Journal
HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL
Volume 24, Issue 3, Pages 177-190Publisher
WILEY
DOI: 10.1002/hup.1005
Keywords
antidepressants; depression; duloxetine; meta-analysis; short-term treatment; SNRIs
Funding
- Bruce J. Anderson Foundation
- McLean Hospital Private Donors' Research Fund
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Background Randomized controlled trials (RCTs) of duloxetine (DLX), an inhibitor of both norepinephrine and serotonin transporters (SNRI), have tested its efficacy in acute major depressive disorder (MDD) versus placebo (PBO) or standard serotonin-reuptake inhibitors (SRIs) and require review, comparing analytical methods. Method Computerized searching to identify reports of RCTs of DLX in adult, acute MDD patients permitted meta-analytic pooling to estimate overall response and remission rates, to compare mixed-model, repeated measures (MMRM) versus last-observations-carried-forward (LOCF) analytical methods, and to assess relations of DLX dose to efficacy and adverse outcomes. Results We identified 17 RCTs involving 22 comparisons (DLX versus PBO [n= 17) and DLX versus an SRI [n = 16]), based on MMRM and LOCF methods that allowed estimates of response ( >= 50% improvement of depression scores) or remission (final depression score <= 7). There was a large overall DLX/PBO contrast (LOCF, RR = 1.42 [CI: 1.31-1.53], p < 0.0001, with a success rate of 65% [11/17]), and somewhat arger effects with MMRM in both response (MMRM: RR = 1.48 [95%Cl: 1.31-1.66] versus LOCF: RR = L41 [CI: 1.28-1.56]; NNT 4.8 versus 6.5) and remission (MMRM: RR = 1.61 [CI: 1.41-1.85] versus LOCF: RR = 1.44 [CI: 1.27-1.63]; NNT = 5.9 versus 8.9). Based on LOCF methods, dropout rates were similar with DLX and PBO (RR = 1.04 [CI: 0.94-1.15]); DLX response was dose-dependent (r = +0.72. p = 0.001), and RCT-dropout rates were inversely related to DLX dose, but possibly artifactually. Limitations RCTs involving DLX are limited, with few direct comparisons to standard antidepressants. Conclusions DLX has good evidence of efficacy in acute, adult MDD, especially at doses of 80-120 mg/day, but remains inadequately tested against standard alternatives. MMRM analyses yielded slightly superior FLX/PBO contrasts than older LOCF methods. Copyright (C) 2009 John Wiley & Sons, Ltd.
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