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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Tondo
L
L
Department of Psychiatry and Neuroscience Program, Harvard Medical School and McLean Division of Massachusetts General Hospital, Boston, MA, USA. ltondo@mclean.harvard.edu
Vázquez
G
G
Baldessarini
R J
RJ
D000328:Adult; D000367:Age Factors; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000009:adverse effects*; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000139:chemically induced / Q000517:prevention & control; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D006801:Humans; D008094:Lithium / Q000627:therapeutic use*; D008875:Middle Aged; D015233:Models, Statistical; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors
D000929:Antidepressive Agents, Tricyclic; D018692:Antimanic Agents; D008094:Lithium; D017367:Selective Serotonin Reuptake Inhibitors