quetiapine-fumarate and Mental-Disorders

Quetiapine is a second-generation antipsychotic that is most favoured for its low propensity for extrapyramidal side effects. However, Quetiapine requires slow titration, which is disadvantageous. The brief review discussed research that trialled rapid titration of Quetiapine The author searched PubMed, Proquest, Embase, Google Scholar and Google Web using the keyword 'rapid titration' and 'quetiapine'. A total of 18 articles were included. The process, safety and efficacy of rapid titration of Quetiapine was examined. In conclusion, preliminary results appear to show that there is minimal difference in efficacy, between the rapid and traditional titration of Quetiapine. Sedation tended to occur more frequently and earlier among experimental group, and this might render rapid titration of Quetiapine to be suitable for agitated patients. There is a need for more large-scale, multisite, randomized clinical trials to examine the safety and efficacy of rapid titration of Quetiapine.

Topics: Antipsychotic Agents; Humans; Mental Disorders; Outcome Assessment, Health Care; Quetiapine Fumarate

Up to 75% of people with serious mental illness (SMI) such as schizophrenia and bipolar disorder have co-occurring substance use disorders (dual diagnosis). Dual diagnosis can have an adverse effect on treatment and prognosis of SMI.. To evaluate the effects of risperidone compared to treatment with other antipsychotics (first-generation and other second-generation antipsychotics) used in people with serious mental illness and co-occurring substance misuse.. On 6 January 2016 and 9 October 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (including trial registers).. We selected randomised trials of risperidone versus any other antipsychotic in people with SMI and substance abuse (dual diagnosis). We included trials meeting our inclusion criteria and reporting useable data. We excluded trials that either did not meet our inclusion criteria or met our inclusion criteria but did not report any useable data.. We independently inspected citations and selected studies. For included studies, we independently extracted data and appraised study quality. For binary outcomes we calculated the risk ratios (RRs) and their 95% confidence intervals. For continuous outcomes we calculated the mean differences (MDs) and their 95% confidence intervals. We pooled data using random-effects meta-analyses and assessed the quality of evidence, creating a 'Summary of findings' table using the GRADE approach.. We identified eight randomised trials containing a total of 1073 participants with SMI and co-occurring substance misuse. Seven of these contributed useable data to the review. There was heterogeneity in trial design and measurement. Risperidone was compared to clozapine, olanzapine, perphenazine, quetiapine and ziprasidone. Few trials compared risperidone with first-generation agents. Few trials examined participants with a dual diagnosis from the outset and most trials only contained separate analyses of subgroups with a dual diagnosis or were secondary data analyses of subgroups of people with a dual diagnosis from existing larger trials.For risperidone versus clozapine we found no clear differences between these two antipsychotics in the reduction of positive psychotic symptoms (1 randomised controlled trial (RCT), n = 36, mean difference (MD) 0.90, 95% CI -2.21 to 4.01, very low quality evidence), or reduction in cannabis use (1 RCT, n = 14, risk ratio (RR) 1.00, 95% CI 0.30 to 3.35, very low quality evidence), improvement in subjective well-being (1 RCT, n = 36, MD -6.00, 95% CI -14.82 to 2.82, very low quality evidence), numbers discontinuing medication (1 RCT, n = 36, RR 4.05, 95% CI 0.21 to 78.76, very low quality evidence), extrapyramidal side-effects (2 RCTs, n = 50, RR 2.71, 95% CI 0.30 to 24.08; I² = 0%, very low quality evidence), or leaving the study early (2 RCTs, n = 45, RR 0.49, 95% CI 0.10 to 2.51; I² = 34%, very low quality evidence). Clozapine was associated with lower levels of craving for cannabis (1 RCT, n = 28, MD 7.00, 95% CI 2.37 to 11.63, very low quality evidence).For risperidone versus olanzapine we found no clear differences in the reduction of positive psychotic symptoms (1 RCT, n = 37, MD -1.50, 95% CI -3.82 to 0.82, very low quality evidence), reduction in cannabis use (1 RCT, n = 41, MD 0.40, 95% CI -4.72 to 5.52, very low quality evidence), craving for cannabis (1 RCT, n = 41, MD 5.00, 95% CI -4.86 to 14.86, very low quality evidence), parkinsonism (1 RCT, n = 16, MD -0.08, 95% CI -1.21 to 1.05, very low quality evidence), or leaving the study early (2 RCT, n = 77, RR 0.68, 95% CI 0.34 to 1.35; I² = 0%, very low quality evidence).For risperidone versus perphenazine, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 281, RR 1.05, 95% CI 0.92 to 1.20, low-quality evidence).For risperidone versus quetiapine, we found no clear differences in the number of participants leaving th. There is not sufficient good-quality evidence available to determine the effects of risperidone compared with other antipsychotics in people with a dual diagnosis. Few trials compared risperidone with first-generation agents, leading to limited applicability to settings where access to second-generation agents is limited, such as in low- and middle-income countries. Moreover, heterogeneity in trial design and measurement of outcomes precluded the use of many trials in our analyses. Future trials in this area need to be sufficiently powered but also need to conform to consistent methods in study population selection, use of measurement scales, definition of outcomes, and measures to counter risk of bias. Investigators should adhere to CONSORT guidelines in the reporting of results.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Diagnosis, Dual (Psychiatry); Humans; Mental Disorders; Olanzapine; Patient Dropouts; Perphenazine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Substance-Related Disorders; Thiazoles

The atypical antipsychotic quetiapine has been used in different psychotic and non-psychotic disorders in children and adolescents in randomized clinical trials, open-label studies and chart reviews. Most of these studies suggest that quetiapine may be a promising agent with a potential for use in young patients. The aim of this paper is to critically review available literature on quetiapine in the treatment of children and adolescents with a variety of psychiatric disorders, including psychotic disorders, bipolar disorders (manic and depressive episodes), conduct disorder, autism spectrum disorder, Tourette's syndrome and personality disorders. Furthermore, we report on possible neurochemical pathways involved during treatment with quetiapine, and discuss some issues that are clinically relevant in daily practice, such as titration strategies, safety and tolerability, and monitoring possible side effects. Controlled studies support the short-term efficacy for treating psychosis, mania, and aggression within certain diagnostic categories. However, although quetiapine seems well tolerated in various pediatric populations during acute and intermediate treatments, and hyper-prolactinemia and extra-pyramidal side effects are consistently low among studies, weight gain and alterations in lipid profile need to be closely monitored. Furthermore, the distal benefit/risk ratio during long-term treatment remains to be determined.

Topics: Adolescent; Antipsychotic Agents; Child; Dibenzothiazepines; Humans; Mental Disorders; Quetiapine Fumarate; Weight Gain

Antipsychotic medications are being prescribed for a growing number of women with mental illnesses. However, evidence regarding their safety in pregnancy is still insufficient to provide adequate support for clinical practice, creating increasing concern among pregnant women and clinicians.. The aim of this article is to review published data regarding the safety of antipsychotic medications in pregnancy with a focus on the most commonly used atypical antipsychotics.. Given the potential harm of not treating severe psychiatric illnesses during pregnancy, careful administration of antipsychotics is recommended for pregnant women who suffer from severe mental disorders. The most frequently used antipsychotics in pregnancy are olanzapine, risperidone and quetiapine, and do not appear to cause consistent, congenital harm to the fetus. No specific patterns of fetal limb or organ malformation related to these drugs have been reported. There is some evidence suggesting an association between antipsychotic use in pregnancy and the development of gestational diabetes. Also there appears to be an association between antipsychotic medication use in pregnancy and increased neonatal respiratory distress and withdrawal symptoms. Further studies are needed for clinicians to balance good maternal mental health, healthy pregnancies and good infant health outcomes.

Topics: Abnormalities, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Maternal-Fetal Exchange; Mental Disorders; Olanzapine; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Prospective Studies; Quetiapine Fumarate; Risperidone

Quetiapine (Seroquel(®)) is a potent U.S. Food and Drug Administration (FDA)-approved antipsychotic agent that has been used extensively for off-label indications. The current study was performed to ascertain the efficacy of some of the most prevalent off-label uses of this agent. An extensive search of electronic databases was completed using the search terms quetiapine or Seroquel, off-label and anxiety, substance abuse, dementia, delirium, personality disorder, insomnia, and sleep. Data were predictably mixed according to the indication being examined. The strongest evidence exists for anxiety and delirium. Moderate evidence exists for quetiapine as a pharmacological intervention for insomnia, dementia, and specific personality disorders. Evidence for quetiapine as a treatment for substance abuse is limited. More data are needed to establish specific dosing regimens for off-label uses and to examine the dose relationship to metabolic side effects and extrapyramidal side effects to determine whether various off-label uses justify the risk incurred with using this powerful drug.

Topics: Antipsychotic Agents; Anxiety Disorders; Delirium; Dementia; Dibenzothiazepines; Humans; Mental Disorders; Off-Label Use; Personality Disorders; Quetiapine Fumarate; Sleep Initiation and Maintenance Disorders; Substance-Related Disorders; Treatment Outcome

We report on seven cases of restless legs syndrome (RLS) in patients treated with quetiapine. Small doses (50-250 mg at bedtime) provoked RLS in a dose-dependent way. Most patients suffered from an affective disorder and all were treated concomitantly with antidepressants. A search of the literature revealed a further nine cases of RLS concerning quetiapine, also afflicting only patients with affective disorders. Quetiapine seems to carry a special risk for RLS in this sort of patient. Possible causes for this concurrence are discussed.

Topics: Adult; Aged; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Male; Mental Disorders; Middle Aged; Quetiapine Fumarate; Restless Legs Syndrome

Quetiapine extended-release (quetiapine-XR) has been studied in patients with schizophrenia, bipolar mania, bipolar depression, major depressive disorder (MDD), and generalized anxiety disorder (GAD). The purpose of this study was to compare the tolerability and sensitivity of quetiapine-XR among these psychiatric conditions. The discontinuation due to adverse events (DAEs) and reported somnolence in randomized, double-blind, placebo-controlled studies of quetiapine-XR in these psychiatric conditions were examined. The absolute risk reduction or increase and the number needed to treat to benefit (NNTB) or harm (NNTH) for DAEs and reported somnolence of quetiapine-XR ≥ 300 mg/d relative to placebo were estimated. Data from one study in schizophrenia (n=465), one in mania (n=316), one in bipolar depression (n=280), two in refractory MDD (n=624), two in MDD (n=669) and three in GAD (n=1109) were available. The risk for DAEs of quetiapine-XR relative to placebo was significantly increased in bipolar depression (NNTH=9), refractory MDD (NNTH=8), MDD (NNTH=9), and GAD (NNTH=5), but not in schizophrenia and mania. The risk for reported somnolence of quetiapine-XR relative to placebo was significantly increased in schizophrenia (600 mg/d NNTH=15 and 800 mg/d NNTH=11), mania (NNTH=8), bipolar depression (NNTH=4), refractory MDD (NNTH=5), MDD (NNTH=5) and GAD (NNTH=5). These results suggest that patients with GAD had the poorest tolerability during treatment with quetiapine-XR, but they had a similar sensitivity as those with bipolar depression and MDD. Patients with schizophrenia or mania had a higher tolerability and a lower sensitivity than those with bipolar depression, MDD, or GAD.

Topics: Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Humans; Mental Disorders; Placebos; Quetiapine Fumarate; Risk; Schizophrenia; Treatment Outcome

The atypical antipsychotic, quetiapine, is frequently prescribed on-label and off-label for the treatment of a variety of psychiatric disorders. As quetiapine has variable affinity for dozens of receptors, its clinical effects should also show a large variation as a function of dose and diagnostic category. This study attempts to elucidate the dose-response and comparative efficacy and tolerability (metabolic data) of quetiapine across psychiatric disorders. A systematic search was carried out in the electronic databases, PubMed and EMBASE, using the keywords 'quetiapine' and 'placebo'. Both monotherapy and add-on studies were included. A total of 41 studies were identified. In unipolar and bipolar depression, studies consistently found quetiapine to be effective versus placebo, at doses of approximately 150-300 and 300-600 mg per day, respectively. In bipolar mania, they consistently found quetiapine to be effective at doses of approximately 600 mg per day. In acute exacerbation of schizophrenia, the majority of studies found quetiapine to be effective at doses of approximately 600 mg per day; however, a few large studies found no difference versus placebo. In contrast, studies consistently found quetiapine to be more effective than placebo for stable schizophrenia. In obsessive-compulsive disorder, studies did not consistently find quetiapine to be effective at doses of approximately 300 mg per day. However, studies may have underestimated the efficacy of quetiapine for obsessive-compulsive disorder due to concomitant administration of antidepressants and the utilization of treatment-refractory patients. In generalized anxiety disorder, studies consistently found quetiapine to be effective at doses of approximately 150 mg per day. Finally, analysis of metabolic tolerability data suggests that even low doses of quetiapine may lead to increase in weight and triglycerides across psychiatric disorders. Interestingly, however, quetiapine-induced elevations in low-density lipoprotein and total cholesterol seem to be restricted to schizophrenia patients.

Topics: Antipsychotic Agents; Controlled Clinical Trials as Topic; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Mental Disorders; Metabolism; Quetiapine Fumarate; Treatment Outcome

The development of effective treatments for alcohol use disorders represents an important public health concern. Quetiapine, a multiple receptor antagonist at 5-HT(1A) and 5-HT(2A), dopamine D(1) and D(2), histamine H(1), and adrenergic α(1) and α(2) receptors, is an atypical antipsychotic medication that has recently shown promise for the treatment of alcoholism.. This manuscript reviews the rationale and empirical literature suggesting that quetiapine may be useful for the treatment of alcohol use disorders, including a discussion of its putative neurobiological and biobehavioural mechanisms of action.. The effects of quetiapine on drinking outcomes may be due to its effects on mood, anxiety and sleep, which may help alleviate protracted withdrawal symptoms and address psychiatric comorbidities often associated with alcohol use disorders.. These findings have implications to treatment development for alcoholism and suggest that the scientific study of quetiapine for alcoholism warrants further resources and attention.. Quetiapine has advanced as a potentially promising pharmacotherapy for alcoholism. Additional research is needed to more clearly ascertain its clinical utility as a stand-alone treatment for this indication, as well as to identify patients who are more likely to respond favourably to this medication.

Topics: Affect; Alcoholism; Antipsychotic Agents; Anxiety; Diagnosis, Dual (Psychiatry); Dibenzothiazepines; Humans; Mental Disorders; Quetiapine Fumarate; Sleep Wake Disorders; Substance Withdrawal Syndrome

To evaluate the use of immediate-release quetiapine for the treatment of insomnia.. Pre-MEDLINE and MEDLINE were searched (1966 to October 2008) using the terms quetiapine, sleep, insomnia, and antipsychotics.. All studies and case reports evaluating insomnia as a primary endpoint were reviewed.. The role of quetiapine for improving sleep in various patient populations is uncertain. Quetiapine has moderately sedative properties, and doses used in treatment of insomnia have ranged from 12.5 to 800 mg. Results of clinical trials and observations in case studies have revealed possible beneficial effects of quetiapine on several subjective and objective sleep parameters. In most studies, significant improvements in sleep were found in areas of total sleep time, sleep efficiency, and subjective sleep scores. However, some of these results may not be clinically significant. Also, quetiapine has been found to have adverse effects such as periodic leg movements, akathisia, and metabolic complications. Additionally, changes in rapid eye movement (REM) and percentage of REM sleep have been noted in different populations and need further study. Despite quetiapine's sedative properties, current data do not appear to support its use as first-line treatment for sleep complications. However, it may be useful for treatment of insomnia in patients with psychiatric disorders (eg, bipolar, schizophrenia) who do not respond to primary or secondary treatments.. Further studies are needed to define the placement, dose, and adverse effects of quetiapine for the treatment of sleep problems.

