An international, randomized, double-blind, parallel-group study was designed to determine the efficacy and safety of quetiapine+Li/DVP compared with placebo+Li/DVP in the prevention of recurrent mood events (manic, mixed, or depressed) in patients with bipolar I disorder.

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) plus Li/DVP (target serum concentrations 0.5–1.2 mEq/L and 50–125 μg/mL, respectively) for up to 36 weeks to achieve at least 12 weeks of clinical stability. Patients were subsequently randomized to double-blind treatment with quetiapine (400–800 mg/day) plus 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 score ≥20 at two consecutive assessments or at final assessment if the patient discontinued, or study discontinuation due to a mood event.

1461 patients entered the stabilization phase and 703 (48%) were randomized to double-blind treatment receiving at least one dose of study medication (ITT population). A markedly lower proportion of patients had a mood event in the quetiapine+Li/DVP versus placebo+Li/DVP group (18.5% vs 49.0%, respectively), with a risk reduction of 72% (hazard ratio 0.28; P<0.0001). The incidence of adverse events was similar between the two treatment groups.

Maintenance treatment with quetiapine+Li/DVP significantly increased the time to recurrence of any mood event compared with placebo+LI/DVP. Long-term treatment with quetiapine was generally well-tolerated.

Supported by funding from AstraZeneca Pharmaceuticals LP.