Objectives: Non evidence-based prescribing of antipsychotics is common in the UK and internationally with high doses and polypharmacy the norm. These practices often remain even after systematic attempts are made to change. We aimed to establish which factors are linked to antipsychotic prescribing quality so we can identify and target patients for interventions to improve quality and allow us to understand further the drivers of non evidence-based prescribing. Objectives: A cross-sectional survey with a collection of factors potentially affecting antipsychotic prescribing quality outcomes was carried out in eight secondary care units in England. Participants were inpatients prescribed regular antipsychotics on the day of the survey. Antipsychotic dose, polypharmacy, type and route were the main outcome measures. Objectives: Data were collected for 1198 patients. Higher total dose was associated with greater weight, higher number of previous admissions, longer length of admission, noncompliance with medication and use of an atypical antipsychotic. A lower total dose was associated with clozapine use. Polypharmacy was associated with not being a patient at the South London and Maudsley NHS Trust centre, the subject having a forensic history, a greater number of previous admissions and higher total dose. Younger age, not being detained under a Mental Health Act section, atypical antipsychotic use and oral route were predictors of antipsychotic monotherapy. Atypical antipsychotic use was associated with oral route, higher total dose, being administered only one antipsychotic, having had fewer previous antipsychotics and no anticholinergic use. Use of the oral route was associated with not being sectioned under the Mental Health Act, atypical antipsychotic use, younger age, non-schizophrenia diagnosis, fewer previous admissions and a lower total dose. Objectives: In patients with chronic illness who are detained, heavier, noncompliant, not taking clozapine and on a depot antipsychotic, prescribers use larger doses and antipsychotic polypharmacy. We found that use of percentage of licensed maximum doses favours typical antipsychotics arbitrarily, and that high doses and polypharmacy are inextricably linked. PMID:25489476
Background: High dose antipsychotic prescribing is common in psychiatric care, despite a lack of its benefit from research evidence. While several studies have explored the prevalence and factors associated with high dose antipsychotic prescribing, no such report has emanated from a developing country like Nigeria. Aim: The aims of this study were to determine the prevalence of high dose prescribing among in-patients at a tertiary psychiatric hospital and to determine the pattern of antipsychotic drugs prescribed. Materials and Methods: An audit of in-patients at a regional tertiary psychiatric facility was carried out. We examined case notes and conducted oral interviews where necessary, on all patients receiving antipsychotics using a proforma designed for the study. Results: The prevalence of high dose prescribing was 38% (65/171) using a prescribed daily dose/defined daily dose ratio of 1.5. The rate of antipsychotic polypharmacy was 7% (12/171). The atypical antipsychotic, olanzapine was the most commonly prescribed antipsychotic in monotherapy. Predictors of high dose prescribing were diagnoses (P = 0.04), polypharmacy (P = 0.04), a history of previous in-patient care (P = 0.02), and use of anticholinergic drugs (P = 0.01). Conclusions: High dose prescribing was common among in-patients audited. Further studies are needed to examine factors that promote “high dose” prescribing. PMID:23634332
Adesola, AO; Anozie, IG; Erohubie, P; James, BO
Objective To examine the recorded indication for antipsychotic prescriptions in UK primary care. Design Cohort study. Setting Primary care. Participants Individuals prescribed antipsychotics between 2007 and 2011. Measures The proportion of individuals prescribed antipsychotics with a diagnosis of (1) psychosis and bipolar disorder, (2) other diagnoses including depression, anxiety and dementia and (3) none of these diagnoses. Results We identified 47?724 individuals prescribed antipsychotic agents. 13?941 received first-generation agents and 27?966 received second-generation agents. The rates of prescribing were higher in females (incidence rate ratio (IRR) 1.092 (95% CI 1.088 to 1.095), older people (80+ vs 40–49; IRR 2.234 (2.222 to 2.246)) and in those from the most deprived areas (most deprived vs least deprived IRR 3.487 (3.567 to 3.606). Of those receiving first-generation antipsychotics, less than 50% had a diagnosis of psychosis/bipolar disorder. For the second-generation agents, the numbers ranged from 4824 (36%) for quetiapine to 7094 (62%) for olanzapine. In patients without psychosis/bipolar disorder, common diagnoses included anxiety, depression, dementia, sleep and personality disorders. For example, in risperidone users, 14% had an anxiety code, 22% depression, 12% dementia, 11% sleep disorder and 4% personality disorder. The median daily doses and duration of treatment were greater in those with schizophrenia (eg, risperidone median daily dose 4?mg; IQR 2–6: median duration 1.2?years) than in those with non-psychotic/bipolar disorders such as depression or anxiety (eg, risperidone 1?mg; IQR 1–2: 0.6?years). A relatively large proportion (between 6% and 17%) of people receiving individual antipsychotics had none of the diagnoses stated above. Conclusions In UK primary care, a large proportion of people prescribed antipsychotics have no record of psychotic or bipolar disorder. They are often older people with conditions including dementia, non-psychotic depression, anxiety and sleep disorders. PMID:25524544
Marston, Louise; Nazareth, Irwin; Petersen, Irene; Walters, Kate; Osborn, David P J
Objective Evidence on antipsychotic comparative effectiveness, regulatory warnings, and formulary and other restrictions on antipsychotics may have influenced physician prescribing behavior. This study measured changes in the degree to which physicians customize treatment choices to individual patients and changes in physician preferences for specific agents following these events. Methods The study used 2002-2007 data from IMS Health Xponent™ and the AMA on the prescribing and characteristics of a longitudinal cohort of 7,399 physicians. Descriptive and multivariable regression analyses of the concentration of prescribing (physician-level Herfindahl index), and preferences for and likelihood of prescribing 2 first-generation antipsychotics and 6 second-generation antipsychotics adjusting for prescribing volume, specialty, demographics, practice setting and education were conducted. Results Antipsychotic prescribing was highly concentrated at the physician-level, with a mean unadjusted Herfindahl index of .33 in 2002 and .29 in 2007. Psychiatrists reduced the concentration of their prescribing more over time than did other physicians. High volume psychiatrists had a Herfindahl that was half that of low-volume physicians in other specialties (.18 vs. .36), a difference that remained significant (p<.001) after adjusting for physician characteristics. The share of physicians preferring olanzapine dropped from 29.9% in 2002 to 10.3% in 2007 (p<.001) while the share favoring quetiapine increased (from 9.4% to 44.5%, p<.001). Few physicians (<5%) preferred a first-generation antipsychotic in 2002 or 2007. Conclusions Preferences for specific antipsychotics changed dramatically during this period. While physician prescribing remained heavily concentrated, it did decrease over time, particularly among psychiatrists. PMID:24337224
Donohue, Julie; O'Malley, A. James; Horvitz-Lennon, Marcela; Taub, Anna Levine; Berndt, Ernest; Huskamp, Haiden
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. PMID:23006528
We characterized prescribing in Connecticut’s State public mental health system to assess the feasibility of implementing an evidence-based medication algorithm. Medication records for a random sample of outpatients with diagnoses of schizophrenia spectrum disorders showed prescribing patterns similar to the entire United States. The base rate of changing antipsychotic medications was moderate. Over half of patients received decanoate medications, polypharmacy
Nancy H. Covell; Carlos T. Jackson; Arthur C. Evans; Susan M. Essock
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. PMID:23890157
Although much attention has been placed on appropriate symptom management at the end of life, little is known about the medications actually prescribed to people in hospice care. The purpose of this study was to determine the most commonly prescribed medications in a population of hospice patients. A retrospective review of a patient information database was conducted. The 6 most common drugs (acetaminophen, morphine, haloperidol, lorazepam, prochlorperazine, and atropine) were included in emergency kits provided to patients at admission. Opioid and nonopioid analgesics, anxiolytics, anticholinergics, and antipsychotics were the most commonly prescribed pharmacologic classes. This description of prescribing practices could be useful in creating more informed care plans, educating health care personnel, and anticipating the changing medication needs of patients as they enter hospice care. PMID:23408370
Sera, Leah; McPherson, Mary Lynn; Holmes, Holly M
Although much attention has been placed on appropriate symptom management at the end of life, little is known about the medications actually prescribed to people in hospice care. The purpose of this study was to determine the most commonly prescribed medications in a population of hospice patients. A retrospective review of a patient information database was conducted. The 6 most common drugs (acetaminophen, morphine, haloperidol, lorazepam, prochlorperazine, and atropine) were included in emergency kits provided to patients at admission. Opioid and nonopioid analgesics, anxiolytics, anticholinergics, and antipsychotics were the most commonly prescribed pharmacologic classes. This description of prescribing practices could be useful in creating more informed care plans, educating health care personnel, and anticipating the changing medication needs of patients as they enter hospice care. PMID:23408370
Sera, Leah; McPherson, Mary Lynn; Holmes, Holly M.
Objectives. To explore the lived experience of youth, caregivers, and prescribers with antipsychotic medications. Design. We conducted a qualitative interpretive phenomenology study. Youth aged 11 to 25 with recent experience taking antipsychotics, the caregivers of youth taking antipsychotics, and the prescribers of antipsychotics were recruited. Subjects. Eighteen youth, 10 caregivers (parents), and 11 prescribers participated. Results. Eleven of 18 youth, six of ten parents, and all prescribers discussed antipsychotic-related weight gain. Participants were attuned to the numeric weight changes usually measured in pounds. Significant discussions occurred around weight changes in the context of body image, adherence and persistence, managing weight increases, and metabolic effects. These concepts were often inextricably linked but maintained the significance as separate issues. Participants discussed tradeoffs regarding the perceived benefits and risks of weight gain, often with uncertainty and inadequate information regarding the short- and long-term consequences. Conclusion. Antipsychotic-related weight gain in youth influences body image and weight management strategies and impacts treatment courses with respect to adherence and persistence. In our study, the experience of monitoring for weight and metabolic changes was primarily reactive in nature. Participants expressed ambiguity regarding the short- and long-term consequences of weight and metabolic changes. PMID:24533223
Murphy, Andrea Lynn; Gardner, David Martin; Cooke, Charmaine; Kutcher, Stanley Paul; Hughes, Jean
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
Aims To examine the effect of licence change for thioridazine at the end of 2000 on the prescription of antipsychotic drugs in England and Scotland, and investigate changes in poisons information inquiries and, for Edinburgh, poisons admissions. Methods Prescription data for antipsychotic drugs were obtained for England and Scotland and quarterly trends examined for 2000 and 2001. Accesses to the UK National Poisons Information Service website TOXBASE for antipsychotic products were examined for the same period. For Scotland telephone enquiry data, and admission data to the Edinburgh Poisons Unit were also evaluated. Trends in poisonings were compared with prescribing change. Results In England prescriptions for thioridazine fell rapidly in 2001 from approximately 35% of market share to less than 5%, and were replaced by risperidone, chlorpromazine and olanzapine. TOXBASE accesses fell from 39.3% of antipsychotics to 4.4%. Accesses for chlorpromazine, olanzapine and risperidone increased. In Scotland prescribing of thioridazine was similar to changes in England, but it was principally replaced by chlorpromazine. These changes were mirrored by TOXBASE accesses, telephone enquiries and in-patient admissions. The ratio of TOXBASE accesses for thioridazine to prescription numbers for the drug increased after the licence change. Conclusions Licence change produced rapid change in prescribing behaviour within 3 months. Prescribing behaviour in England and Scotland was different. Changes in prescribing were mirrored by changes in accesses for poisons information in both England and Scotland, and in Edinburgh by hospital admissions. The increase in the ratio of TOXBASE accesses to prescriptions for thioridazine suggests doctors may have become more aware of its potential toxicity. PMID:12814455
Bateman, D N; Good, A M; Afshari, R; Kelly, C A
Aims and methods It is now well established that antipsychotic medications are associated with adverse effects such as metabolic dysfunction, hyperprolactinaemia and cardiac arrhythmias. We completed an audit cycle between 2008 and 2010 to assess whether the implementation of a high-visibility prompt and an educational programme would improve monitoring rates among patients prescribed regular antipsychotics admitted to a 59-bedded psychiatric hospital in West Sussex. Results There was an improvement in monitoring rates for most audit standards. The greatest improvement was seen in measurement of random plasma glucose and cholesterol levels. Rates improved irrespective of the risk of metabolic dysfunction. However, prolactin measurement remained static and the ECG recording deteriorated. Clinical implications There appears to be a growing awareness of the need to screen for metabolic dysfunction among patients prescribed regular antipsychotic medication. A high-visibility prompt and educational programme helps to increase monitoring rates. However, more needs to be done to improve the mortality and morbidity rates among this patient subpopulation. PMID:24381652
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. PMID:23391323
Background: There is no conclusive evidence that either high doses or combinations of antipsychotics are more effective than standard doses or monotherapy alone. Nonetheless, prescription of both remains prevalent in the UK. In 2006 the South London and Maudsley NHS Foundation Trust (SLAM) participated in a national survey of prescription of antipsychotic medications, organized by the Prescribing Observatory for Mental Health. Over half of the patients on SLAM inpatient or psychiatric intensive care units were prescribed a high-dose antipsychotic or a combination of antipsychotics. Prescribing high-dose antipsychotics and polypharmacy in SLAM was found to be among the highest in the UK. Aim: To assess the impact of a 6-year quality improvement programme aimed at reducing the rates of prescribing high-dose antipsychotics and polypharmacy on SLAM inpatients and psychiatric intensive care units. Results: There was a significant reduction between baseline and final survey in the rates of prescription of both high-dose antipsychotics and polypharmacy on SLAM inpatients and intensive care units (58% versus 10% p < 0.0001 and 57% versus 16%, p < 0.0001 respectively). The proportion of patients at final survey prescribed a high-dose antipsychotic and a combination was substantially lower in SLAM than in the national sample (10% versus 28%, p < 0.0001 and 16% versus 38%, p < 0.0001 respectively). Clinical implications: A sustained change in the prescribing culture of an organization can be achieved through a targeted improvement programme. PMID:25653825
Abstract Objective: The purpose of this study was to examine psychiatrists' attitudes and practices in prescribing second-generation antipsychotics (SGA) to children and adolescents (referred to here as “children”) and identify factors associated with off-label SGA use. Methods: A survey was mailed to a national, randomly selected sample of 1600 child and adolescent psychiatrists identified by the American Medical Association. Multivariable logistic regression was used to identify factors, including psychiatrists' characteristics, practice characteristics, and psychiatrists' attitudes, that are associated with off-label SGA use (i.e., SGAs used in children with attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, or nonbipolar mood disorders). Results: The final sample included 340 psychiatrists. Overall, respondents reported higher use and appropriateness of SGAs for United States Food and Drug Administration (FDA)-approved disorders, symptoms of aggression, and older child age. More than one third (36%) of respondents reported some off-label SGA use. Significant predictors of off-label use were: Practicing at inpatient/residential facilities (odds ratio [OR]=4.2, p=0.001); white/non-Hispanic race/ethnicity (OR=0.3, p<0.0001), agreeing that SGAs should be used for ADHD with aggression (OR=7.1, p<0.0001); and agreeing that SGAs should be used for severe delinquent behaviors (OR=1.9, p=0.03). Conclusions: Psychiatrists' attitudes about prescribing SGAs to children exhibiting aggressive symptoms were associated with off-label SGA use. Research is needed to understand the construct of aggression, potential interaction effects of aggression with diagnostic criteria, and their impact on SGA use. PMID:24679174
Rodday, Angie Mae; Parsons, Susan K.; Correll, Christoph U.; Robb, Adelaide S.; Zima, Bonnie T.; Saunders, Tully S.
Background Shared decision making represents a clinical consultation model where both clinician and service user are conceptualised as experts; information is shared bilaterally and joint treatment decisions are reached. Little previous research has been conducted to assess experience of this model in psychiatric practice. The current project therefore sought to explore the attitudes and experiences of consultant psychiatrists relating to shared decision making in the prescribing of antipsychotic medications. Methods A qualitative research design allowed the experiences and beliefs of participants in relation to shared decision making to be elicited. Purposive sampling was used to recruit participants from a range of clinical backgrounds and with varying length of clinical experience. A semi-structured interview schedule was utilised and was adapted in subsequent interviews to reflect emergent themes. Data analysis was completed in parallel with interviews in order to guide interview topics and to inform recruitment. A directed analysis method was utilised for interview analysis with themes identified being fitted to a framework identified from the research literature as applicable to the practice of shared decision making. Examples of themes contradictory to, or not adequately explained by, the framework were sought. Results A total of 26 consultant psychiatrists were interviewed. Participants expressed support for the shared decision making model, but also acknowledged that it was necessary to be flexible as the clinical situation dictated. A number of potential barriers to the process were perceived however: The commonest barrier was the clinician’s beliefs regarding the service users’ insight into their mental disorder, presented in some cases as an absolute barrier to shared decision making. In addition factors external to the clinician - service user relationship were identified as impacting on the decision making process, including; environmental factors, financial constraints as well as societal perceptions of mental disorder in general and antipsychotic medication in particular. Conclusions This project has allowed identification of potential barriers to shared decision making in psychiatric practice. Further work is necessary to observe the decision making process in clinical practice and also to identify means in which the identified barriers, in particular ‘lack of insight’, may be more effectively managed. PMID:24886121
State mental health authorities can use public-academic partnerships to create professional roles in which leaders can track trends, identify problems, and carry out quality improvement projects to address key issues. Leaders with positions in both academic institutions and state mental health authorities ensure access to resources, technical expertise, and key relationships to improve quality. The authors describe a public-academic partnership in New Hampshire and a quality improvement program it carried out. The program encourages providers at community mental health centers to adopt prescribing practices that limit the cardiometabolic side effects of antipsychotic medicines. PMID:21885576
Brunette, Mary F; de Nesnera, Alexander; Swain, Karin; Riera, Erik G; Lotz, Doris; Bartels, Stephen J
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. PMID:18385207
Parks, Joseph; Radke, Alan; Parker, George; Foti, May-Ellen; Eilers, Robert; Diamond, Mary; Svendsen, Dale; Tandon, Rajiv
Patients with schizophrenia who are nonadherent to medication are at risk for repeated relapse and rehospitalization from this chronic and lifelong mental illness. Effective, oral medications can be difficult for patients to maintain on a daily basis, and long-acting injectable (LAI) antipsychotics can help to alleviate this challenge. However, some physicians' attitudinal barriers that need to be overcome include the belief that patients do not have adherence problems, concerns about LAI antipsychotic efficacy over traditional oral agents, the perception that the time and cost to administer this formulation outweighs its benefit, and the perception that injectable medications undermine patients' autonomy. A better understanding of LAIs and their potential benefits may help physicians to implement a long-term treatment plan that provides the best outcome for patients. PMID:25551245
Kane, John M
The onset of psychosis during pregnancy presents difficult management decisions. A complete and thorough physical and obstetric examination is always warranted to look for possible physiological precipitants. The treatment of pregnant patients with psychotic symptomatology requires close contacts between family members, non-physician professionals involved in the patient's care (e.g. social workers, case managers and home healthcare nurses), and the physicians overseeing the patient's management (e.g. internists, obstetricians and psychiatrists). In mild and less disabling cases it may be possible to avoid medication intervention but this approach risks adverse behaviour consequences resulting from a possible worsening of the patient's symptomatology. Avoiding medication requires an environment in which the patient has strong social supports. Risks are present whether medication is initiated or not, and treatment decisions require a careful assessment of the risks and benefits involved. Initiating medication raises the possibility of obstetric, teratogenic, neurobehavioural and neonatal toxic effects. Research on the risks imposed by antipsychotic drug use during pregnancy is incomplete and raises questions regarding appropriate management. The first trimester represents a period of increased susceptibility to medication-induced teratogenesis. The use of low potency phenothiazines during the first trimester may increase the risk of congenital abnormalities by an additional 4 cases per 1000 (odds ratio = 1.21, p = 0.04) The pharmacological profiles of antipsychotic medications also present adverse effects which need to be considered during pregnancy (hypotension, sedation, etc.). Less is known about the risk of adverse consequences resulting from the use of newer atypical antipsychotic medications. Electroconvulsive therapy is another treatment modality and its use may circumvent the need to introduce antipsychotic medication during pregnancy. It must be stressed that. given current knowledge, no treatment regimen can be considered completely safe. Ultimately many factors must be evaluated when treating psychosis during pregnancy, however, no decision is risk-free. PMID:10937460
Pinkofsky, H B
Atypical antipsychotic medications are increasingly used to treat children and adolescents with a variety of neuropsychiatric disorders. The most common symptom for which atypical antipsychotics are prescribed to young patients is pernicious, pervasive, persistent aggression in the context of dis- ruptive behavior disorders. Unfortunately, the evidence base informing physicians about atypical anti- psychotic dosing in young people is relatively small,
Robert L. Findling
Although fresh frozen plasma (FFP) is one of the most commonly prescribed therapies in clinical practice throughout the world today, there is little medical evidence available supporting its use. Recent guidelines have called for limiting FFP transfusions. Despite this, FFP use does not seem to be decreasing. The reasons for this are likely to be multifactorial, and may be based on ideas regarding medical practices dating back to Galen and Hippocrates. A review of the history of the development of FFP may shed some light on current clinical practice and guide the direction of future investigations and therapies. PMID:23848285
Background The research goal is to better understand prescriber, patient, and caregiver perspectives about long-acting injectable (LAI) antipsychotic therapy and how these perspectives affect LAI use. Addressing these perspectives in the clinic may lead to greater success in achieving therapeutic goals for the patient with schizophrenia. Methods Ethnographic information was collected from a non-random sample of 69 prescriber-patient conversations (60 with community mental health center [CMHC] psychiatrists; 9 with nurse-practitioners) recorded during treatment visits from August 2011 to February 2012, transcribed and analyzed. Discussions were categorized according to 11 predetermined CMHC topics. In-person observations were also conducted at 4 CMHCs, including home visits by researchers (n?=?15 patients) prior to the CMHC visit and observations of patients receiving injections and interacting with staff. Telephone in-depth interviews with psychiatrists, patients, and caregivers to gather additional information on LAI discussion, prescription, or use were conducted. Results Antipsychotic treatment decisions were made without patient or caregiver input in 40 of 60 (67%) of psychiatrist-patient conversations. Involvement of patients or caregivers in treatment decisions was greater when discussing LAI (15 of 60 [25%]) vs oral antipsychotic treatment (5 of 60 [8%]). LAIs were not discussed by psychiatrists in 11 of 22 (50%) patients taking oral antipsychotics. When offered, more LAI-naïve patients expressed neutral (9 of 19 [47%]) rather than favorable (3 of 19 [16%]) or unfavorable (7 of 19 [37%]) responses. Prescribers were most concerned about potentially damaging the therapeutic relationship and side-effects when discussing LAIs while patient resistance was often related to negative feelings about injections. Psychiatrists had some success in overcoming patient objections to LAIs by addressing and decomposing initial resistance. More than half (11 of 19 [58%]) of LAI-naïve patients agreed to start LAI treatment following office visits. Patient-described benefits of LAIs vs orals included perceived rapid symptom improvement and greater overall efficacy. Conclusions In this study, many psychiatrists did not offer LAIs and most patients and caregivers were not involved in antipsychotic treatment decision making. Opportunities to increase active patient engagement, address resistances, guide patient drug-formulation selection, and provide better LAI-relevant information for more individualized approaches to treating the patient with schizophrenia were present. PMID:24131801
Objective: Determine the percentage of subjects taking antipsychotics who meet criteria for metabolic syndrome based on point-of-care testing analyses. Evaluate pharmacist comprehensive medication management services using point-of-care tests to reduce the mean difference in number of metabolic syndrome risk parameters at 6 and 12 months. Method: This 12-month, prospective, multisite, randomized, controlled study included 120 subjects taking antipsychotics (mean [SD] age of 42.9 [11.3] years) recruited from 3 community mental health clinics in Minnesota. Subjects consented to receive either pharmacist (PCS; n = 60) or no pharmacist (NCS; n = 60) comprehensive medication management services. Data were collected from February 2010 to January 2012. Results: No statistical differences in metabolic syndrome based on point-of-care tests were observed between the 2 groups at baseline (PCS: 85.2%, n = 46 versus NCS: 71.2%, n = 42, P = .073) or at 12 months (PCS: 84.4%, n = 38 versus NCS: 70.2%, n = 33, P = .104). Subjects, overall, screened positive at baseline for dyslipidemia (85.8%, n = 106), hypertension (52.5%, n = 63), and diabetes (22.5%, n = 27) based on point-of-care testing for metabolic risk criteria. After 12 months, a nonsignificant (P = .099) higher adjusted mean number of metabolic syndrome parameters in PCS subjects compared to NCS subjects (mean difference [95% CI] = 0.41 [?0.08 to 0.90]) were found. Conclusions: A relatively high proportion of subjects met criteria for metabolic syndrome, although no significant improvement was observed between the groups after 12 months. Point-of-care test analyses identified a high proportion of subjects meeting criteria for dyslipidemia, hypertension, and diabetes. Utilizing point-of-care tests in mental health settings and fostering interprofessional partnerships with comprehensive medication management pharmacists may improve identification and long-term management of metabolic risks among patients prescribed antipsychotics. Trial Registration: ClinicalTrials.gov identifier: NCT02029989 PMID:25667811
Shuster, Sara M.; Davey, Cynthia S.
New safety concerns over diabetes drugs Two drugs commonly prescribed to treat diabetes double of Type II Diabetes. Prescriptions for the drugs, known as thiazolidinediones, have doubled over the last. The results are published in the August edition of the journal Diabetes Care. Congregation 2007 page 5Â9 Race
Objective To review the metabolic consequences of second-generation antipsychotics in youth and current monitoring and intervention guidelines for optimal treatment. Background Second-generation antipsychotics have largely replaced the use of first-generation antipsychotics in treating psychotic disorders in youth. In addition, there has been a dramatic increase in using these medications to treat a variety of nonpsychotic disorders. These medications have significant metabolic side effects, including weight gain. This raises concern, given the problem of pediatric obesity. Materials and methods A review of current literature looking at prescribing practices and possible reasons for the increased use of second-generation antipsychotics in children and adolescents was conducted. Review of the mechanisms for why youth may be particularly vulnerable to the metabolic consequences (particularly weight gain) was similarly completed. In addition, data supporting the efficacy, rationale, and unique side-effect profile of each individual second-generation drug were evaluated to help inform providers on when and what to prescribe, along with current monitoring practices. The current evidence base for possible interventions regarding the management of antipsychotic-induced weight gain was also evaluated. Results and conclusion On the basis of the literature review, there are several speculated reasons for the increase in prescriptions of second-generation antipsychotics. The choice of antipsychotic for youth should be based upon the disorder being treated along with the unique side-effect profile for the most commonly used second-generation antipsychotics. Monitoring strategies are also individualized to each antipsychotic. The current interventions recommended for antipsychotic-induced weight gain include lifestyle management, switching medication to a drug with a lower propensity for weight gain, and pharmacologic (particularly metformin) treatment. PMID:25298741
Krill, Rebecca A; Kumra, Sanjiv
Background To analyse the extent and profile of outpatient regular dispensation of antipsychotics, both in combination and monotherapy, in the Barcelona Health Region (Spain), focusing on the use of clozapine and long-acting injections (LAI). Methods Antipsychotic drugs dispensed for people older than 18 and processed by the Catalan Health Service during 2007 were retrospectively reviewed. First and second generation antipsychotic drugs (FGA and SGA) from the Anatomical Therapeutic Chemical classification (ATC) code N05A (except lithium) were included. A patient selection algorithm was designed to identify prescriptions regularly dispensed. Variables included were age, gender, antipsychotic type, route of administration and number of packages dispensed. Results A total of 117,811 patients were given any antipsychotic, of whom 71,004 regularly received such drugs. Among the latter, 9,855 (13.9%) corresponded to an antipsychotic combination, 47,386 (66.7%) to monotherapy and 13,763 (19.4%) to unspecified combinations. Of the patients given antipsychotics in association, 58% were men. Olanzapine (37.1%) and oral risperidone (36.4%) were the most common dispensations. Analysis of the patients dispensed two antipsychotics (57.8%) revealed 198 different combinations, the most frequent being the association of FGA and SGA (62.0%). Clozapine was dispensed to 2.3% of patients. Of those who were receiving antipsychotics in combination, 6.6% were given clozapine, being clozapine plus amisulpride the most frequent association (22.8%). A total of 3.800 patients (5.4%) were given LAI antipsychotics, and 2.662 of these (70.1%) were in combination. Risperidone was the most widely used LAI. Conclusions The scant evidence available regarding the efficacy of combining different antipsychotics contrasts with the high number and variety of combinations prescribed to outpatients, as well as with the limited use of clozapine. PMID:22587453
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
... frequently used medications are warfarin (Coumadin) and low-molecular weight heparin (LMWH), also known as Lovenox. Warfarin ... surgeon-submitted patient information, including outcomes and which type of blood clot prevention the patient was prescribed. ...
Background Currently a large number of atypical antipsychotics available in the market are endorsed as better option for treating schizophrenia than the typical antipsychotics. Information regarding the utilization pattern of antipsychotic drugs is lacking in Nepalese population particularly in Western Nepal. By means of this study one is expected to acquire an idea concerning clinician’s preference to the antipsychotic drugs in actual clinical setup. The main objective of the study was to find the commonest antipsychotics prescribed in a tertiary care center among hospitalized patients in Western Nepal. Methods This cross sectional study was carried out between 1st January 2009 and 31th December 2010 at Manipal Teaching Hospital, Nepal. The diagnosis of schizophrenia was based on ICD-10 (Tenth revision).The main outcome variables of the study was commonest antipsychotic drug prescribed. Z test, Chi square test and logistic regression were used for analytical purpose. P-value < 0.05 was considered to be statistically significant. This is the first study done on the utilization pattern of antipsychotics drugs among hospitalized patients in Nepal. Results Out of 210 cases of schizophrenia, most of the patients were less than 40 yrs. 78.6%, male 61.9%, unemployed 86.7% and having their monthly income less than NPR 10000 /month 80.5%. As far as religion, 78.1% patients were the Hindus and ethnically schizophrenia was common among the Dalit 26.2%. The study revealed that 46.2% of patients were students followed by 25.2% of housewives. Olanzapine was the commonest antipsychotic drug to be prescribed 34.3%. It was observed that the psychiatrists had a tendency of using antipsychotic drugs by trade names [OR 3.3 (1.407, 8.031)] in male patients as compared to female patients. Conclusion According to the utilization pattern of antipsychotics, it is concluded that atypical antipsychotics were used relatively more commonly than that of typical antipsychotics. Among the atypical antipsychotic drugs, there is a trend of using Olanzapine during Schizophrenia as compared to other atypical antipsychotic drugs in Western Nepal. PMID:23522357
Since antimicrobial resistance among uropathogens against current first line agents has affected the management of severe urinary tract infection, we determined the likelihood that antibiotic regimens achieve bactericidal pharmacodynamic exposures using Monte Carlo simulation for five antimicrobials (ciprofloxacin, ceftriaxone, piperacillin/tazobactam, ertapenem, and meropenem) commonly prescribed as initial empirical treatment of inpatients with severe community acquired urinary tract infections. Minimum inhibitory concentration determination by Etest was performed for 205 Brazilian community urinary tract infection Escherichia coli strains from 2008 to 2012 and 74 E. coli bloodstream strains recovered from a surveillance study. Pharmacodynamic exposure was modeled via a 5000 subject Monte Carlo simulation. All isolates were susceptible to ertapenem and meropenem. Piperacillin/tazobactam, ceftriaxone and ciprofloxacin showed 100%, 97.5% and 83.3% susceptibility among outpatient isolates and 98.6%, 75.7% and 64.3% among inpatient isolates, respectively. Against outpatient isolates, all drugs except ciprofloxacin (82.7% in aggressive and 77.6% in conservative scenarios) achieved high cumulative fraction of response: carbapenems and piperacillin/tazobactam cumulative fraction of responses were close to 100%, and ceftriaxone cumulative fraction of response was 97.5%. Similar results were observed against inpatients isolates for carbapenems (100%) and piperacillin/tazobactam (98.4%), whereas ceftriaxone achieved only 76.9% bactericidal cumulative fraction of response and ciprofloxacin 61.9% (aggressive scenario) and 56.7% (conservative scenario) respectively. Based on this model, standard doses of beta-lactams were predicted to deliver sufficient pharmacodynamic exposure for outpatients. However, ceftriaxone should be avoided for inpatients and ciprofloxacin empirical prescription should be avoided in both inpatients and outpatients with complicated urinary tract infection. PMID:24731938
Cuba, Gabriel Trova; Pignatari, Antonio Carlos Campos; Patekoski, Katya Silva; Luchesi, Lucimila Jorge; Kiffer, Carlos Roberto Veiga
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. PMID:23047785
Gellad, WF; Aspinall, SL; Handler, SM; Stone, RA; Castle, N; Semla, TP; Good, CB; Fine, MJ; Dysken, M; Hanlon, JT
Objectives Refractory major depressive disorder (MDD) is a serious problem leading to a heavy economic burden. Antipsychotic augmentation treatment with aripiprazole and quetiapine is approved for MDD patients and can achieve a high remission rate. This study aimed to examine how psychiatrists in Taiwan choose medications and how that choice is influenced by health insurance payments and administrative policy. Design Descriptive study. Outcome measures Eight questions about the choice of treatment strategy and atypical antipsychotics, and the reason to choose aripiprazole. Intervention We designed an augmentation strategy questionnaire for psychiatrists whose patients had a poor response to antidepressants, and handed it out during the annual meeting of the Taiwanese Society of Psychiatry in October 2012. It included eight questions addressing the choice of treatment strategy and atypical antipsychotics, and the reason whether or not to choose aripiprazole as the augmentation antipsychotic. Results Choosing antipsychotic augmentation therapy or switching to other antidepressant strategies for MDD patients with an inadequate response to antidepressants was common with a similar probability (76.1% vs 76.4%). The most frequently used antipsychotics were aripiprazole and quetiapine, however a substantial number of psychiatrists chose olanzapine, risperidone, and sulpiride. The major reason for not choosing aripiprazole was cost (52.1%), followed by insurance official policy audit and deletion in the claims review system (30.1%). Conclusion The prescribing behavior of Taiwanese psychiatrists for augmentation antipsy-chotics is affected by health insurance policy. PMID:25657586
Hsu, Yi-Chien; Chou, Yu-Ching; Chang, Hsin-An; Kao, Yu-Chen; Huang, San-Yuan; Tzeng, Nian-Sheng
Objective: Antipsychotics have revolutionized psychiatry by allowing significant numbers of patients in long-term hospital settings to be discharged and successfully maintained in the community. However, these medications are also associated with a range of adverse events ranging from mostly annoying to rarely dangerous. This study is carried out to identify the adverse drug reactions (ADRs) to antipsychotics and its management in psychiatric patients. Methods: Prospective interventional study was conducted in the psychiatric unit of a tertiary care hospital. Patients of any age and either sex prescribed with at least one antipsychotic were included and monitored for ADRs. Findings: Among the 517 patients receiving antipsychotics, a total of 289 ADRs were identified from 217 patients at an overall incidence rate of 41.97%. Sixty-seven different kinds of ADRs were observed in the study patients. Central and peripheral nervous system was the most commonly affected system organ class (n = 59) and weight gain (n = 30) was the most commonly observed ADR. Olanzapine was most commonly implicated in reported ADRs (n = 92) followed by risperidone (n = 59). Of the 289 ADRs, 80% required interventions including cessation of drug and/or specific/symptomatic/nonpharmacological treatment. Conclusion: This post marketing surveillance study provides a representative data of the ADR profile of the antipsychotics likely to be encountered in psychiatric patients in an Indian tertiary care hospital. PMID:25114936
Lucca, Jisha Myalil; Madhan, Ramesh; Parthasarathi, Gurumurthy; Ram, Dushad
Antipsychotic medication maintenance and the factors influencing it were analyzed using data from the SOHO study, a large observational study of the outcomes of antipsychotic treatment for schizophrenia in Europe. A total of 7186 adult patients in the outpatient setting who were initiating or changing their antipsychotic medication and who were prescribed only one antipsychotic after the baseline visit were analyzed. Medication maintenance at 12 months varied with the type of antipsychotic prescribed, being highest with clozapine (79.5%) and olanzapine (77.0%), and lowest with quetiapine (51.4%) and amisulpride (58.2%). Multiple logistic regression analysis demonstrated that the type of antipsychotic prescribed at baseline was the most important predictor of medication maintenance. Alcohol dependency, taking mood stabilizers, compulsory admission or arrest in the previous 6 months, greater clinical severity, and changing antipsychotic medication due to lack of effectiveness at baseline predicted a higher frequency of medication discontinuation in the subsequent 12 months. In contrast, medication maintenance was higher among patients who were treatment naïve at baseline, socially active or who had loss of libido at baseline. The findings from this study should be interpreted conservatively because of its non-randomized observational design. PMID:16414249
Haro, Josep Maria; Novick, Diego; Belger, Mark; Jones, Peter B
This article is a review of the various treatments that are currently available, in particular in France, for the treatment of bipolar disorders. This article specifically addresses the use of novel antipsychotic agents as alternative therapy to a lithium therapy and/or the use of conventional antipsychotics. The prevalence of bipolar disorder over a lifetime is around 1% of the general population. Bipolar disorder consists of alternating depressive and manic episodes. It mainly affects younger subjects, and is often associated with alcohol and drug addictions. There are two main subtypes of bipolar disorder. According to the DSM IV-R, type 1 of bipolar disorder is characterised when at least one manic episode (or a mixed episode) has been diagnosed. Type 2 of bipolar disorder is related to patients enduring recurrent depressive episodes but no manic episode. Type 2 affects women more frequently as opposed to type 1 affecting individuals of both sexes. Manic-depressive disorder (or cyclo-thymic disorder) appears in relation to patients who has never suffered manic episode, mixed episode or severe depressive episode but have undergone numerous periods with some symptoms of depression and hypomanic symptoms over a two-year period during which any asymptomatic periods last no longer than two months. The average age of the person going through a first episode (often a depressive one) is 20 years-old. Untreated bipolar patients may endure more than ten manic or depressive episodes. Finally, in relation to 10 to 20% of patients, the bipolar disorder will turn into a fast cycle form, either spontaneously or as a result of certain medical treatments. Psychiatrists are now able to initiate various treating strategies which are most likely to be effective as a result of the identification of clinical subtypes of the bipolar disorder. Lithium therapy has been effectively and acutely used for patients with pure or elated mania and its prophylaxis. However, lithium medication may worsen depressive symptoms when used for a long term maintenance therapy. Additionally, mixed mania, rapid cycling type patients and bipolar disorder associated with substance abuse do not respond well to lithium therapy. In addition to the lithium therapy or in place of a lithium therapy, one can report the frequent use of antipsychotic agents in respect of patients with bipolar disorder during both the acute and maintenance phases of treatment. Antipsychotic agents have been used for almost forty years and may be used in combination with a lithium therapy. Conventional antipsychotics are effective but they may induce late dyskinesia, weight gain, sedation, sexual dysfunction and depression. These adverse side effects often lead to non compliance in particular in circumstances where antipsychotic agents are combined with a lithium therapy. A number of alternative somatic treatment approaches have been reported for patients who do not respond well or who are intolerant to lithium therapy. As such, valproate has received regulatory approval for the acute treatment of mania and carbamazepine has been indicated for this condition in a number of countries. Divalproex (Depakote) has recently obtained the authorization to market in France and may be prescribed for manic states or hypomanic states that do not tolerate lithium therapy or for which lithium therapy is contraindicated. A number of other anticonvulsants (lamotrigine, gabapentin and topiramate) are currently being tested. Because of the side effects of the conventional antipsychotic agents, atypical antipsychotic agents are currently on trial and appear to be of interest in the treatment of bipolar disorders. Currently, a number of prospective studies are available with clozapine, risperidone and olanzapine in the treatment of bipolar disorder. Most are short-term studies. Recent randomised, double-blind, placebo-controlled studies have shown clozapine, risperidone and olanzapine to be effective with antimanic and antidepressive effects, both as monotherapy and as add-on maintenance therapy with lithium
Vacheron-Trystram, M-N; Braitman, A; Cheref, S; Auffray, L
Background: Antipsychotics are the most frequently prescribed psychotropic medication for people with intellectual disabilities. Many people are prescribed this medication for "challenging behaviours" without having had a formal diagnosis of a psychiatric disorder. Antipsychotics have been reported to have severe side-effect profiles, which can…
Crossley, Rachel; Withers, Paul
Background To describe the rates, indications, and adverse effects of psychotropic drug prescription in a specialist tertiary hospital child and adolescent eating disorder service. Methods Retrospective case note study of all active eating disorder patients (N?=?115) over the period of treatment from referral to time of study (M?=?2 years), covering patient demographics, clinical characteristics, drug prescriptions, indications, and adverse effects. Results Psychotropic drugs were prescribed in 45% of cases, most commonly antidepressants (41%), followed by anxiolytics (29%) and antipsychotics (22%), with 8% initiated before referral to the specialist eating disorder program. Common indications were depressed mood, agitation, anxiety, and insomnia. Patient clinical severity and complexity was associated with prescribing. Adverse effects, mostly minor, were recorded in 23% of antidepressant prescriptions, 39% of antipsychotic prescriptions, and 13% of anxiolytic prescriptions. Second generation antipsychotic prescription was associated with subsequent new onset binge eating, in this preliminary observational study. Self-harm by overdose of psychotropics occurred in 11% of patients prescribed medication. Conclusions Psychotropic medications were frequently prescribed to adolescent eating disorder patients to treat distressing symptoms. Prospective randomised controlled trials to clarify efficacy and safety are needed. Given the difficulties of conducting clinical trials in this population, services are encouraged to monitor and audit medication safety and efficacy in everyday practice, and to report their findings. PMID:24999406
Meta-analyses have found conflicting evidence on the link between antipsychotics and cerebrovascular events (CVEs). The primary aim of this study was to evaluate the association between any antipsychotic prescription and CVEs in Italian elderly; second, to compare the effect of typical and atypical antipsychotics on CVEs; and third, to investigate the effect of antipsychotics on CVEs in the subgroup of persons coprescribed with acetylcholinesterase inhibitors (AChEIs). Administrative claims from community-dwelling people aged 65 to 94 years living in Northern Italy were analyzed using a retrospective case-control design, from 2003 to 2005. The primary outcome measure was a hospital discharge diagnosis of CVEs during 2005. Four age-, sex-, and local health unit-matched control subjects were identified for each case. Antihypertensive drugs, anticoagulants, platelet inhibitors, antidiabetic drugs, lipid-lowering drugs, and AChEI were used as covariates in conditional logistic regression models testing the odds ratio (OR) for CVEs due to antipsychotics use. Three thousand eight hundred fifty-five cases of CVEs were identified and matched with 15,420 control subjects. In multiadjusted models, the association of any antipsychotics, typical or atypical with CVEs, was not significant. When antipsychotics were categorized according to the number of boxes prescribed during the observational period, being prescribed with at least 19 boxes of typical antipsychotics was significantly associated with CVEs (OR, 2.4; 95% confidence interval, 1.08-5.5). An interaction was found between any antipsychotic and AChEI coprescription on CVEs (OR, 0.46; 95% confidence interval, 0.23-0.92). In conclusion, only typical antipsychotics were associated with an increased odd of CVEs, but the association was duration dependent. Persons prescribed simultaneously with AChEI and antipsychotics may be at a lower risk of CVEs. PMID:23771200
Franchi, Carlotta; Sequi, Marco; Tettamanti, Mauro; Bonometti, Francesca; Nobili, Alessandro; Fortino, Ida; Bortolotti, Angela; Merlino, Luca; Pasina, Luca; Djade, Codjo Djignefa; Marengoni, Alessandra
Background Information about antibiotic use and resistance patterns of common microorganisms are lacking in hospitals in Western Nepal. Excessive and inappropriate use of antibiotics contributes to the development of bacterial resistance. The parameter: Defined daily dose/100 bed-days, provides an estimate of consumption of drugs among hospital in-patients. This study was carried out to collect relevant demographic information, antibiotic prescribing patterns and the common organisms isolated including their antibiotic sensitivity patterns. Methods The study was carried out over a 3-month period (01.04.2002 to 30.06.2002) at the Manipal Teaching Hospital, Western Nepal. The median number of days of hospitalization and mean ± SD cost of antibiotics prescribed during hospital stay were calculated. The use of antibiotics was classified for prophylaxis, bacteriologically proven infection or non-bacteriologically proven infection. Sensitivity patterns of the common organisms were determined. Defined daily dose/100 bed-days of the ten most commonly prescribed antibiotics were calculated. Results 203 patients were prescribed antibiotics; 112 were male. Median duration of hospitalization was 5 days. 347 antibiotics were prescribed. The most common were ampicillin, amoxicillin, metronidazole, ciprofloxacin and benzylpenicillin. Mean ± SD cost of antibiotics was 16.5 ± 13.4 US$. Culture and sensitivity testing was carried out in 141 patients. The common organisms isolated were H. influenzae, E. coli, K. pneumoniae and S. aureus. Conclusions Antibiotic resistance is becoming a problem in the Internal Medicine ward. Formulation of a policy for hospital antibiotic use and an educational programme especially for junior doctors is required. PMID:12904265
Shankar, Ravi Pathiyil; Partha, Praveen; Shenoy, Nagesh Kumar; Easow, Joshy Maducolil; Brahmadathan, Kottallur Narayanan
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
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
Previous studies have shown significant ethnic differences in prescribing patterns of two or more antipsychotics. This study examined changes in atypical and typical antipsychotic prescriptions among Asian Americans and Pacific Islanders. Five hundred consecutive charts were reviewed for antipsychotics at the time of admission and discharge from each of two inpatient psychiatric facilities in Hawai'i. Multiple antipsychotic prescription rates were 9% at intake and 6% at discharge. For the ethnic groups studied, there were no statistically significant differences by patient ethnicity regarding antipsychotics at intake (?(2) = 29.2, df = 21, P = .110) or discharge (?(2) = 20.5, df = 24, P = .667). There were no significant differences in prescription and polypharmacy patterns among Asian Americans and Pacific Islanders ethnic groups in this study. PMID:25285256
Takeshita, Junji; Goebert, Deborah; Else, Iwalani; Carlton, Barry; Matsu, Courtenay; Guerrero, Anthony
Previous studies have shown significant ethnic differences in prescribing patterns of two or more antipsychotics. This study examined changes in atypical and typical antipsychotic prescriptions among Asian Americans and Pacific Islanders. Five hundred consecutive charts were reviewed for antipsychotics at the time of admission and discharge from each of two inpatient psychiatric facilities in Hawai‘i. Multiple antipsychotic prescription rates were 9% at intake and 6% at discharge. For the ethnic groups studied, there were no statistically significant differences by patient ethnicity regarding antipsychotics at intake (?2 = 29.2, df = 21, P = .110) or discharge (?2 = 20.5, df = 24, P = .667). There were no significant differences in prescription and polypharmacy patterns among Asian Americans and Pacific Islanders ethnic groups in this study. PMID:25285256
Goebert, Deborah; Else, Iwalani; Carlton, Barry; Matsu, Courtenay; Guerrero, Anthony
Background The safety and effectiveness of psychotropic drug use in the paediatric population is widely debated, in particular because of the lack of data concerning long term effects. In Italy the prevalence of psychotropic drug prescriptions increased in the early 2000s and decreased afterwards. In such a context, a study with the aim to estimate the incidence and prevalence of psychotropic drug prescription in the paediatric population and to describe diagnostic and therapeutic approaches was performed. Methods The study population was composed of 76,000 youths less than 18 years and living in the area covered by the local health unit of Verona, Italy. The data source was the Verona local health unit's administrative prescription database. Prevalence and incidence of antidepressant and/or antipsychotic drug prescriptions in the 2004-2008 period were estimated. Children and adolescents receiving antidepressant and/or antipsychotic drug prescriptions between 1 January 2005 and 31 December 2006 were identified and questionnaires were sent to the prescribers with the aim to collect data concerning diagnostic and therapeutic approaches, and care strategies. Results The prevalence of psychotropic drug prescriptions did not change in the 2004-2008 period, while incidence slightly increased (from 7.0 in 2005 to 8.3 per 10,000 in 2008). Between 1 January 2005 and 31 December 2006, 111 youths received at least one psychotropic drug prescription, 91 of whom received antidepressants. Only 28 patients attended child and adolescent psychiatry services. Information concerning diagnostic and therapeutic approaches, and care strategies was collected for 52 patients (47%). Anxiety-depressive syndrome and attention disorders were the diseases for which psychotropic drugs were most commonly prescribed. In all, 75% youths also received psychological support and 20% were prescribed drugs for 2 or more years. Conclusions Despite the low drug prescription prevalence, the finding that most children were not cared for by child and adolescent psychiatric services is of concern and calls for a systematic, continuous monitoring of psychopharmacological treatments. PMID:21605367
Antipsychotics are frequently and increasingly prescribed off-label for the treatment of behavioral and psychological symptoms associated with dementia, despite their modest efficacy. Instead, the safety profile of antipsychotics has been questioned repeatedly in recent years with various concerns, including death. Meta-analyses of randomized controlled trials found that one of the major causes of death associated with atypical antipsychotics use was pneumonia. Only few observational studies, however, have investigated the risk of pneumonia in elderly patients, especially among those receiving conventional antipsychotics. The aim of this editorial is to synthesize the current evidence from observational studies regarding the risk of pneumonia in elderly patients receiving either conventional or atypical antipsychotics. The studies conducted so far document that the risk of pneumonia is two- to threefold increased in a dose-dependent fashion with both classes compared to nonuse, with a possibly higher risk attributable to atypical antipsychotics. The risk seems to peak at the beginning of treatment (e.g., 7 - 30 days), and dissipates over time for both conventional and atypical antipsychotics. The risk-benefit ratio suggests that there will be 1 excess hospitalization for pneumonia for every 2 - 5 patients receiving any clinical improvement in symptoms. Considering the modest improvement in terms of efficacy, the risks associated with antipsychotics in elderly patients may outweigh their benefit. PMID:25431005
Gambassi, Giovanni; Sultana, Janet; Trifirò, Gianluca
This report describes antipsychotic prescription patterns for outpatients with schizophrenia prescribed olanzapine (n=3,222), clozapine (n=236), risperidone (n=1,117), quetiapine (n=189) or haloperidol (n=256) monotherapy at study entry and treated in a naturalistic, clinical practice setting over 24 months. Predictive factors associated with remaining on monotherapy were also identified. Olanzapine patients had significantly greater odds of remaining on their initial monotherapy compared to other treatment groups, while clozapine or risperidone recipients were more likely to remain on monotherapy, compared to haloperidol patients. Switching antipsychotic medication was more common than addition of another antipsychotic agent, and the most common reason for modifying treatment was lack of effectiveness. The odds of modifying antipsychotic prescription due to intolerability were lower for patients treated with olanzapine, compared to patients treated with risperidone or haloperidol (p Bitter, Istvan; Treuer, Tamas; Dyachkova, Yulia; Martenyi, Ferenc; McBride, Margaret; Ungvari, Gabor S 2008-03-01
Bitter, Istvan; Treuer, Tamas; Dyachkova, Yulia; Martenyi, Ferenc; McBride, Margaret; Ungvari, Gabor S
Antipsychotic drugs are thought to produce secondary negative symptoms, which can also exacerbate primary negative symptoms. In the present study, we examined whether motivational deficits in particular were related to antipsychotic treatment in patients with schizophrenia in a dose-dependent manner. Five hundred and twenty individuals with schizophrenia who were receiving antipsychotic monotherapy for at least 6 months and followed prospectively were included in the present study. Participants were receiving one of five antipsychotic medications (olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone), and analyses were conducted for patients receiving each drug separately. Analysis of covariance models were constructed to examine the effect of antipsychotic dose on level of motivational impairment, controlling for selected demographic and clinical variables (eg, positive symptoms). Level of motivation, or deficits therein, were evaluated using a derived measure from the Quality of Life Scale, and in addition with scores derived from the Positive and Negative Syndrome Scale. Antipsychotic dose was not related to the level of amotivation for any of the medications examined. Moreover, severity of sedation was not significantly related to the degree of amotivation. One hundred and twenty-one individuals were identified as antipsychotic-free at baseline, and after 6 months of antipsychotic treatment, no change in motivation was found. Chronic treatment with antipsychotics does not necessarily impede or enhance goal-directed motivation in patients with schizophrenia. It is possible that the negative impact of antipsychotics in this regard is overstated; conversely, the present results also indicate that we must look beyond antipsychotics in our efforts to improve motivation. PMID:25567425
Fervaha, Gagan; Takeuchi, Hiroyoshi; Lee, Jimmy; Foussias, George; Fletcher, Paul J; Agid, Ofer; Remington, Gary
Background: Anti-psychotic medications are widely prescribed to people with intellectual disabilities and have a range of negative side effects. The aim was to identify the level of knowledge of anti-psychotic medications and their side effects among key carers or home managers of adults with intellectual disabilities living in residential group…
Fretwell, Christine; Felce, David
Mechanisms underlying antipsychotic cardiometabolic adverse effects are incompletely understood. This hampers the identification of high-risk patients, low-risk antipsychotics and preventive/ameliorative treatments. Recent clinical, molecular, and genetic data suggest that i) antipsychotic-naïve samples provide the greatest power for mechanistic studies; ii) weight and metabolic effects can be discordant, pointing to overlapping and distinct mechanisms; iii) antipsychotics affect satiety and energy homeostasis signaling; iv) the specific peptides mediating these effects are unknown but likely overlap with those involved in idiopathic obesity; and v) single nucleotide polymorphisms in genes encoding known neurotransmitter receptors and metabolic proteins are promising pharmacogenomic targets for countering adverse affects. However, sophisticated molecular studies and genome-wide association studies, ideally in antipsychotic-naïve/first episode samples, are needed to further advance the field. PMID:21185230
Correll, Christoph U.; Lencz, Todd; Malhotra, Anil K.
