Modafinil as an Adjunct Agent in the Treatment of Major Depressive Disorder: a Meta-Analysis

Abstract

Specific Aims: To assess the effectiveness of modafinil as an adjunct agent in the treatment of major depression and depression-related fatigue. Methods Seven databases were searched for articles that met predetermined inclusion criteria and reported sufficient data. Meta-analysis was employed to synthesize study findings, with standardized mean difference (SMD) being the primary summary measure. The I-squared statistic was used to evaluate heterogeneity among studies. Additionally, publication bias was assessed via funnel plots and Kendall’s tau. Main Results: Ten studies (N = 848) were included in the Hamilton Depression Rating Scale (HAM-D) meta-analysis, composed of 5 RCTs and 5 pre-post studies. The pooled SMD was -0.67, a moderate effect indicating an improvement in depression scores. However, the overall SMD varied when stratified by study design; pre-post studies showed a large pooled effect (SMD = -1.54) that reached significance, whereas RCT's displayed a moderate effect (SMD = -0.41) that was not significant. Additonally, heterogeneity was substantial (I-squared = 91.54) among all studies, and publication bias was suggested by the funnel plot and Kendall's tau. Regarding modafinil and fatigue, the Epworth Sleepiness Scale (ESS) meta-analysis had a small but statistically signficant overall SMD (-0.23; p = 0.03), and the Fatigue Severity Scale (FSS) meta-analysis yielded an overall SMD which was not significant (p = 0.24). Similar to the HAM-D analysis, the overall SMD varied between study designs. Conclusion: The effect of modafinil on major depressive disorder is unclear, as the findings are largely variable and the impact of modafinil was stratified by study design.