Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness.
BACKGROUND
Partial response, no response, or residual symptoms following antidepressant therapy is common in clinical psychiatry. This study evaluated modafinil in patients with major depressive disorder (MDD) who were partial responders to adequate selective serotonin reuptake inhibitor (SSRI) therapy and excessive sleepiness and fatigue.


METHODS
This retrospective analysis pooled the data of patients (18-65 yrs) who participated in two randomized, double-blind, placebo-controlled studies of modafinil (6-week, flexible-dose study of 100-400 mg/day or 8-week, fixed-dose study of 200 mg/day) plus SSRI therapy. Patients (n=348) met criteria for several residual symptoms (Epworth Sleepiness Scale [ESS] score>or=10; 17-item Hamilton Depression Scale [HAM-D] score between 4 and 25; and Fatigue Severity Scale [FSS] score>or=4).


RESULTS
Compared to placebo, modafinil augmentation rapidly (within 1 week) and significantly improved overall clinical condition (Clinical Global Impression-Improvement), wakefulness (ESS), depressive symptoms (17-item HAM-D), and fatigue (FSS) (p<.01 for all). At final visit, patients receiving modafinil augmentation experienced statistically significant improvements in overall clinical condition, wakefulness, and depressive symptoms. Modafinil was well tolerated in combination with SSRI.


CONCLUSIONS
Results of this pooled analysis provide further evidence suggesting that modafinil is an effective and well-tolerated augmentation therapy for partial responders to SSRI therapy, particularly when patients continue to experience fatigue and excessive sleepiness.
Fava
Maurizio
M
Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA 02114, and Department of Psychiatry, University of Pittsburgh Medical Center, PA, USA. Mfava@Partners.org
Thase
Michael E
ME
DeBattista
Charles
C
Doghramji
Karl
K
Arora
Sanjay
S
Hughes
Rod J
RJ
D000328:Adult; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005221:Fatigue / Q000139:chemically induced*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D018579:Patient Selection; D010919:Placebos; D012189:Retrospective Studies; D012893:Sleep Wake Disorders / Q000139:chemically induced*
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D010919:Placebos; D000077408:Modafinil