Evaluate the efficacy and tolerability of quetiapine and lithium monotherapy for major depressive episodes in bipolar disorder during an acute 8-week period and up to 52-week continuation phase.

802 patients (499 bipolar I, 303 bipolar II) were randomized to quetiapine 300mg/d (n=265), quetiapine 600mg/d (n=268), lithium 600mg/d (n=136), or placebo (n=133) for 8 weeks. Primary endpoint was change from baseline to 8 weeks in MADRS total score. After 8 weeks, patients with MADRS ≤12 and YMRS ≤12 entered a 26- to 52-week continuation phase of quetiapine (300mg/d or 600mg/d) or placebo. Patients on lithium received 300mg/day of quetiapine (results of continuation phase not included here and to be presented separately).

LSM MADRS score change at 8 weeks was -15.36 (quetiapine 300mg/d), -16.10 (quetiapine 600mg/d), -13.60 (lithium), and -11.81 (placebo; P<0.001 for both quetiapine doses, P=0.123 for lithium, versus placebo; LOCF ANCOVA). Quetiapine (both doses)-treated, but not lithium-treated, patients showed significantly greater improvements (P≤0.05) in MADRS response and remission rates, HAM-D, CGI-BP-S, CGI-BP-Change, and HAM-A at Week 8 versus placebo; MADRS item 10 (suicidal thoughts) improved with quetiapine 600mg/d versus placebo (P=0.013). Most common adverse events considered drug-related included somnolence, dry mouth, and dizziness with quetiapine (both doses) and nausea with lithium.

Quetiapine (300mg/d or 600mg/d) was more effective than placebo for the treatment of acute depressive episodes in bipolar I and bipolar II disorder. Quetiapine treatment was generally well tolerated.

Supported by funding from AstraZeneca Pharmaceuticals LP.