There are increasing concerns regarding pharmaceutical opioid harms including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin.
To assess the effects of maintenance agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence.
The search included the Cochrane Drugs and Alcohol Group’s Specialised Register of Trials; the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 5); PubMed (January 1966 to May 2015); EMBASE (Ovid) (January 1974 to May 2015); CINAHL (EBSCOhost) (1982 to May 2015); ISI Web of Science (to May 2014); and PsycINFO (Ovid) (1806 to May 2014).
We included randomised controlled trials examining maintenance opioid agonist treatments that made the following two comparisons:
1. full opioid agonists (methadone, morphine, oxycodone, levo-alpha-acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment and
2. full or partial opioid agonist maintenance versus placebo, detoxification only, or psychological treatment (without opioid agonist treatment).
Data collection and analysis
We used standard Cochrane methodological procedures.
We identified six randomised controlled trials that met inclusion criteria (607 participants).
We found moderate quality evidence from two studies of no difference between methadone and buprenorphine in self reported opioid use (risk ratio (RR) 0.37, 95% confidence interval (CI) 0.08 to 1.63) or opioid positive urine drug tests (RR 0.81, 95% CI 0.56 to 1.18). There was low quality evidence from three studies of no difference in retention between buprenorphine and methadone maintenance treatment (RR 0.69, 95% CI 0.39 to 1.22). There was moderate quality evidence from two studies of no difference between methadone and buprenorphine on adverse events (RR 1.10, 95% CI 0.64 to 1.91).
We found low quality evidence from three studies favouring maintenance buprenorphine treatment over detoxification or psychological treatment in terms of fewer opioid positive urine drug tests (RR 0.63, 95% CI 0.43 to 0.91) and self reported opioid use in the past 30 days (RR 0.54, 95% CI 0.31 to 0.93). There was no difference on days of unsanctioned opioid use (standardised mean difference (SMD) -0.31, 95% CI -0.66 to 0.04). There was moderate quality evidence favouring buprenorphine maintenance over detoxification or psychological treatment on retention in treatment (RR 0.33, 95% CI 0.23 to 0.47). There was moderate quality evidence favouring buprenorphine maintenance over detoxification or psychological treatment on adverse events (RR 0.19, 95% CI 0.06 to 0.57).
The main weaknesses in the quality of the data was the use of open-label study designs.
There was low to moderate quality evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine appeared equally effective. Maintenance treatment with buprenorphine appeared more effective than detoxification or psychological treatments.
Due to the overall low to moderate quality of the evidence and small sample sizes, there is the possibility that the further research may change these findings.
Plain language summary
Opioid maintenance medicines for the treatment of dependence on opioid pain medicines
Use of pharmaceutical opioids (medicines that are used to treat pain) has increased dramatically in some parts of the world since the mid-1990s. With the increased use, there has been increasing numbers of people seeking treatment for dependence (addiction) on pharmaceutical opioids. Currently, most treatment guidelines are based on research that was conducted in people who were dependent on heroin (a highly addictive opioid). This review sought to compare different opioid agonist maintenance treatments (i.e. treatments such as methadone or buprenorphine that are given for at least 30 days to help the person to reduce their unsanctioned drug use) for the treatment of pharmaceutical opioid dependence. We also compared results from maintenance treatment to short term treatments such as detoxification (removal of the drug from the body) or psychological treatments (e.g. talking therapy, counselling).
We examined the scientific literature up to May 2015. We identified six randomised controlled trials (studies where people were allocated at random to one of two or more treatment or control conditions) involving 607 people who were dependent on pharmaceutical opioids. The people in the study were 77% male and had an average age of 31.6 years. The average duration of the studies comparing different opioid maintenance treatments (three studies that compared methadone to buprenorphine) was 24 weeks, and the average duration of studies comparing a maintenance treatment (three studies with buprenorphine maintenance) to detoxification or psychological treatment was 10 weeks. Five of the six studies were conducted in the US, with one study from Iran.
We looked at opioid use and leaving treatment early.
Five of the studies were funded by the National Institute of Health (USA), with one study not reporting the funding source. Four studies reported that a drug company provided the medicine.
We found that there is probably little or no difference between how well methadone and buprenorphine worked to keep people in treatment, to reduce opioid use, or side effects. We found that buprenorphine probably keeps more people in treatment, may reduce use of opioids, and has fewer side effects compared to detoxification or psychological treatment alone.
Quality of the evidence
Overall, the evidence was of low to moderate quality. All studies put people into treatment groups randomly, but the participants and researchers knew which medication the participants were taking, which could bias the results and lower the quality of the evidence. Some of the studies had reasonable numbers of people who did not finish the study in both treatment groups, which means there are some missing results, but the number of people with missing results was similar in both treatment groups of the study for most studies. Most of the studies were similar in design and results were collected in a way that allowed them to compare opioid use and number of people completing the study.