A randomized, double-blind study of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with generalized anxiety disorder.

This study evaluated once-daily, extended-release quetiapine fumarate (quetiapine XR) monotherapy in generalized anxiety disorder (GAD). This was a 10-week (8-week active treatment/2-week posttreatment drug-discontinuation/tapering phase), double-blind, randomized, placebo-controlled study (D1448C00009). Primary end point was change from randomization at week 8 in Hamilton Anxiety Rating Scale (HAM-A) total score. Overall, 951 patients with GAD were randomized (quetiapine XR: 50 mg/d, n = 234; 150 mg/d, n = 241; 300 mg/d, n = 241; placebo, n = 235). At week 8, HAM-A total scores significantly (P < 0.001) improved versus placebo (-11.10) with quetiapine XR 50 mg/d (-13.31) and 150 mg/d (-13.54), but not 300 mg/d (-11.87; P = 0.240). At week 1, HAM-A total scores significantly improved versus placebo (-5.94) with quetiapine XR 50 mg/d (-7.47; P < 0.01), 150 mg/d (-8.19; P < 0.001), and 300 mg/d (-7.23; P < 0.01). Versus placebo at week 8, quetiapine XR 50 and 150 mg/d significantly improved HAM-A psychic (P < 0.01 and P < 0.001, respectively) and somatic (P < 0.001; P < 0.01, respectively) cluster scores, HAM-A response (≥ 50% total score reduction; P < 0.05), and Clinical Global Impression-Improvement categorical changes (P < 0.05). For quetiapine XR 150 mg/d, significant (P < 0.05) improvements were seen for HAM-A remission (total score, ≤ 7) and Clinical Global Impression-Severity of Illness scores. For quetiapine XR 300 mg/d, improvements in these secondary variables were not significantly different versus placebo. Pittsburgh Sleep Quality Index global scores improved with all 3 doses (quetiapine: XR 50 mg/d, -4.07 [P < 0.05]; 150 mg/d, -4.38 [P < 0.05]; 300 mg/d, -3.97 [P < 0.05], versus -3.31 with placebo). Adverse events (>10% with quetiapine XR) were dry mouth, somnolence, sedation, dizziness, headache, and fatigue. Quetiapine XR (50/150 mg/d) monotherapy was effective at week 8 in patients with GAD; symptom improvement was seen at week 1 for all doses (50/150/300 mg/d). Safety and tolerability were consistent with the known profile of quetiapine.

Self-reported sedation profile of quetiapine extended-release and quetiapine immediate-release during 6-day initial dose escalation in bipolar depression: a multicenter, randomized, double-blind, phase IV study.

BACKGROUND: A human-volunteer study reported lower sedation intensity during escalation of the extended-release formulation of quetiapine fumarate (quetiapine XR) than the immediate-release (IR) formulation. OBJECTIVE: To test the hypothesis that the profile of initial tolerability, including sedation, differs between the extended-release (XR) and immediate-release (IR) formulations of quetiapine in patients with bipolar depression. METHODS: In a randomized, double-blind, double-dummy, parallel-group, Phase IV study, male and female inpatients aged 18 to 50 years with a Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) diagnosis of bipolar I or II depression were randomized after washout to receive placebo on day 1 and quetiapine XR or IR at escalating doses of 50, 100, 200, 300, and 300 mg once daily on the evenings of days 2 to 6, with hospital discharge on day 7. Sedation intensity was assessed by a self-reported modified Bond-Lader visual analog scale (VAS) score. RESULTS: Of 139 randomized patients, 134 completed the study. Mean patient age was 39.0 years; mean weight, 91.3 kg; and mean body mass index (calculated as weight in kilograms divided by height in meters squared), 31.0. Sedation intensity 1 hour after administration of the 50-mg dose (the primary study measure) was statistically significantly lower with quetiapine XR versus IR (mean [SD] VAS score: 33.4 [26.92] vs 44.0 [31.76]; least squares mean difference: 12.55, P = 0.009; modified intention-to-treat population). Sedation intensity was found in secondary analyses to be significantly lower with quetiapine XR than with quetiapine IR 1, 2, and 3 hours after each dose on days 2 to 6 (P ≤ 0.05), with similar sedation intensity between the treatment groups 4 to 14 hours postdose. Rates of treatment-related adverse events were 47.1% with quetiapine XR versus 59.4% with quetiapine IR. Three serious adverse events (4.3%) occurred in the quetiapine XR group. Adverse events led to study discontinuation in 1 patient (1.4%) in the quetiapine XR group and in 2 patients (2.9%) in the IR group. CONCLUSIONS: During the initial dose-escalation period studied, patients with bipolar depression reported statistically significantly lower sedation intensity in the 1 to 3 hours after taking quetiapine XR compared with the IR formulation. Overall tolerability for both formulations was consistent with the known profile of quetiapine. ClinicalTrials.gov identifier: NCT00926393.