Modafinil for the treatment of hypersomnia associated with myotonic muscular dystrophy in adults: a multicenter, prospective, randomized, double-blind, placebo-controlled, 4-week trial.
BACKGROUND
Myotonic muscular dystrophy type 1 (MMD1) is the most common form of adult MD, with a mean prevalence of 1 in 8000. Excessive daytime sleepiness (ie, hypersomnia) is a common complication of MMD1.


OBJECTIVE
The aim of this study was to evaluate the efficacy and tolerability of modafinil for the treatment of hypersomnia in adults with MMD1.


METHODS
This multicenter, prospective, randomized, double-blind, placebo-controlled study consisted of a prerandomization period (90 to 2 days before randomization) and a 4-week randomization period in which patients were assigned to receive either active treatment (modafinil 300 mg/d) or placebo. The study was conducted at 3 clinics in France between February 2000 and June 2002. Adult patients aged > or =18 years, with genetically proven MMD1, an Epworth Sleepiness Scale (ESS) score >10, and a mean latency to sleep onset < or =8 minutes measured by the Multiple Sleep Latency Test (MSLT) were eligible. The primary efficacy end point was the Maintenance of Wakefulness Test (MWT) score at 4 weeks. Secondary end points included the mean MSLT score and scores from the ESS, physician's assessment of the therapeutic effect and the patient's global self-assessment via visual analog scale, the 17-item Hamilton Depression Rating Scale, and the Short Form Health Survey (SF-36) quality-of-life assessment.


RESULTS
A total of 28 patients (15 men, 13 women; mean [SD] age, 40 [12.7] years [range, 18-69 years]; 100% white; modafinil group, 13; placebo group, 15) completed the study without protocol violations. Of the 28 patients with MMD1 included in the analysis, 21 had adult-onset MMD1. At 4 weeks, the mean MWT score was 16.4 (3.3) minutes in the modafinil group and 15.8 (3.8) minutes in the placebo group (P = NS). At the end of the randomization period, there were no significant between-group differences in any secondary outcome. A total of 8 patients (4 in each group) reported > or =1 adverse event, including digestive, neurologic, and skin symptoms. Weight loss was reported in 1 patient (2 kg).


CONCLUSIONS
In this small study conducted in an adult population with MMD1 and a high prevalence of hyper-somnia, modafinil had no significant effects on daytime somnolence measured using objective MWTs.
Orlikowski
David
D
Center for Neuromuscular Disease, Intensive Care Unit and Sleep Laboratory and Functional Exploration Department, Raymond Poincaré Hospital, Paris Ile de France Ouest, Versailles Saint Quentin University, 92380 Garches, France.
Chevret
Sylvie
S
Quera-Salva
Maria Antonia
MA
Laforêt
Pascal
P
Lofaso
Frédéric
F
Verschueren
Annie
A
Pouget
Jean
J
Eymard
Bruno
B
Annane
Djillali
D
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*; D006970:Disorders of Excessive Somnolence / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D009223:Myotonic Dystrophy / Q000150:complications*; D011446:Prospective Studies; D011788:Quality of Life; D055815:Young Adult
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil