Prader-Willi Syndrome (PWS) is a rare genetic syndrome leading to severe behavioural disorders and
mild cognitive impairment. The objective of this double-blind randomised placebo-controlled trial was to study the efficacy and tolerance of
topiramate on behavioural disorders in patients with PWS. Participants (aged 12-45 years) had genetically confirmed PWS and severe irritability/impulsivity,
eating disorders and/or
obesity, and
skin picking. Thirty-two participants received a placebo (PBO), and 30 participants received
topiramate (TOP) (50-200 mg/day) for 8 weeks. The primary outcome was the rate of responders using the Clinical Global Impression-Improvement (CGI-I) scale. The secondary outcome measures included the Aberrant Behaviour Checklist, the Dykens
Hyperphagia Questionnaire (DHK), the Self-Injurious Behaviour Scale (SIBS) and the body mass index (BMI). We found no significant difference in the primary outcome (the CGI-I): 9 (30%) patients were very much or much improved in the TOP group compared to 7 (22.6%) patients in the PBO group. However, the DHK behaviour and severity scores improved significantly more over time in patients treated with
topiramate versus those receiving a placebo, with a significant dose-effect relationship. DHK scores were also significantly associated with genetic subtypes and hospitalisation status. The effects of
topiramate on eating behaviours remained significant after adjusting for genetic subtype and hospitalisation.
Topiramate had therefore a significant effect on
eating disorders, with a dose-effect relationship. Given the burden of
eating disorders in PWS, we believe that
topiramate may become the first psychotropic option within the global care of
obesity in individuals with PWS.