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Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Buprenorphine (Subutex) was licensed in the UK for the treatment of opiate dependence in 1998 after studies found it to be less addictive than methadone and much safer in overdosage (1). Buprenorphine has been previously been used in lower dosage as an analgesic preparation (Temgesic).

There is evidence that the withdrawal syndrome is milder on discontinuing buprenorphine than methadone, and also that fewer symptoms emerge during detoxification with buprenorphine (2).

A systematic review concluded 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 (3).

Buprenorphine has both partial opioid agonist and opioid antagonist activity, and provides a milder, less euphoric and less sedating effect than full opioid agonists such as diamorphine or methadone (although these effects are less pronounced with methadone than with diamorphine) (4).

  • in the management of opioid dependence, sublingual tablets are used at an initial recommended once-daily dose of 0.8-4 mg, adjusted according to response. In practice, a starting dose of more than 4 mg/day is often used, with an adequate maintenance dose being in the range 12-24 mg/day. The maximum daily dose is 32 mg (4)
  • buprenorphine also has a relatively good safety profile. Even higher than normal therapeutic doses rarely result in clinically significant respiratory depression because of its partial agonist activity at the opioid receptor involved (mu)
    • safety of buprenorphine mixed with high doses of other sedative drugs such as alcohol or benzodiazepines remains unclear
  • starting buprenorphine treatment in opioid-dependent people may precipitate symptoms of withdrawal because buprenorphine displaces any residual illicit opioid agonists from receptors and because its partial agonist activity reduces the stimulation of receptors
    • also, whereas methadone is an agonist, buprenorphine is an antagonist at the receptor subtype involved in mood (kappa), which may mean that it produces less dysphoria
  • buprenorphine has abuse potential, as tablets can be crushed and then injected

Cautions include:

  • asthma, respiratory of hepatic insufficiency; perform regular liver function tests - withdraw if jaundice or hepatic necrosis develop; pregnancy

Contraindications include:

  • severe hepatic or respiratory insufficiency, acute alcoholism, delirium tremens, patients < 16 years, breast feeding

Interactions include:

  • alcohol, MAOIs, CNS depressants, other opiods, benzodiazepines, clonidine, antihistamines

Side effects include:

  • headache, insomnia, constipation, asthenia, nausea, drowsiness, orthostatic hypotension, dizziness, sweating; other possible side effects include withdrawal symptoms, hallucinations

Methadone or buprenorphine in the management of opioid dependence

  • a review of 83 RCTs & 193 observational studies (total > 1 million participants) found, at timepoints beyond 1 month, retention in treatment was better for methadone vs buprenorphine (5)
    • 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

The summary of product characteristics should be consulted before prescribing this drug.


  1. Seivewright N. More than methadone? The case for other substitute drugs. In: Community treatment of drug misuse: more than methadone. Cambridge: Cambridge University Press, 2000, 49-81
  2. Bicel WK, Amass L. Buprenorphine treatment of opiod dependence: a review. Exer Clin Psychopharmacol 1995; 3: 477-89.
  3. Mattick RP et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2004; (3): CD002207.
  4. NICE (January 2007).Methadone and buprenorphine for the management of opioid dependence
  5. 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.

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