received antipsychotics. In this study, we examined the leptin levels of antipsychotic-naïve schizophrenic patients. Method: Seventeen antipsychotic-naïve patients with schizophrenia and 16 sex-, age- and body mass index (BMI)-matched subjects were recruited from the psychiatric outpatient clinic and community, respectively. Serum leptin
Hsuan Chi Wang; Yen Kuang Yang; Po See Chen; I Hui Lee; Tzung Lieh Yeh; Ru Band Lu
Before Euro-American settlement fire was a common process in the forests of the Lake Tahoe Basin. The combination of drought, fire suppression, and past harvesting has produced ecosystems that are susceptible to high-severity wildfires. Consequently, a program of prescribed fire has been recommended but there is incomplete understanding of the ecological effects of fuels treatments, especially with regard to how
Scott L. StephensA; Thomas Meixner; Mark PothC; Dale PayneE
BACKGROUND: To investigate determinants of antibiotic prescription in paediatric care, as a first step of a multilevel intervention to improve prescribing for common respiratory tract infections (RTIs) in a northern Italian region with high antibiotic prescription rate. METHODS: A two-step survey was performed: in phase I, knowledge, and attitudes were explored involving all family and hospital paediatricians of Emilia-Romagna and
Maria Luisa Moro; Massimiliano Marchi; Carlo Gagliotti; Simona Di Mario; Davide Resi
Several studies in rodent models have shown that glycogen synthase kinase 3 ? (GSK3?) plays an important role in the actions of antispychotics and mood stabilizers. Recently it was demonstrated that GSK3? through a ?-arrestin2/protein kinase B (PKB or Akt)/protein phosphatase 2A (PP2A) signaling complex regulates dopamine (DA)- and lithium-sensitive behaviors and is required to mediate endophenotypes of mania and depression in rodents. We have previously shown that atypical antipsychotics antagonize DA D2 receptor (D2R)/?-arrestin2 interactions more efficaciously than G-protein–dependent signaling, whereas typical antipsychotics inhibit both pathways with similar efficacy. To elucidate the site of action of GSK3? in regulating DA- or lithium-sensitive behaviors, we generated conditional knockouts of GSK3?, where GSK3? was deleted in either DA D1- or D2-receptor–expressing neurons. We analyzed these mice for behaviors commonly used to test antipsychotic efficacy or behaviors that are sensitive to lithium treatment. Mice with deletion of GSK3? in D2 (D2GSK3??/?) but not D1 (D1GSK3??/?) neurons mimic antipsychotic action. However, haloperidol (HAL)-induced catalepsy was unchanged in either D2GSK3??/? or D1GSK3??/? mice compared with control mice. Interestingly, genetic stabilization of ?-catenin, a downstream target of GSK3?, in D2 neurons did not affect any of the behaviors tested. Moreover, D2GSK3??/? or D1GSK3??/? mice showed similar responses to controls in the tail suspension test (TST) and dark–light emergence test, behaviors which were previously shown to be ?-arrestin2- and GSK3?-dependent and sensitive to lithium treatment. Taken together these studies suggest that selective deletion of GSK3? but not stabilization of ?-catenin in D2 neurons mimics antipsychotic action without affecting signaling pathways involved in catalepsy or certain mood-related behaviors.
Urs, Nikhil M.; Snyder, Joshua C.; Jacobsen, Jacob P. R.; Peterson, Sean M.; Caron, Marc G.
Background: Neurodevelopmental hypothesis of schizophrenia states abnormal pruning as one of the pathogenetic mechanism in schizophrenia. Though thalamic volume abnormalities have been documented, the shape differences of thalamus in antipsychotic-free schizophrenia in comparison with age- and sex-matched healthy volunteers need validation. Materials and Methods: We examined antipsychotic naïve schizophrenia patients (n=60) and age- and sex-matched healthy volunteers (n=44). The thalamic shape abnormalities were analyzed from their coded structural magnetic resonance imaging (MRI) data using three-dimensional automated image analysis software, FMRIB's (Oxford Center for the functional MRI of the brain) tools-FIRST (FMRIB's Integrated Registration and Segmentation Tool) by creating deformable mesh model. Correlation with the psychopathology scores was carried out using F-statistics. Results: Patients with schizophrenia showed significant inward deformations in the regions corresponding to anterior, ventromedial, mediodorsal, and pulvinar nuclei. There was a direct correlation between negative syndrome score and the deformation in the right mediodorsal and right pulvinar nuclei. Conclusion: The inward deformations of thalamus in antipsychotic naive schizophrenia patients correspond to those nuclei which have reciprocal connections with frontal, superior temporal, and anterior cingulate regions and support the neurodevelopmental hypothesis of schizophrenia.
Danivas, Vijay; Kalmady, Sunil V.; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N.
The ABCG2 transporter breast cancer resistance protein (BCRP) has been identified in several physiological sites. It has been suggested to play an important role in disposition of many drugs and environmental toxins. We investigated the effects of several antipsychotic drugs, including risperidone, 9-hydroxy-risperidone (paliperidone), olanzapine, quetiapine, clozapine, haloperidol and chlorpromazine, and a positive control inhibitor Ko143 on functions of BCRP in MCF7 and BCRP over-expressing MCF7/MX100 cell lines using a BCRP prototypical substrate mitoxantrone. Our findings indicated that the tested antipsychotics rank order of potency of inhibition of BCRP according to concentrations required to reach 50% of maximum inhibition (IC(50)) was as follows: Ko143 (0.07 microM) > risperidone (38.1 microM) > clozapine (42.0 microM) > paliperidone (51 microM) > chlorpromazine (52.2 microM) > quetiapine (66.1 microM) > olanzapine = haloperidol (>100.0 microM). We further tested the effects of various concentrations of risperidone on the BCRP-mediated transport of oestrone-3-sulfate in a colon carcinoma cell line, Caco-2, a widely used model to study drug absorption. Our findings show that risperidone at concentrations ranging from 1 to 100 microM significantly inhibited intracellular accumulation of oestrone-3-sulfate in Caco-2 cell monolayers. The present results suggest that a potential source of pharmacokinetic interactions exists between BCRP substrates and several antipsychotics. PMID:18834354
Wang, Jun-Sheng; Zhu, Hao-Jie; Markowitz, John S; Donovan, Jennifer L; Yuan, Hong-Jie; Devane, C Lindsay
Lower fluctuation, i.e., lower peak-to-trough plasma-concentration variation at steady-state pharmacokinetics, has several advantages for the treatment of schizophrenia with antipsychotics. The reduction of peak concentration can decrease the risk of dose-dependent side effects, such as extrapyramidal symptom and somnolence, and by contrast the increase in trough concentration can decrease the incidence of lack of efficacy due to subtherapeutic drug concentration. Using a one-compartment simulation technique with pharmacokinetic parameters of each atypical antipsychotic collected from package inserts, the fluctuation index was calculated. Among the antipsychotics, the indices varied from 0.018 to 1.9, depending on dosing regimens, formulations and several pharmacokinetic properties. The order of simulated fluctuation index is active-moiety aripiprazole (b.i.d.) Wakamatsu, Akihide; Aoki, Kazuo; Sakiyama, Yojiro; Ohnishi, Takashi; Sugita, Makoto 2013-03-01
Wakamatsu, Akihide; Aoki, Kazuo; Sakiyama, Yojiro; Ohnishi, Takashi; Sugita, Makoto
Although women with serious mental illness have high rates of lifetime sexual partners, they infrequently use contraception. Consequently, the prevalence of sexually transmitted infections is high in this population. In addition, while the overall rate of pregnancy in women with schizophrenia of child-bearing age is lower than in the general population, the percentage of pregnancies that are unwanted is higher than that in the general population. The objective of this paper is to help clinicians explore knowledge of appropriate methods of contraception for women who suffer from schizophrenia. The authors reviewed recent literature on the use of contraceptive methods by women with schizophrenia treated with antipsychotic and adjunctive medications. Contraceptive counseling to women and their partners is an important part of comprehensive care for women with serious and persistent mental illness. Women with schizophrenia who smoke, are overweight, or have diabetes, migraine, cardiovascular disease, or a family history of breast cancer should be offered non-hormonal contraception. Women with more than one sexual partner should be advised on barrier methods in addition to any other contraceptive measures they are using. Clinicians should be alert for potential interactions among oral hormonal contraceptives, smoking, and therapeutic drugs. Long-lasting contraceptive methods, such as intrauterine devices, progesterone depot injections, or tubal ligation are reasonable options for women having no wish to further expand their families. PMID:21775827
Seeman, Mary V; Ross, Ruth
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
Rajender R. Aparasu; Jane R. Mort; Scott Sitzman
Under-prescribing and low attendance continue to be cited as reasons for ongoing asthma symptoms in primary care despite marked increases in prescribing and structured care for asthma over the past 10 years. The objective of this study was to determine the relationship between continuing asthma morbidity and the attendance of and prescribing for symptomatic asthmatic patients in primary care. A
D. NOLAN; P. WHITE
