Lee Kenn, Twohig Matthew, Idoko Nguemo Pauline, Williams Benjamin David
Pennine Care NHS Foundation Trust, Mental Health Liaison Team, Fairfield General Hospital, Bury, Manchester, UK.
Greater Manchester Mental Health NHS Foundation Trust, Rehabilitation Services, Royal Bolton Hospital, Bolton, Manchester, UK.
J Psychopharmacol. 2025 Aug;39(8):790-803. doi: 10.1177/02698811251337374. Epub 2025 May 23.
Antipsychotic-induced weight gain (AIWG) is a major concern in psychiatry, where there is a mortality gap between those with mental illness, particularly schizophrenia, and the general population. One development proposed is using centrally-acting opioid receptor antagonists (CORAs) such as naltrexone and samidorphan.
The systematic review and meta-analysis evaluated the available human clinical trial data on the effect of CORA on AIWG.
Four online databases (MEDLINE, EMBASE, PsycINFO, and Cochrane) were searched for randomized-controlled trials (RCTs) on the topic. The primary outcome was change in bodyweight. Secondary anthropometric outcomes included percentage bodyweight change, BMI change, and absolute risk of weight gain. Meta-analysis was conducted on primary outcome.
Nine RCT articles (samidorphan = 6, naltrexone = 3) and two extension studies from RCTs (both samidorphan) were identified. Meta-analysis of four RCTs ( = 1416) found olanzapine/samidorphan was associated with less weight gain than olanzapine alone (mean difference in bodyweight change: -1.18 kg; 95% CI: -1.67 to -0.68). Olanzapine/samidorphan was also superior to olanzapine for changes in BMI (-0.65 kg/m; 95% CI: -1.1 to -0.28), waist circumference (-1.5 cm; 95% CI: -2.67 to -0.32), and risk reduction for gaining 7% body weight (-12.4%; 95% CI: -18.27 to -6.54) or 10% body weight (-10.8%; 95% CI: -16.21 to -5.45). Naltrexone did not separate from placebo for change in weight or BMI.
CORA, specifically samidorphan, was effective at reducing weight gain in individuals prescribed olanzapine. The small effect sizes and discrepancy between samidorphan and naltrexone suggest effects may be timing dependent, not a class effect, or dependent on the antipsychotic combination.
抗精神病药物所致体重增加（AIWG）是精神病学领域的一个主要问题，在患有精神疾病（尤其是精神分裂症）的人群与普通人群之间存在死亡率差距。一种提议的进展是使用中枢作用的阿片受体拮抗剂（CORAs），如纳曲酮和赛美多芬。
本系统评价和荟萃分析评估了关于CORA对AIWG影响的现有人类临床试验数据。
在四个在线数据库（MEDLINE、EMBASE、PsycINFO和Cochrane）中检索关于该主题的随机对照试验（RCT）。主要结局是体重变化。次要人体测量学结局包括体重变化百分比、BMI变化以及体重增加的绝对风险。对主要结局进行荟萃分析。
确定了9篇RCT文章（赛美多芬=6篇，纳曲酮=3篇）以及来自RCT的2篇扩展研究（均为赛美多芬）。对4项RCT（n=1416）的荟萃分析发现，奥氮平/赛美多芬与单独使用奥氮平相比，体重增加较少（体重变化的平均差异：-1.18kg；95%CI：-1.67至-0.68）。奥氮平/赛美多芬在BMI变化（-0.65kg/m²；95%CI：-1.1至-0.28）、腰围（-1.5cm；95%CI：-2.67至-0.32）以及体重增加7%（-12.4%；95%CI：-18.27至-6.54）或10%（-10.8%；95%CI：-16.21至-5.45）的风险降低方面也优于奥氮平。纳曲酮在体重或BMI变化方面与安慰剂无差异。
CORA，特别是赛美多芬，在减少服用奥氮平个体的体重增加方面有效。效应量较小以及赛美多芬和纳曲酮之间的差异表明，其效应可能与时间有关，而非类别效应，或取决于抗精神病药物的联合使用情况。
