To examine the long-term efficacy and safety of quetiapine in combination with lithium (Li) or divalproex (DVP) in the prevention of recurrent mood events (manic, mixed, or depressed).

Patients with bipolar I disorder (DSM-IV, most recent episode manic, mixed or depressed) received open-label quetiapine (400–800 mg/day; flexible, divided doses)+Li/DVP (target serum concentrations 0.5–1.2 mEq/L and 50–125 μg/mL) for up to 36 weeks to achieve ≥12 weeks of clinical stability. Patients were subsequently randomized to double-blind treatment with quetiapine (400–800 mg/day)+Li/DVP or placebo+Li/DVP for up to 104 weeks. Primary endpoint was time to recurrence of any mood event defined by medication initiation, hospitalization, YMRS or MADRS scores ≥20 at two consecutive assessments, or study discontinuation due to a mood event.

1953 patients entered the stabilization phase and 623 were randomized and received ≥1 dose of study medication. Rates of recurrence of a mood event were 20.3% (63/310) vs 52.1% (163/313) for quetiapine and placebo groups, respectively, a risk reduction of 68% (HR 0.32; P<0.0001). Risk reductions were similar for manic and depressed events (HRs 0.30 and 0.33, respectively; P<0.0001). Safety data were consistent with the recognized safety profile of quetiapine. However, a greater incidence of blood glucose ≥126 mg/dL was observed in the quetiapine treatment group.

Maintenance treatment with quetiapine+Li/DVP was significantly more effective than placebo+Li/DVP in increasing the time to recurrence of a mood event in stable patients with bipolar I disorder.

Supported by funding from AstraZeneca Pharmaceuticals LP.