A comparison of methadone, buprenorphine and alpha2 adrenergic agonists for opioid detoxification: A mixed treatment comparison meta-analysis

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Abstract

Objectives

The aim of this systematic review was to compare the efficacy of methadone, buprenorphine, clonidine and lofexidine for opioid detoxification. Mixed treatment comparison meta-analyses were used to synthesise the data as it is designed for data-sets where limitations in standard pairwise meta-analyses make comparisons difficult to interpret.

Data sources

A systematic search was conducted using the following databases: CENTRAL, CINAHL, Embase, HMIC, Medline and PsycINFO.

Review methods

RCTs that included opioid dependent participants over a mean age of 16 receiving opioid detoxification using buprenorphine, methadone, clonidine or lofexidine were included in the systematic review. Included studies were quality assessed and the completion of treatment data was extracted by the author and a research assistant independently. Mixed treatment comparison methods were used to synthesise the data.

Results

There were 23 RCTs included in the systematic review (and 20 included in the meta-analysis) comprising a total of 2112 participants. Buprenorphine and methadone were ranked as the most effective methods of opioid detoxification followed by lofexidine and clonidine respectively.

Conclusion

Buprenorpine and methadone appear to be the most effective detoxification treatments. While the analysis suggests buprenorphine is the most effective method of detoxification there is some uncertainty on whether it is more effective than methadone and requires further research to confirm this result.

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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    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.

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