Modafinil augmentation of SSRI therapy in patients with major depressive disorder and excessive sleepiness and fatigue: a 12-week, open-label, extension study.
BACKGROUND
Many patients with major depressive disorder (MDD) treated with selective serotonin reuptake inhibitors have residual symptoms (eg, persistent fatigue, excessive sleepiness) despite an overall antidepressant response. Placebo-controlled studies indicate that modafinil, a wake-promoting agent, may relieve residual symptoms.


METHODS
This 12-week, open-label, dose titration, extension study followed an 8-week placebo-controlled study of modafinil augmentation in patients with MDD. The dose was 100-400 mg/day. The median stable dose was 300 mg/day. Assessments were the Epworth Sleepiness Scale, Brief Fatigue Inventory, Clinical Global Impression of Improvement scale, 17-item Hamilton Rating Scale for Depression, and Montgomery-Asberg Depression Rating Scale.


RESULTS
Of the 245 patients treated, 194 completed the study; 70% reported Clinical Global Impression of Improvement scale responses of "much improved" or "very much improved" between open-label baseline and final visit (previous randomized modafinil group: 74%; placebo group: 66%). When data were analyzed for four subsets of patients (former modafinil responders, placebo responders, modafinil nonresponders, and placebo nonresponders), improvements in scores on all outcome measures were at least twice as great among former modafinil and placebo nonresponders compared with responders. Most common adverse events were headache (18%), nausea (9%), and dizziness (7%); all were generally mild to moderate in severity.


CONCLUSIONS
Twelve weeks of modafinil augmentation relieved excessive sleepiness, reduced fatigue, and improved patients' overall clinical condition, including mood.
Thase
Michael E
ME
Division of Adult Academic Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. thaseme@upmc.edu
Fava
Maurizio
M
DeBattista
Charles
C
Arora
Sanjay
S
Hughes
Rod J
RJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000139:chemically induced*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D017374:Paroxetine / Q000009:adverse effects* / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D020280:Sertraline / Q000009:adverse effects* / Q000627:therapeutic use
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline