Benzodiazepine Use and Risk of Recurrence in Bipolar Disorder: A STEP-BD Report

Objective: Benzodiazepines are widely prescribed to patients with bipolar disorder, but their impact on relapse and recurrence has not been examined.

Method: We examined prospective data
from a cohort of DSM-IV bipolar I and II patients who achieved remission during evidence-guided naturalistic treatment in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study (conducted in the United States between 1999 and 2005). Risk for recurrence among individuals who did or did not receive benzodiazepine treatment was examined using survival analysis. Cox regression was used to adjust for clinical and sociodemographic covariates. Propensity score analysis was used in a confirmatory analysis to address the possible impact of confounding variables.

Results: Of 1,365 subjects, 349 (25.6%) were prescribed a benzodiazepine at time of remission from a mood episode. After adjusting for potential confounding variables, the hazard ratio for mood episode recurrence among benzodiazepine-treated patients was 1.21 (95% CI, 1.01-1.45). The effects of benzodiazepine treatment on relapse remained significant after excluding relapses occurring within 90 days of recovery, or stratifying the sample by propensity score, a summary measure of likelihood of receiving benzodiazepine treatment. In an independent cohort of 721 subjects already in remission at study entry, effects of similar magnitude were observed.

Conclusion: Benzodiazepine use may be
associated with greater risk for recurrence of a mood episode among patients with bipolar I and II disorder. The prescribing of benzodiazepines, at a minimum, appears to be a marker for a more severe course of illness.

J Clin Psychiatry 2010;71(2):194-200

Submitted: January 6, 2009; accepted April 21, 2009.

Corresponding author: Roy H. Perlis, MD, MSc, Bipolar Clinic and Research Programs, 50 Staniford St, 5th Floor, Boston, MA 02114
([email protected]).