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Antidepressants in Type II Versus Type I Bipolar Depression

A Randomized Discontinuation Trial

Vöhringer, Paul A. MD*†; Ostacher, Michael J. MD, MPH; El-Mallakh, Rif S. MD§; Holtzman, Niki S. BA*; Thommi, Sairah B. BS*; Whitham, Elizabeth A. MA*; Sullivan, Matthew C. BA*; Baldassano, Claudia F. MD; Goodwin, Fredrick K. MD; Baldessarini, Ross J. MD#**; Ghaemi, S. Nassir MD*††

Journal of Clinical Psychopharmacology: October 2015 - Volume 35 - Issue 5 - p 605–608
doi: 10.1097/JCP.0000000000000384
Brief Reports

Background We sought to test the hypothesis that antidepressants (ADs) may show preferential efficacy and safety among patients with type II bipolar disorder (BD, BD-II) more than patients with type I BD (BD-I).

Methods Patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, BD-I (n = 21) and BD-II (n = 49) in acute major depressive episodes were treated with ADs plus mood stabilizers to euthymia sustained for 2 months and then randomized openly to continue or discontinue ADs for up to 3 years. Outcomes were episode recurrences and changes in standardized symptom ratings.

Results In follow-up averaging 1.64 years, both subgroups showed improvement in depressive episode frequency with AD continuation, but contrary to the hypothesis, more improvement was seen in BD-I than in BD-II (for type II, mean [standard deviation] decrease in depressive episodes per year, 0.21 [0.26]; for type I, mean (SD) decrease, 0.35 [0.15]). Subjects with BD-II who continued on ADs had slightly more depressive, but fewer manic/hypomanic, episodes than subjects with BD-I. No notable differences were seen in either group in time to a recurrence of mood episodes or total time-in-remission.

Conclusions The findings do not confirm the hypothesis that long-term AD treatment in patients with BP-II has better outcomes than in patients with BD-I, except somewhat lower risk of manic/hypomanic episodes.

From the *Mood Disorders Program, Department of Psychiatry, Tufts University Medical Center, Boston, MA; †Department of Psychiatry, Hospital Clinico Universidad de Chile, Facultad de Medicina, Universidad de Chile, Santiago, Chile; ‡Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA; §Department of Psychiatry, College of Medicine, University of Kentucky, Louisville, KY; ∥Department of Psychiatry, School of Medicine, University of Pennsylvania, Philadelphia, PA; ¶Center of Neuroscience, Medical Progress, and Society, The George Washington University School of Medicine, Washington, DC; #Department of Psychiatry, Harvard Medical School, Boston; **International Consortium for Bipolar Disorder Research, McLean Division of Massachusetts General Hospital, Belmont, MA; and ††Tufts University School of Medicine, Boston, MA.

Received December 22, 2011; accepted after revision May 19, 2015.

Reprints: S. Nassir Ghaemi, MD, Tufts Medical Center, 800 Washington St, Box 1007, Boston, MA 02111 (e-mail:

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