Summary Background Antipsychotics and mood stabilisers are prescribed widely to patients with psychiatric disorders worldwide. Despite clear evidence for their efficacy in relapse prevention and symptom relief, their effect on some adverse outcomes, including the perpetration of violent crime, is unclear. We aimed to establish the effect of antipsychotics and mood stabilisers on the rate of violent crime committed by patients with psychiatric disorders in Sweden. Methods We used linked Swedish national registers to study 82?647 patients who were prescribed antipsychotics or mood stabilisers, their psychiatric diagnoses, and subsequent criminal convictions in 2006–09. We did within-individual analyses to compare the rate of violent criminality during the time that patients were prescribed these medications versus the rate for the same patients while they were not receiving the drugs to adjust for all confounders that remained constant within each participant during follow-up. The primary outcome was the occurrence of violent crime, according to Sweden's national crime register. Findings In 2006–09, 40?937 men in Sweden were prescribed antipsychotics or mood stabilisers, of whom 2657 (6·5%) were convicted of a violent crime during the study period. In the same period, 41?710 women were prescribed these drugs, of whom 604 (1·4 %) had convictions for violent crime. Compared with periods when participants were not on medication, violent crime fell by 45% in patients receiving antipsychotics (hazard ratio [HR] 0·55, 95% CI 0·47–0·64) and by 24% in patients prescribed mood stabilisers (0·76, 0·62–0·93). However, we identified potentially important differences by diagnosis—mood stabilisers were associated with a reduced rate of violent crime only in patients with bipolar disorder. The rate of violence reduction for antipsychotics remained between 22% and 29% in sensitivity analyses that used different outcomes (any crime, drug-related crime, less severe crime, and violent arrest), and was stronger in patients who were prescribed higher drug doses than in those prescribed low doses. Notable reductions in violent crime were also recorded for depot medication (HR adjusted for concomitant oral medications 0·60, 95% CI 0·39–0·92). Interpretation In addition to relapse prevention and psychiatric symptom relief, the benefits of antipsychotics and mood stabilisers might also include reductions in the rates of violent crime. The potential effects of these drugs on violence and crime should be taken into account when treatment options for patients with psychiatric disorders are being considered. Funding The Wellcome Trust, the Swedish Prison and Probation Service, the Swedish Research Council, and the Swedish Research Council for Health, Working Life and Welfare. PMID:24816046
Fazel, Seena; Zetterqvist, Johan; Larsson, Henrik; Långström, Niklas; Lichtenstein, Paul
Background Analysis of the prescribing patterns of antipsychotic drugs can improve therapeutic outcomes. The purpose of this study was to evaluate the prescribing pattern of antipsychotics and its conformance to international treatment guidelines. Methods A cross sectional study at primary psychiatric centers was carried out. Patients’ medical files were used to obtain demographic, medication and clinical information. International guidelines for schizophrenia were used to create conformance indicators. All statistical analyses were conducted using Statistical Package for Social Sciences. Results 250 patients were included in this study. A total of 406 antipsychotic agents were used; 348 (85.7%) were first generation antipsychotics (FGA). The prevalence of antipsychotic combination was 50.4% (n=126). There was no significant difference in positive (p=0.3), negative (p=0.06) and psychopathology (p=0.5) scores of schizophrenia symptoms among patients on monotherapy versus those on antipsychotic combination. Furthermore, no significant difference was observed in the annual cost of antipsychotic monotherapy versus combination therapy. One hundred and five patients (42%) were using optimum dose of (300 – 600 mg CPZeq) while the remaining were using sub or supra therapeutic doses. Analysis showed that use of depot, use of anticholinergic agents and increasing amount of total CPZeq were significant factors associated with antipsychotic combination. Conclusions This study indicated that antipsychotic prescribing was not in conformance with international guidelines with respect to maintenance dose and combination therapy. Type of antipsychotic treatment regimen, combination versus monotherapy, was not associated with better clinical or economic outcome. PMID:23816223
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…
Matson, Johnny L.; Mahan, Sara
Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h2~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future. PMID:25733959
Pouget, Jennie G.; Shams, Tahireh A.; Tiwari, Arun K.; Müller, Daniel J.
Schizophrenia is one of the most common global mental diseases, with prevalence of 1%. Patients with schizophrenia are predisposed to diabetes, coronary heart disease, hypertension, and osteoporosis, than the normal. In comparison with the metabolic syndrome, for instance, there are little reports about osteoporosis which occurs secondary to antipsychotic-induced hyperprolactinaemia. There are extensive recent works of literature indicating that osteoporosis is associated with schizophrenia particularly in patients under psychotropic medication therapy. As osteoporotic fractures cause significantly increased morbidity and mortality, it is quite necessary to raise the awareness and understanding of the impact of antipsychotic-induced hyperprolactinaemia on physical health in schizophrenia. In this paper, we will review the relationship between schizophrenia, antipsychotic medication, hyperprolactinaemia, and osteoporosis. PMID:23690768
Wu, Haishan; Deng, Lu; Zhao, Lipin; Zhao, Jingping; Li, Lehua; Chen, Jindong
Background The use of antipsychotic drugs, particularly quetiapine, has increased at an unprecedented rate in the last decade, primarily in relation to nonpsychotic indications. This increased use is concerning because of the high rates of metabolic and extrapyramidal side effects and inadequate monitoring of these complications. The purpose of this study was to measure the use of quetiapine and other second-generation antipsychotics by primary care physicians and psychiatrists and the most common diagnoses associated with quetiapine recommendations. Methods We analyzed data on antipsychotic use from the IMS Brogan Canadian CompuScript Database and the Canadian Disease and Treatment Index, with a focus on quetiapine. We looked at the number of dispensed prescriptions for second-generation antipsychotics written by primary care physicians and psychiatrists and the diagnoses associated with recommendations for quetiapine from 2005 to 2012. Results Between 2005 and 2012, there was a 300% increase in dispensed prescriptions for quetiapine ordered by family physicians: from 1.04 million in 2005 to 4.17 million in 2012. In comparison, dispensed prescriptions from family physicians for risperidone increased 37.4%: from 1.39 million in 2005 to 1.91 million in 2012; those for olanzapine increased 37.1%, from 0.97 million in 2005 to 1.33 million in 2012. Dispensed prescriptions for quetiapine ordered by psychiatrists increased 141.6%: from 0.87 million in 2005 to 2.11 million in 2012. The top 4 diagnoses associated with quetiapine in 2012 were mood disorders, psychotic disorders, anxiety disorders and sleep disturbances. A 10-fold increase in quetiapine recommendations for sleep disturbances was seen over the study period, with almost all coming from family physicians. Interpretation These findings indicate a preferential increase in the use of quetiapine over other antipsychotic drugs and show that most of the increased use is a result of off-label prescribing by family physicians. PMID:25485247
Pringsheim, Tamara; Gardner, David M.
Background Despite concerns over the potential for severe adverse events, antipsychotic medications remain the mainstay of treatment of behaviour disorders and psychosis in elderly patients. Second-generation antipsychotic agents (SGAs; e.g., risperidone, olanzapine, quetiapine) have generally shown a better safety profile compared to the first-generation agents (FGAs; e.g., haloperidol and phenothiazines), particularly in terms of a lower potential for involuntary movement disorders. Risperidone, the only SGA with an official indication for the management of inappropriate behaviour in dementia, has emerged as the antipsychotic most commonly prescribed to older patients. Most clinical trials evaluating the risk of movement disorders in elderly patients receiving antipsychotic therapy have been of limited sample size and/or of relatively short duration. A few observational studies have produced inconsistent results. Methods A population-based retrospective cohort study of all residents of the Canadian province of Manitoba aged 65 and over, who were dispensed antipsychotic medications for the first time during the time period from April 1, 2000 to March 31, 2007, was conducted using Manitoba's Department of Health's administrative databases. Cox proportional hazards models were used to determine the risk of extrapyramidal symptoms (EPS) in new users of risperidone compared to new users of FGAs. Results After controlling for potential confounders (demographics, comorbidity and medication use), risperidone use was associated with a lower risk of EPS compared to FGAs at 30, 60, 90 and 180 days (adjusted hazard ratios [HR] 0.38, 95% CI: 0.22–0.67; 0.45, 95% CI: 0.28–0.73; 0.50, 95% CI: 0.33–0.77; 0.65, 95% CI: 0.45–0.94, respectively). At 360 days, the strength of the association weakened with an adjusted HR of 0.75, 95% CI: 0.54–1.05. Conclusions In a large population of elderly patients the use of risperidone was associated with a lower risk of EPS compared to FGAs. PMID:23696870
Vasilyeva, Irina; Biscontri, Robert G.; Enns, Murray W.; Metge, Colleen J.; Alessi-Severini, Silvia
Only a minority of patients treated with antipsychotics in clinical studies continue their treatments throughout a longer study period. Few studies address this issue from a lifetime perspective. In this naturalistic study, we aimed at analysing the prescription pattern of antipsychotic drugs among a sample of Swedish patients with a diagnosis of psychotic illness, from the first contact with psychiatry (typically between 1973 and 1997) until the last written note in the case history documents. A retrospective descriptive analysis was performed of all case history data of 66 patients diagnosed with schizophrenia or related psychotic disorders. Patients with schizophrenia were prescribed antipsychotic medication more than 90% of the time. Each patient generally had been prescribed several (up to 16) different antipsychotic drugs and a quarter of the patients had been prescribed two or more antipsychotics for a third of their prescription time. Patients with psychosis were exposed to a cumulatively growing number of antipsychotics. Various factors, including clinician and patient expectations, and specific strengths and limitations of available antipsychotics may account for frequent medication changes over time. PMID:21095015
Jönsson, Erik G; Saetre, Peter; Vares, Maria; Strålin, Pontus; Levander, Sten; Lindström, Eva
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
As the sedative use increases due to the effectiveness and relatively safe profile, the abuse potential is also increasing. This study was conducted to examine the usage of four sedative agents in endoscopic examination and to compare the propofol use with the other three sedatives. Using National Health Insurance claims data from 2008 to 2012, we identified the number of cases of conscious sedation during endoscopy using one or more of the following agents: propofol, midazolam, diazepam, and lorazepam. The general characteristics of patients and medical service providers were analyzed, and the regional and annual distributions of frequency of use were compared. We also identified patient cases with excessive number of endoscopic examinations. Among the total of 3,156,231 sedatives users, midazolam was the most commonly used agent (n=2,845,250, 90.1%). However, the largest increase in patient number, which increased from 11,410 in 2008 to 28,170 in 2012, was observed with propofol. While the majority of patients received an annual endoscopy, we identified several suspected abuse cases of patients receiving endoscopies repetitively as many as 114 times in five years. The rise of sedative use in endoscopic examinations and several patient cases of repeated sedative administration suggest a potential risk for abuse. Medical service providers should be cautious when using sedatives and carefully review each patient's medical history prior to the procedure. PMID:25659208
Shin, Ju-Young; Lee, Shin Haeng; Shin, Sun Mi; Kim, Mi Hee; Park, Sung Geon; Park, Byung-Joo
Background Concerns regarding the use of antipsychotic medication in secondary care suggested an examination of primary care prescribing. Aim To audit and intervene in the suboptimal prescribing of antipsychotic drugs to primary care patients. Design of study Cross-sectional prevalence: subsequent open treatment intervention. Setting Seven of the 29 practices in the Eastern Hull Primary Care Trust. Methods Criteria for best practice were developed, against which prescribing standards were tested via audit. Patients identified as suboptimally prescribed for were invited to attend an expert review for intervention. Results 1 in 100 of 53,000 patients was prescribed antipsychotic treatment. Diagnoses indicating this were impossible to ascertain reliably. Half the regimes failed one or more audit criteria, leaving diagnosis aside. Few practices agreed to patients being approached: of 179 invitations sent, only 40 patients attended. Of 32 still taking an antipsychotic drug, 26 required changes. Mean audit criteria failed were 3.4, lack of psychotic disorder diagnosis and problematic side effects being most frequent. Changes were fully implemented in only 16 patients: reasons for complete or partial failure to implement recommendations included the wishes or inaction of patients and professionals, and worsening of symptoms including two cases of antipsychotic withdrawal syndrome. Conclusion Primary care prescribing of antipsychotic drugs is infrequent, but most is unsatisfactory. Intervention is hampered by pluralistic reluctance: even with expert guidance, rationalisation is not without risk. Use of antipsychotic drugs in primary care patients whose diagnosis does not warrant this should be avoided. How this fits in This study adds to concerns regarding high levels of off-licence use of potentially harmful medication. It adds evidence of major difficulties in rationalizing suboptimal regimes despite expert input. Relevance to the clinician is that it is better to avoid such regimes in the first place especially if there is no clear 'exit strategy': if in doubt, seek a specialist opinion. PMID:16316473
Mortimer, Ann M; Shepherd, Charles J; Rymer, Michael; Burrows, Alison
Tardive dyskinesia (TD) is a disfiguring side-effect of antipsychotic medications that is potentially irreversible in affected patients. Newer atypical antipsychotics are felt by many to have a lower risk of TD. As a result, many clinicians may have developed a false sense of security when prescribing these medications. We report five cases of patients taking atypical antipsychotics who developed TD, review the risk of TD, its potential etiologic mechanisms, and treatment options available. The goal of this paper is to alert the reader to continue to be diligent in obtaining informed consent and monitoring for the onset of TD in patients taking atypical antipsychotics. PMID:24744806
Kim, Jungjin; MacMaster, Eric; Schwartz, Thomas L
background The relative effectiveness of second-generation (atypical) antipsychotic drugs as com- pared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study. methods A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and random-
Jeffrey A. Lieberman; T. Scott Stroup; Joseph P. McEvoy; Marvin S. Swartz; Robert A. Rosenheck; Diana O. Perkins; Richard S. E. Keefe; Sonia M. Davis; Clarence E. Davis; Barry D. Lebowitz; Joanne Severe; John K. Hsiao
Aim Antipsychotics increase the risk of stroke. Their effect on myocardial infarction remains uncertain because people prescribed and not prescribed antipsychotic drugs differ in their underlying vascular risk making between-person comparisons difficult to interpret. The aim of our study was to investigate this association using the self-controlled case series design that eliminates between-person confounding effects. Methods and results All the patients with a first recorded myocardial infarction and prescription for an antipsychotic identified in the Clinical Practice Research Datalink linked to the Myocardial Ischaemia National Audit Project were selected for the self-controlled case series. The incidence ratio of myocardial infarction during risk periods following the initiation of antipsychotic use relative to unexposed periods was estimated within individuals. A classical case–control study was undertaken for comparative purposes comparing antipsychotic exposure among cases and matched controls. We identified 1546 exposed cases for the self-controlled case series and found evidence of an association during the first 30 days after the first prescription of an antipsychotic, for first-generation agents [incidence rate ratio (IRR) 2.82, 95% confidence interval (CI) 2.0–3.99] and second-generation agents (IRR: 2.5, 95% CI: 1.18–5.32). Similar results were found for the case–control study for new users of first- (OR: 3.19, 95% CI: 1.9–5.37) and second-generation agents (OR: 2.55, 95% CI: 0.93–7.01) within 30 days of their myocardial infarction. Conclusion We found an increased risk of myocardial infarction in the period following the initiation of antipsychotics that was not attributable to differences between people prescribed and not prescribed antipsychotics. PMID:25005706
Brauer, Ruth; Smeeth, Liam; Anaya-Izquierdo, Karim; Timmis, Adam; Denaxas, Spiros C.; Farrington, C. Paddy; Whitaker, Heather; Hemingway, Harry; Douglas, Ian
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
In France, as in the rest of the world, the prescription of second generation antipsychotics is on the rise in the pediatric population. At the same time, the use of first generation antipsychotics continues, although it is declining in France as in other countries. In France, we lack data on the pediatric population to ensure a safe prescription, unlike other countries such as Canada and the United States. This is disturbing when many adverse events, potentially serious for young patients' health (neuromuscular complications, risk factors, cardiovascular problems) are beginning to be identified. This article reports the current French and international knowledge on antipsychotics in the pediatric population. It appears that data in the French population are nearly nonexistent and that the methodological tools used are not always relevant (population already exposed to psychotropic drugs, short studies, debatable rating scale and somatic parameters). Within this context, a safety monitoring procedure for the naive pediatric population treated with antipsychotics was developed (ETAPE study) to determine the incidence of adverse events appearing with these drugs. Safety monitoring during the 12-month study period will include clinical assessments and laboratory testing. These assessments will be performed before treatment and at 1, 3, 6, 9, and 12 months after the introduction of the antipsychotic drug. This study received funding from the National Security Agency of Medicines (ANSM 2012 No. 40). The results should contribute to educating all practitioners (general physicians, pediatricians, psychiatrists, child psychiatrists) on adverse events, helping practitioners with prescribing decisions, reinforcing the French system of monitoring adverse events caused by atypical antipsychotic drugs, and developing recommendations to improve the safety of atypical antipsychotic drugs in child psychiatry. PMID:25482998
Menard, M-L; Askenazy, F; Auby, P; Bonnot, O; Cohen, D
Synchronized separation of seven medications representing most commonly prescribed antihypertensive classes by using reversed-phase liquid chromatography: Application for analysis in their combined formulations.
A reversed-phase high-performance liquid chromatography method was developed for the simultaneous determination of the diuretic, hydrochlorothiazide, along with six drugs representing the most commonly prescribed antihypertensive pharmacological classes such as atenolol, a selective ?1 blocker, amlodipine besylate, a calcium channel blocker, moexipril hydrochloride, an angiotensin-converting-enzyme inhibitor, valsartan and candesartan cilexetil, which are angiotensin II receptor blockers, and aliskiren hemifumarate, a renin inhibitor, using irbesartan as an internal standard. The chromatographic separation was achieved using acetonitrile/sodium phosphate dibasic buffer (0.02 M, pH 5.5) at a flow rate of 1 mL/min in gradient elution mode at ambient temperature on a stationary phase composed of an Eclipse XDB-C18 (4.6 × 150 mm, 5 ?m) column. UV detection was carried out at 220 nm. The method was validated according to ICH guidelines. Linearity, accuracy, and precision were satisfactory over the concentration ranges of 2-40 ?g/mL for hydrochlorothiazide and candesartan cilexetil, 20-120, 10-160, 5-40, 20-250, and 5-50 ?g/mL for atenolol, valsartan, moexipril hydrochloride, aliskiren hemifumarate, and amlodipine besylate, respectively. The method was successfully applied for the determination of each of the studied drugs in their combined formulations with hydrochlorothiazide. The developed method is suitable for the quality control and routine analysis of the cited drugs in their pharmaceutical dosage forms. PMID:24482404
Ebeid, Walid M; Elkady, Ehab F; El-Zaher, Asmaa A; El-Bagary, Ramzia I; Patonay, Gabor
Antipsychotic as a class of medications became available for treatment of various psychiatric disorders in the early 1950’s. Over the last 60 years many antipsychotics have become available. In line with the west, Indian researchers have evaluated the efficacy of antipsychotics in various conditions. Additionally, researchers have also evaluated the important safety and tolerability issues. Here, we review data originating from India in the form of drug trials, effectiveness, usefulness, safety and tolerability of antipsychotics. Additionally, data with respect to other important treatment related issues is discussed. PMID:21836703
Avasthi, Ajit; Aggarwal, Munish; Grover, Sandeep; Khan, Mohd Khalid Rasheed
The objective of this study was to estimate the prevalence of antipsychotic use and investigate their association with behavioural and psychological symptoms of dementia (BPSD) and other clinical predictors. Patients with dementia, aged 65 and above and resident in 35 Alzheimer special care units were sequentially enrolled into a 18-month prospective observational study. Data on sociodemographic, cognitive, functional, behavioural and clinical characteristics and drug exposure were collected at baseline and at 6-month intervals up to 18 months. The prevalence of antipsychotic use and the association with BPSD and clinical predictors were analysed. Of the 349 patients with dementia enrolled in the study, 209 (60%) were taking at least one antipsychotic. Risperidone and promazine were the most frequently prescribed antipsychotic; 40.7% simultaneously received a benzodiazepine, 20% an antidepressant. More than 50% were still taking antipsychotics at 18 months of follow-up. No associations were found between antipsychotic use and level of cognitive impairment, basal activity of daily living disability and comorbidity. Multivariate analysis showed that the use of antipsychotics was highest in patients in the highest quartiles of Neuropsychiatric Inventory Scale score (III quartile, odds ratio: 1.63; 95% confidence interval: 1.19-2.23; IV quartile, odds ratio: 2.27; 95% confidence interval: 1.61-3.26). This study found high rate of use of antipsychotics in patients with dementia resident in Alzheimer special care units, frequent associations with other psychotropic medications and a strong correlation with BPSD. PMID:21456106
Nobili, Alessandro; Pasina, Luca; Trevisan, Silvia; Riva, Emma; Lucca, Ugo; Tettamanti, Mauro; Matucci, Marina; Tarantola, Massimo
Background. Prior studies of antipsychotic use in individuals with post-traumatic stress disorder (PTSD) are limited because administrative data lacks information on why providers choose particular medications. Methods. This study examined 2613 provider surveys completed at the time any second generation antipsychotic (SGA) was prescribed over a 20-month period at a single Veterans Affairs medical center. Clinical correlates and reasons for SGA selection among individuals with PTSD compared to those with other psychiatric disorders were identified using chi-square. Results. PTSD was the sole diagnosis in n = 339 (13%) and one of several psychiatric diagnoses in n = 236 (9%) surveys. 'Efficacy' was the most common reason given for the prescriptions of SGAs in all surveys (51%) and among individuals with PTSD (46%). 'Sleep/sedation' was the only reason cited, significantly more frequently among those with PTSD (39% with PTSD only, 35% with PTSD plus another diagnosis, and 31% without PTSD [? 2 = 12.86, p < 0.0016)]. The proportion identifying 'efficacy' as a reason for SGA use was smaller in patients with PTSD (44% with PTSD only, 49% with PTSD and another diagnosis, and 53% without PTSD [? 2 = 8.78, p < 0.0125)]. Quetiapine was the most frequently prescribed SGA in the entire sample and among veterans with PTSD (47%). Conclusions. Clinician use of SGAs is often driven by efficacy, for which there is limited evidence, and distinctly driven by the goal of sedation among patients with PTSD. PMID:24007653
Hermes, E; Sernyak, M; Rosenheck, R
Background: Psychiatric disorders are one of the major causes of morbidity. Development of newer drugs like SSRIs and atypical antipsychotics has altered the treatment paradigms. Various factors like cost of drugs, local paradigms, etc. play a role in the selection of drug therapy and hence, affect the outcome. Keeping this in mind, we conducted a study to delineate the various drugs used in psychiatric disorders, to find discrepancies, if any, between the actual and the ideal prescribing pattern of psychotropic drugs and to conduct a cost analysis. Material and Methods: After our institutional ethics committee approved, a retrospective cross sectional drug utilization study of 600 prescriptions was undertaken. Preparation of the protocol and conduct of the study was as per the WHO – DUS and the STROBE guidelines. Results: Drug use indicators – In 600 prescriptions, 1074 (88.25%) were psychotropic drugs. The utilization from the National and WHO EML was 100% and 90%, respectively. Average number of psychotropic drugs per prescription was 1.79 ± 1.02 (SD). 22.5% of the prescriptions contained psychotropic FDCs. 76.01% of drugs were prescribed by generic name. Percentage of psychotropic drugs prescribed from the hospital drug schedule and psychotropic drugs actually dispensed from the hospital drug store were 73.1% and 62.3%, respectively. Drug utilization pattern in different psychiatric disorders – Most commonly prescribed drugs for schizophrenia, bipolar disorders, depression and anxiety disorders were trifluoperazine + trihexiphenydyl (63.9%), carbamazepine (17.2%), amitriptyline (34.9%), and diazepam (23.8%), respectively. The least commonly prescribed drugs were levosulpiride (1.7%), lithium (1.3%), bupropion (4.7%) and clozapine (1.9%), respectively. The PDD/DDD ratio of three drugs – haloperidol, pimozide and amitriptyline – was equal to one. The cost borne by the hospital was 116, i.e., 65.2% of the total cost. The cost index of clozapine was 11.2. Conclusion: Overall, the principles of rational prescribing were followed. The hospital drug schedule should include more SSRIs. The practice of using 1st generation/ typical anti–psychotics as the first line was as per current recommendations. Anti–cholinergics should be used only in selected cases of patients on anti–psychotics. The use of diazepam should be curtailed and it should be used for short term only. PMID:24551631
Thakkar, Karan B.; Jain, Mangal M.; Billa, Gauri; Joshi, Abhijit; Khobragade, Akash A.
Background Nursing home patients with dementia may be more likely to suffer adverse drug events from suboptimal prescribing. Previous studies have not had national samples nor have they examined multiple types of suboptimal prescribing by dementia severity. Objective To examine the prevalence of, and factors associated with, potentially suboptimal prescribing in older Veteran nursing home patients with dementia. Methods This is a retrospective descriptive study of 1303 Veterans 65 years or older admitted between 1/1/04–6/3/05 with dementia for long stays (90+ days) to 133 Veterans Affairs Community Living Centers. Dementia severity was determined by Cognitive Performance Scale and functional status dependencies. Results Overall,70.2% with mild-moderate dementia (n = 1076) had underuse as they did not receive an acetylcholinesterase inhibitor (AChEI), and 27.2% had evidence of inappropriate use due to a drug-disease or drug-drug-disease interaction. Of the 227 with severe dementia, 36.1% had overuse by receiving an AChEI, lipid-lowering or other agents, and 25.1% had evidence of inappropriate use due to a drug-disease or drug-drug interaction. Multinomial logistic regression analyses among those with mild to moderate dementia identified that living in the South versus other regions was the single factor associated with all three types of suboptimal prescribing. In those with severe dementia, antipsychotic use was associated with all three suboptimal prescribing types. Conclusions Potentially suboptimal prescribing was common in older Veteran nursing home patients with dementia. Clinicians should develop a heightened awareness of these problems. Future studies should examine associations between potentially suboptimal prescribing and health outcomes in patients with dementia. PMID:25380592
Hanlon, Joseph T.; Aspinall, Sherrie L.; Handler, Steven M.; Gellad, Walid F.; Stone, Roslyn A.; Semla, Todd P.; Pugh, Mary Jo V.; Dysken, Maurice W.
Antiepileptic and antipsychotic drugs are often prescribed together. Interactions between the drugs may affect both efficacy and toxicity. This is a review of human clinical data on the interactions between the antiepileptic drugs carbamazepine, valproic acid (sodium valproate), vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine, oxcarbazepine, levetiracetam, pregabalin, felbamate, zonisamide, phenobarbital and phenytoin with the antipsychotic drugs risperidone, olanzapine, quetiapine, clozapine, amisulpride, sulpiride, ziprasidone, aripiprazole, haloperidol and chlorpromazine; the limited information on interactions between antiepileptic drugs and zuclopenthixol, periciazine, fluphenazine, flupenthixol and pimozide is also presented. Many of the interactions depend on the induction or inhibition of the cytochrome P450 isoenzymes, but other important mechanisms involve the uridine diphosphate glucuronosyltransferase isoenzymes and protein binding. There is some evidence for the following effects. Carbamazepine decreases the plasma concentrations of both risperidone and its active metabolite. It also decreases concentrations of olanzapine, clozapine, ziprasidone, haloperidol, zuclopenthixol, flupenthixol and probably chlorpromazine and fluphenazine. Quetiapine increases the ratio of carbamazepine epoxide to carbamazepine and this may lead to toxicity. The data on valproic acid are conflicting; it may either increase or decrease clozapine concentrations, and it appears to decrease aripiprazole concentrations. Chlorpromazine possibly increases valproic acid concentrations. Lamotrigine possibly increases clozapine concentrations. Phenobarbital decreases clozapine, haloperidol and chlorpromazine concentrations. Phenytoin decreases quetiapine, clozapine, haloperidol and possibly chlorpromazine concentrations. There are major gaps in the data. In many cases there are no published clinical data on interactions that would be predicted on theoretical grounds. PMID:16454538
Besag, Frank M C; Berry, David
Until the introduction of the first atypical antipsychotic, clozapine, in 1975, hyperprolactinemia was assumed to be an inevitable consequence of treatment with any antipsychotic agent. Now we know that atypical antipsychotics such as clozapine, olanzapine, quetiapine, sertindole, and ziprasidone are not associated with significant prolactin increase. These new antipsychotics appear to spare dopamine blockade within the brain's tubero-infundibular tract, a
Richard G. Petty
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. PMID:23678347
To characterize current treatment practices, we compared the use of atypical antipsychotic drugs among women of childbearing age to men based on electronic medical records of 1073 hospital-based psychiatric outpatients given at least one second-generation antipsychotic drug. One quarter of psychiatric outpatients sampled were prescribed at least one atypical antipsychotic, in more than half of cases for off-label indications. Women were significantly more likely than men to be diagnosed with mood or anxiety disorders than psychotic disorders and to be prescribed quetiapine (60.7 vs. 48.0 %) or aripiprazole (31.2 vs. 23.9 %), but less likely risperidone (15.8 vs. 26.1 %) or ziprasidone (10 vs. 14 %). PMID:25253022
Camsar?, Ulas; Viguera, Adele C; Ralston, Laurel; Baldessarini, Ross J; Cohen, Lee S
We compared classes of medication and inappropriately prescribed medications (IPDs) (potentially not indicated for seniors) to functional status and quality of life (QOL) in 1,099 seniors. We used data from the Physical Health Measure of the Older Americans Resources and Services (OARS) instrument, Functional Independence Measure (FIM), Instrumental Activities of Daily Living (IADL) of the OARS, two QOL questions, and
Sherrilene Classen; L William; Kerry Walsh; William Mann
Background Long-term treatment with antipsychotic medications in early episode schizophrenia spectrum disorders is common, but both short and long-term effects on the illness are unclear. There have been numerous suggestions that people with early episodes of schizophrenia appear to respond differently than those with multiple prior episodes. The number of episodes may moderate response to drug treatment. Objectives To assess the effects of antipsychotic medication treatment on people with early episode schizophrenia spectrum disorders. Search methods We searched the Cochrane Schizophrenia Group register (July 2007) as well as references of included studies. We contacted authors of studies for further data. Selection criteria Studies with a majority of first and second episode schizophrenia spectrum disorders comparing initial antipsychotic medication treatment with placebo, milieu, or psychosocial treatment. Data collection and analysis Working independently, we critically appraised records from 681 studies, of which five studies met inclusion criteria. We calculated risk ratios (RR) and their 95% confidence intervals (CI) where possible. For continuous data, we calculated mean difference (MD). We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results Five studies (combined total n=998) met inclusion criteria. Four studies (n=724) provided leaving the study early data and results suggested that individuals treated with a typical antipsychotic medication are less likely to leave the study early than those treated with placebo (Chlorpromazine: 3 RCTs n=353, RR 0.4 CI 0.3 to 0.5, NNT 3.2, Fluphenaxine: 1 RCT n=240, RR 0.5 CI 0.3 to 0.8, NNT 5; Thioridazine: 1 RCT n=236, RR 0.44 CI 0.3 to 0.7, NNT 4.3, Trifulperazine: 1 RCT n=94, RR 0.96 CI 0.3 to 3.6). Two studies contributed data to assessment of adverse effects and present a general pattern of more frequent side effects among individuals treated with typical antipsychotic medications compared to placebo. One trial suggested a higher rehospitalisation rate for those receiving chlorpromazine compared to placebo (n=80, RR 2.29 CI 1.3 to 4.0, NNH 2.9). However, a higher attrition in the placebo group is likely to have introduced a survivor bias into this comparison, as this difference becomes non-significant in a sensitivity analysis on intent-to-treat participants (n=127, RR 1.69 CI 0.9 to 3.0). One study contributes data to a comparison of trifluoperazine to psychotherapy on long-term health in favour of the trifluoperazine group (n=92, MD 5.8 CI 1.6 to 0.0); however, data from this study are also likely to contain biases due to selection and attrition. One other study contributes data to a comparison of typical antipsychotic medication to psychosocial treatment on six-week outcome measures of global psychopathology (n=89, MD 0.01 CI ?0.6 to 0.6) and global improvement (n=89, MD ?0.03 CI ?0.5 to 0.4), indicating no between-group differences. On the whole, there is very little useable data in the few studies meeting inclusion criteria. Authors’ conclusions With only a few studies meeting inclusion criteria, and with limited useable data in these studies, it is not possible to arrive at definitive conclusions. The preliminary pattern of evidence suggests that people with early episode schizophrenia treated with typical antipsychotic medications are less likely to leave the study early, but more likely to experience medication-related side effects. Data are too sparse to assess the effects of antipsychotic medication on outcomes in early episode schizophrenia. PMID:21678355
Bola, John; Kao, Dennis; Soydan, Haluk; Adams, Clive E
The challenge to achieve safe prescribing merits the adjective ‘titanic’. The organisational and human errors leading to poor prescribing (e.g. underprescribing, overprescribing, misprescribing or medication errors) have parallels in the organisational and human errors that led to the loss of the Titanic 100 years ago this year. Prescribing can be adversely affected by communication failures, critical conditions, complacency, corner cutting, callowness and a lack of courage of conviction, all of which were also factors leading to the Titanic tragedy. These issues need to be addressed by a commitment to excellence, the final component of the ‘Seven C's’. Optimal prescribing is dependent upon close communication and collaborative working between highly trained health professionals, whose role is to ensure maximum clinical effectiveness, whilst also protecting their patients from avoidable harm. Since humans are prone to error, and the environments in which they work are imperfect, it is not surprising that medication errors are common, occurring more often during the prescribing stage than during dispensing or administration. A commitment to excellence in prescribing includes a continued focus on lifelong learning (including interprofessional learning) in pharmacology and therapeutics. This should be accompanied by improvements in the clinical working environment of prescribers, and the encouragement of a strong safety culture (including reporting of adverse incidents as well as suspected adverse drug reactions whenever appropriate). Finally, members of the clinical team must be prepared to challenge each other, when necessary, to ensure that prescribing combines the highest likelihood of benefit with the lowest potential for harm. PMID:22738396
Routledge, Philip A
The challenge to achieve safe prescribing merits the adjective 'titanic'. The organisational and human errors leading to poor prescribing (e.g. underprescribing, overprescribing, misprescribing or medication errors) have parallels in the organisational and human errors that led to the loss of the Titanic 100 years ago this year. Prescribing can be adversely affected by communication failures, critical conditions, complacency, corner cutting, callowness and a lack of courage of conviction, all of which were also factors leading to the Titanic tragedy. These issues need to be addressed by a commitment to excellence, the final component of the 'Seven C's'. Optimal prescribing is dependent upon close communication and collaborative working between highly trained health professionals, whose role is to ensure maximum clinical effectiveness, whilst also protecting their patients from avoidable harm. Since humans are prone to error, and the environments in which they work are imperfect, it is not surprising that medication errors are common, occurring more often during the prescribing stage than during dispensing or administration. A commitment to excellence in prescribing includes a continued focus on lifelong learning (including interprofessional learning) in pharmacology and therapeutics. This should be accompanied by improvements in the clinical working environment of prescribers, and the encouragement of a strong safety culture (including reporting of adverse incidents as well as suspected adverse drug reactions whenever appropriate). Finally, members of the clinical team must be prepared to challenge each other, when necessary, to ensure that prescribing combines the highest likelihood of benefit with the lowest potential for harm. PMID:22738396
Routledge, Philip A
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. PMID:23983926
Patel, Maxine X.; Matonhodze, Jane; Baig, Mirza K.; Gilleen, James; Boydell, Jane; Holloway, Frank; Taylor, David; Szmukler, George; Lambert, Tim; David, Anthony S.