Topics: Animals; Dibenzothiazepines; Humans; Mental Disorders; Quetiapine Fumarate; Sleep; Sleep Initiation and Maintenance Disorders

Topics: Adult; Antipsychotic Agents; Deinstitutionalization; Diagnosis, Dual (Psychiatry); Dibenzothiazepines; Fear; Female; Health Services Needs and Demand; Hospitals, Psychiatric; Hospitals, State; Humans; Malingering; Mental Disorders; Prisoners; Psychiatric Nursing; Quetiapine Fumarate; Social Isolation; Substance-Related Disorders; Treatment Refusal

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Behavioral Symptoms; Benzodiazepines; Dementia; Dibenzothiazepines; Drug Approval; Humans; Mental Disorders; Olanzapine; Quetiapine Fumarate; Risk; Risperidone; United States; United States Food and Drug Administration

To review published reports of the usage of atypical antipsychotics for behavioural problems of dementia patients.. The electronic database Medline was searched from 1999 to 2006 with a combination of search terms including 'behavioural problems' and 'atypical antipsychotics'.. Thirteen eligible studies were included in the overall analysis. The total number of participants was 1,683, of whom 1,015 received medication and 668 received placebo. Medications studied were risperidone, olanzapine, and quetiapine. Other studies examined other types of medications, such as typical versus atypical antipsychotics, but only data for atypical antipsychotics were included in the meta-analysis. The mean effect size for 7 placebo-controlled studies was 0.45 (95% CI = 0.16-0.74) for atypical antipsychotics, and 0.32 (95% CI = 0.10-0.53) for placebo. The mean effect size of all 13 studies included in the analysis was 0.31 (95% CI = 0.08-0.54).. In general, effect sizes of atypical antipsychotics for behavioural problems are medium, and there are no statistically or clinically significant differences between atypical antipsychotics and placebo.

Topics: Antipsychotic Agents; Benzodiazepines; Controlled Clinical Trials as Topic; Dementia; Dibenzothiazepines; Follow-Up Studies; Humans; Mental Disorders; Olanzapine; Quetiapine Fumarate; Risperidone

This article reviews the off-label prescription of quetiapine in the treatment of a broad range of psychiatric disorders including obsessive-compulsive disorder, post-traumatic stress disorder, personality disorder, substance abuse, bipolar disorder (now US FDA approved), anxiety and depression. The article highlights the primary reliance on selective serotonin reuptake inhibitors (SSRIs) in the treatment of these disorders (cf bipolar disorder) and the high percentage of patients (30-60%) that do not respond to SSRIs. The studies suggest that low-dose quetiapine shows good tolerability and efficacy in patients diagnosed with these disorders, particularly in the case of treatment-resistant patients that do not respond to primary treatments including SSRIs and cognitive-behavioral therapy. Quetiapine generally appears to be very effective in trauma-related conditions by improving autonomic stability, and decreasing the stress and anxiety response that arises due to specific fears or triggers. Quetiapine also appears to be particularly useful for normalizing obsessions and compulsions, and improving low mood, irritability and aggressiveness. A greater understanding of the pharmacology of drug alternatives and the neurobiology of psychiatric disorders is required to permit a more personalized medicine approach.

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Prescriptions; Humans; Mental Disorders; Obsessive-Compulsive Disorder; Personality Disorders; Quetiapine Fumarate; Stress Disorders, Post-Traumatic; Substance-Related Disorders

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Dyslipidemias; Glucose Metabolism Disorders; Humans; Insulin Resistance; Mental Disorders; Obesity; Olanzapine; Phenothiazines; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles

Aggression, agitation or psychosis occur in the majority of people with dementia at some point in the illness. There have been a number of trials of atypical antipsychotics to treat these symptoms over the last five years, and a systematic review is needed to evaluate the evidence in a balanced way.. To determine whether evidence supports the use of atypical antipsychotics for the treatment of aggression, agitation and psychosis in people with Alzheimer's disease.. The trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 December 2004 using the terms olanzapine, quetiapine, risperidone, clozapine, amisulpride, sertindole, zotepine, aripiprazole, ziprasidone. This Register contains articles from all major healthcare databases and many ongoing trials databases and is updated regularly.. Randomised, placebo-controlled trials, with concealed allocation, where dementia and psychosis and/or aggression were assessed.. 1. Two reviewers extracted data from included trials2. Data were pooled where possible, and analysed using appropriate statistical methods3. Analysis included patients treated with an atypical antipsychotic, compared with placebo. Sixteen placebo controlled trials have been completed with atypical antipsychotics although only nine had sufficient data to contribute to a meta-analysis and only five have been published in full in peer reviewed journals. No trials of amisulpiride, sertindole or zotepine were identified which met the criteria for inclusion. The included trials led to the following results:1. There was a significant improvement in aggression with risperidone and olanzapine treatment compared to placebo.2. There was a significant improvement in psychosis amongst risperidone treated patients.3. Risperidone and olanzpaine treated patients had a significantly higher incidence of serious adverse cerebrovascular events (including stroke), extra-pyramidal side effects and other important adverse outcomes.4. There was a significant increase in drop-outs in risperidone (2 mg) and olanzapine (5-10 mg) treated patients.5. The data were insufficient to examine impact upon cognitive function.. Evidence suggests that risperidone and olanzapine are useful in reducing aggression and risperidone reduces psychosis, but both are associated with serious adverse cerebrovascular events and extra-pyramidal symptoms. Despite the modest efficacy, the significant increase in adverse events confirms that neither risperidone nor olanzapine should be used routinely to treat dementia patients with aggression or psychosis unless there is marked risk or severe distress. Although insufficient data were available from the considered trials, a meta-analysis of seventeen placebo controlled trials of atypical neuroleptics for the treatment of behavioural symptoms in people with dementia conducted by the Food and Drug Administration (using data not in the public domain) suggested a significant increase in mortality (OR 1.7).

Topics: Aggression; Alzheimer Disease; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Piperazines; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone

Atypical antipsychotics offer superior safety and similar efficacy compared with conventional agents in adults with psychotic disorders. Consequently, atypical antipsychotics have been increasingly used in children and adolescents. Because most information now available on pediatric use comes from case reports and small open-label studies rather than large controlled trials, treatment in pediatric patients is often guided by experience with adults or based on limited evidence in youths. Although the literature contains reports on the use of each agent in this class in children, risperidone has been the focus of the greatest number of reports. However, the atypical antipsychotics are not interchangeable; each has a unique pharmacologic profile and may differ considerably in terms of adverse effects. Evidence on the use of atypical antipsychotics in children and adolescents is summarized in this review.

Topics: Adolescent; Age Factors; Antipsychotic Agents; Attention Deficit and Disruptive Behavior Disorders; Benzodiazepines; Bipolar Disorder; Child; Child Development Disorders, Pervasive; Clozapine; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Tic Disorders

Pharmacotherapy in patients with dementia aims to improve distressing behavioral and psychological signs of dementia after nonpharmacologic interventions fail, without causing unacceptable side effects or exacerbating underlying cognitive impairment. We review data describing risperidone (3 published placebo-controlled trials), olanzapine (1 abstract regarding a placebo-controlled trial and a published placebo-controlled trial), quetiapine (1 published open-label trial and an abstract regarding a placebo-controlled trial), and aripiprazole (1 abstract regarding a placebo-controlled trial). For example, a 12-week study of risperidone in patients with Alzheimer's disease showed a dose-related improvement in psychosis and agitation. The frequency of extrapyramidal symptoms (EPS) was also significantly greater in patients receiving the highest doses. A 6-week study of olanzapine showed greater improvement than placebo in agitation/aggression and psychosis with doses of 5 and 10 mg/day, but not 15 mg/day, with side effects including gait disturbance and sedation at all doses. A 52-week, open-label trial of quetiapine (median dose = 138 mg/day) in elderly patients with psychosis suggested good tolerability with apparent behavioral benefit; EPS improved or remained unchanged in most patients. Limited data describing aripiprazole have shown inconclusive evidence regarding relief of psychosis in elderly patients with Alzheimer's disease-related dementia, with apparently good tolerability over the short term. It appears that, in the aggregate, atypical antipsychotics are efficacious for treatment of agitation in dementia, with less clear impact on psychosis, but their tolerability profiles clearly differ. The National Institute of Mental Health-funded Clinical Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease project will provide the first head-to-head comparisons of atypicals in dementia and will examine possible drug-drug differences between efficacy and effectiveness.

Topics: Aged; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Controlled Clinical Trials as Topic; Dementia; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Treatment Outcome

For any treatment, the impact on quality of life (QoL) is a key consideration. These issues are particularly important in the pharmacologic management of behavioral and psychological symptoms in patients with dementia (BPSD). Although these symptoms can be very distressing for some patients, the overall relationship of the symptoms with QoL is far less clear. In addition, although antipsychotic agents have moderate efficacy in the short- to medium-term management of these symptoms, it cannot be assumed that symptom resolution automatically equates with improved QoL. This is of particular concern in light of the adverse side effect profiles of many of these agents. Indeed, the only empirical study in this area conducted to date indicated that antipsychotics are associated with a worse QoL for nursing home patients. Unfortunately, none of the placebo-controlled trials of antipsychotics for the treatment of BPSD have included formal QoL measures, although preliminary evidence indicates that atypical antipsychotics such as quetiapine may result in QoL improvements. The inclusion of systematic QoL measures in future clinical trials is imperative in order to provide evidence to enable the clinician to make informed judgments regarding the potential benefits or risks of pharmacologic treatment for individual patients. In addition, such information will facilitate a better understanding of the likely factors that may contribute to the impact of treatment on QoL (e.g., side effects) and hence enable physicians to make rational treatment choices between different pharmacologic agents.

Topics: Aged; Antipsychotic Agents; Choice Behavior; Controlled Clinical Trials as Topic; Dementia; Dibenzothiazepines; Double-Blind Method; Homes for the Aged; Humans; Mental Disorders; Nursing Homes; Practice Patterns, Physicians'; Quality of Life; Quetiapine Fumarate; Risperidone; Treatment Outcome

Five new antipsychotic drugs introduced in the United States in the last decade offer physicians the ability to treat patients with schizophrenia and bipolar mania without the adverse effects of the first-generation antipsychotics. In this article, the authors discuss the advantages and side effects of these agents and present a guide to help physicians choose the optimal drug in the most favorable formulation for each patient.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 2; Dibenzothiazepines; Drug Administration Schedule; Humans; Hyperprolactinemia; Mental Disorders; Olanzapine; Patient Compliance; Piperazines; Practice Guidelines as Topic; Prescription Fees; Quetiapine Fumarate; Quinolones; Risk Assessment; Risperidone; Thiazoles; Torsades de Pointes; Treatment Outcome; Weight Gain

There are now five new-generation atypical psychiatric medications currently available. As these new treatments have become more common, they have grown to account for a significant percentage of all psychiatric medications prescribed. This is because of their efficacy in the treatment of several psychiatric disorders, ease of administration, and absence of the well-known extrapyramidal adverse effects long-attributed to the standard dopamine blocking anti-psychotic medications. As these medications have become treatments of choice, we have discovered additional information about their respective side effects. Issues such as bone marrow suppression, endocrine abnormalities, and most recently cardiac arrhythmia have produced concern. This paper will address all in an attempt to inform the primary care physician of the most prominent and clinically relevant adverse effects of these agents. A particular focus will address the increasing concern that these new medications can produce hyperglycemia and diabetes mellitus.

Topics: Adult; Aged; Antipsychotic Agents; Arrhythmias, Cardiac; Benzodiazepines; Black or African American; Bone Marrow Diseases; Child; Dibenzothiazepines; Endocrine System Diseases; Humans; Mental Disorders; Nervous System Diseases; Olanzapine; Piperazines; Pirenzepine; Primary Health Care; Quetiapine Fumarate; Risperidone; Thiazoles

Topics: Adolescent; Adult; Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Body Weight; Clinical Trials as Topic; Clozapine; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Glucose; Haloperidol; Humans; Intellectual Disability; Male; Mental Disorders; Metabolic Syndrome; Middle Aged; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Schizophrenia; Sex Factors; Time Factors; Weight Gain

Although quetiapine was introduced as an atypical antipsychotic drug with clinical efficacy in schizophrenia patients, it has been used in a variety of disease states over the last 5 years. The most common conditions have included mood and anxiety disorders, obsessive-compulsive disorder, aggression, hostility, posttraumatic stress disorder, borderline personality disorder, delirium, and comorbid substance abuse. Considering its efficacy in a wide variety of neuropsychiatric conditions and its excellent tolerability profile, quetiapine could emerge as a broad-spectrum psychotropic medication that may be helpful in psychiatry across various diagnostic categories. Traditionally, studies on the predictive validity of psychiatric disorders help with nosologic issues and controversies. Assessing quetiapine's tolerability and its overall treatment response might help tease out the predictive validity of various psychiatric syndromes (based currently on an atheoretical descriptive approach) and may shape psychiatric nosology in the future. Quetiapine's low affinity and fast dissociation from postsynaptic dopamine-2 receptors give the least risk of producing acute extrapyramidal side effects, tardive dyskinesia, and neuroleptic malignant syndrome. These factors suggest that the clinical utility of quetiapine in psychiatric conditions other than schizophrenia has not been fully exploited thus far.

Topics: Adult; Aggression; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Borderline Personality Disorder; Clinical Trials as Topic; Comorbidity; Delirium; Depressive Disorder; Dibenzothiazepines; Forecasting; Hostility; Humans; Mental Disorders; Obsessive-Compulsive Disorder; Quetiapine Fumarate; Stress Disorders, Post-Traumatic; Substance-Related Disorders; Treatment Outcome

The atypical antipsychotics have been shown to have superior efficacy compared with typical antipsychotics such as haloperidol, particularly in the treatment of negative symptoms of schizophrenia. Furthermore, they induce less extrapyramidal effects. However, following clinical use, marked bodyweight gain has been frequently observed with some of the atypical antipsychotic drugs. In order to examine and compare the frequency, amount and conditions of bodyweight gain during treatment with atypical antipsychotics, studies concerning bodyweight gain with these agents were identified through a MEDLINE search from 1966 to March 2000. Although comparison is limited by the different designs and recruitment procedures of the reviewed studies, the available data support the notion that the frequency as well as the amount of bodyweight gain is high in patients treated with olanzapine (average bodyweight gain 2.3 kg/month), clozapine (1.7 kg/month), quetiapine (1.8 kg/month), and possibly also zotepine (2.3 kg/month). Moderate changes in bodyweight have been observed in the treatment with risperidone (average bodyweight gain 1.0 kg/month). Ziprasidone seems to induce only slight bodyweight changes (0.8 kg/month). Bodyweight gain most frequently occurs in the first 12 weeks of treatment. Patients who were underweight at the beginning of treatment are at highest risk of gaining bodyweight. The underlying pathomechanism still remains largely unclear. The relative receptor affinities of the atypical antipsychotics for histamine H1 receptors as well as the ratio of their affinity for serotonin 5-HT2 and dopamine D2 receptors appear to be the most robust correlate of bodyweight gain. Furthermore, the induction of leptin secretion may have an important impact on bodyweight gain in patients treated with atypical antipsychotics. Although many questions concerning the pathogenesis of bodyweight gain remain unresolved, this adverse effect has to be taken into consideration when prescribing the atypical antipsychotics, particularly in view its affect on compliance during long term treatment and the long term effects of obesity on mortality and morbidity.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Pirenzepine; Quetiapine Fumarate; Receptors, Dopamine D2; Receptors, Histamine H1; Receptors, Serotonin; Risk Factors; Smoking Cessation; Weight Gain

Antipsychotic agents, such as quetiapine fumarate, are frequently overprescribed for indications not supported by clinical evidence, potentially causing harm.. To investigate if peer comparison letters targeting high-volume primary care prescribers of quetiapine meaningfully reduce their prescribing.. Randomized clinical trial (intent to treat) conducted from 2015 to 2017 of prescribers and their patients nationwide in the Medicare program. The trial targeted the 5055 highest-volume primary care prescribers of quetiapine in 2013 and 2014 (approximately 5% of all primary care prescribers of quetiapine).. Prescribers were randomized (1:1 ratio) to receive a placebo letter or 3 peer comparison letters stating that their quetiapine prescribing was high relative to their peers and was under review by Medicare.. The primary outcome was the total quetiapine days supplied by prescribers from the intervention start to 9 months. Secondary outcomes included quetiapine receipt from all prescribers by baseline patients, quetiapine receipt by patients with low-value or guideline-concordant indications for therapy, mortality, and hospital use. In exploratory analyses, the study followed outcomes to 2 years.. Of the 5055 prescribers, 231 (4.6%) were general practitioners, 2428 (48.0%) were in family medicine, and 2396 (47.4%) were in internal medicine; 4155 (82.2%) were male. All were included in the analyses. Over 9 months, the treatment arm supplied 11.1% fewer quetiapine days per prescriber vs the control arm (2456 vs 2864 days; percentage difference, 11.1% fewer days; 95% CI, -13.1% to -9.2% days; P < .001; adjusted difference, -319 days; 95% CI, -374 to -263 days; P < .001), which persisted through 2 years (15.6% fewer days; 95% CI, -18.1% to -13.0%; P < .001). At the patient level, individuals in the treatment arm received 3.9% (95% CI, -5.0% to -2.9%; P < .001) fewer days of quetiapine from all prescribers over 9 months, with a larger decrease among patients with low-value vs guideline-concordant indications (-5.9% [95% CI, -8.0% to -3.9%] vs -2.4% [95% CI, -4.0% to -0.9%], P = .01 for test that effects were equal for both patient groups). There was no evidence of substitution to other antipsychotics, and 9-month mortality and hospital use were similar between the treatment vs control arms.. Peer comparison letters caused substantial and durable reductions in quetiapine prescribing, with no evidence of negative effects on patients.. ClinicalTrials.gov identifier: NCT02467933.

