Rates of remission/euthymia with quetiapine monotherapy compared with placebo in patients with acute mania

Abstract

Objective 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. Methods 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 ≤ 12; (ii) YMRS score ≤ 12 and Montgomery–Asberg Depression Rating Scale (MADRS) score ≤ 10; (iii) YMRS score ≤ 12 and MADRS score ≤ 8; (iv) YMRS score ≤ 8; and (v) YMRS score ≤ 8 plus a score ≤ 2 for the YMRS core items of Irritability, Speech, Content, and Disruptive/Aggressive Behavior. Results 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 ≤ 12), 35.6% versus 21.5% (YMRS ≤ 12 + MADRS ≤ 10), 35.1% versus 20.0% (YMRS ≤ 12 + MADRS ≤ 8), 25.0% versus 14.4% (YMRS ≤ 8), and 21.6% versus 14.4% (YMRS ≤ 8 plus core items ≤ 2) ( p < 0.01 for all comparisons except YMRS ≤ 8 plus core items ≤ 2: p = 0.06). By Day 84, these had increased to: 65.4% versus 35.9% (YMRS ≤ 12), 60.1% versus 30.8% (YMRS ≤ 12 + MADRS ≤ 10), 58.7% versus 29.7% (YMRS ≤ 12 + MADRS ≤ 8), 60.1% versus 30.3% (YMRS ≤ 8), and 56.7% versus 29.7% (YMRS ≤ 8 plus core items ≤ 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. Conclusions 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.