Johansen Karina Glies Vincents, Tarp Simon, Astrup Arne, Lund Hans, Pagsberg Anne K, Christensen Robin
Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
PLoS One. 2017 Aug 29;12(8):e0183821. doi: 10.1371/journal.pone.0183821. eCollection 2017.
Nalmefene is a newly approved drug for alcohol use disorder, but the risk of harms has not been evaluated from empirical trial evidence.
To assess the harm of nalmefene administered to individuals diagnosed with substance use or impulse control disorders by performing a systematic review and meta-analysis of randomised controlled trials.
A search was performed in Cochrane Central Register of Controlled Trials (CENTRAL, 2014), MEDLINE via PubMed (1950), EMBASE via Ovid (1974), and Clinicaltrials.gov through December 2014.
This study included only randomised controlled trials with placebo or active controls that administered nalmefene to adult individuals for treating impulse control and/or substance use disorders. Both published and unpublished randomised controlled trials were eligible for inclusion.
Internal validity was assessed using the Cochrane risk-of-bias tool. Published information from the trials was supplemented by contact between reviewers and industry sponsor. Data were combined using two meta-approaches in fixed effects models; Peto Odds Ratios and risk differences were reported with 95% confidence intervals (95%CIs).
Number of patients with serious adverse events, including specific psychiatric serious adverse events and withdrawals due to adverse events.
Of 20 potentially relevant studies, 15 randomised controlled trials met the inclusion criteria, and 8 of these provided data enabling the meta-analysis. Overall, serious adverse events did not occur more often in the nalmefene group than in the placebo group (Peto Odds Ratio = 0.97 [95% CI 0.64-1.44]; P = 0.86). Risk of psychiatric serious adverse events was slightly elevated, albeit not at a statistically significant level (Peto Odds Ratio = 1.32 [95% CI 0.62, 2.83]; P = 0.47). Withdrawals due to adverse events were significantly more likely to occur with nalmefene compared to placebo (Peto Odds Ratio = 3.22 [95% CI 2.46-4.22]; P<0.001).
The three-fold increased risk of withdrawal from treatment on nalmefene due to adverse events is a matter of safety concern. The nature of these adverse events cannot be elucidated further without access to individual patients data.
纳曲酮是一种新批准用于治疗酒精使用障碍的药物，但尚未从实证试验证据中评估其危害风险。
通过对随机对照试验进行系统评价和荟萃分析，评估纳曲酮用于诊断为物质使用或冲动控制障碍的个体的危害。
在Cochrane对照试验中央注册库（CENTRAL，2014年）、通过PubMed检索的MEDLINE（1950年起）、通过Ovid检索的EMBASE（1974年起）以及截至2014年12月的Clinicaltrials.gov中进行了检索。
本研究仅纳入了以安慰剂或活性对照的随机对照试验，这些试验将纳曲酮用于成年个体以治疗冲动控制和/或物质使用障碍。已发表和未发表的随机对照试验均符合纳入标准。
使用Cochrane偏倚风险工具评估内部效度。试验的已发表信息通过评审人员与行业赞助商之间的联系进行补充。数据在固定效应模型中使用两种荟萃分析方法进行合并；报告Peto比值比和风险差值及其95%置信区间（95%CI）。
发生严重不良事件的患者数量，包括特定的精神科严重不良事件以及因不良事件导致的退出试验情况。
在20项可能相关的研究中，15项随机对照试验符合纳入标准，其中8项提供了可用于荟萃分析的数据。总体而言，纳曲酮组严重不良事件的发生频率并不高于安慰剂组（Peto比值比 = 0.97 [95%CI 0.64 - 1.44]；P = 0.86）。精神科严重不良事件的风险略有升高，尽管未达到统计学显著水平（Peto比值比 = 1.32 [95%CI 0.62, 2.83]；P = 0.47）。与安慰剂相比，纳曲酮导致因不良事件退出试验的可能性显著更高（Peto比值比 = 3.22 [95%CI 2.46 - 4.22]；P<0.001）。
因不良事件导致纳曲酮治疗退出的风险增加了两倍，这是一个安全问题。如果无法获取个体患者数据，这些不良事件的性质无法进一步阐明。
