The Potential Procognitive Effects of Modafinil in Major Depressive Disorder: A Systematic Review

To assess the efficacy of modafinil, a wakefulness-promoting drug, in major depressive disorder (MDD), with a specific focus on the putative procognitive effects of modafinil.

A database search of MEDLINE, PsycINFO, and Embase was conducted. No date limits were applied (the end date of the search was October 26, 2018), and only articles in English were included. The following search terms were used: modafinil, depression, depress*, major depressive disorder, cognition, cognitive dysfunction, and cogniti*.

Studies included were placebo-controlled or open-label trials of modafinil in MDD populations. Participants had to be diagnosed with MDD via DSM-IV or DSM-5 criteria, and no other interventions other than standard antidepressant treatment could be used in the trial. Overall, 540 articles were screened, 22 full-text research articles for inclusion criteria were assessed, and 12 studies were included in this review.

Two independent reviewers extracted data and assessed the quality of publications.

Modafinil was associated with improvements in executive functioning after 4 weeks of open-label adjunctive treatment in currently depressed participants. Furthermore, in a placebo-controlled study of remitted MDD participants, modafinil led to rapid improvements in episodic and working memory after a single dose. There were contradictory findings on the subjective effects of modafinil on concentration.

Modafinil shows preliminary evidence of alleviating specific cognitive symptoms in MDD patients, especially in the short term. However, more research using placebo-controlled longitudinal designs is needed to assess the benefits of modafinil, as there are very few studies addressing modafinil and cognition in MDD.