Chart Review of the Impact of Attention-Deficit/Hyperactivity Disorder Comorbidity on Response to Lithium or Divalproex Sodium in Adolescent Mania

Rosanne C. State, MD; Mark A. Frye, MD; Lori L. Altshuler, MD; Michael Strober, PhD; Mark DeAntonio, MD; Sun Hwang, MS; Jim Mintz, PhD

J Clin Psychiatry 2004;65(8):1057-1063

Article Abstract

Purpose: Although adolescent onset of bipolar disorder is common, the optimal treatment approach for mania in this age group remains understudied. Comorbid attention-deficit/hyperactivity disorder (ADHD) has been reported to predict lithium resistance in adolescents with bipolar disorder. Little is known about response to divalproex sodium in adolescents with bipolar disorder comorbid with ADHD. This study was conducted to evaluate comparative response rates to lithium and divalproex sodium in adolescent mania with and without this comorbidity.

Method: Medical records were reviewed for 42 patients (ages 12-19 years) who were hospitalized for acute mania and discharged with a diagnosis of DSM-III-R or DSM-IV bipolar disorder on either lithium (N = 29) or divalproex sodium (N = 13) treatment. A clinician blinded to treatment status rated improvement on the basis of abstracted notes in each case utilizing the Clinical Global Impressions Scale modified for use in bipolar illness (CGI-BP). Response was defined as a discharge CGI-BP overall change score of 1 or 2 (much or very much improved). Data were collected from January 1992 through May 1999.

Results: 36/42 (85.7%) patients presented with mixed mania, and 14/41 (34.1%) patients had a history of ADHD. The overall response rate was 80.9% (34/42). 92.6% (25/27) of patients without ADHD were responders versus 57.1% (8/14) of subjects with comorbid ADHD (p = .007). There were no significant differences in response rates for lithium versus divalproex sodium in subjects with and without ADHD.

Conclusion: These retrospective data suggest overall equivalent response rates for lithium and divalproex sodium in predominantly mixed adolescent mania. However, a history of ADHD was associated with a significantly diminished acute response to both divalproex sodium and lithium as a primary treatment for the manic phase of bipolar disorder.