Data from: The relative risk of fatal poisoning by methadone or buprenorphine within the wider population of England & Wales

Objective: To examine the population-wide overdose risk emerging from the prescription of methadone and buprenorphine for opioid substitution treatment in England and Wales. Design: Retrospective administrative data study. Setting: National databases for England and Wales. Participants/cases: Drug-related mortality data were drawn from the Office for National Statistics, and prescription data for methadone and buprenorphine were obtained from the National Health Service for the years 2007–2012. During this 6-year period, a total of 2366 methadone-related deaths and 52 buprenorphine-related deaths were registered, corresponding to 17 333 163 methadone and 2 602 374 buprenorphine prescriptions issued. The analysis encompassed poisoning deaths among members of the wider population of England and Wales who consumed, but were not prescribed these medications, in addition to patients prescribed methadone or buprenorphine. Main outcome measures :Mortality risk: substance-specific overdose rate per 1000 prescriptions issued; relative risk ratio of methadone in relation to buprenorphine. Results: During the years 2007–2012, the pooled overdose death rate was 0.137/1000 prescriptions of methadone, compared to 0.022/1000 prescriptions of buprenorphine (including buprenorphine-naloxone). The analysis generated a relative risk ratio of 6.23 (95% CI 4.79 to 8.10) of methadone in relation to buprenorphine. UK Borders Agency data were taken into consideration and revealed that only negligible amounts of methadone and buprenorphine were seized on entering UK territory between 2007 and 2012, suggesting domestic diversion. Conclusions: Our analysis of the relative safety of buprenorphine and methadone for opioid substitution treatment reveals that buprenorphine is six times safer than methadone with regard to overdose risk among the general population. Clinicians should be aware of the increased risk of prescribing methadone, and tighter regulations are needed to prevent its diversion.

研究目的：考察英格兰与威尔士地区，用于阿片类药物替代治疗的美沙酮与丁丙诺啡处方所引发的全人群过量用药风险。
研究设计：回顾性行政数据研究。
研究场景：英格兰与威尔士国家级数据库。
研究对象与病例：药物相关死亡数据取自英国国家统计局（Office for National Statistics），美沙酮与丁丙诺啡的处方数据来源于英国国家医疗服务体系（National Health Service, NHS），统计时段为2007年至2012年。该6年周期内，共登记美沙酮相关死亡2366例、丁丙诺啡相关死亡52例，对应开具的美沙酮处方共计17333163张，丁丙诺啡处方共计2602374张。本分析覆盖了英格兰与威尔士全人群中曾服用上述药物但未获得处方者的中毒死亡病例，同时纳入了开具美沙酮或丁丙诺啡处方的患者数据。
主要结局指标：死亡率风险，即每1000张处方对应的药物特异性过量死亡率；美沙酮相较于丁丙诺啡的相对风险比。
研究结果：2007至2012年间，美沙酮的合并过量死亡率为0.137/1000张处方，丁丙诺啡（含丁丙诺啡-纳洛酮复方制剂）的合并过量死亡率为0.022/1000张处方。分析显示，美沙酮相较于丁丙诺啡的相对风险比为6.23（95%置信区间[CI]：4.79~8.10）。结合英国边境署（UK Borders Agency）的数据，2007至2012年间入境英国的美沙酮与丁丙诺啡缉获量极低，提示存在国内非法流转情况。
研究结论：本研究针对阿片类药物替代治疗所用丁丙诺啡与美沙酮的相对安全性分析表明，在全人群过量用药风险维度上，丁丙诺啡的安全性约为美沙酮的6倍。临床医师应警惕开具美沙酮处方所伴随的更高风险，同时需出台更严格的监管措施以防范其非法流转。