Excessive daytime sleepiness (EDS) is one of those symptoms of Prader-Willi syndrome (PWS) that often does not get the attention it deserves. EDS can profoundly undermine success in older children and adults with PWS.
It is hard to learn anything in school if you cannot stay awake for class, and it is hard to keep a job if you are constantly falling asleep. On top of that, we all tend to be a bit grumpier and more emotionally reactive when we are tired, and that is certainly not something that is helpful in PWS. Because of this, excessive daytime sleepiness can have a significant impact on quality of life.
What Is Modafinil?
Modafinil (brand name Provigil) is a wake-promoting medication commonly used to treat narcolepsy and other causes of excessive sleepiness, such as sleep apnea or shift-work disorder. Modafinil has a strong safety record and a low risk of addiction or abuse. Its most common side effect is decreased appetite, which could actually be a welcome effect in PWS.
Modafinil has also been reported to improve symptoms of ADHD and mood, and there are indications that it may improve cognitive abilities, at least in the short term. Because of these potential benefits, some children and adults with PWS have been prescribed modafinil. Anecdotally, many families have reported favorable results.
Modafinil in PWS: Promising Study Results
A small but important study by Professor M. Tauber and colleagues examined the effectiveness of modafinil for excessive daytime sleepiness in people with PWS.
The study included nine individuals with PWS, ages 8 to 21, who had confirmed excessive daytime sleepiness based on sleep studies. Interestingly, six of the nine participants showed sleep features similar to narcolepsy.
This connection makes sense. Both narcolepsy and PWS are associated with reduced levels of orexin, also known as hypocretin, a brain chemical that plays an important role in staying awake. In addition, research has shown that loss of the MAGEL2 gene, which is inactivated in PWS, decreases orexin levels and disrupts normal sleep-wake rhythms (Kozlov 2007).
Participants received modafinil starting at 100 mg per day, with doses increased as needed up to 300 mg per day. Although the trial was open-label, meaning both doctors and participants knew the medication being given, the results were encouraging:
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All nine participants showed significant improvements in daytime sleepiness, based on caregiver reports and scores on the Epworth Sleepiness Scale
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Some participants remained on modafinil for more than two years
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No adverse side effects were reported
These findings suggest that modafinil may meaningfully improve wakefulness and daily functioning in individuals with PWS.
Appetite Effects
Interestingly, a small study found that individuals without PWS who were taking modafinil tended to eat less. This aligns with earlier research comparing modafinil and amphetamines. While both medications promote wakefulness and reduce appetite, modafinil does not significantly increase heart rate or blood pressure, even at higher doses.
Reference: Makris AP, Rush CR, Frederich RC, Kelly TH. Wake-promoting agents with different mechanisms of action: comparison of effects of modafinil and amphetamine on food intake and cardiovascular activity. Appetite. 2004;42:185–195
Insights from Other Pediatric Studies
Other studies have examined the use of modafinil in children with ADHD and narcolepsy, helping expand understanding of its safety and potential benefits.
In ADHD:
A large, randomized, placebo-controlled trial of children ages 6–17 found that modafinil significantly improved attention and behavior, with no impact on blood pressure, heart rate, or blood chemistry. Side effects included mild insomnia and headache. Participants also lost a small but statistically significant amount of weight—likely not a concern in PWS.
Reference: Biederman J, Swanson JM, Wigal SB, Kratochvil CJ, Boellner SW, Earl CQ, Jiang J, Greenhill L. “Efficacy and Safety of Modafinil Film Coated Tablets in Children and Adolescents With ADHD.” Pediatrics. 2005;116(6):e777–e784.
In Narcolepsy:
A separate study in children with excessive daytime sleepiness (primarily due to narcolepsy) used doses of 200–600 mg/day. The drug was generally well tolerated and effective, though one participant with a prior history of hallucinations experienced worsening symptoms at high doses.
Reference: Ivanenko A, Tauman R, Gozal D. “Modafinil in the treatment of excessive daytime sleepiness in children.” Sleep Med. 4:579–582, 2003.
Looking Ahead
Excessive daytime sleepiness can affect learning, behavior, and daily functioning in people with PWS. While larger and more controlled studies are still needed, existing evidence suggests modafinil may help improve wakefulness and may offer additional benefits related to mood, attention, or appetite for some individuals. As with any medication, families should discuss potential benefits and risks with a healthcare provider familiar with PWS.
