Choosing between buprenorphine and methadone in the treatment of opioid dependence

• a Cochrane systematic review for maintenance treatment evaluated the effects of buprenorphine maintenance against placebo and methadone maintenance in retaining patients in treatment and in suppressing illicit drug use. Cochrane meta-analysis found the following results:
  • at average/common methadone doses currently used in the UK (30 to 60 mg) buprenorphine can achieve broadly comparable outcomes. Specifically, buprenorphine given in flexible doses appeared statistically significantly less effective than methadone in retaining patients in treatment, but there was a trend (not significant) for less heroin use in buprenorphine groups compared with methadone groups
  • optimal doses of methadone (e.g. 80 to 120 mg) are still the gold standard for maintenance
  • efficacy of high-dose buprenorphine (16 to 32 mg) compared with higher-dose methadone (80 to 120 mg) had not been examined in comparative studies
  • the reviewers conclude that buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is not more effective than methadone at adequate dosages. Also, buprenorphine is not significantly different from methadone in the impact on other substance use (e.g. cocaine, benzodiazepines, alcohol)

With similar outcomes, the choice between methadone and buprenorphine should be informed by other factors (2)

• there is limited evidence of the superiority of either medication for particular subgroups, and the decision as to which medication to use should be made in consultation with each patient after consideration of the relative merits of each medication

There appears to be increasing consensus among clinicians experienced in choosing both buprenorphine and methadone that (2):

• buprenorphine may be better suited to those who wish to cease using heroin completely, as the blockade effects of even moderate-dose buprenorphine interfere with the subjective effects of additional heroin use. In contrast, whilst high-dose methadone treatment is also well suited to those who wish to stop using heroin, those patients who wish to continue to use heroin may prefer low-dose methadone treatment
• withdrawal from buprenorphine appears to be easier than from methadone, and as such may be preferred for those considering a detoxification program
• the transition from buprenorphine to naltrexone can be accomplished much earlier than the transition from methadone to naltrexone, and consequently, those considering naltrexone treatment after detoxification may be better suited to buprenorphine
• buprenorphine is less affected by interactions with hepatic enzyme inducers/inhibitors (anti-convulsants, rifampicin, ribavirin)
• buprenorphine is less sedating than methadone. This may be positive or negative for different patients
• using buprenorphine alone is safer in overdose. Patients who are not responding well to adequate doses of methadone or buprenorphine, or who are experiencing persistent unwanted effects or difficulties with their medication may benefit from transferring to the other medication or referral to a specialist practitioner for review. It should be emphasised that patients doing well on either methadone or buprenorphine should remain on that medication

A systematic review revealed that (3):

• buprenorphine given in flexible doses was statistically significantly less effective than methadone in retaining patients in treatment (RR= 0.80; 95% CI: 0.68 - 0.95), but no different in suppression of opioid use for those who remained in treatment
• low dose methadone is more likely to retain patients than low-dose buprenorphine (RR= 0.67; 95% CI: 0.52 - 0.87)
• medium dose buprenorphine does not retain more patients than low-dose methadone but may suppress heroin use better. There was no advantage for medium-dose buprenorphine over medium-dose methadone in retention (RR=0.79; 95% CI: 0.64 - 0.99) and medium-dose buprenorphine was inferior in suppression of heroin use
• the study authors stated that buprenorphine is an effective intervention for use in the maintenance treatment of heroin dependence, but it is less effective than methadone delivered at adequate dosages

A review of 83 RCTs and 193 observational studies (total > 1 million participants) found, at time points beyond 1 month, retention in treatment was better for methadone vs buprenorphine (4)

• also found evidence of reduced cocaine use, cravings, anxiety, and cardiac dysfunction, as well as increased treatment satisfaction among people receiving buprenorphine compared with methadone
• evidence of reduced hospitalisation and alcohol use in people receiving methadone
• note though that most comparisons were based on small numbers of studies

A review of the use of buprenorphine for opioid use disorder stated (5):

• buprenorphine is associated with reduced opioid use and risk of HIV and hepatitis C, lowers all-cause mortality and opioid overdose risk by 60%, and increases treatment retention
• the number needed to treat for buprenorphine to prevent 1 fatal opioid overdose is 52.6; for comparison, the number needed to treat for aspirin to prevent 1 nonfatal myocardial infarction is 333

Notes (6):

• NICE states that either methadone or buprenorphine should be offered as the first-line treatment in opioid detoxification. When deciding between these medications, healthcare professionals should take into account:
  • whether the service user is receiving maintenance treatment with methadone or buprenorphine; if so, opioid detoxification should normally be started with the same medication
  • the preference of the service user
• lofexidine may be considered for people:
  • who have made an informed and clinically appropriate decision not to use methadone or buprenorphine for detoxification
  • who have made an informed and clinically appropriate decision to detoxify within a short period
  • with mild or uncertain dependence (including young people)
• clonidine should not be used routinely in opioid detoxification
• dihydrocodeine should not be used routinely in opioid detoxification

Reference:

1. Mattick RP et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2004; (3): CD002207.
2. Royal College of General Practitioners (UK). Guidance for the use of buprenorphine for the treatment of opioid dependence in primary care, second edition 2004.
3. Mattick RP et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD002207
4. Degenhardt L et al. Buprenorphine versus methadone for the treatment of opioid dependence: a systematic review and meta-analysis of randomised and observational studies. Lancet Psychiatry May 8th 2023.
5. Weimer MB, Morford KL. Buprenorphine for Opioid Use Disorder—An Essential Medical Treatment. JAMA Intern Med. Published online August 26, 2024.
6. NICE (July 2007). Drug misuse - Opioid detoxification