Tara Carney1, Marie Claire Van Hout2, Ian Norman3, Siphokazi Dada4, Nandi Siegfried4, Charles Dh Parry1,5. 1. South African Medical Research Council, Alcohol, Tobacco and Other Drug Research Unit, Francie Van Zijl Drive, Tygerberg, Western Cape, South Africa, 7505. 2. Liverpool John Moores University, Public Health Institute, 2nd Floor Henry Cotton Campus, 15-21 Webster Street, Liverpool, UK, L32ET. 3. King's College London, Florence Nightingale Faculty of Nursing and Midwifery, James Clerk Maxwell Building , Waterloo Road, London, UK, SE1 8WA. 4. South African Medical Research Council, Alcohol, Tobacco and Other Drug Research Unit, Francie Van Zijl Drive, Tygerberg, Cape Town, Western Cape, South Africa, 7505. 5. University of Stellenbosch, Department of Psychiatry, Tygerberg 7505, South Africa.
Abstract
BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: 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 We also searched for ongoing and unpublished studies via ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and Trialsjournal.com.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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: We followed the standard methodological procedures that are outlined by Cochrane. This includes the GRADE approach to appraise the quality of evidence. MAIN RESULTS: 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.
BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: We followed the standard methodological procedures that are outlined by Cochrane. This includes the GRADE approach to appraise the quality of evidence. MAIN RESULTS: 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.
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