The efficacy and tolerability of once-daily extended release quetiapine fumarate in hospitalized patients with acute schizophrenia: a 6-week randomized, double-blind, placebo-controlled study.
ABSTRACT 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.
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ABSTRACT: Objective This study was designed to evaluate the short-term efficacy and safety of once-daily lurasidone (80 mg/day and 160 mg/day) in the treatment of an acute exacerbation of schizophrenia.Methods Participants, who were recently admitted inpatients with schizophrenia with an acute exacerbation of psychotic symptoms, were randomly assigned to 6 weeks of fixed-dose, double-blind treatment with lurasidone 80 mg (n = 125), lurasidone 160 mg (n = 121), quetiapine XR 600 mg (QXR-600 mg; n = 119; active control included to test for assay sensitivity), or placebo (n = 121), all dosed once daily in the evening. Efficacy was evaluated using a mixed-model repeated-measures analysis of the change from Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) total score (the primary efficacy measure) and Clinical Global Impressions severity (CGI-S) score (the key secondary efficacy measure).ResultsTreatment with both doses of lurasidone or with QXR-600 mg was associated with significantly greater improvement at Week 6 on PANSS total score, PANSS positive and negative subscale scores, and CGI-S score compared with placebo. The endpoint responder rate (≥ 20% improvement in PANSS total score) was higher in subjects treated with lurasidone 80 mg (65%; p < 0.001), lurasidone 160 mg (79%; p < 0.001), and QXR-600 mg (79%; p < 0.001) compared with placebo (41%). The proportion of patients experiencing ≥ 7% weight gain was 4% for each lurasidone group, 15% for the QXR-600 mg group, and 3% for the placebo group. Endpoint changes in levels of cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol were comparable for both lurasidone groups and placebo, while the QXR-600 mg group showed a significant median increase compared with the placebo group in levels of cholesterol (p < 0.001), LDL cholesterol (p < 0.01), and triglycerides (p < 0.05).Conclusions Lurasidone 80 mg and 160 mg doses administered once-daily in the evening, were safe and effective treatments for subjects with acute schizophrenia, with increased response rates observed at the higher dose. Dose-related adverse effects were limited, and both doses were generally well-tolerated.Schizophrenia Research 04/2013; 145(s 1–3):101–109. · 4.43 Impact Factor
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ABSTRACT: Background: Clinicians need to know the right antipsychotic dose for optimized treatment, and the concept of dose equivalence is important for many clinical and scientific purposes. Methods: We refined a method presented in 2003, which was based on the minimum effective doses found in fixed-dose studies. We operationalized the selection process, updated the original findings, and expanded them by systematically searching more recent literature and by including 13 second-generation antipsychotics. To qualify for the minimum effective dose, a dose had to be significantly more efficacious than placebo in the primary outcome of at least one randomized, double-blind, fixed-dose trial. In a sensitivity analysis, 2 positive trials were required. The minimum effective doses identified were subsequently used to derive olanzapine, risperidone, haloperidol, and chlorpromazine equivalents. Results: We reviewed 73 included studies. The minimum effective daily doses/olanzapine equivalents based on our primary approach were: aripiprazole 10 mg/1.33, asenapine 10 mg/1.33, clozapine 300 mg/40, haloperidol 4 mg/0.53, iloperidone 8 mg/1.07, lurasidone 40 mg/5.33, olanzapine 7.5 mg/1, paliperidone 3 mg/0.4, quetiapine 150 mg/20, risperidone 2 mg/0.27, sertindole 12 mg/1.60, and ziprasidone 40 mg/5.33. For amisulpride and zotepine, reliable estimates could not be derived. Conclusions: This method for determining antipsychotic dose equivalence entails an operationalized and evidence-based approach that can be applied to the various antipsychotic drugs. As a limitation, the results are not applicable to specific populations such as first-episode or refractory patients. We recommend that alternative methods also be updated in order to minimize further differences between the methods and risk of subsequent bias.Schizophrenia Bulletin 02/2014; · 8.61 Impact Factor
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ABSTRACT: Background Non-adherence to antipsychotic medication in schizophrenic patients is common and associated with symptom relapse and poorer long-term outcomes. The risk factors for treatment non-adherence include dosing frequency and complexity. Besides, slower dose titration in an acute schizophrenic episode may lead to attenuated efficacy. Therefore, the convenient dosage regimen and rapid initiation scheme of quetiapine extended release (XR) were expected to provide better effectiveness and promote adherence in patients with schizophrenia. This study was implemented to assess the efficacy and safety of once-daily quetiapine XR in schizophrenic patients with switched from other antipsychotics which were suboptimal due to insufficient efficacy or tolerability.Methods This was a 12-week, open-label study conducted in the Chinese population in Taiwan.Patients who had a score of 4 (moderate) or greater on any of the 7 items of the Positive and Negative Syndrome Scale (PANSS) Positive Symptom Subscale and needed to switch from previous antipsychotics were recruited. Quetiapine XR was administered at 300 mg on day 1, 600 mg on day 2 and up to 800 mg after day 2. From day 8 until the end of the study, the dose of quetiapine XR was adjusted within 400-800 mg per day, depending on the clinical response and tolerance of the patients. The variable of the primary outcome was the change from baseline to Week 12 in PANSS total and subscale scores. Secondary outcome was the baseline-to-endpoint difference in the Clinical Global Impression-Severity (CGI-S) scores of the participants.ResultsSixty-one patients were recruited and 55.7% of them completed the study. The mean changes in the PANSS total score and CGI-S score showed significant improvement (¿18.4, p¿<¿.001 and ¿1.0, p¿<¿.001, respectively). Four patients (6.7%) experienced adverse events including headache, exacerbation of psychosis and dysuria. The use of concomitant anticholinergics decreased from 15.0% to 8.3%.Conclusions The results of our investigation implicated that quetiapine XR was an effective and well tolerated alternative for Chinese schizophrenic patients with previous suboptimal treatment. Future large-scale studies are warranted to validate our results.Trial registrationClinicalTrials.gov ID NCT02142556. Registered 15 May 2014.BMC Psychiatry 01/2015; 15(1):1. · 2.24 Impact Factor