An Open-Label Study of Adjunctive Modafinil in Patients With Sedation Related to Serotonergic Antidepressant Therapy

Objective: In patients with major depressive disorder (MDD), excessive sleepiness and fatigue not only are major components of the disorder, but also may occur as side effects of antidepressant therapy. In addition, sedation may be a consequence of antidepressant regimens. The novel wake-promoting agent modafinil improves wakefulness and reduces fatigue across a variety of clinical disorders. This study assessed the use of modafinil as an adjunctive treatment in patients with MDD who reported sedation related to serotonergic antidepressant therapy.

Method: Data were collected between September 2001 and December 2003. Twenty men and women with DSM-IV-defined MDD were enrolled in this 3-week, open-label, single-center study. In addition to ongoing and stable treatment with selective serotonin reuptake inhibitors (SSRIs), clinic patients received modafinil once daily. Efficacy assessments were conducted at 1-week intervals.

Results: Sixteen patients (80%) completed the study. Modafinil plus SSRIs significantly improved overall depressive symptoms, as shown by reductions in mean Hamilton Rating Scale for Depression total scores (p < .001 vs. baseline). Adjunctive modafinil significantly improved subjective estimates of wakefulness on the Epworth Sleepiness Scale (p < .001, all weeks) and reduced fatigue on the Fatigue Severity Scale (p = .009). At the final visit, modafinil had improved overall health status and health-related quality of life, as shown by significant improvements in mean Medical Outcomes Study Short-Form 12-Item Health Survey total scores (p = .007) and in physical health (p = .04) and mental health (p = .006) subscores.

Conclusion: In patients with MDD who experience sedation as a side effect of antidepressant therapy, adjunctive modafinil improved wakefulness and reduced fatigue. Modafinil plus SSRIs also improved mood and quality of life.