Schizophrenia is one of the most severe psychiatric diseases noted for its chronic and often debilitating processes; affecting approximately 1% of the world's population, while its etiology and therapeutic strategies still remain elusive. In the 1950s, the discovery of antipsychotic effects of haloperidol and chlorpromazine shifted the paradigm of schizophrenia. These drugs proved to be antagonists of dopamine D2 receptor (D2R), thus dopamine system dysfunction came to be hypothesized in the pathophysiology of schizophrenia, and D2R antagonism against dopamine neurons has been considered as the primary therapeutic target for schizophrenia. In addition, abnormalities of glutamatergic neurons have been indicated in the pathophysiology of schizophrenia. On the other hand, recent neuroimaging studies have shown that not only dementia but also schizophrenic patients have a significant volume reduction of some specific regions in the brain, which indicates that schizophrenia may involve some neurodegenerative process. Microglia, major sources of various inflammatory cytokines and free radicals such as superoxide and nitric oxide (NO) in the CNS, play a crucial role in a variety of neurodegenerative diseases such as dementia. Recent postmortem and positron emission computed tomography (PET) studies have indicated that activated microglia may be present in schizophrenic patients. Recent in vitro studies have suggested the anti-inflammatory effects of antipsychotics on microglial activation. In this article, we review the anti-inflammatory effects of antipsychotics on microglia, and propose a novel therapeutic hypothesis of schizophrenia from the perspective of microglial modulation. PMID:21699487
Kato, T A; Monji, A; Mizoguchi, Y; Hashioka, S; Horikawa, H; Seki, Y; Kasai, M; Utsumi, H; Kanba, S
Our review describes potential weight-altering effects of psychotropic medications (antipsychotics, antidepressants, anti-anxiety medications, mood stabilizers, sedative-hypnotics, medications for attention-deficit/hyperactivity disorder, and other psychotropic medications) and offers guidance on switching a medication if its weight-altering effect becomes problematic. For second-generation antipsychotics, the risk of weight gain is high with clozapine and olanzapine, low with amisulpride, aripiprazole, and ziprasidone, and medium with other second-generation antipsychotics. Switching from a high-risk antipsychotic to a low-risk antipsychotic usually mitigates or reverses weight gain. For second-generation antidepressants, there may be modest weight loss with bupropion and modest weight gain with mirtazapine and paroxetine. Other second-generation antidepressants are weight neutral but individual variations can occur. If significant change in weight occurs, switching to or adding a low-risk second-generation antidepressant should be considered. Mood stabilizers include lithium, valproate, carbamazepine, lamotrigine, oxcarbazepine, and most second-generation antipsychotics. Risk of weight gain is high with lithium and valproate and low with carbamazepine, lamotrigine, and oxcarbazepine. Given the complexity of bipolar disorder and its management, a switch of a mood stabilizer would be best done by a psychiatrist. Benzodiazepines, non-benzodiazepine and melatonergic hypnotics, doxepin, and trazodone are weight neutral. Diphenhydramine may cause weight-gain and can be switched to a weight-neutral hypnotic if needed. Stimulants can cause varying degrees of weight loss and switching to atomoxetine or bupropion may reverse this problem. If that fails, switching to clonidine or guanfacine can be tried. Switching must be evidence-based and take into account status of the condition being treated, efficacy, side effect profile, potential drug-drug interactions, required laboratory monitoring and cost of the drug(s) being considered, and patient's pregnancy status or plan. Non-pharmacological interventions both for mental disorders and overweight/obesity must be fully availed. PMID:24113670
Hasnain, Mehrul; Vieweg, W Victor R
In many Western jurisdictions cannabis, unlike most other psychoactive drugs, cannot be prescribed to patients even in cases where medical professionals believe that it would ease the patient's pain or anxiety. The reasons for this prohibition are mostly ideological, although medical and moral arguments have been formulated to support it. In this paper, it is argued that freedom, properly understood, provides a sound ethical reason to allow the use of cannabis in medicine. Scientific facts, appeals to harm and autonomy, and considerations of symbolic value cannot consistently justify prohibitions. PMID:15289511
OBJECTIVES: The objective was to explore whether prescribing variation is associated with duration of antidepressant use during the acute phase of treatment. Improving quality of care and increasing the extent to which treatment is patient-centered and customized are interrelated goals. Prescribing variation may be considered a marker of customization, and could be associated with better antidepressant treatment adherence. METHODS: A cross-sectional secondary data analysis examining the association between providers' antidepressant prescribing variation and patient continuity of antidepressant treatment. The data source was two states' Medicaid claims for dual-eligible Medicaid/Medicare patients. The sample included 383 patients with new episodes of antidepressant treatment, representing 70 providers with at least four patients in the sample. We tested two alternate measures of prescribing concentration: 1) share of prescriber's initial antidepressant prescribing accounted for by the two most common regimens, and 2) Herfindahl index. The HEDIS performance measure of effective acute-phase treatment (at least 84 out of 114 days with antidepressant) was the dependent variable. KEY FINDINGS: In multivariate analyses, the concentration measure based on the top two regimens was significant and inversely related to duration adequacy (p <.05). The Herfindahl index measure showed a trend towards a similar inverse relationship (p<.10). CONCLUSIONS: The findings provide some support for the hypothesized relationship between prescribing variation and adequate antidepressant treatment duration during the acute phase of treatment. Future work with more detailed, clinical longitudinal data could extend this inquiry to better understand the causal mechanisms using a more direct measure of customized care. PMID:22707982
Merrick, Elizabeth L; Hodgkin, Dominic; Panas, Lee; Soumerai, Stephen B; Ritter, Grant
AIM: 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 (CDS). METHOD: 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), non-steroidal 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=29/80). CONCLUSION: 80 high-risk prescribing errors in the hospital setting have been identified by an expert panel. These indicators can serve as a standardised, 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
Thomas, S K; McDowell, S E; Hodson, J; Nwulu, U; Howard, R L; Avery, A J; Slee, A; Coleman, J J
Non-medical prescribing is increasingly utilized in clinical care and UK Standards have been produced for this. This study was undertaken to investigate compliance with these standards which were adopted by one mental health service and to review whether any changes were necessary to existing arrangements monitoring this compliance. A questionnaire was distributed to all 24 non-medical prescribers from one UK Mental Health Trust. Participants were asked to respond to questions about demographic data and prescribing practices. We also asked them to rate their experience on a 5-point scale. In all, 83% of non-medical prescribers responded. The UK Standards were met even though there was a shortfall in the uptake of training and supervision. Non-medical prescribers from the Community Drug Team and Older People's Service prescribed a narrow range of speciality drugs than any other category of drugs, but prescribed more often. UK Standards were met by the majority of non-medical prescribers. However, concerns were noted about a shortfall in training, supervision and experience of some non-medical prescribers. Conflict with psychiatrists was reported but their availability for support when necessary was valued. Non-medical prescribers believed that their input with non-medical prescribing had benefited patients. PMID:22070189
Gumber, R; Khoosal, D; Gajebasia, N
Background: While antibiotic prophylaxis is recommended to all patients undergoing transurethral resection of prostate (TURP), little data exist regarding prescribing patterns of urologists prior to this procedure. Here, we sought to determine real-world antibiotic prophylaxis prescribing patterns at a high volume Canadian institution and determine compliance rates to recommendations put forth by the American Urological Association’s (AUA) Best Practice Statement (BPS) on antimicrobial prophylaxis. Methods: A retrospective chart review of 488 patients undergoing TURP was conducted. Electronic medical records were reviewed to determine antibiotics prescribed 3 hours preoperatively and 24 hours postoperatively. For patients without a catheter, compliance was defined as those receiving an antibiotic prior to TURP. In patients with an indwelling catheter, compliance was defined as those receiving antibiotics from two different classes prior to surgery. Results: Overall, a total of 30 antibiotic regimens were utilized. The most common single antibiotic regimens prescribed were ciprofloxacin (32%), cefazolin (25%) and gentamicin (3%). In those patients with indwelling Foley catheters prior to TURP, a significant increase in gentamicin, as well as combination antibiotic regimens, was noted. The compliance rate with the AUA BPS in patients without a preoperative catheter was 81%, while the compliance rate for patients with an indwelling catheter prior to TURP was 37%. Interpretation: Collectively, our results demonstrate that prescribing patterns vary significantly prior to TURP, with compliance to AUA BPS being lower than anticipated. Overall, these results support educational efforts in this area, and the development of Canadian recommendations to improve uptake by practicing urologists.
Lawson, Keith A.; Rudzinski, Jan K.; Vicas, Ingrid; Carlson, Kevin V.
