quetiapine-fumarate and Acute-Disease

The dose-response relationships of antipsychotic drugs for schizophrenia are not well defined, but such information would be important for decision making by clinicians. The authors sought to fill this gap by conducting dose-response meta-analyses.. A search of multiple electronic databases (through November 2018) was conducted for all placebo-controlled dose-finding studies for 20 second-generation antipsychotic drugs and haloperidol (oral and long-acting injectable, LAI) in people with acute schizophrenia symptoms. Dose-response curves were constructed with random-effects dose-response meta-analyses and a spline model. The outcome measure was total score reduction from baseline on the Positive and Negative Syndrome Scale or the Brief Psychiatric Rating Scale. The authors identified 95% effective doses, explored whether higher or lower doses than the currently licensed ones might be more appropriate, and derived dose equivalencies from the 95% effective doses.. Sixty-eight studies met the inclusion criteria. The 95% effective doses and the doses equivalent to 1 mg of oral risperidone, respectively, were as follows: amisulpride for patients with positive symptoms, 537 mg/day and 85.8 mg; aripiprazole, 11.5 mg/day and 1.8 mg; aripiprazole LAI (lauroxil), 463 mg every 4 weeks and 264 mg; asenapine, 15.0 mg/day and 2.4 mg; brexpiprazole, 3.36 mg/day and 0.54 mg; haloperidol, 6.3 mg/day and 1.01 mg; iloperidone, 20.13 mg/day and 3.2 mg; lurasidone, 147 mg/day and 23.5 mg; olanzapine, 15.2 mg/day and 2.4 mg; olanzapine LAI, 277 mg every 2 weeks and 3.2 mg; paliperidone, 13.4 mg/day and 2.1 mg; paliperidone LAI, 120 mg every 4 weeks and 1.53 mg; quetiapine, 482 mg/day and 77 mg; risperidone, 6.3 mg/day and 1 mg; risperidone LAI, 36.6 mg every 2 weeks and 0.42 mg; sertindole, 22.5 mg/day and 3.6 mg; and ziprasidone, 186 mg/day and 30 mg. For amisulpride and olanzapine, specific data for patients with predominant negative symptoms were available. The authors have made available on their web site a spreadsheet with this method and other updated methods that can be used to estimate dose equivalencies in practice.. In chronic schizophrenia patients with acute exacerbations, doses higher than the identified 95% effective doses may on average not provide more efficacy. For some drugs, higher than currently licensed doses might be tested in further trials, because their dose-response curves did not plateau.

Topics: Acute Disease; Administration, Oral; Antipsychotic Agents; Aripiprazole; Clozapine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Haloperidol; Humans; Imidazoles; Indoles; Isoxazoles; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Piperidines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Thiophenes

Pancreatitis is a very rare adverse effect of quetiapine treatment, with only 5 cases of quetiapine-associated pancreatitis reported in the English literature to date. Herein, we report one patient who developed severe hypertriglyceridemia (>1000 mg/dL) after quetiapine administration, resulting in acute pancreatitis. An analysis of the underlying pathogenic mechanisms and a review of relevant literature are also presented. Clinicians should be aware of the potentially life-threatening metabolic disturbances and/or pancreatitis associated with quetiapine therapy.

Topics: Acute Disease; Bipolar Disorder; Dibenzothiazepines; Humans; Hypertriglyceridemia; Pancreatitis; Quetiapine Fumarate

Patients with bipolar disorder are symptomatic about half of the time, experiencing depression more often than mania/hypomania. Because patients usually seek treatment during a depressive episode (rather than a manic episode), bipolar depression is commonly misdiagnosed as unipolar depression. Providing an accurate and timely bipolar depression diagnosis is critical for the proper treatment of the patient. Some FDA-approved treatments are helpful during acute and maintenance phases of therapy, but there is a significant unmet need for effective bipolar depression treatments with favorable side-effect profiles. Newer agents offer the promise of improvements in tolerability, but additional research is needed to actualize this promise into better treatments for patients struggling with bipolar depression.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depression; Dibenzothiazepines; Drug Therapy, Combination; Fluoxetine; Humans; Isoindoles; Lurasidone Hydrochloride; Olanzapine; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Thiazoles

Precise estimated risks and benefits of quetiapine for acute bipolar depression are needed for clinical practice.. To systematically review the efficacy and the tolerability of quetiapine, either as monotherapy or combination therapy, for acute bipolar depression.. We included all randomized, controlled trials (RCTs) comparing quetiapine with other treatments, including placebo, in patients with acute bipolar depression (bipolar I or II disorder, major depressive episode). Published and unpublished RCTs were identified using the Cochrane Central Register of Controlled Trials, MEDLINE, Web of Knowledge, CINAHL, PsycINFO, the EU Clinical Trials Register database, and ClinicalTrials.gov. The primary outcome was the change scores of depression rating scales.. Eleven RCTs (n=3,488) were included. Two of them were conducted in children and adolescents. The change in depression scores was significantly greater in the quetiapine group compared with the placebo group (mean difference, [MD] =-4.66, 95% confidence interval [CI] -5.59 to -3.73). The significant difference was observed from week 1. Compared with placebo, quetiapine had higher incidence rates of extrapyramidal side effects, sedation, somnolence, dizziness, fatigue, constipation, dry mouth, increased appetite, and weight gain but lower risks of treatment-emergent mania and headache. Quetiapine treatment was associated with significant improvement of clinical global impression, quality of life, sleep quality, anxiety, and functioning.. Quetiapine monotherapy is effective for acute bipolar depression and the prevention of mania/hypomania switching. Its common adverse effects are extrapyramidal side effects, sedation, somnolence, dizziness, fatigue, constipation, dry mouth, increased appetite, and weight gain. The lower risk of headache in quetiapine-treated patients with acute bipolar depression should be further investigated. The evidence for the use of quetiapine combined with mood stabilizers in children and adolescents with acute bipolar depression is too small to support the clinical practice.

Topics: Acute Disease; Bipolar Disorder; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Bipolar depression is more pervasive than mania, but has fewer evidence-based treatments.. Using data from multicenter, randomized, double-blind, placebo-controlled trials and meta-analyses, we assessed the number needed to treat (NNT) for response and the number needed to harm (NNH) for selected side effects for older and newer acute bipolar depression treatments.. The 2 older FDA-approved treatments for bipolar depression, olanzapine-fluoxetine combination (OFC) and quetiapine (QTP) monotherapy, were efficacious (response NNT=4 for OFC, NNT=6 for QTP), but similarly likely to yield harms (OFC weight gain NNH=6; QTP sedation/somnolence NNH=5). Commonly used unapproved agents (lamotrigine monotherapy and adjunctive antidepressants) tended to be well-tolerated (with double-digit NNHs), although this advantage was at the cost of inadequate efficacy (response NNT=12 for lamotrigine, NNT=29 for antidepressants). In contrast, the newly approved agent lurasidone was not only efficacious (response NNT=5 for monotherapy, NNT=7 as adjunctive therapy), but also had enhanced tolerability (NNH=15 for akathisia [monotherapy], NNH=16 for nausea [adjunctive]). Although adjunctive armodafinil appeared well tolerated, its efficacy in bipolar depression has not been consistently demonstrated in randomized controlled trials.. NNT and NNH are categorical metrics; only selected NNHs were assessed; limited generalizability of efficacy (versus effectiveness) studies.. For acute bipolar depression, older approved treatments may have utility in high-urgency situations, whereas lamotrigine and antidepressants may have utility in low-urgency situations. Newly approved lurasidone may ultimately prove useful in diverse situations. New drug development needs to focus on not only efficacy but also on tolerability.

Topics: Acute Disease; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Combinations; Fluoxetine; Humans; Isoindoles; Lamotrigine; Lurasidone Hydrochloride; Multicenter Studies as Topic; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Thiazoles; Triazines; Weight Gain

Treatment of acute mania with second-generation antipsychotics has been claimed to involve a lower risk of switch to depression than haloperidol. However, clinical guidelines clearly state that this is not a proven fact.. Meta-analysis of double-blind randomized controlled trials in acute mania, comparing rates of switch to depression with atypical antipsychotics and with haloperidol. Search was conducted in MEDLINE and CENTRAL databases (last search: September 2011).. 8 randomized clinical trials fulfilled inclusion criteria. 2 of them were excluded because of low methodological quality or lack of data. 5 second-generation antipsychotics (aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone) were compared to haloperidol. In the mixed effects model the Risk Ratio for depressive switch was 0.71 (0.52, 0.96) favouring atypical antipsychotics. In the random effects model the difference did not reach statistical significance. In the heterogeneity analysis, exclusion of an outlying aripiprazole trial yielded a Risk Ratio of 0.58 (0.42, 0.82) with a non-significant heterogeneity test. Although no atypical antipsychotic was individually significantly superior to haloperidol, a trend could be seen favouring olanzapine (RR=0.56 [0.29, 1.08]), quetiapine (RR=0.36 [0.10, 1.33]), and ziprasidone (RR=0.51 [0.22, 1.18]).. All trials were industry supported, with some variability in dosage of haloperidol. Switch to depression was not the primary outcome of the trials. Heterogeneity could be explained as a lack of class-effect for atypicals.. Treating acute mania with atypicals is associated to 42% less risk of switch to depression than with haloperidol. Nevertheless, caution should be taken when considering this a class effect, as only olanzapine, quetiapine, and ziprasidone may show a better profile.

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Depression; Depressive Disorder; Dibenzothiazepines; Double-Blind Method; Drug Industry; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Research Support as Topic; Risperidone; Thiazoles

Schizophrenia and bipolar depression trials suggest that quetiapine may have an antidepressant effect.. This meta-analysis aimed to determine the efficacy, acceptability and tolerability of quetiapine treatment for major depressive disorder (MDD). Only the randomized controlled trials (RCTs) comparison between quetiapine and placebo were included. The authors searched such clinical trials carried out between 1991 and February 2012.. MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Study populations comprised adults with MDD or major depression. STUDY ELIGIBLE CRITERIA, PARTICIPANTS AND INTERVENTIONS: Eligible studies were randomized, placebo-controlled trials of quetiapine monotherapy carried out in adults with MDD and presenting endpoint outcomes relevant to: i) depression severity, ii) response rate, iii) overall discontinuation rate, or iv) discontinuation rate due to adverse events. No language restriction was applied.. All abstracts identified by the electronic searches were examined. The full reports of relevant studies were assessed, and the data of interest were extracted. Based on the Cochrane methods of bias assessment, risks of bias were determined. The studies with two risks or less were included. The efficacy outcomes were the mean change scores of depression rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate was considered as a measure of acceptability. The discontinuation rate due to adverse events was a measure of tolerability. Relative risks (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were computed by using a random effect model.. A total of 1,497 participants in three RCTs were included. All trials examined the quetiapine extended-release (XR). The pooled mean change scores of the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HAM-D) of the quetiapine-treated group were higher than those of the placebo-treated group with the WMDs (95%CI) of -3.37 (-3.95, -2.79) and -2.46 (-3.47, -1.45), respectively. All studies defined the response and remission as ≥ 50% reduction of the MADRS total score and the MADRS total score of ≤8 at endpoint, respectively. The overall response and remission rates were significantly greater in the quetiapine-treated group with RRs (95%CIs) of 1.44 (1.26, 1.64) and 1.37 (1.12, 1.68), respectively. The pooled discontinuation rate was not significantly different between groups with an RR (95%CI) of 1.16 (0.97, 1.39). The pooled discontinuation rate due to adverse event was greater in the quetiapine group with an RR (95%CI) of 2.90 (1.87, 4.48). With respect to sleep time, the pooled mean change Pittsburgh Sleep Quality Index (PSQI) scores of the quetiapine-treated group was also significantly higher than that of the placebo-treated group [WMD (95%CI) of -1.21 (-1.81, -0.61)].. Variety of quetiapine XR doses and the small number of RCTs were key limitations of this meta-analysis.. Based on the limited evidence obtained from three RCTs, quetiapine XR is effective for adult patients with MDD. The high dropout rate due to adverse events suggests that some MDD patients may not be able to tolerate quetiapine XR. Due to the balance of its efficacy benefit and risk of side effects, as the overall discontinuation rate shown, the acceptability of this agent is not more than placebo. These results should be viewed as the very preliminary one. Further studies in this area are warranted. IMPLICATION OF KEY FINDINGS: Quetiapine may be an alternative antidepressant. However, both risk and benefit of this agent should be taken into account for an individual patient with MDD.

