Olanzapine or Lamotrigine Addition to Lithium in Remitted Bipolar Disorder Patients With Anxiety Disorder Comorbidity: A Randomized, Single-Blind, Pilot Study

Giuseppe Maina, MD; Umberto Albert, MD, PhD; Gianluca Rosso, M.; Filippo Bogetto, MD

J Clin Psychiatry 2008;69(4):609-616

Article Abstract

Objective: The aim of the present randomized, single-blind, pilot study was to assess the efficacy of the addition of a second mood stabilizer, either olanzapine or lamotrigine, to lithium in patients with remitted bipolar disorder and comorbid anxiety disorder.

Method: Adult DSM-IV bipolar disorder patients with a current anxiety disorder and a Hamilton Rating Scale for Anxiety (HAM-A) score of 12 or higher, in remission from an affective episode for at least 2 months while on lithium maintenance treatment, were randomly assigned to receive 12 weeks of single-blind olanzapine 5 to 10 mg/day (N = 24) or lamotrigine 50 to 200 mg/day (N = 23) addition to lithium. The primary outcome measure was the HAM-A; secondary outcome measures were the Clinical Global Impressions-Severity of Illness scale and the Global Assessment of Functioning (GAF) scale. Data were collected from July 2005 to February 2007.

Results: Twenty-two patients in the olanzapine and 18 in the lamotrigine group completed the trial. Mean ± SD final doses of olanzapine and lamotrigine were, respectively, 7.7 ± 4.2 mg/day and 96.7 ± 46.7 mg/day in the intent-to-treat sample (N = 47). Both olanzapine and lamotrigine were effective in reducing HAM-A scores from baseline to endpoint (paired t test for completers: t = 11.361, df = 21, p < .001 for olanzapine and t = 6.301, df = 17, p < .001 for lamotrigine). Both drugs were also effective on the secondary outcome measures. Olanzapine was more effective than lamotrigine at weeks 6 and 12 with a last-observation-carried-forward analysis on all 3 outcome measures, while such differences disappeared on the HAM-A and GAF at week 12 with the visit-wise analysis.

Conclusions: The addition of a second mood stabilizer (olanzapine or lamotrigine) to lithium is effective in reducing anxiety symptoms in bipolar disorder patients with a co-occurring anxiety disorder.