Topics: Adult; Aged; Antipsychotic Agents; Disabled Persons; Drug Prescriptions; Female; General Practitioners; Guideline Adherence; Humans; Internal Medicine; Male; Medicare; Mental Disorders; Middle Aged; Outcome Assessment, Health Care; Peer Group; Physicians, Family; Physicians, Primary Care; Practice Patterns, Physicians'; Quetiapine Fumarate; United States

There is a need for more studies on the clinical effectiveness, tolerability and pharmacokinetics of atypical antipsychotics in adolescents with psychotic disorders, as this represents a vulnerable and difficult population to treat. According to recent concerns regarding disabling side effects of antipsychotics, particularly weight gain, further monitoring of their safety profiles is needed. This situation prompted the authors to carry out an investigation on the clinical effectiveness of quetiapine in psychotic adolescents.. 23 adolescents (13-18 years old) with psychotic disorders participated in a 12-week open label trial, including 6 visits assessing clinical efficacy, tolerability and safety of quetiapine (50-750 mg daily).. Adolescents were treated with lower doses compared to adults. Significant decreases in CGI and PANSS total scores were observed after both 4 and 12 weeks of quetiapine treatment compared to baseline. Sedation was the main adverse effect, but medication was generally well tolerated. Irregular compliance, (as assessed by pill counts, a questionnaire and by plasma quetiapine concentration monitoring), and alcohol and/or cannabis consumption were factors identified in this study which add to the difficulty in treating this population.. The results of the present study help to consolidate evidence of the usefulness of quetiapine as a treatment for adolescents with psychotic disorders. However, this study also highlights the issues encountered in treating this group, including the presence of comorbidities such as drug abuse.

Topics: Adolescent; Anti-Anxiety Agents; Antidepressive Agents; Antipsychotic Agents; Comorbidity; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Male; Mental Disorders; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Research Design; Surveys and Questionnaires

To examine the effect of diagnosis, mood state, and anxiety on subjective wellbeing in patients with affective and non-affective psychotic disorders treated with quetiapine IR.. 2175 patients with schizophrenia-spectrum (SZ, n=1681), schizoaffective (SA, n=249), and bipolar disorder (BPD, n=245) were treated with quetiapine over 6 months and assessed with the Clinical Global Impression-Severity of illness Scale (CGI-S) and the Subjective Wellbeing under Neuroleptic Treatment Scale (SWN-K). Diagnostic group differences and effects of mood state and anxiety on subjective wellbeing were analyzed using multi-factorial linear regression analysis and mixed models repeated measures.. At baseline, despite similar CGI-S scores, significant SWN-K score differences between SZ (57.7 points), SA (64.1 points), and BPD (79.5 points) were detected. At baseline, depression (p<0.001) and anxiety (p<0.001) were independently associated with a worse and mania (p<0.001) with a better subjective wellbeing. Subjective wellbeing improved significantly in all groups (p<0.001; 27.6 points), and endpoint subjective wellbeing was not predicted by baseline depression or anxiety, but by endpoint depression and anxiety.. Interventions to improve subjective wellbeing should take into account the course of mood state and anxiety. Assessment of subjective wellbeing and subjective quality of life in acute mania may need adapted tools.

Topics: Adult; Affect; Analysis of Variance; Antipsychotic Agents; Anxiety; Dibenzothiazepines; Female; Humans; Male; Mental Disorders; Middle Aged; Outpatients; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Time Factors; Young Adult

The second-generation antipsychotics are associated with metabolic abnormalities in patients with schizophrenia. Elderly patients with Alzheimer's disease are frequently treated with these antipsychotics, but limited data are available on their metabolic effects.. The authors assessed 186 male and 235 female Alzheimer's disease outpatients from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) for changes in weight, waist circumference, blood pressure, fasting glucose, and lipids in relation to duration of second-generation antipsychotic use (i.e., olanzapine, quetiapine, and risperidone) throughout the 36-week trial, using logistic regression and mixed-effects models.. Women showed significant weight gain (0.14 lb/week of use) while change was nonsignificant in men. Clinically significant weight gain (i.e., > or = 7% of body weight) was seen among patients with antipsychotic use < or = 12 weeks (odds ratio [OR]=1.56, 95% CI=0.53 to 4.58), between 12 and 24 weeks (OR=2.89, 95% CI=0.97 to 8.64), and > 24 weeks (OR=3.38, 95% CI=1.24 to 9.23) relative to patients who did not use antipsychotics during the trial. Olanzapine and quetiapine treatments were significantly associated with weight gain (0.12 and 0.14 lb/week, respectively). In addition, olanzapine was significantly associated with decreases in HDL cholesterol (-0.19 mg/dl/week) and increased girth (0.07 inches/week) relative to the placebo group. No treatment effects were noted for changes in blood pressure, glucose, and triglycerides.. Second-generation antipsychotic use was associated with weight gain in women, with olanzapine and quetiapine in particular, and with unfavorable change in HDL cholesterol and girth with olanzapine. The potential consequences of these effects suggest that patients with Alzheimer's disease treated with second-generation antipsychotics should be monitored closely.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Drug Monitoring; Female; Humans; Male; Mental Disorders; Obesity; Olanzapine; Quetiapine Fumarate; Risperidone

To assess the efficacy of quetiapine addition to citalopram in treatment-naive or medication-free obsessive-compulsive disorder (OCD) patients.. Seventy-six patients who met DSM-IV criteria for OCD and who were drug-free or drug-naive at entry were randomly assigned in a 10-week, double-blind trial with citalopram (60 mg/day) plus quetiapine (300-450 mg/day) or placebo; treatment-refractory OCD patients were excluded. Of the 76 eligible patients, 66 patients completed the trial-31 in the quetiapine and 35 in the placebo group. The change from baseline to endpoint on the total Yale-Brown Obsessive Compulsive Scale (YBOCS) and the response to treatment in the quetiapine addition compared with the placebo addition group were the primary outcome measures. Response was defined as a 35% or greater reduction on the YBOCS and a Clinical Global Impressions-Improvement (CGI-I) score at endpoint of 1 or 2. The study was conducted from November 2003 to June 2005 at the University Medical Centre Utrecht, The Netherlands.. As measured by the mean reduction in YBOCS scores following an intent-to-treat, last-observation-carried-forward analysis, quetiapine addition (11.9) was significantly superior to placebo (7.8; p = .009). Quetiapine addition was also significantly superior to placebo on the CGI-I scale, with a mean +/- SD CGI-I score of 2.1 +/- 1.3 versus 1.4 +/- 1.2, respectively (p = .023). Quetiapine addition (N = 22, 69%) was also associated with a significantly greater number of patients responding to treatment compared with placebo addition (N = 15, 41%; p = .019). More patients receiving quetiapine (N = 8) than placebo (N = 2; NS) discontinued treatment due to adverse events.. The combination of quetiapine and citalopram was more effective than citalopram alone in reducing OCD symptoms in treatment-naive or medication-free OCD patients.. www.trialregister.nl Identifier NTR116.

Topics: Adolescent; Adult; Antipsychotic Agents; Citalopram; Comorbidity; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Endpoint Determination; Female; Humans; Male; Mental Disorders; Netherlands; Obsessive-Compulsive Disorder; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

Patients with dual diagnosis are often excluded from clinical trials although more than half of all individuals with Bipolar Disorder have a substance abuse problem at some point in their lifetime, representing a high-risk clinical population. The purpose of this study was to investigate the safety and efficacy of quetiapine in the treatment of alcohol dependence comorbid with disorders characterized by high levels of mood and behavioral instability.. Twenty-eight subjects, after a detoxification period, were orally treated with flexible doses of quetiapine for 16 weeks. At each assessment patients were evaluated through the Obsessive Compulsive Drinking Scale (OCDS), the Visual Analogue Scale (VAS) for craving, the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), the Brief Psychiatric Rating Scale (BPRS), the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression (CGI) scale.. Forty-three percent of patients remained totally alcohol free, 32% patients relapsed, with an average of 15.4 drinking days in the period of the study (112 days) and 25% dropped-out. Significant reductions from baseline to exit were observed in the OCDS, VAS, BPRS, HDRS, and number of drinking days per week. Changes in alcohol craving correlated with psychiatric symptoms as to BPRS and HDRS, with the highest level of correlation evidenced for the HDRS items of insomnia.. In this open-label study, quetiapine decreased alcohol consumption, craving for alcohol, and psychiatric symptoms intensity, maintaining a good level of tolerance. A strength of this study is that the use of quetiapine was not adjunctive with other pharmacological and non-pharmacological treatment. Double-blind placebo-controlled studies are required with a larger study population to confirm these data. In the meantime, for a select group of psychiatric patients, quetiapine may offer some advantages in preventing relapse.

Topics: Adult; Alcohol Drinking; Alcoholism; Antipsychotic Agents; Diagnosis, Dual (Psychiatry); Dibenzothiazepines; Female; Humans; Male; Mental Disorders; Psychiatric Status Rating Scales; Quetiapine Fumarate; Secondary Prevention

In this study we directly compared the efficacy and tolerability of the atypical antipsychotics quetiapine and risperidone in elderly patients with dementia and symptoms of disturbed perception, thought content, mood or behaviour (behavioural and psychological symptoms of dementia-BPSD).. We conducted an 8-week, rater-blinded, randomised study of 72 outpatients (55-85 years) with BPSD (assessed by NPI baseline score), who received flexibly-dosed quetiapine (50-400 mg/day) or risperidone (0.5-2 mg/day). Primary efficacy measure: Neuropsychiatric Inventory (NPI) Parts 1 and 2; secondary efficacy measures: Clinical Global Impression (CGI), Cohen-Mansfield Agitation Inventory (CMAI), Mini-Mental State Examination (MMSE), Age-adjusted concentration test (AKT). Safety evaluations included the incidence of extrapyramidal symptoms (EPS) and adverse events (AEs).. Sixty-nine of 72 patients were evaluable for efficacy (72 were evaluated for safety), 4 patients discontinued (3 due to AEs: quetiapine 2, risperidone 1; 1 lost to follow-up). Sixty-five patients received quetiapine (n=34; mean dose 77+/-40 mg/day) or risperidone (n=31; mean dose 0.9+/-0.3 mg/day). There was no significant difference between treatments on NPI scores; within treatment groups, NPI scores decreased significantly from baseline to Week 8 (P

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Dementia; Dibenzothiazepines; Female; Humans; Male; Mental Disorders; Mental Status Schedule; Middle Aged; Mood Disorders; Neuropsychological Tests; Perceptual Disorders; Quetiapine Fumarate; Risperidone; Single-Blind Method; Thinking; Treatment Outcome

To explore the potential for drug interactions on quetiapine pharmacokinetics using in vitro and in vivo assessments.. The CYP enzymes responsible for quetiapine metabolite formation were assessed using recombinant expressed CYPs and CYP-selective inhibitors. P-glycoprotein (Pgp) transport was tested in MDCK cells expressing the human MDR1 gene. The effects of CYP3A4 inhibition were evaluated clinically in 12 healthy volunteers that received 25 mg quetiapine before and after 4 days of treatment with ketoconazole 200 mg daily. To assess CYP3A4 induction in vivo, 18 patients with psychiatric disorders were titrated to steady-state quetiapine levels (300 mg twice daily), then titrated to 600 mg daily carbamazepine for 2 weeks.. CYP3A4 was found to be responsible for formation of quetiapine sulfoxide and N- and O-desalkylquetiapine and not a Pgp substrate. In the clinical studies, ketoconazole increased mean quetiapine plasma C(max) by 3.35-fold, from 45 to 150 ng ml(-1) (mean C(max) ratio 90% CI 2.51, 4.47) and decreased its clearance (Cl/F) by 84%, from 138 to 22 l h(-1) (mean ratio 90% CI 0.13, 0.20). Carbamazepine decreased quetiapine plasma C(max) by 80%, from 1042 to 205 ng ml(-1) (mean C(max) ratio 90% CI 0.14, 0.28) and increased its clearance 7.5-fold, from 65 to 483 l h(-1) (mean ratio 90% CI 6.04, 9.28).. Cytochrome P450 3A4 is a primary enzyme responsible for the metabolic clearance of quetiapine. Quetiapine pharmacokinetics were affected by concomitant administration of ketoconazole and carbamazepine, and therefore other drugs and ingested natural products that strongly modulate the activity or expression of CYP3A4 would be predicted to change exposure to quetiapine.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Carbamazepine; Cross-Over Studies; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Enzyme Induction; Enzyme Inhibitors; Female; Humans; Isoenzymes; Ketoconazole; Male; Mental Disorders; Microsomes, Liver; Middle Aged; Quetiapine Fumarate

This naturalistic, cross-sectional study was designed to assess the risk of prolactin level elevation and associated side effects in youths taking long-term atypical antipsychotic medication.. Subjects were enrolled from outpatient child psychiatric treatment settings in upstate New York who were taking risperidone, olanzapine, or quetiapine for at least 6 months. Demographic data, medication history, and side effects were elicited at the initial interview. Two fasting morning serum prolactin levels were obtained 1 month apart, and the results were averaged.. Fifty outpatient youths, with a median age of 13 years, were enrolled in the study. The median overall duration of use of an atypical antipsychotic was 22.1 months. The median dose of medication for risperidone was 1.5 mg/day, for olanzapine 10 mg/day, and for quetiapine 200 mg/day. The mean prolactin level among all patients on risperidone was significantly greater than controls, as well as for those on quetiapine or olanzapine.. The risk of hyperprolactinemia with long-term use of risperidone appears to be significantly greater than for olanzapine or quetiapine. Overt side effects were infrequent in the overall sample, but serum prolactin assessment is recommended for youths taking risperidone chronically. Because of variability found in sequential prolactin samples, repeat samples may be warranted.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Child, Preschool; Cross-Sectional Studies; Dibenzothiazepines; Female; Humans; Male; Mental Disorders; Olanzapine; Prolactin; Quetiapine Fumarate; Risperidone

Second-generation (atypical) antipsychotic drugs are widely used to treat psychosis, aggression, and agitation in patients with Alzheimer's disease, but their benefits are uncertain and concerns about safety have emerged. We assessed the effectiveness of atypical antipsychotic drugs in outpatients with Alzheimer's disease.. In this 42-site, double-blind, placebo-controlled trial, 421 outpatients with Alzheimer's disease and psychosis, aggression, or agitation were randomly assigned to receive olanzapine (mean dose, 5.5 mg per day), quetiapine (mean dose, 56.5 mg per day), risperidone (mean dose, 1.0 mg per day), or placebo. Doses were adjusted as needed, and patients were followed for up to 36 weeks. The main outcomes were the time from initial treatment to the discontinuation of treatment for any reason and the number of patients with at least minimal improvement on the Clinical Global Impression of Change (CGIC) scale at 12 weeks.. There were no significant differences among treatments with regard to the time to the discontinuation of treatment for any reason: olanzapine (median, 8.1 weeks), quetiapine (median, 5.3 weeks), risperidone (median, 7.4 weeks), and placebo (median, 8.0 weeks) (P=0.52). The median time to the discontinuation of treatment due to a lack of efficacy favored olanzapine (22.1 weeks) and risperidone (26.7 weeks) as compared with quetiapine (9.1 weeks) and placebo (9.0 weeks) (P=0.002). The time to the discontinuation of treatment due to adverse events or intolerability favored placebo. Overall, 24% of patients who received olanzapine, 16% of patients who received quetiapine, 18% of patients who received risperidone, and 5% of patients who received placebo discontinued their assigned treatment owing to intolerability (P=0.009). No significant differences were noted among the groups with regard to improvement on the CGIC scale. Improvement was observed in 32% of patients assigned to olanzapine, 26% of patients assigned to quetiapine, 29% of patients assigned to risperidone, and 21% of patients assigned to placebo (P=0.22).. Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer's disease. (ClinicalTrials.gov number, NCT00015548 [ClinicalTrials.gov].).