Topics: Acute Disease; Adolescent; Adult; Aged; Antidepressive Agents; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Placebos; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Remission Induction

Bipolar II disorder is a common, recurrent, and disabling psychiatric illness, and yet little is known about how best to treat it. The pressing clinical need for evidence-based approaches to the treatment of bipolar II disorder, coupled with recent publication of pertinent studies, calls for an updated review of this literature. This review focuses on a critical examination of the evidence supporting the efficacy of treatments for acute depressive episodes in bipolar II disorder.. A MEDLINE (via Ovid) search of journals, covering the period from January 1950 to January 2009, was performed to identify relevant studies. Keywords used were bipolar II disorder, bipolar disorder, bipolar depression, and pharmacotherapy. Studies were further limited to those that were in adult samples, published in peer-reviewed journals, and written in English.. We examined all randomized trials evaluating the use of pharmacotherapy in the treatment of acute bipolar II depression. Studies with mixed samples of bipolar I and II or bipolar II and unipolar depression were examined as well. Twenty-one randomized trials were identified and reviewed.. Therapeutic agents were rated according to the quality of evidence supporting their efficacy as treatments for bipolar II depression.. Ninety percent of relevant trials were published after 2005. Quetiapine was judged as having compelling evidence supporting its efficacy. Lithium, antidepressants, and pramipexole were judged as having preliminary support for efficacy. Lamotrigine was considered to have mixed support.. Although progress has been made, further research on bipolar II depression is warranted.

Topics: Acute Disease; Antidepressive Agents; Antimanic Agents; Benzhydryl Compounds; Benzothiazoles; Bipolar Disorder; Dibenzothiazepines; Humans; Lamotrigine; Lithium Compounds; Modafinil; Pramipexole; Quetiapine Fumarate; Triazines

Extended release quetiapine fumarate (quetiapine XR) is a new formulation that allows once-daily dosing and a titration regimen that is simpler than that of immediate release quetiapine (quetiapine IR) and may potentially increase patients' adherence to their prescribed medication.. The tolerability of quetiapine XR was examined in an analysis of pooled data from three Phase III, double-blind, placebo-controlled, randomised studies with quetiapine IR as a reference treatment.. The overall incidence of adverse events (AEs) was similar for quetiapine XR (69.5%) and quetiapine IR (72.5%). Most AEs were mild to moderate in severity and in line with those observed with quetiapine IR. The more rapid dose titration of quetiapine XR did not produce any new safety concerns and was as well tolerated as the regimen for quetiapine IR.. The results of this pooled analysis show that quetiapine XR administered once daily is generally as well tolerated as quetiapine IR given twice daily. These data, together with the simpler dose-titration of quetiapine XR that allowed therapeutically effective doses to be reached by Day 2, suggest that this formulation potentially may improve adherence in patients with schizophrenia.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Neutropenia; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Young Adult

Results from pivotal registration trials in major depressive disorder cohere with outcomes from effectiveness studies indicating that the majority of individuals receiving single-agent pharmacotherapy fail to achieve and sustain symptomatic remission. Several factors provided the impetus for this review: suboptimal efficacy with existing pharmacotherapy for major depressive disorder, quetiapine XR efficacy in the acute and maintenance treatment of bipolar depression, emerging pharmacodynamic evidence that quetiapine XR (and/or its metabolites) uniquely engages monoaminergic systems salient to symptom relief in depressive syndromes, the increasing use of second-generation antipsychotics in the treatment of major depressive disorder and the recent FDA review of quetiapine XR in major depressive disorder. Studies reviewed herein are pivotal registration trials that evaluated the acute and maintenance efficacy and tolerability of quetiapine XR (as monotherapy and as adjunctive treatment) in major depressive disorder. In addition, we also review recent investigations characterizing the pharmacodynamic effect of quetiapine's principal active metabolite, norquetiapine. All studies were obtained from AstraZeneca (Wilmington, DE, USA) and have been presented at national/international scientific meetings. Taken together, extant studies demonstrated that quetiapine XR (50 - 300 mg) provides rapid and sustained symptomatic improvement in the acute and maintenance treatment of major depressive disorder. Quetiapine XR may also offer advantages relative to duloxetine in time to onset of antidepressant action. The major limitations of quetiapine XR use in major depressive disorder relate to weight gain and disrupted glucose/lipid homeostasis as well as sedation/somnolence. Quetiapine XR has tolerability advantages compared with duloxetine on measures of sexual dysfunction. The data from the studies reviewed herein also indicate that quetiapine XR poses a low risk for extrapyramidal side effects in middle-aged and elderly individuals with major depressive disorder.

Topics: Acute Disease; Antidepressive Agents; Antipsychotic Agents; Chronic Disease; Depressive Disorder, Major; Dibenzothiazepines; Drug Therapy, Combination; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Topics: Acute Disease; Adult; Affect; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Interview, Psychological; Lithium Carbonate; Long-Term Care; Male; Quetiapine Fumarate

Topics: Acute Disease; Adult; Affect; Anticonvulsants; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Evidence-Based Medicine; Hospitalization; Humans; Male; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Treatment Outcome; Valproic Acid

Individuals with bipolar disorder are euthymic approximately half of the time, but recurring mood episodes are common, and time spent ill is predominated by depressive symptoms. Despite the prevalence of depression in bipolar disorder, evidence suggests that antidepressants are not likely to benefit most patients. Lithium, long considered a first-line treatment for bipolar disorder, is not the most effective agent for preventing bipolar depression. This article reviews multiple pharmacologic options that should be considered by clinicians treating bipolar disorder in both acute and maintenance phases.

Topics: Acute Disease; Adverse Drug Reaction Reporting Systems; Affect; Anticonvulsants; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnosis, Differential; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fluoxetine; Humans; Lithium Carbonate; Long-Term Care; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome; United States; United States Food and Drug Administration

The efficacy and tolerability of quetiapine in the treatment of acute mania were reviewed.. Five randomized, placebo-controlled trials involving quetiapine as monotherapy or adjunct therapy in combination with either divalproex or lithium in the treatment of bipolar mania in either adolescents or adults were identified and reviewed. The primary outcome measure used in the trials was a change in Young Mania Rating Scale total scores. Monotherapy trials evaluated quetiapine, lithium, haloperidol, and placebo. Quetiapine was superior to placebo in both trials. Quetiapine and lithium showed comparable efficacy in one study, though lithium serum concentrations may have been suboptimal. Haloperidol was superior to quetiapine in efficacy at day 21 but similar at day 84. In the two trials evaluating quetiapine or placebo as adjunct therapy to lithium or divalproex, quetiapine was significantly more efficacious than placebo in one trial. In adolescents, quetiapine was more effective than placebo as an adjunct to divalproex. The most common adverse effects clearly attributable to quetiapine in these trials were somnolence and dry mouth. Quetiapine did not induce extrapyramidal effects, but weight gain was notable with the drug.. While quetiapine treatment demonstrated efficacy in the majority of the studies, the robustness of its efficacy is questionable. The use of quetiapine as first-line therapy for acute mania is not recommended based on the available results and cost considerations. However, it may be a useful second-line agent, particularly when sensitivity to extrapyramidal symptoms limits treatment options.

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Haloperidol; Humans; Lithium Compounds; Quetiapine Fumarate; Valproic Acid

A key goal of the pharmacologic treatment of acute bipolar mania is rapid symptom improvement. Medications commonly used to attain this goal include lithium, several anticonvulsants, and both first- and second-generation antipsychotics. Second-generation antipsychotics, which are associated with substantially lower rates of extrapyramidal side effects than first-generation agents, are becoming a mainstay in the treatment of acute mania. Although their efficacy appears to be comparable, second-generation antipsychotics may differ in time to onset and in their side effect profiles. Therefore, selecting a second-generation antipsychotic requires consideration of how an agent's efficacy, onset of action, and adverse events profile influence its appropriateness for each patient.

Topics: Acute Disease; Anticonvulsants; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Double-Blind Method; Humans; Lithium; Olanzapine; Piperazines; Placebos; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Treatment Outcome

Vieta E, Goikolea JM. Atypical antipsychotics: newer options for mania and maintenance therapy. Bipolar Disord 2005: 7 (Suppl. 4): 21-33. (c) Blackwell Munksgaard, 2005Atypical antipsychotics have been used to treat patients with schizophrenia for many years, but now there is increasing evidence of their utility in the treatment of bipolar disorder. In the past few years several atypical agents have received regulatory approval for use in bipolar mania. Through a review of randomized controlled trials for five commonly used atypical drugs, olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole, this article evaluates their efficacy in the acute and maintenance phases of bipolar disorder. The evidence shows that atypical antipsychotics are effective in the treatment of manic symptoms, either alone or in combination with traditional mood stabilizers such as lithium and divalproex. Although emerging data indicate that atypical antipsychotics will be a promising addition to those therapies that are currently available for managing patients during the maintenance phase of bipolar illness, their potential in the long-term management of bipolar disorder remains to be fully explored. Atypical antipsychotics appear to have broadly similar efficacy against manic symptoms of bipolar disorder, but there are important differences in their tolerability profiles, which are likely to be of particular relevance during long-term treatment. A brief assessment of tolerability issues surrounding the use of atypical agents in bipolar disorder and other aspects of treatment that have impact on the clinical effectiveness of the therapy are considered.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Humans; Lithium Carbonate; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles

In this commentary article we describe our clinical experience and provide our views on the use of quetiapine in the treatment of patients with acute exacerbations of schizophrenia. Some patients with acute schizophrenia may require parenteral medication; however, we believe that oral antipsychotics, either alone or in combination with other medications, have a key role to play as an initial and/or subsequent pharmacotherapeutic intervention. Quetiapine has beneficial calming properties and successfully treats the symptoms of aggression, anxiety and hostility that can accompany acute exacerbations of schizophrenia. Based upon a review of published findings, data presented at recent international psychiatric congresses and our clinical experience, we propose that a more rapid initiation schedule (for example, 400 mg by Day 2, increasing to 600 mg/day by Day 3 and often up to 800 mg/day by Day 4, or in severe cases 300 mg on Day 1, 600 mg on Day 2 and 900 mg on Day 3) than that currently described in quetiapine prescribing information can be used to provide safe, effective treatment in hospitalised patients with acute schizophrenia. (Note that lower doses are used in patients with first-episode schizophrenia.) Furthermore, while current prescribing information recommends that quetiapine be administered at doses up to 750 mg/day (800 mg/day in the USA and Canada), there is growing evidence that dosing up to 1600 mg/day of quetiapine has been well tolerated in some patients. In general, newer antipsychotics have superior tolerability profiles compared with conventional agents; however, clear differences in tolerability exist among the new generation antipsychotics. Quetiapine has an excellent tolerability profile offering high patient acceptability that, in turn, may promote patient adherence to medication and an improved quality of life. As such, we consider quetiapine to be a first-choice antipsychotic for the treatment of acute exacerbations of schizophrenia.

Topics: Acute Disease; Administration, Oral; Algorithms; Antipsychotic Agents; Dibenzothiazepines; Humans; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Topics: Acute Disease; Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Dopamine D2 Receptor Antagonists; Dystonia; Humans; Indoles; Isoindoles; Parkinsonian Disorders; Quetiapine Fumarate; Receptors, Muscarinic; Receptors, Serotonin; Risperidone; Serotonin Antagonists; Syndrome; Thiazoles

Bipolar disorder is ranked as the sixth most important worldwide cause of disability. Current treatment is based chiefly on lithium and/or anticonvulsants, of which sodium valproate is the most widely used. A significant minority of patients fail to respond fully to current treatments, particularly those with mixed mania and/or rapid cycling. Many patients are unable to tolerate the side-effects of current therapy in the long term, and adverse effects may contribute to the high rate of noncompliance observed in bipolar disorder. The shortcomings of current treatments are reflected in poor outcomes: two-thirds of patients with bipolar disorder require hospitalization on more than one occasion; employment and social functioning are significantly lower than in control groups; 93% of carers suffer at least moderate distress; and 25-50% of patients are believed to attempt suicide at least once. Bipolar disorder shares some features with schizophrenia, and several atypical antipsychotics have demonstrated efficacy in bipolar disorder. Quetiapine has a particularly favourable tolerability profile, with placebo-level extrapyramidal symptoms and prolactin levels across the entire dose range combined with a neutral effect on weight during long-term use, and may be a valuable treatment option in acute mania and bipolar disorder.

