Modafinil Improves Episodic Memory and Working Memory Cognition in Patients With Remitted Depression: A Double-Blind, Randomized, Placebo-Controlled Study

Abstract

Background: Cognitive dysfunction is a core feature of depression and tends to persist even after mood symptoms recover, leading to detrimental effects on clinical and functional outcomes. However, most currently available treatments have not typically addressed cognition. Modafinil has been shown to have beneficial effects on cognitive function and therefore has the potential to improve cognition in depression. The objective of this double-blind, placebo-controlled study was to investigate the effects of modafinil on cognitive functions in patients with remitted depression.

Methods: In total, 60 patients with remitted depression participated in the study. Cognitive functions were evaluated with tests of working memory, planning, attention, and episodic memory from the Cambridge Neuropsychological Test Automated Battery at the baseline session and after treatment. A double-blind, randomized, placebo-controlled, parallel groups design was used to assess the effects of single-dose (200 mg) modafinil (n = 30) or placebo (n = 30) on cognition and fatigue. The main outcome measures were neurocognitive test scores from the Cambridge Neuropsychological Test Automated Battery. Visual analogue scales for subjective feelings and fatigue were used as secondary measures.

Results: The modafinil group had significantly better performance on tests of episodic memory (p = .01, η_p² = .10) and working memory (p = .04, η_p² = .06). Modafinil did not improve planning or sustained attention.

Conclusions: This study suggested that modafinil (200 mg) could improve episodic memory and working memory performance in patients with remitted depression. Modafinil may have potential as a therapeutic agent to help remitted depressed patients with persistent cognitive difficulties.

Keywords: Cognition; Cognitive enhancer; Depression; Memory; Modafinil; Treatment.

Figure 1

(Left) Episodic memory performance according to the difficulty level is shown. The repeated measures analysis of variance, which controlled for baseline performance, demonstrated a main effect of modafinil (F = 6.199, p = .01, η_p² = .10). (Right) The bar graph shows a significant difference between modafinil and placebo groups at the Paired Associates Learning (PAL) 12 shapes stage after controlling for baseline performance (F = 4.211, p = .02, η_p² = .13).

Figure 2

(Left) Working memory performance according to the difficulty level is shown. Repeated measures analysis of variance, which controlled for baseline performance, showed a trend effect of modafinil (F = 3.023, p = .08, η_p² = .05). (Right) The bar graph shows a significant difference between modafinil and placebo groups at the Spatial Working Memory (SWM) 12 boxes stage after controlling for baseline performance (F = 4.125, p = .04, η_p² = .06).