Objectives to determine whether antipsychotic medication initiation is associated with subsequent fracture in nursing home residents, whether fracture rates differ between first-generation versus second-generation antipsychotic use, and whether fracture rates differ among users of haloperidol, risperidone, olanzapine, and quetiapine. Design time-to-event analyses were conducted in a retrospective cohort using linked Medicaid, Medicare, Minimum Data Set and Online Survey, Certification and Reporting data sets. Setting and Participants nursing home residents aged ? 65 years in CA, FL, MO, NJ and PA. Measurements fracture outcomes (any fracture; hip fracture) in first-versus second-generation antipsychotic users, and specifically among users of haloperidol, risperidone, olanzapine and quetiapine. Comparisons incorporated propensity scores that included patient-level variables (demographics, comorbidity, diagnoses, weight, fall history, concomitant medications, cognitive performance, physical function, aggressivebehavior) and facility-level variables (nursing home size, ownership factors, staffing levels). Results Among 8,262 subjects (within 4,131 pairs), 4.3% suffered any fracture during observation with 1% having a hip fracture during an average follow up period of 93 ± 71 days; range 1 to 293 days). Antipsychotic initiation was associated with any fracture (hazard ratio (HR) 1.39, p=0.004) and with hip fracture (HR 1.76, p=0.024). The highest risk was found for hip fracture when antipsychotic use was adjusted for dose(HR=2.96; p=0.008). However, no differences in time-to-fracture were found in first-versus second-generation agents or across competing individual drugs. Conclusion Antipsychotic initiation is associated with fracture in nursing home residents, but risk does not differ across commonly used antipsychotics. PMID:23590366
Rigler, Sally K.; Shireman, Theresa I.; Cook-Wiens, Galen J.; Ellerbeck, Edward F.; Whittle, Jeffrey C.; Mehr, David R.; Mahnken, Jonathan D.
Background In screening the Intercontinental Medical Statistics (IMS) Health Disease Analyzer database of GP records from the UK, an increased registration of pneumonia subsequent to the prescription of some antipsychotic medicines was identified. Aim To investigate the temporal pattern between antipsychotic prescriptions and pneumonia with respect to age, type of pneumonia and other chest infections, and antipsychotic class. Design of study Self-controlled cohort analysis. Setting Electronic health records from the UK IMS Health Disease Analyzer database. Method Three groups of pneumonia-related International Classification of Diseases (ICD)-10 terms and prescriptions of atypical and conventional antipsychotic medicines were studied. Separate analyses were carried out for patients aged a65 years. The observed rate of pneumonia terms registered in different time periods in connection to antipsychotic prescriptions was contrasted to the overall rate of pneumonia terms relative to prescriptions of other drugs in the same dataset. Results In patients aged ?65 years, an increased registration of a group of terms defined as ‘acute chest infections’, after atypical antipsychotic prescriptions, was identified. The corresponding increase after conventional antipsychotic prescriptions was much smaler. Bronchopneumonia had a striking increase after both atypical and conventional antipsychotic prescriptions, and was commonly recorded with fatal outcome. Few registrations of hypostatic pneumonia were noted. Patients aged <65 years did not have a higher rate of acute chest infections after receiving antipsychotic prescriptions. Conclusion The consistent pattern of an increased rate of chest infections after atypical antipsychotic prescriptions in older people seen in this outpatient study, together with the higher risk shown in a previous study on hospitalised patients, suggests a causal relationship. This is of importance since bronchopneumonia seems highly linked to fatal outcome. In the absence of a mechanism, further investigation of the role of antipsychotics in older people is needed. PMID:20883613
Star, Kristina; Bate, Andrew; Meyboom, Ronald HB; Edwards, I Ralph
Objective: This study was designed to investigate the strategies employed by consumers to manage the common side effects associated with antipsychotic medication use.Method: Focus group discussions and individual interviews involving 238 consumers, 25 carers and 16 mental health staff were employed to identify key side effects and a range of consumer coping strategies for managing these adverse effects.Results: Nine side
Tom Meehan; Terry Stedman; Jane Wallace
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
Objective: During the past decades, increasing efforts have been invested in studies to unravel the influence of genetic factors on antipsychotic (AP) dosage, treatment response, and occurrence of adverse effects. These studies aimed to improve clinical care by predicting outcome of treatment with APs and thus allowing for individualized treatment strategies. We highlight most important findings obtained through both candidate gene and genome-wide association studies, including pharmacokinetic and pharmacodynamic factors. Methods: We reviewed studies on pharmacogenetics of AP response and adverse effects published on PubMed until early 2012. Owing to the high number of published studies, we focused our review on findings that have been replicated in independent studies or are supported by meta-analyses. Results: Most robust findings were reported for associations between polymorphisms of the cytochrome P450 system, the dopamine and the serotonin transmitter systems, and dosage, treatment response, and adverse effects, such as AP-induced weight gain or tardive dyskinesia. These associations were either detected for specific medications or for classes of APs. Conclusion: First promising and robust results show that pharmacogenetics bear promise for a widespread use in future clinical practice. This will likely be achieved by developing algorithms that will include many genetic variants. However, further investigation is warranted to replicate and validate previous findings, as well as to identify new genetic variants involved in AP response and for replication of existing findings. PMID:24881126
Brandl, Eva J; Kennedy, James L; Müller, Daniel J
The typicality of atypical antipsychotic drugs remains debatable. Preclinical studies and findings from randomized, controlled and open trials of clozapine, olanzapine, risperidone, quetiapine, sertindole, ziprasidone and a substituted benzamide were examined. A MEDLINE search was conducted using key words, including "extrapyramidal side effects," "cognition," "schizophrenia" and the generic drug names. Over 140 articles from peer-reviewed journals were reviewed, some of which were based on a meta-analysis. New-generation neuroleptic agents were found to have greater efficacy on the negative symptoms of schizophrenia and to cause fewer unwanted extrapyramidal side effects (EPS) than the traditional antipsychotic drugs. On one hand, atypical neuroleptic agents could be strictly defined as any neuroleptic agent with antipsychotic effects at a dosage that does not cause extrapyramidal side effects. Thus, clozapine is regarded as the "standard" atypical antipsychotic drug. On the other hand, typicality is about dimension rather than category, and we suggest the use of the term "spectrum of atypicality." For example, an emphasis is placed on quetiapine to illustrate where a new compound fits in this spectrum. Although dose-related, atypicality may be more a question of prescription attitude than of a specific characteristic of a compound. The degree to which a new compound is clinically superior to another atypical antipsychotic drug, in terms of improving positive, negative or affective symptoms, cognitive function and long-term outcome, will require further a priori hypotheses based on conceptual frameworks that are clinically meaningful. In addition, the results from industry-sponsored trials should be more comparable to those obtained from investigator-leading trials. Finally, the patient characteristics that define a patient's response to a specific antipsychotic drug are unknown. PMID:10740987
The purpose of this article is to determine prescribing rates and adherence to guidelines with regard to antipsychotic polypharmacy, high-dose prescribing, and sedative use in an outpatient population. A prospective case-note audit involving 250 consecutive attendees of an outpatient clinic was carried out. Data were analyzed using descriptive statistical methods. Differences between the groups were estimated using t test and chi(2) where applicable. Results showed that the rate of polypharmacy was 17.4%. Reasons for polypharmacy were documented in 53% of cases. High-dose antipsychotics were used in 2.5% of the monotherapy group and in 38% of the polypharmacy group. An ECG was done in 35% of patients on high-dose antipsychotic therapy. In the monotherapy group, 6.2% versus 26.5% in the polypharmacy group of patients were on at least 1 sedative or hypnotic (odds ratio [OR], 5.47; 95% confidence interval [CI], 2.02-14.82; P < .001). Forty-two percent of patients prescribed sedatives had schizophrenia spectrum disorders, and none of the patients were diagnosed with anxiety disorders. The current study confirms that despite repeated recommendations against the practice, polypharmacy rates remain consistent at the 20% level. Thorough documentation, calculating the total antipsychotic dose, and obtaining an ECG would constitute good practice. PMID:20056801
Ranceva, Nadezda; Ashraf, Wasim; Odelola, Deji
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.
Second-generation antipsychotics (SGAs) are associated with significant comorbid metabolic abnormalities. Adjunct medications may be prescribed to treat these metabolic side effects, but the evidence supporting this practice (especially for the management of antipsychotic-associated dyslipidemia and hypertension) is limited. The purpose of this review was to evaluate the effects of adjunct medications on triglyceride, total cholesterol, low-density lipoprotein, high-density lipoprotein, and blood pressure levels in participants taking SGAs for psychosis. Studies were systematically searched and evaluated. Studies were included for review if participants were taking SGAs and if lipid and/or blood pressure levels were included as outcome measures. Statins, conventional lipid-lowering agents, fluvoxamine, ramelteon, topiramate, valsartan, telmisartan, omega-3 fatty acids, metformin (including both immediate-release and extended-release formulations), and a combination of metformin-sibutramine seemed to have beneficial effects on lipid levels. Valsartan, telmisartan, and topiramate appeared to be effective for controlling increases in blood pressure. The literature on adjunct medications for the treatment of antipsychotic-associated dyslipidemia and hypertension is not exhaustive, and long-term randomized-controlled trials would offer valuable results. PMID:24169026
Tse, Lurdes; Procyshyn, Ric M; Fredrikson, Diane H; Boyda, Heidi N; Honer, William G; Barr, Alasdair M
Autobiographical memory loss is a common and disturbing problem for individuals with Alzheimer's disease (AD). Patients with AD who are taking antipsychotic medications may be at further risk for loss of recent autobiographical memory because of the potential anticholinergic side effects of antipsychotics. The purpose of this post hoc, descriptive study was to compare the recent autobiographical memory scores of patients with AD taking antipsychotics to those who were not taking antipsychotics. The study population was composed of 35 patients with moderate-stage AD. Patients who were taking antipsychotics scored significantly worse on a recent autobiographical memory measure compared with patients who were not taking antipsychotics. This study provides further evidence for judicious use of antipsychotic medications with AD patients. PMID:17598623
Harrison, Barbara E; Therrien, Barbara
Background Discontinuation of antipsychotic treatment for schizophrenia can interrupt improvement and exacerbate the illness. Reasons for discontinuing treatment are multifactorial and include adherence, efficacy and tolerability issues. Poor adherence may be addressed through non-pharmacological approaches as well as through pharmacological ones, ie ensured delivery of medication, such as that achieved with long-acting injectable (LAI) antipsychotics. However, attitudes of healthcare professionals (HCPs) towards LAI antipsychotics may influence their prescribing decisions and may influence medication choices offered to patients. We therefore conducted a survey to investigate factors driving LAI use as well as physician and nurse attitudes to LAI antipsychotics and to different injection sites. Methods An independent market research agency conducted the survey of HCPs across Europe. Participants were recruited by telephone and completed the survey online. Using conjoint analyses (a multivariate statistical technique analysing preferences on the basis of ranking a limited number of attributes which are presented repetitively), attitudes to oral versus LAI medication and gluteal versus deltoid injection routes were assessed. Results A total of 891 HCPs across Europe were surveyed. Of these, 40% would choose LAI antipsychotics for first episode patients whereas 90% would select LAI antipsychotics for chronic patients with two to five psychotic episodes. Dominant elements in antipsychotic choice were low sedation but no tardive dyskinesia, no or mild pain at injection and low risk of embarrassment or impact upon therapeutic alliance. Eighty-six per cent of respondents considered that having the choice of a deltoid as well as gluteal administration site was beneficial over not having that choice. Two thirds of respondents said they agreed that medication administration via the deltoid muscle may reduce social embarrassment associated with LAI antipsychotics and most respondents (61%) believed that administration of LAI antipsychotics into the deltoid muscle as opposed to the gluteal muscle may be more respectful to the patient. Conclusions In this survey of physicians and nurses, attitudes towards LAI antipsychotics compared with oral medication were generally positive. Respondents considered that the availability of a deltoid administration route would offer increased choice in LAI antipsychotic administration and may be perceived as more respectful and less socially embarrassing. PMID:23414331
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
Objective: To evaluate health care resource utilization in patients with schizophrenia who continued newly prescribed antipsychotic medications, compared with those switching to different treatments. Methods: Adults with schizophrenia in the California Medicaid (MediCal) database who initiated treatment with index medications in 1998–2001, were classified as having: 1) abandoned antipsychotic medications; 2) switched to another medication; or 3) continued with the index antipsychotic, for up to 6 months after the index date. Results: Of 2300 patients meeting eligibility criteria, 1382 (60.1%) continued index medications, 480 (20.9%) switched, and 438 (19.0%) abandoned antipsychotic treatment. Utilization in several resource categories occurred significantly more frequently among patients whose regimens were switched (vs those continuing index medications). These included using psychiatric (24.2% vs 14.5%; P < 0.001) or nonpsychiatric (31.5% vs 24.3%; P < 0.05) emergency services; being admitted to a hospital (10.6% vs 7.4%; P < 0.05); making nonpsychiatric outpatient hospital visits (43.3% vs 36.4%; P < 0.05) or nonpsychiatric physician visits (62.7% vs 56.4%; P < 0.05); and using other outpatient psychiatric (53.3% vs 40.7%; P < 0.001) or nonpsychiatric (82.7% vs 74.6%; P < 0.001) services. Conclusions: Switching antipsychotic medications is associated with significantly increased health care resource utilization (vs continuing treatment). PMID:20694186
Noordsy, Douglas L; Phillips, Glenn A; Ball, Daniel E; Linde-Zwirble, Walter T
Background Postmarketing surveillance that identifies patients at high risk for receiving off-label medications will help ensure that the benefits of such treatment outweigh the risks. Because many off-label uses have little scientific support, tracking the extent to which they occur as well as the particular circumstances under which they occur is important. Objective To describe the drug-use pattern for patients with bipolar disorder, and to identify demographic and clinical factors associated with off-label use of atypical antipsychotics before US Food and Drug Administration approval for this indication. Methods Using the PHARMetrics medical claims database, a total of 105,771 adult patients with a diagnosis of bipolar disorder were evaluated during the 5-year (1998–2002) study period. Study drugs included mood stabilizers, antipsychotics, and antidepressants. Off-label use of an atypical antipsychotic was defined as a patient taking olanzapine before March 2000 (when it received an indication for bipolar disorder) or any other atypical antipsychotic during the entire study period. Logistic regression analysis was used to determine the odds ratio of receiving a drug off-label. Results Utilization of and reimbursement for atypical antipsychotics increased during the 5-year period. Of the 10.5% of patients who took atypical antipsychotics, 7.1% took these drugs off-label. In addition, 11% of patients received lithium, 25% received other anticonvulsants, and 34% received antidepressants. Off-label use of atypical antipsychotics was associated with psychiatry specialist prescribers (odds ratio = 1.52; 95% CI, 1.44–1.59) and certain comorbidities, such as substance abuse (odds ratio = 1.51; 95% CI, 1.38–1.66), anxiety disorder (odds ratio = 1.20; 95% CI, 1.14–1.26), diabetes mellitus (odds ratio = 1.26; 95% CI, 1.16–1.37), cerebral vascular disease (odds ratio = 1.26; 95% CI, 1.10–1.45), and hypertension (odds ratio = 1.12; 95% CI, 1.05–1.20). Over time, there has been an increase in the number of drug therapies, including atypical antipsychotics, used to treat bipolar disorder. Conclusion Because of the significant association found between atypical antipsychotic use and several key comorbidities, it is important for physicians to recognize these associations and weigh the risks and benefits of atypical antipsychotics in their treatment strategies. PMID:25126291
Demland, Jeffery A.; Jing, Yonghua; Kelton, Christina M. L.; Guo, Jeff J.; Li, Hong; Wigle, Patricia R.
Various types of antipsychotics have been developed for the treatment of schizophrenia since the accidental discovery of the antipsychotic activity of chlorpromazine. Although all clinically effective antipsychotic agents have common properties to interact with the dopamine D2 receptor (D2R) activation, their precise mechanisms of action remain elusive. Antipsychotics are well known to induce transcriptional changes of immediate early genes (IEGs), raising the possibility that gene expressions play an essential role to improve psychiatric symptoms. Here, we report that while different classes of antipsychotics have complex pharmacological profiles against D2R, they share common transcriptome fingerprint (TFP) profile of IEGs in the murine brain in vivo by quantitative real-time PCR (qPCR). Our data showed that various types of antipsychotics with a profound interaction of D2R including haloperidol (antagonist), olanzapine (antagonist), and aripiprazole (partial agonist) all share common spatial TFPs closely homologous to those of D2R antagonist sulpiride, and elicited greater transcriptional responses in the striatum than in the nucleus accumbens. Meanwhile, D2R agonist quinpirole and propsychotic NMDA antagonists such as MK-801 and phencyclidine (PCP) exhibited the contrasting TFP profiles. Clozapine and propsychotic drug methamphetamine (MAP) displayed peculiar TFPs that reflect their unique pharmacological property. Our results suggest that transcriptional responses are conserved across various types of antipsychotics clinically effective in positive symptoms of schizophrenia and also show that temporal and spatial TFPs may reflect the pharmacological features of the drugs. Thus, we propose that a TFP approach is beneficial to evaluate novel drug candidates for antipsychotic development. PMID:25693194
Sakuma, Kensuke; Komatsu, Hidetoshi; Maruyama, Minoru; Imaichi, Sachiko; Habata, Yugo; Mori, Masaaki
SAVANNA RESTORATION THROUGH PRESCRIBED FIRE: DEMOGRAPHIC AND PHYSIOLOGICAL RESPONSES OF OAK of Science, Biology By Douglas P. Aubrey July 2004 #12;SAVANNA RESTORATION THROUGH PRESCRIBED FIRE ABSTRACT Prescribed fire is a common tool for restoring and maintaining degraded oak savannas
Wait, D. Alexander
Background Many women diagnosed with varying psychiatric disorders take antipsychotic medications during pregnancy. The safety of antipsychotic medications in pregnancy is largely unknown. Methods We established the National Register of Antipsychotic Medications in Pregnancy in 2005. Women who are pregnant and taking an antipsychotic medication are interviewed every 6 weeks during pregnancy and then followed until their babies are one year old. The baby's progress is closely followed for the first year of life. Findings As of April 18 2012, 147 pregnancies had been followed through to completion. There were 142 live births and data is available for 100 one year old babies. 18% of babies were born preterm, with a higher dose of antipsychotic medication correlating to an increased likelihood of premature delivery; 43% of babies required special care nursery or intensive care after birth; 37% had any degree of respiratory distress and 15% of babies developed withdrawal symptoms. Congenital anomalies were seen in eight babies. Most pregnancies resulted in the birth of live, healthy babies. The use of mood stabilisers or higher doses of antipsychotics during pregnancy increased the likelihood of babies experiencing respiratory distress or admission to Special Care Nursery or Neonatal Intensive Care Units. Conclusion There is a great need for safety and efficacy information about the use of antipsychotic medications in pregnancy. Live, healthy babies are the most common outcome following the use of antipsychotic medication in pregnancy, but clinicians should be particularly mindful of neonatal problems such as respiratory distress. PMID:24787688
Kulkarni, Jayashri; Worsley, Roisin; Gilbert, Heather; Gavrilidis, Emorfia; Van Rheenen, Tamsyn E.; Wang, Wei; McCauley, Kay; Fitzgerald, Paul
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
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
Schizophrenia is a severe psychiatric disorder often associated with cognitive impairment and affective, mainly depressive, symptoms. Antipsychotic medication is the primary intervention for stabilization of acute psychotic episodes and prevention of recurrences and relapses in patients with schizophrenia. Typical antipsychotics, the older class of antipsychotic agents, are currently used much less frequently than newer atypical antipsychotics. Therapeutic drug monitoring (TDM) of antipsychotic drugs is the specific method of clinical pharmacology, which involves measurement of drug serum concentrations followed by interpretation and good cooperation with the clinician. TDM is a powerful tool that allows tailor-made treatment for the specific needs of individual patients. It can help in monitoring adherence, dose adjustment, minimizing the risk of toxicity and in cost-effectiveness in the treatment of psychiatric disorders. The review provides complex knowledge indispensable to clinical pharmacologists, pharmacists and clinicians for interpretation of TDM results. PMID:25531781
Grundmann, Milan; Kacirova, Ivana; Urinovska, Romana
Although the advent of atypical, second-generation antipsychotics (SGAs) has resulted in reduced likelihood of akathisia, this adverse effect remains a problem. It is known that extrapyramidal adverse effects are associated with increased drug occupancy of the dopamine 2 receptors (DRD2). The A1 allele of the DRD2/ANKK1, rs1800497, is associated with decreased striatal DRD2 density. The aim of this study was to identify whether the A1(T) allele of DRD2/ANKK1 was associated with akathisia (as measured by Barnes Akathisia Rating Scale) in a clinical sample of 234 patients who were treated with antipsychotic drugs. Definite akathisia (a score ? 2 in the global clinical assessment of akathisia) was significantly less common in subjects who were prescribed SGAs (16.8%) than those prescribed FGAs (47.6%), p < 0.0001. Overall, 24.1% of A1+ patients (A1A2/A1A1) who were treated with SGAs had akathisia, compared to 10.8% of A1- (thus, A2A2) patients. A1+ patients who were administered SGAs also had higher global clinical assessment of akathisia scores than the A1- subjects (p = 0.01). SGAs maintained their advantage over FGAs regarding akathisia, even in A1+ patients who were treated with SGAs. These results strongly suggested that A1+ variants of the DRD2/ANKK1 Taq1A allele do confer an associated risk for akathisia in patients who were treated with SGAs, and these variants may explain inconsistencies found across prior studies, when comparing FGAs and SGAs. PMID:23118020
Lawford, B R; Barnes, M; Swagell, C D; Connor, J P; Burton, S C; Heslop, K; Voisey, J; Morris, C P; Nyst, P; Noble, E P; Young, R M
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
Introduction Delirium is an independent risk factor for prolonged hospital length of stay (LOS) and increased mortality. Several antipsychotics have been studied for the treatment of intensive care unit (ICU) delirium that has led to a high variability in prescribing patterns for these medications. We hypothesize that in clinical practice the documentation of delirium is lower than the incidence of delirium reported in prospective clinical trials. The objective of this study was to document the incidence of delirium diagnosed in ICU patients and to describe the utilization of antipsychotics in the ICU. Methods This was a retrospective, observational, cohort study conducted at 71 United States academic medical centers that reported data to the University Health System Consortium Clinical Database/Resource Manager. It included all patients 18 years of age and older admitted to the hospital between 1 January 2010 and 30 June 2010 with at least one day in the ICU. Results Delirium was diagnosed in 6% (10,034 of 164,996) of hospitalizations with an ICU admission. Antipsychotics were administered to 11% (17,764 of 164,996) of patients. Of the antipsychotics studied, the most frequently used were haloperidol (62%; n = 10,958) and quetiapine (31%; n = 5,448). Delirium was associated with increased ICU LOS (5 vs. 3 days, P < 0.001) and hospital LOS (11 vs. 6 days, P < 0.001), but not in-hospital mortality (8% vs. 9%, P = 0.419). Antipsychotic exposure was associated with increased ICU LOS (8 vs. 3 days, P < 0.001), hospital LOS (14 vs. 5 days, P < 0.001) and mortality (12% vs. 8%, P < 0.001). Of patients with antipsychotic exposure in the ICU, absence of a documented mental disorder (32%, n = 5,760) was associated with increased ICU LOS (9 vs. 7 days, P < 0.001), hospital LOS (16 vs. 13 days, P < 0.001) and in-hospital mortality (19% vs. 9%, P < 0.001) compared to patients with a documented mental disorder (68%, n = 12,004). Conclusions The incidence of documented delirium in ICU patients is lower than that documented in previous prospective studies with active screening. Antipsychotics are administered to 1 in every 10 ICU patients. When administration occurs in the absence of a documented mental disorder, antipsychotic use is associated with an even higher ICU and hospital LOS, as well as in-hospital mortality. PMID:22591601
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
Despite variations across individuals and agents, antipsychotics are associated with clearly documented weight gain and adverse metabolic effects. Although increased appetite/caloric intake and various receptors, hormones and peptides have been implicated, biological mechanisms contributing to the increase in weight and glucose and lipid abnormalities with antipsychotics are largely unknown. This has hampered the creation of antipsychotics that are free of cardiometabolic effects, even in antipsychotic-naïve/early-phase patients, as well as the development of strategies that can prevent or drastically diminish the adverse cardiometabolic effects. In general, three strategies can reduce the cardiometabolic risk of antipsychotics: 1) switching to a less orexigenenic/metabolically adverse antipsychotic, 2) adjunctive behavioral treatments and 3) adjunctive pharmacologic interventions. However each of these strategies has only been modestly effective. Among different behavioral interventions (N=14, n=746), group and individual treatment, dietary counseling and cognitive-behavioral therapy seem to be similarly effective. Among 15 different pharmacologic strategies (N=35 , n=1,629), only metformin, fenfluramine, sibutramine, topiramate and reboxetine were more effective than placebo, with the most evidence being available for metformin, yet without any head-to-head trials comparing individual pharmacologic interventions. Even in the most successful trials, however, the risk reduction was modest. Weight was not decreased to a pre-treatment level, and despite superiority compared to placebo, weight gain still often occurred, particularly in antipsychotic-naïve patients and when interventions were “preventively” co-initiated with antipsychotics. Future research should focus on combining treatment modalities or agents and on exploring novel mechanism-based interventions. PMID:20586697
Maayan, Lawrence; Correll, Christoph U.
Background: Given the paucity of research in this area, this study attempted to assess attitudes toward antipsychotic medications and its correlates among patients with schizophrenia, either on first-generation antipsychotics (FGAs) or second-generation antipsychotics (SGAs) medications. Materials and Methods: Structured assessments of attitudes to antipsychotics, psychopathology, insight and side-effects were carried out in 120 patients with DSM-IV schizophrenia; 89 of these were on SGAs and 31 on FGAs. Results: Patients had predominantly positive attitudes toward antipsychotics. Severity of side-effects was the principal correlate of attitudes, explaining 19.5% of the variance, followed by greater insight (4.2% of the variance). Other factors such as younger age, male gender, employment, higher family income, urban residence and lower symptom-severity explained only a negligible proportion of the variance (0.2%) in attitudes. Patients on SGAs had more positive views of their medications than those on FGAs. They felt more normal on their medications, believed that their thoughts were clearer on medications, felt that good things about their medications outweighed the bad and believed that their medications helped them from falling ill again. In addition, they did not feel as tired and sluggish on their medications and did not believe that medications were unnatural or controlled their bodies. Conclusions: Positive attitudes toward antipsychotics were common among patients with schizophrenia. Attitudes were principally determined by severity of side-effects and insight levels. Patients on SGAs had better attitudes, possibly because of less severe side-effects and greater insight among them. The importance of exploring patients’ attitudes toward their antipsychotics is highlighted by this study. PMID:25035553
Karthik, M. S.; Warikoo, Nisha; Chakrabarti, Subho; Grover, Sandeep; Kulhara, Parmanand
Background Attitudes towards antipsychotic medication play an important part in the treatment for schizophrenia and related disorders. We aimed measuring general practitioners' attitudes to antipsychotic drugs and their adverse side effects and comparing these with the attitudes of the general population. Methods Analysis and comparison of two representative samples, one comprising 100 General Practitioners (GPs), the other 791 individuals randomly selected from the general population. The setting was the German speaking cantons of Switzerland. Results General practitioners have significantly more positive attitudes towards anti-psychotic drugs than the general public. They reject widespread prejudices about the use of anti-psychotic medication significantly more than the general population. In particular the risk of dependency was assessed as 'low' by GP's (80%), in contrast to only 18% of the general population sample. In no instance did a majority of the GPs advise not tolerating any of the 10 possible adverse effects presented in this study. This is in marked contrast to the general population sample, where a majority recommended discontinuation for movement disorder (63%), strong tremor (59%), risk of dependency (55%) and feelings of unrest (54%). Conclusion As well as effective management of side-effects being a vital aspect of patient and carer education, prescribing doctors need to be aware that their mentally ill patients are likely to be confronted with extremely negative public attitudes towards antipsychotic medication and with strong pressures to stop taking their medication in the event of side-effects. PMID:17049093
Helbling, Josef; Ajdacic-Gross, Vladeta; Lauber, Christoph; Weyermann, Ruth; Burns, Tom; Rössler, Wulf
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. PMID:22966439
Kim, Borah; Lee, Sang-Hyuk; Yang, Yen Kuang; Park, Jong-Il; Chung, Young-Chul
Objective Strong concerns have been raised about whether the risk of ischemic stroke differs between conventional antipsychotics (CAPs) and atypical antipsychotics (AAPs). This study compared the risk of ischemic stroke in elderly patients taking CAPs and AAPs. Method We conducted a retrospective cohort study of 71,584 elderly patients who were newly prescribed the CAPs (haloperidol or chlorpromazine) and those prescribed the AAPs (risperidone, quetiapine, or olanzapine). We used the National Claims Database from the Health Insurance Review and Assessment Service (HIRA) from January 1, 2006 to December 31, 2009. Incident cases for ischemic stroke (ICD-10, I63) were identified. The hazard ratios (HR) for AAPs, CAPs, and for each antipsychotic were calculated using multivariable Cox regression models, with risperidone as a reference. Results Among a total of 71,584 patients, 24,668 patients were on risperidone, 15,860 patients on quetiapine, 3,888 patients on olanzapine, 19,564 patients on haloperidol, and 7,604 patients on chlorpromazine. A substantially higher risk was observed with chlorpromazine (HR = 3.47, 95% CI, 1.97–5.38), which was followed by haloperidol (HR = 2.43, 95% CI, 1.18–3.14), quetiapine (HR = 1.23, 95% CI, 0.78–2.12), and olanzapine (HR = 1.12, 95% CI, 0.59–2.75). Patients who were prescribed chlorpromazine for longer than 150 days showed a higher risk (HR = 3.60, 95% CI, 1.83–6.02) than those who took it for a shorter period of time. Conclusions A much greater risk of ischemic stroke was observed in patients who used chlorpromazine and haloperidol compared to risperidone. The evidence suggested that there is a strong need to exercise caution while prescribing these agents to the elderly in light of severe adverse events with atypical antipsychotics. PMID:25790285
Shin, Ju-Young; Choi, Nam-Kyong; Lee, Joongyub; Seong, Jong-Mi; Park, Mi-Ju; Lee, Shin Haeng; Park, Byung-Joo
Cardiovascular disease is more common in schizophrenia patients than in the general population, with a hypothesized contribution from increases in adiposity produced by antipsychotic medications. We sought to test the relationship between adiposity and insulin resistance using frequently sampled intravenous glucose tolerance tests (FSIVGTTs) to quantify whole-body insulin sensitivity in chronically treated patients with schizophrenia or schizoaffective disorder and untreated
Dan W Haupt; Peter A Fahnestock; Karen A Flavin; Julie A Schweiger; Angela Stevens; Martha J Hessler; Justin Maeda; Michael Yingling; John W Newcomer
Atypical antipsychotics will continue to be prescribed for the behavioral symptoms of dementia in the absence of more effective, better tolerated, and safer alternatives. The evidence base, although incomplete, suggests that modest treatment effect sizes are offset by risk of considerable adverse effects. How might this information be best applied to clinical practice? Non-pharmacologic strategies should be implemented in routine clinical practice. Placebo-controlled clinical trials of individual antipsychotic agents have historically reported high placebo response rates; CATIE-AD reported that the sum total of the risk/benefit equation of atypical antipsychotic therapy was no greater than that achieved by placebo. CATIE-AD was designed to study the effectiveness of atypical antipsychotic treatment in community dwelling patients with AD. It is uncertain whether the results can be generalized to the populations of dementia patients residing in nursing homes with more severe cognitive and behavioral impairment. There is some suggestion that nursing home patients with dementia complicated by severe behavioral symptoms, particularly agitation and aggression without accompanying psychosis, might achieve greater benefit from atypical antipsychotic treatment than patients with milder behavioral symptoms. The finding that dementia patients without psychosis may respond more robustly to antipsychotic treatment seems counterintuitive, but may support the hypothesis that the neurobiology of the "psychosis of AD" differs from the psychosis of schizophrenia or bipolar disease. Adverse effects associated with antipsychotic therapy should be aggressively monitored throughout therapy. Treatment-emergent sedation was associated with all of the atypical antipsychotics in CATIE-AD and is probably an important mediator of mortality risk in patients with dementia. Sedation exacerbates pre-existing cognitive impairment and increases the risk of complications such as aspiration pneumonia, so concomitant use of benzodiazepines should be discouraged or limited to short periods with careful observation.' Once initiated, the effectiveness and tolerability of antipsychotic therapy should be evaluated routinely. In Alzheimer's disease, the severity and frequency of behavioral symptoms often decreases as illness progresses. In a stable patient, it is prudent to attempt to taper and discontinue the antipsychotic after 2-8 months of therapy. Better understanding of the potential adverse effects of antipsychotic therapy has increased interest in the effects of the dementia-specific medications on behavioral symptoms. Reductions in neuropsychiatric symptoms have been reported from trials of individual cholinesterase inhibitors, memantine monotherapy, and memantine combined with donepezil in AD patients. Studies of small numbers of patients in open trials of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and one double-blind placebo controlled trial (rivastigmine) have reported varying degrees of improvement of behavioral symptoms and psychosis of dementia with Lewy bodies (DLB). Delusions, hallucinations, apathy, and agitation/aggression are cited as the symptom categories most likely to show significant improvement. Since few of these studies were prospectively designed to study behavioral symptoms, results must be interpreted cautiously. Treatment of behavioral symptoms in AD and other dementias is challenging. The limitations of current approaches drive the search for effective, well tolerated therapies. PMID:17633594
Daiello, Lori A
PRESCRIBED BURN CERTIFICATION AFFIDAVIT State of County I, (name) (title) Being an employee study of materials provided by mail prior to the program, followed by a two-day training session of study materials. How to Register: Online at www.ugatiftonconference.org or Mail your registration form
Scott, Robert A.
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…
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. PMID:23236256
de Araújo, Arão Nogueira; de Sena, Eduardo Pondé; de Oliveira, Irismar Reis; Juruena, Mario F
ANTIPSYCHOTIC drugs, or neuroleptics, are thought to act by blocking dopamine receptors in the nervous system1-4. Recent direct evidence, based on stereospecific binding assays, supports this hypothesis of antipsychotic drug action5-9. As only a few antipsychotic drugs had been tested for their effects on the binding of haloperidol5-8, the question remained whether all antipsychotic drugs, regardless of chemical structure, would
P. Seeman; T. Lee; M. Chau-Wong; K. Wong
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
Background: Based on randomized clinical trials, consensus has been emerging that the first line of treatment for individuals with psychotic disorders should be the newer atypical or second generation antipsychotic medications rather than the older neuroleptics. Given that acquisition costs of atypical antipsychotics are generally higher than typical antipsychotics, uncertainty exists whether the newer atypicals are cost effective alternatives when
Aileen Rothbard; Mary Rose Murrin; Neil Jordan; Eri Kuno; Bentson H. McFarland; T. Scott Stroup; Joseph P. Morrissey; Paul G. Stiles; Roger A. Boothroyd; Elizabeth Merwin; David L. Shern
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
Dahl, Matthew; Schultz, Jennifer; Metge, Colleen; Raymond, Colette
The use of antipsychotics, particularly second generation antipsychotics, among children and adolescents has increased markedly during the past 20 years. Existing evidence gaps make this practice controversial and hinder treatment decision-making. This article describes and prioritizes future research needs regarding antipsychotic treatment in youth, focusing on within-class and between-class drug comparisons with regard to key population subgroups, efficacy and effectiveness outcomes, and adverse event outcomes. Using as a foundation a recent systematic review of antipsychotic treatment among youth, which was completed by a different Evidence-based Practice Center, we worked with a diverse group of 12 stakeholders representing researchers, funders, health care providers, patients, and families to identify and prioritize research needs. From an initial list of 16 evidence gaps, we enumerated 6 high-priority research needs: 1) long-term comparative effectiveness across all psychiatric disorders; 2) comparative long-term risks of adverse outcomes; 3) short-term risks of adverse events; 4) differentials of efficacy, effectiveness, and safety for population subgroups; 5) comparative effectiveness among those with attention-deficit/hyperactivity disorder and disruptive behavior disorders and common comorbidities; 6) comparative effectiveness among those with bipolar disorder and common comorbidities. In this article, we describe these future research needs in detail and discuss study designs that could be used to address them. PMID:25603449
Christian, Robert B; Gaynes, Bradley N; Saavedra, Lissette M; Sheitman, Brian; Wines, Roberta; Jonas, Daniel E; Viswanathan, Meera; Ellis, Alan R; Woodell, Carol; Carey, Timothy S
This article will review evidence-based hormonal contraception prescribing options in the primary care setting for reproductive age women who experience headaches. Safe prescribing of hormonal contraception requires the nurse practitioner to be able to differentiate between the common primary headache phenotypes, such as the migraine and the tension-type headache. PMID:24177025
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
In dementia depressive symptoms, anxiety, hallucinations and delusions often occur and are accompanied by unspecific behavioral changes. A targeted pharmacotherapy is complicated by the underlying cognitive impairment and physical comorbidities. The current review focusses on recent evidence on the use of antidepressives and antipsychotics for psychotic disturbances, agitation and depression in dementia and analyzes currently published randomized controlled clinical trials and meta-analyses. The evidence on the use of antipsychotics for different indications favors risperidone, with lower evidence levels for quetiapine and aripiprazole, whereas haloperidol should be avoided. Increased mortality and the risk of cerebrovascular events due to antipsychotics are of major concern. With respect to antidepressives, the benefit of antidepressive pharmacotherapy in dementia is critically discussed because of limited efficacy and increased side effects; however, selective serotonin reuptake inhibitors (SSRI), such as citalopram and sertraline have demonstrated efficacy on neuropsychiatric behavioral symptoms in general. These conclusions on the risk-benefit ratio of antidepressives and antipsychotics in dementia are in accordance with the recommendations of the German Society of Neurology and German Association for Psychiatry, Psychotherapy and Psychosomatics (DGN/DGPPN) S3 guidelines on the treatment of dementia. PMID:25787724
Frölich, L; Hausner, L
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
Commentary Cognition, schizophrenia, and the atypical antipsychotic drugs Herbert Y. Meltzer the term to categorize a group of young psychotic patients who went on to develop dementia. A decade later impairment to schizophrenia further diminished in the 1950s, after the development of antipsy- chotic drugs
The prevalence of overweight and obesity in untreated patients with severe mental illness mimicks the trends seen in the general population. Furthermore, weight gain is likely to occur with the addition of pharmacotherapy with an antipsychotic. The literature does indicate that despite fundamental cognitive and psychosocial deficits seen in patients with severe and persistent mental disorders such as schizophrenia and
Approximately 80% of patients with the first-episode schizophrenia reach symptomatic remission after antipsychotic therapy. However, within two years most of them relapse, mainly due to low levels of insight into the illness and nonadherence to their oral medication. Therefore, although the formal data available is limited, many experts recommend prescribing long-acting injectable second-generation antipsychotics (mostly risperidone or alternatively paliperidone) in the early stages of schizophrenia, particularly in patients who have benefited from the original oral molecule in the past and agree to receive long-term injectable treatment. Early application of long-acting injectable second-generation antipsychotics can significantly reduce the risk of relapse in the future and thus improve not only the social and working potential of patients with schizophrenia but also their quality of life. PMID:22966444
P?ikryl, Radovan; P?ikrylová Ku?erová, Hana; Vrzalová, Michaela; ?ešková, Eva
Approximately 50-75% of all patients do not take their antipsychotic medication as prescribed. The current study examined reasons why patients continue versus discontinue antipsychotic medication. We were particularly interested to which extent positive attitudes towards psychotic symptoms foster medication nonadherence. An anonymous online questionnaire was set up to decrease response biases. After a strict selection process, 91 participants with schizophrenia spectrum disorders were retained for the final analyses. On average, 6.2 different reasons for nonadherence were reported. Side-effects (71.4%), sudden subjective symptom improvement (52.4%) and forgetfulness (33.3%) emerged as the most frequent reasons for drug discontinuation. Approximately one fourth of all participants (27.3%) reported at least one positive aspect of psychosis as a reason for nonadherence. In contrast, patients reported on average 3.5 different reasons for adherence (e.g., want to live a normal life (74.6%) and fear of psychotic symptoms (49.3%)). The belief that paranoia represents a survival strategy (subscale derived from the Beliefs about Paranoia Scale) was significantly associated with nonadherence. Patients' attitudes toward medication and the individual illness model need to be carefully considered when prescribing medication. In particular for patients who are likely to discontinue psychopharmacological treatment complementary or alternative psychological treatment should be sought because of a largely increased risk of relapse in the case of sudden drug discontinuation. PMID:25444234
Moritz, Steffen; Hünsche, Alexandra; Lincoln, Tania M
Background: Mental disorders among older adults are mainly treated with psychotropic drugs. Few of these drugs are, however, prescribed by specialized geriatricians or psychiatrists, but rather from general practitioners (GPs). Socioeconomic inequalities in access to specialist prescribing have been found in younger age groups. Hence, we aimed to investigate whether there are socioeconomic differences in access to geriatrician and psychiatrist prescribing of psychotropic drugs among older adults. Methods: By record-linkage of The Swedish Prescribed Drug Register and The Swedish Education Register, we obtained information for persons aged 75–89 years who had filled a prescription for psychotropic drugs (antipsychotics, anxiolytics, hypnotic/sedatives or antidepressants) with information on prescriber specialty from July to October 2005 (n = 221 579). Multinomial regression analysis was used to investigate whether education was associated with geriatrician and psychiatrist prescribing of psychotropic drugs. Results: The vast majority of the psychotropic drugs were prescribed by ‘GPs and other specialists’ (?95% GPs). Older adults with higher educational level were more likely to be prescribed psychotropic drugs from psychiatrists and geriatricians. However, after adjustment for place of residence, the association between patient’s education and prescription by a geriatrician disappeared, whereas the association with seeing a psychiatrist was only attenuated. Conclusion: Access to specialized prescribing of psychotropics is unequally distributed between socioeconomic groups of older adults in Sweden. This finding was partially confounded by place of residence for geriatrician but not for psychiatrist prescribing. Further research should examine if inequalities in specialized psychotropic prescribing translate into worse outcomes for socioeconomically deprived and non-metropolitan-living older individuals. PMID:24860048
Fastbom, Johan; Ringbäck Weitoft, Gunilla; Fors, Stefan; Johnell, Kristina
OBJECTIVE: To describe benzodiazepine prescribing for elderly people living in the community in British Columbia, and to compare such prescribing with an indicator of current guidelines. DESIGN: Descriptive analysis of pharmacy billing data. SETTING: Province of British Columbia. PARTICIPANTS: All elderly persons (age 65 and older) dispensed benzodiazepines by community pharmacies in British Columbia during 1990. MAIN OUTCOME MEASURE: Potentially inappropriate prescriptions were defined by a maximum 2-month limit of 20 diazepam equivalents daily, as determined by the BC Drug Usage Review Program in consultation with experts in the field. Physicians' rates of potentially inappropriate prescribing were determined per 100 benzodiazepine prescriptions written. RESULTS: Almost 24% of elderly people in British Columbia were prescribed benzodiazepines at least once during 1990. Of these, 17.1% were given potentially inappropriate prescriptions. Physicians who prescribed benzodiazepines most frequently had the highest rates of potentially inappropriate prescriptions. CONCLUSION: Prescribing practice does not correspond with our indicator of current guidelines. PMID:7756916
Thomson, M.; Smith, W. A.