BACKGROUND: Adults with congenital heart disease (CHD) are often cared for at pediatric hospitals. There are no data describing the incidence or type of medication prescribing errors in adult patients admitted to a pediatric cardiovascular intensive care unit (CVICU). METHODS: A review of patients >18 years of age admitted to the pediatric CVICU at our institution from 2009 to 2011 occurred. A comparator group <18 years of age but >70?kg (a typical adult weight) was identified. Medication prescribing errors were determined according to a commonly used adult drug reference. An independent panel consisting of a physician specializing in the care of adult CHD patients, a nurse, and a pharmacist evaluated all errors. Medication prescribing orders were classified as appropriate, underdose, overdose, or nonstandard (dosing per weight instead of standard adult dosing), and severity of error was classified. RESULTS: Eighty-five adult (74 patients) and 33 pediatric admissions (32 patients) met study criteria (mean age 27.5 ± 9.4 years, 53% male vs. 14.9 ± 1.8 years, 63% male). A cardiothoracic surgical procedure occurred in 81.4% of admissions. Adult admissions weighed less than pediatric admissions (72.8 ± 22.4?kg vs. 85.6 ± 14.9?kg, P < .01) but hospital length of stay was similar. (Adult 6 days [range 1-216 days]; pediatric 5 days [Range 2-123 days], P = .52.) A total of 112 prescribing errors were identified and they occurred less often in adults (42.4% of admissions vs. 66.7% of admissions, P = .02). Adults had a lower mean number of errors (0.7 errors per adult admission vs. 1.7 errors per pediatric admission, P < .01). Prescribing errors occurred most commonly with antimicrobials (n = 27). Underdosing was the most common category of prescribing error. Most prescribing errors were determined to have not caused harm to the patient. CONCLUSIONS: Prescribing errors occur frequently in adult patients admitted to a pediatric CVICU but occur more often in pediatric patients of adult weight. PMID:23773504
Echeta, Genevieve; Moffett, Brady S; Checchia, Paul; Benton, Mary Kay; Klouda, Leda; Rodriguez, Fred H; Franklin, Wayne
Objective: The objective of this study was to identify the patterns of prescribing for Acute respiratory infections in patients attending primary health care centers in the Aseer region, southwestern Saudi Arabia. Materials & Methods: This study was conducted at primary health care centers in the Aseer region during November 2003. A master sheet designed by the investigator was distributed to all the working physicians in the primary health care center in the Aseer region. The master sheet included the age, sex, complaints, signs, clinical diagnosis and the type of medications prescribed. Physicians were asked to include all patients attending on 17th November 2003, and send the master sheet to the Technical Supervision Unit at Primary Care Department, General Directorate of Health Affairs. Data of the master sheet was entered and analyzed by using SPSS. Results: The total number of patients attending with acute respiratory infections(ARIs) was 3000 which represented 25% of the patients attending primary health care centers that day. Children formed 60% of the total number of cases. Regarding symptoms and signs, it was found that 70% had a cough, 59% had a runny nose, and 43% had a sore throat . The common cold was the most common diagnosis (42%). Antipyretics, antihistamines, antibiotics and antitussives were prescribed for 78%, 48%, 45% and 25% respectively. Statistical analysis using logistic regression revealed that the higher the temperature, the more severe the throat congestion and the presence of exudates on pharynx, the higher the likelihood to prescribe antibiotics. Conclusion: In this study, it was found that the prescription of all drugs for ARIs was still high in spite of the fact that these conditions are self-limiting. To rationalize prescribing for ARI, implementation of the national protocol for diagnosis and treatment of ARIs is mandatory. Further studies to explore the physician's knowledge, attitudes and behavior concerning prescribing for ARI is strongly recommended.
Al-Khaldi, Yahia M.; Diab, Mohamed M.A.A.; Al-Gelban, Khalid S.; Al-Asmari, Ali S.; Al-Amin, Salaheddin; Al-Shahrani, Mesfer S.
Electronic-Prescribing, Computerized Prescribing, or E-RX has increased dramatically of late in the American health care system, a long overdue alternative to the written form for the almost five billion drug treatments annually. This paper examines the history and selected issues in the rise of E-RX by a review of salient literature, interviews, and field observations in Pharmacy. Pharmacies were early adopters of computerization for a variety of factors. The profession in its new corporate forms of chain drug stores and pharmacy benefits firms has sought efficiencies, profit enhancements, and clinical improvements through managed care strategies that rely upon data automation. E-RX seems to be a leading factor in overall physician acceptance of Electronic Medical Records (EMRs), although the Centers for Medicare and Medicaid (CMS) incentives seem to be the propelling force in acceptance. We conclude that greater research should be conducted by public health professionals to focus on resolutions to pharmaceutical use, safety, and cost escalation, which persist and remain dire following health reform. PMID:23569654
Salmon, J Warren; Jiang, Ruixuan
The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Phase 1 Schizophrenia trial compared the effectiveness of one typical and four atypical antipsychotic medications. Although trials such as CATIE present important opportunities for pharmacogenetics research, the very richness of the clinical data presents challenges for statistical interpretation, and in particular the risk that data mining will lead to false-positive discoveries. For
Anna C Need; Richard SE Keefe; Dongliang Ge; Iris Grossman; Sam Dickson; Joseph P McEvoy; David B Goldstein
This systematic review assesses the effectiveness of antipsychotic medication for improving core psychopathology and behavioral symptoms of anorexia nervosa. The Cochrane Depression, Anxiety and Neurosis Group Trials Register, reference lists of retrieved studies and conference abstracts were searched. Four randomized controlled trials comparing typical or atypical antipsychotic medication to other interventions were included. Clinical heterogeneity precluded meta-analysis. Overall, there is
Andrew Court; Claudia Mulder; Sarah E. Hetrick; Rosemary Purcell; Patrick D. McGorry
Many anti-psychotic medications produce marked weight gain. In this study, we estimate the expected impact of degrees of antipsychotic-induced weight gain on selected mortality rate and incidence rates of impaired glucose tolerance (IGT) and hypertension (HTN) among US adults. Using raw data from 5209 respondents from the Framingham Heart Study's public use data set and national statistics on population demographics,
Kevin R Fontaine; Moonseong Heo; Edmund P Harrigan; Charles L Shear; Mani Lakshminarayanan; Daniel E Casey; David B Allison
Atypical antipsychotics are a class of novel agents increasingly employed for the treatment of psychotic disorders. The pharmacodynamic properties of the atypicals appear to impact a broader spectrum of psychotic symptoms than had been appreciated with older generation antipsychotics. In addition, the atypical agents appear to have a reduced risk of neurologic side effects compared with conventional antipsychotic use. Both of these features enhance the appeal of the atypical antipsychotics and may be associated with enhanced patient compliance. The atypical antipsychotics appear to be effective for schizophrenia as well as other psychotic disorders, including schizoaffective disorder and mood disorders with psychotic features. Consequently, atypical antipsychotics are now considered to be the first-line treatment for schizophrenia, with the exception of clozapine, which is considered a second-line agent because of risks associated with its use. This review will discuss the literature on atypical antipsychotic efficacy in psychotic disorders. Issues related to antipsychotic use, dosing, adverse effects, and drug interactions are also discussed.
Leo, Raphael J.; Regno, Paula Del
Background: In two recent randomised clinical trials, a meta- analysis and in an effectiveness study analysing routine data from the U.S. Veterans Administration the superiority of the newer atypical drugs over typical antipsychotic drugs, concerning both their efficacy and their side-effect profile, has been questioned. Aims of the Study: To analyse the effectiveness and cost of atypical versus typical antipsychotic
Tom Stargardt; Susanne Weinbrenner; Reinhard Busse; Georg Juckel; Christian A. Gericke
Neurocognitive deficits are a core feature of schizophrenia and, therefore, represent potentially critical outcome variables for assessing antipsychotic treatment response. We performed genome-wide association studies (GWAS) with 492K single nucleotide polymorphisms (SNPs) in a sample of 738 patients with schizophrenia from the Clinical Antipsychotic Trials of Intervention Effectiveness study. Outcome variables consisted of a neurocognitive battery administered at multiple time
Joseph L McClay; Daniel E Adkins; Karolina Åberg; Jozsef Bukszár; Amit N Khachane; Richard S E Keefe; Diana O Perkins; Joseph P McEvoy; T Scott Stroup; Robert E Vann; Patrick M Beardsley; Jeffrey A Lieberman; Patrick F Sullivan; Edwin J C G van den Oord
OBJECTIVE: To compare the rate of relapse as a function of antipsychotic treatment (monotherapy vs. polypharmacy) in schizophrenic patients over a 2-year period. METHODS: Using data from a multicenter cohort study conducted in France, we performed a propensity-adjusted analysis to examine the association between the rate of relapse over a 2-year period and antipsychotic treatment (monotherapy vs. polypharmacy). RESULTS: Our
Aurelie Millier; Emmanuelle Sarlon; Jean-Michel Azorin; Laurent Boyer; Samuel Aballea; Pascal Auquier; Mondher Toumi
Risperidone is a widely used atypical antipsychotic with certain advantages over typical antipsychotics. Although variations in the efficacy of treatment with risperidone have been observed, no specific predictable marker has been identified as of yet. In all, 73 Japanese patients with schizophrenia were given risperidone for 8 weeks, and clinical symptoms were evaluated using the Positive and Negative Syndrome Scale
Y Yamanouchi; N Iwata; T Suzuki; T Kitajima; M Ikeda; N Ozaki
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
Stefan Wilhelm; Alexander Schacht; Thomas Wagner
Clinical expectations in schizophrenia treatment have greatly increased since the introduction of new atypical antipsychotics, but the choice of therapeutic strategy has become more complex and reference guidelines are scarce. This paper summarizes the consensus of a broad range of professionals after long-term commercialization in France of an atypical antipsychotic, amisulpride. Participants were from psychiatric hospitals, private clinics, out-patients settings
Yves Lecrubier; Michel Azorin; Thierry Bottai; Jean Dalery; Gérard Garreau; Thérèse Lempérière; Agnès Lisoprawski; François Petitjean; Jean-Marie Vanelle
|Objective: To estimate prevalence rates of antipsychotic use in children and adolescents from 1996 to 2001 in three state Medicaid programs (midwestern [MM], southern [SM], and western [WM]) and one private managed care organization (MCO). Method: Prescription claims were used to evaluate antipsychotic prevalence, defined as the number of…
Patel, Nick C.; Crismon, M. Lynn; Hoagwood, Kimberly; Johnsrud, Michael T.; Rascati, Karen L.; Wilson, James P.; Jensen, Peter S.