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Mental Disorders; Olanzapine; Proportional Hazards Models; Quetiapine Fumarate; Risperidone; Survival Analysis; Treatment Outcome

Treatment of depression and anxiety disorders with selective serotonin reuptake inhibitors (SSRIs) has been shown by numerous studies to be generally effective. Less well understood is how clinically to address the residual anxiety symptoms a significant minority of such patients treated with SSRIs continue to experience. We assessed quetiapine as adjunctive therapy to SSRIs for patients with anxiety symptoms complicating a depressive or anxiety disorder. Patients receiving a stable dosage of an SSRI for at least 6 weeks who also had persistent anxiety symptoms (Hamilton Anxiety scale [HAM-A] > or =16), were enrolled in a 9-week, open-label, variable dose study. Changes in clinical status were assessed with the Hamilton Depression Rating Scale (HAM-D), HAM-A, and State Anxiety Inventory (SAI). Statistically and clinically significant reductions of > or =50% in the HAM-D and HAM-A occurred by the second week of treatment in 10 of the 11 patients. These improvements continued throughout the study along with a significant improvement on the SAI scale. The most frequent side effects reported were mild dry mouth, constipation, and transient drowsiness with dose escalation. The results provide evidence that quetiapine may be an effective adjunctive treatment for recalcitrant anxiety symptoms in individuals treated with SSRIs for either anxiety or depressive disorders. Given the open-label design of the trial, more rigorous studies are clearly indicated.

Topics: Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Mental Disorders; Middle Aged; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Surveys and Questionnaires

This open-label study investigated the strategy of switching patients who had gained excessive weight on olanzapine to quetiapine, with assessments of safety and continued efficacy as well as weight change. Patients who were psychiatrically stable on olanzapine but had gained >20% in weight and had body mass index >25 mg/kg(2) were switched to quetiapine over a 4-week period and followed for 6 weeks, the total study duration being 10 weeks. Assessments included weight change, antipsychotic efficacy using the Positive and Negative Symptom Syndrome Scale (PANSS), extrapyramidal adverse events using the Simpson-Angus Scale (SAS), and laboratory studies for metabolic measures. Of 16 enrolled patients, 12 completed the study. Mean weight loss was 2.25 kg (Cohen's d = 0.12; P = 0.03). There were no significant changes in PANSS total scores, SAS scores, or metabolic parameters. Switching patients to quetiapine, appears to be a viable strategy for managing olanzapine-induced weight gain as indicated by this 10-week open-label study. Prospective controlled trials of longer duration and larger number of subjects are needed.

Topics: Basal Ganglia Diseases; Benzodiazepines; Body Weight; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Quetiapine Fumarate; Weight Loss

Quetiapine is an atypical antipsychotic agent that does not appear to increase patient risk for treatment-emergent extrapyramidal symptoms (EPS) or anticholinergic symptoms. Previous studies of quetiapine use in elderly patients with schizophrenia and other psychoses examined short-term administration (< or = 12 weeks). Given the growing elderly population, the commensurate increase in elderly patients with psychoses, and the expected increase in disease treatment-years, the effect of long-term quetiapine administration in older patients is of considerable interest.. This study assesses the long-term tolerability, safety, and clinical benefit of quetiapine in elderly patients with psychosis.. Elderly patients (> or = 65 years of age) with psychotic disorders, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, participated in this 52-week, open-label, multicenter trial. Investigators increased (and later adjusted) daily doses of quetiapine on the basis of clinical response and tolerability, and assessed safety and efficacy. Efficacy assessments were made using the 18-item Brief Psychiatric Rating Scale (BPRS), Clinical Global Impressions (CGI), Simpson-Angus Scale, and the Abnormal Involuntary Movement Scale (AIMS). For patients who withdrew before week 52, analyses were performed using observed data and the last observation carried forward.. One hundred eighty-four patients with psychotic disorders (98 women and 86 men) with a mean age of 76.1 years entered the trial. Seventy-two percent had psychotic disorders due to general medical conditions such as Alzheimer's disease, and 28% had other psychotic disorders, most commonly schizophrenia. Overall, 89 (48%) patients completed treatment through 52 weeks. Median total daily dose was 137.5 mg. Reasons, for withdrawal included lack of efficacy (19%), adverse events or intercurrent illness (15%), failure to return for follow-up (13%), protocol noncompliance (3%), and diminished need for treatment (2%). Somnolence (31%), dizziness (17%), and postural hypotension (15%) were common adverse events, but they rarely resulted in withdrawal from therapy. EPS-related adverse events occurred in 13% of patients. At end point (week 52), mean total score on the Simpson-Angus Scale had decreased from baseline by 1.8 points, whereas changes in AIMS scores were negligible. No clinically important effects were reported relative to mean changes in hematologic, thyroid function, or hepatic function variables. Quetiapine treatment appeared to have no associated cardiovascular adverse outcomes despite cardiovascular comorbidities and unrestricted use of concomitant cardiovascular medications. Significant decreases in BPRS total score (n = 170, P < 0.001) and CGI Severity of Illness item score (n = 177, P < 0.002) were seen at end point (observed data and last observation carried forward). Decreases of > or = 20% in mean BPRS total score were observed in 83 (49%) patients.. These results provide preliminary information to clinicians regarding tolerability, safety, and clinical improvement with quetiapine in elderly patients with psychotic symptoms, and support controlled studies of quetiapine in this patient population.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Male; Mental Disorders; Middle Aged; Neuropsychological Tests; Quetiapine Fumarate

Polypharmacy increases the risk of potential drug-drug interactions (pDDIs). This retrospective analysis was conducted to detect pDDIs and adverse drug reactions (ADRs) among older adults with psychiatric disorder, and identify pDDIs with clinical significance.. A retrospective analysis was carried out based on the medical records of older adults with psychiatric disorders. Data on demographic characteristics, substance abuse, medical history, and medications were extracted. The Lexi-Interact online database was used to detect pDDIs. The minimal clinically important difference (MCID) was set as the change in the Treatment Emergent Symptom Scale (TESS) score between admission and discharge. The median and interquartile ranges were used for continuous variables, and frequencies were calculated for dichotomous variables. Poisson regression was implemented to determine the factors influencing the number of ADR types. The influencing factors of each ADR and the clinical significance of the severity of the ADR were analysed using binary logistic regression. P < 0.05 was considered statistically significant.. A total of 308 older adults were enrolled, 171 (55.52%) of whom had at least 1 pDDI. Thirty-six types of pDDIs that should be avoided were found, and the most frequent pDDI was the coadministration of lorazepam and olanzapine (55.5%). A total of 26 ADRs induced by pDDIs were identified, and the most common ADR was constipation (26.05%). There was a 9.4 and 10.3% increase in the number of ADR types for each extra medical diagnosis and for each extra drug, respectively. There was a 120% increase in the number of ADR types for older adults hospitalized for 18-28 days compared with those hospitalized for 3-17 days. There was an 11.1% decrease in the number of ADR types for each extra readmission. The length of hospitalization was a risk factor for abnormal liver function (P < 0.05). The use of a large number of drugs was a risk factor for gastric distress (P < 0.05) and dizziness and fainting (P < 0.05). None of the four pDDIs, including coadministrations of olanzapine and lorazepam, quetiapine and potassium chloride, quetiapine and escitalopram, and olanzapine and clonazepam, showed clinical significance of ADR severity (P > 0.05).. pDDIs are prevalent in older adults, and the rate is increasing. However, many pDDIs may have no clinical significance in terms of ADR severity. Further research on assessing pDDIs, and possible measures to prevent serious ADRs induced by DDIs is needed to reduce the clinical significance of pDDIs.

Topics: Aged; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Lorazepam; Mental Disorders; Olanzapine; Quetiapine Fumarate; Retrospective Studies

Off-label drug prescribing in psychiatry is increasing. Many psychotropic drugs are approved for psychopathologic syndromes rather than based on international standard diagnostic classification systems which might facilitate the clinical decision for off-label prescriptions. The objective of this study was to analyze the prevalence and category of off-label use of psychotropic drugs. The study was conducted in 10 psychiatric hospitals in Germany over a period of 2 years. Prescription data of all patients were retrospectively analyzed after identification of antidepressants, antipsychotics, and mood-stabilizers, which were classified as off-label according to the German prescribing information and diagnostic classification according to ICD-10. In total, 53,909 patient cases (46% female) with a mean age of 46.8 (SD: 18) years were included in the study. 30.2% of the cases received at least one off-label prescription of a psychotropic drug during hospital stay. Off-label prevalence rates differed markedly between different diagnostic groups (ICD-10 F0/G3: 47%, F1: 33%, F2: 25%, F3: 21%, F4: 27%, F6: 46%, F7: 84%). The most often off-label prescribed drugs were quetiapine and mirtazapine for organic mental disorders (F0/G3), valproate and quetiapine in patients with disorders due to psychoactive substance use (F1), valproate in patients with psychotic disorders (F2), and risperidone and olanzapine in patients with affective disorders (F3). The prevalence rate of psychotropic off-label prescriptions is high if restricted to product description and ICD-10 diagnosis. Therefore, current psychiatric guidelines should drug-specifically issue this problem by defining psychiatric off-label indications based on a clear benefit-risk assessment.

Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Female; Humans; Male; Mental Disorders; Middle Aged; Mirtazapine; Off-Label Use; Olanzapine; Psychiatry; Psychotic Disorders; Psychotropic Drugs; Quetiapine Fumarate; Retrospective Studies; Risperidone; Valproic Acid

The clinical applications of antipsychotics for symptoms unrelated to schizophrenia, such as behavioral and psychological symptoms, in patients with Alzheimer's disease, and the likelihood of doctors prescribing antipsychotics for elderly people are increasing. In elderly people, drug-induced and aging-associated urinary disorders are likely to occur. The most significant factor causing drug-induced urinary disorders is a decrease in urinary bladder smooth muscle (UBSM) contraction induced by the anticholinergic action of therapeutics. However, the anticholinergic action-associated inhibitory effects of antipsychotics on UBSM contraction have not been sufficiently assessed. In this study, we examined 26 clinically available antipsychotics to determine the extent to which they inhibit acetylcholine (ACh)-induced contraction in rat UBSM to predict the drugs that should not be used by elderly people to avoid urinary disorders. Of the 26 antipsychotics, six (chlorpromazine, levomepromazine (phenothiazines), zotepine (a thiepine), olanzapine, quetiapine, clozapine (multi-acting receptor targeted antipsychotics (MARTAs))) competitively inhibited ACh-induced contractions at concentrations corresponding to clinically significant doses. Further, 11 antipsychotics (perphenazine, fluphenazine, prochlorperazine (phenothiazines), haloperidol, bromperidol, timiperone, spiperone (butyrophenones), pimozide (a diphenylbutylpiperidine), perospirone, blonanserin (serotonin-dopamine antagonists; SDAs), and asenapine (a MARTA)) significantly suppressed ACh-induced contraction; however, suppression occurred at concentrations substantially exceeding clinically achievable blood levels. The remaining nine antipsychotics (pipamperone (a butyrophenone), sulpiride, sultopride, tiapride, nemonapride (benzamides), risperidone, paliperidone (SDAs), aripiprazole, and brexpiprazole (dopamine partial agonists)) did not inhibit ACh-induced contractions at concentrations up to 10

Topics: Acetylcholine; Aging; Animals; Antipsychotic Agents; Chlorpromazine; Cholinergic Antagonists; Clozapine; Dibenzothiepins; Male; Mental Disorders; Methotrimeprazine; Muscle Contraction; Muscle, Smooth; Olanzapine; Quetiapine Fumarate; Rats, Wistar; Urinary Bladder; Urologic Diseases

Topics: Adult; Agoraphobia; Antibodies, Monoclonal, Humanized; Antidepressive Agents; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Depressive Disorder, Major; Female; Humans; Lithium Carbonate; Male; Mental Disorders; Middle Aged; Nordazepam; Panic Disorder; Paroxetine; Psoriasis; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome; Valproic Acid

The second-generation antipsychotic quetiapine has been demonstrated to undergo gestation-related changes in pharmacokinetics. This study applied pharmacokinetic modelling principles to investigate the mechanism of these changes and to propose new dosing strategies to counteract these changes.. A pharmacokinetic modelling approach was implemented using virtual population groups. Changes in quetiapine trough plasma concentration during gestation were quantified across all trimesters, and dose adjustment strategies were applied to counteract these changes by targeting a therapeutic range of 50-500 ng/ml throughout gestation.. The application of the model during gestation predicted a decrease in trough concentration. A maximum decrease of 58% was predicted during trimester 2, and being associated with a statistically significant decrease in oral clearance at gestation week 25, 204 l/h ± 100.8 l/h compared with non-pregnant subjects, 121.9 l/h ± 51.8 l/h. A dosing optimisation strategy identified that dose increases to 500-700 mg twice daily would result in 32-55% of subjects possessing trough concentration in excess of 50 ng/ml.. Quetiapine doses in pregnancy should be increased to 500-700 mg twice daily to counteract a concomitant increase in metabolic clearance, increase in volume of distribution and decrease in plasma protein binding.

Topics: Adult; Antipsychotic Agents; Computer Simulation; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Mental Disorders; Metabolic Clearance Rate; Middle Aged; Models, Biological; Pregnancy; Pregnancy Complications; Quetiapine Fumarate

Topics: Anti-Bacterial Agents; Antipsychotic Agents; Butyrophenones; Ceftriaxone; Chronic Disease; Humans; Male; Mental Disorders; Middle Aged; Neurosyphilis; Quetiapine Fumarate; Treatment Outcome

Antipsychotic drug use among children and adolescents is increasing, and there is growing concern about off-label use and adverse effects. The present study aims to investigate the incidence, psychiatric co-morbidity and pharmacological treatment of severe mental disorder in Norwegian children and adolescents.. We obtained data on mental disorders from the Norwegian Patient Registry on 0-18 year olds who during 2009-2011 were diagnosed for the first time with schizophrenia-like disorder (International Classification of Diseases, 10th revision codes F20-F29), bipolar disorder (F30-F31), or severe depressive episode with psychotic symptoms (F32.3 or F33.3). Data on filled prescriptions for psychotropic drugs were obtained from the Norwegian Prescription Database.. A total of 884 children and adolescents (25.1 per 100 000 person years) were first time diagnosed with schizophrenia-like disorder (12.6 per 100 000 person years), bipolar disorder (9.2 per 100 000 person years), or severe depressive episode with psychotic symptoms (3.3 per 100 000 person years) during 2009-2011. The most common co-morbid mental disorders were depressive (38.1%) and anxiety disorders (31.2%). Antipsychotic drugs were prescribed to 62.4% of the patients, 72.0% of the schizophrenia-like disorder patients, 51.7% of the bipolar disorder patients, and 55.4% of the patients with psychotic depression. The most commonly prescribed drugs were quetiapine (29.5%), aripiprazole (19.6%), olanzapine (17.3%), and risperidone (16.6%).. When a severe mental disorder was diagnosed in children and adolescents, the patient was usually also prescribed antipsychotic medication. Clinicians must be aware of the high prevalence of depressive and anxiety disorders among early psychosis patients.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Child, Preschool; Comorbidity; Depressive Disorder, Major; Female; Humans; Incidence; Infant; Male; Mental Disorders; Norway; Olanzapine; Prevalence; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Drug analysis in hair is useful when seeking to establish drug intake over a period of months to years. Segmental hair analysis can also document whether psychiatric patients are receiving a stable intake of antipsychotics. This study describes segmental analysis of the antipsychotic drug quetiapine in post-mortem hair samples from long-term quetiapine users by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. The aim was to obtain more knowledge on quetiapine concentrations in hair and to relate the concentration in hair to the administered dose and the post-mortem concentration in femoral blood. We analyzed hair samples from 22 deceased quetiapine-treated individuals, who were divided into two groups: natural hair colour and dyed/bleached hair. Two to six 1cm long segments were analyzed per individual, depending on the length of the hair, with 6cm corresponding to the last six months before death. The average daily quetiapine dose and average concentration in hair for the last six months prior to death were examined for potential correlation. Estimated doses ranged from 45 to 1040mg quetiapine daily over the period, and the average concentration in hair ranged from 0.18 to 13ng/mg. A significant positive correlation was observed between estimated daily dosage of quetiapine and average concentration in hair for individuals with natural hair colour (p=0.00005), but statistical significance was not reached for individuals with dyed/bleached hair (p=0.31). The individual coefficient of variation (CV) of the quetiapine concentrations between segments ranged from 3 to 34% for individuals with natural hair colour and 22-62% for individuals with dyed/bleached hair. Dose-adjusted concentrations in hair were significantly lower in females with dyed/bleached hair than in individuals with natural hair colour. The quetiapine concentrations in post-mortem femoral blood and in the proximal hair segment, segment 1 (S1), representing the last month before death were also investigated for correlation. A significant positive correlation was observed between quetiapine concentrations in blood at the time of death and concentrations in S1 for individuals with natural hair colour (p=0.003) but not for individuals with dyed/bleached hair (p=0.31). The blood concentrations of quetiapine ranged from 0.006 to 1.9mg/kg, and the quetiapine concentrations in S1 ranged from 0.22 to 24ng/mg. The results of this study suggest a positive corr

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Chromatography, High Pressure Liquid; Female; Hair; Hair Color; Hair Dyes; Humans; Male; Mental Disorders; Middle Aged; Quetiapine Fumarate; Tandem Mass Spectrometry; Young Adult

Therapeutic drug monitoring has become increasingly important in psychiatric therapy. However, it is not yet implemented as a daily routine in clinical settings. To evaluate new, noninvasive procedures, we compared blood and saliva venlafaxine, quetiapine, and citalopram concentrations in samples collected from psychiatric patients.. We collected blood and saliva samples from 75 psychiatric patients (39 venlafaxine, 19 quetiapine, and 17 citalopram). Saliva sampling was achieved by the use of cotton pads. Venlafaxine (and its metabolite O-desmethylvenlafaxine) and quetiapine were analyzed by LC-MS/MS, whereas citalopram was analyzed by HPLC.. We observed significant correlations between concentrations of venlafaxine (ratio saliva/serum ± SD: 18.3 ± 9.5, P < 0.01, r = 0.895) and its metabolite O-desmethylvenlafaxine (ratio saliva/serum ± SD: 4.1 ± 3.2, P < 0.05, r = 0.344), quetiapine (ratio saliva/serum ± SD: 0.2 ± 0.2, P < 0.01, r = 0.935), and citalopram (ratio saliva/serum ± SD: 2.6 ± 1.2, P < 0.05, r = 0.54) in serum and in saliva. Furthermore, measured concentrations of venlafaxine (and its metabolite O-desmethylvenlafaxine) and citalopram were higher in saliva than in serum, whereas measured concentrations of quetiapine were higher in serum than in saliva.. Using cotton pad saliva sampling, venlafaxine and quetiapine demonstrate high correlations between saliva and serum concentrations, whereas for O-desmethylvenlafaxine and citalopram, other methods of sampling might be preferable. Saliva therapeutic drug monitoring of psychoactive drugs might become a useful approach to achieving individual treatment regimens.

