Quetiapine: Dose-Response Relationship in Schizophrenia (original) (raw)
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Managing acute exacerbations of schizophrenia: focus on quetiapine
Current Medical Research and Opinion, 2004
In this commentary article we describe our clinical experience and provide our views on the use of quetiapine in tIle treatment of patients with acute exacerbations of schizophrenia. Some patients with acute schizophrenia may require parenteral medication; however, we believe tIlat oral antipsychotics, eitller alone or in combination witll other medications, have a key role to playas an initial and/or subsequent pharmacotherapeutic intervention. Quetiapine has beneficial calming properties and successfully treats tIle symptoms of aggression, anxiety and hostility that can accompany acute exacerbations of schizophrenia. Based upon a review of published findings, data presented at recent intemational psychiatric congresses and our clinical experience, we propose that a more rapid initiation schedule (for example, 400 mg by Day 2, increasing to 600 mglday by Day 3 and often up to 800 mglday by Day 4, or in severe cases 300 mg on Day 1, 600 mg on Day 2 and 900 mg on Day 3) than tIlat 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 mglday (800 mglday in the USA and Canada), there is growing evidence tIlat dosing up to 1600 mglday 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 tIle new generation antipsychotics. Quetiapine has an excellent tolerability profile offering high patient acceptability that, in tum, may pro mote patient adherence to medication and an improved quality of lite. As such, we consider quetiapine to be a first-choice antipsychotic for the treatment of acute exacerbations of schizophrenia.
Quetiapine: efficacy and tolerability in schizophrenia
European Neuropsychopharmacology, 2001
Quetiapine, in common with clozapine, has a greater affinity for 5-HT receptors than D receptors and preclinical studies have 2 2 consistently predicted efficacy against schizophrenia, with a low potential for causing extrapyramidal symptoms (EPS). In clinical trials, the efficacy of quetiapine was consistently superior to placebo and it was effective against both positive and negative symptoms.
High-dose quetiapine in treatment refractory schizophrenia
Schizophrenia …, 2005
Corresponding author. VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd., Bldg. 210, Room 15, Los Angeles, CA 90073. Tel.: +310 478 3711x43846; fax: +310 312 0572. ... Received 16 April 2004; received in revised form 20 July 2004; accepted 23 July ...
Quetiapine in the treatment of schizophrenia and related disorders
Neuropsychiatric Disease and Treatment, 2007
Quetiapine was developed in 1985 by scientists at AstraZeneca (formerly Zeneca) Pharmaceuticals. It received offi cial US Food and Drug Administration approval in September 1997 and approval in Germany in 2000. Since then, quetiapine has been used in the treatment of severe mental illness in approximately 70 countries including Canada, most Western European countries, and Japan. Quetiapine is a dibenzothiazepine derivative with a relatively broad receptor binding profi le. It has major affi nity to cerebral serotonergic (5HT 2A ), histaminergic (H1), and dopaminergic D 1 and D 2 receptors, moderate affi nity to α 1 -und α 2 -adrenergic receptors, and minor affi nity to muscarinergic M1 receptors; it demonstrates a substantial selectivity for the limbic system. This receptor occupancy profi le with relatively higher affi nity for the 5HT 2A receptor compared with the D 2 receptor is in part responsible for the antipsychotic characteristics and low incidence of extrapyramidal side-effects of quetiapine. The effi cacy of quetiapine in reducing positive and negative symptoms of schizophrenia has been proven in several clinical trials with placebo-controlled comparators. Quetiapine has also demonstrated robust effi cacy for treatment of cognitive, anxious-depressive, and aggressive symptoms in schizophrenia. Long-term trials show sustained tolerability for a broad spectrum of symptoms. Quetiapine has also proven effi cacy and tolerability in the treatment of moderate to severe manic episodes, and in the treatment of juveniles with oppositional-defi ant or conduct disorders, and in the geriatric dementia population. Recent data indicate that quetiapine may also be effective in the treatment of bipolar depressive symptoms without increasing the risk of triggering manic episodes, and in borderline personality disorder. In comparison with other antipsychotics, quetiapine has a favorable side-effect profi le. In clinical trials only small insignifi cant prolongations of the QT interval were observed. Weight-gain liabilities and new-onset metabolic side-effects occupy a middle-ground among newer antipsychotics. As a result of its good effi cacy and tolerability profi le quetiapine has become well established in the treatment of schizophrenia and manic episodes.
Therapeutic advances in psychopharmacology, 2012
Quetiapine fumarate, a first-line treatment for schizophrenia, exists in two formulations: extended release (XR) and immediate release (IR). This naturalistic, noninterventional study evaluated use of quetiapine XR/IR among in-patients with schizophrenia [ClinicalTrials.gov identifier: NCT01214135]. Data were collected from medical records. Categorical and numerical outcomes were compared using χ(2) and t tests. Of 178 enrolled patients, 66% and 34% used quetiapine XR and IR respectively. Based on mean daily dose, XR was used as antipsychotic medication in 64% of patients compared with 40% of patients on IR (dose ≥ 400 mg/day; p = 0.002) and in higher doses than IR (494 versus 345 mg/day; p = 0.001; calculated averages). Schizophrenia was more commonly reported as reason for use of XR than IR (20% versus 0%; p = 0.0003). Patients with comorbid substance abuse or somatic disease were more likely to receive XR (p = 0.003; p = 0.03). Treatment cessation due to nonadherence was less com...