Atypical antipsychotic drugs offer several notable benefits over typical antipsychotics, including greater improvement in negative symptoms, cognitive function, prevention of deterioration, and quality of life, and fewer extrapyramidal symptoms (EPS). However, concerns about EPS have been replaced by concerns about other side effects, such as weight gain, glucose dysregulation and dyslipidemia. These side effects are associated with potential long-term cardiovascular
H A Nasrallah
Objective: Following the presentation of a case study and an overview of current data highlighting the need for further research into the use of antipsychotic medication during pregnancy, the aim of the present paper was to outline the establishment of, and present preliminary data from, the National Register of Antipsychotic Medication in Pregnancy (NRAMP). Method: Australian women with a history
Jayashri Kulkarni; Kay McCauley-Elsom; Natasha Marston; Heather Gilbert; Caroline Gurvich; Anthony de Castella; Paul Fitzgerald
Typical antipsychotic drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors. Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors, and a high degree of occupancy of the serotoninergic receptors 5-HT2A. Whether these different pharmacological actions produce different effects on brain structure remains unclear. We explored the effects of different types of antipsychotic treatment
Paola Dazzan; Kevin D Morgan; Ken Orr; Gerard Hutchinson; Xavier Chitnis; John Suckling; Paul Fearon; Philip K McGuire; Rosemarie M Mallett; Peter B Jones; Julian Leff; Robin M Murray
Background: Decision support (i.e., alerts and reminders) at the time of medication prescribing has been shown to be an effective method for reducing potential medication errors for inpatients, but much less is known about the effects in the outpatient setting. Using qualitative methods to inform our work, medication safety decision support and provider education interventions were designed to improve the
Adrianne C. Feldstein; David H. Smith; Nan R. Robertson; Christine A. Kovach; Stephen B. Soumerai; Steven R. Simon; Dean F. Sittig; Daniel S. Laferriere; Mara Kalter
Cognitive deficits in schizophrenia are associated with prefrontal cortex (PFC) abnormalities. Schizophrenic patients show a reduced performance in tasks engaging the PFC and a reduction of markers of cellular integrity and function. Non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists are widely used as pharmacological models of schizophrenia due to their ability to exacerbate schizophrenia symptoms in patients and to elicit psychotomimetic actions in healthy volunteers. Also, these drugs evoke behavioral alterations in experimental animals that resemble schizophrenia symptoms. The PFC seems to be a key target area for these agents. However, the cellular and network elements involved are poorly known. Cognitive deficits are of particular interest since an early antipsychotic-induced improvement in cognitive performance predicts a better long-term clinical outcome. Here we report that the non-competitive NMDA receptor antagonist phencyclidine (PCP) induces a marked disruption of the activity of PFC. PCP administration increased the activity of a substantial proportion of pyramidal neurons, as evidenced by an increase in discharge rate and in c-fos expression. Examination of the effects of PCP on other brain areas revealed an increased c-fos expression in a number of cortical and subcortical areas, but notably in thalamic nuclei projecting to the PFC. The administration of classical (haloperidol) and/or atypical (clozapine) antipsychotic drugs reversed PCP effects. These results indicate that PCP induces a marked disruption of the network activity in PFC and that antipsychotic drugs may partly exert their therapeutic effect by normalizing hyperactive cortico-thalamocortical circuits. PMID:19073421
Kargieman, Lucila; Santana, Noemí; Mengod, Guadalupe; Celada, Pau; Artigas, Francesc
Although clozapine, olanzapine, and other atypical antipsychotic drugs (APDs) have fewer extrapyramidal side effects, they have serious metabolic side effects such as substantial weight gain, intra-abdominal obesity, and type 2 diabetes mellitus. Given that most patients with mental disorders face chronic, even life-long, treatment with APDs, the risks of weight gain/obesity and other metabolic symptoms are major considerations for APD maintenance treatment. This review focuses on the effects of APDs on weight gain, appetite, insulin resistance, and glucose dysregulation, and the relevant underlying mechanisms that may be help to prevent and treat metabolic side effects caused by APD therapy. PMID:24011886
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
Kelleher, James P; Centorrino, Franca; Huxley, Nancy A; Bates, John A; Drake, Jennifer Kidwell; Egli, Samy; Baldessarini, Ross J
Most of typical and atypical neuroleptics belonging to various chemical groups produce a significant, dose-dependent increase in the brain tolerance to global ischemia. This activity of neuroleptics is related to their structure and exhibits no correlation with their antipsychotic properties. Therefore, the ability to increase the brain tolerance to global ischemia is an independent property of neuroleptics. The neuroprotective effect is also not correlated with their affinity to serotonin 5-HT2A and dopamine D2 receptors, but is closely related to the development of deep hypothermia. Thermoneutral conditions prevent both effects. Tolerant strategy plays the main role in the development of the neuroprotective effect of neuroleptics. PMID:16995432
Kulinski?, V I; Gavrilov, S S
Despite the significant burden of delirium among hospitalized adults, no pharmacologic intervention is approved for delirium treatment. Antipsychotic agents are the best studied but there are uncertainties as to how these agents can be optimally applied in everyday practice. We searched Medline and PubMed databases for publications from 1980 to April 2012 to identify studies of delirium treatment with antipsychotic agents. Studies of primary prevention using pharmacotherapy were not included. We identified 28 prospective studies that met our inclusion criteria, of which 15 were comparison studies (11 randomized), 2 of which were placebo-controlled. The quality of comparison studies was assessed using the Jadad scale. The DRS (N = 12) and DRS-R98 (N = 9) were the most commonly used instruments for measuring responsiveness. These studies suggest that around 75% of delirious patients who receive short-term treatment with low-dose antipsychotics experience clinical response. Response rates appear quite consistent across different patient groups and treatment settings. Studies do not suggest significant differences in efficacy for haloperidol versus atypical agents, but report higher rates of extrapyramidal side effects with haloperidol. Comorbid dementia may be associated with reduced response rates but this requires further study. The available evidence does not indicate major differences in response rates between clinical subtypes of delirium. The extent to which therapeutic effects can be explained by alleviation of specific symptoms (e.g. sleep or behavioral disturbances) versus a syndromal effect that encompasses both cognitive and noncognitive symptoms of delirium is not known. Future research needs to explore the relationship between therapeutic effects and changes in pathophysiological markers of delirium. Less than half of reports were rated as reasonable quality evidence on the Jadad scale, highlighting the need for future studies of better quality design, and in particular incorporating placebo-controlled work. PMID:23567421
Meagher, David J; McLoughlin, Lisa; Leonard, Maeve; Hannon, Noel; Dunne, Colum; O'Regan, Niamh
In the UK, nurse prescribing training is delivered within a Higher Education Institution (HEI). Although prescribing courses are regularly evaluated by individual HEIs and associated commissioning bodies, there has been little focus on the perspective of the lecturers who provide the training. The aim of this paper is to explore nurse lecturers' experiences of delivering nurse prescribing courses and their views on how well they prepare nurses for the prescribing role. Eight members of lecturing staff (7 female and 1 male) from four HEIs across the West Midlands participated in one-to-one, semi-structured interviews to discuss their experiences of prescribing training. Key issues to emerge were the selection criteria for acceptance onto prescribing courses; the diverse skills, experience and background of the nurses accepted; the addition of supplementary prescribing to independent prescribing courses, and the problems of providing pharmacology input into courses. Feedback from students and lecturers is vital to ensure the quality of training. The study recommends that selection criteria for prescribing training courses should receive further attention. Providing more material for potential students prior to their embarking on training would help applicants understand better what is involved and ultimately improve implementation of nurse prescribing in practice. PMID:16529849
Bradley, Eleanor; Blackshaw, Carole; Nolan, Peter
