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Case-Control Analyses of the Impact of Pharmacotherapy on Prospectively Observed Suicide Attempts and Completed Suicides in Bipolar Disorder: Findings From STEP-BD

Lauren B. Marangell, M.D.; Ellen B. Dennehy, Ph.D.; Stephen R. Wisniewski, Ph.D.; Mark S. Bauer, M.D.; Sachiko Miyahara, M.S.; Michael H. Allen, M.D.; Melissa Martinez, M.D.; Rayan K. Al Jurdi, M.D.; and Michael E. Thase, M.D.

Objective: Given high rates of suicide and suicide attempts in bipolar disorder and the data suggesting a suicide-protective effect of lithium, we evaluated the impact of pharmacotherapy on prospectively observed suicides and suicide attempts in subjects in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

Method: The STEP-BD study enrolled 4360 participants with DSM-IV bipolar disorder diagnoses from September 1998 through November 2004. There were 270 suicide events in STEP-BD (8 completed suicides, 262 attempts). These occurred in 182 of STEP-BD participants (cases). Inclusion criteria required cases to be white or Caucasian, have at least 1 postbaseline visit, and have prescription information within 30 days of the suicide event. This reduced the available cohort to 106 cases. Matching included age, gender, history of previous suicide attempt, and a propensity score that considered bipolar subtype, marital status, age at onset, and history of psychosis, resulting in 93 matched pairs. A secondary analysis added mood state status within 30 days of the suicide event to the propensity score (N = 54 pairs). The association of drug prescriptions with suicide attempts/completions was assessed using a conditional logistic regression model.

Results: The results do not indicate a relationship between lithium use and suicide attempts or completions (p = .41). Similar findings were found for exposure to valproate, carbamazepine, lamotrigine, and the atypical antipsychotic medications. An association between selective serotonin reuptake inhibitor (SSRI) prescription and suicide events was observed (p < .0001). Findings were similar in a secondary analysis that controlled for mood state.

Conclusion: Our data are not consistent with a suicide-protective effect of lithium. The association between suicide events and SSRI prescriptions requires cautious interpretation due to complex relationships between treatment, severity, and suicidality.

Trial Registration: Identifier: NCT00012558


(J Clin Psychiatry 2008;69:916-922. Online Ahead of Print April 8, 2008.)

Received July 26, 2007; accepted Dec. 7, 2007. From the Mood Disorders Center, Menninger Department of Psychiatry, Baylor College of Medicine and South Central Mental Illness Research and Education Core, Department of Veterans Affairs, Houston, Tex. (Drs. Marangell, Martinez, and Al Jurdi); Department of Psychological Sciences, Purdue University, West Lafayette, Ind. (Dr. Dennehy); Epidemiology Data Center (Dr. Wisniewski and Ms. Miyahara) and Department of Psychiatry, Western Psychiatric Institute (Ms. Miyahara), University of Pittsburgh, Pittsburgh, Pa.; Harvard Medical School and the Veterans Affairs Boston Healthcare System, Boston, Mass. (Dr. Bauer); University of Colorado Health Sciences Center, Denver (Dr. Allen); and Department of Psychiatry, University of Pennsylvania School of Medicine and Philadelphia Veterans Affairs Medical Center, Philadelphia, and Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pa. (Dr. Thase). Dr. Marangell is now with Eli Lilly and Co., Indianapolis, Ind.

This project was funded by an Independent Investigator Award from the National Alliance for Research in Schizophrenia and Depression (NARSAD) (L.B.M.) and a grant from the American Foundation for Suicide Prevention (L.B.M.). The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study was conducted with federal funds from the National Institute of Mental Health (NIMH), National Institutes of Health, under contract N01MH80001.

This article was approved by the publication committee of the STEP-BD study. Additional details on STEP-BD can be located at

Any opinions, findings, and conclusions or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of NARSAD, the American Foundation for Suicide Prevention, the Department of Veterans Affairs, NIMH, or Eli Lilly.

Financial disclosure appears at the end of this article.

Corresponding author and reprints: Lauren B. Marangell, M.D., Lilly Corporate Center, Indianapolis, IN 46285 (e-mail: