To determine the efficacy of QTP in patients with bipolar I disorder with mixed symptoms.

Data from 2 phase III studies (D1447C00126 and D1447C00127) were pooled. Unlike previous analyses of these studies, mixed events were analyzed separately. Patients received QTP (400-800 mg/d)+Li/DVP to achieve ≥12 weeks of clinical stability followed by double-blind treatment with QTP (400-800 mg/d)+Li/DVP or PBO+Li/DVP for up to 104 weeks. Primary endpoint was time to first mood event post-randomization.

1326 patients were included in the ITT population. Relative to PBO, QTP significantly increased time to recurrence of mixed events (P< 0.0001). 445 ITT patients had a most recent mixed episode at study entry. In these patients, mood events were reported by fewer patients on QTP+Li/DVP (21.0%) than on PBO+Li/DVP (53.9%). These events included mixed (6.4% vs 22.1%), pure manic (5.0% vs 13.3%), and pure depressed events (9.6% vs 18.6%). Time to recurrence of mood events was significantly longer for patients on QTP+Li/DVP than for those on PBO+Li/DVP 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.

In stable patients with bipolar I disorder, QTP+Li/DVP significantly increased: a) time to recurrence of mood events compared with PBO in patients with mixed symptoms at study entry; and b) time to occurrence of mixed mood events in patients with any mood episode at study entry.

Supported by funding from AstraZeneca Pharmaceuticals.