The purpose of this study is to evaluate the drug utilization trends and to describe the prevalence and type of medication-related prescribing errors in infants treated at primary care health centers in Bahrain. Prescriptions issued for infants were collected over a 2-week period in May 2004 from 20 health centers. Prescribing errors were classified as omission (minor and major), commission (incorrect information) and integration errors. Medications were classified according to the British National Formulary. In infants with a mean age of 6.5 months (+/-3.1) drugs per prescription were 2.52 (+/-1.1). Paracetamol and sodium chloride nasal drops were the topmost prescribed systemic and topical drugs, respectively. In 2282 prescriptions, 2066 (90.5%) were with omission (major), commission, and integration errors. In 54.1% of prescriptions with omission errors, length of therapy was not specified in 27.7%, and in 12.8% the dosage form was not stated. In 43.5% of prescriptions with errors of commission, dosing frequency (20.8%) and dose/strength (17.7%)-related errors were most common. Errors of integration such as potential drug-drug interaction comprised 2.4% of all prescribing errors. The proportion of drugs prescribed irrationally were: contraindicated medications, notably chlorpheniramine, promethazine, and corticosteroids (16.1%); medications prescribed on a p.r.n. basis (13.3%); missed information regarding strength of medications (2.8%); medications prescribed over extended periods (2.7%); low dosing frequency (2.6%); supratherapeutic doses (2.3%); excessive dosing frequency (0.8%). Irrational drug therapy in infants, with prescribing errors were apparent in primary care practice, which may be related to a lack of drug information, pharmacovigilance programme, and nonadherence to basic principles of prescribing. Establishing a national drug policy and pharmacovigilance programme for promoting rational drug use are to be considered. There is also a need to evaluate the effectiveness of interventions by measuring the outcomes. PMID:16930762
Al Khaja, Khalid A J; Al Ansari, Thuraya M; Damanhori, Awatif H H; Sequeira, Reginald P
Background: Enhanced functionality is a major goal in the treatment of schizophrenia. However, possible differences in the effectiveness of first- vs. second-generation antipsychotics or between depot/long-acting injectable (D/LAI) vs. D/LAI plus oral antipsychotics are not clear. Aims: This study was designed to evaluate possible differences between the effects of different antipsychotic treatment types or regimens on the functionality of patients with schizophrenia. Methods: 85 outpatients with schizophrenia, who were being treated with D/LAI antipsychotics- co-administered or not with oral antipsychotics-and had been adherent to the treatment during the previous year were evaluated. Socio-demographic, clinical, treatment-related, global severity and functionality variables were evaluated. Patients were grouped according to the type of antipsychotic drug (first- vs. second-generation) or according to the co-administration (or not) of oral antipsychotics. Results: No differences were found between first- and second-generation antipsychotics in terms of global functionality. Patients treated with LAI risperidone showed better global functionality and better performance in their habitual social activities and personal-social relationships than patients treated with risperidone plus oral second-generation antipsychotics. Better functionality was also found to be associated with higher education level, paranoid subtype of schizophrenia, harmful use of nicotine, adherence to oral treatment and absence of concomitant oral anticholinergic or psychopharmacological treatment. Conclusions: Our results suggest that D/LAI antipsychotic treatments should be administered in monotherapy whenever possible and that the treatment schedule should be simple, in order to achieve better functionality. PMID:23672274
Acosta, Francisco J; Chinea, Eugenio; Hernández, José L; Rodríguez, Fernando; García-Bello, Miguel; Medina, Gema; Nieves, Wilson
Background Several reports on patients with chronic schizophrenia suggest that atypical versus typical antipsychotics are expected to lead to better quality of life (QOL) and cognitive function. Our aim was to examine the association of chronic treatment with typical or atypical antipsychotics with cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms in long-hospitalized patients with schizophrenia. Methodology and Principal Findings The Hasegawa Dementia Scale-Revised (HDS-R), Brief Psychiatric Rating Scale (BPRS), the Schizophrenia Quality of Life Scale, translated into Japanese (JSQLS), and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) were used to evaluate cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms. We examined the correlation between the dose of antipsychotics and each measure derived from these psychometric tests. The student t-test was used to compare scores obtained from psychometric tests between patients receiving typical and atypical antipsychotics. Results showed significant correlations between chlorpromazine (CPZ)-equivalent doses of typical antipsychotics and atypical antipsychotics, and the total BPRS score and BPRS subscale scores for positive symptoms. CPZ-equivalent doses of typical antipsychotics were correlated with the JSQLS subscale score for dysfunction of psycho-social activity and DIEPSS score. Furthermore, the total BPRS scores, BPRS subscale score for positive symptoms, the JSQLS subscale score for dysfunction of psycho-social activity, and the DIEPSS score were significantly higher in patients receiving typical antipsychotics than atypical antipsychotics. Conclusion and Significance These findings suggest that long-term administration of typical antipsychotics has an unfavorable association with feelings of difficulties mixing in social situations in patients with chronic schizophrenia.
Fujimaki, Koichiro; Takahashi, Terumichi; Morinobu, Shigeru
White teeth have been an indicator of physical attractiveness throughout history. Only recently have we been able to whiten teeth with few side effects, making tooth bleaching a popular and effective dental treatment. The American Dental Association (ADA) has established guidelines on safety and effectiveness for tooth bleaching. External stains from aging or inherent dark color are more responsive to bleaching than internal stains. Dentist-prescribed home bleaching--including a careful dental exam, custom-fabricated trays, tacky high-viscosity gels, adequate instructions, and recall exams--has been shown to be an effective method for bleaching teeth. Trays can be worn overnight or during the day with similar effectiveness. The bleaching effect can last up to 3 years with more than 50% success. PMID:9918100
Dunn, J R
Introduction: To use Colorado's prescription drug monitoring program (PDMP) to describe the recent opioid prescription history of patients discharged from our emergency department (ED) with a prescription for opioid pain medications. Methods: Retrospective cohort study of 300 adult ED patients who received an opioid prescription. We abstracted prescription histories for the six months prior to the ED visit from the PDMP, and abstracted clinical and demographic variables from the chart. Results: There were 5,379 ED visits during the study month, 3,732 of which were discharged. Providers wrote 1,165 prescriptions for opioid analgesics to 1,124/3,732 (30%) of the patients. Median age was 36 years. Thirty-nine percent were male. Patients were 46% Caucasian, 26% African American, 22% Hispanic, 2% Asian and 4% other. These were similar to our overall ED population. There was substantial variability in the number of prescriptions, prescribers and total number of pills. A majority (205/296) of patients had zero or one prescription. The 90th percentile for number of prescriptions was seven, while the 10th percentile was zero. Patients in the highest decile tended to be older, with a higher proportion of Caucasians and females. Patients in the lowest decile resembled the general ED population. The most common diagnoses associated with opioid prescriptions were abdominal pain (11.5%), cold/flu symptoms (9.5%), back pain (5.4%), flank pain (5.0%) and motor vehicle crash (4.7%). Conclusion: Substantial variability exists in the opioid prescription histories of ED patients, but a majority received zero or one prescription in the preceding six months. The top decile of patients averaged more than two prescriptions per month over the six months prior to ED visit, written by more than 6 different prescribers. There was a trend toward these patients being older, Caucasian and female. PMID:23687544
Hoppe, Jason A; Houghland, John; Yaron, Michael; Heard, Kennon
Rationale Quetiapine, an atypical neuroleptic, has beneficial antipsychotic effects in schizophrenic patients, but with a lower incidence of extrapyramidal symptoms (EPS) compared with typical antipsychotics. While typical antipsychotics are often switched to atypical agents when adverse effects become limiting, there is little preclinical information to support this strategy, both in terms of efficacy and side effects. Objectives The antipsychotic effects
Miho Tada; Kiyoharu Shirakawa; Nobuya Matsuoka; Seitaro Mutoh
Importance of the field Antipsychotic drug is the mainstay of treatment for schizophrenia, and there are large inter-individual differences is clinical response and side effects. Pharmacogenetics provides a valuable tool to fulfill the promise of personalized medicine by tailoring treatment based on one's genetic markers. Areas covered in this review This article reviews the pharmacogenetic literature from early 1990s to 2010, focusing on two aspects of drug action: pharmacokinetics and pharmacodynamics. Genetic variants in the neurotransmitter receptors including dopamine and serotonin, and metabolic pathways of drugs including CYP2D6 and COMT, were discussed in association with clinical drug response and side effects. What the reader will gain Readers are expected to learn the up-to-date evidence in pharmacogenetic research, and to gain familiarity to the issues and challenges facing the field. Take home message Pharmacogenetic research of antipsychotic drugs is both promising and challenging. There is consistent evidence that some genetic variants can affect clinical response and side effects. However, more studies that are designed specifically to test pharmacogenetic hypotheses are clearly needed to advance the field.
