Comparative risk for harms of second-generation antidepressants : a systematic review and meta-analysis.
BACKGROUND
Evidence indicates that only minor differences in efficacy exist among second-generation antidepressants for the treatment of major depressive disorder (MDD). However, a comprehensive assessment of both benefits and harms is crucial to evaluate the net benefit.


OBJECTIVE
To review systematically the comparative harms of second-generation antidepressants for the treatment of MDD in adults by including both experimental and observational evidence.


METHODS
We searched MEDLINE, EMBASE, PsychLit, The Cochrane Library and the International Pharmaceutical Abstracts from 1980 to April 2007. We manually searched reference lists of pertinent review articles and explored the Center for Drug Evaluation and Research database to identify unpublished research.


METHODS
Eligible study designs were trials and observational studies comparing one drug of interest with another.


METHODS
Two persons independently reviewed abstracts and full-text articles. One investigator extracted relevant data. A senior reviewer checked data for completeness and accuracy.


RESULTS
We included 104 experimental and observational studies. If data were sufficient, we conducted meta-analyses of randomized controlled trials on the relative risk of specific adverse events. Findings indicate that the spectrum of adverse events is similar. The frequency of specific adverse events, however, differed across drugs. Venlafaxine was associated with a significantly higher rate of nausea and vomiting than selective serotonin reuptake inhibitors. Compared with other drugs, paroxetine frequently led to more sexual adverse effects and bupropion to fewer such effects; mirtazapine and paroxetine was associated with more weight gain and sertraline with a higher rate of diarrhoea. Overall, however, these differences did not lead to different discontinuation rates. The evidence is insufficient to draw conclusions about rare but severe adverse events.


CONCLUSIONS
Adverse event profiles are similar among second-generation antidepressants. However, different frequencies of specific adverse events might be clinically relevant and influence the choice of a treatment.
Gartlehner
Gerald
G
Department for Evidence-Based Medicine and Clinical Epidemiology, Danube University Krems, Krems, Austria. gerald.gartlehner@donau-uni.ac.at
Thieda
Patricia
P
Hansen
Richard A
RA
Gaynes
Bradley N
BN
Deveaugh-Geiss
Angela
A
Krebs
Erin E
EE
Lohr
Kathleen N
KN