The Cognitive Effects of Antidepressants in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Joshua D Rosenblat; Ron Kakar; Roger S McIntyre

doi:10.1093/ijnp/pyv082

The Cognitive Effects of Antidepressants in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Int J Neuropsychopharmacol. 2015 Jul 25;19(2):pyv082. doi: 10.1093/ijnp/pyv082.

Authors

Joshua D Rosenblat¹, Ron Kakar¹, Roger S McIntyre²

Affiliations

¹ Mood Disorder Psychopharmacology Unit, University Health Network, Department of Psychiatry, University of Toronto, Canada (Drs Rosenblat, Kakar, and McIntyre); Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Canada (Drs Rosenblat and McIntyre); Department of Psychiatry, Western University, London, and Windsor, Ontario, Canada (Dr Kakar).
² Mood Disorder Psychopharmacology Unit, University Health Network, Department of Psychiatry, University of Toronto, Canada (Drs Rosenblat, Kakar, and McIntyre); Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Canada (Drs Rosenblat and McIntyre); Department of Psychiatry, Western University, London, and Windsor, Ontario, Canada (Dr Kakar). roger.mcintyre@uhn.ca.

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; I(2) = 46%) and delayed recall (SMD 0.24; 95% CI 0.15-0.34; I(2) = 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.

Keywords: antidepressants; cognitive function; executive function; major depressive disorder; psychomotor speed; working memory.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

MeSH terms

Antidepressive Agents / pharmacology
Antidepressive Agents / therapeutic use*
Cognition / drug effects*
Cognition Disorders / drug therapy*
Cognition Disorders / epidemiology
Cognition Disorders / psychology
Depressive Disorder, Major / drug therapy*
Depressive Disorder, Major / epidemiology
Depressive Disorder, Major / psychology
Humans
Randomized Controlled Trials as Topic / methods*
Treatment Outcome

Substances

Antidepressive Agents