Quetiapine at high doses for the treatment of refractory schizophrenia
Schizophrenia Research, 2008
Selecting the appropriate dose of antipsychotic medication is essential for successful long-term treatment in people with schizophrenia. However, there is much debate in the literature about the correct dosing of antipsychotics. This is especially true for quetiapine, a second-generation antipsychotic which experts have advocated using doses above the maximum recommended by the FDA of 800 mg/day. In this letter we report on a 12-week open label trial of high dose quetiapine for subjects with documented treatment refractory schizophrenia. All subjects were titrated to the target dose of 1,200 ± 200 mg/day over a three-week period. Subjects were evaluated weekly with the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Scale (CGI). Response was defined as ≥ 20% decrease in total BPRS score from baseline. Other weekly measurements included vital signs, the Simpson Angus Scale (SAS), Barnes Akathisia Scale (BAS), and the Assessment of Involuntary Movements Scale (AIMS). Laboratory assessments and electrocardiogram monitoring were done at baseline and end of study. Statistical analysis was conducted using the Cochran-Mantel-Haenszel method for monotonic correlations between scores and time, using a summary χ 2 statistic for evidence of time by visit correlations, stratifying the analysis with subject. Within-subject Spearman correlation coefficients between symptom scores and time were calculated, and the mean of these correlations calculated. Dichotomous variables were evaluated with Fisher's exact test. All analysis was done using SAS® 9.1 (SAS Institute Inc., Cary, NC) using two-tailed tests at α = 0.05.
Dose-response and comparative efficacy and tolerability of quetiapine across psychiatric disorders
International Clinical Psychopharmacology, 2011
The atypical antipsychotic, quetiapine, is frequently prescribed on-label and off-label for the treatment of a variety of psychiatric disorders. As quetiapine has variable affinity for dozens of receptors, its clinical effects should also show a large variation as a function of dose and diagnostic category. This study attempts to elucidate the dose-response and comparative efficacy and tolerability (metabolic data) of quetiapine across psychiatric disorders. A systematic search was carried out in the electronic databases, PubMed and EMBASE, using the keywords 'quetiapine' and 'placebo'. Both monotherapy and add-on studies were included. A total of 41 studies were identified. In unipolar and bipolar depression, studies consistently found quetiapine to be effective versus placebo, at doses of approximately 150-300 and 300-600 mg per day, respectively. In bipolar mania, they consistently found quetiapine to be effective at doses of approximately 600 mg per day. In acute exacerbation of schizophrenia, the majority of studies found quetiapine to be effective at doses of approximately 600 mg per day; however, a few large studies found no difference versus placebo. In contrast, studies consistently found quetiapine to be more effective than placebo for stable schizophrenia. In obsessive-compulsive disorder, studies did not consistently find quetiapine to be effective at doses of approximately 300 mg per day. However, studies may have underestimated the efficacy of quetiapine for obsessive-compulsive disorder due to concomitant administration of antidepressants and the utilization of treatment-refractory patients. In generalized anxiety disorder, studies consistently found quetiapine to be effective at doses of approximately 150 mg per day. Finally, analysis of metabolic tolerability data suggests that even low doses of quetiapine may lead to increase in weight and triglycerides across psychiatric disorders. Interestingly, however, quetiapine-induced elevations in low-density lipoprotein and total cholesterol seem to be restricted to schizophrenia patients.
The International Journal of Neuropsychopharmacology, 2010
Quetiapine extended-release (quetiapine-XR) has been studied in patients with schizophrenia, bipolar mania, bipolar depression, major depressive disorder (MDD), and generalized anxiety disorder (GAD). The purpose of this study was to compare the tolerability and sensitivity of quetiapine-XR among these psychiatric conditions. The discontinuation due to adverse events (DAEs) and reported somnolence in randomized, double-blind, placebo-controlled studies of quetiapine-XR in these psychiatric conditions were examined. The absolute risk reduction or increase and the number needed to treat to benefit (NNTB) or harm (NNTH) for DAEs and reported somnolence of quetiapine-XR ≥300 mg/d relative to placebo were estimated. Data from one study in schizophrenia (n=465), one in mania (n=316), one in bipolar depression (n=280), two in refractory MDD (n=624), two in MDD (n=669) and three in GAD (n=1109) were available. The risk for DAEs of quetiapine-XR relative to placebo was significantly increased in bipolar depression (NNTH=9), refractory MDD (NNTH=8), MDD (NNTH=9), and GAD (NNTH=5), but not in schizophrenia and mania. The risk for reported somnolence of quetiapine-XR relative to placebo was significantly increased in schizophrenia (600 mg/d NNTH=15 and 800 mg/d NNTH=11), mania (NNTH=8), bipolar depression (NNTH=4), refractory MDD (NNTH=5), MDD (NNTH=5) and GAD (NNTH=5). These results suggest that patients with GAD had the poorest tolerability during treatment with quetiapine-XR, but they had a similar sensitivity as those with bipolar depression and MDD. Patients with schizophrenia or mania had a higher tolerability and a lower sensitivity than those with bipolar depression, MDD, or GAD.