Modafinil Augmentation of SSRI Therapy in Patients with Major Depressive Disorder and Excessive Sleepiness and Fatigue: A 12-Week, Open-Label, Extension Study
Thase ME, Fava M, Debattista C, Arora S, Hughes RJ.
Division of Adult Academic Psychiatry,
University of Pittsburgh Medical Center,
Pittsburgh, PA, USA.
CNS Spectr. 2006 Feb;11(2):93-102.

Introduction: 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. Conclusion: Twelve weeks of modafinil augmentation relieved excessive sleepiness, reduced fatigue, and improved patients' overall clinical condition, including mood.

Atypical depression
The modafinil switch
Modafinil and the aviator
Modafinil as an antidepressant
Modafinil versus amphetamine
Modafinil and the hypothalamus
Modafinil versus methylphenidate
Modafinil, amphetamine and sleep
Modafinil, antidepressants and serotonin