Zhang, Jian-Ping; Malhotra, Anil K.
Placebo-controlled maintenance studies of conventional antipsychotic agents demonstrate a significant reduction in the risk of schizophrenic relapse in neuroleptic-treated patients. Neuroleptic discontinuation even in patients who remained in remission for as long as 5 years results in a relapse rate comparable to that seen for patients initially assigned to placebo. Yet, patients maintained on conventional neuroleptics are exposed to the risk of tardive dyskinesia (approximately 5% per year for patients with up to 10 years of neuroleptic exposure). Attempts have been made to reduce neuroleptic exposure. A lower maintenance dose was associated with higher relapse rates, as was intermittent, targeted therapy. Psychoeducational treatment studies reaffirmed that the major influence on the rate of rehospitalization was the dose of conventional maintenance medication. Although data are scarce for maintenance treatment with atypical antipsychotic drugs, findings suggest that atypical agents are at least as efficacious and may be better tolerated. Olanzapine has demonstrated efficacy in maintenance treatment as well as a reduced risk of tardive dyskinesia compared with haloperidol. PMID:9847048
Kinon, B J
The dopamine hypothesis of schizophrenia remains the primary theoretical framework for the pharmacological treatment of the disorder. Despite various lines of evidence of dopaminergic abnormalities and reasonable efficacy of current antipsychotic medication, a significant proportion of patients show suboptimal treatment responses, poor tolerability, and a subsequent lack of treatment concordance. In recent decades, intriguing evidence for the critical involvement of other neurotransmitter systems in the pathophysiology of schizophrenia has emerged, most notably of dysfunctions within the glutamate pathways. Consequently, the glutamate synapse has arisen as a promising target for urgently needed novel antipsychotic compounds—particularly in regards to debilitating negative and cognitive symptoms poorly controlled by currently available drugs. In this paper, recent findings integrating glutamatergic and dopaminergic abnormalities in schizophrenia and their implications for novel pharmacological targets are discussed. An overview of compounds in various stages of development is given: drugs enhancing NMDA receptor function as well as metabotropic glutamate receptor (mGluR) agonist and positive allosteric modulators (PAMs) are emphasised. Together with other agents more indirectly affecting glutamatergic neurotransmission, their potential future role in the pharmacotherapy of schizophrenia is critically evaluated.
Sendt, Kyra-Verena; Giaroli, Giovanni; Tracy, Derek K.
Antipsychotic drugs are limited in their efficacy by the relatively poor response of negative and cognitive symptoms of schizophrenia as well as by the substantial variability in response between patients. Pharmacogenetic studies have sought to identify the genetic factors that underlie the individual variability in response to treatment, with a past emphasis on dopamine and serotonin receptors as candidate genes. Few studies have separated effects on positive and negative symptoms, despite the established differences in response to drug treatment between these syndromes. Where this has been done most findings are consistent with the conclusion that dopamine receptor polymorphisms relate to positive symptom response, while negative symptom improvement is influenced by polymorphisms of genes involved in 5-HT neurotransmission. A wide range of polymorphisms in other candidate genes have been investigated, with some positive findings in those genes associated with glutamatergic transmission and/or risk factors for schizophrenia. However, there remains a lack of good replicated findings; furthermore there is little evidence to support drug-specific genetic associations with treatment response. While most past studies focused on single candidate genes, technology now permits genome-wide association studies with response to antipsychotics. Although not without major limitations, these "hypothesis-free" approaches are beginning to identify further important risk factors for treatment response. Again there is little consistency between various studies, although some of the polymorphisms identified are in genes involved in neurodevelopment, which is increasingly being recognized as important in the pathophysiology of schizophrenia.
The molecular mechanism of action of antipsychotic drugs is not well understood. Their complex receptor affinity profiles indicate that their action could extend beyond dopamine receptor blockade. Single gene expression studies and high-throughput gene profiling have shown the induction of genes from several molecular classes and functional categories. Using a focused microarray approach we investigated gene regulation in rat striatum, frontal cortex and hippocampus after chronic administration of haloperidol or olanzapine. Regulated genes were validated by in-situ hybridization, realtime PCR and immunohistochemistry. Only limited overlap was observed in genes regulated by haloperidol and olanzapine. Both drugs elicited maximal gene regulation in the striatum and least in the hippocampus. Striatal gene induction by haloperidol was predominantly in neurotransmitter signaling, G-protein coupled receptors and transcription factors. Olanzapine prominently induced retinoic acid and trophic factor signaling genes in the frontal cortex. The data also revealed the induction of several genes that could be targeted in future drug development efforts. The study uncovered the induction of several novel genes, including somatostatin receptors and metabotropic glutamate receptors. The results demonstrating the regulation of multiple receptors and transcription factors suggests that both typical and atypical antipsychotics could possess a complex molecular mechanism of action.
Girgenti, Matthew James; Nisenbaum, Laura K.; Bymaster, Franklin; Terwilliger, Rosemarie; Duman, Ronald S; Newton, Samuel Sathyanesan
Background Nonadherence with antipsychotic medication is an important clinical and economic problem in the treatment of schizophrenia. This study identified treatment patterns and clinical characteristics that immediately precede the initiation of depot typical antipsychotics in the usual treatment of schizophrenia patients with a recent history of nonadherence with oral antipsychotic regimens. Methods Data were drawn from a large, multisite, 3-year prospective noninterventional observational study of persons treated for schizophrenia in the United States, which was conducted between 7/1997 and 9/2003. The analytical sample included patients who, in the 6 months prior to enrollment, were considered nonadherent with oral antipsychotics and were not treated with depot antipsychotics (N = 314). Patients who were subsequently initiated on typical depots during the 3-year follow-up were compared with patients who continued therapy with only oral antipsychotic agents. Group comparisons were made on patient baseline characteristics and precedent variables that were assessed 1 to 6 months prior to depot initiation. Patient assessments were made at predetermined intervals throughout the 3-year study using standard psychiatric measures, a patient-reported questionnaire, and medical record information. Results A small proportion of patients (12.4%) who were recently nonadherent with oral antipsychotics were subsequently initiated on depot therapy during the 3-year study. Compared to patients treated with only oral antipsychotics, those subsequently initiated on a depot were significantly more likely to be hospitalized at depot initiation or the previous 30 days, to have recent involvement with the criminal justice system (arrests), recent illicit drug use, recent switching or augmentation of oral antipsychotics, and recent treatment with oral typical antipsychotics. Conclusion Despite prior nonadherence with oral antipsychotic medication, only a small proportion of nonadherent schizophrenia patients were initiated on depot antipsychotics in this 3-year prospective study. Patients subsequently initiated on depot had a more severe treatment pattern and clinical profile immediately preceding depot initiation. This profile may have triggered the decision to initiate a depot. Findings have important clinical and economic ramifications for practitioners, policy makers, and other decision makers, highlighting the need for early identification of and tailored therapeutics for schizophrenia patients with a history of nonadherence with their recent oral antipsychotic regimens.
Ascher-Svanum, Haya; Peng, Xiaomei; Faries, Douglas; Montgomery, William; Haddad, Peter M
Polyunsaturated fatty acids (PUFA), a lipid family comprised of omega-3 (n-3) and n-6 fatty acids, are a critical component of cellular membranes, and recent in vitro studies have found that antipsychotic medications up-regulate genes responsible for PUFA biosynthesis. To evaluate this effect in vivo, rats were treated with risperidone (1.5, 3, 6 mg/kg/d), paliperidone (1.5, 3, 6 mg/kg/d), olanzapine (2.5, 5, 10 mg/kg/d), quetiapine (5, 10, 20 mg/kg/d), haloperidol (1, 3 mg/kg/d) or vehicle through their drinking water for 40 d. Effects on liver Fads1, Fads2, Elovl2, and Elovl5 mRNA expression, plasma indices of n-3 (plasma 22:6/18:3 & 20:5/18:3 ratios) and n-6 (plasma 20:4/18:2 & 20:3/18:2 ratios) biosynthesis, and peripheral (erythrocyte, heart) and central (frontal cortex) membrane PUFA composition were determined. Only risperidone and its metabolite paliperidone significantly and selectively up-regulated liver delta-6 desaturase (Fads2) mRNA expression, and robustly increased plasma indices of n-3 and n-6 fatty acid biosynthesis. In risperidone- and paliperidone-treated rats, plasma indices of n-3 and n-6 fatty acid biosynthesis were all positively correlated with liver Fads2 mRNA expression, but not Fads1, Elovl2, or Elovl5 mRNA expression. All antipsychotics at specific doses increased erythrocyte docosahexaenoic acid (DHA, 22:6n-3) composition, and all except quetiapine increased arachidonic acid (AA, 20:4n-6) composition. Risperidone, paliperidone, and olanzapine increased heart DHA and AA composition, and no antipsychotic altered frontal cortex DHA or AA composition. These in vivo data demonstrate that augmentation of PUFA biosynthesis is not common to all antipsychotic medications, and that risperidone and paliperidone uniquely increase delta-6 desaturase (Fads2) mRNA expression and most robustly increase PUFA biosynthesis and peripheral membrane composition.
