Adjunct Modafinil for the Short-Term Treatment of Fatigue and Sleepiness in Patients With Major Depressive Disorder: A Preliminary Double-Blind, Placebo-Controlled Study
J Clin Psychiatry 2003;64(9):1057-1064
© Copyright 2015 Physicians Postgraduate Press, Inc.
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Background: Fatigue and sleepiness are primary
symptoms of depression that may not resolve with antidepressant
therapy. Modafinil is a novel agent that has been shown to
improve wakefulness and lessen fatigue in a variety of
conditions. In this study, we examined the utility of modafinil
as an adjunct therapy to treat fatigue and sleepiness in patients
with major depression who are partial responders to
Method: Patients with partial response to
antidepressant therapy given for at least a 6-week period for a
current major depressive episode (DSM-IV criteria) were enrolled
in this 6-week, randomized, double-blind, placebo-controlled,
parallel-group, multicenter study. Patients received once-daily
doses (100-400 mg) of modafinil or matching placebo as adjunct
treatment to ongoing antidepressant therapy. The effects of
modafinil were evaluated using the Hamilton Rating Scale for
Depression (HAM-D), the Fatigue Severity Scale (FSS), the Epworth
Sleepiness Scale (ESS), the Clinical Global Impression of Change
(CGI-C), and the Medical Outcomes Study 36-Item Short-Form Health
Survey (SF-36). Adverse events were monitored throughout the
Results: One hundred thirty-six patients
were randomized to treatment, with 118 patients (87%) completing
the study. Most patients (82%) were fatigued, and one half of
patients (51%) were sleepy. Modafinil rapidly improved fatigue
and daytime wakefulness, with significantly greater mean
improvements from baseline than placebo in fatigue (FSS) scores
at week 2 (p < .05) and sleepiness (ESS) scores at week 1 (p
< .01); the differences between modafinil and placebo at week
6 were not statistically significant. Assessment of the
augmentation effects of modafinil (HAM-D, CGI-C, and SF-36) did
not significantly distinguish modafinil from placebo. Modafinil
was well tolerated in combination with a variety of
Conclusion: Modafinil may be a useful
adjunct therapy for the short-term management of residual fatigue
and sleepiness in patients who are partial responders to