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.