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. PMID:20520598
Nielsen, Jimmi; Skadhede, Søren; Correll, Christoph U
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.
Background Management of acute psychotic episodes in schizophrenic patients remains a significant challenge for clinicians. Despite treatment guidelines recommending that second-generation antipsychotics (SGAs) should be used as monotherapy, first-generation antipsychotics, polypharmacy, and lower than recommended doses are frequently administered in clinical practice. Minimal data exist regarding the use of SGAs in the Middle East. The objective of this study was to examine the discrepancies between current clinical practice and guideline recommendations in the region. Methods RECONNECT-S Beta was a multicenter, noninterventional study conducted in Egypt, Kuwait, Saudi Arabia, and the United Arab Emirates to observe the management of schizophrenic patients who were hospitalized due to an acute psychotic episode. Patients underwent one visit on the day of discharge. Demographic and medical history, together with data on antipsychotic treatment and concomitant medication during the hospitalization period and medication recommendations at discharge were recorded. Results Of the 1,057 patients, 180 (17.0%) and 692 (65.5%) received SGAs as monotherapy and in combination therapy, respectively. Overall, the most frequently administered medications were given orally, and included risperidone (40.3%), olanzapine (32.5%), and quetiapine (24.6%); the doses administered varied between countries and deviated from the recommended guidelines. Upon discharge, 93.9% of patients were prescribed SGAs as maintenance therapy, and 84.8% were prescribed the same medication(s) as during hospitalization. Conclusion Current clinical practice in the Middle East differs from guideline recommendations. Patients frequently received antipsychotics in combination therapy, by various methods of administration, and at doses above and below the recommended guidelines for the management of their acute psychotic episodes.
Alkhadhari, Sulaiman; Al Zain, Nasser; Darwish, Tarek; Khan, Suhail; Okasha, Tarek; Ramy, Hisham; Tadros, Talaat Matar
The objective of our study was to investigate whether use of antipsychotics is associated with hip\\/femur fractures and whether pharmacological differences between antipsychotics are related to the occurrence of fractures.A case-control study was conducted, in which cases were defined as patients with a hip\\/femur fracture. Each patient was matched to one control patient. The association between use of antipsychotics and
Gerard W. K. Hugenholtz; Eibert R. Heerdink; Tjeerd P. van Staa; Willem A. Nolen; Antoine C. G. Egberts
Every year numerous reports on antipsychotic drug trials are being published in neuropsychiatric journals, adding new information to our knowledge in the field. The information however is often hard for the reader to interpret, sometimes contradictory to comparable available studies and leaves more questions open than it actually answers. Although the overall quality of the studies is rather good, there are manifold options for further improvement in the conception, conduct, and reporting of antipsychotic drug trials. In this survey, we address methodological challenges such as the limited generalizability of outcomes due to patient selection and sample size; the vague or even lacking definition of key outcome parameters such as response, remission or relapse, insufficient blinding techniques, the pitfalls of surrogate outcomes and their assessment tools; the varying complex statistical approaches; and the challenge of balancing various ways of reporting outcomes. The authors present practical examples to highlight the current problems and propose a concrete series of suggestions on how to further optimize antipsychotic drug trials in the future. PMID:18234700
Leucht, Stefan; Heres, Stephan; Hamann, Johannes; Kane, John M.
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.
Florida Department of Forestry
Behavioral and psychological symptoms of dementia (BPSD), i.e. verbal and physical aggression, agitation, psychotic symptoms (hallucinations and delusions), sleep disturbances, oppositional behavior, and wandering, are a common and potentially severe problem complicating dementia. Their prevalence is very high and it is estimated that up to 90% of patients with Alzheimer’s disease (AD) may present at least one BPSD. Beside the obvious impact on the quality of life of people with dementia, BPSD are responsible for increased risk of patient institutionalization and increased costs. Furthermore, they are associated with caregivers’ stress and depression. Drugs used include antipsychotics, antidepressants, anticonvulsivants, anxiolytics, cholinesterase inhibitors and N-methyl-D-aspartate receptor modulators. Among these, the most commonly used are anti-psychotics. These drugs have been used for many decades, but in the last years new compounds have been marketed with the promise of comparable efficacy but less frequent adverse effects (especially extra-pyramidal side effects). Their safety, however, has been challenged by data showing a potential increase in adverse cerebrovascular side effects and mortality. This review will summarize the pathophysiology and neuropharmacology of BPSD, it will describe the characteristics of the anti-psychotics most commonly used focusing on their efficacy and safety in BPSD. PMID:19305792
Liperoti, Rosa; Pedone, Claudio; Corsonello, Andrea
Correctional facilities are a major provider of mental health care throughout the United States. In spite of the numerous benefits of providing care in this setting, clinicians are sometimes concerned about entering into correctional care because of uncertainty in prescribing practices. This article provides an introduction to prescription drug use, abuse, and diversion in the correctional setting, including systems issues in prescribing, commonly abused prescription medications, motivation for and detection of prescription drug abuse, and the use of laboratory monitoring. By understanding the personal and systemic factors that affect prescribing habits, the clinician can develop a more rewarding correctional practice and improve care for inmates with mental illness. PMID:24532812
Pilkinton, Patricia D; Pilkinton, James C
Individuals with schizophrenia are at very high risk for drug abuse and addiction. Patients with a coexisting drug problem fare worse than patients who do not use drugs, and are also more difficult to treat. Current hypotheses cannot adequately account for why patients with schizophrenia so often have a co-morbid drug problem. I present here a complementary hypothesis based on evidence showing that chronic exposure to antipsychotic medications can induce supersensitivity within the brain's dopamine systems, and that this in turn can enhance the rewarding and incentive motivational effects of drugs and reward cues. At the neurobiological level, these effects of antipsychotics are potentially linked to antipsychotic-induced increases in the striatal levels of dopamine D2 receptors and D2 receptors in a high-affinity state for dopamine, particularly at postsynaptic sites. Antipsychotic-induced dopamine supersensitivity and enhanced reward function are not inevitable consequences of prolonged antipsychotic treatment. At least two parameters appear to promote these effects; the use of antipsychotics of the typical class, and continuous rather than intermittent antipsychotic exposure, such that silencing of dopaminergic neurotransmission via D2/3 receptors is unremitting. Thus, by inducing forms of neural plasticity that facilitate the ability of drugs and reward cues to gain control over behaviour, some currently used treatment strategies with typical antipsychotics might contribute to compulsive drug seeking and drug taking behaviours in vulnerable schizophrenia patients. PMID:23793001
Progressive enlargement of basal ganglia volume has been observed in schizophrenia individuals, potentially being sustained by chronic administration of antipsychotic drugs. Here we briefly summarise the state of the art of the role of antipsychotic in leading to increased basal ganglia in schizophrenia, particularly focusing on the caudate nucleus. PMID:25335548
Zampieri, E; Bellani, M; Crespo-Facorro, B; Brambilla, P
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
Abstract Second-generation antipsychotics (SGAs) are increasingly prescribed to treat psychiatric symptoms in pediatric patients infected with HIV. We examined the relationship between prescribed SGAs and physical growth in a cohort of youth with perinatally acquired HIV-1 infection. Pediatric AIDS Clinical Trials Group (PACTG), Protocol 219C (P219C), a multicenter, longitudinal observational study of children and adolescents perinatally exposed to HIV, was conducted from September 2000 until May 2007. The analysis included P219C participants who were perinatally HIV-infected, 3–18 years old, prescribed first SGA for at least 1 month, and had available baseline data prior to starting first SGA. Each participant prescribed an SGA was matched (based on gender, age, Tanner stage, baseline body mass index [BMI] z score) with 1–3 controls without antipsychotic prescriptions. The main outcomes were short-term (approximately 6 months) and long-term (approximately 2 years) changes in BMI z scores from baseline. There were 236 participants in the short-term and 198 in the long-term analysis. In linear regression models, youth with SGA prescriptions had increased BMI z scores relative to youth without antipsychotic prescriptions, for all SGAs (short-term increase?=?0.192, p?=?0.003; long-term increase?=?0.350, p?0.001), and for risperidone alone (short-term?=?0.239, p?=?0.002; long-term?=?0.360, p?=?0.001). Participants receiving both protease inhibitors (PIs) and SGAs showed especially large increases. These findings suggest that growth should be carefully monitored in youth with perinatally acquired HIV who are prescribed SGAs. Future research should investigate the interaction between PIs and SGAs in children and adolescents with perinatally acquired HIV infection. PMID:19827949
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.
Background In Japan, combination therapy with high doses of antipsychotic drugs is common, but as a consequence, many patients with schizophrenia report extrapyramidal and autonomic nervous system side effects. To resolve this, we proposed a method of safety correction of high dose antipsychotic polypharmacy (the SCAP method), in which the initial total dose of all antipsychotic drugs is calculated and converted to a chlorpromazine equivalent (expressed as milligrams of chlorpromazine, mg CP). The doses of low-potency antipsychotic drugs are then reduced by???25 mg CP/week, and the doses of high-potency antipsychotics are decreased at a rate of ?50 mg CP/week. Although a randomized, case-controlled comparative study has demonstrated the safety of this method, the number of participants was relatively small and its results required further validation. In this study of the SCAP method, we aimed to substantially increase the number of participants. Methods/design The participants were in- or outpatients treated with two or more antipsychotics at doses of 500–1,500 mg CP/day. Consenting participants were randomized into control and dose reduction groups. In the control group, patients continued with their normal regimen for 3 months without a dose change before undergoing the SCAP protocol. The dose reduction group followed the SCAP strategy over 3–6 months with a subsequent 3-month follow-up period. Outcome measures were measured at baseline and then at 3-month intervals, and included clinical symptoms measured on the Manchester scale, the extent of extrapyramidal and autonomic side effects, and quality of life using the Euro QOL scale. We also measured blood drug concentrations and drug efficacy-associated biochemical parameters. The Brief Assessment of Cognition in Schizophrenia, Japanese version, was also undertaken in centers where it was available. Discussion The safety and efficacy of the SCAP method required further validation in a large randomized trial. The design of this study aimed to address some of the limitations of the previous case-controlled study, to build a more robust evidence base to assist clinicians in their efforts to reduce potentially harmful polypharmacy in this vulnerable group of patients. Trial registration UMIN Clinical Trials Registry 000004511. PMID:24708857
Background: Valproic acid (VPA) is one of the most commonly used antiepileptic medications worldwide; it is also a popular mood stabilizer for use in bipolar disorder and dementia. This study assessed whether VPA may potentiate metabolic side effects in patients with psychiatric disorders taking concomitant antipsychotics (APs). VPA alone has been associated with weight gain, dyslipidemia, hypertension, and diabetes. Patients with psychiatric disorders, especially those on second-generation (atypical) APs, appear to be at increased risk of these metabolic effects. A secondary purpose was to determine if a linear dose–response relationship exists between the VPA dose and adverse metabolic effects. Methods: This cross-sectional study was conducted using data collected on all patients in the four state-operated psychiatric hospitals in Michigan using a comprehensive assessment instrument, the interRAI Mental Health. All patients taking both VPA and APs (n = 200) were compared to a control group of patients taking APs without VPA (n = 426). Patients were assessed for the presence of the following surrogate indicators of metabolic syndrome: weight gain; high body mass index (BMI greater than 30 kg/m2); very high BMI (BMI greater than 40 kg/m2); a diagnosis of diabetes mellitus; use of a prescribed statin medication; diagnosis of hyperlipidemia or dyslipidemia; hypertension; or the combination of any three of these factors: high BMI, hyperlipidemia or dyslipidemia, diabetes, and hypertension. Analysis also included assessment of the effect of VPA dosage on metabolic side effects. Results: Patients in the VPA plus APs group were 3.2 kg heavier than those in the APs group (P = 0.05) at baseline. Compared with the APs group, the VPA plus APs group had a higher prevalence of high and very high BMI, diabetes, hypertension, and the combination of any three factors of high BMI, hyperlipidemia/dyslipidemia, diabetes, and hypertension. However, these differences were not statistically significant. Conversely, there was a slight but non-significant reduction in the prevalence of weight gain, prescribed statins, and hyperlipidemia/dyslipidemia in the VPA plus APs group than the APs group. Finally, higher doses of VPA were not found to be associated with a higher incidence of these metabolic side effects. Conclusion: Although the patients on VPA were slightly more than 3 kg heavier, VPA did not appear to be associated with significant metabolic effects in patients with psychiatric conditions taking typical and atypical APs. These metabolic effects also do not appear to be related to the dose of VPA. PMID:25673963
Zuo, Silu; Fries, Brant E.; Szafara, Kristina; Regal, Randolph
OBJECTIVES--To assess the validity of the item as a measure of the volume of a drug prescribed; and to investigate the possibility that higher quantities per item are prescribed for patients who are not exempt from the prescription charge. DESIGN--Five substudies. For the first, a frequency distribution was derived of the different quantities per item of 10 commonly used drugs prescribed by 20 randomly selected practices in each of five family health service authority areas. For the second, the variation in average quantity per item for the same drugs in the same practices was calculated. For the third and fourth, variation in average quantity per item for 90 commonly used drugs was calculated for all 90 family health service authorities and for all 14 regional health authorities in England. For the fifth, the average quantity per item for each of the 90 drugs was regressed on the percentage of items exempt from the prescription charge, at family health service authority level, and the percentage of variation explained by the regression found. MAIN OUTCOME MEASURE--Distribution of quantity per item; variation in average quantity per item between the practices, between family health service authorities, and between regions; and percentage of variation between family health service authorities accounted for by exemption from the prescription charge. RESULTS--Wide variation was found in the quantities per item prescribed by the practices, and in the average quantity per item between practices and between family health service authorities. No family health service authority was consistently high or low in quantity per item across the 90 drugs. Variation in average quantity per item was less at regional than at family health service authority level, though still high for many of the drugs. The proportion of variation accounted for by exemption from prescription charges ranged from 0% to 49% across the 90 drugs. CONCLUSIONS--The item is unsuitable as a measure of prescribing volume, even at regional level: a new measure, based on standard daily dosages, is needed. The percentage of the variation in quantity per item accounted for by exemption is inconsistent, and in over half the 90 drugs it was below 20%--therefore it is not a useful predictor. PMID:8148715
Bogle, S. M.; Harris, C. M.
The large number of medications available has complicated the learning of drug therapy for medical students at a time when pharmacology training has been substantially reduced. Attempts to remedy this include: improving the pharmaco-therapeutics curriculum; interactive web-based learning and students developing a personal formulary. The approach adopted by the University of Wollongong Medical School is to integrate clinical pharmacology throughout the course, with the Student Preferred-drugs Formulary linking pharmacology and common diseases. Evidence from other countries suggests this should enhance prescribing by medical graduates. PMID:24020344
Gaetani, L; Yeo, W W
Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest), high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability. PMID:24995318
Antipsychotic drugs are tranquilizing psychiatric medications primarily used in the treatment of schizophrenia and similar severe mental disorders. So far, most of these drugs have been discovered without knowing much on the molecular mechanisms of their actions. The available large amount of pharmacogenetics, pharmacometabolomics, and pharmacoproteomics data for many drugs makes it possible to systematically explore the molecular mechanisms underlying drug actions. In this study, we applied a unique network-based approach to investigate antipsychotic drugs and their targets. We first retrieved 43 antipsychotic drugs, 42 unique target genes, and 46 adverse drug interactions from the DrugBank database and then generated a drug-gene network and a drug-drug interaction network. Through drug-gene network analysis, we found that seven atypical antipsychotic drugs tended to form two clusters that could be defined by drugs with different target receptor profiles. In the drug-drug interaction network, we found that three drugs (zuclopenthixol, ziprasidone, and thiothixene) tended to have more adverse drug interactions than others, while clozapine had fewer adverse drug interactions. This investigation indicated that these antipsychotics might have different molecular mechanisms underlying the drug actions. This pilot network-assisted investigation of antipsychotics demonstrates that network-based analysis is useful for uncovering the molecular actions of antipsychotics. PMID:22589091
Sun, Jingchun; Xu, Hua; Zhao, Zhongming
While the prevalence of mental illness is higher in prisons than in the community, less is known about comparative rates of psychotropic medicine prescribing. This is the first study in a decade to determine the prevalence and patterns of psychotropic medication prescribing in prisons. It is also the first study to comprehensively adjust for age when making comparisons with the general population. Four East of England prisons, housing a total of 2222 men and 341 women were recruited to the study. On census days, clinical records were used to identify and collect data on all prisoners with current, valid prescriptions for hypnotic, anxiolytic, antipsychotic, antimanic, antidepressant and/or stimulant medication, as listed in chapters 4.1 to 4.4 of the British National Formulary. Data on 280,168 patients were obtained for comparison purposes from the Clinical Practice Research Datalink. After adjusting for age, rates of psychotropic prescribing in prison were 5.5 and 5.9 times higher than in community-based men and women, respectively. We also found marked differences in the individual psychotropic drugs prescribed in prison and community settings. Further work is necessary to determine whether psychotropic prescribing patterns in prison reflect an appropriate balance between managing mental illness, physical health risks and medication misuse. PMID:24569096
Hassan, Lamiece; Senior, Jane; Frisher, Martin; Edge, Dawn; Shaw, Jenny
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. PMID:23476805
Gervasini, Guillermo; Caballero, Maria J.; Carrillo, Juan A.; Benitez, Julio
Securinega virosa (Roxb ex. Willd) Baill. is a plant which is commonly used in African traditional medicine in management of mental illness. Previous study showed that the crude methanolic root bark extract of the plant possesses antipsychotic activity. In this study, the antipsychotic potential of the residual aqueous fraction of the plant was evaluated using two experimental models, apomorphine induced stereotypic climbing behaviour and swim induced grooming, all in mice. The effect of the fraction on haloperidol-induced catalepsy was also evaluated. The fraction significantly reduced the mean climbing score at the highest dose tested (500 mg/kg). In the swim-induced grooming test, the fraction significantly and dose-dependently (125-500 mg/kg) decreased the mean number and mean duration of swim-induced grooming activity in mice. Similarly, the standard haloperidol (1 mg/kg) significantly (p?0.001) decreased the mean grooming episodes and duration. However, the fraction did not significantly potentiate haloperidol-induced catalepsy. These results suggest that the residual aqueous fraction of methanol root bark extract of Securinega virosa contains biological active principle with antipsychotic potential. PMID:24445435
Magaji, M G; Mohammed, M; Magaji, R A; Musa, A M; Abdu-Aguye, I; Hussaini, I M
The provision of drugs to hospitalised patients is a complex process with the involvement of different healthcare professionals. As pharmacotherapy is (1) one of the most common medical interventions, (2) a high-risk procedure, and (3) affects the majority of hospitalised patients, medication errors have sustainable impact on patient safety. Although medication errors can occur at different stages of drug use (prescribing, dispensing, administration), they are most likely within the prescribing process. According to the Reason's model of accident causation, these errors can be divided into active failures, error-provoking conditions, and latent conditions. Commonly, the complex interaction between lacking knowledge and/or experience, rule-based mistakes, skill-based slips and memory lapses, inadequate working environment (exessive work load, fatigue) as well as poor communication and safety culture is causative for prescribing errors. Therefore, good prescribing should include the following items: Adherence to formal criteria (e. g. avoidance of abbreviations), performance of medication reconciliation, implementation of an electronic prescribing system (computerised physician order entry, CPOE) - preferably combined with a clinical decision support system (CDSS), education and training as well as the establishment of a positive error management culture. The implementation of recommendations to reduce prescribing errors is described on the basis of established processes in hospitals. PMID:24867349
Langebrake, Claudia; Melzer, Simone; Baehr, Michael
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
Grasslands of the central Great Plains developed with periodic fire. Prescribed burning is an important tool for managing grasslands to maintain desirable species composition, increase grazing livestock performance, maintain productivity, and control invasive weeds. The safe and effective use of pre...
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
Association analysis between functional polymorphism of the rs4606 SNP in the RGS2 gene and antipsychotic-induced Parkinsonism in Japanese patients with schizophrenia: Results from the Juntendo University Schizophrenia Projects (JUSP)
Antipsychotic-induced extrapyramidal symptoms (AIEPSs) are commonly recognized side effects of typical 1st generation antipsychotics, and considerable variability is seen in the susceptibility of individual patients to AIEPSs. Regulator of G-protein signaling 2 (RGS2) proteins regulate intracellular signaling and second messenger activation of molecules including dopamine, serotonin, and acetylcholine receptors, all of which appear to be involved in the pathophysiology of
Masayuki Higa; Tohru Ohnuma; Hitoshi Maeshima; Tokiko Hatano; Ryo Hanzawa; Nobuto Shibata; Yoshie Sakai; Toshihito Suzuki; Heii Arai
Background Clozapine is an atypical antipsychotic demonstrated to be superior in the treatment of refractory schizophrenia which causes fewer movement disorders. Clozapine, however, entails a significant risk of serious blood disorders such as agranulocytosis which could be potentially fatal. Currently there are a number of newer antipsychotics which have been developed with the purpose to find both a better tolerability profile and a superior effectiveness. Objectives To compare the clinical effects of clozapine with other atypical antipsychotics (such as amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and zotepine) in the treatment of schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Groups Register (June 2007) and reference lists of all included randomised controlled trials. We also manually searched appropriate journals and conference proceedings relating to clozapine combination strategies and contacted relevant pharmaceutical companies. Selection criteria All relevant randomised, at least single-blind trials, comparing clozapine with other atypical antipsychotics, any dose and oral formulations, for people with schizophrenia or related disorders. Data collection and analysis We selected trials and extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) again based on a random-effects model. Main results The review currently includes 27 blinded randomised controlled trials, which involved 3099 participants. Twelve randomised control trials compared clozapine with olanzapine, five with quetiapine, nine with risperidone, one with ziprasidone and two with zotepine. Attrition from these studies was high (overall 30.1%), leaving the interpretation of results problematic. Clozapine had a higher attrition rate due to adverse effects than olanzapine (9 RCTs, n=1674, RR 1.60 CI 1.07 to 2.40, NNT 25 CI 15 to 73) and risperidone (6 RCTs, n=627, RR 1.88 CI 1.11 to 3.21, NNT 16 CI 9 to 59). Fewer participants in the clozapine groups left the trials early due to inefficacy than risperidone (6 RCTs, n=627, RR 0.40 CI 0.23 to 0.70, NNT 11 CI 7 to 21), suggesting a certain higher efficacy of clozapine. Clozapine was more efficacious than zotepine in improving the participants general mental state (BPRS total score: 1 RCT, n=59, MD ?6.00 CI ?9.83 to ?2.17), but not consistently more than olanzapine, quetiapine, risperidone and ziprasidone. There was no significant difference between clozapine and olanzapine or risperidone in terms of positive or negative symptoms of schizophrenia. According to two studies from China quetiapine was more efficacious for negative symptoms than clozapine (2 RCTs, n=142, MD 2.23 CI 0.99 to 3.48). Clozapine produced somewhat fewer extrapyramidal side-effects than risperidone (use of antiparkinson medication: 6 RCTs, n=304, RR 0.39 CI 0.22 to 0.68, NNT 7 CI 5 to 18) and zotepine (n=59, RR 0.05 CI 0.00 to 0.86, NNT 3 CI 2 to 5). More participants in the clozapine group showed decreased white blood cells than those taking olanzapine, more hypersalivation and sedation than those on olanzapine, risperidone and quetiapine and more seizures than people on olanzapine and risperidone. Also clozapine produced an important weight gain not seen with risperidone. Other differences in adverse effects were less documented and should be replicated, for example, clozapine did not alter prolactin levels whereas olanzapine, risperidone and zotepine did; compared with quetiapine, clozapine produced a higher incidence of electrocardiogram (ECG) alterations; and compared with quetiapine and risperidone clozapine produced a higher increase of triglyceride levels. Other findings that should be replicated were: clozapine improved social functioning less than risperidone and fewer participants
Asenjo Lobos, Claudia; Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Leucht, Stefan
In a prime example of finding new uses for older drugs, studies in zebrafish show that a 50-year-old antipsychotic medication called perphenazine can actively combat the cells of a difficult-to-treat form of acute lymphoblastic leukemia (ALL). The drug works by turning on a cancer-suppressing enzyme called PP2A and causing malignant tumor cells to self-destruct.The findings, by a team from the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, the Dana-Farber Cancer Institute, and Brigham and Women's Hospital suggest that developing medications that activate PP2A, while avoiding perphenazine's psychotropic effects, could help clinicians make much-needed headway against T-cell ALL, and perhaps other tumors as well.
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. PMID:22768007
Price, Scott A.; Brahm, Nancy C.
Utilization of Antihypertensives, Antidepressants, Antipsychotics, and Hormones in Alzheimer) that showed significant changes in use rates over time in patients with Alzheimer disease. Patient accurate modeling of the Alzheimer disease treatment paradigm for certain subgroups of patients should
Since 1997, we have been studying the effects of prescribed burns conducted during late winter on shortgrass steppe on the Pawnee National Grassland. During 1997 – 2002, we studied burns on the western (Crow Valley) portion of the Pawnee by comparing plant growth on burns conducted by the Forest Ser...
OBJECTIVE: To examine the association between treatment with antipsychotics (both conventional and atypical) and all-cause mortality.\\u000aDESIGN: Population-based, retrospective cohort study.\\u000aSETTING: Ontario, Canada.\\u000aPATIENTS: Older adults with dementia who were followed between 1 April 1997 and 31 March 2003.\\u000aMEASUREMENTS: The risk for death was determined at 30, 60, 120, and 180 days after the initial dispensing of antipsychotic
Sudeep S. Gill; Susan E. Bronskill; Sharon-Lise T. Normand; Geoffrey M. Anderson; Kathy Sykora; Kelvin Lam; Chaim M. Bell; Philip E. Lee; Hadas D. Fischer; Nathan Herrmann; Jerry H. Gurwitz; Paula A. Rochon
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. PMID:18827289
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. PMID:21206806
Grünze, H; Möller, H J
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 diminished. Method: All PubMed sources in which the search term gender (or sex) was linked to a side effect of antipsychotic medication were reviewed. Result: There is general agreement in the literature on women's increased susceptibility to weight gain, diabetes, and specific cardiovascular risks of antipsychotics, with less consensus on malignancy risks and risks to the fetus. Cardiovascular death, to which men are more susceptible than women, is disproportionately increased in women by the use of antipsychotics. Sedating antipsychotics raise the risk of embolic phenomena during pregnancy, and postpartum. Prolactin-elevating drugs suppress gonadal hormone secretion and may enhance autoimmune proclivity. Conclusions: Clinicians need to be aware of the differential harm that women (and their offspring) can incur from the side effects of antipsychotics. PMID:18400811
Seeman, Mary V.
Although all currently used antipsychotic drugs act as dopamine (DA) D2 receptor antagonists, clozapine, the prototype for atypical antipsychotics, shows superior efficacy, especially regarding negative and cognitive symptoms, in spite of a significantly reduced central D2 receptor occupancy compared with typical (conventional) antipsychotic drugs. Clozapine, as well as several other atypicals, displays significant affinities also for several other neurotransmitter receptors, including other dopaminergic receptors, alpha-adrenergic receptors and different serotonergic and cholinergic receptors, which in several ways may contribute to the clinical effectiveness of the drugs. Preclinical and clinical results suggest a dysregulated mesocorticolimbic DA system in schizophrenia, with an impaired prefrontal DA projection, which may relate to negative and cognitive symptoms, concomitant with an overactive or overreactive striatal DA projection, with bearing on psychotic (positive) symptomatology. Available data suggest that blockage of alpha1-adrenoceptors by antipsychotics may contribute to suppress positive symptoms, especially in acute schizophrenia, whereas alpha2-adrenoceptor blockage, a prominent effect of clozapine and, to some extent, risperidone but not other antipsychotics, may rather be involved in relief of negative and cognitive symptoms. Whereas alpha1-adrenoceptor blockage may act by suppressing, at the presynaptic level, striatal hyperdopaminergia, alpha2-adrenoceptor blockage may act by augmenting and improving prefrontal dopaminergic functioning. Thus, the prominent alpha1- and alpha2-adrenoceptor blocking effects of clozapine may generally serve to stabilize dysregulated central dopaminergic systems in schizophrenia, allowing for improved efficacy in spite of a reduced central D2 receptor occupancy compared with typical antipsychotic drugs. PMID:14642973
Svensson, Torgny H
In the management of schizophrenia, mental health outcomes are the principal focus of treatment. The objective is to control the psychotic symptoms while minimising negative features of the illness, to achieve an overall improvement in the societal functioning of patients. Physical health is also important because if it is compromised, many of the benefits of improved mental health will be offset. Compared with the general population, schizophrenia patients are at increased risk of weight gain, abdominal obesity, diabetes, metabolic syndrome, and cardiovascular disease. These physical health problems can contribute to the decreased quality of life, lowered self-esteem and reduced life expectancy commonly reported in schizophrenia. For these reasons there is a pressing need to improve both the monitoring and the management of physical health in patients with schizophrenia as a part of their overall care. A consensus for metabolic monitoring of patients receiving treatment with antipsychotic drugs is available. However, the practicing clinician requires guidance about management of physical health in routine clinical practice. This should include recommendations for measurements that have strong predictive value about physical health risks yet are easy to make, and about the use of medications that have the least effect on physical health parameters. This article will review the gravity of the physical health risks facing schizophrenia patients. PMID:20620888
Background Generic atypical antipsychotic drugs offer health authorities opportunities for considerable savings. However, schizophrenia and bipolar disorders are complex diseases that require tailored treatments. Consequently, generally there have been limited demand-side measures by health authorities to encourage the preferential prescribing of generics. This is unlike the situation with hypertension, hypercholaesterolaemia or acid-related stomach disorders. The objectives of this study were to compare the effect of the limited demand-side measures in Western European countries and regions on the subsequent prescribing of risperidone following generics; to utilise the findings to provide future guidance to health authorities; and where possible, to investigate the utilisation of generic versus originator risperidone and the prices for generic risperidone. Methods Principally, this was a segmented regression analysis of retrospective time-series data of the effect of the various initiatives in Belgium, Ireland, Scotland and Sweden following the introduction of generic risperidone. The study included patients prescribed at least one atypical antipsychotic drug up to 20 months before and up to 20 months after generic risperidone. In addition, retrospective observational studies were carried out in Austria and Spain (Catalonia) from 2005 to 2011 as well as one English primary care organisation (Bury Primary Care Trust (PCT)). Results There was a consistent steady reduction in risperidone as a percentage of total selected atypical antipsychotic utilisation following generics. A similar pattern was seen in Austria and Spain, with stable utilisation in one English PCT. However, there was considerable variation in the utilisation of generic risperidone, ranging from 98% of total risperidone in Scotland to only 14% in Ireland. Similarly, the price of generic risperidone varied considerably. In Scotland, generic risperidone was only 16% of pre-patent loss prices versus 72% in Ireland. Conclusion Consistent findings of no increased prescribing of risperidone post generics with limited specific demand-side measures suggests no ‘spillover’ effect from one class to another encouraging the preferential prescribing of generic atypical antipsychotic drugs. This is exacerbated by the complexity of the disease area and differences in the side-effects between treatments. There appeared to be no clinical issues with generic risperidone, and prices inversely reflected measures to enhance their utilisation. PMID:24927744
Background In many countries of the industrialised world second generation (“atypical”) antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics. Objectives To evaluate the effects of olanzapine compared to other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. 2. Reference searching We inspected the reference of all identified studies for more trials. 3. Personal contact We contacted the first author of each included study for missing information. 4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. Selection criteria We included all randomised trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. Main results The review currently includes 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole, clozapine, quetiapine, risperidone or ziprasidone). The overall attrition from the included studies was considerable (49.2%) leaving the interpretation of results problematic. Olanzapine improved the general mental state (PANSS total score) more than aripiprazole (2 RCTs, n=794, WMD ?4.96 CI ?8.06 to ?1.85), quetiapine (10 RCTs, n=1449, WMD ?3.66 CI ?5.39 to ?1.93), risperidone (15 RCTs, n=2390, WMD ?1.94 CI ?3.31 to ?0.58) and ziprasidone (4 RCTs, n=1291, WMD ?8.32 CI ?10.99 to ?5.64), but not more than amisulpride or clozapine. This somewhat better efficacy was confirmed by fewer participants in the olanzapine groups leaving the studies early due to inefficacy of treatment compared to quetiapine (8 RCTs, n=1563, RR 0.56 CI 0.44 to 0.70, NNT 11 CI 6 to 50), risperidone (14 RCTs, n=2744, RR 0.78 CI 0.62 to 0.98, NNT 50 CI 17 to 100) and ziprasidone (5 RCTs, n=1937, RR 0.64 CI 0.51 to 0.79, NNT 17, CI 11 to 33). Fewer participants in the olanzapine group than in the quetiapine (2 RCTs, n=876, RR 0.56 CI 0.41 to 0.77, NNT 11 CI 7 to 25) and ziprasidone (2 RCTs, n=766, RR 0.65 CI 0.45 to 0.93, NNT 17 CI 9 to 100) treatment groups, but not in the clozapine group (1 RCT, n=980, RR 1.28 CI 1.02 to 1.61, NNH not estimable), had to be re-hospitalised in the trials. Except for clozapine, all comparators induced less weight gain than olanzapine (olanzapine compared to amisulpride: 3 RCTs, n=671, WMD 2.11kg CI 1.29kg to 2.94kg; aripiprazole: 1 RCT, n=90, WMD 5.60kg CI 2.15kg to 9.05kg; quetiapine: 7 RCTs, n=1173, WMD 2.68kg CI 1.10kg to 4.26kg; risperidone: 13 RCTs, n=2116, WMD 2.61kg CI 1.48kg to 3.74kg; ziprasidone: 5 RCTs, n=1659, WMD 3.82kg CI 2.96kg to 4.69kg). Associated problems such as glucose and cholesterol increase were usually also more frequent in the olanzapine group. Other differences in adverse effects were less well documented. Nevertheless, olanzapine may be associated with slightly more extrapyramidal side effects than quetiapine (use of antiparkinson medication (6
Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Duggan, Lorna; Kissling, Werner; Leucht, Stefan
Antipsychotic induced weight gain is the most common and distressing side effect. This also affects the compliance toward the treatment and hence the prognosis. Non - pharmacological interventions such as exercise and diet modifications alone might not be sufficient most of the times; also ensuring compliance toward this is difficult in patients with psychiatric illness. So, the role of weight - reducing drugs become important. In this case report, we describe the use of low - dose topiramate as a weight - reducing agent, in a patient with a bipolar affective disorder - mania with psychotic symptoms, who had significant risperidone - induced weight gain. PMID:22661816
Shivakumar, Venkataram; Jayaram, Naveen; Rao, Naren P.; Venkatasubramanian, Ganesan
Antipsychotic induced weight gain is the most common and distressing side effect. This also affects the compliance toward the treatment and hence the prognosis. Non - pharmacological interventions such as exercise and diet modifications alone might not be sufficient most of the times; also ensuring compliance toward this is difficult in patients with psychiatric illness. So, the role of weight - reducing drugs become important. In this case report, we describe the use of low - dose topiramate as a weight - reducing agent, in a patient with a bipolar affective disorder - mania with psychotic symptoms, who had significant risperidone - induced weight gain. PMID:22661816
Shivakumar, Venkataram; Jayaram, Naveen; Rao, Naren P; Venkatasubramanian, Ganesan
Antipsychotic-induced movement disorders are major side effects of antipsychotic drugs among schizophrenia patients, and include antipsychotic-induced parkinsonism (AIP) and tardive dyskinesia (TD). Substantial pharmacogenetic work has been done in this field, and several susceptibility variants have been suggested. In this paper, the genetics of antipsychotic-induced movement disorders is considered in a broader context. We hypothesize that genetic variants that are risk factors for AIP and TD may provide insights into the pathophysiology of motor symptoms in Parkinson’s disease (PD). Since loss of dopaminergic stimulation (albeit pharmacological in AIP and degenerative in PD) is shared by the two clinical entities, genes associated with susceptibility to AIP may be modifier genes that influence clinical expression of PD motor sub-phenotypes, such as age at onset, disease severity, or rate of progression. This is due to their possible functional influence on compensatory mechanisms for striatal dopamine loss. Better compensatory potential might be beneficial at the early and later stages of the PD course. AIP vulnerability variants could also be related to latent impairment in the nigrostriatal pathway, affecting its functionality, and leading to subclinical dopaminergic deficits in the striatum. Susceptibility of PD patients to early development of l-DOPA induced dyskinesia (LID) is an additional relevant sub-phenotype. LID might share a common genetic background with TD, with which it shares clinical features. Genetic risk variants may predispose to both phenotypes, exerting a pleiotropic effect. According to this hypothesis, elucidating the genetics of antipsychotic-induced movement disorders may advance our understanding of multiple aspects of PD and it clinical course, rendering this a potentially rewarding field of study.
