Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study.
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 antidepressants.


METHODS
Patients with partial response to anti-depressant 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 study.


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 antidepressants.


CONCLUSIONS
Modafinil may be a useful adjunct therapy for the short-term management of residual fatigue and sleepiness in patients who are partial responders to antidepressant therapy.
DeBattista
Charles
C
Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, 401 Quarry Road, Room 2137, Stanford, CA 94305, USA. debattista@leland.stanford.edu
Doghramji
Karl
K
Menza
Matthew A
MA
Rosenthal
Murray H
MH
Fieve
Ronald R
RR
D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D006970:Disorders of Excessive Somnolence / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil
D000928:Antidepressive Agents; D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil