The International Journal of Neuropsychopharmacology


Overview of antidepressant treatment of bipolar depression

Gustavo H. Vázqueza1a2 c1, Leonardo Tondoa1a3a4, Juan Undurragaa1a5 and Ross J. Baldessarinia1a3

a1 International Consortium for Bipolar and Psychotic Disorder Research, McLean Hospital, Belmont, MA, USA

a2 Department of Neuroscience, Palermo University, Buenos Aires, Argentina

a3 Department of Psychiatry, Harvard Medical School, Boston, MA, USA

a4 Lucio Bini Mood Disorders Center, Cagliari, Sardinia, Italy

a5 Bipolar Disorders Program, Institute of Neuroscience, Hospital Clínic Barcelona, IDIBAPS, CIBERSAM, University of Barcelona, Spain


Bipolar depression remains a major unresolved challenge for psychiatric therapeutics. It is associated with significant disability and mortality and represents the major proportion of the approximately half of follow-up time spent in morbid states despite use of available treatments. Evidence regarding effectiveness of standard treatments, particularly with antidepressants, remains limited and inconsistent. We reviewed available clinical and research literature concerning treatment with antidepressants in bipolar depression and its comparison with unipolar depression. Research evidence concerning efficacy and safety of commonly used antidepressant treatments for acute bipolar depression is very limited. Nevertheless, an updated meta-analysis indicated that overall efficacy was significantly greater with antidepressants than with placebo-treatment and not less than was found in trials for unipolar major depression. Moreover, risks of non-spontaneous mood-switching specifically associated with antidepressant treatment are less than appears to be widely believed. The findings encourage additional efforts to test antidepressants adequately in bipolar depression, and to consider options for depression in types I vs. II bipolar disorder, depression with subsyndromal hypomania and optimal treatment of mixed agitated-dysphoric states – both short- and long-term. Many therapeutic trials considered were small, varied in design, often involved co-treatments, or lacked adequate controls.

(Received November 02 2012)

(Reviewed November 20 2012)

(Revised December 29 2012)

(Accepted January 08 2013)

(Online publication February 22 2013)

Key words

  • Antidepressants;
  • bipolar disorders;
  • depression;
  • treatment


c1 Address for correspondence: Dr G. Vázquez, Department of Neuroscience, Palermo University, Buenos Aires, Argentina. Tel.: 0054 11 4826 0770 Fax: 0054 11 4826 0770 Email: