Combined data are presented from two long-term, phase III studies (D1447C00126; D1447C00127) that examined the efficacy and safety of quetiapine in combination with lithium/divalproex in the prevention of mood events (manic, mixed, or depressed) in bipolar I disorder.

During a stabilization phase (12–36 weeks), patients received quetiapine (400–800 mg/day; open-label; flexible, divided doses) with lithium or divalproex (target serum concentrations 0.5–1.2 mEq/L and 50–125 μg/mL). Thereafter, patients were randomized to double-blind treatment with quetiapine (400–800 mg/day)+lithium/divalproex or placebo+lithium/divalproex for up to 104 weeks. The primary endpoint was time to the first mood event, defined by medication initiation, hospitalization for a mood event, YMRS or MADRS scores ≥20 at 2 consecutive assessments, or discontinuation due to a mood event.

In total, 3414 patients entered the stabilization phase and 1326 were randomized and received ≥1 dose of study medication. Rates of recurrence were 19.3% vs 50.4% for quetiapine and placebo groups, respectively. The risk of recurrence of a mood event was significantly reduced in the quetiapine group relative to the placebo group (HR=0.30, P<0.0001). HRs for the risk of recurrence of manic and depressed events were both 0.30 (P<0.0001). Long-term treatment with quetiapine was generally well tolerated; safety data including glucose changes will also be presented.

Quetiapine in combination with lithium/divalproex is significantly more effective than lithium/divalproex alone in the prevention of mood episodes associated with bipolar I disorder, irrespective of the index episode.

Supported by funding from AstraZeneca Pharmaceuticals LP.