Greenbaum, Lior; Lerer, Bernard
There have been widespread changes in society and the roles of professionals. This change is also reflected in health care, where there is now acceptance of the need to involve patients in decision making. In prescribing specifically, the concordance agenda was developed alongside these initiatives to encourage improved medication taking and reduce wastage. However the extent to which these partnerships are delivered in practice remains unclear. This paper explores some of the issues to be considered when preparing patients and professionals for partnership and summarizes the limited evidence of barriers to, and benefits of, this approach. Firstly patients must be given the confidence, skills and knowledge to be partners. They need information about medicines, provided in ways known to be acceptable to them. Likewise professionals may need new skills to be partners. They need to understand the patient agenda and may need training and support to change the ways in which they consult with patients. There are also practical issues such as the perceived increase in time taken when consulting in partnership mode, room layout, computer interfaces and record keeping. Health care professionals other than doctors are also expected to behave in partnership mode, whether this is as prescribers in their own right or in supporting the prescribing of others. Whilst much has been claimed for the benefit of partnership approaches, hard evidence is limited. However whilst there is still much more to understand there will be no going back to the paternalistic model of the mid 20th century. PMID:22621201
Bond, Christine; Blenkinsopp, Alison; Raynor, David K
Opinions about district nurses prescribing The aim of this study was to investigate the opinions of district nurses (DNs) and general practitioners (GPs) about nurse prescribing in Sweden in order to elucidate similarities and differences, and relate different opinions to background and psychosocial working factors. In a questionnaire about psychosocial working conditions, seven statements about DNs prescribing were included. The questionnaire was sent to 554 DNs and 566 GPs with a participant rate of 83%. On all items as well as on the total score DNs rated more positively compared with GPs. Amongst the DNs a positive opinion was related to a traditional primary care organization, age < 50, good social support at work, and high workload. A positive opinion amongst GPs was associated with working in a traditional primary care organization, being male GP, and a good social support at work. In a multiple regression analysis, occupation and organization were independently associated with the total score. The result shows a strong professional solidarity amongst GPs and seems to be based on concern about the profession rather than patient care. PMID:12453174
Wilhelmsson, S; Ek, A C; Akerlind, I
Although antidepressant and antipsychotic utilization by gestational trimester has been described, longitudinal prescription patterns within pregnancies have received less attention. All mothers in the Clinical Practice Research Datalink's Mother Baby Link enrolled from 6 months before pregnancy to 3 months after delivery, with delivery date between 01/1989 and 12/2010 were included (n = 421,645). Drug use prevalence was calculated as the number of women with prescriptions for antidepressants or antipsychotics in capsules/tablets in the 3 months before pregnancy (T0), the first (T1), second (T2), or third (T3) pregnancy trimesters, or the 3 months after delivery (T4). In each pregnancy, prescriptions in T0 and T3 were compared to identify treatment discontinuation, simplification (some drugs discontinued or dose lowered), no treatment change, intensification (drugs added to prior treatment or dose increased), and start. Antidepressant use in T0 through T4 was 4.69, 2.81, 1.31, 1.34, and 5.46 %, respectively. Of 19,774 T0 antidepressant users, 79.57 % discontinued, 5.13 % simplified, 9.06 % did not change, and 2.19 % intensified treatment. 0.40 % of non-users in T0 started antidepressants by T3. Antipsychotic use in T0 through T4 was 0.57, 1.34, 0.54, 0.28 and 0.38 %. Excluding prochlorperazine, it was 0.15, 0.13, 0.08, 0.07 and 0.15 %, respectively; of 639 T0 users, 72.30 % discontinued, 7.51 % simplified, 11.11 % did not change, and 4.07 % intensified treatment. 0.03 % of non-users in T0 started antipsychotics by T3. Cross-sectional and longitudinal analyses identified a post-conception decrease in antidepressant and antipsychotic prescribing. Longitudinal treatment assessment additionally captured several treatment patterns among those who do not discontinue treatment that usually stay unrecognized. PMID:24374729
Margulis, Andrea V; Kang, Elizabeth M; Hammad, Tarek A
Objective To investigate the executive function among adolescents with antipsychotic-treated schizophrenia in Child and Adolescent Outpatient Clinic at Cipto Mangunkusumo General Hospital, Jakarta. Methods This was a cross sectional study with control group. Case was defined as adolescents with antipsychotic-treated schizophrenia without any mental retardation or other physical illnesses (n=45). The control group consisted of healthy and age-matched adolescents (n=135). Executive function is determined by using Indonesian version of Behavior Rating Inventory of Executive Function (BRIEF-Indonesian version). We used SPSS 16.0 program for windows to calculate the prevalence risk ratio (PRR) and set up the p value <0.05. Results Mean of age was 16.27 (standard deviation 1.86) year-old. Most of the case group (95%) has been treated with atypical antipsychotic such as risperidone, aripipripazole, olanzapine, and clozapine. Duration of having antipsychotic medication was ranged from one to 36 months. Adolescents with antipsychotic treated-schizophrenia had higher BRIEF T-score, except for inhibit scale, shift scale and behavior regulation index. The prevalence risk ratio on several clinical scales were higher in children with antipsychotic-treated schizophrenia compared to control group, such as on emotional state (PRR=7.43, 95% confidence interval [CI]=2.38-23.15), initiate scale (PRR=6.32, 95% CI=2.51-15.95), monitor scale (PRR=8.11, 95% CI=2.0-32.86), and behavior regulation index (PRR=4.09, 95% CI=1.05-15.98). Conclusion In general, the results showed that adolescents with atypical antipsychotic treated-schizophrenia had higher BRIEF T-score compared, and comparable with their normal group control. PMID:25598823
Guerrero, Anthony Paul Sison; Honjo, Shuji; Ismail, Irawati; WR, Noorhana Setyowati; Kaligis, Fransiska
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. PMID:10586534
Remington, G; Chong, S A
The atypical antipsychotics are a group of second generation drugs used for the treatment of schizophrenia, schizoaffective disorder, as well as some forms of bipolar and major depressive disorder. First generation or the "typical antipsychotics...
Hughes, John Clayton
whether antipsychotic medication modulates behavioral and neural responses to prediction error coding condition. Specifically, patients taking higher doses of medication showed attenuated prediction error-based learning. However, it remains un- known how treatment with antipsychotic medication impacts the behavioral
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 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
Objective The strong association between psychiatric patients who receive antipsychotics and the incidence of venous thromboembolism (VTE) is known. Although previous reports suggest that hyperprolactinemia often increases markers of activated coagulation, few studies have examined the direct relationship between the prolactin level elevated by antipsychotics and activated markers of activated coagulation. Method The participants included 182 patients with schizophrenia (male =89, female =93) who received antipsychotic treatments for at least 3 months. Markers of VTE (D-dimer, fibrin/fibrinogen degradation products, and thrombin–antithrombin complex) and serum prolactin concentrations were measured. Results Prolactin levels were significantly correlated with the logarithmic transformation of the D-dimer (r=0.320, P=0.002) and fibrin/fibrinogen degradation product levels (r=0.236, P=0.026) but not of the thrombin–antithrombin complex level (r=0.117, ns) among men. However, no correlations were found between the VTE markers and prolactin levels among women. These results were confirmed using multiple regression analyses that included demographic factors and antipsychotic dosages. Conclusion The current study indicates that hyperprolactinemia is associated with an increase in markers of activated coagulation among men receiving antipsychotics. This finding clinically implies that monitoring and modulating prolactin levels among men are important to decrease the risk of VTE. PMID:25750528
Ishioka, Masamichi; Yasui-Furukori, Norio; Sugawara, Norio; Furukori, Hanako; Kudo, Shuhei; Nakamura, Kazuhiko
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. PMID:17932088
Hill, S. Kristian; Reilly, James L.; Harris, Margret S. H.; Khine, Tin; Sweeney, John A.
Social cognition is described as the higher mental processes that are engaged while people store, process, and use social information to make sense of themselves and others. Aspects of social cognition include emotion perception, social cue interpretation, attribution style, and theory of mind, all of which appear disordered in schizophrenia. Such social cognitive deficits are believed to be important predictors of functional outcome in schizophrenia, therefore they may represent a crucial treatment target. Few studies have evaluated the influence of antipsychotic treatment on these deficits. The purpose of this review is to examine the relationship between antipsychotic treatment and social cognition, whether antipsychotics improve social cognitive function, and if so to explore differential medication effects. Comprehensive searches of PsycINFO and MEDLINE/PUBMED were conducted to identify relevant published manuscripts. Fifteen relevant papers published in English were found, describing original studies. On the basis of this review, we have drawn the following conclusions: first, the results do not engender optimism for the possibility that antipsychotic drugs can specifically facilitate social recovery. Second, the actions of antipsychotics on social cognition are inconclusive, due to lack of standardization across research groups, leading to inconsistencies between study designs, methods used, and medication dosages. Third, large-scale longitudinal investigations are needed to explore the unclear relationships between social cognition, symptoms, and functional outcome. Other non-pharmacological treatments focusing on training patients in the social cognitive areas may hold more promise. PMID:23533009
Kucharska-Pietura, Katarzyna; Mortimer, Ann
Background This article describes the personal, societal, and economic burden attributable to schizophrenia in the People’s Republic of China and highlights the potential for effective outpatient treatment to reduce this burden given recent changes in the Chinese health care system. The importance of effective antipsychotic therapy in reducing the burden of schizophrenia is also examined. Methods Published research on the burden, disability, management, and economic costs of schizophrenia in the People’s Republic of China was examined in the context of the larger body of global research. Research written in English or Chinese and published before June 2012 was identified using PubMed, CNKI, and Wanfang Med database searches. The contribution of effective antipsychotic therapy in reducing the risk for relapse and hospitalization and improving patients’ functioning is described. Results Schizophrenia imposes a substantial burden on Chinese society, with indirect costs accounting for the majority of the total cost. Functional impairment is high, leading to lost wages and work impairment. In the People’s Republic of China, schizophrenia is the most common diagnosis among hospitalized psychiatric patients. Ongoing changes in the Chinese health care system may reduce some barriers to effective relapse prevention in schizophrenia and potentially reduce hospitalizations. The use of antipsychotics for acute episodes and maintenance treatment has been shown to decrease symptom severity and reduce the risk for relapse and hospitalization. However, discontinuing antipsychotic medication appears common and is a strong predictor of relapse. Cost-effectiveness research in the People’s Republic of China is needed to examine the potential gains from improved outpatient antipsychotic treatment. Conclusion Schizophrenia is a very costly mental illness in terms of personal, economic, and societal burden, both in the People’s Republic of China and globally. When treated effectively, patients tend to persist longer with antipsychotic treatment, have fewer costly relapses, and have improved functioning. Further research examining the long-term effects of reducing barriers to effective treatments on the societal burden of schizophrenia in the People’s Republic of China is needed. PMID:23983478
Montgomery, William; Liu, Li; Stensland, Michael D; Xue, Hai Bo; Treuer, Tamas; Ascher-Svanum, Haya
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.
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. PMID:23983972
Omoaregba, Joyce O.; Okonoda, Kingsley M.; Otefe, Edebi U.; Patel, Maxine X.
Medications are commonly used during pregnancy; in fact, female patients take an average of 2.9 medications during pregnancy. Due to this high prevalence, malpractice litigation poses a high legal risk to dermatologists who prescribe medications to female patients who are or may become pregnant. This article introduces the medicolegal risks involved in prescribing dermatological medications to a pregnant patient and discusses ways for a dermatologist to mitigate those risks. International safety classification systems are reviewed, and potential high risk dermatologic medications prescribed in acne, psoriasis, atopic dermatitis, and connective tissue disease are discussed. In addition, the article summarizes resources available to patients as well as the important elements for dermatologists to include when documenting their discussion with the patient in the medical record. PMID:24800428
Gupta, Rishu; High, Whitney A; Butler, Daniel; Murase, Jenny E
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
Haya Ascher-Svanum; Xiaomei Peng; Douglas Faries; William Montgomery; Peter M Haddad
Background: Antipsychotic utilization in elderly nursing home residents has increased substantially in recent years, primarily due to the use of atypical antipsychotic agents. However, few studies have examined antipsychotic utilization patterns in nursing home residents in the United States since the introduction of atypical agents in the 1990s.Objective: The goal of this study was to examine the prevalence of and
Pravin Kamble; Hua Chen; Jeff Sherer; Rajender R. Aparasu
Objective To develop an evidence base for recommendations on the use of atypical antipsychotics for patients with schizophrenia. Design Systematic overview and meta›regression analyses of randomised controlled trials, as a basis for formal development of guidelines. Subjects 12 649 patients in 52 randomised trials comparing atypical antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, risperidone, and sertindole) with conventional antipsychotics (usually haloperidol or
J. Geddes; N. Freemantle; P. Harrison; P. Bebbington
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.
Introduction Antipsychotics are commonly used for management of behavioural symptoms in dementia, among people in residential care. This continues to occur despite their modest effectiveness, potential harms including increased risk of death and stroke, and absence of detrimental effect when people with dementia were randomised to antipsychotic withdrawal. This study aims to test the hypothesis that the multifaceted REducing Anti-Psychotic use in residential care-Huntington Disease (REAP-HD) programme is more effective than standard staff education (SSE) in reducing antipsychotic use for people with HD in residential care facilities (RCF). Methods and analysis this is a cluster randomised controlled trial with blinded outcome assessment. The study population is healthcare professionals looking after people with HD in individual RCF, in the state of New South Wales. Each RCF will be centrally randomised to the REAP-HD programme or the comparator, SSE. Blinded outcome assessment will be performed by examining drug charts and using the Neuropsychiatric Inventory-Q (NPI-Q). Primary outcome is the proportion of people with HD who have had a reduction in antipsychotic use 4?months after the intervention. Secondary outcome measures are (1) change in severity of behavioural symptoms, as measured by the NPI-Q at 4?months (to ensure antipsychotic reduction has not lead to worsening behavioural symptoms), and (2) proportion of people with HD who have had a reduction in antipsychotic dosage at 4?months for each strategy, compared to 4?months prior to enrolment (to capture the possibility that both arms reduced antipsychotic use). Analysis will be by Intention-To-Treat and take into account the clustering. Recruitment is ongoing, as of July 2014. Ethics and dissemination This protocol has been approved by the Western Sydney Local Health District Human Research Ethics Committee, trial registration ACTRN12614000083695. Study results will be disseminated through peer-reviewed publication in an anonymous manner. Trial registration number ACTRN12614000083695, the Australian New Zealand Clinical Trials Registry. PMID:25468506
Loy, Clement T; Hayen, Andrew; McKinnon, Colleen
Objective: To develop a practitioner led definition of a prescribing error for use in prevalence/incidence studies in paediatric practice. Design: A two stage Delphi technique was used to obtain the views of a panel of expert health professionals working in the hospital paediatric setting. The extent of their agreement on a definition of a prescribing error, and on 40 scenarios that might be classified as prescribing errors in paediatric practice, was obtained. Results: Response rates were 84% (n = 42) in the first Delphi round and 95% (n = 40) in the second. Consensus was to accept the general definition of a prescribing error. In addition, there was consensus that 27 of the 40 scenarios should be included as prescribing errors, 10 should be excluded, and three may be considered prescribing errors depending on the individual clinical situation. Failure to communicate essential information, transcription errors and the use of drugs, formulations, or doses inappropriate for the individual patient were considered prescribing errors. Deviations from policies or guidelines, use of unlicensed and off-label drugs, and omission of non-essential information were not considered prescribing errors. Conclusion: A general definition of a prescribing error has been developed that is applicable to the paediatric setting, together with more detailed guidance regarding the types of events that should be included. These findings are suitable for use in future research into the incidence and nature of prescribing errors in paediatrics. PMID:16195569
Ghaleb, M; Barber, N; Dean, F; Wong, I
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. PMID:22144698
Cohn, Lisa; Rocchini, Albert; Kershaw, David; Freed, Gary; Ascione, Frank; Clark, Sarah
Objective: A substantial gap exists between patients and their mental health providers about patient's perceived barriers, facilitators, and motivators (BFMs) for taking antipsychotic medications. This article describes how we used an intervention mapping (IM) framework coupled with qualitative and quantitative item-selection methods to…
Pyne, Jeffrey M.; Fischer, Ellen P.; Gilmore, LaNissa; McSweeney, Jean C.; Stewart, Katharine E.; Mittal, Dinesh; Bost, James E.; Valenstein, Marcia
the risk for coronaryoccur together and increase the risk for coronary artery disease, stroke, and type 2 al 2004; NCEP/ATP III Guidelines #12;Background Â· Community Prevalence of Metabolic Syndrome: 24 34 of MS prevalence by antipsychotics with incarcerated populationp y p p Â· Individual variation (with
Oliver, Douglas L.
Objective: Both first- (FGAs) and second-generation antipsychotics (SGAs) are routinely used in treating severe and persistent psychiatric disorders. However, until now no articles have analyzed systematically the safety of both classes of psychotropics during pregnancy. Data sources and search strategy: Medical literature information published in any language since 1950 was identified using MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from companies developing drugs. Search terms were pregnancy, psychotropic drugs, (a)typical-first-second-generation antipsychotics, and neuroleptics. A separate search was also conducted to complete the safety profile of each reviewed medication. Searches were last updated on July 2008. Data selection: All articles reporting primary data on the outcome of pregnancies exposed to antipsychotics were acquired, without methodological limitations. Conclusions: Reviewed information was too limited to draw definite conclusions on structural teratogenicity of FGAs and SGAs. Both classes of drugs seem to be associated with an increased risk of neonatal complications. However, most SGAs appear to increase risk of gestational metabolic complications and babies large for gestational age and with mean birth weight significantly heavier as compared with those exposed to FGAs. These risks have been reported rarely with FGAs. Hence, the choice of the less harmful option in pregnancy should be limited to FGAs in drug-naive patients. When pregnancy occurs during antipsychotic treatment, the choice to continue the previous therapy should be preferred. PMID:18787227
Background Treatment of psychotic disorders consists primarily of second generation antipsychotics, which are associated with metabolic side effects such as overweight/obesity, diabetes, and dyslipidemia. Evidence-based clinical practice guidelines recommend timely assessment and management of these conditions; however, research studies show deficits and delays in metabolic monitoring and management for these patients. This protocol article describes the project ‘Monitoring and Management for Metabolic Side Effects of Antipsychotics,’ which is testing an approach to implement recommendations for these practices. Methods/Design This project employs a cluster randomized clinical trial design to test effectiveness of an evidence-based quality improvement plus facilitation intervention. Eligible study sites were VA Medical Centers with ?300 patients started on a new antipsychotic prescription in a six-month period. A total of 12 sites, matched in pairs based on scores on an organizational practice survey, were then randomized within pairs to intervention or control conditions. Study participants include VA employees involved in metabolic monitoring and management of patients treated with antipsychotics at participating sites. The intervention involves researchers partnering with clinical stakeholders to facilitate tailoring of local implementation strategies to address barriers to metabolic side-effect monitoring and management. The intervention includes a Design Phase (initial site visit and subsequent development of a local implementation plan); Implementation Phase (guided by an experienced external facilitator); and a Sustainability Phase. Evaluation includes developmental, implementation-focused, progress-focused and interpretative formative evaluation components, as well as summative evaluation. Evaluation methods include surveys, qualitative data collection from provider participants, and quantitative data analysis of data for all patients prescribed a new antipsychotic medication at a study site who are due for monitoring or management of metabolic side effects during the study phases. Changes in rates of recommended monitoring and management actions at intervention and control sites will be compared using time series analyses. Discussion Improving monitoring for metabolic side effects of antipsychotics, as well as promoting timely evidence-based management when these effects emerge, will lead to improved patient safety and long-term outcomes. This article discusses key strengths and challenges of the study. Trial registration NCT01875861 PMID:24103648
The vast majority of approved antidepressants and antipsychotics exhibit a complex pharmacology. The mechanistic understanding of how these psychotropic medications are related to adverse drug reactions (ADRs) is crucial for the development of novel drug candidates and patient adherence. This study aims to associate in vitro assessed binding affinity profiles (39 compounds, 24 molecular drug targets) and ADRs (n=22) reported in clinical trials of antidepressants and antipsychotics (n>59.000 patients) by the use of robust multivariate statistics. Orthogonal projection to latent structures (O-PLS) regression models with reasonable predictability were found for several frequent ADRs such as nausea, diarrhea, hypotension, dizziness, headache, insomnia, sedation, sleepiness, increased sweating, and weight gain. Results of the present study support many well-known pharmacological principles such as the association of hypotension and dizziness with ?1-receptor or sedation with H1-receptor antagonism. Moreover, the analyses revealed novel or hardly investigated mechanisms for common ADRs including the potential involvement of 5-HT6-antagonism in weight gain, muscarinic receptor antagonism in dizziness, or 5-HT7-antagonism in sedation. To summarize, the presented study underlines the feasibility and value of a multivariate data mining approach in psychopharmacological development of antidepressants and antipsychotics. PMID:25044049
Michl, Johanna; Scharinger, Christian; Zauner, Miriam; Kasper, Siegfried; Freissmuth, Michael; Sitte, Harald H; Ecker, Gerhard F; Pezawas, Lukas
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. PMID:22118459
Fribourg, Miguel; Moreno, José L.; Holloway, Terrell; Provasi, Davide; Baki, Lia; Mahajan, Rahul; Park, Gyu; Adney, Scott K.; Hatcher, Candice; Eltit, José M.; Ruta, Jeffrey D.; Albizu, Laura; Li, Zheng; Umali, Adrienne; Shim, Jihyun; Fabiato, Alexandre; MacKerell, Alexander D.; Brezina, Vladimir; Sealfon, Stuart C.; Filizola, Marta; González-Maeso, Javier; Logothetis, Diomedes E.
Objective Description of demographics of an outpatient population of clozapine users. Methods Retrospective chart review study of an urban population diagnosed with schizophrenia. Assessment of therapeutic histories in relation to clinical practice guidelines. Results Seventy-seven of the 467 patients were on clozapine therapy. Average patients’ age was 39.4 ± 11.8 years) and 68% were males. The majority of patients (68%) had tried 3 or more antipsychotics before switching to clozapine, 21% had tried two and 11% had tried one. Median length of therapy prior to clozapine initiation was 8.9 years in males and 7.7 years in females. Conclusion Until 2010, the use of clozapine was often delayed and more than 2 antipsychotic medications were tried for relatively long periods of time before patients were switched to this effective agent. PMID:24358290
Alessi-Severini, Silvia; Le Dorze, Josee-Anne; Nguyen, David; Honcharik, Patricia; Eleff, Michael
Prescribing medicines is an essential part of comprehensive dental care. Behind this seemingly simple act lies a range of skills. These include understanding the physiological interaction of the medicines in the body as well as their potential for harm either to body systems or when conflicting with other medicines taken by the patient. The decision to prescribe is thus complex even before the efficacy of the drug for the dental condition is considered. This paper reviews some of the issues that the primary care practitioner must consider when prescribing, as well as practical concerns to make prescribing safe and effective. PMID:25668379
Background Respiratory tract infections (RTIs) in children are common and often result in antibiotic prescription despite their typically self-limiting course. Aim To assess the effectiveness of primary care based interventions to reduce antibiotic prescribing for children with RTIs. Design and setting Systematic review. Method MEDLINE®, Embase, CINAHL®, PsycINFO, and the Cochrane library were searched for randomised, cluster randomised, and non-randomised studies testing educational and/or behavioural interventions to change antibiotic prescribing for children (<18 years) with RTIs. Main outcomes included change in proportion of total antibiotic prescribing or change in ‘appropriate’ prescribing for RTIs. Narrative analysis of included studies was used to identify components of effective interventions. Results Of 6301 references identified through database searching, 17 studies were included. Interventions that combined parent education with clinician behaviour change decreased antibiotic prescribing rates by between 6–21%; structuring the parent–clinician interaction during the consultation may further increase the effectiveness of these interventions. Automatic computerised prescribing prompts increased prescribing appropriateness, while passive information, in the form of waiting room educational materials, yielded no benefit. Conclusion Conflicting evidence from the included studies found that interventions directed towards parents and/or clinicians can reduce rates of antibiotic prescribing. The most effective interventions target both parents and clinicians during consultations, provide automatic prescribing prompts, and promote clinician leadership in the intervention design. PMID:23834881
Vodicka, Talley A; Thompson, Matthew; Lucas, Patricia; Heneghan, Carl; Blair, Peter S; Buckley, David I; Redmond, Niamh; Hay, Alastair D
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. PMID:22712004
Fiedorowicz, Jess G.; Miller, Del D.; Bishop, Jeffrey R.; Calarge, Chadi A.; Ellingrod, Vicki L.; Haynes, William G.
Objectives: Patients with chronic kidney disease (CKD) suffer with multiple comorbidities and complications like secondary hyperparathyroidism and hyperphosphotemia. Altered mineral metabolism contributes to bone disease and cardiovascular disease. In patients of CKD, despite dietary phosphorus restriction, phosphate binders (PBs) are recommended to control phosphorous level. No studies about the utilization pattern of PBs in CKD patients have been reported from India. This study analyses the current prescribing trends in the management of CKD patients undergoing tertiary care with focus on PBs. Materials and Methods: This cross-sectional, observational study was conducted in nephrology department of a government super speciality hospital over 8-month period from January to August 2011. Demographic, clinical, and medication details were collected in a specially designed proforma. Results: A total 111 prescriptions were included in the study. Average number of drugs per prescription was 9.47. About 41.53% of the prescribed drugs were from the World Health Organization essential medicines list. Out of total prescribed drugs (1052), most commonly prescribed were vitamins and minerals (24.71%), cardiovascular drugs, (22.14%), and hematopoietic agents (20.15%). Considering individual drugs, five most commonly prescribed drugs were multivitamins (14.82%), iron (8.65%), folic acid (8.55%), calcium carbonate (8.17%), and calcitriol (5.60%). A total of 11.02% of prescribed drug were PBs. Among PBs, calcium carbonate was the most frequently prescribed and sevelamer was the least prescribed PB. No patient was prescribed lanthanum carbonate. Conclusion: This study identified a wide variety of drug classes including PBs prescribed in CKD patients. Although sevelamer hydrochloride has less side effects as compared to calcium salts, it was less prescribed since it is costlier. PMID:24550582
Bajait, Chaitali S; Pimpalkhute, Sonali A; Sontakke, Smita D; Jaiswal, Kavita M; Dawri, Amruta V
Patients with schizophrenia and their physicians face a number of challenges, such as long-term control of symptoms, maintaining cognitive function and subjective well-being, and preventing relapse. While randomised, placebo-controlled trials and open-label extensions can provide valuable information about the long-term efficacy and tolerability of newer antipsychotic agents, they cannot address all the variables that may affect treatment outcome. Factors such as cognitive function, antipsychotic side effects, patients' attitudes to medication and subjective well being can all affect the results of treatment in real-life clinical practice. Moreover, the patient cohorts enrolled in clinical trials are often not reflective of the wider population with schizophrenia. For example, patients with conditions such as anxiety and panic disorders or comorbid substance abuse, as well as those with severe illness and patients from certain ethnic or age groups, may often be excluded from clinical trials. In addition, patients themselves may refuse to participate in placebo-controlled studies because of a fear of being under-treated. Naturalistic studies are, therefore, an important means of providing additional data on the safety and effectiveness of antipsychotic agents in 'real-world' settings. Studies such as the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, the Schizophrenia Outpatient Health Outcomes (SOHO) study and the Broad Effectiveness Trial with Aripiprazole (BETA) studies, together with large-scale database analyses, are now producing results supplementary to those observed in long-term, open-label extension studies. Such naturalistic studies will continue to provide important data on the real-world effectiveness of atypical antipsychotics with respect to key outcomes such as treatment continuation and prolonged recovery. PMID:16872807
Objectives: Antipsychotic drug side effects are common and can cause stigmatisation, decreased quality of life, poor adherence, and secondary morbidity and mortality. Systematic assessment of anticipated side effects is recommended as part of good clinical care, but is uncommon in practice and patients may not spontaneously report side effects. We aimed to develop a simple patient-completed checklist to screen systematically for potential antipsychotic side effects. Methods: The SMARTS checklist was developed over a series of group meetings by an international faculty of 12 experts (including psychiatrists, a general physician and a psychopharmacologist) based on their clinical experience and knowledge of the literature. The emphasis is on tolerability (i.e. assessment of side effects that ‘trouble’ the patient) as subjective impact of side effects is most relevant to medication adherence. The development took account of feedback from practising psychiatrists in Europe, the Middle East and Africa, a process that contributed to face validity. Results: The SMARTS checklist assesses whether patients are currently ‘troubled’ by 11 well-established potential antipsychotic side effects. Patients provide their responses to these questions by circling relevant side effects. An additional open question enquires about any other possible side effects. The checklist has been translated into Italian and Turkish. Conclusions: The SMARTS checklist aims to strike a balance between brevity and capturing the most common and important antipsychotic side effects. It is appropriate for completion by patients prior to a clinical consultation, for example, in the waiting room. It can then form the focus for a more detailed clinical discussion about side effects. It can be used alone or form part of a more comprehensive assessment of antipsychotic side effects including blood tests and a physical examination when appropriate. The checklist assesses current problems and can be used longitudinally to assess change. PMID:24490026
Fleischhacker, W Wolfgang; Peuskens, Joseph; Cavallaro, Roberto; Lean, Michael EJ; Morozova, Margarita; Reynolds, Gavin; Azorin, Jean-Michel; Thomas, Pierre; Möller, Hans-Jürgen
We have examined the prescribing patterns among general practitioners (GPs) in a Norwegian county in relation to the patients' age and sex and the diagnosis for prescribing. Altogether 69,843 contacts with patients were recorded during which 56,758 items were prescribed. The average number of items prescribed per patient contact was 0.81 (male 0.76, female 0.83). Diazepam, the compound analgesic of
Kirsten Rokstad; Jørund Straand; Per Fugelli
The use of combination therapy with mood stabilizers and antipsychotics in acute mania in bipolar disorder (BD) is widespread, although most treatment guidelines recommend monotherapy as the first option, and reserve combination therapy, which is associated with more frequent and more severe side effects, for when patients do not respond to the former treatment option. Reasons to prescribe combination therapy include the lack of efficacy of the current treatment (either real or due to undisclosed poor adherence), psychiatric comorbidities, severe previous course of illness, slow cross-tapering during treatment switching, and potential benefits from particular combinations. The decision to start with monotherapy or combination therapy may depend on the patient characteristics, and is still under debate. Clinical trials designed to ascertain whether combination therapy or monotherapy is more advantageous for patients in acute mania and beyond, according to illness severity, are urgently needed. Adding a third monotherapy arm to the conventional two-arm, adjunctive-design trials or initiating combination therapy from the beginning may help to shed some light on the issue. PMID:25711483
Grande, Iria; Vieta, Eduard
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 the striatum. Anatomical changes have been documented at the level of regional brain volume, synapse morphology, and synapse number. At the molecular level, haloperidol has been shown to cause phosphorylation of proteins and to induce gene expression. The molecular responses to conventional antipsychotic drugs are predominantly observed in the striatum and nucleus accumbens, whereas atypical anti-psychotic drugs have a subtler and more widespread impact. We conclude that the ability of antipsychotic drugs to induce anatomical and molecular changes in the brain may be relevant for their antipsychotic properties. The delayed therapeutic action of antipsychotic drugs, together with their promotion of neuroplasticity suggests that modification of synaptic connections by antipsychotic drugs is important for their mode of action. The concept of schizophrenia as a disorder of synaptic organization will benefit from a better understanding of the synaptic changes induced by antipsychotic drugs. PMID:11720691
Konradi, Christine; Heckers, Stephan
This paper describes a method to design the periodic microstructure of a material to obtain prescribed constitutive properties. The microstructure is modelled as a truss or thin frame structure in 2 and 3 dimensions. The problem of finding the simplest possible microstructure with the prescribed elastic properties can be called an inverse homogenization problem, and is formulated as an optimization
Many forests that historically experienced frequent low-intensity wildfires have undergone extensive alterations during the past century. Prescribed fire is now commonly used to restore these fire-adapted forest ecosystems. In this study, we examined the influence of prescribed burn season on levels of tree mortality attributed to prescribed fire effects (direct mortality) and bark beetles (Coleoptera: Curculionidae, Scolytinae) (indirect mortality) in
Christopher J. Fettig; Stephen R. McKelvey; Daniel R. Cluck; Sheri L. Smith; William J. Otrosina
OBJECTIVES: In 2011, the Food and Drug Administration (FDA) approved intravenous esomeprazole 0.5 mg/day for children aged >1 month and oral esomeprazole for infants aged 1 month to <1 year at doses of 2.5, 5, and 10 mg based on weight. Prior to 2011, proton pump inhibitors (PPIs) were not approved for use in infants aged <1 year. This study determined PPI usage rates prior to the FDA approval among newborns and infants in both the inpatient and outpatient settings and compared PPI and histamine-2 receptor antagonist (H2RA) usage in the inpatient setting. METHODS: We conducted a retrospective analysis of PPI prescribing patterns for newborns and infants from 2003 to 2008 using data from the Premier Perspective Inpatient Hospital Database and the PharMetrics Patient-Centric Database for inpatient and outpatient data, respectively. PPI use and diagnoses were determined from clinical and charge records from more than 500 hospitals. Descriptive statistics were used to summarize the findings. RESULTS: Our analysis showed that PPIs were prescribed for approximately 5000 newborns (0.13%) and 15,000 infants (2.65%) each year in the hospital setting and 1.6% of newborns and infants, as a group, in the outpatient setting. Newborns and infants receiving PPIs most often had diagnoses of gastroesophageal reflux disease (GERD) and were generally prescribed an adult PPI dose, although the actual dose administered could not be substantiated. CONCLUSIONS: Although no PPI was approved by the FDA for patients aged <1 year at the time of this study, results of this analysis indicate that PPIs were commonly prescribed for newborns and infants, mostly in hospital, but also in outpatient settings. Most PPIs were prescribed for infants with a diagnosis of GERD.
Illueca, Marta; Shoetan, Nze; Yang, Huiying
Errors in prescribing of dangerous medications, such as extended release or long acting (ER/LA) opioid forlmulations, remain an important cause of patient harm. Prescribing errors often relate to the failure to note warnings regarding contraindications and drug interactions. Many prescribers utilize electronic pharmacopoeia (EP) to improve medication ordering. The purpose of this study is to assess the ability of commonly used apps to provide accurate safety information about the boxed warning for ER/LA opioids. We evaluated a convenience sample of six popular EP apps available for the iPhone and an online reference for the presence of relevant safety warnings. We accessed the dosing information for each of six ER/LA medications and assessed for the presence of an easily identifiable indication that a boxed warning was present, even if the warning itself was not provided. The prominence of precautionary drug information presented to the user was assessed for each app. Provided information was classified based on the presence of the warning in the ordering pathway, located separately but within the prescribers view, or available in a separate screen of the drug information but non-highlighted. Each program provided a consistent level of warning information for each of the six ER/LA medications. Only 2/7 programs placed a warning in line with dosing information (level 1); 3/7 programs offered level 2 warning and 1/7 offered level 3 warning. One program made no mention of a boxed warning. Most EP apps isolate important safety warnings, and this represents a missed opportunity to improve prescribing practices. PMID:24081616
Lapoint, Jeff; Perrone, Jeanmarie; Nelson, Lewis S
It is one of the major psychiatric dogmas that the efficacy of all antipsychotic drugs is same. This statement originated from old, narrative reviews on first-generation antipsychotics, but this old literature has never been meta-analysed. We therefore conducted a meta-analysis of randomised controlled trials on the efficacy of chlorpromazine versus any other antipsychotic in the treatment of schizophrenia. If the benchmark drug chlorpromazine were significantly more or less effective than other antipsychotics, the notion of equal efficacy would have to be rejected. We searched the Cochrane Schizophrenia Group?s specialized register, MEDLINE, EMBASE, PsychInfo and reference lists of relevant articles. The primary outcome was response to treatment. We also analyzed mean values of schizophrenia rating scales at endpoint and drop-out rates. 128, mostly small, RCTs with 10667 participants were included. Chlorpromazine was compared with 43 other antipsychotics and was more efficacious than four (butaperazine, mepazine, oxypertine and reserpine) and less efficacious than other four antipsychotics (clomacran, clozapine, olanzapine and zotepine) in the primary outcome. There were no statistically significant efficacy differences between chlorpromazine and the remaining 28 antipsychotics. The most important finding was that, due to low numbers of participants (median 50, range 8-692), most comparisons were underpowered. Thus we infer that the old antipsychotic drug literature was inconclusive and the claim for equal efficacy of antipsychotics was never evidence-based. Recent meta-analyses on second-generation antipsychotics were in a better position to address this question and small, but consistent differences between drugs were found. PMID:24766970
Samara, Myrto T; Cao, Haoyin; Helfer, Bartosz; Davis, John M; Leucht, Stefan
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. PMID:21172575
Caroff, Stanley N.; Hurford, Irene; Lybrand, Janice; Campbell, E. Cabrina
Background Hyperprolactinemia (HPL) is a common side effect of antipsychotic medications. Recent reports suggest that aripiprazole can ameliorate antipsychotic-induced HPL, but results are inconsistent and the single available systematic review only considered five studies. Aim Conduct an updated meta-analysis of all randomized controlled trials (RCTs) about the efficacy and safety of aripiprazole as an adjunctive treatment for antipsychotic-induced hyperprolactinemia. Methods English and Chinese databases were searched for RCTs about the use of aripiprazole in treating antipsychotic-induced HPL published by January 20, 2015. Studies were selected using pre-defined inclusion and exclusion criteria. The Cochrane Risk of Bias tool was used to evaluate risk of biases, the Cochrane GRADE measure was used to assess the quality of evidence, and Review Manager 5.3 software was used for data analysis. Results A total of 21 studies, 19 of which were conducted in mainland China, were included in the analysis. Meta-analysis of data from 8 of the studies with a pooled sample of 604 individuals found that compared to the control condition adjunctive aripiprazole significantly increased the proportion of participants who experienced HPL recovery (risk ratio [RR]=19.2, 95%CI=11.0-33.5). The proportion who experienced any adverse effect during follow-up did not differ between the two groups, but the aripiprazole group was more likely to report somnolence (RR=2.76, 95%CI=1.34-5.69) and headaches (RR=2.31, 95%CI=1.08-4.92). High-dose aripiprazole (>5mg/day) was more effective than low-dose (<5mg/day) aripiprazole (RR=30.0, 95%CI=10.2-120.7 v. RR=15.1, 95%CI=8.1-28.1), but this difference was not statistically significant. The risk of bias in the studies was rated as ‘high’ in 6 of the studies and ‘unclear’ in 15 studies, and the quality of evidence was rated as ‘high’ for only 7 of the 57 outcome measures assessed. Conclusions This study systematically reviewed and evaluated all relevant RCTs and found that adjunctive aripiprazole is effective and safe to use in the treatment of antipsychotic-induced HPL. However, the low quality of some of the studies, the incomplete methodological information provided for most of the studies, and the relatively short follow-up time of the studies raises question about the validity of the results. Further work that resolves these methodological and reporting issues is needed.
MENG, Meiling; LI, Wei; ZHANG, Shaowei; WANG, Hongyan; SHENG, Jianhua; WANG, Jijun; LI, Chunbo
This column presents findings of an analysis conducted to quantify the potential net savings to state budgets from interventions to improve adherence to antipsychotic drugs among patients with schizophrenia. Using a financial model based on published data, the authors estimated costs of direct medical care and criminal justice system involvement at state and national levels and validated it against findings from other cost studies. The model estimated an annual cost of $21.4 billion (in 2013 dollars) to Medicaid programs and other state agencies for people with schizophrenia. On the basis of data on the effect on outcomes of increased medication adherence, better adherence could yield annual net savings of $3.28 billion to states or $1,580 per patient per year. Innovations to improve adherence to antipsychotic drugs among schizophrenia patients can yield substantial savings in state budgets. States should consider interventions shown to increase medication adherence in this patient group. PMID:25555222
Predmore, Zachary S; Mattke, Soeren; Horvitz-Lennon, Marcela
In the field of schizophrenia research, as in other areas of psychiatry, there is a sense of frustration that greater advances have not been made over the years, calling into question existing research strategies. Arguably, many purported gains claimed by research have been “lost in translation,” resulting in limited impact on diagnosis and treatment in the clinical setting. There are exceptions; for example, we would argue that different lines of preclinical and clinical research have substantially altered how we look at antipsychotic dosing. While this story remains a work in progress, advances “found in translation” have played an important role. Detailing these changes, the present paper speaks to a body of evidence that has already shifted clinical practice and raises questions that may further alter the manner in which antipsychotics have been administered over the last 6 decades. PMID:24467943
Remington, Gary; Fervaha, Gagan; Foussias, George; Agid, Ofer; Turrone, Peter
People today are living longer. Old age is the number one risk factor for dementia, which is often associated with behavioral disturbances and psychosis as well as cognitive and memory impairment. Elderly persons with dementia—particularly those who are agitated or aggressive—are often placed in nursing homes and consequently treated with antipsychotic medications. Most of the studies of antipsychotic efficacy and safety have been conducted in young schizophrenic patients, but there are differences in dosing schedules, efficacy, and compliance when these drugs are used in elderly patients with dementia and psychosis. A review of both nonpharmacologic and pharmacologic treatment is herewith presented for the treatment of elderly dementia patients, especially those living in long-term care facilities. PMID:15014638
Maguire, Gerald A.
Background Health care policy-makers look for prescribing indicators at the population level to evaluate the performance of prescribers, improve quality and control drug costs. The aim of this research was to; (i) estimate the level of variation in potentially inappropriate prescribing (PIP) across prescribers in the national Irish older population using the STOPP criteria; (ii) estimate how reliably the criteria could distinguish between prescribers in terms of their proportion of PIP and; (iii) examine how PIP varies between prescribers and by patient and prescriber characteristics in a multilevel regression model. Methods 1,938 general practitioners (GPs) with 338,375 registered patients’ ?70 years were extracted from the Health Service Executive Primary Care Reimbursement Service (HSE-PCRS) pharmacy claims database. HSE-PCRS prescriptions are WHO ATC coded. Demographic data for claimants’ and prescribers’ are available. Thirty STOPP indicators were applied to prescription claims in 2007. Multilevel logistic regression examined how PIP varied between prescribers and by individual patient and prescriber level variables. Results The unadjusted variation in PIP between prescribers was considerable (median 35%, IQR 30-40%). The STOPP criteria were reliable measures of PIP (average >0.8 reliability). The multilevel regression models found that only the patient level variable, number of different repeat drug classes was strongly associated with PIP (>2 drugs v none; adjusted OR, 4.0; 95% CI 3.7, 4.3). After adjustment for patient level variables the proportion of PIP varied fourfold (0.5 to 2 times the expected proportion) between prescribers but the majority of this variation was not significant. Conclusion PIP is of concern for all prescribers. Interventions aimed at enhancing appropriateness of prescribing should target patients taking multiple medications. PMID:24690127
Introduction Guidelines for the treatment of psychoses recommend antipsychotic monotherapy. However, the rate of antipsychotic polytherapy has increased over the last decade, reaching up to 60% in some settings. Studies evaluating the costs and impact of antipsychotic polytherapy in the health system are scarce. Objective To estimate the costs of antipsychotic polytherapy and its impact on public health costs in a sample of subjects with psychotic disorders living in residential facilities in the city of Sao Paulo, Brazil. Method A cross-sectional study that used a bottom-up approach for collecting costs data in a public health provider´s perspective. Subjects with psychosis living in 20 fully-staffed residential facilities in the city of Sao Paulo were assessed for clinical and psychosocial profile, severity of symptoms, quality of life, use of health services and pharmacological treatment. The impact of polytherapy on total direct costs was evaluated. Results 147 subjects were included, 134 used antipsychotics regularly and 38% were in use of antipsychotic polytherapy. There were no significant differences in clinical and psychosocial characteristics between polytherapy and monotherapy groups. Four variables explained 30% of direct costs: the number of antipsychotics, location of the residential facility, time living in the facility and use of olanzapine. The costs of antipsychotics corresponded to 94.4% of the total psychotropic costs and to 49.5% of all health services use when excluding accommodation costs. Olanzapine costs corresponded to 51% of all psychotropic costs. Conclusion Antipsychotic polytherapy is a huge economic burden to public health service, despite the lack of evidence supporting this practice. Great variations on antipsychotic costs explicit the need of establishing protocols for rational antipsychotic prescriptions and consequently optimising resource allocation. Cost-effectiveness studies are necessary to estimate the best value for money among antipsychotics, especially in low and middle income countries. PMID:25853709
Razzouk, Denise; Kayo, Monica; Sousa, Aglaé; Gregorio, Guilherme; Cogo-Moreira, Hugo; Cardoso, Andrea Alves; Mari, Jair de Jesus
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. PMID:19721433
McClay, Joseph L.; Adkins, Daniel E.; Åberg, Karolina; Stroup, Scott; Perkins, Diana O.; Vladimirov, Vladimir I.; Lieberman, Jeffrey A.; Sullivan, Patrick F.; van den Oord, Edwin J.C.G.
