ournal of Affective Disorders 148 (2013) 129–135

Contents lists available at SciVerse ScienceDirect

Journal of Affective Disorders

0165-03

http://d

n Corr

Medical

02478-9

E-m

journal homepage: www.elsevier.com/locate/jad

Brief report

Antidepressant-associated mood-switching and transition from unipolar major depression to bipolar disorder: A review

Ross J. Baldessarini a,b,n, Gianni L. Faedda b,c,d, Emanuela Offidani e, Gustavo H. Vázquez b,f, Ciro Marangoni g, Giulia Serra h, Leonardo Tondo b,i

a Department of Psychiatry, Harvard Medical School, Boston, MA, USA b International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont, MA, USA c Lucio Bini Mood Disorders Center, New York, NY, USA d Department of Child & Adolescent Psychiatry–Child Study Center, New York University Medical Center, USA e Department of Psychology, University of Bologna, Bologna, Italy f Department of Neurosciences, University of Palermo, Buenos Aires, Argentina g Department of Psychiatry, University of Bologna, Italy h 23*Department of Psychiatry, University (La Sapienza) of Rome and Sant’Andrea Hospital, Rome, Italy i Lucio Bini Mood Disorders Center, Cagliari, Sardinia, Italy

a r t i c l e i n f o

Article history:

Received 5 October 2012

Accepted 23 October 2012 Available online 6 December 2012

Keywords:

Antidepressants

Bipolar disorder

Depression

Diagnostic conversion

Mood-switches

27/$ – see front matter & 2012 Elsevier B.V. A

x.doi.org/10.1016/j.jad.2012.10.033

esponding author at: McLean Hospital, Depar

School, Mailman Research Center, Rm 314, 1

106, USA. Tel.: þ1 617 855 3203; fax: þ1 61 ail address: rbaldessarini@mclean.harvard.edu

a b s t r a c t

Objectives: Compare reported rates of mood-shifts from major depression to mania/hypomania/mixed-

states during antidepressant (AD)-treatment and rates of diagnostic change from major depressive

disorder (MDD) to bipolar disorder (BPD).

Methods: Searching computerized literature databases, followed by summary analyses.

Results: In 51 reports of patients diagnosed with MDD and treated with an AD, the overall risk of mood-

switching was 8.18% (7837/95,786) within 2.3972.99 years of treatment, or 3.42 (95% CI: 3.34–3.50) %/year. Risk was 2.6 (CI: 2.5–2.8) times greater with/without AD-treatment by meta-analysis

of 10 controlled trials. Risk increased with time up to 24 months of treatment, with no secular change

(1968–2012). Incidence rates were 4.5 (CI: 4.1–4.8)-times greater among juveniles than adults (5.62/

1.26 %/year; po0.0001). In 12 studies the overall rate of new BPD-diagnoses was 3.29% (1928/56,754) within 5.38 years (0.61 [0.58–0.64] %/year), or 5.6-times lower (3.42/0.61) than annualized rates of

mood-switching.

Conclusions: AD-treatment was associated with new mania-like responses in 8.18% of patients

diagnosed with unipolar MDD. Contributions to mood-switching due to unrecognized BPD versus

mood-elevating pharmacological effects, as well as quantitative associations between switching and

later diagnosis of BPD not associated with AD-treatment remain uncertain.

Limitations: Rates and definitions of mood-switching with ADs varied greatly, exposure-times rarely

were precisely defined, and there was little information on predictive associations between mood-

switches and BPD-diagnosis.

& 2012 Elsevier B.V. All rights reserved.

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