Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea: a 12-week, open-label study.
OBJECTIVE
The purpose of this 12-week study was to evaluate the efficacy and safety of adjunct modafinil to treat excessive sleepiness in patients with obstructive sleep apnea (OSA) who experience residual sleepiness despite regular nasal continuous positive airway pressure (nCPAP) use.


METHODS
Twelve-week, open-label trial.


METHODS
Twenty-two centers in the United States.


METHODS
We studied 125 patients with moderate-to-severe OSA (ie, respiratory disturbance index > or =15) before nCPAP therapy and residual daytime sleepiness (Epworth sleepiness scale [ESS] score > or =10) despite effective and regular nCPAP therapy. Patients were studied after completing a 4-week, double-blind, placebo-controlled trial of nCPAP plus modafinil for the treatment of residual daytime sleepiness.


METHODS
Patients received individually titrated doses of modafinil (200 to 400 mg qd). Sleepiness was assessed using the ESS, quality of life was evaluated using the Functional Outcomes of Sleep Questionnaire (FOSQ), and the overall clinical effect was indexed using the clinical global impression of change scale. Adverse events, nCPAP use, and vital sign measurements were also recorded.


RESULTS
The significant improvements in daytime wakefulness and sleep-related functional status observed with modafinil treatment during the 4-week, double-blind study were maintained throughout 12 weeks of open-label treatment: week 12 ESS, 7.8 (4.7) vs 14.4 (3.1) at double-blind baseline; week 12 FOSQ, 3.3 (0.6) vs 14.4 (2.7) at double-blind baseline (mean [SD]). The percentage of patients rated as clinically improved increased from 83% after 1 week to > or =93% after 2 to 12 weeks of open-label treatment. Mean (SD) nCPAP use decreased from 6.3 (1.3) h/night at baseline to 5.9 (1.4) h/night (p = 0.004) during open-label treatment. The most common adverse events were headache (28%), anxiety (16%), and nervousness (14%).


CONCLUSIONS
Modafinil remained effective and well tolerated as an adjunct therapy for residual daytime sleepiness even after 12 weeks of daily dosing in patients with OSA receiving nCPAP therapy.
Schwartz
Jonathan R L
JR
Integris Sleep Disorders Center of Oklahoma, 4200 S. Douglas, Suite 313, Oklahoma City, OK 73109, USA. SchwJR@integris-health.com
Hirshkowitz
Max
M
Erman
Milton K
MK
Schmidt-Nowara
Wolfgang
W
D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D045422:Continuous Positive Airway Pressure; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D020181:Sleep Apnea, Obstructive / Q000150:complications* / Q000188:drug therapy; D020178:Sleep Disorders, Circadian Rhythm / Q000188:drug therapy* / Q000209:etiology
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil