Antidepressants for Poststroke Depression: Comparative Efficacy and Acceptability

The best antidepressant for poststroke depression treatment is likely paroxetine.

A multiple-treatment meta-analysis, published in BMJ Open, was conducted to establish a rank order of the comparative efficacy and acceptability of various antidepressant treatments used in patients with poststroke depression (PSD). PSD reportedly affects approximately one-third of all stroke survivors.

The primary outcome of the analysis was the overall efficacy of the various antidepressants being compared, defined as the mean change in total depression score. The secondary outcome was the acceptability of the antidepressant, defined as the risk for all-cause discontinuation.

Data were collected from 707 patients diagnosed with depression following stroke. A total of 12 randomized, controlled studies published between 1984 and 2012 were included in the meta-analysis. The treatment duration of the trials was between 6 and 12 weeks; the studies had small sample sizes (22-123 participants). The meta-analysis evaluated 10 antidepressants most often used for the treatment of PSD (citalopram, doxepin, duloxetine, fluoxetine, nefiracetam, nortriptyline, paroxetine, reboxetine, sertraline, and trazodone) vs placebo.

Of the 10 drugs studied, with the exception of sertraline, nefiracetam, and fluoxetine, 7 were significantly more effective than placebo for the treatment of poststroke depression. Regarding efficacy, standardized mean differences vs placebo ranged from -6.54 for reboxetine (the most effective antidepressant) to 0.51 for nefiracetam (the least effective antidepressant). In efficacy rank, reboxetine, paroxetine, doxepin, and duloxetine were considered the most efficacious therapies, with cumulative probabilities of 100%, 85.7%, 83.2%, and 62.4%, respectively.

With respect to acceptability comparisons, paroxetine was associated with significantly lower all-cause discontinuation than doxepin, citalopram, and fluoxetine. Odds ratios for acceptability vs placebo varied from 0.09 for paroxetine (the most tolerable drug) to 3.42 for citalopram (the least tolerable drug).

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The investigators concluded that after examining the efficacy and acceptability of the various antidepressants, paroxetine might be the best choice of antidepressant and fluoxetine might be the poorest choice of antidepressant for the treatment of PSD.


Sun Y, Liang Y, Jiao Y, et al. Comparative efficacy and acceptability of antidepressant treatment in poststroke depression: a multiple-treatments meta-analysis. BMJ Open. 2017;7(8):e016499.