Metformin缓解自闭症患者使用抗精神病药后的体重增加情况


  【24drs.com】对于泛自闭症障碍症候群(ASD)孩童,Metformin或许可以抵消非典型抗精神病药引起的体重增加情况。
  
  在一篇控制试验中,对于前述患者群使用非典型抗精神病药的体重增加情况,metformin比安慰剂更能显著有效地降低。
  
  加拿大安大略多伦多Holland Bloorview儿童复健医院自闭症研究中心Evdokia Anagnostou医师表示,根据我们的研究结果,对于必须使用非典型抗精神病药控制易怒/侵略,但是体重显著增加的ASD孩童与青少年,我们建议医师考虑使用metformin。
  
  这篇研究在线发表于8月24日的JAMA Psychiatry期刊。
  
  非典型抗精神病药risperidone(商品名Risperdal, Janssen Pharmaceuticals药厂)以及aripiprazole(商品名Abilify, Otsuka Pharmaceuticals药厂)获得美国食品药物管理局核准用于控制ASD孩童与青少年的易怒,但是,已知其副作用为增加食慾与体重。
  
  Anagnostou医师与跨中心的团队检测了metformin用于60名6-17岁(平均12.8岁)ASD孩童与青少年减轻前述体重增加情况的安全性、耐受性与效果。
  
  所有研究对象都接受稳定剂量的非典型抗精神病药,大部份是常见的risperidone与aripiprazole,用了至少1个月且没计画改变。被纳入研究的孩童必须:自服药后,如果身体质量指数(BMI)为85百分位以上,BMI至少增加7%,体重每年增加5%以上。
  
  对于6-9岁孩童,metformin或安慰剂被调整到最多500 mg、每天两次,10-17岁者则是调整到850 mg、每天两次,metformin组有28名孩童,安慰剂组有32名孩童。
  
  主要结果测量是治疗16周时的BMI z值变化,根据这个测量,metformin优于安慰剂(与安慰剂比较,16周时的分数变化差异, -0.10; 95%信赖区间[CI] -0.16 to -0.04;P = .003)。
  
  使用安慰剂的孩童,16周时的BMI z值没有改变(0.02; 95% CI, -0.03 - 0.06),服用metformin的孩童则是比开始时大幅减少(-0.08; 95% CI, -0.13 to -0.04)。
  
  Metformin在统计上也显著改善了原BMI (-0.95; 95% CI, -1.46 至 - 0.45)与原体重(-2.73; 95% CI, -4.04 至 -1.43)这两个次级身体组成测量。
  
  服用metformin的3名孩童(11%)的BMI降低8%-9%,在16周的治疗期间,没有其它孩童的BMI减少超过5%。
  
  总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、三酸甘油脂、葡萄糖、空腹胰岛素、糖化血色素A1c等血液代谢参数的测量方面,并无显著的组内差异。
  
  作者们指出,metformin的治疗期间可能太短,而无法获得代谢效益与评估是否可维持初步改善。
  
  5名孩童因为副作用(4个躁动、1个镇静)而停用metformin,metformin治疗期间的胃肠道副作用比率显著高于安慰剂组 (25.1% vs 6.8%; P = .005)。
  
  Anagnostou医师表示,整体而言,metformin耐受良好,不过,最常见的副作用与胃肠道症状有关,因为ASD孩童与青少年比一般孩童经历更多胃肠道压力,处方时必须谨记此点。另外,metformin需要进行肝脏酵素血液监测,正因为如此,处方此药的孩童与青少年必须忍耐血液检查。
  
  作者们结论指出,对于使用非典型抗精神病药物治疗易怒与侵略症状、但难以控制随之产生体重大幅增加的孩童,这些研究结果有重要意义。
  
  Anagnostou医师表示,我们需要更多研究以回答「在开始使用非典型抗精神病药物时加入metformin是否可以预防体重增加」这个问题。
  
  麻塞诸塞州麻州综合医院与哈佛医学院Lurie自闭症中心Christopher J. McDougle医师在相关的编辑评论中写道,显然,Anagnostou等人了解我们正面对以非典型抗精神病药物治疗ASD少年时,风险与利益之间的平衡困境。
  
  McDougle医师表示,藉由此篇研究,他们对文献做出了显著贡献,于使用非典型抗精神病药物治疗ASD少年时,提供一个管理体重增加的有效方法给医师。
  
  除了需要有关这个方法的更多研究,也需探讨其它替代策略,如同时服用topiramate、使用ziprasidone单一治疗、以及其它。
  
  资料来源:http://www.24drs.com/
  
  Native link:Metformin Mitigates Antipsychotic Weight Gain in Autism

Metformin Mitigates Antipsychotic Weight Gain in Autism

By Megan Brooks
Medscape Medical News

Metformin may counteract atypical antipsychotic–induced weight gain in children with autism spectrum disorder (ASD).