Topics: Adult; Aged; Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram; Desvenlafaxine Succinate; Drug Monitoring; Female; Humans; Male; Mental Disorders; Middle Aged; Protein Binding; Quetiapine Fumarate; Saliva; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride; Young Adult

Topics: Adult; Antipsychotic Agents; Delusions; Female; Humans; Magnetic Resonance Imaging; Mental Disorders; Quetiapine Fumarate; Septum Pellucidum

An 81-year-old woman was hospitalised for behavioural disorders that had been progressively emerging over a period of few weeks. The symptoms appeared to worsen over time. A diagnosis of vascular dementia, complicated by psychosis, was initially hypothesised. The inefficacy of the antipsychotic/benzodiazepine medications used, along with the presence of hypertension, hypokalaemia and metabolic alkalosis (resistant to pharmacological attempts of correction), as well as the hirsutism and the development of several infections, led us to consider Cushing's syndrome. Endocrinological analysis suggested ectopic adrenocorticotropic hormone (ACTH) secretion. Although endogenous Cushing's syndrome is rare in older people, it should always be considered among the differential diagnosis of behavioural disorders.

Topics: Aged, 80 and over; Antipsychotic Agents; Cushing Syndrome; Diagnosis, Differential; Enzyme Inhibitors; Fatal Outcome; Female; Humans; Mental Disorders; Metyrapone; Predictive Value of Tests; Quetiapine Fumarate; Risk Factors; Treatment Outcome

Antipsychotics produce electroencephalogram (EEG) modifications and increase the risk of epileptic seizure. These modifications remain sparsely studied specifically for atypical antipsychotics. In this context, our study focuses on EEG modifications associated with atypical strict antipsychotic monotherapies.. Electroencephalogram recordings of 84 psychiatric patients treated with atypical antipsychotics in strict monotherapy (clozapine, n = 22; aripiprazole, n = 22; olanzapine, n = 17; risperidone, n = 9; quetiapine, n = 8; risperidone long-acting injection, n = 4; and paliperidone long-acting injection, n = 2) were analyzed. The modifications were ranked according to both slowing and excitability scores.. Electroencephalogram modifications (in 51 subjects, 60.71%) were graded according to 4 stages combining general slowing and sharp slow waves and/or epileptiform activities. The presence of sharp or epileptiform activities was significantly greater for clozapine (90.9%) compared with other second-generation antipsychotics (aripiprazole, 50%; olanzapine, 58.8%; quetiapine, 37.5%; risperidone, 44.4%). Age, duration of disease progression, and diagnosis were not associated as risk factors. Electroencephalogram modifications were associated with lower doses for treatment with quetiapine but not for specific antipsychotics. Electroencephalogram modifications and severe excitability were associated with higher chlorpromazine equivalent doses.. Atypical antipsychotics (clozapine, aripiprazole, quetiapine, olanzapine, and risperidone) induce EEG modifications, and these are significantly greater for clozapine and appear dependent on chlorpromazine equivalent dose. No encephalopathy was observed in these antipsychotic monotherapies, whatever dose.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Cerebral Cortex; Clozapine; Depressive Disorder, Major; Electroencephalography; Female; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Young Adult

Second-generation antipsychotics (SGAs) are commonly used to treat children with mental health conditions (MHCs) but are associated with adverse effects including obesity, hypertension, dyslipidemia, and type 2 diabetes. The mechanisms underlying these complications are unknown, but it has been suggested that SGAs increase appetite leading to weight gain. The present objective was to perform a pilot study to investigate appetite and satiety hormones in SGA-treated (risperidone or quetiapine) and SGA-naive children with similar mental health conditions.. Oral glucose tolerance tests (OGTTs) were conducted in SGA-naive (n = 18), risperidone-treated (n = 20), and quetiapine-treated (n = 16) children recruited from the British Columbia Children's Hospital Psychiatry Department. Over 5 time-points during the OGTT, appetite questionnaires using a visual analogue scale were administered, and blood was collected to measure ghrelin, peptide YY, glucose-dependent insulinotropic polypeptide, glucagon-like protein 1, leptin, and adiponectin. Mixed model analyses were conducted to examine between-group differences.. The children were similar in age, psychiatric diagnosis, and global assessment of functioning scores. Body mass index z-scores were also similar between groups. Appetite was increased during the OGTT in the risperidone-treated compared with the SGA-naive group for 2 questions ("How strong is your desire to eat"; P = 0.003 and "How much food do you think you can eat"; P = 0.028). No differences in satiety hormones were observed between the 3 groups.. Risperidone treatment in youth is associated with elevated appetite during an OGTT, with no differences in gut peptides or adipocytokines to explain risperidone's effect on appetite. Further research is needed to explore other mediators of weight gain and metabolic dysfunction in SGA-treated youth.

Topics: Adolescent; Antipsychotic Agents; Appetite; Child; Cross-Sectional Studies; Female; Humans; Male; Mental Disorders; Peptide Hormones; Pilot Projects; Quetiapine Fumarate; Risperidone; Satiation

4β-Hydroxycholesterol (4βOHC) is sensitive towards induction or inhibition of CYP3A4, but its potential usefulness as a dosing biomarker remains to be demonstrated. The aim of this study was to investigate the correlation between 4βOHC levels and steady-state concentrations (Css) of quetiapine, a CYP3A4 substrate with high presystemic metabolism, in psychiatric patients.. Serum samples from 151 patients treated with quetiapine as immediate release (IR; n = 98) or slow release (XR; n = 53) tablets were included for analysis of 4βOHC. In all patients, Css of quetiapine had been measured at trough level, i.e. 10-14 and 17-25 h post-dosing for IR and XR tablets, respectively. Correlations between 4βOHC levels and dose-adjusted Css (C/D ratios) of quetiapine were tested by univariate (Spearman's) and multivariate (multiple linear regression) analyses. Gender, age (≥60 vs. <60 years) and tablet formulation were included as potential covariates in the multivariate analysis.. Correlations between 4βOHC levels and quetiapine C/D ratios were highly significant both for IR- and XR-treated patients (P < 0.0001). Estimated Spearman r values were -0.47 (95% confidence interval -0.62, -0.30) and -0.56 (-0.72, -0.33), respectively. The relationship between 4βOHC level and quetiapine C/D ratio was also significant in the multiple linear regression analysis (P < 0.001), including gender (P = 0.023) and age (P = 0.003) as significant covariates.. The present study shows that 4βOHC level is significantly correlated with steady-state concentration of quetiapine. This supports the potential usefulness of 4βOHC as a phenotype biomarker for individualized dosing of quetiapine and other drugs where systemic exposure is mainly determined by CYP3A4 metabolism.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Biomarkers, Pharmacological; Cytochrome P-450 CYP3A; Delayed-Action Preparations; Female; Humans; Hydroxycholesterols; Male; Mental Disorders; Middle Aged; Prospective Studies; Quetiapine Fumarate; Sex Factors; Tablets; Young Adult

Oculogyric crises are involuntary movements of the eyeballs and can occur due to different etiologies.. This video abstract shows a man with oculogyric crises due to side effect of neuroleptics.. Oculogyric crises are easy to recognize if once seen.

Topics: Antipsychotic Agents; Dibenzocycloheptenes; Dystonic Disorders; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Mental Disorders; Ocular Motility Disorders; Quetiapine Fumarate; Young Adult

Following Good Pharmacovigilance Practices Module XVI, two complementary studies were performed that included process and outcome measurements of the effectiveness of physician education on metabolic monitoring of patients receiving quetiapine. A multinational survey of 800 European Union physicians was utilized to assess the receipt of educational materials and also to assess the degree of monitoring as reported by physicians. Recall of receipt of educational materials ranged from 16.0 to 69.0% across the participating countries; however, physicians reported that 64.5% of patients were being monitored, with the majority reporting performance of three or more of four key metabolic-monitoring activities. Higher rates of monitoring were reported by those who reported receiving materials. Assessment of outcomes in a separate retrospective analysis of electronic medical record data showed lower levels of monitoring performed by specialist physicians. The monitoring activities observed were assessed as acceptable on the basis of the established performance of UK physicians, who are incentivized to deliver preventive screening.

Topics: Antipsychotic Agents; Education, Medical, Continuing; Electronic Health Records; European Union; Harm Reduction; Humans; Mental Disorders; Metabolism; Monitoring, Physiologic; Pharmacovigilance; Physicians; Practice Patterns, Physicians'; Quetiapine Fumarate; Retrospective Studies; Surveys and Questionnaires

To investigate the impact of genetic variability in CYP2D6, CYP3A5, and ABCB1 on steady-state serum concentrations of quetiapine and the active metabolite, N-desalkylquetiapine, in psychiatric patients.. Measured serum concentrations of quetiapine and N-desalkylquetiapine from patients with biobanked DNA samples were included retrospectively from a routine therapeutic drug monitoring database. The impact of CYP2D6, CYP3A5, and ABCB1 (345C>T) genotypes on dose-adjusted serum concentrations (C/D ratios) of quetiapine and N-desalkylquetiapine was investigated by multivariate mixed model analysis.. In total, 289 patients with 633 serum measurements were included. In the multivariate analysis, mean C/D ratio of N-desalkylquetiapine was estimated to be 33% and 22% higher in inherent CYP2D6 poor metabolizers (P = 0.03) and heterozygous extensive metabolizers (P < 0.001), respectively, compared with inherent extensive metabolizers. The ABCB1 3435C>T polymorphism and CYP3A5 genotype had no significant influence on either of the substances in the present material.. Genetic variability in CYP2D6 contributes to the interindividual variability in steady-state serum concentrations of N-desalkylquetiapine. Although the metabolite exhibits relevant pharmacological activity, the quantitative effect of CYP2D6 genotype on serum concentration of N-desalkylquetiapine is probably of limited clinical relevance for quetiapine treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; ATP Binding Cassette Transporter, Subfamily B; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Drug Monitoring; Female; Genotype; Humans; Male; Mental Disorders; Middle Aged; Multivariate Analysis; Polymorphism, Genetic; Quetiapine Fumarate; Retrospective Studies; Young Adult

Antipsychotic drugs (APs) are of great benefit in several psychiatric disorders, but they can be associated with various adverse effects, including seizures. To investigate the effects of chronic antipsychotic treatment on seizure susceptibility in genetically epilepsy-prone rats, some APs were administered for 7 weeks, and seizure susceptibility (audiogenic seizures) was evaluated once a week during treatment and for 5 weeks after drug withdrawal. Furthermore, acute and subchronic (5-day treatment) effects were also measured. Rats received haloperidol (0.2-1.0 mg/kg), clozapine (1-5 mg/kg), risperidone (0.03-0.50 mg/kg), quetiapine (2-10 mg/kg), aripriprazole (0.2-1.0 mg/kg), and olanzapine (0.13-0.66 mg/kg), and tested according to treatment duration. Acute administration of APs had no effect on seizures, whereas, after regular treatment, aripiprazole reduced seizure severity; haloperidol had no effects and all other APs increased seizure severity. In chronically treated rats, clozapine showed the most marked proconvulsant effects, followed by risperidone and olanzapine. Quetiapine and haloperidol had only modest effects, and aripiprazole was anticonvulsant. Finally, the proconvulsant effects lasted at least 2-3 weeks after treatment suspension; for aripiprazole, a proconvulsant rebound effect was observed. Taken together, these results indicate and confirm that APs might have the potential to increase the severity of audiogenic seizures but that aripiprazole may exert anticonvulsant effects. The use of APs in patients, particularly in patients with epilepsy, should be monitored for seizure occurrence, including during the time after cessation of therapy. Further studies will determine whether aripiprazole really has a potential as an anticonvulsant drug and might also be clinically relevant for epileptic patients with psychiatric comorbidities.

Topics: Animals; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Disease Models, Animal; Epilepsy; Haloperidol; Mental Disorders; Olanzapine; Quetiapine Fumarate; Rats; Risperidone; Seizures

In 2004, the American Diabetes Association (ADA) released treatment guidelines recommending metabolic screening for children and adolescents before and after initiation of second-generation antipsychotics. Prior studies showed that the guidelines coincided with a small increase in glucose testing of children and adults but had limited follow-up. This study sought to evaluate changes in metabolic screening of children initiating second-generation antipsychotics around the time of the 2004 guidelines and in the following eight years.. Study patients (N=52,407) were identified in a large nationwide commercial insurance claims database for the period January 1, 2003, through December 31, 2011. The study population was a cohort of nondiabetic new users of second-generation antipsychotics who were ages 5-18. Glucose and HbA1c tests completed before and after second-generation antipsychotic initiation were identified with Current Procedural Terminology-4 codes. Metabolic screening was also examined by second-generation antipsychotic agent prescribed and psychiatric diagnosis.. The proportion of patients receiving a glucose test preinitiation increased from 17.9% in 2003 to 18.9% in 2004, and testing postinitiation increased from 14.7% to 16.6% in the same period. The slight increase in glucose testing was not sustained; the proportion tested dropped in the following years before rising again in 2008. Glucose screening was most common for patients taking aripiprazole. Patients with a diagnosis of hyperkinetic disorder were less likely to be tested. HbA1c testing was less frequent but had a similar usage pattern.. The small improvement in metabolic screening immediately after the 2004 ADA guidelines were issued was not sustained. Overall, metabolic screening rates remained suboptimal throughout the study period.