McNamara, Robert K.; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Cole-Strauss, Allyson; Lipton, Jack W.
Polyunsaturated fatty acids (PUFA), a lipid family comprised of omega-3 (n-3) and n-6 fatty acids, are a critical component of cellular membranes, and recent in vitro studies have found that antipsychotic medications up-regulate genes responsible for PUFA biosynthesis. To evaluate this effect in vivo, rats were treated with risperidone (1.5, 3, 6mg/kg/day), paliperidone (1.5, 3, 6mg/kg/day), olanzapine (2.5, 5, 10mg/kg/day), quetiapine (5, 10, 20mg/kg/day), haloperidol (1, 3mg/kg/day) or vehicle through their drinking water for 40day. Effects on liver Fads1, Fads2, Elovl2, and Elovl5 mRNA expression, plasma indices of n-3 (plasma 22:6/18:3 and 20:5/18:3 ratios) and n-6 (plasma 20:4/18:2 and 20:3/18:2 ratios) biosynthesis, and peripheral (erythrocyte, heart) and central (frontal cortex) membrane PUFA composition were determined. Only risperidone and its metabolite paliperidone significantly and selectively up-regulated liver delta-6 desaturase (Fads2) mRNA expression, and robustly increased plasma indices of n-3 and n-6 fatty acid biosynthesis. In risperidone- and paliperidone-treated rats, plasma indices of n-3 and n-6 fatty acid biosynthesis were all positively correlated with liver Fads2 mRNA expression, but not Fads1, Elovl2, or Elovl5 mRNA expression. All antipsychotics at specific doses increased erythrocyte docosahexaenoic acid (DHA, 22:6n-3) composition, and all except quetiapine increased arachidonic acid (AA, 20:4n-6) composition. Risperidone, paliperidone, and olanzapine increased heart DHA and AA composition, and no antipsychotic altered frontal cortex DHA or AA composition. These in vivo data demonstrate that augmentation of PUFA biosynthesis is not common to all antipsychotic medications, and that risperidone and paliperidone uniquely increase delta-6 desaturase (Fads2) mRNA expression and most robustly increase PUFA biosynthesis and peripheral membrane composition. PMID:21458237
McNamara, Robert K; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Cole-Strauss, Allyson; Lipton, Jack W
Objective To examine trends in osteoporosis drug prescribing after hip fracture from 1995 to 2004. Methods We conducted a population-based study of enrollees in the Pennsylvania Pharmaceutical Assistance Contract for the Elderly. Hip fractures were identified using Medicare hospital claims between January 1, 1995, and June 30, 2004. Osteoporosis treatment comprised oral bisphosphonates, calcitonin, hormone therapy, raloxifene, and/or teriparatide. Kaplan-Meier methods were used to estimate the probability of treatment within 6 months of fracture, censoring patients on their date of death or 6 months postfracture. Results Treatment within 6 months after hip fracture improved from 7% in 1995 to 31% in 2002, and then remained stable through 2004. Similar patterns were observed among new users, with treatment increasing from 4% in 1995 to 17% in 2002, with no subsequent increase through 2004. Bisphosphonates led other treatments in the frequency of prescribing, except during 1997–99, when calcitonin was the most common. Among women, hormone therapy prescribing decreased from 22% of those treated in 1995 to 4% in 2004, and raloxifene prescribing remained relatively constant (4%–10%) since its introduction (p for trend = 0.15). Of patients treated before and after hip fracture, 18% changed therapy postfracture. Significantly more patients changed therapy following fracture if a different physician prescribed treatment (26%) compared to those treated by the same physician pre- and postfracture (13%; p < 0.0001). Conclusion Prescribing practices changed substantially over the 10 years of study. The proportion of hip fracture patients treated with osteoporosis drugs has increased, but remains low, with fewer than one-third receiving pharmacotherapy.
Cadarette, Suzanne M.; Katz, Jeffrey N.; Brookhart, M. Alan; Levin, Raisa; Stedman, Margaret R.; Choudhry, Niteesh K.; Solomon, Daniel H.
Background Guidelines and performance measures recommend avoiding antibiotics for acute cough/acute bronchitis and presume visits are straightforward with simple diagnostic decision-making. We evaluated clinician-assigned diagnoses, diagnostic uncertainty, and antibiotic prescribing for acute cough visits in primary care. Methods We conducted a retrospective analysis of acute cough visits – cough lasting ?21 days in adults 18–64 years old without chronic lung disease – in a primary care practice from March 2011 through June 2012. Results Of 56,301 visits, 962 (2%) were for acute cough. Clinicians diagnosed patients with 1, 2, or???3 cough-related diagnoses in 54%, 35%, and 11% of visits, respectively. The most common principal diagnoses were upper respiratory infection (46%), sinusitis (10%), acute bronchitis (9%), and pneumonia (8%). Clinicians prescribed antibiotics in 22% of all visits: 65% of visits with antibiotic-appropriate diagnoses and 4% of visits with non-antibiotic-appropriate diagnoses. Clinicians expressed diagnostic uncertainty in 16% of all visits: 43% of visits with antibiotic-appropriate diagnoses and 5% of visits with non-antibiotic-appropriate diagnoses. Clinicians expressed uncertainty more often when prescribing antibiotics than when not prescribing antibiotics (30% vs. 12%; p?0.001). As the number of visit diagnoses increased from 1 to 2 to???3, clinicians were more likely to express diagnostic uncertainty (5%, 25%, 40%, respectively; p?0.001) and prescribe antibiotics (16%, 25%, 41%, respectively; p?0.001). Conclusions Acute cough may be more complex and have more diagnostic uncertainty than guidelines and performance measures presume. Efforts to reduce antibiotic prescribing for acute cough should address diagnostic complexity and uncertainty that clinicians face.
In this issue, Reidenberg and Willis(1) highlight the legal dangers associated with prescribing opioids for patients when federal or state governments believe that such prescribing is outside the "usual course of medical practice." This article expands on the themes identified by the authors and addresses the problems faced by both prescribers and patients when "Big Brother" enters the treatment room and looks over the physician's shoulder. PMID:17505492
Benjamin, D M
Objective To investigate whether clinical audit can improve general dental practitioners' prescribing of antibiotics.Design An intervention study carried out in general dental practice in the North West of England.Method Information was collected over an initial six-week period from 175 general dental practitioners on their current antibiotic prescribing practices. The information collected was the antibiotic prescribed including dose, frequency and duration,
Background: prescribing in nursing homes is frequently suboptimal. Indicators to measure prescribing quality, including appropriateness of prescribing certain drugs or combinations of drugs, to hospital inpatients have been developed previously. Objective: to modify prescribing indicators, including appropriateness of prescribing algorithms developed in the hospital setting, for use in nursing homes. Design: an audit of prescribing to patients resident in a
C. Alice Oborne; R ICHARD HOOPER; C AMERON G. SWIFT; H. D. JACKSON
Background: Scrutiny over pharmaceutical expenditure is increasing leading to multiple reforms. This includes Austria with measures to lower generic prices and enhance their utilization. However the situation for newer antidepressants and atypical antipsychotic medicines (AAPs) is different to PPIs, statins, and renin-angiotensin inhibitor drugs with greater tailoring of therapy and no wish to switch products in stable patients. Authorities welcome generics though given the high costs particularly of single-sourced AAPs. Objective: Assess (a) changes in utilization of venlafaxine versus other newer antidepressants before and after availability of generics, (b) utilization of generic versus originator venlafaxine, (c) price reductions of venlafaxine over time and their influence on total expenditure, (d) utilization of risperidone versus other AAPs, (e) suggest potential additional reforms that could be introduced if pertinent to further enhance the use of generics. Methodology: A quasi-experimental study design with a segmented time series and an observational study. Utilization measured in defined daily doses (DDDs) and total expenditure per DDD and over time. Results: No appreciable changes in the utilization of venlafaxine and risperidone after generics. The reduction in expenditure/DDD for venlafaxine decreased overall expenditure on newer antidepressants by 5% by the end of the study versus just before generics despite a 37% increase in utilization. Expenditure will further decrease if reduced prescribing of duloxetine. Conclusion: Depression, schizophrenia, and bipolar diseases are complex diseases. As a result, specific measures are needed to encourage the prescribing of generic risperidone and venlafaxine when multiple choices are appropriate. Authorities cannot rely on a "Hawthorne" effect between classes to enhance the use of generics. Measures may include prescribing restrictions for duloxetine. No specific measures planned for AAPs with more multiple-sourced AAPs becoming available. PMID:23308071
Godman, Brian; Bucsics, Anna; Burkhardt, Thomas; Piessnegger, Jutta; Schmitzer, Manuela; Barbui, Corrado; Raschi, Emanuel; Bennie, Marion; Gustafsson, Lars L
Summary Background Effectiveness of antipsychotics in treating emotional and cognitive deficits in schizophrenia still remains controversial. The aim of our study was to assess emotional and cognitive functioning in schizophrenic inpatients currently treated with typical antipsychotics (perphenazine, perazine, fluphenazine, and haloperidol) and in another group of schizophrenic inpatients currently on atypical antipsychotics (olanzapine, risperidone, amisulpride, and quetiapine). Material/Methods One hundred patients with DSM-IV schizophrenia or schizoaffective disorders (39 treated using typical antipsychotics and 61 treated with atypical antipsychotics) under naturalistic treatment conditions, and 50 healthy controls were given the following: Test of Everyday Attention, Facial Emotion Recognition Test, Facial Memory Recognition Test, and “Reading the mind in the eyes” Test. Results Patients with a diagnosis of schizophrenia revealed the following deficits: facial emotion perception, empathy/theory of mind, visual selective attention/speed, attentional switching, and auditory-verbal working memory. Our results show a significant difference between schizophrenic and healthy controls in all tasks, with schizophrenic patients performing worse than controls. Interestingly, our patients on atypical neuroleptics performed similarly compared to schizophrenic patients treated with conventional neuroleptics on all tasks provided. There were some significant relationships between emotional and cognitive deficits and clinical variables. Conclusions Our findings remain consistent with other recent studies in which atypical antipsychotics did not show a clear advantage over typical antipsychotics on both emotional and cognitive functioning.
