There are approximately 15-39 million opioid users in the world, (Degenhardt, 2012) and while opioid use is prevalent in a relatively small portion of the global population (0.6-0.8%); it poses significant health problems to both the individual and community. These risks include the spread of infectious disease such as HIV and hepatitis B & C, as well as overdose and death (Degenhardt, 2011; Mather, 2008; Nelson, 2011).

Currently, the main treatment for opioid dependence is methadone maintenance treatment (MMT). Although MMT can result in continued dependence if a dose is skipped due to its lengthy withdrawal process.

A recent Cochrane systematic review (Mattick et al, 2014) investigates the use of buprenorphine maintenance therapy as an alternative. Opposed to methadone and heroin, which are full agonists, buprenorphine is a partial agonist, thus exerting fewer effects on receptor sites. This results in an easier withdrawal phase, due to the longer duration of action and the option of alternate-day dosing.

Methods

A comprehensive search was conducted of the published literature, bibliographic databases, and trial registers. From an identified initial 6,495 studies, the reviewers included 31 studies (5,430 participants) in the final analysis.

• 20 studies compared methadone and buprenorphine
• 11 studies compared buprenorphine and placebo
• 11 studies used flexible-dosing (Fischer, 1999) whereby dosing is titrated to participants’ preference within an upper and lower limit
• 20 studies used fixed-dosing, which did not allow for adjustment of dosing after stabilisation

The primary outcomes of this review included treatment retention, opioid use (self-report and urine screen), other substance use (self-report and urine screen), criminal activity, and mortality. Secondary outcomes included adverse medication effects, and physical and psychological health (Mattick et al, 2014).

Results

Buprenorphine maintenance versus placebo:

• Buprenorphine (all doses 2mg to ≥16mg) was more effective than placebo at patient retention
• Only high dose Buprenorphine (≥16mg) was more effective than placebo in supressing illicit opioid use (measured by urinalysis)

Buprenorphine maintenance versus methadone maintenance:

• Buprenorphine in flexible doses was less effective than methadone in retaining participants, nor was a difference observed in the suppression of opioid use for the participants who remained in treatment (measured by urinalysis)
• In low-dose studies, methadone (≤40mg) was more likely to retain participants than low-dose Buprenorphine (2-6mg)
• There was no difference between medium-dose buprenorphine (7-15mg) and methadone (40-85mg) in retention or suppression of illicit opioid use
• Additionally, there was no difference between high dose buprenorphine (≥16mg) and methadone (≥85mg) in retention or heroin use

Discussion

• While this review shows that high-dose buprenorphine is an effective maintenance treatment for heroin compared to placebo, fixed flexible-dosing methadone proved more superior to buprenorphine at participant retention
• Additionally, as flexible dosing is uncommon in clinical practice, the fixed dosing findings are more relevant to primary care (Mattick et al, 2014)
• As both maintenance therapies are effective in the suppression of heroin use, buprenorphine should be supported in cases where methadone cannot be tolerated or administered
• Additionally, buprenorphine could be provided as an alternative choice to the patient, when they may circumstantially benefit from the alternate-day dosing, not permitted in methadone maintenance (Mattick et al, 2014)

Links

Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD002207. DOI: 10.1002/14651858.CD002207

Degenhardt L, Hall W. Extent of illicit drug use and dependence, and their contribution to the global burden of disease. Lancet 2012;379(9810):55–70. [PubMed abstract]

Degenhardt L, Bucello C, Mathers B, Briegleb C, Ali H, Hickman M, et al. Mortality among regular or dependent users of heroin and other opioids: A systematic review and meta-analysis of cohort studies. Addiction 2011;106(1): 32–51. [PubMed abstract]

Mathers BM, Degenhardt L, Phillips B, Wiessing L, Hickman M, Strathdee SA, et al. Global epidemiology of  injecting drug use and HIV among people who inject drugs: a systematic review. Lancet 2008;372(9651):1733–45. [PubMed abstract]

Nelson PK, Mathers BM, Cowie B, Hagan H, Des Jarlais D, Horyniak D, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet 2011;378(9791):571–83. [PubMed abstract]

Fischer G, Gombas W, Eder H, Jagsch R, Peternell A, Stuhlinger G, et al. Buprenorphine versus methadone maintenance for the treatment of opioid dependence. Addiction 1999;94(9):1337–47. [PubMed abstract]