Topics: Adolescent; Affective Disorders, Psychotic; Antipsychotic Agents; Anxiety Disorders; Aripiprazole; Benzodiazepines; Blood Glucose; Child; Child, Preschool; Cohort Studies; Conduct Disorder; Databases, Factual; Depressive Disorder; Diabetes Mellitus; Female; Glycated Hemoglobin; Guideline Adherence; Humans; Hyperkinesis; Male; Mass Screening; Mental Disorders; Olanzapine; Piperazines; Practice Guidelines as Topic; Practice Patterns, Physicians'; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Thiazoles

Second-generation antipsychotic (SGA) effects in youth were monitored to quantify extrapyramidal side effects (EPS) and to identify risk profiles for treatment-emergent EPS.. Data were analyzed for the nonrandomized, prospective Second-generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) inception cohort study. EPS were assessed at baseline and 4, 8, and 12 weeks after naturalistic SGA initiation for schizophrenia, mood, disruptive behavior, and autism spectrum disorders using the Simpson-Angus Scale (SAS), Barnes Akathisia Scale, Abnormal Involuntary Movement Scale (AIMS), and Treatment Emergent Side Effect Scale. Drug-induced parkinsonism was defined by incident mean SAS score >0.33, anticholinergic initiation, or increasing total SAS score ≥2 in patients with baseline EPS.. In 342 youth aged 13.6 ± 3.5 years (male = 58.2%, antipsychotic-naive = 65.8%), 15.2% developed drug-induced parkinsonism. Raw SGA-grouped drug-induced parkinsonism rates were as follows: quetiapine = 1.5%, olanzapine = 13.8%, risperidone = 16.1%, ziprasidone = 20.0%, and aripiprazole = 27.3%. SGA type, dose, higher age, and lower baseline functioning were jointly associated with drug-induced parkinsonism (R(2) = 0.18; p < .0001). Controlling for these factors, drug-induced parkinsonism rates were significantly lower only for quetiapine and olanzapine. Subjectively reported EPS (5%), EPS-related treatment discontinuation (3.3%), and anticholinergic initiation (3%) were infrequent. Anticholinergic initiation was most frequent with risperidone (10.2%; p = .0004). Treatment-emergent dyskinesia ranged from 4.5% (aripiprazole) to 15.5% (olanzapine). SGA type, younger age, white race/ethnicity, and baseline AIMS were jointly associated with treatment-emergent dyskinesia (R(2) = 0.31; p < .0001). Controlling for these factors, treatment-emergent dyskinesia rates differed among SGA subgroups, with higher rates with olanzapine and ziprasidone. At baseline, psychostimulant use was associated with dyskinesia, and number of psychotropic comedications was associated with subjective EPS.. In youth, SGA-related EPS rates did not generally exceed those reported in adults, with particularly low rates with quetiapine and olanzapine.

Topics: Adolescent; Akathisia, Drug-Induced; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Male; Mental Disorders; Multivariate Analysis; New York; Olanzapine; Parkinson Disease, Secondary; Piperazines; Prospective Studies; Quetiapine Fumarate; Regression Analysis; Risperidone; Thiazoles

To determine the risk of developing obesity and related metabolic complications in children following long-term treatment with risperidone or quetiapine.. This was a 1-year naturalistic longitudinal study conducted between February 2009 and March 2012. A total of 130 children aged 2 to 18 years without prior exposure to second-generation antipsychotics (SGAs) were enrolled at initiation of treatment with either risperidone or quetiapine. Metabolic parameters were measured at baseline and months 6 and 12. Data of 37 participants (20 treated with risperidone and 17 treated with quetiapine) who completed 12-month monitoring were used in the analysis.. After 1 year of SGA treatment, mean weight increased significantly by 10.8 kg (95% CI 7.9 kg to 13.7 kg) for risperidone and 9.7 kg (95% CI 6.5 kg to 12.8 kg) for quetiapine. Body mass index z score also increased significantly in both groups (P < 0.001). There was a high incidence of children becoming overweight or obese (6/15 [40.0%] for risperidone-treated and 7/14 [50.0%] for quetiapine-treated). The mean levels of fasting glucose (for risperidone-treated) and ratio of total cholesterol to high-density lipoprotein cholesterol (for quetiapine-treated) increased significantly by 0.23 mmol/L (95% CI 0.03 mmol/L to 0.42 mmol/L) and 0.48 mmol/L (95% CI 0.15 mmol/L to 0.80 mmol/L), respectively.. Children treated with risperidone or quetiapine are at a significant risk for developing obesity, elevated waist circumference, and dyslipidemia during 12 months of treatment. These data emphasize the importance of regular monitoring for early identification and treatment of metabolic side effects.

Topics: Adolescent; Antipsychotic Agents; Anxiety Disorders; Attention Deficit and Disruptive Behavior Disorders; Blood Pressure; Body Mass Index; British Columbia; Child; Child Development Disorders, Pervasive; Child, Preschool; Cholesterol; Cholesterol, HDL; Cohort Studies; Dyslipidemias; Female; Humans; Incidence; Longitudinal Studies; Male; Mental Disorders; Metabolic Syndrome; Mood Disorders; Obesity; Overweight; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Waist Circumference

Medicaid programs are concerned about inappropriate, potentially hazardous, and costly off-label use of second-generation antipsychotics (SGAs). Several states are exploring policies aimed at managing low-dose quetiapine, commonly prescribed for off-label conditions. This study aimed to characterize longitudinal trends and patient characteristics associated with low-dose quetiapine in two state Medicaid programs. We further aimed to quantify changes in the use of quetiapine associated with a legal settlement that curtailed off-label promotion of this product.. Using administrative data from two state Medicaid programs, Oregon and Colorado, we identified SGA initiators and determined patient level factors associated with receipt of low-dose SGAs. We evaluated changes in low-dose quetiapine initiation during and after a period in which quetiapine was being promoted illegally for off-label purposes.. We identified 14,763 new SGA starts during the study period. Low-dose (versus therapeutic dose) SGA use was common in both states, representing 53% to 56% of initiators. Quetiapine was the most commonly used SGA in both states and both dose ranges. Diagnoses of schizophrenia, bipolar disorder, posttraumatic stress disorder, anxiety disorder, and use of newer sedative hypnotics were associated with lower likelihood of initiating low-dose quetiapine. Initiation of low-dose quetiapine as a proportion of all SGA initiation and of all quetiapine initiation significantly declined in Oregon following suspension of off-label promotional activities.. Low-dose SGA and specifically low-dose quetiapine use remains common. Medicaid programs must set policies carefully to maximize the net safety of prescription use while optimizing disease management considering the potential for substitution effects.

Topics: Adult; Antipsychotic Agents; Cohort Studies; Colorado; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Medicaid; Mental Disorders; Middle Aged; Oregon; Quetiapine Fumarate; Retrospective Studies; Treatment Outcome; United States

Besides dietary, hormonal, or pathological factors, mutations in cytochrome P450 enzymes are thought to be responsible for the interindividual differences in serum concentrations of cytochrome P450 (CYP450)-dependent drugs. Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of greater than 50% of the prescribed drugs. Recently, a new single-nucleotide polymorphism (SNP) was found (CYP3A4*22), which results in a decreased enzyme activity, in contrast to the other known SNPs in CYP3A4. We investigated to which degree the CYP3A4*22 SNP affects serum concentrations of patients receiving quetiapine, a drug exclusively metabolized by CYP3A4.. Two hundred thirty-eight adult patients receiving quetiapine were included in this study, based on availability of DNA, serum quetiapine levels, and information on dose. Patients were genotyped for CYP3A4*22 using allele-specific polymerase chain reaction, and, as a control, restriction fragment length polymorphism analysis.. Carriers of the CYP3A4*22 allele (*1/*22 and *22/*22, n = 31) had 2.5-fold higher serum levels of quetiapine than did wild-type patients (n = 207; P = 0.03) when using a comparable dose (median, 300 mg/d for both wild-type and carriers; P = 0.67). The dose-corrected serum concentration (C/D) was 67% higher in carriers than in wild-type patients (P = 0.01). The number of patients who achieved serum levels above the therapeutic range (>500 µg/L) was also higher in *22-allele carriers (16.1% vs 2.9%; P = 0.007).. Being a carrier of the CYP3A4*22 allele increases the serum concentration of quetiapine at comparable doses.

Topics: Adolescent; Adult; Antipsychotic Agents; Case-Control Studies; Cytochrome P-450 CYP3A; Dibenzothiazepines; Female; Heterozygote; Humans; Male; Mental Disorders; Middle Aged; Netherlands; Polymorphism, Single Nucleotide; Quetiapine Fumarate; Retrospective Studies; Young Adult

Second-generation antipsychotics (SGAs) are commonly prescribed to youth but are associated with metabolic effects including obesity and diabetes. The mechanisms underlying diabetes development are unclear. The purpose of this study was to compare glucose homeostasis, insulin sensitivity, insulin secretion, and overall β-cell function in risperidone-treated, quetiapine-treated, and SGA-naive youth with mental illness. We conducted a cross-sectional study in which youth aged 9 to 18 years underwent a 2-hour oral glucose tolerance test. Indices for insulin sensitivity (Matsuda index), insulin secretion (insulinogenic index), and β-cell function (insulin secretion-sensitivity index-2 [ISSI-2]) were calculated. A total of 18 SGA-naive, 20 risperidone-treated, and 16 quetiapine-treated youth participated. The 3 groups were similar in age, sex, ethnicity, body mass index standardized for age and sex, pubertal status, degree of psychiatric illness, psychiatric diagnoses, and other medications. The median treatment duration was 17 months (range, 3-91 months) for risperidone-treated youth and 10 months (range, 3-44 months) for quetiapine-treated youth. The quetiapine-treated group had lower insulinogenic index (P < 0.01) and lower ISSI-2 (P < 0.01) compared with that in the SGA-naive group. Only the body mass index standardized for age and sex was negatively associated with Matsuda index (β = -0.540, P < 0.001) in all youth. Quetiapine treatment was negatively associated with insulinogenic index (β = -0.426, P = 0.007) and ISSI-2 (β = -0.433, P = 0.008). Quetiapine reduced the insulin expression in isolated mouse islets suggesting a direct β-cell effect. Our results suggest that quetiapine treatment in youth is associated with impaired β-cell function, specifically lower insulin secretion. Prospective longitudinal studies are required to understand the progression of β-cell dysfunction after quetiapine initiation.

Topics: Adolescent; Animals; Antipsychotic Agents; Blood Glucose; Body Mass Index; Child; Cross-Sectional Studies; Dibenzothiazepines; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Mental Disorders; Mice; Mice, Inbred C57BL; Quetiapine Fumarate; Risperidone

To assess weight and metabolic effects of 6 months of treatment with second-generation antipsychotics in naïve/quasi-naïve youths.. This study looked at a nonrandomized, naturalistic, multicenter, inception cohort study of 279 patients aged 4 to 17 years (mean = 14.6 ± 2.9 years). Of those, 248 (88.8%) received a single antipsychotic (risperidone, olanzapine, or quetiapine) and completed 2 visits, and 178 (63.8%) completed the 6-month follow-up. Patients had schizophrenia-spectrum disorders (44.5%), mood-spectrum disorders (23.2%), disruptive behavioral disorders (17.3%), or other disorders (15.1%). Fifteen age- and gender-matched, healthy, nonmedicated individuals served as a comparison group.. From baseline to 1 month, 3 months, and 6 months, all anthropometric measures increased significantly with each antipsychotic, that is, 6-month changes with risperidone (n = 157; 7.1 kg and 0.66 body mass index [BMI] z score), olanzapine (n = 44; 11.5 kg and 1.08 BMI z score), and quetiapine (n = 47; 6.3 kg and 0.54 BMI z score), but not in healthy control participants (-0.11 kg and 0.006 BMI z score). Fasting metabolic parameters increased significantly with risperidone (glucose [3.8] mg/dL, insulin [4.9] mU/L, homeostasis model assessment of insulin resistance [HOMA-IR: 1.2], triglycerides [15.6] mg/dL), and olanzapine (glucose [5.0] mg/dL, total cholesterol [21.2] mg/dL, and low-density lipoprotein cholesterol [44.6] mg/dL), but not with quetiapine or in healthy control participants. The percentage of research participants considered to be "at risk of adverse health outcome" increased during the 6 months from 8.9% to 29.2% for risperidone (p < .0001), 6.8% to 38.1% for olanzapine (p < .0001), and 6.3% to 4.0% for quetiapine (p = .91).. Olanzapine, quetiapine, and risperidone increase body weight but have different cardiometabolic side effect profiles and different temporal side effect patterns.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Dibenzothiazepines; Female; Humans; Male; Mental Disorders; Olanzapine; Prognosis; Prospective Studies; Quetiapine Fumarate; Risk Factors; Risperidone

A retrospective analysis was followed on 20 case reports covering the possible correlation between the atypical antipsychotic, quetiapine, and neuroleptic malignant syndrome (NMS), determined by the study of 7 different NMS criteria guidelines. A great majority (19) of the case studies did not meet the requirements of all 7 guidelines, frequently due to unreported information. Nor was quetiapine proven to be the sole cause of the possible NMS in the two age groups investigated. Only one case was found to have no other medication or medical conditions confounding the relationship of quetiapine and NMS symptoms, and that case was in the context of a significant quetiapine overdose. The other 19 cases demonstrated the difficulty of identifying the cause of NMS when polypharmacy and other medical conditions are involved. The authors note the need for caution in deciding both the presence of NMS and the causal factors of the symptoms.

Topics: Adult; Age Factors; Antiparkinson Agents; Antipsychotic Agents; Diagnosis, Differential; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Dose-Response Relationship, Drug; Fever; Guideline Adherence; Humans; Mental Disorders; Middle Aged; Muscle Rigidity; Neuroleptic Malignant Syndrome; Practice Guidelines as Topic; Quetiapine Fumarate; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome; Young Adult

A 64-year-old man presented with 40 years history of chronic alcohol excess. On average, he had six hospital admissions a year with alcohol-related problems for at least a 10-year period. In 2009, he considered reducing his alcohol intake. He was noted to have mood disturbances, was seen by a psychogeriatrician who diagnosed bipolar disorder. He tried various bipolar medications including lithium and sodium valproate which was unsuccessful. He was then started on quetiapine 600 mg a day in divided doses. Subsequently this has not only controlled the bipolar disorder but also resulted in significant reduction in alcohol intake. He now shares a bottle of wine with his wife while in the past he was consuming a bottle of scotch daily. This case illustrates the benefits of quetiapine in assisting with this man's addiction to alcohol.

Topics: Alcoholism; Antipsychotic Agents; Dibenzothiazepines; Humans; Male; Mental Disorders; Middle Aged; Patient Admission; Quetiapine Fumarate

To investigate the influence of a single episode of psychiatric inpatient treatment on metabolic parameters.. A total of 294 consecutive patients of an Upper Austrian psychiatric department were assessed at admission and discharge regarding bodyweight, body mass index (BMI), high density cholesterol (HDL), low density cholesterol (LDL), triglycerides (TG) and fasting glucose (FG), and the TG/HDL ratio.. Patients showed an increase of BMI of 0.35 kg/m² (+ 1.3%) during a mean duration of inpatient stay of 25.8 days. LDL rose by 10.7 mg/dl (+ 8.1%), triglycerides by 23.0 mg/dl (+ 17%), HDL decreased by 4.4 mg/dl (-7.4%). Fasting glucose decreased by 3.6 mg/dl (-3.8%), yet the TG/HDL ratio, as a marker for insulin resistance, increased significantly from 2.86 to 3.58 (+ 25.2%) on average. Patients with psychotic disorders gained about three times more weight than patients with other diagnoses. Negative alterations of serum lipids were to be found in all diagnostic groups but were especially pronounced in patients with psychotic disorders who were treated with second-generation antipsychotics clozapine, olanzapine and quetiapine.. Psychiatric inpatient treatment leads to clinically relevant deterioration of metabolic parameters within a short time, most pronouncedly in patients with psychotic disorders.

Topics: Antipsychotic Agents; Austria; Benzodiazepines; Biomarkers; Body Mass Index; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Clozapine; Dibenzothiazepines; Female; Glucose; Hospitalization; Humans; Insulin Resistance; Length of Stay; Lipid Metabolism; Male; Mental Disorders; Middle Aged; Multivariate Analysis; Olanzapine; Polypharmacy; Prospective Studies; Psychiatric Department, Hospital; Psychotic Disorders; Quetiapine Fumarate; Regression Analysis; Triglycerides; Weight Gain

Peripheral arterial compliance is a measure of elasticity of the arteries that has been found to be a robust predictor of prevalent arteriosclerosis as well as incident stroke and myocardial infarction. Psychiatric diagnoses and second generation antipsychotics may contribute to cardiovascular risk and stroke, but effects on peripheral arterial compliance are unknown. This study compared peripheral arterial compliance in healthy male controls to male patients with psychiatric diagnoses who were treated with quetiapine or risperidone or off antipsychotics at time of testing.. The groups consisted of 63 patients with mental illness taking quetiapine, risperidone, or no antipsychotics. There were 111 males in the control group. Mean thigh and calf arterial compliance among four groups were compared by ANCOVA, adjusting for body mass index and Framingham Risk Score. All patients were also compared to the control group. Compliance was measured with a computerized plethysmography device.. Patients (n=63) had significantly lower arterial compliance in both thigh and calf than the controls. Arterial compliance in the calf was significantly lower in the subgroups of quetiapine (n=16) and risperidone (n=19) treated, and in unmedicated (n=28) patients than in controls. In the thigh, patients taking either quetiapine or risperidone had significantly lower arterial compliance than controls. These subgroups did not differ from each other in arterial compliance.. The presence of psychiatric diagnoses is associated with reduced arterial compliance. A large study may be required to measure any specific affects of antipsychotics such as quetiapine and risperidone on compliance compared to controls.