Topics: Acute Disease; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Patient Care Planning; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Suicide

Atypical neuroleptic agents are an excellent, safer, and more effective alternative to the widespread practice of maintenance adjunctive treatment with traditional neuroleptic agents in patients with bipolar disorder. Currently, a number of prospective studies are available with clozapine, risperidone, olanzapine, and quetiapine in the treatment of bipolar disorder. Most are short-term studies, although longer-term data are becoming available. Four double-blind studies of acute mania have been conducted with risperidone and olanzapine, leading to recent Food and Drug Administration approval for olanzapine in the indication of acute mania. Given the limited longer-term data, and the evidence for mostly adjunctive benefits with these agents, it seems unlikely that these agents will prove to be primary mood stabilizers in their own right. Nonetheless, they serve an important role as adjunctive treatments along with standard mood stabilizers in the rational polypharmacy of bipolar disorder. To date, differences in efficacy have not been established. However, differences in the side effect of weight gain may be even more relevant in bipolar disorder than in schizophrenia due to the need to use standard mood stabilizers that often potentiate such weight gain.

Topics: Acute Disease; Algorithms; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Humans; Lithium; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome; Valproic Acid

When a patient with an acute exacerbation of schizophrenia is admitted into the hospital, the target symptoms include pathologic excitement/agitation and exacerbated psychotic symptoms. The goal of hospitalization becomes attenuation of these symptoms to a level compatible with safe discharge. The mainstay of stabilization is antipsychotic treatment. A risk/benefit analysis of the conventional versus the newer antipsychotics favors the use of the newer agents as first-line drugs. These newer antipsychotic agents represent the first significant advance in the pharmacologic treatment of schizophrenia in the past four decades. They are at least as effective as conventional agents and are clearly superior from a safety perspective. Because of short inpatient stays, the challenge for clinicians is to provide an adequate treatment period without aggressively escalating the dose.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Hospitalization; Humans; Length of Stay; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risk Assessment; Risperidone; Schizophrenia; Schizophrenic Psychology

This study aimed to evaluate the efficacy and safety of quetiapine fumarate extended-release (XR) in the treatment of Chinese patients with acute schizophrenia. Multicenter, double-blind, double-dummy, active-controlled non-inferiority randomized study in Chinese patients (n = 388) with schizophrenia randomly assigned to quetiapine XR or chlorpromazine for 6 weeks. Primary outcome was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at the end of treatment. Safety objectives included adverse event (AE) monitoring, laboratory test results, and electrocardiograms. Changes in PANSS total score were -33.4 for quetiapine XR and -35.9 for chlorpromazine (P > 0.05). Least squares mean changes were: positive subscale, -9.9 ± 0.53 and -11.1 ± 0.51; negative subscale, -5.9 ± 0.50 and -6.7 ± 0.48; general psychopathology subscale, -12.9 ± 0.74 and -13.9 ± 0.71; aggression and hostility cluster scores, -4.8 ± 0.33 and -5.4 ± 0.32; and depression cluster scores, -1.8 ± 0.18 and -1.7 ± 0.18, for quetiapine XR and chlorpromazine, respectively. For quetiapine XR, AEs were constipation, dizziness, insomnia, and agitation, and nine patients (4.6%) discontinued due to AEs. For chlorpromazine, AEs were extrapyramidal symptoms, constipation, insomnia, dizziness, and agitation, and 17 patients (8.9%) discontinued due to AEs; two patients reported serious AEs. Quetiapine XR monotherapy was not inferior to chlorpromazine for treating acute schizophrenia in Chinese patients and was well tolerated.

Topics: Acute Disease; Adult; Aggression; Antipsychotic Agents; Anxiety; Chlorpromazine; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Young Adult

The aim of this study was to evaluate the effectiveness of Quetiapine versus Risperidone in control of acute psychotic signs and symptoms in hospitalized patients during four weeks.. In this double-blind, randomized controlled study, a total of 90 patients with a confirmed diagnosis acute psychosis and were hospitalized in Zare Hospital, Sari, Iran, and they were treated with Quetiapine (mean 500 mg/day) or Risperidone (mean 5.2 mg/day), in a 4 week period. The positive and negative symptoms scale (PANSS) and Clinical Global Impression-Severity scale (CGI-s) were used to assess psychotic symptoms and severity of illness in first and the last day of the study.. No significant difference found between two groups in decreasing positive and negative sub-scores in the PANSS. Risperidone was superior to Quetiapine in decreasing the PANSS general psychopathology sub-scores and total score (p<0.05). No significant difference found between two groups in decreasing CGI-s score.

Topics: Acute Disease; Adult; Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Young Adult

Quetiapine (QTP) has been shown to be effective as an acute treatment in patients with bipolar depression. Nonetheless, the time at onset of QTP antidepressant action has not been clarified. We aimed to evaluate the onset of the antidepressant effect of QTP extended release (XR) in bipolar depression. We also compared the different efficacy and adverse effect profile of 300- and 600-mg/d dosages.. Twenty-one acutely bipolar depressed patients were recruited; 13 were treated with QTP XR 300 and 8 with 600 mg/d. Assessment was performed with Hamilton Depression Rating Scale (also considering clusters "core," "somatic anxiety," "psychic anxiety," "activity," and "delusion"), Hamilton Anxiety Rating Scale, Dosage Record and Treatment Emergent Symptom Scale.. Quetiapine XR was effective since the first 3 days of treatment in reducing all the efficacy measures except for somatic anxiety. The comparison of 300- and 600-mg dosages was limited by the small sample size. However, the analysis did not show any significant difference in terms of efficacy, although with a trend in favor of 600 mg. The incidence of hypotension was significantly higher in patients taking QTP 600 mg (P = 0.004).. Quetiapine seems to be effective in bipolar depression within the first days of treatment. There may be not a significant advantage for the 600-mg dose in comparison with the 300-mg one. The clinical effect seems to be not associated with sedation, suggesting that it may be due to the molecular drug effect. Further studies focusing on the first days of treatment are needed to confirm our findings.

Topics: Acute Disease; Adult; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Time Factors; Treatment Outcome

To study the efficacy and safety of quetiapine-XR as monotherapy or adjunctive therapy to a mood stabilizer in acute bipolar I or II depression with comorbid generalized anxiety disorder (GAD) and other comorbidities.. The study was conducted from January 2007 to November 2011. The Mini-International Neuropsychiatric Interview was used to ascertain the diagnosis of DSM-IV bipolar disorder, GAD, and other Axis I disorders. Eligible patients were randomly assigned to quetiapine-XR or placebo for up to 8 weeks. The Hamilton Depression Rating Scale-17 items (HDRS-17) was used as a primary outcome to evaluate the difference between the 2 groups using the change from baseline to end of study. Last observation carried forward and mixed-effects modeling for repeated measures were used to analyze the primary and secondary outcome measures.. Of the 120 patients screened, 100 patients were randomized to receive quetiapine-XR (n = 50) or placebo (n = 50). Twenty-six patients in the quetiapine-XR and 18 in the placebo group completed the study. The mean quetiapine-XR dose was 276 ± 50 mg/d (50-300 mg/d). There was no significant difference between the 2 groups in the change from baseline to end of study in HDRS-17 total score with an effect size of 0.19 favoring quetiapine-XR. There were also no significant differences between the 2 groups in secondary efficacy and safety outcome measures.. Quetiapine-XR was not significantly superior to placebo in bipolar I or II depression with GAD and other comorbidities, suggesting that data from relatively "pure" bipolar patients may not be generalizable to a highly comorbid population.. ClinicalTrials.gov identifier: NCT00671853.

Topics: Acute Disease; Adult; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Comorbidity; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Drug Synergism; Female; Humans; Male; Middle Aged; Placebos; Quetiapine Fumarate; Treatment Outcome

The main objective of this study was to evaluate efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in generalized anxiety disorder (GAD). This was a 8 week randomized, 2-week follow-up, double-blind, placebo-controlled, and active-controlled study. Patients were randomized to quetiapine XR 150 (n=219) or 300 mg/day (n=207); escitalopram, 10 mg/day (n=213); or placebo (n=215). The primary endpoint was the change from randomization at week 8 in Hamilton Anxiety Rating (HAM-A) total score. Week 8 mean HAM-A total score was significantly reduced from randomization with quetiapine XR 150 mg/day (-13.9, P<0.001), 300 mg/day (-12.3, P<0.05) and escitalopram (-12.3, P<0.05) versus placebo (-10.7); significant improvements with quetiapine XR (150 and 300 mg/day) versus placebo (P<0.001) were also shown at day 4. At week 8, significant improvements versus placebo were observed in HAM-A psychic [quetiapine XR (both doses) and escitalopram] and somatic (quetiapine XR 150 mg/day and escitalopram) cluster scores and HAM-A response and remission rates (quetiapine XR 150 mg/day). Most common adverse events were dry mouth, somnolence and sedation (quetiapine XR), headache, and nausea (escitalopram). In patients with GAD, quetiapine XR (150 and 300 mg/day) demonstrated significant efficacy at week 8 with symptom improvement as early as day 4. We concluded that quetiapine XR safety and tolerability results were consistent with the known profile of quetiapine.

Topics: Acute Disease; Adult; Anti-Anxiety Agents; Anxiety Disorders; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Female; Humans; Logistic Models; Male; Middle Aged; Placebos; Predictive Value of Tests; Psychiatric Status Rating Scales; Quetiapine Fumarate; Time Factors; Treatment Outcome; United States; Young Adult

The aim of this study was to evaluate the efficacy and safety of quetiapine fumarate extended release (XR) in the treatment of Korean subjects with acute schizophrenia.. This was an 8-week, multi-center, open-label, non-comparative study to evaluate the efficacy and safety of quetiapine fumarate XR at a daily dose of 400-800 mg. Changes in total scores on the Positive and Negative Syndrome Scale (PANSS) from baseline to week 8 were analyzed to evaluate the efficacy of quetiapine XR. Additionally, the Clinical Global Impression scale and the Montgomery-Åsberg Depression Rating Scale were administered.. The mean change in PANSS total scores was -26.8, and the mean PANSS total score at the endpoint was significantly lower than that at baseline. The mean PANSS positive score, negative score, and general score showed statistically significant reductions at the end of the study. Statistically significant changes were also observed in Clinical Global Impression-Severity and Montgomery-Åsberg Depression Rating Scale scores. The most common treatment-related adverse events in the group receiving quetiapine XR were sedation (10.6%) and constipation (9.6%).. In this study of Korean patients with acute schizophrenia, quetiapine XR showed clinical efficacy and relatively good tolerability.

Topics: Acute Disease; Adult; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Republic of Korea; Schizophrenia; Severity of Illness Index; Treatment Outcome; Young Adult

Molecules that are involved in neuronal intercommunication and adaptability of neural networks, such as brain-derived neurotrophic factor (BDNF), are targets of pathophysiological investigation in bipolar disorder (BD). Quetiapine is an attested treatment in this disorder, used in acute mood episodes. The aim of this study was to report prospective changes in serum BDNF levels in drug-free patients in acute mood episodes of BD who received treatment with extended-release quetiapine along a 16 week follow-up. Assessments were performed at baseline and weeks 2, 4, 8 and 16 with the Young Mania Rating Scale, the Hamilton Depression Rating Scale and the Clinical Global Impression severity scale. In these visits, serum BDNF levels were measured. Mixed effect models were used to investigate longitudinal changes. Twenty-five patients were included for this analysis, seventeen in a current depressive episode and eight in a manic/mixed episode. A significant improvement from baseline to endpoint was displayed. In the mixed model, significant main effects for episode and time appeared, and a time versus episode interaction showing increasing BDNF levels with time in those with a depressive episode, but a decrease in BDNF levels with time in those with a manic/mixed episode. BDNF may be a biomarker with differential response according to the polarity of mood episodes.

