Cognitive effects of pharmacotherapy for major depressive disorder: A systematic review

Richard S E Keefe, Shawn M. McClintock, Robert M. Roth, P. Murali Doraiswamy, Steven Tiger, Manisha Madhoo

Research output: Contribution to journalReview articlepeer-review

90 Scopus citations


Objective: Cognitive impairment frequently accompanies major depressive disorder (MDD) and can persist during remission.This review examined pharmacotherapy effects on cognitive function in MDD. Data Sources: PubMed and EMBASE searches were conducted on July 30,2013, for English language reports of cognitive assessments following pharmacologic monotherapy or augmentation therapy in MDD. Study Selection: A total of 43 research reports were identified (31 monotherapy [8 placebo-controlled, 11 active-comparator, 12 open-label], 12 augmentation therapy [7 placebo-controlled, 5 open-label]). Data Extraction: Results reported in each publication were examined for open-label and placebo- or active comparator-controlled studies. Results: Studies varied widely in terms of size (median, 50 participants; interquartile range, 21-143 participants), populations examined, duration (median, 8 weeks; interquartile range, 6-12 weeks), and neurocognitive assessments used. Most individual studies reported some benefit to cognition with pharmacotherapy, but there was no pattern of response in specific domains and only 12% of individually analyzed changes favored active treatment over placebo or untreated healthy controls. Sample weighted mean effect sizes revealed that verbal memory improved with monotherapy, while the largest treatment effect with augmentation therapy was for visual memory. Conclusions: Pharmacotherapy may have benefit in reducing cognitive impairment in MDD, with augmentation therapy being a potential approach for addressing cognitive deficits that persist after monotherapy has brought about clinical response or remission. However, given the wide variability in study design and treatment duration across studies, these findings should be interpreted cautiously. More definitive research is required before firm conclusions can be reached.

Original languageEnglish (US)
Pages (from-to)864-876
Number of pages13
JournalJournal of Clinical Psychiatry
Issue number8
StatePublished - Aug 1 2014

ASJC Scopus subject areas

  • Psychiatry and Mental health


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