“Excessive daytime sleepiness” (EDS) is one of those symptoms of PWS that tends not to get too much attention – although very common, it just doesn’t seem that serious. However, EDS can profoundly undermine success in older children and adults with PWS. It’s hard to learn anything in school if you can’t stay awake for your classes, and it’s hard to keep a job if you’re constantly falling asleep. On top of that, we all tend to be a bit grumpier and emotionally volatile when we’re tired, and that’s certainly something that’s not needed in PWS. So, in fact, excessive daytime sleepiness has a significant impact on quality of life.
The drug modafinil is a ‘wake promoting’ drug that has been used for treating narcolepsy as well as EDS due to other factors (apnea, shift work). It has a good safety record, a low risk of addiction/abuse and its major side effect in the typical population (decreased appetite) would be welcome in PWS. Modafinil has also been reported to improve symptoms of ADHD, improve mood, and there are hints that it may improve cognitive abilities (at least short term).
Because of these reasons, some older children and adults with PWS have been prescribed modafinil and, anecdotally, the results have generally been quite favorable. However, some doctors may be reluctant to prescribe modafinil since efficacy hasn’t been shown in PWS. Now Prof. M. Tauber and colleagues have published a small study that demonstrates the positive effects of modafinil in children and adolescents with PWS:
Efficacy of modafinil on excessive daytime sleepiness in Prader-Willi syndrome. This study included nine individuals with PWS, age 8-21, who had their excessive daytime sleepiness confirmed by sleep studies, with six of the nine showing sleep features that were highly reminiscent of patients with narcolepsy. This is not surprising; patients with narcolepsy as well as individuals with PWS show a reduction in orexin (a.k.a hypocretin) – a neuropeptide critical to maintaining wakefulness. Further, loss of the Magel2 gene, which is inactivated in PWS, has been shown to decrease the amount of orexin in the hypothalamus and disrupt normal circadian rhythms in the mouse [Kozlov 2007]. In this study, the individuals with PWS received modafinil at a starting dose of 100mg per day, and were increased up to a dose of 300 mg per day (one patient) as needed. The study was “open label”, meaning that both doctors and patients knew they were getting the drug.
Although not the most stringent clinical trial design (a “double blind” study uses a placebo and keeps both doctor and patient unaware of who is getting the test drug), the results were nonetheless compelling. All nine patients showed significant improvements in daytime sleepiness as reported by patients and caregivers and as measured by the “Epworth sleepiness scale”. The patients took modafinil for more than two years in some cases, and the drug was well tolerated with no side effects were reported. Overall, this study suggests that modafinil might be a good choice to improve sleepiness and overall functioning in PWS.