Topics: Acute Disease; Adult; Antipsychotic Agents; Biomarkers; Bipolar Disorder; Brain-Derived Neurotrophic Factor; Delayed-Action Preparations; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Treatment Outcome

Bipolar disorder, a highly recurrent and chronic condition, often necessitates periods of hospitalization and requires lifelong treatment with medication. It is characterized by alternating episodes of mania and depression. Given the severity of mania, physicians must be able to control symptoms rapidly.. The purpose of this pivotal, Phase III trial was to evaluate the efficacy and tolerability of once-daily extended-release quetiapine fumarate (quetiapine XR) monotherapy in improving manic symptoms in patients with bipolar I disorder.. This was a 3-week, randomized, parallel-group, double-blind, placebo-controlled study. Patients aged 18 to 65 years with bipolar I disorder (most recent episode manic or mixed; with or without rapid cycling) were randomized to receive placebo or quetiapine XR monotherapy once daily (300 mg on day 1; 600 mg on day 2; flexible dosing, 400-800 mg, from day 3 through day 22 [study end point, week 3]). The primary outcome measure was the change from baseline to study end in the Young Mania Rating Scale (YMRS) total score. Secondary outcome measures included the Montgomery-Åsberg Depression Rating Scale (MADRS) total score, YMRS response (≥50% reduction in YMRS) and remission (YMRS score ≤12 at final visit) rates, and change from baseline to week 3 in Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S) and CGI-BP-Change (CGI-BP-C) scores. Safety profile and tolerability evaluations included monitoring of adverse events, clinical laboratory values, vital signs, extrapyramidal symptoms (including akathisia), and electrocardiogram results.. Compared with placebo (n = 159), quetiapine XR monotherapy (n = 149; mean daily dose, 604 mg) significantly improved manic symptoms starting at day 4 (first assessment; P < 0.001), with sustained improvement to study end (week 3; P < 0.001). MADRS scores showed greater improvement from baseline to study end with quetiapine XR than with placebo (P = 0.004). Response and remission rates were significantly greater (P < 0.01) with quetiapine XR than with placebo at study end. Quetiapine XR also resulted in significant improvements over placebo in CGI-BP-S and CGI-BP-C scores (P < 0.001 and P < 0.001, respectively). Adverse events were mild to moderate in intensity; the most common ones associated with quetiapine XR were sedation, dry mouth, and somnolence.. This 3-week trial suggests that quetiapine XR (400-800 mg) once-daily monotherapy is efficacious (from day 4) and generally well tolerated in patients with manic or mixed episodes of bipolar I disorder.

Topics: Acute Disease; Adult; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Quetiapine Fumarate

To evaluate the effectiveness of quetiapine extended release once daily in bipolar depression.. Double-blind, placebo-controlled study in acutely depressed adults with bipolar I or II disorder, with or without rapid cycling. Patients were randomized to 8 weeks of quetiapine extended release (XR) 300 mg daily monotherapy or placebo. The primary outcome measure was change from baseline to Week 8 in MADRS total score.. Quetiapine XR 300 mg once daily (N=133) showed significantly greater improvement in depressive symptoms compared with placebo (N=137) from Week 1 (p<0.001) through to Week 8 (p<0.001). Mean change in MADRS total score at Week 8 was -17.4 in the quetiapine XR group and -11.9 in the placebo group (p<0.001). Response (>or=50 reduction in MADRS total score) and remission (MADRS total score

Topics: Acute Disease; Adult; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate

To demonstrate the efficacy of once-daily extended release quetiapine fumarate (quetiapine XR) versus placebo in adults with acute exacerbation of schizophrenia.. A 6-week, double-blind, randomized, placebo-controlled study. In- or out-patients with a DSM-IV diagnosis of schizophrenia were randomized to fixed-dose quetiapine XR 400, 600, or 800 mg/day, quetiapine immediate release (IR) 800 mg/day, or placebo. Primary endpoint was change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 6. Other efficacy assessments included Clinical Global Impressions (CGI) of Severity (CGI-S) and of Improvement (CGI-I) ratings. Safety assessments included adverse event (AE) reporting and laboratory measures.. 565 patients were randomized; 333 (58.9%) completed the study. Greater numeric improvements in PANSS total score were seen for quetiapine XR (all doses) and quetiapine IR versus placebo at Week 6; the differences were not statistically significant. Secondary efficacy endpoint results were similar. There was not a high placebo response in this study, but rather an attenuation of drug effect. In general, quetiapine XR was well tolerated over 6-weeks' treatment; there were no unexpected AEs.. The efficacy of quetiapine XR (400, 600, and 800 mg/day) was not established at Week 6. Quetiapine IR, an agent with established efficacy in schizophrenia, also did not separate from placebo at endpoint. Therefore, this is considered a failed study and possible reasons for this are discussed. Quetiapine XR was generally well tolerated and its safety profile was consistent with the known profile of quetiapine.

Topics: Acute Disease; Adult; Analysis of Variance; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Failure; United States

The depressive symptoms of bipolar disorder impact health-related quality of life, quality of sleep and functioning. The BOLDER I and II trials demonstrated that quetiapine significantly improves depressive symptoms in patients with acute bipolar depression. Post-hoc analysis of the BOLDER I and II data permits a detailed investigation of the effects of quetiapine on these other measures in this patient population.. Secondary analysis was performed on data from BOLDER I and II, which were two 8-week, double-blind, randomized, placebo-controlled studies of quetiapine at fixed doses (300 or 600 mg/day) in a total of 1051 patients with acute depressive episodes of bipolar I or II disorder. Measures included the Short-Form Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q SF) in BOLDER I and II, the Pittsburgh Sleep Quality Index (PSQI) in BOLDER I, and the Sheehan Disability Scale (SDS) in BOLDER II. Analyses of Q-LES-Q SF score changes were based on data from the combined BOLDER I and II populations, and analyses of PSQI and SDS score changes were based on BOLDER I and BOLDER II populations, respectively.. Assessments at day 57 by mixed-model repeated measures analysis demonstrated that quetiapine relative to placebo provided significant or numerical improvements in rating scale score on the Q-LES-Q SF (10.89 with 300 mg/day and 12.14 with 600 mg/day vs. 7.79 with placebo; p<0.001 for each quetiapine dose), PSQI (-5.34 and -6.00 vs. -3.35; p<0.001, each dose), and SDS (-7.78 and -8.25 vs. -6.49; p=0.156 and 0.054, respectively). Effect sizes at day 57 with quetiapine 300 and 600 mg/day, respectively, were 0.34 and 0.46 for Q-LES-Q SF, 0.59 and 0.79 for PSQI, and 0.17 and 0.23 for SDS. Improvements were evident at first post-baseline assessment on day 29 and were consistent over the majority of rating scale domains. Quetiapine was generally well tolerated and most adverse events were of mild to moderate intensity.. Quetiapine monotherapy is effective in improving impairment in important aspects of life that accompany improvements in depressive symptoms in patients with acute bipolar depression.

Topics: Acute Disease; Adolescent; Adult; Aged; Ambulatory Care; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Health Status; Humans; Male; Middle Aged; Personal Satisfaction; Placebos; Psychiatric Status Rating Scales; Quality of Life; Quetiapine Fumarate; Severity of Illness Index; Sleep; Surveys and Questionnaires; Treatment Outcome

This study aimed to demonstrate efficacy of once-daily extended release quetiapine fumarate (quetiapine XR) versus placebo in patients with acute schizophrenia.. In this 6-week, randomized, double-blind study (5077IL/0041) patients were randomized to receive quetiapine XR (300, 600, or 800 mg/day), quetiapine fumarate immediate release (quetiapine IR) [300 or 600 mg/day], or placebo. Primary endpoint was change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at Day 42. Secondary variables included PANSS response rate at Day 42 (>/=30% decrease in PANSS total score from baseline) and Clinical Global Impressions Severity (CGI-S) and Improvement (CGI-I) ratings. Safety assessments included adverse event (AE) reporting and laboratory measures.. Of 532 patients randomized, 222 (41.7%) completed the study. Improvements in PANSS total scores from baseline to Day 42 across treatment groups were: quetiapine XR 300 mg/day -5.01, 600 mg/day -13.01 and 800 mg/day -11.17, quetiapine IR 300 mg/day -9.42 and 600 mg/day -6.97, and placebo -5.19; the difference in change was statistically significant only for quetiapine XR 600 mg/day (p = 0.033). There were no statistically significant differences between active treatment groups and placebo for PANSS response rates. Several post hoc analyses were conducted to explain the study efficacy outcome but these were inconclusive. Quetiapine XR was generally well tolerated with the majority of AEs being mild or moderate in intensity and no unexpected AEs.. Superior efficacy of quetiapine XR versus placebo in patients with schizophrenia was demonstrated for quetiapine XR 600 mg/day. The safety and tolerability profile of quetiapine XR was similar to that of quetiapine IR.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Female; Hospitalization; Humans; Male; Middle Aged; Placebos; Quetiapine Fumarate; Schizophrenia

To assess the effectiveness of aripiprazole in the treatment of patients with psychotic symptoms in the emergency psychiatric setting.. We considered all patients admitted to a psychiatric intensive care unit of a general hospital in a two year-period, treated with at least one dose of aripiprazole. We measured 1) the rate of cases starting aripiprazole who did not change antipsychotic in the course of hospitalization; 2) the rate of cases who were concurrently treated with another antipsychotic; 3) the CGI Improvement score.. In 63 cases, aripiprazole was started on admission. Forty-nine (77.7%) of these cases were treated with aripiprazole also on discharge. Among the 63 cases who started aripiprazole on admission, 22 (34.9%) were concurrently treated with another antipsychotic. Among the 53 cases discharged with aripiprazole, 15 (28.3%) were concurrently treated with another antipsychotic. Of the 49 cases treated with aripiprazole both on admission and on discharge, 24 cases were much improved, 11 cases moderately improved, 10 cases mildly improved, and 4 cases were not improved at the CGI Improvement Score.. Aripiprazole should be considered as first line treatment in some patients affected by psychotic disorders visited in the emergency psychiatric setting.

Topics: Acute Disease; Adult; Antipsychotic Agents; Aripiprazole; Clozapine; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Drug Therapy, Combination; Emergency Services, Psychiatric; Female; Humans; Intensive Care Units; Male; Middle Aged; Piperazines; Psychiatric Department, Hospital; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Severity of Illness Index; Treatment Outcome

The aim of the study was to assess the efficacy, tolerability and safety of the own developed generic quetiapine, Ketilept (EGIS Pharmaceutical Ltd, Budapest) in patients with an acute episode of schizophrenia and schizoaffective disorder.. These was a multicenter, non comparative, open label, 12-week trial on oral generic quetiapine conducted in 110 patients with DSM-IV acute schizophrenia or schizoaffective disorder. Patients received Ketilept 50 mg on day 1, 100 mg on day 2, 200 mg on day 3, 300 mg on day 4. The flexible dosing (150-750 mg/day) started on day 5. Patients were evaluated at baseline, at day 7, 14, 28 and 84. Baseline and outcome assessment included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity of Illness Subscale (CGI-S) and Global Improvement Subscale (CGI-I), Subjective Well-being on Neuroleptics Scale (SWN), Simpson-Angus Extrapyramidal Rating Scale (SAS), Barnes Akathisia Rating Scale (BARS) and UKU Side Effects Rating Scale (UKU). Changes in overall body weight, body mass index (BMI) and abdominal circumference were also evaluated.. After 12 weeks on Ketilept therapy, significant improvements were observed on all major symptoms measures and subscales. 44 (44%) of patients were rated much or very much improved on CGI-I at week 12. The mean SAS and BARS score significantly reduced during the generic quetiapine treatment period (p = 0.0001, p = 0.001). No change was found in the body weight, BMI and abdominal circumference during treatment with Ketilept for 12 weeks. The most common side effects were sedation, and dizziness. 14 adverse events occurred in 6 subjects (5%), of whom 3 patients (2.7%) encountered 3 serious adverse events. The adverse events were mainly mild and moderate. 103 patients (93.6)% completed the study, 2 patients (1.8%) were discontinued from the study due to serious adverse events (insufficient clinical response, sedation).. Despite the limitations of the design, our results suggest that the generic quetiapine, Ketilept in patients with acute schizophrenia and schizoaffective disorder is therapeutic equivalent to the innovator drug in terms of efficacy, tolerability and safety.

