Predictors of Bipolar Disorder Risk Among Patients Currently Treated for Major Depression

Joseph R. Calabrese, MD; David J. Muzina, MD; David E. Kemp, MD; Gary S. Sachs, MD; Mark A. Frye, MD; Thomas R. Thompson, MD; David Klingman, PhD; Michael L. Reed, PhD; Robert M.A. Hirschfeld, MD

In This Article


Objective: The primary objective of this study was to assess the rate of bipolar disorder (BPD) risk among patients unsuccessfully treated for major depression and to identify predictors of bipolarity.
Patients, Design, and Setting: Psychiatrists from community and private practice settings sequentially selected patients with unipolar depression who exhibited nonresponse to at least 1 antidepressant (AD) trial.
Main Outcome Measures: Patients self-reported their demographics, family history, comorbid health status, and legal problems. Current depression symptoms were assessed via the Centers for Epidemiologic Studies - Depression (CES-D) scale. Bipolar screening was performed using the Mood Disorder Questionnaire (MDQ). A psychiatrist recorded patient history and current and prior AD medication use.
Results: Of 602 patients enrolled, 18.6% screened positive on the MDQ. This rate was not affected by the number of prior AD failures or patient demographics. A prior history of BPD was reported by 12.3% of patients of which the psychiatrist was not aware or did not report, and 41.2% of these patients were MDQ+. Stepwise logistic regression identified 5 variables associated with bipolar disorder risk: the CES-D item "people were unfriendly," comorbid anxiety, initial depression diagnosis within 5 years, family history of BPD, and legal problems. In the subset of patients with complete data for the 5 variables (n = 483), 41.3% of the patients endorsing any 3 or more risk factors (n = 109) were MDQ+.
Conclusions: Almost 20% of patients with AD nonresponsive unipolar depression screened positive for BPD and the number of past medication trials had no effect on bipolarity. This suggests that clinicians should carefully screen for BPD in patients who have failed at least 1 antidepressant. Comorbid anxiety, feelings of people being unfriendly, recent depression diagnosis, BPD family history, and legal problems may prove useful indicators of BPD risk among patients who have failed at least 1 antidepressant. Future studies are needed to confirm that these risk factors are useful clinical variables to screen for bipolarity.

Readers are encouraged to respond to George Lundberg, MD, Editor of MedGenMed, for the editor's eye only or for possible publication via email:


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.