What is Pitolisant (Wakix™)?
Pitolisant (Wakix™) is a new medication which has been approved in Europe for the treatment of narcolepsy in adults based on its ability to improve wakefulness. It has recently attracted attention as having potential application in PWS to alleviate excessive daytime sleepiness.
How does Pitolisant (Wakix™) work?
The active substance in Wakix, pitolisant, works by attaching to receptors in the brain called 'histamine H3 receptors'. This increases the activity of certain brain cells called 'histamine neurons', which are important for keeping the body awake (from EU Med Agency). Scientific Journal Neuropharmacology recently published a special issue on histamine receptors, where researchers suggested there may be potential applications (and overlap) in obesity, energy homeostasis and sleep disorders. Prof Dr Holgar Stark spoke at IPWSO16 on the topic and notes in his abstract that at this stage "the therapeutic potential is highly speculative" but worth investigating. PWRFA agrees with this view noting that "at this point it is theoretical and speculative but worth considering for future studies".
The reported side effects of Pitolisant can include anxiety, depression, nausea and insomnia.
Are there other alternative medications available?
It's worth noting that there is a drug already available which has been shown to successfully treat excessive daytime sleepiness in PWS, Modafinal. Modafinal has also been shown in several studies (in typically developing individuals) to enhance certain aspects of cognitive function and has the reported side effect of decreasing appetite. In the US and France, Modafinil is being prescribed to people with PWS. In Australia, it can only be obtained by prescription from an appropriate healthcare professional.
Note that Modafinil can also cause increase anxiety, particularly in those in who have a high baseline.
What is the difference between Pitolisant and Modafinil?
The two treatments work on different pathways, which may indicate that they could have different effects in PWS. To our knowledge, no head-to-head comparisons of the two drugs that have been conducted in PWS. In a head-to-head comparison in typical patients with narcolepsy, the efficacy of Pitolisant is very similar to that of Modafinil despite the fact each is thought to work on different pathways. Each has similar reported safety profiles, although we note that data has not yet been published for Pitolisant in children.
What else should I know?
In the short-term, people with PWS who display narcolepsy or similar symptoms should discuss the condition with an appropriately qualified health professional and investigate appropriate medications.
You can read more about Pitolisant at:
You can read more about the effects of Modafinil:
Our thanks to PWRFA Research Director Dr Diane Webster for answering this question from a member of our Facebook community. You can join the community at facebook.com/PWRFA