Topics: Acute Disease; Aged; Body Mass Index; Body Weight; Dibenzothiazepines; Drug Therapy, Combination; Drugs, Generic; Fatigue; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sleep; Time Factors; Treatment Outcome; Waist Circumference

Rapid resolution of symptoms is a priority for clinicians treating acute psychosis, and rapid initiation of pharmacotherapy may prove beneficial. This study examined rapid dose initiation of quetiapine in acutely ill patients.. A 2-week, multicentre, randomised, parallel-group, open study. Inpatients (n = 269) diagnosed with schizophrenia or schizoaffective disorder received rapid (n = 139) or conventional (n = 130) initiation of quetiapine, followed by flexible dosing (maximum 800 mg/day). Primary outcome included proportion of patients experiencing > or =1 episode of selected AEs (somnolence, dizziness, orthostatic hypotension) during Week 1. Secondary outcomes included discontinuations due to AEs, and efficacy assessed by BPRS and CGI-S scores.. The proportion of patients with > or =1 selected AE during Week 1 was 5.4% and 10.1% in the conventional and rapid initiation groups, respectively. Most common AEs (>5% patients) were hypotension, tachycardia, somnolence and sedation. Overall, four (3.1%) and three (2.1%) patients from the conventional and rapid initiation group, respectively, withdrew due to AEs. BPRS and CGI-S scores decreased significantly (p < 0.001) from baseline in both groups.. A higher proportion of patients experienced AEs with rapid initiation of quetiapine (800 mg/day by Day 4), although withdrawals due to AEs were comparable. Rapid initiation of quetiapine was generally well tolerated and effective in this setting.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

To evaluate the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) in a 6-week, double-blind, randomized study.. Patients with a DSM-IV diagnosis of acute schizophrenia were randomly assigned to fixed-dose quetiapine XR 400, 600, or 800 mg/day (once daily in the evening), quetiapine immediate release (IR) 400 mg/day (200 mg twice daily), or placebo. Dual-matched placebo was used to maintain blinding. Quetiapine XR target doses were reached by day 2 (400 and 600 mg) and day 3 (800 mg). The primary endpoint was least squares mean change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score. PANSS response rate (percentage of patients with > or = 30% reduction in total score), Clinical Global Impressions-Improvement scale (CGI-I) response rate (percentage of patients with score < or = 3), change in CGI-Severity of Illness (CGI-S), and adverse events (AEs) were also assessed. The study was conducted from November 2004 to December 2005.. 588 patients were enrolled and 446 (76%) completed the study. Improvement in PANSS total score at week 6 was significant versus placebo (-18.8) in all groups: -24.8 (p = .03), -30.9 (p < .001), and -31.3 (p < .001) for quetiapine XR 400, 600, and 800 mg, respectively, and -26.6 (p = .004) for quetiapine IR. There were also statistically significant differences in PANSS and CGI-I response rates for all active treatments versus placebo (all p < .05). The most common AEs in all quetiapine groups were somnolence and dizziness; there were no unexpected AEs with quetiapine XR. Incidence of AEs potentially related to extrapyramidal symptoms was similar to placebo.. Once-daily quetiapine XR (400-800 mg/day) was effective versus placebo in patients with acute schizophrenia. Treatment, including rapid dose escalation, was well tolerated, with a therapeutically effective dose reached by day 2.. ClinicalTrials.gov identifier NCT00206115.

Topics: Acute Disease; Adult; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

This study compared the effects of atypical antipsychotics (risperidone or quetiapine) with placebo and with each other in recently exacerbated patients with schizophrenia requiring hospitalization.. This international, randomized, double-blind study included a 2-week monotherapy phase followed by a 4-week additive therapy phase. Recently exacerbated patients with schizophrenia or schizoaffective disorder (DSM-IV) were randomized (2:2:1) to risperidone (n = 153), quetiapine (n = 156), or placebo (n = 73). Target doses were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5, with the ability to increase to 600 or 800 mg/day of quetiapine on day 8. The main outcome measures were the total Positive and Negative Syndrome Scale (PANSS) and need for additional psychotropic medications.. Monotherapy Phase: The combined atypical antipsychotic group (n = 308) reached borderline superiority to placebo (n = 71) at the 2-week endpoint on mean change in total PANSS score (-24.1 +/- 1.2 and -20.2 +/- 2.0, respectively; p = 0.067). The change in the atypical group was driven by the improvement with risperidone (-27.7 +/- 1.5 vs. -20.2 +/- 2.0 with placebo, p < 0.01; and vs. -20.5 +/- 1.5 with quetiapine, p < 0.01); the improvement with quetiapine was similar to placebo, p = 0.879. Results were similar on other efficacy endpoints. Additive Therapy Phase: Additional psychotropics were prescribed to fewer (p < 0.01) risperidone (36%) than quetiapine (53%) or placebo patients (59%). The overall discontinuation rate was 18%, 26%, and 38%, respectively. Risperidone, compared with placebo, was associated with more parkinsonism, akathisia, plasma prolactin changes, and weight gain; while quetiapine was associated with more somnolence, sedation, dizziness, constipation, tachycardia, thyroid dysregulation, and weight gain.. While the combined atypical antipsychotic group did not experience greater improvements than the placebo group, risperidone, but not quetiapine, was significantly superior in all measured domains to placebo in the management of recently exacerbated hospitalized patients with schizophrenia or schizoaffective disorder, with no unexpected tolerability findings.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Dibenzothiazepines; Double-Blind Method; Female; Hospitalization; Humans; Male; Middle Aged; Quetiapine Fumarate; Risperidone; Schizophrenia

The original dosing recommendations for quetiapine in the treatment of schizophrenia suggested escalation to 400 mg/d using the following schedule, administered twice daily in divided doses: Day 1, 50 mg; Day 2, 100 mg; Day 3, 200 mg; Day 4, 300 mg; Day 5, 400 mg. In practice, however, clinicians often exceed these recommendations because of the need to obtain a therapeutic response in patients with psychosis as quickly as possible. This study was designed to determine a faster tolerable dosage-escalation schedule for quetiapine in acutely ill, hospitalized patients with schizophrenia. In this multicenter, placebo-controlled, double-blind pilot study, adult patients were randomly assigned to escalation schedules that would achieve a target dosage of 400 mg/d in either 5, 3, or 2 days. Safety and tolerability were assessed by interviews, physical examinations and vital signs, laboratory tests, and electrocardiograms. The enrolled population consisted of 69 patients who were randomized to 1 of the 3 dose-escalation schedules. Treatment-related adverse events were few among the 67 evaluable patients, with most rated as mild in intensity. Among 69 enrolled patients, only 3 withdrew because of an adverse event (agitation). Objective assessments and adverse events were similar between the 3 groups. In this study of patients with acute schizophrenia, quetiapine dosage was increased to 400 mg/d in 5, 3, and 2 days with similar safety and tolerability, suggesting that escalation to therapeutically effective dosages can be accomplished in less than 5 days.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Pilot Projects; Prospective Studies; Quetiapine Fumarate; Schizophrenia

In the present naturalistic study, the effectiveness and safety of quetiapine, risperidone and olanzapine were compared in the treatment of non selected acutely psychotic patients. It was observed that the rate of antipsychotic switch because of a lack of efficacy or side effects was higher in the quetiapine treated cases in comparison with the risperidone or olanzapine treated cases. The proportion of cases concomitantly treated with typical neuroleptics was significantly higher in the quetiapine group compared with the other two groups. In the outcome of non crossover cases, there were more improvements in the risperidone and olanzapine groups than in the quetiapine group. The results of this study suggest that quetiapine is not as efficacious as risperidone or olanzapine in the emergency psychiatric setting. Due to the methodological limitations of the study, these results must be considered preliminary and need confirmation.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Emergency Services, Psychiatric; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Sampling Studies; Treatment Outcome

This randomized, double-blind, placebo-controlled study examined the efficacy and tolerability of quetiapine in combination with divalproex (DVP) for acute mania in adolescents with bipolar disorder. It was hypothesized that DVP in combination with quetiapine would be more effective than DVP alone for treating mania associated with adolescent bipolar disorder. Furthermore, it was hypothesized that quetiapine would be well tolerated.. Thirty manic or mixed bipolar I adolescents (12-18 years) received an initial DVP dose of 20 mg/kg and were randomly assigned to 6 weeks of combination therapy with quetiapine, which was titrated to 450 mg/day (n = 15) or placebo (n = 15). Primary efficacy measures were change from baseline to endpoint in Young Mania Rating Scale (YMRS) score and YMRS response rate. Safety and tolerability were assessed weekly.. The DVP + quetiapine group demonstrated a statistically significantly greater reduction in YMRS scores from baseline to endpoint than the DVP + placebo group (F(1,27) = 5.04, p =.03). Moreover, YMRS response rate was significantly greater in the DVP + quetiapine group than in the DVP + placebo group (87% versus 53%; Fisher exact test, p =.05). No significant group differences from baseline to endpoint in safety measures were noted. Sedation, rated as mild or moderate, was significantly more common in the DVP + quetiapine group than in the DVP + placebo group.. The findings of this study indicate that quetiapine in combination with DVP is more effective for the treatment of adolescent bipolar mania than DVP alone. In addition, the results suggest that quetiapine is well tolerated when used in combination with DVP for the treatment of mania.

Topics: Acute Disease; Adolescent; Analysis of Variance; Antimanic Agents; Bipolar Disorder; Child; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Quetiapine Fumarate; Valproic Acid

Five fixed doses of the atypical antipsychotic "Seroquel" (quetiapine) were evaluated to delineate a dose-response relationship, as measured by changes from baseline in Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), and Modified Scale for the Assessment of Negative Symptoms (SANS) summary scores, and to compare efficacy and tolerability opposite placebo and haloperidol. Three hundred sixty-one patients from 26 North American centers entered this double-blind, placebo-controlled trial with acute exacerbation of chronic schizophrenia (DSM-III-R). Patients who completed a single-blind, placebo washout phase were randomized to double-blind treatment with quetiapine (75, 150, 300, 600, or 750 mg daily), haloperidol (12 mg daily), or placebo and evaluated weekly for 6 weeks. At end point, significant differences (p < 0.05, analysis of covariance) in adjusted mean changes from baseline were identified between the four highest doses of quetiapine and placebo for BPRS total, BPRS positive-symptom cluster, and CGI Severity of Illness item scores and between quetiapine 300 mg and placebo for SANS summary score. Differences between quetiapine and haloperidol were not significant. Dose-response modeling showed significant linear and quadratic functions of quetiapine dose for all primary efficacy variables. Notably, no significant safety concerns were identified as dose increased. Quetiapine was no different from placebo across the dose range studied regarding incidence of extrapyramidal symptoms or change in prolactin concentrations. Quetiapine is well tolerated and clinically effective in the treatment of schizophrenia. It is both superior to placebo and comparable to haloperidol in reducing positive symptoms at doses ranging from 150 to 750 mg/day and in reducing negative symptoms at a dose of 300 mg/day.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Haloperidol; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