Kucharska-Pietura, Katarzyna; Tylec, Aneta; Czernikiewicz, Andrzej; Mortimer, Ann
The present study was carried out to establish whether the Defined Daily Doses (DDDs) system could be reliably applied to standardize antipsychotic dosages. Initially, the relationship between antipsychotic doses expressed as DDDs, chlorpromazine equivalents (CPZEs) and percentages of the British National Formulary (BNF) maximum recommended daily dose were investigated by calculating Spearman's rank correlation coefficients. Second, factors associated with antipsychotic dose, expressed as DDDs, CPZEs and percentages of the BNF maximum recommended daily dose, were investigated by means of linear regression analysis. The study sample consisted of 277 patients with schizophrenia. The relationship between antipsychotic daily doses expressed as multiples of DDDs and CPZEs revealed a significant correlation (Spearman's rho=0.779, P<0.001). Similarly, the relationship between antipsychotic daily doses expressed as multiples of DDDs and percentages of the BNF maximum recommended daily dose revealed a significant correlation (Spearman's rho=0.869, P<0.001). Linear regression analyses highlighted a high degree of coherence between antipsychotic doses expressed as DDDs, CPZEs and percentages of the BNF maximum recommended daily dose. In conclusion, this study found that the DDD system is a reliable tool for standardizing antipsychotic doses in drug utilization research. PMID:18703938
Nosè, Michela; Tansella, Michele; Thornicroft, Graham; Schene, Aart; Becker, Thomas; Veronese, Antonio; Leese, Morven; Koeter, Maarten; Angermeyer, Matthias; Barbui, Corrado
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.
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; Glenth?j, Birte; Schubart, Chris D.; Cahn, Wiepke; Kahn, Rene S.; Horvath, Steve; Ophoff, Roel A.
Context: Understanding the association between use of antipsychotics and onset of diabetes. Objective: To compare the rates of new-onset diabetes mellitus (DM) between patients treated for schizophrenia with atypical or conventional antipsychotics. Design: Retrospective analysis of medical and pharmacy claims data. Setting: 61 US health plans. Patients: Patients with schizophrenia who were treated with atypical or conventional antipsychotics between September 1996 and June 2001 and were enrolled for 12 or more months before and 3 or more months after therapy initiation. Main Outcome Measures: New-onset DM was defined based on 2 or more claims with a diabetes diagnosis or initiation of antidiabetic therapy during follow-up. Rates of DM were compared between patients receiving atypical and conventional antipsychotics, and among 4 subgroups of patients receiving atypical antipsychotics (olanzapine, clozapine, risperidone, quetiapine). Statistical analyses employed logistic regression and Cox proportional hazards models. Results: Patients treated with atypical antipsychotics (N = 1826) were younger, had a lower rate of diagnosed hypertension, and longer duration of therapy than those receiving conventional antipsychotics (N = 617). The crude incidence of DM did not differ (2.46% vs 2.76% for atypical antipsychotics and conventional antipsychotics, P = .525). In Cox proportional hazards models, patients treated with atypical antipsychotics had a statistically significant, moderately increased risk of DM relative to conventional antipsychotics (hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.06, 1.30); no significant differences in risk were observed when atypical antipsychotic cohorts were compared. In logistic regression models, no significant differences in DM risk were observed. Conclusions: Patients with schizophrenia treated with atypical antipsychotics had a moderately increased risk of DM relative to those treated with conventional antipsychotics, as measured by Cox proportional hazards models; such risk was not significantly different among patients treated with individual atypical medications.
Ollendorf, Daniel A; Joyce, Amie T; Rucker, Malcolm
Background Psychiatric patients often require chronic treatment with antipsychotic drugs, and while rats are frequently used to study antipsychotic-induced metabolic adverse effects, long-term exposure has only partially mimicked the appetite-stimulating and weight-inducing effects found in the clinical setting. Antipsychotic-induced effects on serum lipids are also inconsistent in rats, but in a recent study we demonstrated that subchronic treatment with the orexigenic antipsychotic olanzapine resulted in weight-independent increase in serum triglycerides and activation of lipogenic gene expression in female rats. In addition, a recent long-term study in male rats showed that chronic treatment with antipsychotic drugs induced dyslipidemic effects, despite the lack of weight gain. Aims In the current study, we sought to examine long-term effects of antipsychotic drugs on weight gain, lipid levels and lipid composition after twice-daily administration of antipsychotics to female rats, and to investigate potential beneficial effects of the lipid-lowering agent tetradecylthioacetic acid (TTA), a modified fatty acid. Methods Female rats were exposed to orexigenic antipsychotics (olanzapine or clozapine), metabolically neutral antipsychotics (aripiprazole or ziprasidone), or TTA for 8 weeks. Separate groups received a combination of clozapine and TTA or olanzapine and TTA. The effects of TTA and the combination of olanzapine and TTA after 2 weeks were also investigated. Results The antipsychotic-induced weight gain and serum triglyceride increase observed in the subchronic setting was not present after 8 weeks of treatment with antipsychotics, while lipid-lowering effect of TTA was much more pronounced in the chronic than in the subchronic setting, with concomitant upregulation of key oxidative enzymes in the liver. Unexpectedly, TTA potentiated weight gain in rats treated with antipsychotics. Conclusion TTA is a promising candidate for prophylactic treatment of antipsychotic-induced dyslipidemic effects, but a more valid long-term rat model for antipsychotic-induced metabolic adverse effects is required.
Skrede, Silje; Fern?, Johan; Bj?rndal, Bodil; Brede, Wenche R?dseth; Bohov, Pavol; Berge, Rolf Kristian; Steen, Vidar Martin
Aims Previous studies of the prescription patterns of psychotropic medications in patients with schizophrenia have highlighted a high rate of antipsychotic polypharmacy, but data in Asia are sparse. This study seeks to examine the prevalence of antipsychotic polypharmacy in patients with schizophrenia and compare the differences between patients receiving one vs. those receiving more than one antipsychotic. Methods Antipsychotic prescription for a sample of 2399 patients with schizophrenia from six countries and territories was evaluated. Daily doses of antipsychotic medications were converted to standard chlorpromazine equivalents (CPZ). Results Antipsychotic polypharmacy was found in 45.7% (n = 1097) of the patients with wide intercountry variations. Polypharmacy was associated with male gender [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.06, 1.46, P < 0.01], advanced age (t = ?7.81, d.f. = 2396, P < 0.001), psychiatric hospital setting (OR 1.34, 95% CI 1.11, 1.62) as well as higher daily CPZeq doses (411.47 vs. 983.10 CPZeq day?1, z = ?25.94, P < 0.001), anticholinergic use (OR 3.17, 95% CI 2.65, 3.79, P < 0.001) and less use of an atypical antipsychotic drug (OR 0.83, 95% CI 0.71, 0.98, P < 0.05). On multivariate analysis, country, age and duration of illness were significantly associated with antipsychotic polypharmacy. Conclusion This study highlighted the wide intercountry variations of antipsychotic polypharmacy which are likely to be influenced by a complex combination of clinical, setting, cultural and personal practice factors, requiring more research.
Sim, Kang; Su, Alex; Fujii, Senta; Yang, Shu-yu; Chong, Mian-Yoon; Ungvari, Gabor S; Si, Tianmei; Chung, Eun K; Tsang, Hin-Yeung; Chan, Yiong H; Heckers, Stephan; Shinfuku, Naotaka; Tan, Chay H