Topics: Adult; Aged; Analysis of Variance; Antipsychotic Agents; Blood Pressure; Compliance; Dibenzothiazepines; Femoral Artery; Humans; Male; Mental Disorders; Middle Aged; Quetiapine Fumarate; Retrospective Studies; Risperidone

There exists a growing argument in favour of a more dimensional approach to the diagnosis and treatment of psychiatric patients. This encompasses first the idea of a spectrum of symptoms correlating to severity within a single disorder, and secondly, the idea of spectra of different disorders sharing overlapping collections of symptoms. Here we consider the issue in light of specific clinical examples we have observed, which support the idea of a 'mental illness spectrum', both with symptoms within a single disorder, and between different mental disorders.

Topics: Antipsychotic Agents; Bipolar Disorder; Borderline Personality Disorder; Combined Modality Therapy; Comorbidity; Depressive Disorder, Major; Diagnosis, Differential; Dibenzothiazepines; Humans; International Classification of Diseases; Mental Disorders; Prodromal Symptoms; Psychotherapy; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The abuse of medications in prison is a phenomenon well known among correctional health care professionals, and quetiapine has emerged as a drug of abuse in these settings. Considering the risks of abuse and diversion and the high cost compared with effective alternative antipsychotic medications, the New Jersey Department of Corrections (NJDOC) Pharmacy and Therapeutics Committee voted to remove quetiapine from the formulary. In a retrospective chart review, clinically relevant outcome measures were evaluated in patients prescribed quetiapine at the time of this change. Psychiatrists attempted to stop the quetiapine in 63.4 percent of the cases and were successful (not requiring continuation or restarting of the medicine) 95.7 percent of the time. There were no statistically significant differences in the number of patients who needed a higher level of care, days in a higher level of care, number of patients needing constant (e.g., suicide) watch, days on constant watch, suicidal behavior, or disciplinary charges when the subjects in whom an attempt to discontinue quetiapine was made was compared with those in whom it was continued. In 44.7 percent of cases in which an attempt was made to stop quetiapine (and in 28.3% of cases in the entire NJDOC population as of January 2009), no antipsychotic medication was needed to manage the patients during the study period. This study supports the decision to remove quetiapine from the NJDOC formulary.

Topics: Antipsychotic Agents; Cost Savings; Dibenzothiazepines; Drug Costs; Drug Substitution; Formularies as Topic; Humans; Illicit Drugs; Mental Disorders; New Jersey; Prescription Drugs; Prisons; Quality Assurance, Health Care; Quetiapine Fumarate; Retrospective Studies; Substance-Related Disorders

Weight gain is an undesirable side effect of second-generation antipsychotics (SGAs). We performed this study to examine the influence of SGAs on resting energy expenditure (REE) and the relationship of REE to weight gain in adolescent patients.. Antipsychotic-naïve or quasi-naïve (<72 h of exposure to antipsychotics) adolescent patients taking olanzapine, quetiapine, or risperidone in monotherapy were followed up for one year. We performed a prospective study (baseline, 1, 3, 6, and 12 months after treatment) based on anthropometric measurements, bioelectrical impedance analysis, and indirect calorimetry (Deltatrac™ II MBM-200) to measure REE. We also analyzed metabolic and hormonal data and adiponectin concentrations.. Forty-six out of the 54 patients that started treatment attended at least 2 visits, and 16 completed 1 year of follow-up. Patients gained 10.8 ± 6.2 kg (60% in the form of fat mass) and increased their waist circumference by 11.1 ± 5.0 cm after 1 year of treatment. The REE/kg body mass ratio decreased (p = 0.027), and the REE/percentage fat-free mass (FFM) ratio increased (p = 0.007) following the fall in the percentage of FFM during treatment. Weight increase was significantly correlated with the REE/percentage FFM ratio at all the visits (1-3-6-12 months) (r = 0.69, p = 0.004 at 12 months).. SGAs seem to induce a hypometabolic state (reflected as decreased REE/kg body mass and increased REE/percentage FFM). This could explain, at least in part, the changes in weight and body composition observed in these patients.

Topics: Adiponectin; Adolescent; Adolescent Development; Antipsychotic Agents; Basal Metabolism; Benzodiazepines; Biomarkers; Body Composition; Child; Cohort Studies; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Mental Disorders; Olanzapine; Prospective Studies; Quetiapine Fumarate; Risperidone; Waist Circumference; Weight Gain

Topics: Adolescent; Analysis of Variance; Antipsychotic Agents; Aripiprazole; Attention Deficit and Disruptive Behavior Disorders; Benzodiazepines; Bipolar Disorder; Body Mass Index; Body Weight; Child; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Mental Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Spain; Time Factors

The purpose of this study was to identify children in a state Medicaid population who were newly treated with second-generation antipsychotics from 2001 through 2005, to classify each use of these agents as evidence based or not depending on the child's diagnoses, and to identify factors associated with the likelihood of evidence-based use of the medication.. A Medicaid claims database was used to retrospectively identify enrollees receiving initial outpatient treatment with a second-generation antipsychotic between 2001 and 2005. To capture all relevant treatments and diagnoses, claims were examined from January 2000 through December 2006. The final sample included 11,700 children under age 18. The primary measure of interest was the proportion for whom use of the antipsychotic was based on evidence. Evidence-based use (categorized as strong, plausible, or weak evidence) was defined as any use of the agent for a diagnosis supported by a clinical trial published before the end of 2005. Trend analysis and logistic regression were used.. The number of children newly treated with second-generation antipsychotics increased from 1,482 in 2001 to 3,110 in 2005. Of the new users of these agents during the study period, 41.3% had no diagnosis for which such treatment was supported by a published study. The medication with the highest level of non-evidence-based use was aripiprazole (77.1%), and risperidone had the lowest (30.6%).. The number of children receiving second-generation antipsychotics doubled in this Medicaid population between 2001 and 2005, and a large proportion of the treatments were not supported by evidence from clinical studies.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Child, Preschool; Clozapine; Dibenzothiazepines; Drug Utilization; Evidence-Based Medicine; Female; Humans; Infant; Insurance Claim Review; Male; Medicaid; Mental Disorders; Off-Label Use; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; United States; United States Food and Drug Administration

Patterns of discontinuation of atypical antipsychotic drugs, including the return to therapy after an interruption, have not been examined longitudinally.. This study was conducted to describe discontinuation patterns of atypical antipsychotic drugs across a spectrum of outpatients in the province of Québec.. This retrospective, inception cohort study employed data from the Québec health insurance board databases and the Québec hospitalization registry on Québec Drug Plan beneficiaries between the ages of 20 and 64 years who first filled a prescription for any antipsychotic drug between January 1, 2000, and December 31, 2007. Five subcohorts were constructed according to the initial antipsychotic received: either 1 of the 4 atypical antipsychotics covered by the Québec drug plan at the time of the study-olanzapine, quetiapine, risperidone, and clozapine-or polytherapy (>1 atypical antipsychotic, or 1 atypical and 1 typical antipsychotic). Discontinuation was defined as a failure to refill the initial prescription within 2 times the days' supply of the preceding claim. In individuals who discontinued initial drug treatment, a new course of treatment was defined as initiation of treatment with any antipsychotic drug after a first treatment discontinuation. Discontinuation of a second course of treatment was defined as failure to refill a prescription for the second drug within 2 times the days' supply of the preceding claim. Patients were followed from initiation to December 31, 2004, ineligibility for the drug plan, or death, whichever came first. Kaplan-Meier curves and Cox regression models were used to compare discontinuations and new courses of treatment by initial atypical antipsychotic.. The overall cohort consisted of 46,074 drug plan beneficiaries who had initiated antipsychotic treatment during the specified period. The majority of individuals were female (54.6%) and lived in urban areas (79.2%); the median age ranged from 40 to 44 years. The mean (SD) duration of follow-up was 2.67 (1.91) years. Compared with individuals whose initial therapy was olanzapine, those whose initial therapy was quetiapine had a significantly higher likelihood of discontinuing initial treatment (adjusted hazard ratio [AHR] = 1.06; 95% CI, 1.04-1.09; P < 0.001). The likelihood of discontinuing initial treatment was significantly lower among those whose initial therapy was risperidone (AHR = 0.93; 95% CI, 0.90-0.95; P < 0.001), clozapine (AHR = 0.56; 95% CI, 0.46-0.68; P < 0.001), or polytherapy (AHR = 0.69; 95% CI, 0.64-0.74; P < 0.001). Those whose initial therapy was quetiapine were significantly less likely than those whose initial therapy was olanzapine to begin a second course of treatment (AHR = 0.95; 95% CI, 0.90-0.99; P = 0.02). Compared with individuals who initiated a second course of treatment with olanzapine, those who initiated a second course with quetiapine were more likely to discontinue again (AHR = 1.09; 95% CI, 1.04-1.14; P < 0.001), whereas those who initiated a second course with risperidone were less likely to discontinue again (AHR = 0.95; 95% CI, 0.90-1.00; P = 0.04).. This study population had a high risk of discontinuing initial atypical antipsychotic therapy within 1 year. Those who discontinued had a low likelihood of returning to treatment, and those who did return to treatment had a high likelihood of discontinuing again. These patterns of use may have serious consequences for patients' health and for the utilization of health services.

Topics: Adult; Age Distribution; Antipsychotic Agents; Benzodiazepines; Clozapine; Cohort Studies; Databases, Factual; Dibenzothiazepines; Drug Prescriptions; Drug Therapy, Combination; Drug Utilization; Drug Utilization Review; Female; Humans; Kaplan-Meier Estimate; Male; Mental Disorders; Middle Aged; Olanzapine; Patient Compliance; Quebec; Quetiapine Fumarate; Registries; Retrospective Studies; Risperidone; Sex Distribution; Young Adult

Despite known metabolic effects of second-generation antipsychotics (SGAs) on children and adolescents, comparative effects in youth with different diagnoses remain underreported. We compared differences in metabolic changes three months after starting treatment with SGAs in youth with bipolar disorder and with other psychotic and nonpsychotic disorders.. Weight and metabolic differences among diagnostic groups before and three months after starting treatment with SGAs were compared in a naturalistic cohort of children and adolescents (14.9 +/- 3.0 years) diagnosed with bipolar disorder (n = 31), other psychotic disorders (n = 29), and other nonpsychotic disorders (n = 30), with no (35.6%) or very little (6.6 +/- 9.0 days) previous exposure to antipsychotics. Composite measurements of significant weight gain [weight increase > or = 5% at three months or increase > or = 0.5 in body mass index (BMI) z-score] and 'risk for adverse health outcome' (> or = 95(th) BMI percentile, or > or = 85(th) BMI percentile plus presence of one other obesity-related complication) were included. SGAs (risperidone, olanzapine, and quetiapine) were prescribed in comparable proportion among groups.. Baseline weight and metabolic indices were not significantly different among diagnoses. Three months after starting treatment with SGAs, more than 70% patients had significant weight gain, BMI z-score increased in all diagnostic groups (p < 0.001 for all comparisons), total cholesterol increased in the bipolar (p = 0.02) and psychotic (p = 0.01) disorder groups, low-density lipoprotein cholesterol increased in the bipolar group (p = 0.02), and free T4 decreased in the psychotic disorder group (p = 0.05). More patients with bipolar disorder presented overweight plus > or = 1 obesity-related complication at follow-up.. There are early weight gain and metabolic changes across diagnoses in youth treated with SGAs.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Biomarkers; Bipolar Disorder; Body Mass Index; Child; Cholesterol, LDL; Chromatography, High Pressure Liquid; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Mental Disorders; Obesity; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thyroxine; Treatment Outcome; Weight Gain

Topics: Antipsychotic Agents; Dibenzothiazepines; Drug Industry; Humans; Marketing of Health Services; Mental Disorders; Off-Label Use; Quetiapine Fumarate

Topics: Adult; Antipsychotic Agents; Axilla; Dibenzothiazepines; Female; Humans; Hyperhidrosis; Male; Mental Disorders; Middle Aged; Quetiapine Fumarate; Treatment Outcome; Young Adult

The aim of the current study was to evaluate quetiapine doses used across diagnosis categories in a sample of psychiatric inpatients.. Discharge letters of all adult inpatients who had received quetiapine between 1999 and 2005 were retrospectively reviewed. Logistic regressions were carried-out to assess links between quetiapine discharge dosage (> or =800 mg/day vs. <800 mg/day), diagnostic categories, substance abuse or dependence, benzodiazepine discharge doses, age and sex.. The data of 231 patients were included. Five hundred and for discharge documents were analyzed: 113 for psychotic disorders, 190 for personality disorders, 134 for bipolar and schizoaffective bipolar disorders, 29 for unipolar depression or anxiety disorders, and 35 for mental retardation. Considering psychotic disorders as a reference group, patients with personality disorders were statistically significantly less likely to be in the high quetiapine dosage group at discharge (P = 0.007, OR = 0.1 and CI [0.03; 0.6]).. Quetiapine seems to be used in a variety of clinical situations, with a wide range of doses and a lower dosage in patients treated for personality disorders.

Topics: Adult; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Bipolar Disorder; Cross-Sectional Studies; Depressive Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Intellectual Disability; Male; Mental Disorders; Middle Aged; Patient Discharge; Patient Readmission; Personality Disorders; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies

Quetiapine is frequently prescribed for insomnia that is comorbid with psychiatric disorders, but there has been no documentation of metabolic adverse effects associated with this practice. The objective of this study was to document changes in weight, body mass index, and waist circumference that occurred when low-dose quetiapine was used at bedtime for insomnia. The study was a retrospective chart review conducted at a community mental health center. Patients were non-elderly (19-65 years old) psychiatric patients who received quetiapine at < or =200 mg at bedtime for the explicit indication of insomnia. Forty-three patients were included in the study. Weight and BMI increased by an average of 4.9 lb. (P = 0.037) and 0.8 points (P = 0.048), respectively. Males experienced statistically significant increases in weight and BMI, and Caucasians experienced a statistically significant increase in BMI. There were no significant differences between baseline and endpoint metabolic parameters when examined by baseline BMI, age category, psychiatric diagnosis, or concomitant psychotropic medication. Despite the low doses typically used when quetiapine is prescribed for insomnia, metabolic adverse effects can occur and should be considered in the overall benefit to risk analysis.

Topics: Adult; Alabama; Antipsychotic Agents; Body Mass Index; Comorbidity; Dibenzothiazepines; Female; Humans; Male; Medical Audit; Mental Disorders; Middle Aged; Quetiapine Fumarate; Retrospective Studies; Sleep Initiation and Maintenance Disorders; Weight Gain; Young Adult

Topics: Antipsychotic Agents; Child; Dibenzothiazepines; Female; Humans; Hyperglycemia; Mental Disorders; Quetiapine Fumarate

To examine a cohort of Medicaid patients with new prescriptions for atypical antipsychotic medication to determine the prevalence of subtherapeutic atypical antipsychotic medication use and to identify patient and prescribing provider characteristics associated with occurrence of subtherapeutic use.. This observational cohort study examined Medicaid administrative claims data for patients aged 20 to 64 years with a new prescription for an atypical antipsychotic medication (clozapine, olanzapine, quetiapine, risperidone, ziprasidone) between January 1, 2004, and December 31, 2004. Patient diagnostic information was identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes on submitted medical claims. Patient characteristics, prescribing provider characteristics, length of therapy, and dosing were examined. A logistic regression assessed the probability of subtherapeutic dosing.. Among 830 individuals in our sample who began treatment with an atypical antipsychotic, only 15% had a documented diagnosis of schizophrenia, subtherapeutic dosing was common (up to 86% of patients taking quetiapine), and 40% continued less than 30 days with the index prescription. A logistic model indicated that a general practitioner as prescribing provider, length of therapy equal to or less than 30 days, and prescription of quetiapine were significantly associated with a subtherapeutic dose (p < .001, p = .028, and p < .001, respectively).. These results suggest that there is extensive use of expensive atypical antipsychotic medications for off-label purposes such as sedation or for other practice patterns that should be explored further. Approaches that minimize off-label atypical antipsychotic use could be of considerable value to Medicaid programs. In addition, these findings support the need for the introduction or increased use of utilization monitoring and the implementation of medication practice guidelines as appropriate decision support for prescribing providers.

