Metformin緩解自閉症患者使用抗精神病藥後的體重增加情況


  【24drs.com】對於泛自閉症障礙症候群(ASD)孩童,Metformin或許可以抵消非典型抗精神病藥引起的體重增加情況。
  
  在一篇控制試驗中,對於前述患者群使用非典型抗精神病藥的體重增加情況,metformin比安慰劑更能顯著有效地降低。
  
  加拿大安大略多倫多Holland Bloorview兒童復健醫院自閉症研究中心Evdokia Anagnostou醫師表示,根據我們的研究結果,對於必須使用非典型抗精神病藥控制易怒/侵略,但是體重顯著增加的ASD孩童與青少年,我們建議醫師考慮使用metformin。
  
  這篇研究線上發表於8月24日的JAMA Psychiatry期刊。
  
  非典型抗精神病藥risperidone(商品名Risperdal, Janssen Pharmaceuticals藥廠)以及aripiprazole(商品名Abilify, Otsuka Pharmaceuticals藥廠)獲得美國食品藥物管理局核准用於控制ASD孩童與青少年的易怒,但是,已知其副作用為增加食慾與體重。
  
  Anagnostou醫師與跨中心的團隊檢測了metformin用於60名6-17歲(平均12.8歲)ASD孩童與青少年減輕前述體重增加情況的安全性、耐受性與效果。
  
  所有研究對象都接受穩定劑量的非典型抗精神病藥,大部份是常見的risperidone與aripiprazole,用了至少1個月且沒計畫改變。被納入研究的孩童必須:自服藥後,如果身體質量指數(BMI)為85百分位以上,BMI至少增加7%,體重每年增加5%以上。
  
  對於6-9歲孩童,metformin或安慰劑被調整到最多500 mg、每天兩次,10-17歲者則是調整到850 mg、每天兩次,metformin組有28名孩童,安慰劑組有32名孩童。
  
  主要結果測量是治療16週時的BMI z值變化,根據這個測量,metformin優於安慰劑(與安慰劑比較,16週時的分數變化差異, -0.10; 95%信賴區間[CI] -0.16 to -0.04;P = .003)。
  
  使用安慰劑的孩童,16週時的BMI z值沒有改變(0.02; 95% CI, -0.03 - 0.06),服用metformin的孩童則是比開始時大幅減少(-0.08; 95% CI, -0.13 to -0.04)。
  
  Metformin在統計上也顯著改善了原BMI (-0.95; 95% CI, -1.46 至 - 0.45)與原體重(-2.73; 95% CI, -4.04 至 -1.43)這兩個次級身體組成測量。
  
  服用metformin的3名孩童(11%)的BMI降低8%-9%,在16週的治療期間,沒有其他孩童的BMI減少超過5%。
  
  總膽固醇、低密度脂蛋白膽固醇、高密度脂蛋白膽固醇、三酸甘油脂、葡萄糖、空腹胰島素、糖化血色素A1c等血液代謝參數的測量方面,並無顯著的組內差異。
  
  作者們指出,metformin的治療期間可能太短,而無法獲得代謝效益與評估是否可維持初步改善。
  
  5名孩童因為副作用(4個躁動、1個鎮靜)而停用metformin,metformin治療期間的胃腸道副作用比率顯著高於安慰劑組 (25.1% vs 6.8%; P = .005)。
  
  Anagnostou醫師表示,整體而言,metformin耐受良好,不過,最常見的副作用與胃腸道症狀有關,因為ASD孩童與青少年比一般孩童經歷更多胃腸道壓力,處方時必須謹記此點。另外,metformin需要進行肝臟酵素血液監測,正因為如此,處方此藥的孩童與青少年必須忍耐血液檢查。
  
  作者們結論指出,對於使用非典型抗精神病藥物治療易怒與侵略症狀、但難以控制隨之產生體重大幅增加的孩童,這些研究結果有重要意義。
  
  Anagnostou醫師表示,我們需要更多研究以回答「在開始使用非典型抗精神病藥物時加入metformin是否可以預防體重增加」這個問題。
  
  麻塞諸塞州麻州綜合醫院與哈佛醫學院Lurie自閉症中心Christopher J. McDougle醫師在相關的編輯評論中寫道,顯然,Anagnostou等人瞭解我們正面對以非典型抗精神病藥物治療ASD少年時,風險與利益之間的平衡困境。
  
  McDougle醫師表示,藉由此篇研究,他們對文獻做出了顯著貢獻,於使用非典型抗精神病藥物治療ASD少年時,提供一個管理體重增加的有效方法給醫師。
  
  除了需要有關這個方法的更多研究,也需探討其他替代策略,如同時服用topiramate、使用ziprasidone單一治療、以及其他。
  
  資料來源: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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