ICI 204,636 is a new, potentially atypical antipsychotic. In early phase II trials, the antipsychotic was well tolerated and results suggested efficacy in the treatment of the positive and negative symptoms of schizophrenia. The efficacy and safety of ICI 204,636 were evaluated on a larger scale in a 6-week, multicenter, double-blind trial. Hospitalized patients who met DSM-III-R criteria for chronic or subchronic schizophrenia with acute exacerbation, as well as other criteria, were randomized to ICI 204,636 (75 to 750 mg daily) (N = 54) or placebo (N = 55). Patients were assessed weekly by use of the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), and Clinical Global Impression Scale (CGI) for efficacy and the Simpson Scale and Abnormal Involuntary Movement Scale for extrapyramidal side effects (EPS). Significant differences (p < or = 0.05) between treatment groups, which favored ICI 204,636, were identified throughout the trial. Endpoint differences were significant (by analysis of covariance) for BPRS factor IV (activation) and SANS scores and were marginally significant for total BPRS, BPRS factor III (thought disturbance), BPRS positive-symptom cluster, and CGI Severity of Illness item scores (p = 0.07, 0.09, 0.06, and 0.09, respectively). ICI 204,636 was well tolerated, although it was associated with mild transient increases in alanine aminotransferase and a higher incidence of somnolence and anticholinergic effects compared with placebo. In the dose range studied, treatment with ICI 204,636 did not induce EPS as determined by analysis of Simpson Scale total scores and lack of treatment-emergent acute dystonic reactions. Furthermore, ICI 204,636 did not produce sustained levels of prolactin; the mean change from baseline at endpoint (-7.2 micrograms/L) was comparable (p = 0.44) to that for placebo (-8.2 micrograms/L). These findings distinguish ICI 204,636 from standard antipsychotics and confirm preclinical predictions that ICI 204,636 is an atypical antipsychotic.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Topics: Acute Disease; Acute Kidney Injury; Adult; Antipsychotic Agents; Brachial Plexus Neuropathies; Compartment Syndromes; Creatine Kinase; Deltoid Muscle; Fasciotomy; Humans; Male; Myositis; Pectoralis Muscles; Quetiapine Fumarate; Rhabdomyolysis; Tomography Scanners, X-Ray Computed; Treatment Outcome

Topics: Acute Disease; Antipsychotic Agents; Drug Synergism; Humans; Pancreatitis; Quetiapine Fumarate

It is well known that treatment modalities against secondary damage due to spinal cord injury (SCI) are very important. This phase has been researched in many experimental studies. Apoptosis is one of the major mechanisms of secondary damage on spinal cord. The present study was undertaken to determine if quetiapine, a 5-HT2 receptor blocker atypical antipsychotic agent can rescue neuronal cells from apoptosis in a SCI model.. Thirty-two female Wistar rats were separated to 4 equal groups. Total laminectomy was performed at T5-7 level and spinal cord injury was produced by using the clip compression technique. Each rat from groups "1 day" (D-I) and "7 days" (D-II) was daily injected intraperitoneally with Quetiapine (10 mg/kg/day). No treatment was administered to the control groups "1 day" (K-I) and "7 days" (K-II). At the end of follow-up periods, all animals were sacrificed and spinal cords were removed. Apoptotic cells were evaluated by using immunohistochemical technique (TUNEL) in injured spinal cord specimens.. There was a statistically significant difference while counting ApopTag positive cells, both at 1 day groups of K-I and D-I (p=0.00000008) and at 7 day groups of K-II and D-II (p=0.000005). Unlike the 1-day period, a statistically significant difference was found between grey and white matter ApopTag positive cells at the 7 < sup > th < /sup > day (p=0.0001).. Quetiapine has a protective effect on secondary damage caused by SCI, while also can be used in post-traumatic stress disorder, depression and agitation as a versatile agent.

Topics: Acute Disease; Animals; Female; Laminectomy; Male; Quetiapine Fumarate; Random Allocation; Rats; Rats, Wistar; Spinal Cord Injuries; Treatment Outcome

Evaluate the impact of quetiapine extended release (XR) versus quetiapine immediate release (IR) on hospitalization length in acute bipolar mania using Truven Health Analytics MarketScan Hospital Drug Database.. Generalized linear model analyses were used, adjusting for patient and hospital characteristics.. Using data from 3088 discharges, quetiapine XR reduced hospitalization length by 6.7% versus quetiapine IR (p = 0.11; no statistically significant differences between groups), corresponding to 0.6 fewer days in hospital. Excluding the outlier, quetiapine XR significantly reduced hospitalization length by 9.6% versus quetiapine IR (p = 0.02), corresponding to 0.9 days.. Inpatient use of quetiapine XR in acute bipolar mania may be associated with reduced hospitalization length (7-10%), possibly owing to the faster titration schedule versus quetiapine IR.

Topics: Acute Disease; Adult; Antipsychotic Agents; Bipolar Disorder; Comparative Effectiveness Research; Delayed-Action Preparations; Dibenzothiazepines; Female; Hospitalization; Humans; Length of Stay; Male; Quetiapine Fumarate; Retrospective Studies

Second-generation antipsychotics have well-known metabolic side effects such as hyperlipidaemia and hyperglycaemia. A middle-aged man presented with epigastric and flank pain associated with nausea, and was noted to have elevated triglycerides (3590 mg/dL or 40.53 mmol/L), lipase and glucose. Haematological parameters revealed neutropenia with pancytopaenia. The patient was started on conservative management for acute pancreatitis, and on intravenous insulin and oral gemfibrozil for lowering of his triglycerides. He gradually improved and was transitioned to oral atorvastatin and fenofibrate. His triglycerides, glucose and leucocyte counts normalised at discharge and he was transitioned to ziprasidone. The combination of hypertriglyceridaemia, worsening hyperglycaemia and neutropenia made us suspect quetiapine as the causative agent. Medications cause only 0.1-7% of acute pancreatitis cases, with quetiapine implicated in only five-reported cases. Hypertriglyceridaemia (>600 mg/dL or 6.77 mmol/L) is frequently reported with quetiapine use, but severe hypertriglyceridaemia (>1000 mg/dL or 11.29 mmol/L) has been reported in <10 patients.

Topics: Acute Disease; Antipsychotic Agents; Bipolar Disorder; Humans; Hypertriglyceridemia; Male; Middle Aged; Pancreatitis; Quetiapine Fumarate; Treatment Outcome

We report a case of acute psychotic symptoms following exposure to a single high dose of styrene monomer. The 24-year-old male patient showed psychotic and cognitive symptoms immediately after exposure. His psychotic symptoms included auditory hallucinations and delusions of reference. Brain magnetic resonance imaging, electroencephalography, and laboratory examinations were performed to evaluate any other causes. The clinical, neuroimaging, and laboratory review in this case suggested that the suddenly developed psychotic symptoms that led to chronic deterioration were caused by the single exposure to styrene monomer. This is the first recent report in which acute psychotic symptoms developed from a single high dose of styrene suffocation compared with previous findings showing symptoms because of long-term low-dose exposure.

Topics: Acute Disease; Antipsychotic Agents; Humans; Male; Occupational Exposure; Psychoses, Substance-Induced; Quetiapine Fumarate; Styrene; Young Adult

Topics: Acute Disease; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Male; Middle Aged; Pancreatitis; Quetiapine Fumarate; Schizophrenia; Time Factors

Bipolar disorder has a significant impact upon a patient's quality of life, imposing a considerable economic burden on the individual, family members and society as a whole. Several medications are indicated for the acute treatment of mania and depression associated with bipolar disorder as well as for maintenance therapy; however, these have varying efficacy, tolerability and costs.. The objective of this study was to develop a new discrete-event simulation model to analyse the long-term consequences of pharmacological therapy for the management of bipolar I and II disorders (acute treatment of episodes of mania and depression as well as maintenance therapy).. Probabilities of remission and relapse were obtained from clinical trial data and meta-analyses. Costs (year 2011 values) were assessed from a UK healthcare payer's perspective, and included pharmacological therapy and resource use associated with the treatment of mood events and selected adverse events. The health effects were measured in terms of QALYs.. For a patient starting with acute depression or in remission at 40 years of age (which was the average age in the clinical trials), quetiapine 300 mg/day was a cost-effective strategy compared with olanzapine 15 mg/day over a 5-year time frame. With acute bipolar depression as a starting episode, the 5-year medical costs were £323 higher and QALYs were 0.038 higher for quetiapine compared with olanzapine, corresponding to a cost-effectiveness ratio of £8600 per QALY gained.. Compared with olanzapine, the results suggest that quetiapine is cost effective as a maintenance treatment for bipolar depression.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Computer Simulation; Cost-Benefit Analysis; Dibenzothiazepines; Humans; Meta-Analysis as Topic; Models, Economic; Olanzapine; Quality-Adjusted Life Years; Quetiapine Fumarate; Remission Induction; Secondary Prevention; United Kingdom

This study was conducted to explore the efficacy and tolerability of quetiapine extended release (XR) to treat psychosis and accompanying acute behavioral disturbance in hospitalized psychiatric patients.. Patients with psychosis who displayed aggression were administered quetiapine XR (day 1 mean dose: 293.3 mg). Symptoms and side effects were assessed prospectively over an 8-day period. Symptoms were measured by the Overt Aggression Scale and Brief Psychiatric Rating Scale (BPRS), and side effects were measured using the Simpson-Angus Scale and Barnes Akathisia Rating Scale.. Fifteen of 16 consenting patients completed the study. Aggression was significantly reduced by day 3. Psychopathology also was significantly reduced, with the greatest improvement in BPRS Thinking Disturbance subscale scores. No significant increase in movement side effects was seen by day 8. Seven participants were administered a concomitant sedating antipsychotic on an as-needed basis, particularly in the first 4 days of treatment; these participants displayed much greater aggression--but not psychopathology--at day 1, and it took longer for their aggression and psychopathology to improve compared with patients treated with quetiapine XR as the sole antipsychotic.. Further research is needed before definitive recommendations can be made. However, current findings provide tentative support for quetiapine XR as a safe and effective medication for treating concurrent psychosis and behavioral disturbance, particularly in less severely aggressive patients.

Topics: Acute Disease; Adult; Aggression; Antipsychotic Agents; Brief Psychiatric Rating Scale; Delayed-Action Preparations; Dibenzothiazepines; Female; Humans; Inpatients; Male; Psychotic Disorders; Quetiapine Fumarate

Topics: Acute Disease; Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Hypnotics and Sedatives; Lorazepam; Quetiapine Fumarate; Schizophrenia; Thirst; Water Intoxication

Topics: Acromegaly; Acute Disease; Adenoma; Adult; Antipsychotic Agents; Basal Ganglia; Brain Ischemia; Chorea; Diabetes Complications; Diabetic Ketoacidosis; Dibenzothiazepines; Dyskinesias; Female; Growth Hormone; Humans; Hyperglycemia; Insulin; Magnetic Resonance Imaging; Pituitary Gland; Pituitary Neoplasms; Quetiapine Fumarate; Syndrome

Drug hepatotoxicity is the most common cause of fulminant hepatic failure in the USA. We describe a rare case of a patient who developed an acute liver injury after initiation of therapy with quetiapine, but after conservative management and a trial of steroids, has fully recovered. This is the second reported case of quetiapine-induced liver injury in the published literature.

Topics: Acute Disease; Antipsychotic Agents; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Young Adult

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Approval; Humans; Quetiapine Fumarate; United States; United States Food and Drug Administration

We performed a post marketing surveillance study (PMS study) to reveal the efficacy and tolerability of orally administered quetiapine in the treatment of acute psychosis over a period of up to three weeks. 398 respective inpatients were assessed in 88 psychiatric departments in Germany by use of the Clinical Global Impression Scale (CGI) and the Brief Psychiatric Rating Scale (BPRS) as well as the clinical impression of psychiatric raters. Safety and tolerability were assessed by vital parameters such as blood pressure, hearth rate and weight as well as the clinical impression of the psychiatric raters. In addition, dosing, concomitant and/or previous pharmacotherapies as well as certain aspects of psychiatric and medical history were documented. A significant reduction of psychopathology was found during three weeks of drug treatment. Daily dosages of quetiapine between 400 and 1200 mg were well tolerated with a limited number of adverse and no serious adverse events. Noteworthy, more than 35 % of all patients received and tolerated excellently more than 800 mg of quetiapine per day under naturalistic treatment conditions, well above the approved maximum daily dosage. This study reflects the clinical efficacy and good tolerability of quetiapine under real world treatment conditions and is in line with the results of the controlled clinical trials of phase II and III.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Body Mass Index; Child, Preschool; Dibenzothiazepines; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Humans; Inpatients; Male; Middle Aged; Product Surveillance, Postmarketing; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Clinical efficacy, safety and tolerability of quetiapine in the treatment of 23 hospitalized psychotic adolescents were evaluated retrospectively. Twelve patients were changed to quetiapine from another antipsychotic medication during their hospital stay. In these patients, CGI-S improved from 4.75+/-0.87 to 2.92+/-0.67 (observation period 3.7+/-1.6 months). The most common adverse events were transient tachycardia and sedation. Mild EPS occurred only in one patient under quetiapine monotherapy. Transaminase increases more than threefold above norm were observed in two patients. fT4 values were slightly below the norm in 67% of the cases. In 11 patients, quetiapine was initiated using a rapid titration schedule with high dosages in the acute phase. Receiving a mean maximum daily dose of 927+/-300 mg, CGI-S improved from 6.00+/-0.63 to 3.18+/-1.25 (observation period 2.9+/-1.8 months). Severe adverse events did not occur. Besides applying lorazepam temporarily in nine of the 11 patients, antipsychotic co-medication was not necessary in this group. In line with other studies, quetiapine may be considered as an effective treatment for adolescents with a severe psychotic disorder showing a favourable side-effect profile. Our preliminary data suggest that a rapid initiation with high doses could be a promising approach in acute psychotic adolescents.

