A 12-week single-blind trial of quetiapine for the treatment of mood symptoms in adolescents at high risk for developing bipolar I disorder

Objective: To investigate the effectiveness and tolerability of quetiapine for the treatment of adolescents at high risk for developing bipolar I disorder. Method: Twenty adolescents (aged 12-18 years) with mood symptoms that did not meet DSM-IV-TR criteria for bipolar I disorder and who had at least one first-degree relative with bipolar I disorder were recruited from August 2003 to June 2005 to participate in a single-blind, 12-week prospective study of quetiapine. Subjects were diagnosed using the Washington University in St. Louis Kiddie Schedule of Affective Disorders and Schizophrenia and were symptomatic, defined by a Young Mania Rating Scale (YMRS) score >= 12 or a Childhood Depression Rating Scale-Revised Version (CDRS-R) score >= 28 at baseline. The primary effectiveness measure was an endpoint Clinical Global Impressions-Improvement scale (CGI-I) score <= 2 ("much" or "very much" improved). Secondary efficacy measures included change from baseline to endpoint in YMRS and CDRS-R scores. Results: Mood disorder diagnoses in the adolescents consisted of bipolar disorder not otherwise specified (N = 11), dysthymia (N = 3), bipolar II disorder (N = 3), cyclothymia (N = 2), and major depressive disorder (N = 1). The majority of patients (N = 12, 60%) were non-responders to previous trials of psychotropic agents. Fifteen subjects (75%) completed all study visits. Eighty-seven percent of patients were responders (CGI-I <= 2) to quetiapine at week 12 (mean +/- SD endpoint dose = 460 +/- 88 mg/day). YMRS scores decreased from 18.1 +/- 5.5 at baseline to 8.7 +/- 7.9 at endpoint (p <.0001), and CDRS-R scores decreased from 38.2 +/- 9.8 to 27.7 +/- 9.3, (p =.0003). The most frequently reported adverse events were somnolence, headache, musculoskeletal pain, and dyspepsia. No subjects discontinued study participation due to adverse events. Conclusion: Although these findings are limited by the small sample size and open-label treatment, the results suggest that quetiapine may be an effective treatment for mood symptoms in adolescents with a familial risk for developing bipolar I disorder.