A Randomized, Double-Blind, Placebo-Controlled Trial of Quetiapine in the Treatment of Bipolar I or II Depression

TLDR

Bipolar depression lacks effective treatments, prompting a large randomized trial of 542 outpatients to evaluate quetiapine versus placebo while noting low rates of treatment‑emergent mania. The study was an 8‑week, double‑blind, placebo‑controlled RCT comparing quetiapine 600 mg/day, 300 mg/day, and placebo, with the primary endpoint being change in Montgomery‑Åsberg Depression Rating Scale scores and secondary assessments including HAMD, CGI, HAM‑A, PSQI, and Q‑LES‑Q. Quetiapine 600 mg/day and 300 mg/day produced response rates of 58.2 % and 57.6 % versus 36.1 % for placebo, remission rates of 52.9 % versus 28.4 %, and significant improvement in most MADRS items, confirming its efficacy and tolerability in bipolar depression.

Abstract

There is a major unmet need for effective options in the treatment of bipolar depression.Five hundred forty-two outpatients with bipolar I (N=360) or II (N=182) disorder experiencing a major depressive episode (DSM-IV) were randomly assigned to 8 weeks of quetiapine (600 or 300 mg/day) or placebo. The primary efficacy measure was mean change from baseline to week 8 in the Montgomery-Asberg Depression Rating Scale total score. Additional efficacy assessments included the Hamilton Depression Rating Scale, Clinical Global Impression of severity and improvement, Hamilton Anxiety Rating Scale, Pittsburgh Sleep Quality Index, and Quality of Life Enjoyment and Satisfaction Questionnaire.Quetiapine at either dose demonstrated statistically significant improvement in Montgomery-Asberg Depression Rating Scale total scores compared with placebo from week 1 onward. The proportions of patients meeting response criteria (> or =50% Montgomery-Asberg Depression Rating Scale score improvement) at the final assessment in the groups taking 600 and 300 mg/day of quetiapine were 58.2% and 57.6%, respectively, versus 36.1% for placebo. The proportions of patients meeting remission criteria (Montgomery-Asberg Depression Rating Scale < or =12) were 52.9% in the groups taking 600 and 300 mg/day of quetiapine versus 28.4% for placebo. Quetiapine at 600 and 300 mg/day significantly improved 9 of 10 and 8 of 10 Montgomery-Asberg Depression Rating Scale items, respectively, compared to placebo, including the core symptoms of depression. Treatment-emergent mania rates were low and similar for the quetiapine and placebo groups (3.2% and 3.9%, respectively).Quetiapine monotherapy is efficacious and well tolerated for the treatment of bipolar depression.