Abstract
Background:Cognitive dysfunction is often present in major depressive disorder (MDD). Several clinical trials have noted a pro-cognitive effect of antidepressants in MDD. The objective of the current systematic review and meta-analysis was to assess the pooled efficacy of antidepressants on various domains of cognition in MDD.Methods:Trials published prior to April 15, 2015, were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, Embase, PsychINFO, Clinicaltrials.gov, and relevant review articles. Data from randomized clinical trials assessing the cognitive effects of antidepressants were pooled to determine standard mean differences (SMD) using a random-effects model.Results:Nine placebo-controlled randomized trials (2 550 participants) evaluating the cognitive effects of vortioxetine (n = 728), duloxetine (n = 714), paroxetine (n = 23), citalopram (n = 84), phenelzine (n = 28), nortryptiline (n = 32), and sertraline (n = 49) were identified. Antidepressants had a positive effect on psychomotor speed (SMD 0.16; 95% confidence interval [CI] 0.05–0.27; I2 = 46%) and delayed recall (SMD 0.24; 95% CI 0.15–0.34; I2 = 0%). The effect on cognitive control and executive function did not reach statistical significance. Of note, after removal of vortioxetine from the analysis, statistical significance was lost for psychomotor speed. Eight head-to-head randomized trials comparing the effects of selective serotonin reuptake inhibitors (SSRIs; n = 371), selective serotonin and norepinephrine reuptake inhibitors (SNRIs; n = 25), tricyclic antidepressants (TCAs; n = 138), and norepinephrine and dopamine reuptake inhibitors (NDRIs; n = 46) were identified. No statistically significant difference in cognitive effects was found when pooling results from head-to-head trials of SSRIs, SNRIs, TCAs, and NDRIs. Significant limitations were the heterogeneity of results, limited number of studies, and small sample sizes.Conclusions:Available evidence suggests that antidepressants have a significant positive effect on psychomotor speed and delayed recall.
Highlights
Major depressive disorder (MDD) is a highly prevalent and disabling illness affecting greater than 350 million people worldwide (Kessler et al, 2006)
Several investigators have studied the cognitive effects of various antidepressants (Keefe et al, 2014); the majority of these studies were limited by small sample sizes, absence of placebo controls, a lack of pre-specification of cognition as a primary outcome, and insufficient statistical analytic approaches to parse direct versus indirect effects
The PubMed search was limited to human studies, including clinical trials, observational studies, meta-analyses, and review articles written in the English language using the following search string: AND
Summary
Major depressive disorder (MDD) is a highly prevalent and disabling illness affecting greater than 350 million people worldwide (Kessler et al, 2006). Given the significant and persistent functional impairment mediated by cognitive dysfunction, increased attention is being given to this domain in the treatment of MDD (Bortolato et al, 2014). Many studies have reported a positive effect of various antidepressants on cognition, yielding a statistically significant difference between groups receiving treatment versus placebo; quantification of the overall and relative magnitude of effect (e.g. the pooled standard mean difference [SMD]) of all currently available antidepressants on cognition has yet to be conducted. No statistically significant difference in cognitive effects was found when pooling results from head-to-head trials of SSRIs, SNRIs, TCAs, and NDRIs. Significant limitations were the heterogeneity of results, limited number of studies, and small sample sizes. Conclusions: Available evidence suggests that antidepressants have a significant positive effect on psychomotor speed and delayed recall
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