Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians.
BACKGROUND
Second-generation antidepressants dominate the management of major depressive disorder, dysthymia, and subsyndromal depression. Evidence on the comparative benefits and harms is still accruing.


OBJECTIVE
To compare the benefits and harms of second-generation antidepressants (bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine) for the treatment of depressive disorders in adults.


METHODS
MEDLINE, EMBASE, PsychLit, Cochrane Central Register of Controlled Trials, and International Pharmaceutical Abstracts from 1980 to April 2007, limited to English-language articles. Reference lists of pertinent review articles were manually searched and the Center for Drug Evaluation and Research database was explored to identify unpublished research.


METHODS
Abstracts and full-text articles were independently reviewed by 2 persons. Six previous good- or fair-quality systematic reviews or meta-analyses were included, as were 155 good- or fair-quality double-blind, placebo-controlled, or head-to-head randomized, controlled trials of at least 6 weeks' duration. For harms, 35 observational studies with at least 100 participants and follow-up of at least 12 weeks were also included.


METHODS
Using a standard protocol, investigators abstracted data on study design and quality-related details, funding, settings, patients, and outcomes.


RESULTS
If data were sufficient, meta-analyses of head-to-head trials were conducted to determine the relative benefit of response to treatment and the weighted mean differences on specific depression rating scales. If sufficient evidence was not available, adjusted indirect comparisons were conducted by using meta-regressions and network meta-analyses. Second-generation antidepressants did not substantially differ in efficacy or effectiveness for the treatment of major depressive disorder on the basis of 203 studies; however, the incidence of specific adverse events and the onset of action differed. The evidence is insufficient to draw conclusions about the comparative efficacy, effectiveness, or harms of these agents for the treatment of dysthymia and subsyndromal depression.


CONCLUSIONS
Adjusted indirect comparisons have methodological limitations and cannot conclusively rule out differences in efficacy.


CONCLUSIONS
Current evidence does not warrant the choice of one second-generation antidepressant over another on the basis of differences in efficacy and effectiveness. Other differences with respect to onset of action and adverse events may be relevant for the choice of a medication.
Gartlehner
Gerald
G
Danube University, Krems, Austria. gerald.gartlehner@donau-uni.ac.at
Gaynes
Bradley N
BN
Hansen
Richard A
RA
Thieda
Patricia
P
DeVeaugh-Geiss
Angela
A
Krebs
Erin E
EE
Moore
Charity G
CG
Morgan
Laura
L
Lohr
Kathleen N
KN
D000328:Adult; D000367:Age Factors; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000150:complications / Q000188:drug therapy* / Q000208:ethnology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D011788:Quality of Life; D012008:Recurrence; D012074:Remission Induction; D012737:Sex Factors
D018687:Antidepressive Agents, Second-Generation