ournal of Affective Disorders 148 (2013) 129–135
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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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