A Cochrane review [Abstract] 1 included 171 studies with 24 868 participants with major depression. A total of 105 trials enrolled outpatients, 14 trials inpatients, and both inpatients and outpatients were enrolled in 52 trials.The studies were undertaken between 1984 and 2012. Fluoxetine was as effective as the tricyclic antidepressants (TCAs) when considered as a group both on a dichotomous outcome (reduction of at least 50% on the Hamilton Depression Scale) (OR 0.97, 95% CI 0.77 to 1.22, 24 RCTs, n=2124) and a continuous outcome (mean scores at the end of the trial or change score on depression measures) (SMD 0.03, 95% CI -0.07 to 0.14, 50 RCTs, n=3393). On a dichotomous outcome, fluoxetine was less effective than dothiepin or dosulepin (OR 2.13, 95% CI 1.08 to 4.20; NNT = 6, 95% CI 3 to 50, 2 RCTs, n=144), sertraline (OR 1.37, 95% CI 1.08 to 1.74; NNT = 13, 95% CI 7 to 58, 6 RCTs, n=1188), mirtazapine (OR 1.46, 95% CI 1.04 to 2.04; NNT = 12, 95% CI 6 to 134, 4 RCTs, n=600) and venlafaxine (OR 1.29, 95% CI 1.10 to 1.51; NNT = 11, 95% CI 8 to 16, 12 RCTs, n=3387). On a continuous outcome, fluoxetine was more effective than milnacipran (SMD -0.36, 95% CI -0.63 to -0.08, 2 RCTs, n=213); conversely, it was less effective than venlafaxine (SMD 0.10, 95% CI 0 to 0.19, 13 RCTs, n=3097). Fluoxetine was better tolerated than TCAs considered as a group (total dropout OR 0.79, 95% CI 0.65 to 0.96; NNT = 20, 95% CI 13 to 48, 49 RCTs, n=4194) and was better tolerated in comparison with individual antidepressants (AD), in particular amitriptyline (total dropout OR 0.62, 95% CI 0.46 to 0.85; NNT = 13, 95% CI 8 to 39, 18 RCTs, n=1089), and among the newer ADs pramipexole (total dropout OR 0.12, 95% CI 0.03 to 0.42, NNT = 3, 95% CI 2 to 5, 1 RCT, n=105), and reboxetine (total dropout OR 0.60, 95% CI 0.44 to 0.82, NNT = 9, 95% CI 6 to 24, 4 RCTs, n=764).
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment).
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