Quetiapine or haloperidol as monotherapy for bipolar mania-a 12-week, double-blind, randomised, parallel-group, placebo-controlled trial

Methods: Patients (n = 302) with bipolar I disorder (manic episode) were randomised to 12 weeks' double-blind treatment with quetiapine (flexibly dosed up to 800 mg/day), placebo, or haloperidol (up to 8 mg/day). The primary efficacy outcome variable was change from baseline to Day 21 in Young Mania Rating Scale (YMRS) score. Results: YMRS score improved with quetiapine at Day 21 (−12.29 versus −8.32 for placebo; P < 0.01). The difference in favor of quetiapine increased by Day 84 (−17.52 versus −9.48; P < 0.001). Haloperidol also showed an advantage over placebo at Days 21 and 84 (P < 0.001). There was no significant difference in efficacy measures between quetiapine and haloperidol groups at any assessment except Day 21. The only common adverse event with quetiapine was somnolence (12.7%). Extrapyramidal symptoms (EPS), including akathisia, occurred at 59.6% with haloperidol, 12.7% with quetiapine, 15.8% with placebo. Most quetiapine responders (84%) received a dose of 400-800 mg/day. Conclusions: Quetiapine was effective and well tolerated. The efficacy and tolerability profile of haloperidol (including its propensity for EPS) supported study validity.