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
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 Patients under antipsychotic treatment for schizophrenia commonly exhibit poor adherence to treatment, high rates of treatment discontinuation, and frequent treatment changes. The ETOS study aimed to identify the reasons leading physicians to decide to switch antipsychotic treatment in outpatients with schizophrenia and to evaluate the outcome of this switch. Methods ETOS was an observational 18-week (four visits) study in outpatients 18 to 65 years old, diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders - 4th edition criteria at least 6 months prior to enrolment, who were initiated on a new antipsychotic monotherapy treatment within the 2 weeks prior to enrollment. A total of 574 patients were recruited by 87 hospital- and office-based physicians. Ethical approval was obtained prior to study initiation (NCT00999895). Results The final analysis included 568 patients, 39.0?±?11.2 years old with mean disease duration of 11.7 years. The male-to-female ratio was 53:47. The main reason for switching antipsychotic treatment was lack of tolerability (n?=?369, 65.0%), followed by lack of efficacy (n?=?249, 43.8%). Following treatment switch, 87.9% of patients (n?=?499) showed meaningful clinical benefit by achieving a Clinical Global Impression-Clinical Benefit score of ?4 at the final visit. By the end of the study, total Positive and Negative Syndrome Scale, Clinical Global Impression-Improvement, Clinical Global Impression-Severity, and Simpson-Angus Scale scores demonstrated significant mean decreases of 31.69, 0.70, 1.14, and 11.30, respectively (all p?0.0001). Treatment adherence remarkably improved. Conclusion In the ETOS study, switch of antipsychotic monotherapy for reasons relating to lack of efficacy and/or tolerability was associated with significantly improved clinical benefit and significant increase of patients' adherence to treatment. PMID:24359635
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. PMID:23188793
Urs, Nikhil M.; Snyder, Joshua C.; Jacobsen, Jacob P. R.; Peterson, Sean M.; Caron, Marc G.
Measuring antipsychotic concentrations in human matrices is important for both therapeutic drug monitoring and forensic toxicology. This review provides a critical overview of the analytical methods for detection and quantification of antipsychotics published in the last four years. Focus lies on advances in sample preparation, analytical techniques and alternative matrices. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used most often for quantification of antipsychotics. This sensitive technique makes it possible to determine low concentrations not only in serum, plasma or whole blood, but also in alternative matrices like oral fluid, dried blood spots, hair, nails and other body tissues. Current literature on analytical techniques for alternative matrices is still limited and often requires a more thorough validation including a comparison between conventional and alternative results to determine their actual value. Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) makes it possible to quantify a high amount of compounds within a shorter run time. This technique is widely used for multi-analyte methods. Only recently, high-resolution mass spectrometry has gained importance when a combination of screening of (un)known metabolites, and quantification is required. PMID:25512162
Patteet, Lisbeth; Cappelle, Delphine; Maudens, Kristof E; Crunelle, Cleo L; Sabbe, Bernard; Neels, Hugo
The first- and second-generation antipsychotic drugs have become mainstay drug treatment for schizophrenia. However, patients who receive antipsychotic drugs differ with respect to treatment response and drug-induced adverse events. The biological predictors of treatment response are being researched worldwide, with emphasis on molecular genetic predictors of treatment response. Because of the rapid and exciting developments in the field, we reviewed the recent studies of the molecular genetic basis of treatment response in schizophrenia. The accumulating data suggest that DNA information in the pathways for drug metabolism and drug target sites may be an important predictor of treatment response in schizophrenia. The data suggest that clinicians may soon be using a patient's genotype to decide initial choice of antipsychotic drug treatment in schizophrenia. The pharmacogenetics of schizophrenia can improve the prospects of individualized treatment and drug discovery. Pharmacogenetic investigations of schizophrenia susceptibility loci, and genes controlling drug target site receptors, drug-metabolizing enzymes, the blood–brain barrier systems, and epigenetic mechanisms could lead to a molecular classification of treatment response and adverse events of psychotropic drugs. PMID:17880863
Nnadi, Charles U.; Malhotra, Anil K.
The search for clinical outcome predictors for schizophrenia is as old as the field of psychiatry. However, despite a wealth of large, longitudinal studies into prognostic factors, only very few clinically useful outcome predictors have been identified. The goal of future treatment is to either affect modifiable risk factors, or use nonmodifiable factors to parse patients into therapeutically meaningful subgroups. Most clinical outcome predictors are nonspecific and/or nonmodifiable. Nonmodifiable predictors for poor odds of remission include male sex, younger age at disease onset, poor premorbid adjustment, and severe baseline psychopathology. Modifiable risk factors for poor therapeutic outcomes that clinicians can act upon include longer duration of untreated illness, nonadherence to antipsychotics, comorbidities (especially substance-use disorders), lack of early antipsychotic response, and lack of improvement with non-clozapine antipsychotics, predicting clozapine response. It is hoped that this limited capacity for prediction will improve as pathophysiological understanding increases and/or new treatments for specific aspects of schizophrenia become available. PMID:25733955
Carbon, Maren; Correll, Christoph U.
A majority of psychiatric medications are known to generate weight gain and ultimately obesity in some patients. There is much speculation about the prevalence of weight gain and the degree of weight gain during acute and longitudinal treatment with these agents. There is newer literature looking at the etiology of this weight gain and the potential treatments being used to alleviate this side effect. The authors undertook a comprehensive literature review in order to present epidemiology, etiology, and treatment options of weight gain associated with antipsychotics, mood stabilizers, and antidepressants. PMID:21318056
Nihalani, Nikhil; Schwartz, Thomas L.; Siddiqui, Umar A.; Megna, James L.
Typical and atypical antipsychotics are thought to exert their effects on different neurotransmitter pathways with specific action of atypical compounds on the prefrontal cortex, but studies directly investigating the effect of those drugs on neurophysiological measures of prefrontal brain function are sparse. We therefore investigated the influence of different antipsychotics on an electrophysiological marker of prefrontal brain function (NoGo anteriorization, NGA) and neuropsychological test scores. For this purpose, 38 patients with endogenous psychoses were investigated at the beginning of a stationary psychiatric treatment and at a 6-week-follow-up. Patients were treated with typical or atypical antipsychotics, or a combination of both. They underwent psychopathological diagnostic and neuropsychological testing, as well as electrophysiological investigations during a Continuous Performance Test. The results indicate that typical and atypical antipsychotics differentially affected the development of the NGA over the course of the treatment, typical antipsychotics tending to result in decreased values at follow-up, and atypical antipsychotics stabilizing, or increasing this parameter. Performance in tests of frontal lobe function generally declined under typical antipsychotics and improved with atypical compounds, changes in Stroop interference correlated with changes in the NGA. We conclude that typical and atypical antipsychotics differ regarding their effect on prefrontal brain function in schizophrenia, atypical neuroleptics often showing a more favorable impact than conventional antipsychotics on respective parameters. PMID:17203015
Ehlis, Ann-Christine; Herrmann, Martin J; Pauli, Paul; Stoeber, Gerald; Pfuhlmann, Bruno; Fallgatter, Andreas J
Implementation of electronic prescribing system can overcome many problems of the paper prescribing system, and provide numerous opportunities of more effective and advantageous prescribing. Successful implementation of such a system requires complete and deep understanding of work content, human force, and workflow of paper prescribing. The current study was designed in order to model the current business process of outpatient prescribing in Iran and clarify different actions during this process. In order to describe the prescribing process and the system features in Iran, the methodology of business process modeling and analysis was used in the present study. The results of the process documentation were analyzed using a conceptual model of workflow elements and the technique of modeling "As-Is" business processes. Analysis of the current (as-is) prescribing process demonstrated that Iran stood at the first levels of sophistication in graduated levels of electronic prescribing, namely electronic prescription reference, and that there were problematic areas including bottlenecks, redundant and duplicated work, concentration of decision nodes, and communicative weaknesses among stakeholders of the process. Using information technology in some activities of medication prescription in Iran has not eliminated the dependence of the stakeholders on paper-based documents and prescriptions. Therefore, it is necessary to implement proper system programming in order to support change management and solve the problems in the existing prescribing process. To this end, a suitable basis should be provided for reorganization and improvement of the prescribing process for the future electronic systems. PMID:25237369
Ahmadi, Maryam; Samadbeik, Mahnaz; Sadoughi, Farahnaz
Implementation of electronic prescribing system can overcome many problems of the paper prescribing system, and provide numerous opportunities of more effective and advantageous prescribing. Successful implementation of such a system requires complete and deep understanding of work content, human force, and workflow of paper prescribing. The current study was designed in order to model the current business process of outpatient prescribing in Iran and clarify different actions during this process. In order to describe the prescribing process and the system features in Iran, the methodology of business process modeling and analysis was used in the present study. The results of the process documentation were analyzed using a conceptual model of workflow elements and the technique of modeling “As-Is” business processes. Analysis of the current (as-is) prescribing process demonstrated that Iran stood at the first levels of sophistication in graduated levels of electronic prescribing, namely electronic prescription reference, and that there were problematic areas including bottlenecks, redundant and duplicated work, concentration of decision nodes, and communicative weaknesses among stakeholders of the process. Using information technology in some activities of medication prescription in Iran has not eliminated the dependence of the stakeholders on paper-based documents and prescriptions. Therefore, it is necessary to implement proper system programming in order to support change management and solve the problems in the existing prescribing process. To this end, a suitable basis should be provided for reorganization and improvement of the prescribing process for the future electronic systems. PMID:25237369
Ahmadi, Maryam; Samadbeik, Mahnaz; Sadoughi, Farahnaz
...Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS PRODUCTION OF VOLATILE FRUIT-FLAVOR CONCENTRATE Administrative and Miscellaneous Provisions § 18.16 Forms prescribed. (a) The appropriate...
...Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS PRODUCTION OF VOLATILE FRUIT-FLAVOR CONCENTRATE Administrative and Miscellaneous Provisions § 18.16 Forms prescribed. (a) The appropriate...
The prescription of opioids often poses a difficult problem for the practitioner, particularly when they are confronted with institutionalised fears and restrictive regulations. This article compares prescribing policies for opioids in three European countries, Austria, Israel and Portugal. PMID:17844728
Beubler, Eckhard; Eisenberg, Elon; Castro-Lopes, Jose; Rhodin, Annica
... (1) For prescriptions presented to the seller: the prescription itself, or the facsimile version thereof (including an email containing a digital image of the prescription), that was presented to the seller by the patient or prescriber. (2)...
... (1) For prescriptions presented to the seller: the prescription itself, or the facsimile version thereof (including an email containing a digital image of the prescription), that was presented to the seller by the patient or prescriber. (2)...
...verification request. (d) Invalid prescription . If a prescriber...inaccurate, expired, or otherwise invalid, the seller shall not...A seller shall maintain a record of all direct communications...a) of this section. Such record shall consist of the...
Subjects at their first psychotic episode show an enlarged volume of the pituitary gland, but whether this is due to hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, or to stimulation of the prolactin-secreting cells by antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm, coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic episode and 78 age- and
Carmine M Pariante; Paola Dazzan; Andrea Danese; Kevin D Morgan; Flora Brudaglio; Craig Morgan; Paul Fearon; Ken Orr; Gerard Hutchinson; Christos Pantelis; Dennis Velakoulis; Peter B Jones; Julian Leff; Robin M Murray
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
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...
OBJECTIVE: The goal of this study was to investigate patterns of ambulatory antibiotic use and to identify factors associated with broad-spectrum antibiotic prescribing for pediatric urinary tract infections (UTIs). METHODS: We examined antibiotics prescribed for UTIs for children aged younger than 18 years from 1998 to 2007 using the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey. Amoxicillin-clavulanate, quinolones, macrolides, and second- and third-generation cephalosporins were classified as broad-spectrum antibiotics. We evaluated trends in broad-spectrum antibiotic prescribing patterns and performed multivariable logistic regression to identify factors associated with broad-spectrum antibiotic use. RESULTS: Antibiotics were prescribed for 70% of pediatric UTI visits. Trimethoprim-sulfamethoxazole was the most commonly prescribed antibiotic (49% of visits). Broad-spectrum antibiotics were prescribed one third of the time. There was no increase in overall use of broad-spectrum antibiotics (P = .67); however, third-generation cephalosporin use doubled from 12% to 25% (P = .02). Children younger than 2 years old (odds ratio: 6.4 [95% confidence interval: 2.2–18.7, compared with children 13–17 years old]), females (odds ratio: 3.6 [95% confidence interval: 1.6–8.5]), and temperature ?100.4°F (odds ratio: 2.9 [95% confidence interval: 1.0–8.6]) were independent predictors of broad-spectrum antibiotic prescribing. Race, physician specialty, region, and insurance status were not associated with antibiotic selection. CONCLUSIONS: Ambulatory care physicians commonly prescribe broad-spectrum antibiotics for the treatment of pediatric UTIs, especially for febrile infants in whom complicated infections are more likely. The doubling in use of third-generation cephalosporins suggests that opportunities exist to promote more judicious antibiotic prescribing because most pediatric UTIs are susceptible to narrower alternatives. PMID:21555502
Shapiro, Daniel J.; Hersh, Adam L.
Hanna, Tamer; Bajorek, Beata; LeMay, Kate; Armour, Carol L.
Background: Rational prescription is a considerable issue which must be paid more attention to assess the behavior of prescribers. The aim of this study was to examine factors affecting family physicians’ drug prescribing. Methods: We carried out a retrospective cross-sectional study in Khuzestan province, Iran in 2011. Nine hundred eighty-six prescriptions of 421 family physicians (including 324 urban and 97 rural family physicians) were selected randomly. A multivariate Poisson regression was used to investigate potential determinants of the number of prescribed drug per patient. Results: The mean of medication per patient was 2.6 ± 1.2 items. In the majority (91.9%) of visits a drugs was prescribed. The most frequent dosage forms were tablets, syrups and injection in 30.1%, 26.9%, and 18.7% of cases respectively. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and antibiotics were 29.7% and 17.1% of prescribed drugs respectively. The tablets were the most frequent dosage forms (38.6% of cases) in adult’s patients and syrups were the most frequent dosage forms (49% of cases) in less than 18 years old. Paracetamols were popular form of NSAIDs in two patients groups. The most common prescribed medications were oral form. Conclusion: In Khuzestan, the mean of medication per patient was fewer than national average. Approximately, pattern of prescribed drug by family physicians (including dosage form and type of drugs) was similar to other provinces of Iran. PMID:25489595
Arab, Mohammad; Torabipour, Amin; Rahimifrooshani, Abbas; Rashidian, Arash; Fadai, Nayeb; Askari, Roohollah
BackgroundConcern has been raised regarding the potential contributions of veterinary antimicrobial use to increasing levels of resistance in bacteria critically important to human health. Canine pyoderma is a frequent, often recurrent diagnosis in pet dogs, usually attributable to secondary bacterial infection of the skin. Lesions can range in severity based on the location, total area and depth of tissue affected and antimicrobial therapy is recommended for resolution. This study aimed to describe patient signalment, disease characteristics and treatment prescribed in a large number of UK, primary-care canine pyoderma cases and to estimate pyoderma prevalence in the UK vet-visiting canine population.ResultsOf 54,600 dogs presented to 73 participating practices in 2010, 683 (1.3%) had a pyoderma diagnosis recorded in available electronic patient record (EPR) data. Antimicrobials were dispensed in 97% of cases and most dogs were prescribed systemic therapy (92%). Agents most frequently prescribed were amoxicillin-clavulanate, cefalexin, clindamycin and cefovecin. Systemic antimicrobials were prescribed for fewer than 14 days in around 40% of study cases reviewed in detail. Prescribed daily doses were below minimum recommended daily dose (MRDD) in 26% of 43 dogs with sufficient information for calculation of minimum dose.ConclusionsAntimicrobial prescribing behaviour for treatment of canine pyoderma was variable but frequently appeared inconsistent with current recommendations. Use of clinical data from primary practice EPRs can provide valuable insight into common clinical conditions and associated prescribing. PMID:25293803
Summers, Jennifer F; Hendricks, Anke; Brodbelt, David C
Postmortem studies in schizophrenic patients revealed alterations in NMDA receptor binding and gene expression of specific subunits. Because most of the patients had been treated with antipsychotics over long periods, medication effects might have influenced those findings. We treated animals with haloperidol and clozapine in clinical doses to investigate the effects of long-term antipsychotic treatment on NMDA receptor binding and
Andrea Schmitt; Mathias Zink; Bettina Müller; Brigitte May; Anne Herb; Alexander Jatzko; Dieter F. Braus; Fritz A. Henn
... the hospital. Antipsychotic Medicines Brand Name Drug Name Generic Available * These medicines were not studied in the research for this ... amount) of medicine you need, and whether the medicine comes in a generic form. Wholesale Prices of Prescription Antipsychotics Brand Name ...
When treating patients with psychoses, clinicians must often consider changing their treatment from one antipsychotic agent to another. The transition may be necessary because the patient experiences serious side effects or because the existing therapy no longer controls the patient's symptoms. A principal problem in changing antipsychotic agents is the potential for withdrawal symptoms resulting from discontinuation of the existing
Richard L Borison
Objective: This study describes recent trends and patterns in antipsychotic treatment of privately insured children aged 2 through 5 years. Method: A trend analysis is presented of antipsychotic medication use (1999-2001 versus 2007) stratified by patient characteristics. Data are analyzed from a large administrative database of privately insured…
Olfson, Mark; Crystal, Stephen; Huang, Cecilia; Gerhard, Tobias
Metabolic syndrome (MetS) has been recognized as a risk factor for cardiovascular morbidity and mortality in general population and in patients with severe mental illnesses like schizophrenia. This paper reviews studies on MetS in schizophrenia and related psychotic disorders, and assesses the contribution of antipsychotics toward the development of MetS. Databases of Medline (PubMed), PsycINFO, and Scopus were searched for MetS, psychotic disorders, and antipsychotic drugs from inception till present. Prevalence of MetS in patients with schizophrenia was found to be ranging from 3.3% to 68.0%. Prevalence in antipsychotic-naïve and antipsychotic-treated patients ranged between 3.3-26.0% and 32.0-68.0% respectively, and was higher in younger patients, female gender and Hispanics, and lower in African-Americans and Orientals. Prevalence of metabolic abnormalities was higher in patients receiving second generation antipsychotics (SGAs), especially with clozapine, olanzapine, and risperidone, as compared to first generation antipsychotics (FGAs). Antipsychotic-induced changes on metabolic indices became evident after 2 weeks and reached maximum at 3 months of treatment. There is a need to sensitize the mental health professionals at all levels about the need of screening and monitoring for MetS in patients receiving antipsychotics. PMID:23960422
Chadda, Rakesh K.; Ramshankar, Prashanth; Deb, Koushik S.; Sood, Mamta
The treatment of schizophrenia has evolved over the past half century primarily in the context of antipsychotic drug development. Although there has been significant progress resulting in the availability and use of numerous medications, these reflect three basic classes of medications (conventional (typical), atypical and dopamine partial agonist antipsychotics) all of which, despite working by varying mechanisms of actions, act
S Miyamoto; G E Duncan; C E Marx; J A Lieberman
OBJECTIVE: Although antipsychotics are important in the treatment of behavioural and psychological symptoms of dementia (BPSD), they have moderate efficacy and often cause adverse events. Recent safety warnings about increased frequency of cerebrovascular adverse events in elderly patients who use atypical antipsychotics mean that physicians now face a dilemma when weighing the benefits and risks of use of antipsychotics in
Marianne B van Iersel; Sytse U Zuidema; Raymond T C M Koopmans; Frans R J Verhey; Marcel G M Olde Rikkert
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 Suicide and violence often co-occur in the general population as well as in mentally ill individuals. Few studies, however, have assessed whether these suicidal behaviors are predictive of violence risk in mental illness. Aims The aim of this study is to investigate whether suicidal behaviors, including suicidal ideation, threats, and attempts, are significantly associated with increased violence risk in individuals with schizophrenia. Method Data for these analyses were obtained from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial, a randomized controlled trial of antipsychotic medication in 1460 adults with schizophrenia. Univariate Cox regression analyses were used to calculate hazard ratios (HRs) for suicidal ideation, threats, and attempts. Multivariate analyses were conducted to adjust for common confounding factors, including: age, alcohol or drug misuse, major depression, antisocial personality disorder, depression, hostility, positive symptom, and poor impulse control scores. Tests of discrimination, calibration, and reclassification assessed the incremental predictive validity of suicidal behaviors for the prediction of violence risk. Results Suicidal threats and attempts were significantly associated with violence in both males and females with schizophrenia with little change following adjustment for common confounders. Only suicidal threats, however, were associated with a significant increase in incremental validity beyond age, diagnosis with a comorbid substance use disorder, and recent violent behavior. Conclusions Suicidal threats are independently associated with violence risk in both males and females with schizophrenia, and may improve violence risk prediction. PMID:24581550
Witt, Katrina; Hawton, Keith; Fazel, Seena
Rational prescribing increases the quality of health care and patient outcomes. In this study, the quality of drug prescription in specialist physicians in Isfahan province of Iran was assessed for evaluating the rational use of drugs and improving the therapeutic outcomes. This retrospective survey was conducted on a total of 7999530 prescriptions from all general and specialist physicians. The most frequently prescribed drugs and World Health Organization (WHO) prescribing indicators were evaluated in prescriptions of all medical specialties. Assessment of prescribing indicators revealed poor-quality prescribing performance by general practitioners including high number of medicines prescribed per clients, wide range of prescribed medicines in each prescription, over-prescribing of antibiotics, corticosteroids and injectable drugs. There were also wide differences in the pattern of drug prescribing depending on the medical specialties. The average number of drugs prescribed per encounter by specialists was less than generalists except for the cardiologists. General practitioners, otorhinolaryngologists and general surgeons prescribed more antibiotics. Orthopedic surgeons and general practitioners were the top prescribers of injectable and corticosteroid drugs. The most frequently prescribed medicine groups varied according to the prescribers’ medical specialty. Analgesics and antipyretics were the most prescribed preparations in general medicine, pediatrics, orthopedics, general surgery and cardiology. Because of the wide variability in the pattern of drug prescribing depending on the medical specialties, specific performance indicators should be developed for each specific medical specialty for better assessing of prescribing quality in specialist physicians. PMID:24250595
Sadeghian, Gholam-Hossein; Safaeian, Leila; Mahdanian, Ali-Reza; Salami, Solmaz; Kebriaee-Zadeh, Javad
Rational prescribing increases the quality of health care and patient outcomes. In this study, the quality of drug prescription in specialist physicians in Isfahan province of Iran was assessed for evaluating the rational use of drugs and improving the therapeutic outcomes. This retrospective survey was conducted on a total of 7999530 prescriptions from all general and specialist physicians. The most frequently prescribed drugs and World Health Organization (WHO) prescribing indicators were evaluated in prescriptions of all medical specialties. Assessment of prescribing indicators revealed poor-quality prescribing performance by general practitioners including high number of medicines prescribed per clients, wide range of prescribed medicines in each prescription, over-prescribing of antibiotics, corticosteroids and injectable drugs. There were also wide differences in the pattern of drug prescribing depending on the medical specialties. The average number of drugs prescribed per encounter by specialists was less than generalists except for the cardiologists. General practitioners, otorhinolaryngologists and general surgeons prescribed more antibiotics. Orthopedic surgeons and general practitioners were the top prescribers of injectable and corticosteroid drugs. The most frequently prescribed medicine groups varied according to the prescribers' medical specialty. Analgesics and antipyretics were the most prescribed preparations in general medicine, pediatrics, orthopedics, general surgery and cardiology. Because of the wide variability in the pattern of drug prescribing depending on the medical specialties, specific performance indicators should be developed for each specific medical specialty for better assessing of prescribing quality in specialist physicians. PMID:24250595
Sadeghian, Gholam-Hossein; Safaeian, Leila; Mahdanian, Ali-Reza; Salami, Solmaz; Kebriaee-Zadeh, Javad
Antipsychotic discontinuation rates are a powerful indicator of medication effectiveness in schizophrenia. We examined antipsychotic discontinuation in the Schizophrenia Outpatient Health Outcomes (SOHO) study, a 3-year prospective, observational study in outpatients with schizophrenia in 10 European countries. Patients (n=7728) who started antipsychotic monotherapy were analyzed. Medication discontinuation for any cause ranged from 34% and 36% for clozapine and olanzapine, respectively, to 66% for quetiapine. Compared to olanzapine, the risk of treatment discontinuation before 36 months was significantly higher for quetiapine, risperidone, amisulpride, and typical antipsychotics (oral and depot), but similar for clozapine. Longer medication maintenance was associated with being socially active and having a longer time since first treatment contact for schizophrenia, whereas higher symptom severity, treatment with mood stabilizers, substance abuse, having hostile behaviour were associated with lower medication maintenance. Antipsychotic maintenance in SOHO was higher than the results of previous randomized studies. PMID:17137759
Haro, Josep Maria; Suarez, David; Novick, Diego; Brown, Jacqueline; Usall, Judith; Naber, Dieter
The overall impact of first and second generation antipsychotics on quality of life and symptoms of people with schizophrenia remains controversial. We applied health state modeling to data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia study, a randomized trial of antipsychotic medications, and evaluated the likelihood of patients moving to more favorable health states over time. We applied K-means clustering to the data to create discrete groupings of patients with symptom and side effect characteristics that were then validated using quality of life measures. We compared cluster distributions across medications at baseline and 6 months after randomization. 1,049 patients were included in the initial cluster analysis. Five health states were identified: (1) low symptoms and low side effects (LS + LSE) (2) low symptoms and obesity (LS + Ob) (3) high symptoms and low side effects (HS + LSE) (4) high symptoms with depression and akathisia (HS + Dp + Ak) and (5) moderate symptoms and high side effects (MS + HSE). Six-month outcomes among patients randomly assigned to perphenazine, olanzapine, risperidone and quetiapine were compared. At baseline, almost 20 % of patients were in the worst health state (HS + Dp + Ak), with greater decreases at 6 months in this health state for perphenazine (9.2 % decrease) and olanzapine (11.1 %) groups compared to risperidone (4.7 %) and quetiapine (6.7 %). This study demonstrated that health state analysis can provide insight into the overall clinical state of patients beyond the mere comparison of average scores and largely confirmed original CATIE findings. PMID:25294277
Lin, Lewei Allison; Rosenheck, Robert; Sugar, Catherine; Zbrozek, Arthur
The appropriate use of systemic antifungals is vital in the prevention and treatment of invasive fungal infection (IFI) in immunosuppressed children and neonates. This multicenter observational study describes the inpatient prescribing practice of antifungal drugs for children and neonates and identifies factors associated with prescribing variability. A single-day point prevalence study of antimicrobial use in hospitalized neonates and children was performed between October and December 2012. The data were entered through a study-specific Web-based portal using a standardized data entry protocol. Data were recorded from 17,693 patients from 226 centers. A total of 136 centers recorded data from 1,092 children and 380 neonates receiving at least one antifungal agent. The most frequently prescribed systemic antifungals were fluconazole (n=355) and amphotericin B deoxycholate (n=195). The most common indications for antifungal administration in children were medical prophylaxis (n=325), empirical treatment of febrile neutropenia (n=122), and treatment of confirmed or suspected IFI (n=100 [14%]). The treatment of suspected IFI in low-birthweight neonates accounted for the majority of prescriptions in the neonatal units (n=103). An analysis of variance (ANOVA) demonstrated no significant effect of clinical indication (prophylaxis or treatment of systemic or localized infection) on the total daily dose (TDD). Fewer than one-half of the patients (n=371) received a TDD within the dosing range recommended in the current guidelines. Subtherapeutic doses were prescribed in 416 cases (47%). The predominance of fluconazole and high incidence of subtherapeutic doses in participating hospitals may contribute to suboptimal clinical outcomes and an increased predominance of resistant pathogenic fungi. A global consensus on antifungal dosing and coordinated stewardship programs are needed to promote the consistent and appropriate use of antifungal drugs in neonates and children. PMID:25403672
Lestner, J M; Versporten, A; Doerholt, K; Warris, A; Roilides, E; Sharland, M; Bielicki, J; Goossens, H
To examine psychiatric prescribing in response to perinatal/neonatal death, we analyzed data from a cross-sectional survey of 235 bereaved parents participating in an online support community. Of the 88 respondents prescribed medication, antidepressants were most common (n = 70, 79.5%) followed by benzodiazepines/sleep aids (n = 18, 20.5%). Many prescriptions were written shortly after the death (32.2% within 48 hr, 43.7% within a week, and 74.7% within a month). Obstetrician/gynecologists wrote most prescriptions given shortly after loss. Most respondents prescribed antidepressants took them long-term. This sample is select, but these data raise disturbing questions about prescribing practices for grieving parents. PMID:24588074
Lacasse, Jeffrey R; Cacciatore, Joanne
What is prescribed fire? Prescribed fire is the controlled application of fire to the land and become available for new plants to grow. } Naturally thins overcrowded forests Historically, natural fire of vigor and health. } Creates diversity needed by wildlife Fire creates a varied land and vegetation
There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease. PMID:23894336
McEvoy, Joseph; Baillie, Rebecca A.; Zhu, Hongjie; Buckley, Peter; Keshavan, Matcheri S.; Nasrallah, Henry A.; Dougherty, George G.; Yao, Jeffrey K.; Kaddurah-Daouk, Rima
Repeated administration of haloperidol and olanzapine causes a progressively enhanced disruption of conditioned avoidance response (CAR) and a progressively enhanced inhibition of phencyclidine (PCP)-induced hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are thought to reflect intrinsic antipsychotic activity. The present study examined to the extent to which antipsychotic-induced sensitization in one model (e.g. CAR) can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means of investigating the contextual and behavioral controls of antipsychotic sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested in the CAR or PCP (3.2 mg/kg, sc) hyperlocomotion model under haloperidol or olanzapine for five consecutive days. Then they were switched to the other model and tested for the expression of sensitization. Finally, all rats were switched back to the original model and retested for the expression of sensitization. Repeated haloperidol or olanzapine treatment progressively disrupted avoidance responding and decreased PCP-induced hyperlocomotion, indicating a robust sensitization. When tested in a different model, rats previously treated with haloperidol or olanzapine did not show a stronger inhibition of CAR or PCP-induced hyperlocomotion than those treated with these drugs for the first time; however, they did show such an effect when tested in the original model in which they received repeated antipsychotic treatment. These findings suggest that the expression of antipsychotic sensitization is strongly influenced by the testing environment and/or selected behavioral response under certain experimental conditions. Distinct contextual cues and behavioral responses may enter an association with unconditional drug effects via a Pavlovian conditioning process. They may also serve as occasion-setters to modulate the expression of sensitized responses. Because antipsychotic sensitization mimics clinical effects of antipsychotic treatment, understanding the neurobiological mechanisms of antipsychotic sensitization and its contextual control would greatly enhance our understanding of the psychological and neurochemical nature of antipsychotic treatment in the clinic. PMID:22157143
Zhang, Chen; Li, Ming
Purpose To estimate the prevalence of off-label and unlicensed prescribing during 2008 at a major paediatric teaching hospital in Western Australia. Methods A 12-month retrospective study was conducted at Princess Margaret Hospital using medication chart records randomly selected from 145,550 patient encounters from the Emergency Department, Inpatient Wards and Outpatient Clinics. Patient and prescribing data were collected. Drugs were classified as off-label or unlicensed based on Australian registration data. A hierarchical system of age, indication, route of administration and dosage was used. Drugs were classified according to the Anatomical Therapeutic Chemical Code. Results A total of 1,037 paediatric patients were selected where 2,654 prescriptions for 330 different drugs were prescribed to 699 patients (67.4%). Most off-label drugs (n = 295; 43.3%) were from the nervous system; a majority of unlicensed drugs were systemic hormonal preparations excluding sex hormones (n = 22, 32.4%). Inpatients were prescribed more off-label drugs than outpatients or Emergency Department patients (p < 0.0001). Most off-label prescribing occurred in infants and children (31.7% and 35.9% respectively) and the highest percentage of unlicensed prescribing (7.2%) occurred in infants (p < 0.0001). There were 25.7% of off-label and 2.6% of unlicensed medications prescribed across all three settings. Common reasons for off-label prescribing were dosage (47.4%) and age (43.2%). Conclusion This study confirmed off-label and unlicensed use of drugs remains common. Further, that prevalence of both is influenced by the clinical setting, which has implications in regards to medication misadventure, and the need to have systems in place to minimise medication errors. Further, there remains a need for changes in the regulatory system in Australia to ensure that manufacturers incorporate, as it becomes available, evidence regarding efficacy and safety of their drugs in children in the official product information. PMID:25756896
Czarniak, Petra; Bint, Lewis; Favié, Laurent; Parsons, Richard; Hughes, Jeff; Sunderland, Bruce
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. PMID:23572483
Charani, E.; Castro-Sanchez, E.; Sevdalis, N.; Kyratsis, Y.; Drumright, L.; Shah, N.; Holmes, A.
E-prescribing is coming of age. It promises to reduce medication errors and adverse reactions from incompatible drug combinations. This article provides an overview of the factors that have driven greater adoption of e-prescribing, principally the promulgation of HIPAA regulations and the Medicare Modernization Act of 2004. It discusses the financial considerations that have delayed the greater use of existing methodology, addresses current government and industry initiatives, and defines some of the standards that have been set forth to date. PMID:15672904
Trimetazidine (TMZ) has been used as an anti-ischemic agent for angina pectoris, chorioretinal disturbances, and vertigo. Also, it can induce extrapyramidal type adverse reaction such as parkinsonism, gait disorder, and tremor via blockade of D2 receptors. In the present study, we evaluated the effect of TMZ on novelty-induced rearing behavior and apomorphine-induced stereotypy behavior in male rats. Four groups of rat (n = 7) were administrated with TMZ (10 and 20?mg/kg, i.p.), chlorpromazine (1?mg/kg, i.p.), or isotonic saline. One hour later, apomorphine (2?mg/kg, s.c.) was administrated to each rat. Our results showed that both doses of TMZ significantly decreased the rearing behavior in rats, whereas the decrease with chlorpromazine was higher. TMZ also decreased the stereotypy scores in a dose-dependent manner. We concluded that TMZ has beneficial effects on rearing behavior and stereotypy, which are accepted to be indicators of antipsychotic effect. Taken together, with its antioxidative and cytoprotective properties, TMZ is worthy of being investigated for its anti-psychotic effects as a primary or an adjunctive drug. PMID:24250273
Erba?, Oytun; Akseki, Hüseyin Serdar; Eliküçük, Betül; Ta?k?ran, Dilek
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. PMID:20070867
Girgenti, Matthew James; Nisenbaum, Laura K.; Bymaster, Franklin; Terwilliger, Rosemarie; Duman, Ronald S; Newton, Samuel Sathyanesan
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. PMID:22830044
Sendt, Kyra-Verena; Giaroli, Giovanni; Tracy, Derek K.
Electronic prescribing (e-prescribing) is an important part of the nation's push to enhance the safety and quality of the prescribing process. E-prescribing allows providers in the ambulatory care setting to send prescriptions electronically to the pharmacy and can be a stand-alone system or part of an integrated electronic health record system. The methodology for this study followed the basic principles of a systematic review. A total of 47 sources were referenced. Results of this research study suggest that e-prescribing reduces prescribing errors, increases efficiency, and helps to save on healthcare costs. Medication errors have been reduced to as little as a seventh of their previous level, and cost savings due to improved patient outcomes and decreased patient visits are estimated to be between $140 billion and $240 billion over 10 years for practices that implement e-prescribing. However, there have been significant barriers to implementation including cost, lack of provider support, patient privacy, system errors, and legal issues. PMID:24808808
Porterfield, Amber; Engelbert, Kate; Coustasse, Alberto
Objective. Although fitting orders to renal function avoids overdosage and therefore iatrogenic risk, dosage adjustment is rarely made. The objective of this study was to assess residents' prescribing behavior in renal impairment, through a standardized simulated clinical setting. Method. This criterion-referenced study was carried out in a French teaching hospital. The hospital had 118 residents; 71 of them were asked
L. SALOMON; S. LEVU; G. DERAY; V. LAUNAY-VACHER; G. BRUCKER; P. RAVAUD
General mathematical expression found for energy storage shows that for linear, passive networks there is a minimum possible energy storage corresponding to a prescribed impedance. The electromagnetic energy storage is determined at different excitation frequencies through analysis of the networks terminal and reactance characteristics.
Smith, W. E.
This paper considers the prescribed scalar curvature problem onSn forn>-3. We consider the limits of solutions of the regularization obtained by decreasing the critical exponent. We characterize those subcritical solutions which blow up at the least possible energy level, determining the points at which they can concentrate, and their Morse indices. We then show that forn=3 this is the only
Richard Schoen; Dong Zhang
LUBRICATION APPROXIMATION WITH PRESCRIBED NONZERO CONTACT ANGLE Felix Otto Department--time existence for a weak solution s(t; x) â?? 0 of the lubrication approximation @ t s + @ x (s @ 3 x s) = 0 in fs will later motivate the way we construct approximate solutions for the lubrication approximation we are going
Schizophrenia is characterized by an abnormal dopamine system, and dopamine blockade is the primary mechanism of antipsychotic treatment. Consistent with the known role of dopamine in reward processing, prior research has demonstrated that patients with schizophrenia exhibit impairments in reward-based learning. However, it remains unknown how treatment with antipsychotic medication impacts the behavioral and neural signatures of reinforcement learning in schizophrenia. The goal of this study was to examine whether antipsychotic medication modulates behavioral and neural responses to prediction error coding during reinforcement learning. Patients with schizophrenia completed a reinforcement learning task while undergoing functional magnetic resonance imaging. The task consisted of two separate conditions in which participants accumulated monetary gain or avoided monetary loss. Behavioral results indicated that antipsychotic medication dose was associated with altered behavioral approaches to learning, such that patients taking higher doses of medication showed increased sensitivity to negative reinforcement. Higher doses of antipsychotic medication were also associated with higher learning rates (LRs), suggesting that medication enhanced sensitivity to trial-by-trial feedback. Neuroimaging data demonstrated that antipsychotic dose was related to differences in neural signatures of feedback prediction error during the loss condition. Specifically, patients taking higher doses of medication showed attenuated prediction error responses in the striatum and the medial prefrontal cortex. These findings indicate that antipsychotic medication treatment may influence motivational processes in patients with schizophrenia. PMID:24557585
Insel, Catherine; Reinen, Jenna; Weber, Jochen; Wager, Tor D; Jarskog, L Fredrik; Shohamy, Daphna; Smith, Edward E
Real-world, effectiveness studies add an important new dimension to the evaluation of the benefits of individual antipsychotics. Efficacy studies have already shown the unique effectiveness of clozapine, and suggested improved outcomes for olanzapine compared with some atypical antipsychotics and a reduced tendency to produce acute and chronic movement disorders for atypical compared with typical drugs. Recent effectiveness studies largely confirm these prior observations. The CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness), CUtLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study) and SOHO (Schizophrenia Outpatient Health Outcomes) programmes confirmed the superiority of clozapine over other antipsychotics; CATIE and SOHO also confirmed olanzapine as probably the second most effective antipsychotic. Effectiveness studies have confirmed the high incidence of adverse metabolic effects with clozapine, olanzapine and (with less certainty) quetiapine but the ZODIAC (Ziprasidone Observational Study of Cardiac Outcomes) study found no excess cardiovascular events or deaths for olanzapine compared with ziprasidone. Prior observations on reduced frequency of movement disorders for second-generation versus first-generation antipsychotics were also largely (but not uniformly) supported. Overall, recent real-world studies have done much to confirm prior observations from efficacy-based randomized, controlled trials. PMID:22668246
Attard, Azizah; Taylor, David M
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. PMID:23226405
Skrede, Silje; Fernø, Johan; Bjørndal, Bodil; Brede, Wenche Rødseth; Bohov, Pavol; Berge, Rolf Kristian; Steen, Vidar Martin
Objective Second generation antipsychotics captured the majority of the US antipsychotic market shortly after their introduction. Little is known about how second generation antipsychotics diffused in other countries with different health systems. The objective was to describe trends in antipsychotic use in the US and France from 1998 to 2008. Methods After presenting a brief background section on pharmaceutical policies in France and the US, descriptive data on quarterly prescriptions dispensed between 01/1998–09/2008 for oral antipsychotics from Xponent™ for the US, and sales recorded in the GERS database for France are presented. Trends in the share of antipsychotic use for first vs. second generation antipsychotics, and in ingredient-level of second generation antipsychotics use are reported. Results In the US, between 1998 and 2008, total antipsychotic use increased by 78%. Total use was consistently higher in France despite a 9% decrease during the period. By 2008, second generation antipsychotics represented 90% of the antipsychotic US market vs. only 40% in France. However, average annual growth rates in second generation antipsychotics use were similar in the two countries. In France, there was a steady increase in use of all but one second generation antipsychotic; whereas trends in the use of newer drugs varied substantially by drug in the US (e.g. use of olanzapine decreased after 2003 whereas use of quetiapine increased). Conclusions These results highlight markedly divergent trends in the diffusion of new antipsychotics in France and the US. Some of these differences may be explained by differences in health systems, while others may reflect physicians’ preferences and norms of practice. PMID:23584568
Gallini, Adeline; Huskamp, Haiden A.; Donohue, Julie M.