Topics: Acute Disease; Adolescent; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Hospitalization; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Schizophrenia

To analyze the available evidence from randomized clinical trials regarding the effective dose range and optimal dose of quetiapine when treating bipolar I disorder patients with acute mania.. Patients with acute mania were treated with quetiapine as monotherapy (for 12 weeks) or in combination with lithium (mean serum concentration 0.76 mEq/L) or divalproex (mean serum concentration 69.5 microg/mL) (Li/DVP) (for 3-6 weeks) in four double-blind, placebo-controlled studies according to a predetermined dosing schedule. Guidance for the dosing of quetiapine involved increasing the first day's dose (100 mg/day) by 100 mg on a daily basis until Day 4 (400 mg/day), then adjusting the dose up to 600 mg/day at Day 5, and up to 800 mg/day thereafter. Pooled data from the two monotherapy studies and the two combination therapy studies have been used to evaluate the effective quetiapine dose range. As the dose was flexible, effective dose was estimated by the mean last-week dose among responders. The mean last-week dose was defined as the median dose during the 7 days before the last available Young Mania Rating Scale (YMRS) assessment. Patients who achieved a > or = 50% decrease in the YMRS total score from baseline to end of treatment with quetiapine were considered responders. Tolerability was assessed from direct patient reports.. According to randomized clinical trials, administration of quetiapine compared with placebo achieved a statistically significant improvement in change from baseline YMRS score within the first week and onward, as monotherapy or in combination with Li/DVP. The average quetiapine dose (+/-SD) in responders during the last week of treatment was 575 (+/-175) at Day 21 and 598 (+/-198) mg/day at Day 84 for monotherapy, and 584+/-208 mg/day at Day 21 for combination therapy, with most responders receiving doses within the range of 400-800 mg/day. Dose escalation was rapid, with 92% of patients treated with monotherapy and 80% of patients treated with combination therapy reaching doses of 400 mg/day by Day 4, in accordance with protocol-defined dosing guidance. This dose administration schedule was generally well tolerated.. The mean last-week median dose among responders suggests that 600 mg/day of quetiapine is an effective target dose in acute mania.

Topics: Acute Disease; Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lithium Compounds; Male; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome; Valproic Acid

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Clinical Trials as Topic; Dibenzothiazepines; Humans; Quetiapine Fumarate; Treatment Outcome

To evaluate the effects of quetiapine monotherapy compared with placebo on acute (3-week) and more sustained (12-week) rates of response and remission/euthymia in bipolar disorder patients with acute mania.. Two similar 12-week multicenter, double-blind, placebo-controlled, parallel-group studies were conducted, with an a priori decision to combine the data and analyze response and remission rates. Response was measured as a decrease of at least 50% in Young Mania Rating Scale (YMRS) scores from baseline to Day 21 and Day 84. Five remission/euthymia criteria were employed to determine efficacy at Day 21 and Day 84: (i) YMRS score < or = 12; (ii) YMRS score < or = 12 and Montgomery-Asberg Depression Rating Scale (MADRS) score < or = 10; (iii) YMRS score < or = 12 and MADRS score < or = 8; (iv) YMRS score < or = 8; and (v) YMRS score < or = 8 plus a score < or = 2 for the YMRS core items of Irritability, Speech, Content, and Disruptive/Aggressive Behavior.. Patients treated with quetiapine (n=208) and placebo (n=195) had mean YMRS scores at entry of 33.3+/-6.3 and 33.5+/-6.7, respectively. Significantly higher response rates were observed with quetiapine compared with placebo, at Days 21 (48.1% versus 31.3%; p<0.001) and 84 (66.8% versus 40.0%; p<0.001). At Day 21, remission/euthymia rates with quetiapine monotherapy versus placebo were: 37.5% versus 23.1% (YMRS < or = 12), 35.6% versus 21.5% (YMRS < or = 12+MADRS < or = 10), 35.1% versus 20.0% (YMRS < or = 12+MADRS < or = 8), 25.0% versus 14.4% (YMRS < or = 8), and 21.6% versus 14.4% (YMRS < or = 8 plus core items < or = 2) (p<0.01 for all comparisons except YMRS < or = 8 plus core items < or = 2: p=0.06). By Day 84, these had increased to: 65.4% versus 35.9% (YMRS < or = 12), 60.1% versus 30.8% (YMRS < or = 12+MADRS < or = 10), 58.7% versus 29.7% (YMRS < or = 12+MADRS < or = 8), 60.1% versus 30.3% (YMRS < or = 8), and 56.7% versus 29.7% (YMRS < or = 8 plus core items < or = 2) (p<0.001 for all comparisons). The average daily dose of quetiapine in responders was 575 mg/day at Day 21 and 598 mg/day at Day 84. Quetiapine was generally well tolerated.. Quetiapine was associated with significantly higher response and remission/euthymia rates compared with placebo with most criteria used, in patients with acute mania at the end of both 3 and 12 weeks.

Topics: Acute Disease; Adolescent; Adult; Affect; Aged; Antimanic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multicenter Studies as Topic; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome

To review the safety/tolerability of quetiapine in four placebo-controlled studies in patients with bipolar I disorder experiencing acute mania.. Four double-blind, placebo-controlled studies evaluated quetiapine monotherapy (12 weeks) or quetiapine in combination with lithium (mean serum concentration 0.76 mEq/L) or divalproex (mean serum concentration 68.6 microg/mL) (Li/DVP) (3 and 6 weeks) in patients with acute mania. Pooled data from the two monotherapy studies and the two combination therapy studies have been evaluated in the analysis presented here. Adverse event reporting, Simpson Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) scores were recorded.. Most adverse events were mild to moderate. Common adverse events (> or = 5% and at least twice the placebo rate) with quetiapine monotherapy and combination therapy were somnolence, dry mouth, weight gain, dizziness, asthenia, pharyngitis, and postural hypotension. Treatment-related discontinuations due to adverse events were not significantly different between quetiapine and placebo, nor was the incidence of extrapyramidal symptoms (including akathisia) (quetiapine monotherapy 12.9% vs placebo 13.1%; combination therapy 21.4% vs placebo 19.2%). Mean change from baseline to endpoint in SAS and BARS scores was not significantly different between groups. Mean weight change at treatment end with quetiapine compared with placebo was +1.8 vs -0.15 kg in monotherapy; and +1.97 vs +0.27 kg with combination therapy. No patients discontinued due to weight gain. The effect of quetiapine monotherapy on serum prolactin levels was no different from placebo.. Quetiapine monotherapy and combination therapy were well tolerated in the treatment of acute mania.

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Humans; Lithium Compounds; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome; Valproic Acid

The aim of this analysis was to compare the rates of remission/euthymia in patients with bipolar mania receiving quetiapine in combination with lithium/divalproex (QTP+Li/DVP) versus placebo (PBO) in combination with Li/DVP (PBO+Li/DVP).. A pooled analysis of two (one 3-week and one 6-week) double-blind studies of a total of 370 patients hospitalized with bipolar I mania who received quetiapine (up to 800 mg/day) in combination with Li (mean serum concentration 0.76 mEq/L) or DVP (mean serum concentration 69.5 microg/mL) was performed. For both studies, data were analyzed at Day 21. In addition, for the 6-week study, data were analyzed at Day 42. Five different criteria for remission/euthymia were used: (i) Young Mania Rating Scale (YMRS) score < or = 12; (ii) YMRS score < or = 12 plus a Montgomery-Asberg Depression Rating Scale (MADRS) score < or = 10; (iii) YMRS score < or = 12+MADRS score < or = 8; (iv) YMRS score < or = 8; and (v) YMRS score < or = 8 plus a score < or = 2 for the YMRS core items of Irritability, Speech, Content, and Disruptive/Aggressive Behavior.. In the pooled analysis, Day 21 remission rates (YMRS < or = 12) were significantly higher in patients treated with QTP+Li/DVP compared with those who received PBO+Li/DVP (48.7% versus 33.0%, p=0.003). Rates of remission/euthymia (YMRS < or = 12+MADRS < or = 10) were similarly improved with QTP+Li/DVP compared with Li/DVP alone (43.2% versus 26.5%, p=0.001). Using the most stringent criteria (YMRS < or = 12+MADRS < or = 8), rates of remission/euthymia were again significantly higher with QTP+Li/DVP than with Li/DVP alone (38.4% versus 25.9%, p=0.014). More patients treated with quetiapine met the stringent criterion of YMRS < or = 8 (31.9% versus 24.3%; p=NS). A trend in favor of quetiapine was also observed for the more stringent criterion of YMRS < or = 8 plus core items < or = 2 (28.1% versus 23.2%; p=NS). For the 6-week study, at Day 42, YMRS was < or = 12 in 68.3% of patients treated with QTP+Li/DVP compared with 57.3% of those who received PBO+Li/DVP (p=NS). Respective rates based on the remission criterion of YMRS < or = 8 were 36.5% and 32.3% (p=NS), and with YMRS < or = 8 and core items < or = 2 were 53.8% and 45.8% (p=NS). However, a significant difference was observed between patients treated with QTP+Li/DVP versus those treated with PBO+Li/DVP using criteria of YMRS < or = 12+MADRS < or = 10 (63.5% versus 49.0%, p<0.05) or YMRS < or = 12+MADRS < or = 8 (61.5% versus 46.9%, p<0.05).. At Days 21 and 42, quetiapine combined with Li/DVP compared to Li/DVP monotherapy yielded significant, sustained improvements in the rate of clinical remission/euthymia in patients with bipolar mania. Longer-term studies are warranted to assess whether quetiapine combined with other mood stabilizing medications can yield even longer-term resolution of symptoms of acute mania while concurrently preventing emergence of depressive symptoms.

