Coadministration of modafinil and a selective serotonin reuptake inhibitor from the initiation of treatment of major depressive disorder with fatigue and sleepiness: a double-blind, placebo-controlled study.
BACKGROUND
Previous studies suggest that adjunctive modafinil treatment provides benefit for patients with depression with significant sleepiness and fatigue.


METHODS
We conducted a multisite, double-blind, placebo-controlled study of the treatment of major depression characterized by excessive sleepiness and fatigue, adding adjunctive modafinil or placebo to a selective serotonin reuptake inhibitor from the beginning of treatment. Seventy-three of 90 consenting patients met all screening criteria to begin treatment with open-label selective serotonin reuptake inhibitor therapy and double-blind addition of either modafinil (100 mg/d for 1 week then 200 mg/d) or matching placebo for 6 weeks.


RESULTS
Mixed-model analysis of the change in the Epworth Sleepiness Scale, the primary outcome measure, showed no difference between modafinil- and placebo-treated patients. However, the hypersomnia items on the 31-item Hamilton Depression Scale were significantly more improved with modafinil than placebo. The total 31-item Hamilton Depression Scale score was significantly better with modafinil than placebo at Weeks 4 and 5, but not at the final study visit. There was no difference in dropout rates caused by adverse events, but 2 patients in the modafinil-treated group developed new onset or worsening of suicidal ideation, leading to the trial being discontinued prematurely.


CONCLUSIONS
Power to detect differences between modafinil and placebo was limited because of the premature discontinuation of the trial. Although modafinil did not show evidence of benefit over placebo on the Epworth Sleepiness Scale, secondary measures suggested modafinil may have provided benefit for symptoms of excessive sleepiness in patients with depression.
Dunlop
Boadie W
BW
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1841 Clifton Road NE, Atlanta, GA 30307, USA. bdunlop@emory.edu
Crits-Christoph
Paul
P
Evans
Dwight L
DL
Hirschowitz
Jack
J
Solvason
H Brent
HB
Rickels
Karl
K
Garlow
Steven J
SJ
Gallop
Robert J
RJ
Ninan
Philip T
PT
D000293:Adolescent; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D003967:Diarrhea / Q000139:chemically induced; D006970:Disorders of Excessive Somnolence / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000150:complications / Q000188:drug therapy*; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D000077408:Modafinil; D009325:Nausea / Q000139:chemically induced; D017286:Polysomnography / Q000379:methods; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D013405:Suicide / Q000523:psychology / Q000706:statistics & numerical data; D016896:Treatment Outcome
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil; D017367:Selective Serotonin Reuptake Inhibitors