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 < 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.
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 < 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.
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.