A comparison of methadone, buprenorphine and alpha2 adrenergic agonists for opioid detoxification: A mixed treatment comparison meta-analysis☆
Introduction
There have been several Cochrane reviews focusing specifically on buprenorphine, methadone, and the alpha2 adrenergic agonists (see Amato et al., 2004 for a summary of these reviews). Despite the number of trials and meta-analyses on opioid detoxification it is often quite difficult to compare the efficacy of these different interventions. Due to the limitations of standard pairwise meta-analysis, it is very difficult to synthesise these studies in a parsimonious and straightforward manner. Amato et al. (2004) summary of the different Cochrane reviews on opioid detoxification shows the vast number of separate meta-analyses required to summarise the data, and the overlap in studies between these different analyses (10 studies were included in more than one review of opioid detoxification).
Not surprisingly, the conclusions from these meta-analyses are necessarily tentative despite a relatively large number of trials conducted on opioid detoxification. The inevitable difficulty in interpreting the results of such meta-analyses may inadvertently contribute to inconsistency in clinical practice.
A clear and concise synthesis of the data is an important component in facilitating evidence based practice. The complexity of the evidence base on opioid detoxification and the limitations of standard pairwise meta-analysis suggest the use of a more flexible approach to evidence synthesis that is better able to take into account the data fully. An additional benefit of mixed treatment comparison analyses is that it is possible to rank treatments in terms of their likelihood of being the most effective treatment.
The mixed treatment comparison approach has been used recently in the analysis of stroke prevention (Cooper et al., 2006), antidepressants (Cipriani et al., 2009) and psychological interventions in heart disease (Welton et al., 2009). However, this approach has not yet been used in the field of drug misuse. This review seeks to simultaneously compare buprenorphine, methadone, clonidine and lofexidine on completion of detoxification treatment in one meta-analysis assessing both direct and indirect comparisons.
Section snippets
Interventions
The most straightforward pharmacological approach to detoxify a dependent opioid user is by reducing over a period the dose of an opioid substitute medication, such as methadone or buprenorphine. For methadone, more rapid regimes last 7–21 days, while ‘slow tapering’ regimens can last up to 6 months or longer (DH, 2007, National Institute for Health and Clinical Excellence, 2007). Detoxification with buprenorphine is usually faster than with methadone, and can in theory be completed within less
Results
A total of 23 RCTs were identified providing data on 2112 participants (for further details of included and excluded studies, see Fig. 1). Table 1 summarises the study characteristics of these trials. Five trials compared methadone and clonidine, two trials compared methadone and lofexidine, three trials compared methadone and buprenorphine, eight trials compared buprenorphine and clonidine, one trial compared buprenorphine and lofexidine and four trials compared clonidine and lofexidine. Of
Discussion
This present review suggests that buprenorphine and methadone are more effective than the alpha2 adrenergic agonists for opioid detoxification. In addition, it appears buprenorphine may be the most effective detoxification treatment. However, it should be noted that the mixed treatment comparisons between methadone and buprenorphine did not show a statistically significant difference.
These results build upon current systematic reviews using traditional pairwise meta-analysis including the
Role of funding source
No interests to declare.
Contributors
Nothing declared.
Conflict of interest
No conflict declared.
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2020, Journal of Emergency MedicineCitation Excerpt :Buprenorphine is markedly safer than full agonists (such as methadone or hydromorphone) if the patient uses street opioids or sedatives after discharge (137–139). The alternative, which is to discharge the patient without treating withdrawal or to use comparatively ineffective nonagonists (e.g., clonidine) to treat withdrawal, impels the patient to use street opioids, which have become progressively dangerous due to unpredictable adulteration with fentanyl, among other critical hazards (140–143). Even if it is likely that the patient will ultimately return to street opioids, buprenorphine provides comparative safety from overdose, craving, and withdrawal during its therapeutic interval, as well as a period for the patient to contemplate recovery (144).
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Supplementary information on the search strategy for the meta-analysis is available with the online version of this paper at doi:10.1016/j.drugalcdep.2009.12.008.