Long-term efficacy of quetiapine in combination with lithium or divalproex on mixed symptoms in bipolar I disorder.

BACKGROUND

To evaluate quetiapine in patients with bipolar I disorder with mixed symptoms.

METHODS

Data from 2 studies (D1447C00126, D1447C00127) were pooled and mixed events analyzed separately. Patients received quetiapine (400-800mg/day) plus lithium/divalproex to achieve ≥12 weeks of clinical stability, followed by double-blind quetiapine (400-800mg/day) or placebo, plus lithium/divalproex, for up to 104 weeks. Primary endpoint was time to first mood event post-randomization.

RESULTS

The ITT population included 1326 patients, of whom 445 had a mixed episode at study entry, 219 received quetiapine plus lithium/divalproex, and 226 received placebo plus lithium/divalproex. Mood events were reported by fewer quetiapine-plus-lithium/divalproex than placebo-plus-lithium/divalproex-treated patients (21.0% vs 54.0%), and included mixed (6.4% vs 22.1%), pure manic (5.0% vs 13.3%), and pure depressed events (9.6% vs 18.6%). Hazard ratios (HR) for time to recurrence were longer for quetiapine plus lithium/divalproex than placebo plus lithium/divalproex for mixed (HR=0.23; 95% CI: 0.13-0.42; p<0.0001), pure manic (HR=0.30; 95% CI: 0.15-0.60; p=0.0007), and pure depressed events (HR=0.38; 95% CI: 0.22-0.64; p=0.0003). No new safety concerns were noted.

LIMITATIONS: The post hoc nature of the analyses as patients were not randomized according to index symptom status.

CONCLUSIONS

In stable patients with bipolar I disorder, quetiapine plus lithium/divalproex significantly increased time to recurrence of mood events versus placebo in patients with mixed symptoms at study entry and time to occurrence of mixed-mood events in patients with any mood episode at study entry.