In a controlled trial, metformin was significantly more effective than placebo in decreasing weight gain associated with the use of atypical antipsychotics in this population.

"Based on our findings, we recommend that physicians consider using metformin in children and youth with ASD who have to stay on their atypical antipsychotics for management of irritability/aggression but experience significant weight gain," Evdokia Anagnostou, MD, of the Holland Bloorview Kids Rehabilitation Hospital Autism Research Center, Toronto, Ontario, Canada, told Medscape Medical News.

The study was published online August 24 in JAMA Psychiatry.

The atypical antipsychotics risperidone (Risperdal, Janssen Pharmaceuticals), and aripiprazole (Abilify, Otsuka Pharmaceuticals) are approved by the US Food and Drug Administration to manage irritability in children and adolescents with ASD, but increased appetite and weight gain are well-known side effects.

Dr Anagnostou and a multicenter team tested the safety, tolerability, and efficacy of metformin in decreasing weight gain associated with their use in 60 children and adolescents aged 6 to 17 years (mean age, 12.8 years) with ASD.

All participants had been receiving a stable dose of an atypical antipsychotic, most commonly risperidone and aripiprazole, for at least 1 month with no plans to change. To be included in the study, the children also had to have had at least a 7% increase in body mass index (BMI) since starting the medication or, if the BMI was in the 85th percentile or higher, a greater than 5% increase in body weight per year since starting the medication.

Metformin or matching placebo was titrated up to 500 mg twice daily for children aged 6 to 9 years and 850 mg twice daily for those aged 10 to 17 years. There were 28 children in the metformin group and 32 in the placebo group.

The primary outcome measure was change in BMI z score over 16 weeks of treatment. On this measure, metformin was superior to placebo (difference in 16-week change in scores vs placebo, -0.10; 95% confidence interval [CI] -0.16 to -0.04; P = .003).

Children receiving placebo experienced no change over 16 weeks in BMI z scores (0.02; 95% CI, -0.03 to 0.06), whereas children taking metformin saw a substantial reduction from baseline (-0.08; 95% CI, -0.13 to -0.04).

Metformin also led to statistically significant improvements in secondary body composition measures of raw BMI (-0.95; 95% CI, -1.46 to -0.45) and raw weight (-2.73; 95% CI, -4.04 to -1.43).

Three children taking metformin (11%) saw declines of 8% to 9% in BMI. No other children experienced declines of more than 5% in BMI during the 16-week treatment period.

No significant between-group differences were noted in metabolic parameters measured in blood, including total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, glucose, fasting insulin, or hemoglobin A1c levels.

The authors note that the length of metformin treatment may have been too short to capture metabolic benefits and to evaluate whether initial improvements will be maintained.

Five children stopped metformin owing to adverse events (agitation in four and sedation in one). Gastrointestinal side effects were reported during a significantly higher percentage of treatment days with metformin than placebo (25.1% vs 6.8%; P = .005).

"Metformin was well tolerated overall," Dr Anagnostou told Medscape Medical News. "However, the most common side effects were related to gastrointestinal symptoms. Given that children and youth with ASD experience more GI distress than typically developing children, that's something to keep in mind when prescribing. Also, metformin requires blood monitoring of liver enzymes, and as such, children and youth prescribed this medication would have to tolerate blood work."

"Effective Approach to Consider"

"These findings have important implications for children in whom the benefits of atypical antipsychotics for treating irritability and agitation symptoms are difficult to balance with the substantial weight gain that often accompanies their use," the authors conclude.

"Where we need more study," Dr Anagnostou said, "is to answer the question whether adding metformin at the onset of treatment with atypical antipsychotics may prevent weight gain altogether."

"Clearly, Anagnostou et al understand the dilemma our field faces in balancing the risk-benefit ratio of treating youths with ASD with atypical antipsychotics," Christopher J. McDougle, MD, Lurie Center for Autism, Massachusetts General Hospital and Harvard Medical School, Lexington, Massachusetts, writes in a related editorial.

With this study, they have made a "significant contribution to the literature and provided clinicians with an effective approach to consider for managing weight gain in youths with ASD treated with atypical antipsychotics," Dr McDougle says.

"In addition to more studies of this approach, alternative strategies that warrant investigation include the coadministration of topiramate, monotherapy with ziprasidone, and undoubtedly others."

Dr Anagnostou has received consultation fees and has served on advisory boards for Roche and has received industry funding from SynapDx and Aventis. A complete list of author disclosures is available with the original article. Dr McDougle has disclosed no relevant financial relationships.

JAMA Psychiatry. Published online August 24, 2016.

    
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