Quetiapine versus placebo in combination with lithium or divalproex for the treatment of bipolar mania.

Quetiapine (QTP) combined with lithium (Li) or divalproex (DVP) for the treatment of mania was evaluated in 2 double-blind, placebo-controlled studies. Patients were randomized to 3 or 6 weeks of treatment with QTP plus Li/DVP or placebo (PBO) plus Li/DVP. Quetiapine was dosed up to 800 mg/d; Li was dosed to achieve serum concentrations of 0.7-1.0 mEq/L and DVP to 50-100 microg/mL. A total of 402 patients were randomized: 197 to QTP + Li/DVP and 205 to PBO + Li/DVP. The mean quetiapine dose in responders was 492 (+/-204) mg/d. Improvement in the Young Mania Rating Scale (YMRS) at day 21 in the QTP + Li/DVP group (-15.29) was statistically superior to the PBO + Li/DVP group (-12.19) (P < 0.05). A statistically significant difference in favor of quetiapine was observed within the first week (P < 0.05). Significantly more QTP + Li/DVP patients achieved a response (> or =50% decrease in the YMRS) at day 21 (QTP + Li/DVP, 55.7%; PBO + Li/DVP, 41.6%;P < 0.01). Improvements in Clinical Global Impression-Bipolar Severity of Illness scores by day 21 were also significantly greater in QTP + Li/DVP-treated patients (-1.59) versus PBO + Li/DVP (-1.19) (P < 0.01). Common adverse events (> or =5% and twice that in the PBO + Li/DVP group) in the QTP + Li/DVP group were somnolence, dry mouth, and asthenia. Quetiapine combined with Li/DVP was not associated with extrapyramidal symptoms (including akathisia) or emergent depression. More QTP + Li/DVP-treated patients completed the trial, and there was no difference in discontinuation rates due to adverse events between the two groups. Quetiapine, in combination with lithium or divalproex, is well tolerated and has superior efficacy to lithium or divalproex alone in the treatment of bipolar mania.