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Acta Psychiatr Scand. 2010 Jun;121(6):404-14. doi: 10.1111/j.1600-0447.2009.01514.x. Epub 2009 Dec 2.

Mania associated with antidepressant treatment: comprehensive meta-analytic review.

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  • 1Department of Psychiatry and Neuroscience Program, Harvard Medical School and McLean Division of Massachusetts General Hospital, Boston, MA, USA.



To review available data pertaining to risk of mania-hypomania among bipolar (BPD) and major depressive disorder (MDD) patients with vs. without exposure to antidepressant drugs (ADs) and consider effects of mood stabilizers.


Computerized searching yielded 73 reports (109 trials, 114 521 adult patients); 35 were suitable for random effects meta-analysis, and multivariate-regression modeling included all available trials to test for effects of trial design, AD type, and mood-stabilizer use.


The overall risk of mania with/without ADs averaged 12.5%/7.5%. The AD-associated mania was more frequent in BPD than MDD patients, but increased more in MDD cases. Tricyclic antidepressants were riskier than serotonin-reuptake inhibitors (SRIs); data for other types of ADs were inconclusive. Mood stabilizers had minor effects probably confounded by their preferential use in mania-prone patients.


Use of ADs in adults with BPD or MDD was highly prevalent and moderately increased the risk of mania overall, with little protection by mood stabilizers.

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