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. PMID:23996821
Kamarudin, Gritta; Penm, Jonathan; Chaar, Betty; Moles, Rebekah
To assess baseline predictors and consequences of antipsychotic adherence during the long-term treatment of schizophrenia outpatients, data were taken from the 3-year, prospective, observational, European Schizophrenia Outpatients Health Outcomes (SOHO) study, in which outpatients starting or changing antipsychotics were assessed every 6 months. Physician-rated adherence was dichotomized as adherence/non-adherence. Regression models tested for predictors of adherence during follow-up, and associations between adherence and outcome measures. Of the 6731 patients analysed, 71.2% were adherent and 28.8% were non-adherent over 3 years. The strongest predictor of adherence was adherence in the month before baseline assessment. Other baseline predictors of adherence included initial treatment for schizophrenia and greater social activities. Baseline predictors of non-adherence were alcohol dependence and substance abuse in the previous month, hospitalization in the previous 6 months, independent housing and the presence of hostility. Non-adherence was significantly associated with an increased risk of relapse, hospitalization and suicide attempts. In conclusion, non-adherence is common but can partly be predicted. This may allow strategies to improve adherence to be targeted to high-risk patients. Also, reversal of some risk factors may improve adherence. Non-adherence is associated with a range of poorer long-term outcomes, with clinical and economic implications. PMID:20185182
Novick, Diego; Haro, Josep Maria; Suarez, David; Perez, Victor; Dittmann, Ralf W; Haddad, Peter M
Schizophrenia is a chronic mental disorder generally treated with antipsychotic medication. However, non-adherence and partial adherence to antipsychotic medication treatment is common and long-acting injectable “depot” preparations of antipsychotic medications have been used as an alternative to oral medication therapy for patients for whom adherence is a clinically significant problem, as well as for the sake of convenience and in response to patient preference. Olanzapine long-acting injection (OLAI) is a new treatment option and has been approved by several regulatory agencies for the treatment of schizophrenia. OLAI is a crystalline salt formulation of olanzapine and pamoic acid. Efficacy was established in 2 double-blind randomized clinical trials of OLAI for the treatment of acute schizophrenia and for the maintenance of response. The therapeutic OLAI dosages are 150 mg q2 weeks, 210 mg q2 weeks, 300 mg q2 weeks or q4 weeks, and 405 mg q4 weeks, administered by deep intramuscular gluteal injection with a 19-gauge needle. Injection volume ranges from 1 to 2.7 mL. OLAI has essentially the same general tolerability as that of oral olanzapine; however with the depot there is the additional risk of a post-injection delirium sedation syndrome occurring at a rate of 0.07% of injections, requiring a risk management plan that includes observing the patient for 3 hours post injection. PMID:20016798
Use of concomitant medications with antipsychotic agents in the treatment of schizophrenia is common but lacks a clear scientific rationale. We evaluated concomitant medication usage during the first 6 months of the prospective, observational, European Schizophrenia Outpatient Health Outcomes (SOHO) study, examining its frequency, variation according to type of antipsychotic drug used, and impact on treatment tolerability. We also determined factors that were associated with concomitant medication use. The use of concomitant medications differed greatly among the countries participating in the SOHO study. The presence of depressive symptoms and being female were associated with the use of concomitant antidepressants. Certain antipsychotics were associated with less use of concomitant medications: significantly fewer olanzapine-, quetiapine- and clozapine-treated patients used concomitant anticholinergics or anxiolytics/hypnotics. Patients using concomitant medications had an increased incidence of sexually related side effects and extrapyramidal side effects (EPS) at 6 months follow-up compared with patients not using concomitant medications. The results should be interpreted conservatively due to the observational design of SOHO. PMID:16023776
Novick, Diego; Bousono, Manuel; Suarez, David; Olivares, Jose M; Montejo, Angel L; Haro, Josep Maria; Edgell, Eric T; Ratcliffe, Mark
Abstract Background The rate-corrected QT interval (QTc) prolongation is a risk factor for sudden cardiac death and may be induced by antipsychotic drugs. Objective To determine the clinical characteristics associated with QTc prolongation (440?msec or greater) in children and adolescents hospitalized for treatment of psychiatric disorders. Method We determined the frequency of baseline prolongation of QTc in 811 psychiatric pediatric inpatients (15.5?±?2.4 years of age). QTc duration was 440?msec or greater (range 441–481?msec) in 16 patients (1.97%). In a 1:5 nested case–control design, the 16 patients with prolonged QTc were age- and gender-matched with 80 patients with QTc of <421?msec. Results Patients with normal and prolonged QTc had similar utilization of antipsychotics (43.8% vs. 40.8%) and daily chlorpromazine equivalents (165?±?110 vs. 168?±?218?mg). Hypokalemia (p?=?0.009) and obesity (p?=?0.032) were more common among patients with prolonged QTc. The correlation between obesity and QTc prolongation was confirmed in logistic regression analysis. Conclusions In a large cohort of youth hospitalized for treatment of psychiatric disorders, a prolonged QTc on admission was rare and correlated with the presence of obesity, but not with current use of antipsychotic drugs. PMID:21823910
Correll, Christoph U.; Harris, Jennifer; Figen, Vicki; Kane, John M.
Background Major depressive disorder (MDD) is a debilitating and costly mental disorder. Although commercially available antidepressants have proliferated over the last 20 years, a substantial number of patients either do not respond adequately to these drugs or are unable to tolerate their adverse effects. One common approach has been to augment conventional antidepressants with an adjunctive agent, but the optimal selection of atypical antipsychotic agents for adjunctive treatment of treatment-resistant depression (TRD) remains controversial. Methods/Design An electronic literature search of PubMed, the Cochrane Library, Embase, Web of Science, LiLACS, CINAHL, and PsycINFO for studies will be conducted with no restrictions on language, publication year, or publication type. Several clinical trial registry agencies, pharmaceutical company websites, and FDA reports will also be reviewed. Randomized clinical trials (RCTs) with atypical antipsychotic augmentation treatment for treatment-resistant depression will be considered. Data will be independently extracted by two reviewers. Traditional pairwise meta-analyses will be performed for RCTs that directly compare different treatment arms. Then, Bayesian network meta-analyses will be performed to compare the relative efficacy and acceptability of different atypical antipsychotic agents (and doses). A sensitivity analysis will be performed by excluding studies classified as a small sample size, having a high placebo effect. Discussion This systematic review and network meta-analysis will comparatively analyze the efficacy, quality of life, and acceptability profiles of atypical antipsychotic medications used for the adjunctive treatment of TRD. The findings should provide clinically relevant implications for comprehensively understanding the risk–benefit profiles of these adjunctive treatments. Systematic review registration PROSPERO CRD 42014009666. PMID:25373601
Background Atypical antipsychotic medications are widely prescribed for the adjunctive treatment of depression, yet their total risk–benefit profile is not well understood. We thus conducted a systematic review of the efficacy and safety profiles of atypical antipsychotic medications used for the adjunctive treatment of depression. Methods and Findings We included randomized trials comparing adjunctive antipsychotic medication to placebo for treatment-resistant depression in adults. Our literature search (conducted in December 2011 and updated on December 14, 2012) identified 14 short-term trials of aripiprazole, olanzapine/fluoxetine combination (OFC), quetiapine, and risperidone. When possible, we supplemented published literature with data from manufacturers' clinical trial registries and US Food and Drug Administration New Drug Applications. Study duration ranged from 4 to 12 wk. All four drugs had statistically significant effects on remission, as follows: aripiprazole (odds ratio [OR], 2.01; 95% CI, 1.48–2.73), OFC (OR, 1.42; 95% CI, 1.01–2.0), quetiapine (OR, 1.79; 95% CI, 1.33–2.42), and risperidone (OR, 2.37; 95% CI, 1.31–4.30). The number needed to treat (NNT) was 19 for OFC and nine for each other drug. All drugs with the exception of OFC also had statistically significant effects on response rates, as follows: aripiprazole (OR, 2.07; 95% CI, 1.58–2.72; NNT, 7), OFC (OR, 1.30, 95% CI, 0.87–1.93), quetiapine (OR, 1.53, 95% CI, 1.17–2.0; NNT, 10), and risperidone (OR, 1.83, 95% CI, 1.16–2.88; NNT, 8). All four drugs showed statistically significant effects on clinician-rated depression severity measures (Hedges' g ranged from 0.26 to 0.48; mean difference of 2.69 points on the Montgomery–Asberg Depression Rating Scale across drugs). On measures of functioning and quality of life, these medications produced either no benefit or a very small benefit, except for risperidone, which had a small-to-moderate effect on quality of life (g?=?0.49). Treatment was linked to several adverse events, including akathisia (aripiprazole), sedation (quetiapine, OFC, and aripiprazole), abnormal metabolic laboratory results (quetiapine and OFC), and weight gain (all four drugs, especially OFC). Shortcomings in study design and data reporting, as well as use of post hoc analyses, may have inflated the apparent benefits of treatment and reduced the apparent incidence of adverse events. Conclusions Atypical antipsychotic medications for the adjunctive treatment of depression are efficacious in reducing observer-rated depressive symptoms, but clinicians should interpret these findings cautiously in light of (1) the small-to-moderate-sized benefits, (2) the lack of benefit with regards to quality of life or functional impairment, and (3) the abundant evidence of potential treatment-related harm. Please see later in the article for the Editors' Summary PMID:23554581
Spielmans, Glen I.; Berman, Margit I.; Linardatos, Eftihia; Rosenlicht, Nicholas Z.; Perry, Angela; Tsai, Alexander C.
OBJECTIVE: To analyze the prevalence and types of prescribing and dispensing errors occurring with high-alert medications and to propose preventive measures to avoid errors with these medications. INTRODUCTION: The prevalence of adverse events in health care has increased, and medication errors are probably the most common cause of these events. Pediatric patients are known to be a high-risk group and are an important target in medication error prevention. METHODS: Observers collected data on prescribing and dispensing errors occurring with high-alert medications for pediatric inpatients in a university hospital. In addition to classifying the types of error that occurred, we identified cases of concomitant prescribing and dispensing errors. RESULTS: One or more prescribing errors, totaling 1,632 errors, were found in 632 (89.6%) of the 705 high-alert medications that were prescribed and dispensed. We also identified at least one dispensing error in each high-alert medication dispensed, totaling 1,707 errors. Among these dispensing errors, 723 (42.4%) content errors occurred concomitantly with the prescribing errors. A subset of dispensing errors may have occurred because of poor prescription quality. The observed concomitancy should be examined carefully because improvements in the prescribing process could potentially prevent these problems. CONCLUSION: The system of drug prescribing and dispensing at the hospital investigated in this study should be improved by incorporating the best practices of medication safety and preventing medication errors. High-alert medications may be used as triggers for improving the safety of the drug-utilization system. PMID:22012039
Silva, Maria das Dores Graciano; Rosa, Mário Borges; Franklin, Bryony Dean; Reis, Adriano Max Moreira; Anchieta, Lêni Márcia; Mota, Joaquim Antônio César
Background: Studying drug use pattern among medical practitioners is of vital importance in the present scenario where irrational drug use and development of drug resistance is becoming rampant. Objective: To assess, the pattern of prescribing practices among the general practitioners in a defined rural and urban area of Tamil Nadu. Materials and Methods: A community based descriptive study was conducted to collect 600 prescriptions from the catchment areas of rural and urban health training centers of a medical college using prescribing indicators as per the WHO “How to investigate drug use in health facilities” tool. Results: This prescription study revealed that multivitamins (19.5%), antibiotics (19.3%), drugs for gastro-intestinal tract (GIT) (18%), analgesic non-steroidal anti-inflammatory drugs/ (NSAID's) (15.1%), and antihistaminic (12.5%) were prescribed frequently. Among the antibiotics, amoxicillin (49.2%) was the most commonly prescribed followed by gentamicin (31.7%). Percentage of prescriptions with an antibiotic was 55% and nearly 62% of the practitioners prescribed drugs by their generic names. As a practice of poly-pharmacy, it was observed that the average number of drugs prescribed in urban and rural area was nearly 5 and 4, respectively. Nearly 80% of the urban and rural practitioners were prescribing at least one injection. Study of the quality of prescriptions revealed that there was poor legibility, high usage of abbreviations, inadequate details of the drugs, and absence of signature by practitioners in the prescriptions. Conclusion: This study clearly highlights the practice of poly-pharmacy, low usage of generic drugs, injudicious usage of antibiotics and injections and low usage of drugs prescribed from essential drugs list. PMID:23833368
Gopalakrishnan, Sekharan; Ganeshkumar, Parasuraman; Katta, Ajitha
The purpose of this study was to gain understanding about nurse practitioners' (NPs') prescriptive decision making for geriatric patients with attention to pharmaceutical marketing influences. Prior research has focused on physician prescribers and identified suboptimal practices. Because the majority of medications are prescribed to older adults, NPs in geriatric practice were targeted as an information-rich group to interview about prescribing issues. Given the exploratory nature of this research, qualitative focus group methods were employed using content analysis. Fifteen NPs were recruited at an annual national geriatric NP conference. They worked in all regions of the United States, had an average of 9 years prescribing experience, and participated in 1 of the 2 focus groups. The key theme that emerged was that they were more than a prescriber. Findings revealed overwhelming consistency among the NP participants that their nursing background instilled a holistic approach that encompassed both nondrug and therapeutic drug options and skepticism about drug marketing, as well as offered a positive difference by tailoring to their patients' biophysical, psychological, and economic needs with an involvement in the interplay of geriatric care issues not typically addressed by physicians. The participants' reported approaches were in alignment with geriatric prescribing recommendations. PMID:20159350
Mahoney, Diane Feeney; Ladd, Elissa
Atypical antipsychotics (AAPs) have been successfully used in early-onset schizophrenia (EOS). This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. PMID:25897226
Hrdlicka, Michal; Dudova, Iva
t is commonly thought that the U.S. Food and Drug Administration (FDA) regulates the use of all pharmaceutical drugs in the United States. In fact, most hospital patients are given drugs that are not FDA-approved for the prescribed use. The FDA does require that drugs undergo extensive testing before they are re- leased onto the market and, if it concludes
ALEXANDER T. TABARROK
Post-fire Pezizales fruit commonly in many forest types after fire. The objectives of this study were to determine which Pezizales appeared as sporocarps after a prescribed fire in the Blue Mountains of eastern Oregon, and whether species of Pezizales formed mycorrhizas on ponderosa pine, whether or not they were detected from sporocarps. Forty-two sporocarp collections in five genera (Anthracobia, Morchella,
K. E. Fujimura; J. E. Smith; T. R. Horton; N. S. Weber; J. W. Spatafora
Prescribed fire is commonly applied world wide as tool for enhancing habitats and altering resource selection patterns of grazing animals. A scientific basic for this management practice has been established in some rangeland ecosystems (e.g montane grasslands, tall grass prairie, mixed prairie, ...
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
Unless the equivalence of different products has been established, the prescriber must define the product he requires by using the trade name. Present pharmacopoeial standards based on in vitro methods are inadequate to predict equivalence in man. There are many ways in which differences in formulation may influence absorption of drugs, and only comparable absorption profiles can be taken as evidence of equivalence. PMID:4465774
Beckett, A. H.
BACKGROUND: Good clinical practice in primary care includes periodic review of repeat prescriptions. Markers of prescriptions that may need review have been described, but manually checking all repeat prescriptions against the markers would be impractical. AIM: To investigate the feasibility of computerising the application of repeat prescribing quality checks to electronic patient records in United Kingdom (UK) primary care. DESIGN OF STUDY: Software performance test against benchmark manual analysis of cross-sectional convenience sample of prescribing documentation. SETTING: Three general practices in Greater Manchester, in the north west of England, during a 4-month period in 2001. METHOD: A machine-readable drug information resource, based on the British National Formulary (BNF) as the 'gold standard' for valid drug indications, was installed in three practices. Software raised alerts for each repeat prescribed item where the electronic patient record contained no valid indication for the medication. Alerts raised by the software in two practices were analysed manually. Clinical reaction to the software was assessed by semi-structured interviews in three practices. RESULTS: There was no valid indication in the electronic medical records for 14.8% of repeat prescribed items. Sixty-two per cent of all alerts generated were incorrect. Forty-three per cent of all incorrect alerts were as a result of errors in the drug information resource, 44% to locally idiosyncratic clinical coding, 8% to the use of the BNF without adaptation as a gold standard, and 5% to the inability of the system to infer diagnoses that, although unrecorded, would be 'obvious' to a clinical reading the record. The interviewed clinicians supported the goals of the software. CONCLUSION: Using electronic records for secondary decision support purposes will benefit from (and may require) both more consistent electronic clinical data collection across multiple sites, and reconciling clinicians' willingness to infer unstated but 'obvious' diagnoses with the machine's inability to do the same. PMID:14702902
Rogers, Jeremy E; Wroe, Christopher J; Roberts, Angus; Swallow, Angela; Stables, David; Cantrill, Judith A; Rector, Alan L
Results: The proportion of outpatient psychiatric vis- its in which an antidepressant was prescribed increased from 23.1% (95% confidence interval (CI), 19.7%- 26.5%) in 1985 to 48.6% (95% CI, 47.5%-49.7%) in 1993- 1994. After controlling for several patient variables, psy- chiatric patients were approximately 2.3 (95% CI, 1.8- 2.9) times more likely to receive an antidepressant in 1993- 1994 than
Mark Olfson; Steve C. Marcus; Harold Alan Pincus; Julie M. Zito; James W. Thompson; Deborah A. Zarin
Nonadherence with medication occurs in all chronic medical disorders. It is a particular challenge in schizophrenia due to the illness’s association with social isolation, stigma, and comorbid substance misuse, plus the effect of symptom domains on adherence, including positive and negative symptoms, lack of insight, depression, and cognitive impairment. Nonadherence lies on a spectrum, is often covert, and is underestimated by clinicians, but affects more than one third of patients with schizophrenia per annum. It increases the risk of relapse, rehospitalization, and self-harm, increases inpatient costs, and lowers quality of life. It results from multiple patient, clinician, illness, medication, and service factors, but a useful distinction is between intentional and unintentional nonadherence. There is no gold standard approach to the measurement of adherence as all methods have pros and cons. Interventions to improve adherence include psychoeducation and other psychosocial interventions, antipsychotic long-acting injections, electronic reminders, service-based interventions, and financial incentives. These overlap, all have some evidence of effectiveness, and the intervention adopted should be tailored to the individual. Psychosocial interventions that utilize combined approaches seem more effective than unidimensional approaches. There is increasing interest in electronic reminders and monitoring systems to enhance adherence, eg, Short Message Service text messaging and real-time medication monitoring linked to smart pill containers or an electronic ingestible event marker. Financial incentives to enhance antipsychotic adherence raise ethical issues, and their place in practice remains unclear. Simple pragmatic strategies to improve medication adherence include shared decision-making, regular assessment of adherence, simplification of the medication regimen, ensuring that treatment is effective and that side effects are managed, and promoting a positive therapeutic alliance and good communication between the clinician and patient. These elements remain essential for all patients, not least for the small minority where vulnerability and risk issue dictate that compulsory treatment is necessary to ensure adherence. PMID:25061342
Haddad, Peter M; Brain, Cecilia; Scott, Jan
What is already known about this subject Homoeopathy and herbalism are increasingly popular among the public and prescribed by general practitioners in the NHS. Doctors and regulatory authorities have expressed concerns about their efficacy and safety. Studies from the 1990s suggest that between 5.9 and 7.5% of English NHS general practitioners have prescribed homoeopathy, while less than 1% have prescribed herbal remedies. Current levels of prescribing are unknown but are thought to have increased. What this study adds Sixty percent of Scottish general practices now prescribe homoeopathic or herbal remedies. The prevalence of homoeopathic prescribing in those under 16 years has doubled since 2000 and is maximal in children < 1 year old, of whom 1% are prescribed a homoeopathic remedy. Recognized drug–herb interactions were identified in 4% of patients prescribed oral herbal remedies. Aims To investigate the current levels of homoeopathic and herbal prescribing in Scottish general practice. Methods Prescribing of homoeopathic and herbal remedies in primary care was assessed in 1891 669 patients for the year 2003–2004, using computerized prescribing data retrieved from 323 general practices in Scotland. Results Forty-nine percent of practices prescribed homoeopathic and 32% herbal remedies. A total of 193 homoeopathic and 17 herbal remedies were prescribed, with 5% of practices accounting for 46% of patients and 50% of remedies. Four thousand one hundred and sixty patients (2.2/1000 registered patients) were prescribed at least one homoeopathic remedy during the study period, with the highest prevalence to children under 12 months of age (9.5/1000 children of that age). Children under the age of 16 made up 16% of the population prescribed homoeopathic remedies (2.2/1000 registered patients of that age). Three hundred and sixty-one patients (0.2/1000 registered patients) were prescribed at least one herbal remedy during the study period, 44 of whom were children < 16 years old. Patients prescribed a homoeopathic or herbal remedy were also prescribed a median of four and five conventional medicines, respectively. Of patients prescribed an oral herbal remedy, 4% were also concomitantly prescribed a conventional medicine with which a drug–herb interaction has been documented. Conclusions Our study reports that a substantial number of Scottish general practitioners prescribe homoeopathic and herbal remedies, with an approximate doubling in the number of children prescribed homoeopathic remedies. The level of homoeopathic and herbal prescribing raises questions about homoeopathic/herbal provision in the National Health Service and should prompt critical review. PMID:16796701
Ross, Sarah; Simpson, Colin R; McLay, James S
Second-generation antipsychotics can greatly improve symptoms of psychosis-spectrum disorders. Unfortunately, these drugs are associated with weight gain, which increases a patient’s risk for developing chronic diseases including Type 2 diabetes, cardiovascular diseases or other obesity-related complications. There are interindividual differences in weight gain resulting from antipsychotic drug use that may be explained by pharmacodynamic characteristics of these agents as well as clinical factors. In addition, genetic variations in pathways associated with satiety are increasingly recognized as potential contributors to antipsychotic-associated weight gain. Polymorphisms in the leptin gene, as well as the leptin receptor gene, are potential pharmacogenetic markers associated with these outcomes. This article summarizes evidence for the associations of the leptin gene and the leptin receptor gene polymorphisms with antipsychotic-induced weight gain, potential mechanisms underlying these relationships, and discusses areas for future pharmacogenetic investigation. PMID:21787190
Lee, Amy K; Bishop, Jefrey R
In contrast to other atypical antipsychotics, aripiprazole (ARZ) acts as a partial agonist, rather than an antagonist, at dopamine D2 receptors (Burris et al, 2002; Jordan et al, 2002). This unique pharmacology is thought ...
Latif, Shaheen Azhar
Objectives To examine the relation between antipsychotic drugs and myocarditis and cardiomyopathy. Design Data mining using bayesian statistics implemented in a neural network architecture. Setting International database on adverse drug reactions run by the World Health Organization programme for international drug monitoring. Main outcome measures Reports mentioning antipsychotic drugs, cardiomyopathy, or myocarditis. Results A strong signal existed for an association between clozapine and cardiomyopathy and myocarditis. An association was also seen with other antipsychotics as a group. The association was based on sufficient cases with adequate documentation and apparent lack of confounding to constitute a signal. Associations between myocarditis or cardiomyopathy and lithium, chlorpromazine, fluphenazine, haloperidol, and risperidone need further investigation. Conclusions Some antipsychotic drugs seem to be linked to cardiomyopathy and myocarditis. The study shows the potential of bayesian neural networks in analysing data on drug safety. PMID:11358771
Coulter, David M; Bate, Andrew; Meyboom, Ronald H B; Lindquist, Marie; Edwards, I Ralph
... 1 through 18) has one of these conditions: Schizophrenia and related psychosis Bipolar disorder Developmental disorders, including ... Researchers found that: Antipsychotics improve the symptoms of schizophrenia. Olanzapine (Zyprexa®), risperidone (Risperdol®), and clozapine (Clozaril® or ...
... and risperidone— come as generics. Our advice: For schizophrenia: In general, almost everyone who is diagnosed with ... Should Know Antipsychotic drugs can help people with schizophrenia lead more stable lives and spend less time ...
Researchers at the University of California, San Diego School of Medicine have discovered that FDA-approved anti-psychotic drugs possess tumor-killing activity against the most aggressive form of primary brain cancer, glioblastoma.
Background Potentially inappropriate prescribing (PIP) in older people is associated with increases in morbidity, hospitalisation and mortality. The objective of this study was to estimate the prevalence of and factors associated with PIP, among those aged ?70 years, in the United Kingdom, using a comprehensive set of prescribing indicators and comparing these to estimates obtained from a truncated set of the same indicators. Methods A retrospective cross-sectional study was carried out in the UK Clinical Practice Research Datalink (CPRD), in 2007. Participants included those aged???70 years, in CPRD. Fifty-two PIP indicators from the Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) criteria were applied to data on prescribed drugs and clinical diagnoses. Overall prevalence of PIP and prevalence according to individual STOPP criteria were estimated. The relationship between PIP and polypharmacy (?4 medications), comorbidity, age, and gender was examined. A truncated, subset of 28 STOPP criteria that were used in two previous studies, were further applied to the data to facilitate comparison. Results Using 52 indicators, the overall prevalence of PIP in the study population (n?=?1,019,491) was 29%. The most common examples of PIP were therapeutic duplication (11.9%), followed by use of aspirin with no indication (11.3%) and inappropriate use of proton pump inhibitors (PPIs) (3.7%). PIP was strongly associated with polypharmacy (Odds Ratio 18.2, 95% Confidence Intervals, 18.0-18.4, P?0.05). PIP was more common in those aged 70–74 years vs. 85 years or more and in males. Application of the smaller subset of the STOPP criteria resulted in a lower PIP prevalence at 14.9% (95% CIs 14.8-14.9%) (n?=?151,598). The most common PIP issues identified with this subset were use of PPIs at maximum dose for?>?8 weeks, NSAIDs for?>?3 months, and use of long-term neuroleptics. Conclusions PIP was prevalent in the UK and increased with polypharmacy. Application of the comprehensive set of STOPP criteria allowed more accurate estimation of PIP compared to the subset of criteria used in previous studies. These findings may provide a focus for targeted interventions to reduce PIP. PMID:24919523
Background: Although falls are multifactorial, medications are a key risk factor that may be modifiable. Falls were among the most common occurrences entered into a risk identification system at the authors’ hospital. Objectives: To identify whether general medicine inpatients who had experienced a fall were taking any medications known to be associated with falls. Methods: The literature was reviewed to develop a list of high-risk medications that have been associated with falls. In a retrospective quality-improvement database-based study, information from the risk identification system was merged with data from the pharmacy dispensing system for general medicine inpatients who had experienced a fall. The primary end point was the percentage of patients with a documented fall who had a prescription for a high-risk medication. The number of such medications that had been prescribed for patients who fell was also calculated. Results: Eighty-one unique medications were found to be associated with falls. During the study period (April 1, 2008, to March 31, 2009), 151 patients experienced a fall. Of those, 144 (95.4%) were taking at least one high-risk medication. The mean number of high-risk medications per patient who experienced a fall was 2.2. Of all documented falls, a new high-risk medication had been started within 7 days before the fall for 74 (49.0%) and within 24 h before the fall for 17 (11.3%). The most commonly prescribed drugs during all time periods (i.e., within 24 h or 7 days before the fall or since the patient’s admission) were lorazepam and zopiclone. The pharmacy database did not track administration of medications, so it is possible that some of the drugs prescribed were not actually taken by the patient. Conclusion: Almost all inpatients who experienced a fall during the hospital stay had a prescription for at least one medication associated with a high risk for falls. Lorazepam and zopiclone were the drugs most commonly associated with falls in this hospital, and their use should be reviewed. PMID:22479083
Cashin, Richard P; Yang, Meiti
Background Long-acting injectable (LAI) formulations are not widely used in routine practice even though they offer advantages in terms of relapse prevention. As part of a process to improve the quality of care, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) elaborated guidelines for the use and management of antipsychotic depots in clinical practice. Methods Based on a literature review, a written survey was prepared that asked about 539 options in 32 specific clinical situations concerning 3 fields: target-population, prescription and use, and specific populations. We contacted 53 national experts, 42 of whom (79%) completed the survey. The options were scored using a 9-point scale derived from the Rand Corporation and the University of California in the USA. According to the answers, a categorical rank (first-line/preferred choice, second-line/alternate choice, third-line/usually inappropriate) was assigned to each option. The first-line option was defined as a strategy rated as 7–9 (extremely appropriate) by at least 50% of the experts. The following results summarize the key recommendations from the guidelines after data analysis and interpretation of the results of the survey by the scientific committee. Results LAI antipsychotics are indicated in patients with schizophrenia, schizoaffective disorder, delusional disorder and bipolar disorder. LAI second-generation antipsychotics are recommended as maintenance treatment after the first episode of schizophrenia. LAI first-generation antipsychotics are not recommended in the early course of schizophrenia and are not usually appropriate in bipolar disorder. LAI antipsychotics have long been viewed as a treatment that should only be used for a small subgroup of patients with non-compliance, frequent relapses or who pose a risk to others. The panel considers that LAI antipsychotics should be considered and systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated. Recommendations for medication management when switching oral antipsychotics to LAI antipsychotics are proposed. Recommendations are also given for the use of LAI in specific populations. Conclusion In an evidence-based clinical approach, psychiatrists, through shared decision-making, should be systematically offering to most patients that require long-term antipsychotic treatment an LAI antipsychotic as a first-line treatment. PMID:24359031
Introduction: Exposure to antipsychotic medication has been extensively associated with structural brain changes in the basal ganglia (BG). Traditionally antipsychotics have been divided into first and second generation antipsychotics (FGAs and SGAs) however, the validity of this classification has become increasingly controversial. To address if specific antipsychotics induce differential effects on BG volumes or whether volumetric effects are explained by FGA or SGA classification, we reviewed longitudinal structural magnetic resonance imaging (MRI) studies investigating effects of antipsychotic monotherapy. Material and Methods: We systematically searched PubMed for longitudinal MRI studies of patients with schizophrenia or non-affective psychosis who had undergone a period of antipsychotic monotherapy. We used specific, predefined search terms and extracted studies were hand searched for additional studies. Results: We identified 13 studies published in the period from 1996 to 2011. Overall six compounds (two classified as FGAs and four as SGAs) have been investigated: haloperidol, zuclophentixol, risperidone, olanzapine, clozapine, and quetiapine. The follow-up period ranged from 3-24 months. Unexpectedly, no studies found that specific FGAs induce significant BG volume increases. Conversely, both volumetric increases and decreases in the BG have been associated with SGA monotherapy. Discussion: Induction of striatal volume increases is not a specific feature of FGAs. Except for clozapine treatment in chronic patients, volume reductions are not restricted to specific SGAs. The current review adds brain structural support to the notion that antipsychotics should no longer be classified as either FGAs or SGAs. Future clinical MRI studies should strive to elucidate effects of specific antipsychotic drugs. PMID:23157636
Ebdrup, B.H; Nørbak, H; Borgwardt, S; Glenthøj, B
Schizophrenia is a serious, chronic, and devastating mental illness with a substantial impact on psychological, physical, social, and economical areas of an individual and society. To treat such critical mental illness, a number of first-generation (typical) and second-generation (atypical) antipsychotics are currently available in the market. Despite such treatment options, most of patients with schizophrenia have a poor treatment outcome and become treatment resistant, causing continual deterioration on positive, negative, and cognitive symptoms, resulting in impairment of socio-occupational functioning. Hence, additional novel antipsychotics with better efficacy, safety, and tolerability profiles are needed to enable clinicians to diversify treatment options to improve treatment of schizophrenia. Recently, the 3 antipsychotics, including iloperidone (2009), asenapine (2009), and lurasidone (2010), have been approved by the US Food and Drug Administration. Two other atypical antipsychotics, including sertindole and blonanserin, are approved and used outside the United States for treatment of schizophrenia. Sertindole, after it has been voluntarily suspended by the manufacturer in 1998 due to its potential risk in causing cardiovascular-related death, was relaunched to the European market in 2005. More recently, blonanserin was approved in Japan (2008) and in Korea (2009) for the management of schizophrenia. Individual antipsychotic may have differential pros and cons compared with other antipsychotic in terms of efficacy, safety, tolerability, restoration of functional capacity, and economic aspect reflecting relapse prevention. The purpose of this review was to provide distinctive clinical characteristics and up-to-date of clinical trial data of the 5 novel atypical antipsychotics for the management of schizophrenia, which may deliver clinicians better understanding in the use of such atypical antipsychotics for the treatment of schizophrenia in clinical practice. PMID:24201235
Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un
The predictive value of currently available preclinical models for the selection of non-dopaminergic antipsychotic agents is unknown. Although devoid of direct antidopaminergic activity, MDL 100,907 has demonstrated activity in a wide-range of paradigms believed to indicate antipsychotic efficacy. In electrophysiological tests, acute administration of MDL 100,907 reverses amphetamine-induced slowing of A10 dopaminergic neurons and blocks MK-801-induced increases in firing without
CJ Schmidt; JH Kehne; PC Moser; SM Sorensen
As many as half of obsessive-compulsive disorder (OCD) patients treated with an adequate trial of serotonin reuptake inhibitors (SRIs) fail to fully respond to treatment and continue to exhibit significant symptoms. Many studies have assessed the effectiveness of antipsychotic augmentation in SRI-refractory OCD. In this systematic review, we evaluate the efficacy of antipsychotic augmentation in treatment-refractory OCD. The electronic databases
M H Bloch; A Landeros-Weisenberger; B Kelmendi; V Coric; M B Bracken; J F Leckman
...benefits. (c) Acceptable reasons for failure to follow prescribed treatment. ...determining if you have an acceptable reason for failure to follow prescribed treatment. The...because of its enormity (e.g. open heart surgery), unusual nature...
...benefits. (c) Acceptable reasons for failure to follow prescribed treatment. ...determining if you have an acceptable reason for failure to follow prescribed treatment. The...because of its magnitude (e.g., open heart surgery), unusual nature...
...benefits. (c) Acceptable reasons for failure to follow prescribed treatment. ...determining if you have an acceptable reason for failure to follow prescribed treatment. The...because of its enormity (e.g. open heart surgery), unusual nature...
...benefits. (c) Acceptable reasons for failure to follow prescribed treatment. ...determining if you have an acceptable reason for failure to follow prescribed treatment. The...because of its magnitude (e.g., open heart surgery), unusual nature...
...benefits. (c) Acceptable reasons for failure to follow prescribed treatment. ...determining if you have an acceptable reason for failure to follow prescribed treatment. The...because of its enormity (e.g. open heart surgery), unusual nature...
...benefits. (c) Acceptable reasons for failure to follow prescribed treatment. ...determining if you have an acceptable reason for failure to follow prescribed treatment. The...because of its magnitude (e.g., open heart surgery), unusual nature...
Physicians in an experimental group were surveyed to assess their knowledge of the effectiveness, cost, and side effects of antibiotics, and a tutorial was developed to modify some prescribing patterns. Prescribing patterns were statistically different. (Author/MLW)
Klein, Lawrence E.; And Others
Serotonergic transmission is considered relevant in the pathophysiology and the treatment of schizophrenia. Tryptophan hydroxylase (TPH) is the rate limiting enzyme in the biosynthesis of serotonin. While the TPH1 gene has been found to be associated with schizophrenia, studies focusing on TPH2 variants did not yield conclusive results for schizophrenia or the response to antipsychotic medication. We analyzed eleven TPH2 SNPs in two case-control samples consisting of 4453 individuals in total. Six SNPs were selected because of their potential functional relevance (rs4570625, rs11178997, rs11178998, rs7954758, rs7305115, and, rs4290270) and were supported by another 5 tagging SNPs selected based on HapMap LD information. In the discovery sample (1476 individuals), we observed a significant association with schizophrenia for rs10784941 (p = 0.009, OR minor G-allele 0.82 [0.71-0.95]) and rs4565946 (p = 0.011, OR minor T-allele 0.83 [0.71-0.96]). Association was also observed with a common rs4570625-rs4565946 haplotype (OR G-C haplotype 1.20 [1.02-1.40]; p = 0.0046). Single-marker associations could not be replicated in the replication sample consisting of 2977 individuals, but there was a strong trend regarding the rs4570625-rs4565946 G-C haplotype (OR 1.10 [0.98-1.24]; p(one-sided test) = 0.054). In smaller sub-samples, the rare rs4570625-rs4565946 T-T haplotype was associated with reduced processing speed (n = 193, p = 0.004) and sensorimotor gating (n = 68, p = 0.006) of schizophrenia patients. TPH2 variants and the rs4570625-rs4565946 G-C haplotype did not influence the beneficial response to antipsychotic drugs (n = 210) after four weeks of treatment administering the Positive and Negative Syndrome Scale of Schizophrenia (PANSS). We also investigated the association of the SNPs to treatment response, but did not get significant results. In sum, our results argue for only a minor role of TPH2 in schizophrenia. PMID:22655589
Schuhmacher, Anna; Becker, Tim; Rujescu, Dan; Quednow, Boris B; Lennertz, Leonhard; Wagner, Michael; Benninghoff, Jens; Rietschel, Marcella; Häfner, Heinz; Franke, Petra; Wölwer, Wolfgang; Gaebel, Wolfgang; Maier, Wolfgang; Mössner, Rainald
Medication nonadherence has been associated with persistence of psychotic symptoms, relapse, and hospitalization in patients with schizophrenia. Patients with untreated psychosis are significantly less likely to achieve remission, whereas antipsychotic drug adherence has been associated with recovery. As such, adherence to antipsychotic drug treatment is a key issue for nurses and treatment team members caring for patients who typically are on chronic, progressive disease course. Long-acting injectable (LAI) anti-psychotic drugs, developed to improve adherence and provide and alternative antipsychotic drug treatment fro schizophrenia, have been associated with improved treatment outcomes including reduction of relapse rates approximately 30% and reduction in hospitalizations. However, LAI antipsychotic drugs remain underutilized in the United States despite a growing body of literature supporting positive outcomes of LAI versus oral antipsychotic drugs. Mental health nurses are in a key position to support improved adherence inpatients with schizophrenia through use of practical educational strategies that help patients, family members, and health care providers better understand and manage treatment. PMID:23547305
Kirk Morton, N; Zubek, Donna
Medication is critical in schizophrenia therapy, and prescription patterns have changed considerably over the past 20 years in China. This study attempts to evaluate the prescription patterns of antipsychotics for inpatients with schizophrenia in China and to identify factors influencing these patterns. Claims data of inpatients diagnosed with schizophrenia in 2010 were derived from the reimbursement database of Wuhan and Wuxi. A total of 5251 inpatients received antipsychotic medications, of whom 29.0% received second-generation antipsychotics apart from clozapine (SGAs#), 13.7% received clozapine (CLO), 13.5% received first-generation antipsychotics (FGAs), 43.8% received at least both drug classes, and 5.1% used FGAs, CLO as well as SGAs#. Multinomial logistic regression for 2904 identified inpatients showed that factors of drug reimbursement policy, duration of hospitalization, age group, and municipality were statistically significant in antipsychotic medication. Drug list B and the 25-45 age group presented a significant relationship with SGAs# prescription (FGAs vs. SGAs#). Furthermore, the 12-30-day duration of hospitalization and the 25-45 age group showed a significant relationship with SGAs# prescription (CLO vs. SGAs#). Socioeconomic factors such as health insurance policies, especially reimbursement policy of drugs and payment system, as well as mental health resource distribution are important in antipsychotic prescription in China. PMID:24323200
Xue, Qiuji; Xiong, Xianjun; Feng, Yi; Yao, Lan; Chen, Shanquan; Xiang, Li
Background Rates of discontinuation of antipsychotic treatment for patients with schizophrenia are high and evidence is limited by selective inclusion and high attrition in randomized controlled trials. Aims To study time to discontinuation of antipsychotic treatment for patients with schizophrenia. Method All patients with schizophrenia (n = 396) discharged between 2005 and 2011 were followed until discontinuation (clinician or patient decided) of antipsychotic treatment or other endpoints. Univariate and multivariate survival analyses (with time on antipsychotic treatment as the dependent variable) using time-dependent variables were performed. Results Clozapine displayed lower risk for all-cause (p < 0.001), clinician-decided (p = 0.012) and patient-decided (p = 0.039) discontinuation versus olanzapine oral treatment in the multivariate Cox regression. Second-generation long-acting injection antipsychotics (LAI) (p = 0.015) and first-generation long-acting injection antipsychotics (p = 0.013) showed significantly lower risks for patient-decided discontinuation than olanzapine oral. Conclusion Higher effectiveness of clozapine and LAI treatment versus oral olanzapine were identified in a clinical cohort of patients with schizophrenia. PMID:25489474
Kjelby, Eirik; Wentzel-Larsen, Tore; Mellesdal, Liv S.; Jørgensen, Hugo A.; Johnsen, Erik
The aim of this study is to evaluate gender differences in schizophrenia in response to typical and atypical antipsychotics. The SOHO (Schizophrenia Outpatient Health Outcomes) study is a 3-year, prospective, observational study of health outcomes associated with antipsychotic treatment in 10 European countries that included over 10,000 outpatients initiating or changing their antipsychotic medication. The analyzed sample included 4529 men (56.68%) and 3461 women (43.32%). Findings showed that gender was a significant predictor for response based on the Clinical Global Impression (CGI) scale and for improvement in quality of life measured with the EuroQol-5D (EQ-VAS) scale, with women having a better response. The highest gender differences were found in typical antipsychotics and clozapine. Olanzapine only showed differences in quality of life, and no differences were found for risperidone. In conclusion, in this group of outpatients with schizophrenia, gender is a predictor of clinical response to antipsychotic treatment, but its influence is not the same for all antipsychotics. PMID:17681611
Usall, Judith; Suarez, David; Haro, Josep Maria
OBJECTIVE Cannabis use disorder is the most common co-occurring drug use disorder in people with schizophrenia and is associated with poor outcomes. We launched a randomized controlled trial to assess the impact of clozapine compared with treatment as usual on cannabis use in patients with schizophrenia and co-occurring cannabis use disorder. METHODS Thirty-one patients with schizophrenia and co-occurring cannabis use disorder were randomly assigned to switch to clozapine or to stay on their current antipsychotic and were then followed weekly for 12 weeks. Blinded raters assessed participants weekly with the Timeline Follow-back for substance use and the expanded Brief Psychiatric Rating Scale for symptoms. Longitudinal random effects models were used to investigate the time-varying differences in cannabis use and other outcomes between the treatment as usual and clozapine groups. RESULTS The two groups differed in average intensity of cannabis use by approximately 4.5 joints/week, with lesser use in the clozapine group (t = ?1.77; df = 28.5; p=.086; effect size ~ 0.6). Symptoms and functioning were not different between the two groups. CONCLUSIONS Clozapine may reduce cannabis use among patients with schizophrenia and co-occurring cannabis use disorder. Further controlled trials are warranted.
Brunette, Mary F.; Dawson, Ree; O’Keefe, Christopher D.; Narasimhan, Meera; Noordsy, Douglas L.; Wojcik, Joanne; Green, Alan I.
1. Exotic weeds and woody plants are degrading the World’s grasslands, and ecologists are attempting to reverse the degradation with prescribed grazing. Prescribed grazing entails introducing livestock (e.g. sheep, goats) that eat unwanted plants. Prescribed grazing has shown modest potential in ...
When final year medical students reporting poor prescribing confidence were tested, key prescribing weaknesses emerged. This study aimed to characterize student variability in both the experience of and cognitive levels displayed during prescribing. Blooms Taxonomy cognitive categories were assigned to each question of a student test measuring…
Harries, C. S.; Botha, J.
