Substance Use Disorder and Other Predictorsof Antidepressant-Induced Mania: A Retrospective Chart Review

Sumita G. Manwani, M.D.; Tamara B. Pardo, A.B.; Mark J. Albanese, M.D.; Benjamin Zablotsky, B.A.; Frederick K. Goodwin, M.D.;and S. Nassir Ghaemi, M.D., M.P.H. 

Objective: To determine if substance use disorder (SUD) is a predictor of antidepressant-induced mania (ADM) in bipolar disorder, correcting for confounding factors in a regression model.

Method: 335 antidepressant trials were identified in 98 patients treated in an academic bipolar specialty clinic from 2000 to 2004. Patient charts were reviewed, and histories of SUD and ADM (primary outcome; defined as a hypomanic or manic episode within 12 weeks of beginning an antidepressant trial) were identified. Mood disorder diagnoses were made using the Structured Clinical Interview for DSM-IV mood module, and SUD diagnoses were defined using DSM-IV criteria. Potential confounding variables were also examined and included in a multivariable regression model. Concomitant mood stabilizer, antimanic, and antidepressant use was adjusted for in the regression model.

Results: In univariate analyses, there was no evidence of an association between ADM and past SUD. However, after adjustment for confounding variables in a multivariable regression model, there was a strong relationship (OR = 5.06, 95% CI = 1.31 to 19.64, p < .05). Other statistically significant predictors of ADM in the regression model were type II subtype of bipolar illness, female gender, and tricyclic antidepressant (TCA) use (vs. bupropion).

Conclusions: Along with other factors, a history of SUD was a strong predictor of ADM. Possible underestimation of ADM in randomized clinical trials may occur due to the exclusion of subjects with SUD. Type II illness, female gender, and TCA use also appeared to be predictors of ADM, while bupropion use appeared to predict lower likelihood of ADM.

(J Clin Psychiatry 2006;67:1341-1345)

Received March 28, 2006; accepted July 3, 2006. From the Bipolar Disorder Research Program (Dr. Manwani, Ms. Pardo, and Mr. Zablotsky) and the Addictions Program (Dr. Albanese), Department of Psychiatry, Cambridge Health Alliance, Cambridge, Mass.; the Department of Psychiatry, Harvard Medical School, Boston, Mass. (Drs. Manwani and Albanese, Ms. Pardo, and Mr. Zablotsky); the Psychopharmacology Research Center, Department of Psychiatry and Behavioral Sciences, The George Washington University School of Medicine, Washington, D.C. (Dr. Goodwin); and the Bipolar Disorder Research Program, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Ga. (Dr. Ghaemi).

Supported in part by National Institute of Mental Health Research Career Award MH-64189 (Dr. Ghaemi). This project received funding from Abbott Laboratories.

Dr. Albanese has been on the speakers/advisory boards of Forest and Reckitt Benckiser. Dr. Goodwin has been a consultant to Glaxo, Eli Lilly, Pfizer, Bristol-Myers Squibb, and Solvay; has received grant/research support from Abbott, Glaxo, Solvay, Janssen, Pfizer, Eli Lilly, Forest, Sanofi, and Bristol-Myers Squibb; and has received honoraria from and been on the speakers/advisory boards of Glaxo, Pfizer, Eli Lilly, and Bristol-Myers Squibb. Dr. Ghaemi has received grant/research support from and been on the advisory boards of GlaxoSmithKline and Pfizer and has been on the speakers bureaus of GlaxoSmithKline, Abbott, and AstraZeneca. Dr. Manwani, Ms. Pardo, and Mr. Zablotsky report no additional financial or other relationship relevant to the subject of this article.

Corresponding author and reprints: S. Nassir Ghaemi, M.D., Department of Psychiatry, Emory University, The Emory Clinic, Building B, Suite 6100, 1365 Clifton Rd., Atlanta, GA 30322 (e-mail: nghaemi@emory.edu).