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Original Research

Why Do Clinicians Maintain Antidepressants in Some Patients With Acute Mania? Hints From the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM), a Large Naturalistic Study

Adriane R. Rosa, PharmD, PhD; Nùria Cruz, MD; Carolina Franco, MD; Josep Maria Haro, MD; Jordan Bertsch, PhD; Catherine Reed, MSc; Trond F. Aarre, MD; Jose Sanchez-Moreno, PsyD; and Eduard Vieta, MD, PhD

Published: March 23, 2010

Article Abstract

Objective: Antidepressants are supposed to be withdrawn during a manic episode. The aim of this study was to analyze the characteristics of manic patients who received antidepressants during a manic phase in a large, naturalistic study.

Method: The European Mania in Bipolar Longitudinal Evaluation of Medication was a 2-year prospective observational study of inpatients and outpatients with acute mania/mixed mania (DSM-IV or ICD-10 criteria) conducted in 14 European countries. Of 2,416 manic patients who continued into the maintenance phase of the study, 345 (14%) were taking an antidepressant and 2,071 (86%) were not taking an antidepressant at baseline, week 1, and/or week 2 postbaseline. Demographic and clinical variables were collected at baseline and each study visit up to 24 months. Outcome measures included the Clinical Global Impressions-Bipolar Disorder scale (CGI-BP overall, mania, and depression scores) at 12 weeks and 24 months, the 5-item Hamilton Depression Rating Scale (HDRS-5), and the Young Mania Rating Scale (YMRS) at 12 weeks only. The present study was conducted from December 2002 to June 2004.

Results: More antidepressant maintenance use was seen in patients with mixed episodes (P‘ ‰<‘ ‰.001), rapid cyclers (P‘ ‰<‘ ‰.02), patients with more previous depressive episodes (P‘ ‰<‘ ‰.001), and patients with higher mean HDRS-5 score at baseline (P‘ ‰<‘ ‰.001)—specifically patients with anxiety (P‘ ‰=‘ ‰.013). Patients in the antidepressant group had significantly higher CGI-BP depression scores (P‘ ‰<‘ ‰.001) and a significantly higher rate of depression relapse (P‘ ‰<‘ ‰.001) at both 12 weeks and 24 months.

Conclusions: Patients with mania receiving antidepressants are more likely to be outpatients with mixed episodes, anxiety, or rapid cycling and have a higher risk of depression relapse during follow-up.

J Clin Psychiatry 2010;71(8):1000-1006

Submitted: January 8, 2009; accepted March 6, 2009.

Online ahead of print: March 23, 2010 (doi:10.4088/JCP.09m05026gre).

Corresponding author: Eduard Vieta, MD, PhD, Clinical Institute of Neuroscience, University Clinic Hospital of Barcelona, Villarroel 170, 08036-Barcelona, Spain ( and

Volume: 71

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