ADJUNCT MODAFINIL FOR FATIGUE AND WAKEFULNESS IN MDD

Karl Doghramji, M.D., Department of Psychiatry, Thomas Jefferson University, 1015 Walnut Street, Suite 319, Philadelphia, PA 19107; Matthew A. Menza, M.D., Murray H. Rosenthal, D.O., Ronald R. Fieve, M.D.

Objective: Fatigue and sleepiness are primary symptoms of major depressive disorder (MDD) that often do not resolve with antidepressant therapy and may require additional therapeutic measures. Modafinil, a novel wake-promoting agent, improves wakefulness in patients with excessive sleepiness, and reduces fatigue in patients with multiple sclerosis. This study evaluated the effects of modafinil on fatigue and sleepiness in patients with MDD.
Methods:Patients with partial response to antidepressants given for at least six weeks prior to study for a current major depressive episode were enrolled in this six-week, randomized, double-blind, placebo-controlled, multicenter study. Patients received modafinil (100-400 mg/day) or placebo as adjunct treatment to ongoing antidepressant therapy. Changes in fatigue and daytime sleepiness were evaluated using the Fatigue Severity Scale (FSS) and Epworth Sleepiness Scale (ESS), respectively. Adverse events were recorded.
Results: Of 136 patients randomized, 118 (87%) completed the study. Most patients were fatigued (82%), and half (51%) were sleepy. Modafinil rapidly improved fatigue and daytime wakefulness, with significantly greater mean changes from baseline than placebo in FSS scores at week 2 (p < 0.05) and ESS scores at week 1 (p < 0.01). Modafinil was generally well tolerated.
Conclusions: Modafinil may be a useful adjunct for the management of fatigue and sleepiness in patients who are partial responders to antidepressant therapy.