Topics: Adult; Antipsychotic Agents; Case-Control Studies; Dibenzothiazepines; Drug Administration Schedule; Drug Utilization; Female; Humans; Insurance Claim Review; Logistic Models; Longitudinal Studies; Male; Medicaid; Medication Adherence; Mental Disorders; Middle Aged; Multivariate Analysis; Oregon; Practice Patterns, Physicians'; Quetiapine Fumarate; United States

Topics: Alzheimer Disease; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Humans; Mental Disorders; Quetiapine Fumarate

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Mental Disorders; Olanzapine; Proportional Hazards Models; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Survival Analysis; Treatment Outcome

The aim of this study was to compare clinical and health services outcomes in pediatric inpatients prescribed an atypical antipsychotic (AA) to those not prescribed an AA at discharge.. Descriptive statistics, analysis of variance (ANOVA), and, where necessary, analysis of covariance (ANCOVA) were used to compare differences between and within an inpatient group prescribed risperidone, olanzapine, or quetiapine (n=1,131) with an inpatient group not prescribed an antipsychotic at discharge (n=1,741).. The AA treatment group showed greater psychiatric symptom difficulty at admission as measured by the Brief Psychiatric Rating Scale for Children (Mean BPRS-C) than the group not prescribed AAs (40.3 [n=433] vs. 35.2 [n=452], respectively, p<0.001). AA-treated inpatients also had a higher number of mental health outpatient visits during the 6 months prior to admission. Patients receiving AAs (n=1,050) had significantly longer adjusted length of stay (LOS) than those not receiving antipsychotics (n=1,664): 26.4 days versus 22.4 days, respectively (p<0.04).. The findings suggested pediatric inpatients presenting with greater psychiatric symptom difficulty at hospital admission were more likely to be prescribed an AA. Choice of AA may influence certain clinical and health services outcomes. Additional prospective controlled studies evaluating AA efficacy and safety, including head-to-head comparisons, in pediatric inpatients are warranted.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Child; Child, Preschool; Dibenzothiazepines; Female; Humans; Length of Stay; Male; Mental Disorders; Olanzapine; Outcome and Process Assessment, Health Care; Practice Patterns, Physicians'; Quetiapine Fumarate; Retrospective Studies; Risperidone; Weight Gain

Topics: Antipsychotic Agents; Benzodiazepines; Cohort Studies; Dibenzothiazepines; Drug Administration Schedule; Drug Resistance; Humans; Mental Disorders; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Selection Bias; Thiazoles; Treatment Outcome

Therapeutic drug monitoring (TDM) is used increasingly for managing psychiatric outpatients, where the preanalytic error risk is high. Blood samples must be collected under steady-state conditions immediately before ingestion of the morning dose or before the next injection. In order to interpret the plasma levels accurately, age, gender, ethnicity, compliance, drug dosage, renal and hepatic function and comedication incl. smoking habits and diet (esp. caffeine intake and consumption of grapefruit juice) have to be taken into account. If in doubt, aberrant plasma levels should be confirmed by a second control under optimized conditions. Pharmacogenetic testing enables the identification of abnormal metabolizers. TDM and pharmacogenetic tests are useful tools to improve pharmacotherapy by preventing dose-dependent adverse drug events, optimizing dosage during long-term treatment and identifying ultrarapid metabolizers and malcompliance.

Topics: Adverse Drug Reaction Reporting Systems; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Biological Availability; Clomipramine; Cytochrome P-450 CYP2D6; Delusions; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Female; Genotype; Humans; Male; Mental Disorders; Metabolic Clearance Rate; Middle Aged; Pharmacogenetics; Psychotropic Drugs; Quetiapine Fumarate

Weight gain and the risk of developing alterations in lipid and glucose metabolism are possible side effects of atypical antipsychotic therapy in young and adult patients. The objective of this study was to examine whether elderly patients with Alzheimer's disease (AD) gain weight or develop disturbances in lipid and glucose metabolism while being treated with atypical antipsychotic drugs.. This retrospective study identified 36 out of 99 patients (mean age: 75.4+/-7.1, 27 female, 9 males) who were taking risperidone (N=9, mean dosage: 1.42+/-0.49 mg/day), olanzapine (N=17: 4.42+/-1.10 mg/day), and quetiapine (N=10: 75+/-27 mg/day) over a 12 months period. Anthropometric parameters, mini nutritional assessment (MNA), total, HDL and LDL cholesterol, triglycerides, glycaemia were assessed at baseline (T0) and 12 (T1) months.. Body weight (BMI=23+/-5 vs 23+/-5), MNA score (21+/-4 vs 21+/-4), blood glucose (5.7+/-2 vs 4.9+/-0.9 mmol/L) or total cholesterol (4.9+/-1.1 vs 4.3+/-0.7 mmol/L), HDL cholesterol (1.3+/-0.3 vs 1.1+/-0.3 mmol/L), LDL cholesterol (3.3+/-0.7 vs 3 +/- 0.4 mmol/L), triglycerides (1.1+/-0 vs 1+/-0.3 mmol/L) did not reveal treatment-induced changes in the patients evaluated (T0 vs T1).. These results suggest that the treatment with low-dose of atypical antipsychotic drugs is not associated with weight gain or increase the risk of developing type II diabetes or abnormalities of lipid metabolism among elderly patients with AD, who were residing in long-term nursing home.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Dibenzothiazepines; Female; Humans; Lipids; Male; Mental Disorders; Nursing Homes; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Risperidone; Weight Gain

To outline the prescribing patterns of atypical antipsychotics for adult mental health outpatients in Auckland and Northland in 2004.. All community files were reviewed retrospectively (n = 6165). Patient characteristics, diagnosis, and antipsychotic and concurrent medication were recorded and analysed.. Overall, 71.3% of outpatients were prescribed an antipsychotic, of which 82.5% were atypicals: oral risperidone (30.9%), olanzapine (30.3%), quetiapine (17.1%), clozapine (26.3%), and depot risperidone (0.4%). Psychotic disorders accounted for 73.2% of outpatients on atypicals, and schizophrenia was the most common disorder overall (62.5%). Combination antipsychotic treatment occurred in 13.5% of those prescribed atypicals; 4.8% had another atypical and 8.7% had a typical co-prescribed. Clozapine was least likely to be combined with a typical antipsychotic. Those receiving combination typical and atypical antipsychotics had a greater likelihood of being prescribed an anticholinergic medication.. Atypical antipsychotics are the preferred treatment for outpatients with psychotic illness and are being prescribed in a manner consistent with clinical practice guidelines. Co-prescribing of antipsychotics was low, but may be causing unnecessary adverse effects and risks.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Prescriptions; Drug Therapy, Combination; Drug Utilization Review; Female; Humans; Male; Mental Disorders; Middle Aged; New Zealand; Olanzapine; Practice Patterns, Physicians'; Quetiapine Fumarate; Retrospective Studies; Risperidone

The purpose of this study is to determine sociodemographic, clinical, and pharmacotherapeutic characteristics, especially use of atypical antipsychotics, associated with incident diabetes mellitus in a population of privately insured patients with mental health diagnoses. Patients with a mental health diagnosis stably medicated for a 3-month period during January 1999 through October 2000 and having no diabetes were followed through December 2000. Cox proportional hazards models were developed to identify antipsychotic medications associated with newly diagnosed diabetes. Of the 7381 patients identified, 339 developed diabetes, representing an annual incidence rate of 4.7%. Diabetes risk among the entire sample was lowest for risperidone (hazard ratio [HR] = 0.69; p < 0.05), while quetiapine (HR = 0.74), olanzapine (HR = 0.95), and clozapine (HR = 1.22) were not significantly different from first-generation antipsychotics. Diabetes risk was significantly lower among males receiving risperidone (HR = 0.49; p < 0.01) or quetiapine (HR = 0.50; p < 0.10), while diabetes risk among females did not differ significantly from first-generation antipsychotics for any atypical examined. These findings are substantially different from other reports.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Incidence; Insurance Coverage; Male; Mental Disorders; Olanzapine; Proportional Hazards Models; Quetiapine Fumarate; Risk Factors; Risperidone; Sex Factors; United States

The purpose of this study was to assess trends in utilization and costs of antipsychotic drugs among a population of older adults over time, with respect to the prevalence of users, shifts in prescribing patterns, and related financial implications.. Cross-sectional time series of quarterly and annual antipsychotic utilization and cost were obtained from administrative databases for calendar years 1993 through 2002.. A population-based study of more than 1.4 million residents of the province of Ontario aged 65 years or older.. Data sources used included the Ontario Drug Benefits (ODB) database and Statistics Canada census data.. The prevalence of antipsychotic users increased by 34.8% over the study period from 2.2% at the beginning of 1993 to 3.0% of the elderly at the end of 2002 (p < 0.01). This was associated with a 749% increase in total cost (from $3.7 million in 1993 to $31.4 million in 2002; p < 0.01). The atypical antipsychotics, which were not available in 1993, made up 82.5% of the antipsychotics dispensed and 95.2% of costs in 2002.. The modest increase in antipsychotic prevalence in the elderly over the last ten years has been associated with a substantial increase in cost, with a significant shift towards use of the atypical antipsychotics. As the atypical antipsychotics are increasingly used for patients with dementia, which is becoming more prevalent in the aging population, an understanding of the benefits of these medications must be balanced with a detailed understanding of the material and financial implications.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Cross-Sectional Studies; Dibenzothiazepines; Drug Costs; Humans; Mental Disorders; Olanzapine; Ontario; Population Surveillance; Quetiapine Fumarate; Risperidone

Topics: Administration, Intranasal; Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Mental Disorders; Prisoners; Quetiapine Fumarate; Substance Abuse, Intravenous

The incidence of neuroleptic malignant syndrome (NMS) is not known, but the frequency of its occurrence with conventional antipsychotic agents has been reported to vary from 0.02% to 2.44%.. MEDLINE search conducted in January 2003 and review of references within the retrieved articles.. Our MEDLINE research yielded 68 cases (21 females and 47 males) of NMS associated with atypical antipsychotic drugs (clozapine, N = 21; risperidone, N = 23; olanzapine, N = 19; and quetiapine, N = 5). The fact that 21 cases of NMS with clozapine were found indicates that low occurrence of extrapyramidal symptoms (EPS) and low EPS-inducing potential do not prevent the occurrence of NMS and D(2) dopamine receptor blocking potential does not have direct correlation with the occurrence of NMS. One of the cardinal features of NMS is an increasing manifestation of EPS, and the conventional antipsychotic drugs are known to produce EPS in 95% or more of NMS cases. With atypical antipsychotic drugs, the incidence of EPS during NMS is of a similar magnitude.. For NMS associated with atypical antipsychotic drugs, the mortality rate was lower than that with conventional antipsychotic drugs. However, the mortality rate may simply be a reflection of physicians' awareness and ensuing early treatment.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bromocriptine; Clozapine; Dantrolene; Dibenzothiazepines; Dopamine Agonists; Female; Humans; Intubation; Male; MEDLINE; Mental Disorders; Middle Aged; Muscle Relaxants, Central; Neuroleptic Malignant Syndrome; Olanzapine; Quetiapine Fumarate; Respiration, Artificial; Risperidone; Treatment Outcome

Topics: Adolescent; Antipsychotic Agents; Dibenzothiazepines; Humans; Hypothyroidism; Intellectual Disability; Male; Mental Disorders; Quetiapine Fumarate; Thyroid Function Tests

Combination therapy with atypical antipsychotic agents has not been well studied. Duration of persistence with a prescribed treatment regimen can be used to estimate overall treatment success.. The aim of this study was to determine whether valproate augmentation improved treatment efficacy (ie, persistence with the prescribed regimen) and efficacy (ie, reduction of antipsychotic dose) with atypical antipsychotic drugs for older and younger patients, using a retrospective database analysis.. Prescription refill data for atypical antipsychotics during calendar-year 2001 from a national pharmacy chain was used for longitudinal analyses. The database was used to identify patients aged 15 to 64 years and > or =65 years taking risperidone, quetiapine, or olanzapine (but not valproate). Patients who switched to another atypical antipsychotic (group A) or added valproate (group B) were followed after the index prescription to determine the duration of persistence with the treatment regimen and dose changes.. We identified 10,262 patients who were prescribed an atypical antipsychotic, of whom 1022 patients switched to an alternative atypical and 1651 added valproate to the index atypical. The addition of valproate provided significantly longer duration of treatment regimen (mean, 155-159 days) than switching from any atypical antipsychotic drug (mean, 127-130 days) for patients aged 15 to 64 years or > or =65 years (all P<0.001). Atypical antipsychotic doses did not change significantly from baseline to final prescription in groups A or B. The final mean (SD) dose of valproate added to risperidone (389.1 [130.7] mg/d) was significantly lower than valproate added to quetiapine (424.6 [117.1] mg/d; P=0.002) or olanzapine (411.6 [122.8] mg/d; P=0.007).. In this naturalistic study, the addition of valproate to an atypical antipsychotic increased the duration of treatment compared with switching among atypical antipsychotics. Valproate augmentation may be a good treatment strategy for patients whose atypical antipsychotic monotherapy is inadequate.

Topics: Adolescent; Adult; Age Factors; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Synergism; Drug Therapy, Combination; Female; Humans; Longitudinal Studies; Male; Mental Disorders; Middle Aged; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Risperidone; Survival Analysis; Time Factors; Treatment Outcome; Valproic Acid

To explore the clinical characteristics of hyperglycemia in patients treated with quetiapine.. A pharmacovigilance survey of spontaneously reported adverse events in quetiapine-treated patients was conducted using reports from the U.S. Food and Drug Administration MedWatch program (January 1, 1997, through July 31, 2002) and published cases using the search terms hyperglycemia, diabetes, acidosis, ketosis, and ketoacidosis.. We identified 46 reports of quetiapine-associated hyperglycemia or diabetes and 9 additional reports of acidosis that occurred in the absence of hyperglycemia and were excluded from the immediate analyses. Of the reports of quetiapine-associated hyperglycemia, 34 patients had newly diagnosed hyperglycemia, 8 had exacerbation of preexisting diabetes mellitus, and 4 could not be classified. The mean +/- SD age was 35.3 +/- 16.2 years (range, 5-76 years). New-onset patients (aged 31.2 +/- 14.8 years) tended to be younger than those with preexisting diabetes (43.5 +/- 16.4 years, p = .08). The overall male:female ratio was 1.9. Most cases appeared within 6 months of quetiapine initiation. The severity of cases ranged from mild glucose intolerance to diabetic ketoacidosis or hyperosmolar coma. There were 21 cases of ketoacidosis or ketosis. There were 11 deaths.. Atypical antipsychotic use may unmask or precipitate hyperglycemia.. An additional 23 cases were identified since August 1, 2002, the end of the first survey, by extending the search through November 30, 2003, bringing the total to 69.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Antipsychotic Agents; Child; Child, Preschool; Comorbidity; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Dibenzothiazepines; Female; Humans; Hyperglycemia; Hyperglycemic Hyperosmolar Nonketotic Coma; Male; MEDLINE; Mental Disorders; Middle Aged; Pharmacoepidemiology; Quetiapine Fumarate; Schizophrenia; Sex Distribution; United States; United States Food and Drug Administration

This study evaluated length of stay (LOS) associated with atypical antipsychotic monotherapy in inpatients with Alzheimer's disease. In addition to sociodemographic information, data were also obtained on severity of illness, medications, used, patient satisfaction, and hospitalization. Sociodemographics and severity of illness at admission were similar in groups taking olanzapine (N = 66), quetiapine (N = 41), and risperidone (N = 147). The mean LOS for risperidone was significantly shorter than that for quetiapine (12.3 vs. 16.4 days, respectively; P < .02), but the difference between risperidone and olanzapine did not reach statistical significance (12.3 vs. 14.9 days, respectively; P < .08). The savings associated with risperidone versus quetiapine therapy, based on an estimated daily hospital care cost of $492, was $2,017.20 per patient.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cost Savings; Dibenzothiazepines; Drug Costs; Drug Utilization Review; Female; Geriatric Assessment; Health Services Research; Humans; Length of Stay; Male; Mental Disorders; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; United States

Increasingly, atypical antipsychotic drugs are prescribed for elderly patients with symptoms of psychosis and behavioral disturbances. These symptoms often occur in patients with Alzheimer's disease, other dementias, or Parkinson's disease. As the average age of Americans increases, the prevalence of Alzheimer's disease and Parkinson's disease will rise accordingly. Although nonpharmacologic treatments for behavioral disturbances should be tried first, medications often are needed to enable the patient to be adequately cared for. Current guidelines recommend using risperidone and olanzapine to treat psychosis in patients with Alzheimer's dementia. Quetiapine and clozapine are recommended for treatment of psychosis in patients with Parkinson's disease. Additional research is needed for a recently approved agent, ziprasidone. To minimize side effects, these medications should be started at low dosages that are increased incrementally. Drug interactions, especially those involving the cytochrome P450 system, must be considered. Clozapine's potentially lethal side effects limit its use in the primary care setting. Informed use of atypical antipsychotic drugs allows family physicians to greatly improve quality of life in elderly patients with dementia and behavior disturbances.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Comorbidity; Dementia; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone