A Randomized, Double-Blind, Controlled Trial of Lithium Versus Quetiapine for the Treatment of Acute Mania in Youth with Early Course Bipolar Disorder

Abstract

Objective: To compare the efficacy and tolerability of lithium versus quetiapine for the treatment of manic or mixed episodes in youths with early course bipolar I disorder. Methods: Six-week, randomized, double-blind clinical trial of lithium versus quetiapine for the treatment of adolescents with acute manic/mixed episode. Target dose of quetiapine dose was adjusted to a target dose of 400-600 mg and target serum level for lithium was 1.0-1.2 mEq/L. Primary outcome measure was baseline-to-endpoint change in the Young Mania Rating Scale (YMRS). Secondary outcomes were treatment response (50% or more decrease from baseline in YMRS score) and remission (YMRS score ≤12, Children's Depression Rating Scale-Revised [CDRS-R] total score ≤28 and Clinical Global Impression Bipolar Severity Scale [CGI-BP-S] overall score of ≤3, respectively). Results: A total of 109 patients were randomized (quetiapine = 58 and lithium = 51). Participants in the quetiapine treatment group showed a significantly greater reduction in YMRS score than those in the lithium group (-11.0 vs. -13.2; p < 0.001; effect size 0.39). Response rate was 72% in the quetiapine group and 49% in the lithium group (p = 0.012); no differences in remission rates between groups were observed. Most frequent side effects for lithium were headaches (60.8%), nausea (39.2%), somnolence (27.5%), and tremor (27.5%); for quetiapine somnolence (63.8%), headaches (55.2%), tremor (36.2%), and dizziness (36.2%) were evidenced. Participants receiving quetiapine experienced more somnolence (p < 0.001), dizziness (p < 0.05), and weight gain (p < 0.05). Conclusions: Treatment with both lithium and quetiapine led to clinical improvement. Most study participants in this study experienced a clinical response; however, less than half of the participants in this study achieved symptomatic remission. The head-to-head comparison of both treatment groups showed quetiapine was associated with a statistically significant greater rate of response and overall symptom reduction compared with lithium. Trial registration: clinicaltrials.gov NCT00893581.

Keywords: bipolar disorder; early-course; lithium; mania; quetiapine.

Figures

FIG. 1.

Patient disposition. Safety includes subjects who had at least one dose of the medications and had one post-follow-up visit. The intent-to-treat populations include all subjects randomized to receive medications.

FIG. 2.

Clinical efficacy measures over time. (A) Estimated marginal mean change in YMRS score from baseline (liner mixed model for repeated measurements analysis of intent-to-treat population). (B) Proportion of treatment response (change in YMRS ≥50%) with LOCF; *p < 0.05; **p < 0.01; ***p < 0.001. LOCF, last observation carried forward; YMRS, Young Mania Rating Scale.