Carney Tara, Van Hout Marie Claire, Norman Ian, Dada Siphokazi, Siegfried Nandi, Parry Charles Dh
South African Medical Research Council, Alcohol, Tobacco and Other Drug Research Unit, Francie Van Zijl Drive, Tygerberg, Western Cape, South Africa, 7505.
Liverpool John Moores University, Public Health Institute, 2nd Floor Henry Cotton Campus, 15-21 Webster Street, Liverpool, UK, L32ET.
Cochrane Database Syst Rev. 2020 Feb 18;2(2):CD012254. doi: 10.1002/14651858.CD012254.pub2.
Medical treatment and detoxification from opiate disorders includes oral administration of opioid agonists. Dihydrocodeine (DHC) substitution treatment is typically low threshold and therefore has the capacity to reach wider groups of opiate users. Decisions to prescribe DHC to patients with less severe opiate disorders centre on its perceived safety, reduced toxicity, shorter half-life and more rapid onset of action, and potential retention of patients. This review set out to investigate the effects of DHC in comparison to other pharmaceutical opioids and placebos in the detoxification and substitution of individuals with opiate use disorders.
To investigate the effectiveness of DHC in reducing illicit opiate use and other health-related outcomes among adults compared to other drugs or placebos used for detoxification or substitution therapy.
In February 2019 we searched Cochrane Drugs and Alcohol's Specialised Register, CENTRAL, PubMed, Embase and Web of Science. We also searched for ongoing and unpublished studies via ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and Trialsjournal.com. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies.
We included randomised controlled trials that evaluated the effect of DHC for detoxification and maintenance substitution therapy for adolescent (aged 15 years and older) and adult illicit opiate users. The primary outcomes were abstinence from illicit opiate use following detoxification or maintenance therapy measured by self-report or urinalysis. The secondary outcomes were treatment retention and other health and behaviour outcomes.
We followed the standard methodological procedures that are outlined by Cochrane. This includes the GRADE approach to appraise the quality of evidence.
We included three trials (in five articles) with 385 opiate-using participants that measured outcomes at different follow-up periods in this review. Two studies with 150 individuals compared DHC with buprenorphine for detoxification, and one study with 235 participants compared DHC to methadone for maintenance substitution therapy. We downgraded the quality of evidence mainly due to risk of bias and imprecision. For the two studies that compared DHC to buprenorphine, we found low-quality evidence of no significant difference between DHC and buprenorphine for detoxification at six-month follow-up (risk ratio (RR) 0.59, 95% confidence interval (CI) 0.25 to 1.39; P = 0.23) in the meta-analysis for the primary outcome of abstinence from illicit opiates. Similarly, low-quality evidence indicated no difference for treatment retention (RR 1.29, 95% CI 0.99 to 1.68; P = 0.06). In the single trial that compared DHC to methadone for maintenance substitution therapy, the evidence was also of low quality, and there may be no difference in effects between DHC and methadone for reported abstinence from illicit opiates (mean difference (MD) -0.01, 95% CI -0.31 to 0.29). For treatment retention at six months' follow-up in this single trial, the RR calculated with an intention-to-treat analysis also indicated that there may be no difference between DHC and methadone (RR 1.04, 95% CI 0.94 to 1.16). The studies that compared DHC to buprenorphine reported no serious adverse events, while the DHC versus methadone study reported one death due to methadone overdose.
AUTHORS' CONCLUSIONS: We found low-quality evidence that DHC may be no more effective than other commonly used pharmacological interventions in reducing illicit opiate use. It is therefore premature to make any conclusive statements about the effectiveness of DHC, and it is suggested that further high-quality studies are conducted, especially in low- to middle-income countries.
阿片类药物成瘾的医学治疗和脱毒包括口服阿片类激动剂。双氢可待因（DHC）替代治疗的门槛通常较低，因此有能力覆盖更广泛的阿片类药物使用者群体。对于阿片类药物成瘾不太严重的患者，开具DHC的决定主要基于其公认的安全性、较低的毒性、较短的半衰期和更快的起效速度，以及对患者的潜在保留作用。本综述旨在研究DHC与其他药物性阿片类药物及安慰剂相比，在阿片类药物使用障碍患者的脱毒和替代治疗中的效果。
与用于脱毒或替代治疗的其他药物或安慰剂相比，研究DHC在减少成人非法阿片类药物使用及其他与健康相关结局方面的有效性。
2019年2月，我们检索了Cochrane毒品与酒精专业注册库、CENTRAL、PubMed、Embase和科学网。我们还通过ClinicalTrials.gov、世界卫生组织（WHO）国际临床试验注册平台（ICTRP）和Trialsjournal.com搜索正在进行和未发表的研究。所有检索均包括非英语文献。我们手工检索了主题相关系统评价和纳入研究的参考文献。
我们纳入了评估DHC对青少年（15岁及以上）和成人非法阿片类药物使用者进行脱毒和维持替代治疗效果的随机对照试验。主要结局是通过自我报告或尿液分析测量的脱毒或维持治疗后非法阿片类药物使用的戒断情况。次要结局是治疗保留率以及其他健康和行为结局。
我们遵循Cochrane概述的标准方法程序。这包括采用GRADE方法评估证据质量。
我们在本综述中纳入了三项试验（五篇文章），共385名使用阿片类药物的参与者，这些试验在不同随访期测量了结局。两项共150人的研究比较了DHC与丁丙诺啡用于脱毒，一项有235名参与者的研究比较了DHC与美沙酮用于维持替代治疗。我们主要由于偏倚风险和不精确性而降低了证据质量。对于两项比较DHC与丁丙诺啡的研究，我们发现低质量证据表明，在非法阿片类药物戒断这一主要结局的荟萃分析中，在六个月随访时DHC与丁丙诺啡在脱毒方面无显著差异（风险比（RR）0.59，95%置信区间（CI）0.25至1.39；P = 0.23）。同样，低质量证据表明在治疗保留率方面无差异（RR 1.29，95% CI 0.99至1.68；P = 0.06）。在比较DHC与美沙酮用于维持替代治疗的单项试验中，证据质量也较低，对于报告的非法阿片类药物戒断情况，DHC与美沙酮之间的效果可能无差异（平均差（MD）-0.01，95% CI -0.31至0.29）。在该单项试验的六个月随访时的治疗保留率方面，意向性分析计算的RR也表明DHC与美沙酮之间可能无差异（RR 1.04，95% CI 0.94至1.16）。比较DHC与丁丙诺啡的研究未报告严重不良事件，而DHC与美沙酮的研究报告了1例因美沙酮过量导致的死亡。
我们发现低质量证据表明，DHC在减少非法阿片类药物使用方面可能并不比其他常用的药物干预更有效。因此，就DHC的有效性做出任何确定性陈述还为时过早，建议开展进一步的高质量研究，尤其是在低收入和中等收入国家。