Background Prescribing is a core activity for general practitioners, yet significant variation in the quality of prescribing has been reported. This suggests there may be room for improvement in the application of the current best research evidence. There has been substantial investment in technologies and interventions to address this issue, but effect sizes so far have been small to moderate. This suggests that prescribing is a decision-making process that is not sufficiently understood. By understanding more about prescribing processes and the implementation of research evidence, variation may more easily be understood and more effective interventions proposed. Methods An ethnographic study in three Scottish general practices with diverse organizational characteristics. Practices were ranked by their performance against Audit Scotland prescribing quality indicators, incorporating established best research evidence. Two practices of high prescribing quality and one practice of low prescribing quality were recruited. Participant observation, formal and informal interviews, and a review of practice documentation were employed. Results Practices ranked as high prescribing quality consistently made and applied macro and micro prescribing decisions, whereas the low-ranking practice only made micro prescribing decisions. Macro prescribing decisions were collective, policy decisions made considering research evidence in light of the average patient, one disease, condition, or drug. Micro prescribing decisions were made in consultation with the patient considering their views, preferences, circumstances and other conditions (if necessary). Although micro prescribing can operate independently, the implementation of evidence-based, quality prescribing was attributable to an interdependent relationship. Macro prescribing policy enabled prescribing decisions to be based on scientific evidence and applied consistently where possible. Ultimately, this influenced prescribing decisions that occur at the micro level in consultation with patients. Conclusion General practitioners in the higher prescribing quality practices made two different ‘types’ of prescribing decision; macro and micro. Macro prescribing informs micro prescribing and without a macro basis to draw upon the low-ranked practice had no effective mechanism to engage with, reflect on and implement relevant evidence. Practices that recognize these two levels of decision making about prescribing are more likely to be able to implement higher quality evidence. PMID:23799906
Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N=225) of risperidone for treatment of irritability in children/adolescents aged 4-17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P=1.0 × 10(-6)), CNR1 (P=9.6 × 10(-5)) and the leptin (LEP) promoter (P=1.4 × 10(-4)) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P=1.3 × 10(-9)) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event. PMID:23799528
Nurmi, E L; Spilman, S L; Whelan, F; Scahill, L L; Aman, M G; McDougle, C J; Arnold, L E; Handen, B; Johnson, C; Sukhodolsky, D G; Posey, D J; Lecavalier, L; Stigler, K A; Ritz, L; Tierney, E; Vitiello, B; McCracken, J T
Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N=225) of risperidone for treatment of irritability in children/adolescents aged 4–17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P=1.0 × 10?6), CNR1 (P=9.6 × 10?5) and the leptin (LEP) promoter (P=1.4 × 10?4) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P=1.3 × 10?9) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event. PMID:23799528
Nurmi, E L; Spilman, S L; Whelan, F; Scahill, L L; Aman, M G; McDougle, C J; Arnold, L E; Handen, B; Johnson, C; Sukhodolsky, D G; Posey, D J; Lecavalier, L; Stigler, K A; Ritz, L; Tierney, E; Vitiello, B; McCracken, J T
Hospital formularies, guided by the Pharmacy and Therapeutics Committee, exist to optimize medication use by identifying and designating drugs of choice to guide rational prescribing, ultimately reducing patient risk and costs and improving patient outcomes. Guidelines and a framework exist to guide critical evaluations of medications for formulary listing; however, there may be opportunities to improve and standardize how a formulary change could be instituted in Canadian hospitals. A formulary change at an Ontario hospital revealed that there are some key challenges to the formulary change process including the importance of a robust project plan, appropriate resources, healthcare staff education, and acceptance. PMID:25046967
Karas, Albert; Kuehl, Bonnie
Objective To synthesise qualitative studies that explore prescribers’ perceived barriers and enablers to minimising potentially inappropriate medications (PIMs) chronically prescribed in adults. Design A qualitative systematic review was undertaken by searching PubMed, EMBASE, Scopus, PsycINFO, CINAHL and INFORMIT from inception to March 2014, combined with an extensive manual search of reference lists and related citations. A quality checklist was used to assess the transparency of the reporting of included studies and the potential for bias. Thematic synthesis identified common subthemes and descriptive themes across studies from which an analytical construct was developed. Study characteristics were examined to explain differences in findings. Setting All healthcare settings. Participants Medical and non-medical prescribers of medicines to adults. Outcomes Prescribers’ perspectives on factors which shape their behaviour towards continuing or discontinuing PIMs in adults. Results 21 studies were included; most explored primary care physicians’ perspectives on managing older, community-based adults. Barriers and enablers to minimising PIMs emerged within four analytical themes: problem awareness; inertia secondary to lower perceived value proposition for ceasing versus continuing PIMs; self-efficacy in regard to personal ability to alter prescribing; and feasibility of altering prescribing in routine care environments given external constraints. The first three themes are intrinsic to the prescriber (eg, beliefs, attitudes, knowledge, skills, behaviour) and the fourth is extrinsic (eg, patient, work setting, health system and cultural factors). The PIMs examined and practice setting influenced the themes reported. Conclusions A multitude of highly interdependent factors shape prescribers’ behaviour towards continuing or discontinuing PIMs. A full understanding of prescriber barriers and enablers to changing prescribing behaviour is critical to the development of targeted interventions aimed at deprescribing PIMs and reducing the risk of iatrogenic harm. PMID:25488097
Anderson, Kristen; Stowasser, Danielle; Freeman, Christopher; Scott, Ian
Aims To ascertain the effects of the Medicines and Healthcare products Regulatory Agency's (MHRA) safety update in June 2010 on the volume of prescribing of quinine and on indices of quinine toxicity. Methods We analysed quarterly primary care total and quinine prescribing data for England and quinine prescribing volume for individual Primary Care Trusts in the North East of England from 2007/8 to 2011/12 obtained from the ePACT.net database. We also analysed quinine toxicity enquiries to the National Poisons Information Service (NPIS) via Toxbase® and by telephone between 2004/5 and 2011/12. Joinpoint regression and Pearson's correlation tests were used to ascertain changes in trends in prescribing and indices of toxicity and associations between prescribing and indices of toxicity, respectively. Results Total prescribing continued to increase, but annual growth in quinine prescribing in England declined from 6.0 to ?0.6% following the MHRA update [difference ?0.04 (95% confidence interval ?0.07 to ?0.01) quinine prescriptions per 100 patients per quarter, P = 0.0111]. Much larger reductions were observed in Primary Care Trusts that introduced comprehensive prescribing reviews. The previously increasing trend in Toxbase® quinine searches was reversed [difference ?19.76 (95% confidence interval ?39.28 to ?9.20) user sessions per quarter, P = 0.0575]. Telephone enquiries to NPIS for quinine have declined, with stabilization of the proportion of moderate to severe cases of quinine poisoning since the update. Conclusions The MHRA advice was followed by limited reductions in the growth in quinine prescribing and in indicators of quinine overdose and toxicity. Quinine prescribing, however, remains common, and further efforts are needed to reduce availability and use. PMID:23594200
Acheampong, Paul; Cooper, Gill; Khazaeli, Behshad; Lupton, David J; White, Sue; May, Margaret T; Thomas, Simon H L
Background Relatively little is known about prescribing errors in general practice, or the factors associated with error. Aim To determine the prevalence and nature of prescribing and monitoring errors in general practices in England. Design and setting Retrospective case-note review of unique medication items prescribed over a 12-month period to a 2% random sample of patients. Fifteen general practices across three primary care trusts in England. Method A total of 6048 unique prescription items prescribed over the previous 12 months for 1777 patients were examined. The data were analysed by mixed effects logistic regression. The main outcome measures were prevalence of prescribing and monitoring errors, and severity of errors, using validated definitions. Results Prescribing and/or monitoring errors were detected in 4.9% (296/6048) of all prescription items (95% confidence interval [CI] = 4.4% to 5.5%). The vast majority of errors were of mild to moderate severity, with 0.2% (11/6048) of items having a severe error. After adjusting for covariates, patient-related factors associated with an increased risk of prescribing and/or monitoring errors were: age <15 years (odds ratio [OR] = 1.87, 95% CI = 1.19 to 2.94, P = 0.006) or >64 years (OR = 1.68, 95% CI = 1.04 to 2.73, P = 0.035), and higher numbers of unique medication items prescribed (OR = 1.16, 95% CI = 1.12 to 1.19, P<0.001). Conclusion Prescribing and monitoring errors are common in English general practice, although severe errors are unusual. Many factors increase the risk of error. Having identified the most common and important errors, and the factors associated with these, strategies to prevent future errors should be developed, based on the study findings. PMID:23972195
Avery, Anthony J; Ghaleb, Maisoon; Barber, Nick; Dean Franklin, Bryony; Armstrong, Sarah J; Serumaga, Brian; Dhillon, Soraya; Freyer, Anette; Howard, Rachel; Talabi, Olanrewaju; Mehta, Rajnikant L
Objective A nationwide, primary care-based prescription audit in infants to determine the prescribing pattern and prescribing errors\\u000a of topical corticosteroid preparations in Bahrain.\\u000a \\u000a \\u000a \\u000a Method Prescriptions dispensed for infants were collected for two successive weeks from 20 primary-care health centres.\\u000a \\u000a \\u000a \\u000a Results Among 2282 out of 102,084 prescriptions (2.2%) dispensed for infants, 296 (13.0%) had corticosteroids for topical application\\u000a to the skin, eye and ear.
Khalid A. J. Al Khaja; Awatif H. H. Damanhori; Thuraya M. Al-Ansari; Reginald P. Sequeira
Food and Drug Administration-approved information and public advertisements belie neurodegenerative risks for second-generation antipsychotics in affective illness. Package inserts label tardive syndromes "potentially reversible" while uniformly omitting patient counseling for long-term neurodegenerative side effects. I found that only 2 of 78 outpatients exposed to second-generation antipsychotics reported awareness of tardive syndromes. Updated literature challenges safety advantages of atypical versus typical antipsychotics. Physician and patient information regarding tardive syndromes from second-generation antipsychotics approved for affective illness is inadequate. PMID:25521884
Jacobsen, Frederick M
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. PMID:24032065
Lawson, Keith A.; Rudzinski, Jan K.; Vicas, Ingrid; Carlson, Kevin V.
Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI) forms of antipsychotics allow for rapid identification of non-adherence, obviate the need for the patient to take the medication on a daily basis and increase adherence to some significant degree. Eli Lilly has developed a long-acting depot formulation of olanzapine, olanzapine pamoate, which has recently been approved by the FDA for the US market, and which will be reviewed here. Olanzapine LAI appears to be an effective antipsychotic at dosages of 210 mg every 2 weeks, 300 mg every 2 weeks and 405 mg every 4 weeks in patients with acute schizophrenia, and at 150 mg every 2 weeks, 300 mg every 2 weeks and at 405 mg every 4 weeks for the maintenance treatment of stable patients. Oral supplementation appears not to be needed, particularly not at the onset of treatment with the LAI as is necessary with risperidone LAI. Its efficacy is in general comparable to the efficacy seen with oral olanzapine at a corresponding dose. The side effect profile is also comparable to the side effects observed with oral olanzapine, including lower rates of extrapyramidal symptoms, prolactin elevation and cardiovascular side effects, but significant metabolic effects. The latter include significant weight gain, lipid abnormalities and glucose dysregulation. While the injection site adverse events are overall mild, the most significant serious adverse event is the post-injection delirium sedation syndrome (PDSS). While rare, this syndrome results from inadvertent intravascular injection of olanzapine LAI and can cause a range of olanzapine overdose-type of symptoms. Olanzapine LAI needs therefore to be administered by trained personnel in settings where a post-injection observation period for at least 3 hours by medical personnel is available. The overall use of olanzapine LAI will probably be limited by the possibility of a PDSS event. Patients who have a history of good response to oral olanzapine and are in need of assured medication administration may present a good indication for its use, provided that the appropriate mental health delivery setting is available. PMID:20628628
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
Aims Prescribing for athletes requires an up-to-date knowledge of the World Anti-Doping Agency's list of prohibited substances. As the London 2012 Olympic Games attract athletes from around the world, we review the current guidelines with respect to all medications licensed for ophthalmic use in the United Kingdom. We describe the process that an ophthalmologist can use to check for permissible medications and also highlight treatments that are contraindicated. Methods We systematically reviewed all 77 drugs listed in Section 11 of the British National Formulary (Issue 63) for use in the treatment of ophthalmic conditions, and referenced these against the 2012 Prohibited List published by the World Anti-Doping Agency. Results The majority of ophthalmic preparations are suitable for use in- and out-of-competition. Some preparations, such as glucocorticoids, are prohibited when administered systemically but permitted for topical administration. Beta-blockers are prohibited in-competition and oral carbonic anhydrase inhibitors are prohibited in- and out-of competition. Conclusion The 2012 Prohibited List has important implications for the pharmacological treatment of ophthalmic conditions in athletes. Clinicians prescribing for athletes have a duty to familiarise themselves with the list in order to avoid causing significant damage to their patient's career and reputation. PMID:22744394
Nicholson, R G H; Thomas, G P L; Potter, M J; Norris, J H
Tourette's syndrome (TS) is a neuropsychiatric disorder of childhood onset characterized by multiple motor and phonic tics that fluctuate over time. Tic symptoms often improve by late adolescence, but some children and adults with TS may experience significant tic-related morbidity, including social and family problems, academic difficulties, and pain. When more conservative interventions are not successful, and when certain psychiatric co-morbidities further complicate the clinical profile, treating TS with an atypical antipsychotic medication may be a reasonable second-tier approach. However, the evidence supporting efficacy and safety of the atypical antipsychotics for treatment of tics is still very limited. The objective of this paper is to provide an updated overview of the role of atypical antipsychotics for treatment of TS, with evidence-based guidance on their use. Evidence for efficacy of different typical and atypical antipsychotics for treatment of tics was examined by conducting a systematic, keyword-related search of 'atypical antipsychotics' and 'Tourette's syndrome' in PubMed (National Library of Medicine, Washington, DC, USA). Four recent treatment consensus publications were also reviewed. This review focused on literature published from 2000 to 2013 and on available randomized controlled trials in TS. Evidence supporting the use of atypical antipsychotics for treatment of TS is limited. There are few randomized medication treatment trials in TS (i.e. risperidone, aripiprazole, ziprasidone), which employed varying methodologies, thereby restricting meaningful comparisons among studies. Future collaborations among clinical sites with TS expertise employing high-quality study design may better elucidate the role of atypical antipsychotics for treatment of TS. PMID:25034359
Budman, Cathy L
Based on evidence of an increased risk of death, drug agencies issued safety warnings about the use of second generation antipsychotics (SGAs) in the elderly with dementia in 2004. This warning was extended to all antipsychotics in 2008. Little is known about the impact of these warnings on use. We conducted a quasi-experimental study (interrupted time-series) in France, for 2003–2011, including subjects aged ?65 with dementia and subjects aged ?65 without dementia in the EGB database (1/97th representative random sample of claims from the main Health Insurance scheme). Outcomes were monthly rates of use of antipsychotics (by class and agent) and of 5 comparison drug classes (antidepressants, benzodiazepines, dermatologicals, antidiabetics, antiasthmatics). Trends were analyzed by joinpoint regression, impact of warnings by linear segmented regression. In patients with dementia (n=7169), there was a 40% reduction in antipsychotic use from 14.2% in 2003 to 10.2% in 2011. The reduction began before 2004 and was unaffected by the warnings. Use of first generation antipsychotics declined over the period, while use of SGAs increased and leveled off from 2007. Use of the 5 comparison drug classes increased on the period. In subjects without dementia (n=91942), rates of overall antipsychotic use decreased from 2.3% in 2003 to 1.8% in 2011 with no effect of the warnings. Meanwhile, use of SGAs continuously increased from 0.37% to 0.64%. Antipsychotic use decreased in the elderly between 2003 and 2011, especially in dementia. The timing of the decrease, however, did not coincide with safety warnings. PMID:24126116
Gallini, Adeline; Andrieu, Sandrine; Donohue, Julie M; Oumouhou, Naïma; Lapeyre-Mestre, Maryse; Gardette, Virginie
It is well known that abdominal obesity, dyslipidemia, and insulin resistance are highly prevalent in patients receiving maintenance treatment with antipsychotics, but there is limited knowledge about the association between cardiovascular risk factors and treatment with antipsychotic drugs. In this naturalistic study we investigated a sample of 809 antipsychotic-treated patients from Swedish psychosis outpatient teams. Cardiovascular risk factors (eg, metabolic syndrome, homeostasis model assessment of insulin resistance, and low-density lipoprotein values) were measured, and their associations to current antipsychotic pharmacotherapy were studied. Ten antipsychotic drugs were compared in a stepwise logistic regression model. For the patients, the presence of the components of metabolic syndrome ranged from 35% for hyperglycemia to 64% for elevated waist circumference. Hypertriglyceridemia was associated with clozapine (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.08–3.04), reduced high-density lipoprotein with both clozapine and olanzapine (OR = 1.73, 95% CI 1.01–2.97; and OR = 2.03, 95% CI 1.32–3.13), hypertension with perphenazine (OR = 2.00, 95% CI 1.21–3.59), and hyperglycemia inversely with ziprasidone (OR = 0.21, 95% CI 0.05–0.89) and positively with haloperidol (OR = 2.02, 95% CI 1.18–3.48). There were no significant relationships between any of the antipsychotic drugs and increased waist circumference, homeostasis model assessment of insulin resistance, or low-density lipoprotein levels. In conclusion, treatment with antipsychotic drugs is differentially associated with cardiovascular risk factors, even after adjusting for waist circumference, sex, age, and smoking. PMID:23682213
Bodén, Robert; Edman, Gunnar; Reutfors, Johan; Östenson, Claes-Göran; Ösby, Urban
Based on evidence of an increased risk of death, drug agencies issued safety warnings about the use of second generation antipsychotics (SGAs) in the elderly with dementia. The French agency issued a warning in 2004. which was extended to all antipsychotics in 2008. Little is known about the impact of these warnings on use. We conducted a quasi-experimental study (interrupted time-series) in France, for 2003-2011, including subjects aged ?65 with dementia and subjects aged ?65 without dementia in the EGB database (1/97th representative random sample of claims from the main Health Insurance scheme). Outcomes were monthly rates of use of antipsychotics (by class and agent) and of five comparison drug classes (antidepressants, benzodiazepines, dermatologicals, antidiabetics, antiasthmatics). Trends were analyzed by joinpoint regression, impact of warnings by linear segmented regression. In patients with dementia (n=7169), there was a 40% reduction in antipsychotic use from 14.2% in 2003 to 10.2% in 2011. The reduction began before 2004 and was unaffected by the warnings. Use of first generation antipsychotics declined over the period, while use of SGAs increased and leveled off from 2007. Use of the five comparison drug classes increased on the period. In subjects without dementia (n=91,942), rates of overall antipsychotic use decreased from 2.3% in 2003 to 1.8% in 2011 with no effect of the warnings. Meanwhile, use of SGAs continuously increased from 0.37% to 0.64%. Antipsychotic use decreased in the elderly between 2003 and 2011, especially in dementia. The timing of the decrease, however, did not coincide with safety warnings. PMID:24126116
Gallini, Adeline; Andrieu, Sandrine; Donohue, Julie M; Oumouhou, Naïma; Lapeyre-Mestre, Maryse; Gardette, Virginie
Background Chronic non-cancer pain (CNCP) is common in the UK. GPs manage most patients with such pain. Previous research has suggested that prescribing is influenced by patient and doctor factors, but less is known about the decision- making process involved in prescribing opioid drugs for CNCP. Aim To describe the factors influencing GPs’ prescribing of strong opioid drugs for CNCP. Design and setting Semi-structured interviews and a focus group of a purposive sample of GPs from a range of practice settings including male and female GPs with experience of prescribing strong opioids. Method Transcripts of interviews and a focus group were analysed using qualitative research methodology (thematic analysis). Results GPs described prescribing opioid drugs for patients with CNCP as being different from treating cancer related pain. GPs followed accepted stepwise approaches in their prescribing for CNCP. They reported difficulty in assessing the level of pain and concern over duration of use of strong opioids and their possible side effects, tolerance, and addiction. Variation in reported practice was observed, which may be linked to experience and significant events. Conclusion GPs in this study demonstrated a thoughtful attitude towards prescribing strong opioids for CNCP. They were aware of the difficulties of long-term strong opioid prescription. Only a few GPs had had specific training in chronic pain management and this may explain some of the variation in practice reported. GPs may benefit from training in pain assessment and long-term management of patients with CNCP. PMID:24351498
Seamark, David; Seamark, Clare; Greaves, Colin; Blake, Susan
Heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) are the largest group of structurally related proteins encoded by the human genome. As signal effectors and allosteric regulators, GPCRs dynamically recruit not only specific heterotrimeric G proteins but also the cytosolic scaffold proteins, ?-arrestin 1 and 2, which were originally thought only to serve as negative regulators of GPCR signaling. Although about half of currently available therapeutics target GPCR function, usually at the ligand-binding, orthosteric site, evidence suggests that ?-arrestins may be therapeutic targets themselves. Indeed, a hitherto undiscovered action of various antipsychotics is to inhibit the ability of the dopamine D2 receptor to engage ?-arrestin 2 and activate glycogen synthase kinase 3, which may be a target for developing therapeutics for schizophrenia. Also, certain ?-antagonists (blockers) used to treat heart failure, such as carvedilol, have the added effect of promoting activation of extracellular signal-regulated kinase through ?-arrestin. It seems likely that the structure of ?-arrestins allows them to detect different types and conformational states of GPCRs and to respond in functionally distinct fashions by using separate cohorts of signaling proteins, thus generating additional possibilities for therapeutic intervention.
Miles D. Houslay (University of Glasgow; Faculty of Biomedical and Life Sciences REV)
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.
AIMS To establish whether a standard national inpatient medication chart (NIMC) could be implemented across a range of sites in Australia and reduce frequency of prescribing errors and improve the completion of adverse drug reaction (ADR) and warfarin documentation. METHODS A medication chart, which had previously been implemented in one state, was piloted in 22 public hospitals across Australia. Prospective before and after observational audits of prescribing errors were undertaken by trained nurse and pharmacist teams. The introduction of the chart was accompanied by local education of prescribers and presentation of baseline audit findings. RESULTS After the introduction of the NIMC, prescribing errors decreased by almost one-third, from 6383 errors in 15 557 orders, a median (range) of 3 (0–48) per patient to 4293 in 15 416 orders, 2 (0–45) per patient (Wilcoxon Rank Sum test, P < 0.001). The documentation of drugs causing previous ADRs increased significantly from 81.9% to 88.9% of drugs (?2 test, P < 0.001). The documentation of the indication for warfarin increased from 12.1 to 34.3% (?2 test, P = 0.001) and the documentation of target INR increased from 10.8 to 70.0% (?2 test, P < 0.001) after implementation of the chart. CONCLUSIONS National implementation of a standard medication chart is possible. Similar reduction in the rate of prescribing errors can be achieved in multiple sites across one country. The consequent benefits for patient care and training of staff could be significant. PMID:21426371
Coombes, Ian D; Reid, Carol; McDougall, David; Stowasser, Danielle; Duiguid, Margaret; Mitchell, Charles
The aim of this study was to investigate the use of psychotropic medication and therapeutic drug monitoring in a high-security psychiatric unit and to compare the doses and serum concentrations both with the recommended intervals and with the doses and serum concentrations in a control group. One hundred thirty-two patients were admitted in the period from January 2000 to December 2005. All available samples were used when comparing serum concentrations and doses with the recommended ranges. For the comparison of doses and serum concentration-to-dose (C:D) ratios with the control group only 1 sample from each patient was used. A total of 459 analyses of 27 different drugs in samples from 8 women and 73 men were included. The median number of therapeutic drug monitoring analyses per patient was 4 (range 1-29). Thirty-seven of the 81 patients (46%) used 2 or more antipsychotics at the same time. Clozapine, lamotrigine, olanzapine, quetiapine, ziprasidone, and zuclopenthixol were often given in doses above the recommended. The serum levels were frequently above those recommended for clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and zuclopenthixol. The serum levels were significantly higher in the study group than in the control group for clozapine, lamotrigine, quetiapine, and zuclopenthixol. The given dose was significantly higher in the study group than in the control group for clozapine, lamotrigine and zuclopenthixol. The C:D ratio was significantly lower in the study group than in the control group for olanzapine but higher for quetiapine. The non-evidence based practice of high-dose polypharmacy with several antipsychotics is widely used in this unit. The use of higher doses in the study group than in the control group was not due to differences in metabolism or adherence to treatment between the 2 groups. The frequent use of therapeutic drug monitoring did not seem to have a great impact on the prescribed doses. PMID:18708990
Castberg, Ingrid; Spigset, Olav
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
Disturbance of prefrontal brain functions is assumed to be responsible for prominent psychopathological symptoms in psychotic disorders. Treatment with atypical, in contrast to typical antipsychotics is considered as a possible strategy for an improvement of prefrontal brain function. In the present study, response control as a specific prefrontal brain function was assessed by means of the Nogo-anteriorization (NGA) derived from the event-related potentials elicited during a Go-NoGo task in a consecutive sample of 39 patients suffering from acute psychotic disorders (brief psychotic disorders, 298.8, n = 34 and schizoaffective disorders, 295.70, n = 5; cycloid psychoses according to the Leonhard classification). A highly significant positive correlation between the amount of antipsychotic medication in terms of chlorpromazine equivalents per day and the NGA as a measure of prefrontal response control was only found in the subgroup of patients treated exclusively or predominantly with atypical antipsychotics but not for those treated with typical antipsychotics. These results are in line with the notion that atypical antipsychotics may exert a beneficial effect on prefrontal brain function. PMID:15645162
Ehlis, Ann-Christine; Zielasek, Jürgen; Herrmann, Martin J; Ringel, Thomas; Jacob, Christian; Fallgatter, Andreas J
Antipsychotic drugs have been used to treat patients with schizophrenia and other psychotic disorders. Long-acting injectable antipsychotic drugs are useful for improving medication compliance with a better therapeutic option to treat patients who lack insight or adhere poorly to oral medication. Several long-acting injectable antipsychotic drugs are clinically available. Haloperidol decanoate and fluphenazine decanoate are first-generation depot drugs, but the use of these medicines has declined since the advent of second-generation depot agents, such as long-acting risperidone, paliperidone palmitate, and olanzapine pamoate. The second-generation depot drugs are better tolerated and have fewer adverse neurological side effects. Long-acting injectable risperidone, the first depot formulation of an atypical antipsychotic drug, was prepared by encapsulating risperidone into biodegradable microspheres. Paliperidone palmitate is an aqueous suspension of nanocrystal molecules, and olanzapine pamoate is a microcrystalline salt of olanzapine and pamoic acid suspended in aqueous solution. This review summarizes the characteristics and recent research of formulations of each long-acting injectable antipsychotic drug. PMID:23543652
Park, Eun Ji; Amatya, Sarmila; Kim, Myung Sun; Park, Jong Hoon; Seol, Eunyoung; Lee, Heeyong; Shin, Young-Hee; Na, Dong Hee
Depot antipsychotics have been used as a strategy to reduce non-adherence to medications in schizophrenia and bipolar disorder (BD). This article reviews the literature on the efficacy and safety of first- and second-generation depot antipsychotics (FGDA and SGDA, respectively) for the maintenance treatment of BD. Although FGDA have been studied in BD, they have not been approved for use in this disease. Among the SGDA, only depot risperidone has been studied and approved for the maintenance treatment of BD. We found eight studies on FGDA (three on flupenthixol, two on depot haloperidol, one on fluphenazine and flupenthixol, two on a mix of diverse antipsychotics) and ten studies on SGDA (all on depot risperidone). Differences in efficacy and safety were found between the two classes of depot antipsychotics. Although FGDA may be effective in reducing manic relapses, they possibly increase the risk of worsening depression. Depot risperidone is effective as a maintenance treatment in BD with effect noted predominantly for preventing mania. However, no worsening in depression was observed. Depot risperidone also is better tolerated than FGDA, mainly in relation to extrapyramidal symptoms. Studies with the new depot antipsychotics, olanzapine pamoate and paliperidone palmitate, are needed in BD patients. Further, there is currently little information on the metabolic changes (apart from bodyweight gain) that may occur with the use of depot risperidone in patients with bipolar disorder, and this issue needs further investigation. PMID:22494448
Gigante, Alexandre Duarte; Lafer, Beny; Yatham, Lakshmi N
The present post-hoc analysis investigated the speed of onset of therapeutic effect of the atypical antipsychotic, risperidone, in direct comparison with conventional antipsychotics. Data were pooled from four double-blind active comparator-controlled clinical trials involving 757 patients with schizophrenia treated for up to 8 weeks with either risperidone (4-6 mg/day) or a conventional antipsychotic such as haloperidol (10 or 20 mg/day), perphenazine (mean dose 28 mg/day), or zuclopenthixol (mean dose 38 mg/day). Primary outcome was assessed using the Positive and Negative Syndrome Scale. A significantly greater proportion of patients treated with risperidone achieved > or =20% reduction from baseline Positive and Negative Syndrome Scale total score at weeks 1, 2, 6, and at end point (last observation carried forward: P< or =0.04). A significant difference exists in mean reduction from baseline to end point in Positive and Negative Syndrome Scale total scores in favor of patients treated with risperidone compared with those treated with conventional antipsychotics (-18.4 vs -13.5; P=0.0013). The mean time to response was 23.8 days with risperidone and 28.2 days with conventional drugs (hazard ratio 1.3; 95% confidence interval 1.1-1.5). These findings are clinically relevant because the faster onset of therapeutic effect with atypical antipsychotics can be important in the acute setting and have a considerable impact on healthcare systems. PMID:16877896
Glick, Ira D; Shkedy, Ziv; Schreiner, Andreas
We used the electric organ of Torpedo, a modified neuromuscular system, to investigate the direct effects of antipsychotic drugs on cholinergic transmission. All the antipsychotic drugs tested inhibited transmission by decreasing the amount of ACh released by nerve impulses. Their potency for this action was as follows: trifluoperazine less than clozapine less than thiethylperazine less than droperidol less than haloperidol less than chlorpromazine = beta-flupentixol less than alpha-flupentixol. Depression of ACh release by antipsychotics was poorly reversible, and was not mediated by dopamine receptors in this system since neither dopamine nor apomorphine had any effect on transmission. Antipsychotics did not act through presynaptic cholinergic receptors since the effect was not antagonized by atropine or quinuclidinyl benzilate. Trifluoperazine had no effect on the total ACh content of the tissue, on the compartmentation of ACh inside and outside synaptic vesicles, or on the rate of ACh turnover or the accumulation of 45Ca observed after repetitive stimulation. We conclude that antipsychotic drugs depress the neurally evoked release of ACh by acting directly on the releasing mechanism. PMID:2862052
Schaller-Clostre, F; Dunant, Y
The ability to assemble functional materials with precise spatial arrangements is important for applications ranging from protein crystallography to photovoltaics. Here, we describe a general framework for constructing two-dimensional crystals with prescribed depths and sophisticated three-dimensional features. The crystals are self-assembled from single-stranded DNA components called DNA bricks. We demonstrate the experimental construction of DNA brick crystals that can grow to micrometre size in their lateral dimensions with precisely controlled depths up to 80 nm. They can be designed to pack DNA helices at angles parallel or perpendicular to the plane of the crystal and to display user-specified sophisticated three-dimensional nanoscale features, such as continuous or discontinuous cavities and channels. PMID:25343605
Ke, Yonggang; Ong, Luvena L; Sun, Wei; Song, Jie; Dong, Mingdong; Shih, William M; Yin, Peng
We use the format of a hypothetical case study to review issues related to pharmaceutical product approval and physician prescribing practices. In this case, a new FDA-approved drug is recommended for a patient who subsequently experiences an adverse event that may or may not be related to the prescription. This case raises a number of ethical and legal considerations physicians routinely face when deciding whether to recommend such drugs for their patients. Despite the need for ongoing observation by the regulatory apparatus, physicians should be cognizant of the limitations of the drug approval system and the post-approval prescription drug surveillance system. We discuss physicians' ethical obligations when faced with a newly approved drug, including seeking out independent sources of learning, reporting adverse effects, and notifying patients about limitations in available knowledge about therapeutic recommendations. PMID:23180203
Cole, Lindsay W; Kesselheim, Jennifer C; Kesselheim, Aaron S
Complications resulting from the use of compounded medications have become a troubling trend nationwide. There is a significant potential for patients to suffer serious harm from the use of substandard medications prepared by compounding pharmacies, and the reality of this problem has been demonstrated in several well-publicized incidences of serious medical complications, including patient deaths, that directly resulted from the use of medications prepared at compounding pharmacies. Unlike US Food and Drug Administration (FDA)-approved drugs, compounded products are not required to meet evidentiary standards for establishing safety and efficacy. Moreover, these products are not held to Good Manufacturing Practices, which require regular inspections, quality control testing, and rejection of material not meeting specifications. Physicians, as well as other prescribers, need to be aware that when a patient suffers harm from using a compounded medication, those injured patients may bring negligence and malpractice claims, not only against the pharmacy and the pharmacist responsible for preparing the medication, but also against the prescribing physician and the physician’s practice. Consequently, the best way for physicians to manage professional risk and avoid both litigation and potential negative patient outcomes related to compounded pharmaceuticals is to not use these products if there is an FDA-approved product available. However, if the use of a compounded medication is medically necessary, then physicians should adhere to the FDA guidance concerning traditional compounding. Moreover, it would be prudent for any physician who intends to either resell or participate in the distribution of compounded products beyond the direct treatment of their patients to consider obtaining the appropriate insurance coverage for this activity. PMID:25276868
Randell, Michael D; Duffy, Phillip J
Purpose Perinatally HIV-infected children, who are increasingly aging into adolescence and early adulthood, have significant rates of psychiatric co-morbidities, some of which are treated with second-generation antipsychotics (SGAs). SGAs have been associated with elevated total cholesterol (TC) in youth, but no studies have examined this association in perinatally HIV-infected youth. This study examined changes in TC levels of youth with perinatally acquired HIV infection and co-morbid psychiatric conditions treated with SGAs. Patients and methods Long-term changes in TC levels were examined using data from the US multisite prospective Pediatric AIDS Clinical Trials Group 219C cohort study. The change in TC levels from baseline to 12 months after initiating SGA use was compared between 52 SGA-exposed and 148 matched SGA-unexposed perinatally HIV-infected youth, using generalized estimating equation models adjusting for other covariates. The prevalence and time to incident hypercholesterolemia were also compared between these 2 groups. Results After adjustment for confounders, 52 youth with prescriptions for SGAs had a larger increase in TC levels than 148 matched youth without antipsychotic prescriptions (mean difference = 9 mg/dL, z = 1.96, df = 1, P = 0.0496). Among youth with TC below 220 mg/dL at baseline, 27% of SGA-exposed youth developed hypercholesterolemia (defined as two consecutive TC measurements ?220 mg/dL), compared with 13% of SGA-unexposed patients (Fisher's exact test, P = 0.046). Conclusions Caution should be used in prescribing SGAs to perinatally HIV-infected youth with psychiatric co-morbidities due to increased risk of hypercholesterolemia. Patients should be monitored, and alternative evidence-based treatments considered when available. PMID:20865061
Kapetanovic, Suad; Aaron, Lisa; Williams, Paige L; Farley, John; Sirois, Patricia A; Garvie, Patricia A; Pearson, Deborah A; Oleske, James M; Montepiedra, Grace
Context: Drug-drug interactions(DDIs) are significant but avoidable causes of iatrogenic morbidity and hospital admission. Aim: To detect potential drug-drug interactions among medications received by hypertensive patients. Materials and Methods: Patients of both sex and all adult age groups, who were attending medicine out -patient department (OPD) of a tertiary care teaching rural hospital since last six months and were being prescribed antihypertensive drug/s for essential hypertension, were selected for the study. Hypertensive patient with co-morbities diabetes mellitus, ischemic heart diseases, congestive heart failure, and chronic renal diseases were also included in the study. Potential drug drug interactions were checked with medscape drug interaction software. Results: With the help of medscape drug interaction software, 71.50% prescriptions were identified having atleast one drug-drug interaction. Total 918 DDIs were found in between 58 drug pairs. 55.23% DDIs were pharmacodynamic, 4.79% pharmacokinetic type of DDIs. 32.24% DDIs were found affecting serum potassium level. 95.42% DDIs were found significant type of DDIs. Drug drug interaction between atenolol & amlodipine was the most common DDI (136) followed by metoprolol and amlodine (88) in this study. Atenolol and amlodipine ( 25.92%) was the most common drugs to cause DDIs in our study. Conclusion: We detected a significant number of drug drug interaction in hypertensive patients. These interactions were between antihypertensive agents or between hypertensive and drug for co-morbid condition. PMID:25584241
In the past few decades, opioid use for the treatment of chronic noncancer pain has slowly gained acceptance. With this increase in prescription opioid use, there has also been an increase in prescription opioid abuse. To help detect aberrant drug related behaviors, clinicians have utilized urine drug screens to determine patient noncompliance in outpatient pain clinics. The primary objective is to determine how the use of urine drug testing (UDT) affects health care outcomes. The secondary outcome is to evaluate these findings as it relates to pharmacoeconomics and aberrant behaviors in an outpatient clinical setting. In this study we will determine if UDT influences prescribing practices among physicians. Patients at an academic center's chronic pain outpatient clinic were categorized as having urine screens that were "normal" (expected findings based on their prescribed drugs) or abnormal. Abnormal findings were those with either 1) the absence of a prescribed opioid, 2) the presence of an additional nonprescribed controlled substance, 3) detection of an illicit substance, or 4) an adulterated urine sample. We examined the incidence of such aberrant behaviors as well as concomitant pain diagnoses, psychiatric comorbidities, and the ultimate effect upon the prescribing patterns of the physicians in this clinic. Results of the study showed that the patients exhibiting aberrant drug behaviors have similar pain and psychiatric diagnoses as other chronic pain patients. The most common aberrancy detected was an abnormal urine drug screen, often with the presence of illegal substances. However, in the great majority of aberrancies detected, providers chose to continue prescribing opioids. We speculate on the reasons for this, and discuss the role of the urine drug screen in influencing prescriber behaviors. PMID:21785482
Gupta, Anita; Patton, Christopher; Diskina, Dina; Cheatle, Martin
The prevalence of diabetes mellitus and metabolic syndrome is higher in patients with schizophrenia than in the normal population. Atypical antipsychotic drugs are used in psychiatry since the beginning of 1990. These drugs differ from the “typical” antipsychotics used previously, as they have less extrapyramidal side effects, and because of this they are tolerated better, but are associated with weight-gain
E. Palik; K. D. Birkás; G. Faludi; I. Karádi; K. Cseh
Background: We investigated antipsychotic drug prescription practice of Dutch ID physicians, studying prevalence of antipsychotic drug use, reasons for prescription and the relationship between these reasons and patient characteristics. Methods: A cross-sectional study of medical and pharmaceutical records in a population living in residential…
de Kuijper, G.; Hoekstra, P.; Visser, F.; Scholte, F. A.; Penning, C.; Evenhuis, H.
Background: Rising public and private expenditure on antipsychotic medications is concentrated on the cost of second generation or `atypical' medications, which are more expensive than first generation medications and make up a rapidly growing share of all antipsychotic prescriptions. Previous studies have examined whether the higher acquisition costs of atypicals are offset by other cost and\\/or utilisation benefits. This paper
David Salkever; Eric Slade; Mustafa Karakus
Antipsychotic medication-induced dysphoria is a relatively under-recognized and understudied effect of antipsychotic medication. Although the term is encountered in clinical practice and in the literature, there is no consensus regarding its exact meaning. This article is a narrative review of the literature on antipsychotic medication and dysphoria based on a pubmed database search. We found that antipsychotic medication-induced dysphoria is a term used to describe a negative and unpleasant affective state which seems to be more often associated with high potency first-generation antipsychotics and could potentially lead to medication non-adherence. Though it is plausible to expect antipsychotic medication-induced dysphoria to be related to extrapyramidal symptoms, most especially akathisia, the nature of the association remains unspecified. Furthermore, there is some evidence that dopamine blockade maybe involved in the pathogenesis of antipsychotic medication-induced dysphoria. However, the limited methods of the currently available studies make it impossible to conclusively address the question of which class of antipsychotic (first- or second-generation) has a higher prevalence and severity of the syndrome. PMID:25164199
Wu, Hanjing Emily; Okusaga, Olaoluwa O
Aims The aim of this study was to investigate the prolactin (PRL) secretion and the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis in relation to gender and side-effects and dose of antipsychotic drugs during long-term treatment. Methods Forty-seven patients (21 men and 26 women), diagnosed with schizophrenia or related psychoses according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria and treated with different classical antipsychotics, were studied. Prolactin, GH and IGF-I were measured, as well as the serum concentration of the antipsychotics. In addition, body mass index (BMI) was calculated. Results The median daily, as well as the median body weight, adjusted daily dose of antipsychotic drugs was twofold higher in male compared with female patients. Antipsychotic-induced hyperprolactinaemia was more frequent and occurred at a lower daily dose of antipsychotics in women. Irrespective of sex, more than half of the patients had elevated BMI. Two patients had a slight increment in IGF-I levels, whereas the GH concentration, as assessed on a single occasion, was normal in all patients. Conclusions Patients on long-term antipsychotic therapy, with doses adjusted according to therapeutic efficiency, exhibited hyperprolactinaemia and elevated BMI, but no obvious influence on the GH-IGF-I axis. Furthermore, it appeared that the males required twice the dose of antipsychotic compared with females. PMID:11318766
Melkersson, Kristina I; Hulting, Anna-Lena; Rane, Anders J
The National Institute of Mental Health initiated the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) program to evaluate the effectiveness of antipsychotic drugs in typical settings and populations so that the study results will be maximally useful in routine clinical situations. The CATIE schizophrenia trial blends features of efficacy studies and large, simple trials to create a pragmatic trial that
T. Scott Stroup; Joseph P. McEvoy; Marvin S. Swartz; Matthew J. Byerly; Ira D. Glick; Jose M. Canive; Mark F. McGee; George M. Simpson; Michael C. Stevens; Jeffrey A. Lieberman
Microglia are resident innate immune cells which release many factors including proinflammatory cytokines, nitric oxide (NO) and neurotrophic factors when they are activated in response to immunological stimuli. Recent reports show that pathophysiology of schizophrenia is related to the inflammatory responses mediated by microglia. Intracellular Ca2+ signaling, which is mainly controlled by the endoplasmic reticulum (ER), is important for microglial functions such as release of NO and cytokines, migration, ramification and deramification. In addition, alteration of intracellular Ca2+ signaling underlies the pathophysiology of schizophrenia, while it remains unclear how typical or atypical antipsychotics affect intracellular Ca2+ mobilization in microglial cells. This mini-review article summarizes recent findings on cellular mechanisms underlying the characteristic differences in the actions of antipsychotics on microglial intracellular Ca2+ signaling and reinforces the importance of the ER of microglial cells as a target of antipsychotics for the treatment of schizophrenia. PMID:25414641
Mizoguchi, Yoshito; Kato, Takahiro A.; Horikawa, Hideki; Monji, Akira