Topics: Acute Disease; Affect; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Humans; Lithium Compounds; Multicenter Studies as Topic; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome; Valproic Acid

An ideal antimanic therapy is well tolerated and offers full multidimensional symptom relief. The efficacy of quetiapine in the treatment of acute bipolar mania has previously been established. This post-hoc analysis aims to extend our understanding of quetiapine's antimanic efficacy by evaluating its therapeutic effect across the full spectrum of manic symptoms.. Patient-level data from four similar, randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of quetiapine in bipolar disorder patients with DSM-IV acute mania were combined. Two trials investigated quetiapine as monotherapy (twice daily) and two trials assessed the combination of quetiapine with either lithium (Li) or divalproex (DVP). Changes in scores on the total Young Mania Rating Scale (YMRS), and on each of the 11 items comprising the YMRS, were the primary measures of interest in this analysis. Changes in the Supplemental Aggression and Agitation subscales of the Positive and Negative Syndrome Scale (PANSS) were secondary measures analyzed.. Quetiapine as monotherapy, or in combination with Li or DVP, was a highly effective treatment for acute mania, as shown by overall change scores in the total YMRS. Patients treated with quetiapine monotherapy exhibited a significantly greater reduction (versus placebo) in YMRS total scores at Day 4 (-3.5 versus -2.2; p=0.021), with an increasing between-group difference reported throughout the duration of the trials at Day 21 (-13.6 versus -7.8; p<0.001) and at study endpoint on Day 84 (-19.0 versus -9.6; p<0.001). Quetiapine was also superior in efficacy to placebo on all categorical (i.e., response and remission rates) and secondary outcome parameters. On each of the 11 YMRS items, including the double-weighted core manic items, quetiapine was significantly superior to placebo (p<0.05). Effect sizes at Day 84 ranged from 0.37 to 0.61. Quetiapine in combination with Li/DVP offered a significant benefit over Li/DVP monotherapy, starting at Day 7 (p<0.05) and continuing to the primary study endpoint on Day 21 (p=0.01). Four of 11 YMRS items improved significantly more on quetiapine combination therapy than on Li/DVP monotherapy. The efficacy of quetiapine in these trials appeared independent of baseline disease severity, the presence of psychosis, and treatment-emergent sedation/somnolence. Quetiapine monotherapy produced significantly greater improvement than placebo on the PANSS Activation and the PANSS Supplemental Aggression Risk subscale scores. Similar findings were obtained with quetiapine combined with Li or DVP.. Patients with bipolar disorder may report severe and complex manic symptoms. The results herein indicate that quetiapine is efficacious across the multiple dimensions of mania, including medically serious symptoms commonly encountered in practice.

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Humans; Lithium Compounds; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome; Valproic Acid

The purpose of this study was to determine optimal criteria for defining response and remission in adolescents with acute mania.. Data were analyzed from three treatment studies of adolescents with acute mania (N = 99). Trained raters completed the Young Mania Rating Scale (YMRS), and clinicians completed the Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) independent of YMRS ratings. For response, the percentages of reduction in YMRS scores from baseline to endpoint were compared with CGI-BP Mania Improvement scores. For remission, endpoint YMRS scores were compared with CGI-BP Mania Severity scores. Signal detection analyses were conducted to evaluate the efficiency of selected cutoffs associated with response and remission.. A > or =55% reduction in YMRS scores from baseline to endpoint was the optimal cutoff defining response. An absolute endpoint YMRS score < or =12 was the optimal cutoff defining remission.. The results of this signal detection analysis in adolescent mania suggest that current commonly used cutoffs to define response (> or =50% reduction) and remission (< or =12) may be appropriate with regard to efficiency. Studies with methods specifically tailored to evaluate and compare these rating scales and larger patient samples from multiple sites are needed to confirm these preliminary findings.

Topics: Acute Disease; Adolescent; Antimanic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Quetiapine Fumarate; Remission Induction; Sensitivity and Specificity; Signal Detection, Psychological; Surveys and Questionnaires; Treatment Outcome; Valproic Acid

Topics: Acute Disease; Anesthetics, Intravenous; Antipsychotic Agents; Delirium; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Male; Propofol; Quetiapine Fumarate; Respiration, Artificial; Ventilator Weaning

To evaluate clinical outcomes and the tolerability of 2 weeks' quetiapine (QTP) treatment for hospitalised patients in a naturalistic setting.. Patients with schizophrenia (n = 18), drug-induced psychosis (n = 10; 3 cocaine, 4 hashish and marijuana, and 3 all three substances) or borderline personality disorder (n = 13), were diagnosed by two expert clinicians on the basis of an unstructured clinical interview, and were treated with QTP (250-1000 mg/day). The subjects were then clinically assessed at baseline, and after 7 and 15 days, using the Brief Psychiatric Rating Scale, the Positive and Negative Symptoms Scale (PANSS) and the Hamilton Rating Scale for Depression. At the end of the study, plasma QTP levels were determined and examined in relation to clinical outcome and tolerability.. The mean scores of each rating scale were significantly lower at the end of the study in the population as a whole, and within each diagnostic group. The percentage improvement was significantly greater in the patients with drug-induced psychosis than in those with schizophrenia (42.4 +/- 9.1% versus 23.6 +/- 13.5%). QTP was well tolerated, and the incidence of extrapyramidal side effects was low. There was a linear correlation between plasma levels and dose/kg of QTP (r = 0.31; p < 0.05). The improvement in PANSS significantly correlated with plasma levels and dose/kg in each diagnostic category (Spearman's coefficient was 0.75 [p < 0.01] for schizophrenia and borderline personality disorder, and was 0.68 [p < 0.05] for drug-induced psychosis).. The results suggest that 2 weeks' QTP treatment may improve the clinical outcome of psychotic re-exacerbation phases in different diagnostic categories and indicate that QTP improves clinical outcome in drug-induced psychosis, as QTP levels correlated with the clinical improvement measured by PANSS.

Topics: Acute Disease; Adolescent; Adult; Aged; Borderline Personality Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychoses, Substance-Induced; Quetiapine Fumarate; Schizophrenia; Time Factors

To quickly reduce symptoms and to optimize long-term outcome, patients with an acute episode of schizophrenia or mania require prompt treatment intervention. The atypical antipsychotic quetiapine ('Seroquel') has been approved for the treatment of schizophrenia and manic episodes associated with bipolar disorder. For patients with acute symptoms such as aggression or agitation, higher doses of quetiapine than the recommended initiation schedule are often required. This report presents the tolerability findings from rapid initiation with high-dose quetiapine for eight patients who were consecutively admitted with acute symptoms of schizophrenia (n 5) or mania (n 3). The results from this case series show that quetiapine treatment could be safely titrated at a more rapid rate and to doses greater than that described in the current prescribing information. For most patients, rapid dose escalation was well tolerated; no serious side effects were observed and vital clinical parameters were unchanged; one patient experienced transient somnolence. In conclusion, these results suggest that rapid dose escalation of quetiapine could be a useful treatment approach for acutely ill patients with schizophrenia and bipolar mania in order to improve acute symptoms and support the need for randomized controlled trials. However, dose adjustments should be considered with respect to each patient's individual level of tolerability.

Topics: Acute Disease; Adolescent; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Quetiapine is an atypical antipsychotic that has shown efficacy in the treatment of positive and negative symptoms in schizophrenia without causing extrapyramidal symptoms (EPS). To date, there are two monotherapy and two combination therapy studies with a double blind, placebo-controlled design on the use of quetiapine in mania. Several open studies and case reports support the results of the controlled trials suggesting that quetiapine is effective in treating the broad spectrum of manic symptoms and is tolerated well.

Topics: Acute Disease; Antipsychotic Agents; Bipolar Disorder; Controlled Clinical Trials as Topic; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Humans; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

In 2005, the Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder. This update reviews new evidence since the previous publication and incorporates recommendations based on the most current evidence for treatment of various phases of bipolar disorder. It is designed to be used in conjunction with the 2005 CANMAT Guidelines. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate and several atypical antipsychotics continue to be recommended as first-line treatments for acute mania. For the management of bipolar depression, new data support quetiapine monotherapy as a first-line option. Lithium and lamotrigine monotherapy, olanzapine plus selective serotonin reuptake inhibitors (SSRI), and lithium or divalproex plus SSRI/bupropion continue to remain the other first-line options. First-line options in the maintenance treatment of bipolar disorder continue to be lithium, lamotrigine, valproate and olanzapine. There is recent evidence to support the combination of olanzapine and fluoxetine as a second-line maintenance therapy for bipolar depression. New data also support quetiapine monotherapy as a second-line option for the management of acute bipolar II depression. The importance of comorbid psychiatric and medical conditions cannot be understated, and this update provides an expanded look at the prevalence, impact and management of comorbid conditions in patients with bipolar disorder.

Topics: Acute Disease; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Bipolar Disorder; Canada; Comorbidity; Dibenzothiazepines; Drug Therapy, Combination; Humans; Lamotrigine; Lithium Carbonate; Mood Disorders; Olanzapine; Quetiapine Fumarate; Triazines; Valproic Acid

This study evaluated the overall efficacy and tolerability of quetiapine in the treatment of inpatients with acute mania who are intolerant to risperidone in combination with a mood stabilizer. Eighteen patients completed this 3-week trial. The efficacy and tolerability was assessed upon admission, at baseline, and 1 and 3 weeks later. The Young mania rating scale (YMRS) and clinical global impression-severity (CGI-s) scores from the baseline to the endpoint, decreased by 39.8% and 40.0%, respectively. Fifteen (78.9%) and 18 (94.7%) patients exhibited at least a 50% improvement in the YMRS and CGI-s scores by the end of the trial. Measurements taken through the Barnes akathisia rating scale (BARS), the Simpson-Angus rating scale (SARS) and the drug attitude inventory shortened version-10 (DAI-10) also showed significant improvement. This study suggests that quetiapine may hold promise as an alternative regimen that does not worsen the psychopathology, particularly for those vulnerable to the side effects of drugs, including atypical agents such as risperidone, in naturalistic treatment settings.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Treatment Outcome

Ziprasidone, a novel antipsychotic agent for the treatment of schizophrenia, undergoes partial metabolism by cytochrome P450 3A4. It is associated with moderate prolongation of QT interval, but no increased risk for ventricular tachyarrhythmia or sudden death was demonstrated.. A 70-year-old male was initiated on quetiapine therapy for an acute exacerbation of chronic schizophrenia. The baseline electrocardiogram (ECG) showed a normal QT interval (QTc: 417 ms). In combination therapy of quetiapine and ziprasidone the patient developed suddenly cardiac arrhythmia with extrasystoles and the ECG revealed a prolonged QTc interval of 482 ms. After breaking off treatment with quetiapine and reduction of ziprasidone a normalized QT interval (QTc: 428 ms) was measured.. We suppose a potential of pharmacokinetic interaction between quetiapine and ziprasidone because of the same metabolic pathway by CYP3A4. Combining treatment of quetiapine and ziprasidone is therefore contraindicated. In addition we suggest caution using ziprasidone with any potential 3A4 substrate or inhibitor.

Topics: Acute Disease; Aged; Antipsychotic Agents; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Electrocardiography; Hallucinations; Humans; Long QT Syndrome; Male; Piperazines; Quetiapine Fumarate; Schizophrenia, Paranoid; Thiazoles

Neurosarcoidosis is a rare disorder in which psychosis and dementia may occur. They usually appear subsequently to the diagnosis of pulmonary sarcoidosis. We report on a 39-year-old patient who presented with long-term decline and acute onset of psychosis and delirium, and who was found to have neurosarcoidosis.

Topics: Acute Disease; Adult; Antipsychotic Agents; Brain; Brain Diseases; Cognition Disorders; Diagnosis, Differential; Dibenzothiazepines; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Psychotic Disorders; Quetiapine Fumarate; Sarcoidosis; Tomography, X-Ray Computed

We present a case of acute Quetiapine (SeroQuel) overdose in an 11-y-old girl who ingested 1,300 mg (22.2 mg/kg bw). Initial lethargy developed within I h followed by an episode of agitation and combativeness 3 h after ingestion. After treatment with lorazepam the patient experienced extended somnolence followed by return to normal mental status 16 h after ingestion. No cardiotoxic or laboratory abnormalities were found. This is the first report of acute Quetiapine overdose in an adolescent and suggests a relatively benign clinical course.

Topics: Acute Disease; Antipsychotic Agents; Child; Diagnosis, Differential; Dibenzothiazepines; Drug Overdose; Emergency Treatment; Female; Humans; Quetiapine Fumarate

Topics: Acute Disease; Antipsychotic Agents; Confusion; Delirium; Dibenzothiazepines; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia

Topics: Acute Disease; Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Cost-Benefit Analysis; Dibenzothiazepines; Dibenzothiepins; Dyskinesia, Drug-Induced; Germany; Humans; Neurotransmitter Agents; Olanzapine; Patient Compliance; Pirenzepine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Sulpiride

In the first of a new series of updates on recent advances in medication, RICHARD GRAY outlines the dibenzothiazepine quetiapine, which offers an alternative to conventional antipsychotics for the treatment of schizophrenia, with fewer side effects.

Topics: Acute Disease; Antipsychotic Agents; Dibenzothiazepines; Drug Costs; Humans; Patient Selection; Quetiapine Fumarate; Schizophrenia