Effect of topiramate on eating behaviours in Prader-Willi syndrome: TOPRADER double-blind randomised placebo-controlled study
Effect of topiramate on eating behaviours in Prader-Willi syndrome: TOPRADER double-blind randomised placebo-controlled study
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DOI：
10.1038/s41398-019-0597-0
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发表时间：
2019-11-04
影响因子：
6.8
通讯作者：
Bonnot, Olivier
中科院分区：
文献类型：
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作者：
Consoli, Angele;Berthoumieu, Sophie Cabal;Bonnot, Olivier
Prader-Willi综合征（PWS）是一种罕见的遗传综合征，可导致严重的行为障碍和轻度认知障碍。这项双盲随机安慰剂对照试验的目的是研究托吡酯治疗PWS患者行为障碍的疗效和耐受性。参与者（年龄12-45岁）有遗传学证实的PWS和严重的易怒/冲动，饮食失调和/或肥胖，以及皮肤采摘。32名参与者接受安慰剂（PBO），30名参与者接受托吡酯（TOP）（50-200 mg/天），持续8周。主要结局是使用临床总体印象改善（CGI-I）量表的应答率。次要结局指标包括异常行为检查表、戴肯斯暴食问卷（DHK）、自伤行为量表（SIBS）和体重指数（BMI）。我们发现主要结局（CGI-I）无显著差异：TOP组9例（30%）患者的改善非常大或非常大，而PBO组7例（22.6%）患者的改善非常大或非常大。然而，与接受安慰剂的患者相比，接受托吡酯治疗的患者的DHK行为和严重程度评分随时间推移显著改善，具有显著的剂量效应关系。DHK评分也与遗传亚型和住院状态显著相关。调整遗传亚型和住院治疗后，托吡酯对饮食行为的影响仍然显着。因此，托吡酯对进食障碍有显著疗效，且存在剂量-效应关系。考虑到PWS患者饮食失调的负担，我们认为托吡酯可能成为PWS患者肥胖全球治疗的第一个精神药物选择。
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.