COMMUNITY PRESCRIBING FOR OPIATE DEPENDENCY

Buprenorphine is a partial agonist at opioid µ receptors. Simplistically speaking this means that at lower doses it has an agonist effect at the µ receptor, whilst at higher doses it has an antagonist effect. Together with its high binding affinity for the µ receptor, this translates into various theoretical benefits for its use in the treatment of opiate drug dependency.

POTENTIAL ADVANTAGES

• One prominent risk of opiate drug use (whether illicit or prescribed) is the potential for respiratory depression and death in overdose. Due to its antagonist effect at higher doses, buprenorphine is thought to be safer in overdose than other opiates such as heroin or methadone.
• One common problem with opiate substitution therapy is the continued use of illicit opiates 'on-top' of prescribed opioids in some patients. Due to its high affinity for the opioid µ receptor, buprenorphine should not be displaced by most abused opiates, theoretically leading to ineffectiveness of illicit drug use and thus to a reduction in illicit drug use by the patient. Equally, due to its partial agonist activity, the use of buprenorphine in doses greater than those prescribed should have little euphorigenic effect, decreasing its abuse potential.
• One advantage of methadone treatment is its ability to stabilise the drug-using pattern of the individual due to its long half-life and once a day dosing schedule. Buprenorphine's high affinity for and prolonged binding to the µ receptor results in a similar effect through a pharmacodynamic rather than pharmacokinetic action. In fact, buprenorphine may be dispensed on a thrice-weekly schedule, which potentially has advantages over methadone in terms of improved compliance, greater normalisation of the patient's daily routine and reduced costs associated with dispensing.

Despite the pharmacological differences between buprenorphine and most other opioids, it should be regarded as posing the same risks as the opioid group in general. These include the risk of overdose leading to respiratory depression and death, the risk of dependency, and the risk of personal misuse of or diversion of prescribed medication.

POTENTIAL DISADVANTAGES

• Due to its antagonism of µ receptors at higher doses, buprenorphine may induce an opiate withdrawal syndrome in patients who are dependent on and concurrently using other opioid drugs. The first dose of buprenorphine should thus be administered at a period after the last use of opioids which is dependent on the duration of action of the particular opioid. In general this will be at about six hours after the last dose of heroin, or 36 hours after the last dose of methadone. An alternative approach is to wait for the onset of opioid withdrawal symptoms before administering the first dose of buprenorphine. Additionally, it is not recommended to commence buprenorphine in subjects on doses of methadone greater than 30mg.
• Whilst buprenorphine is theoretically safer than other opioids in overdose due to its partial agonist activity, it has still been associated with drug-related deaths (usually when taken together with other CNS depressant drugs such as benzodiazepines). Opioid overdose is usually fully reversible by administration of parenteral naloxone, which may be effective for as long as four hours following overdose. However, due to its high affinity for the µ receptor, a buprenorphine associated respiratory depression may be only partially reversible with naloxone.
• Liver function tests should be performed threemonthly due to a theoretical risk of inducing liver disease.

DOSAGE AND PRESCRIBING

Buprenorphine may now be prescribed on a blue FP10 for daily dispensing, (as commonly used for methadone dispensing). If it is to be used in this way, it must always be prescribed as Subutex, as this is the only formulation licensed for the treatment of opiate addiction.

Various dosage regimes have been published. The first dose will be 2mg to 4mg sublingually, following which dosage should be titrated against continuing withdrawal symptoms. The majority of patients are stabilised on a maximum of 8mg daily, although buprenorphine is licensed for use at doses of up to 32mg daily. The above mentioned precautions should be taken when initiating prescribing. One commonly used regime is 2mg on day 1, 4mg on day 2 and 8mg from day 3 onwards.

SLOW REDUCTION REGIMES

There is some evidence to indicate that the use of Subutex in slow community reduction regimes may be significantly more effective than similar methadone regimes. It is too early to make a clear statement regarding this, but it may be considered good practice to institute a slow reduction of Subutex over a period of weeks or months if the patient wishes to follow this route to abstinence.

CONCLUSION

Potential advantages of Subutex over methadone.

• Less likely to be associated with accidental opiate overdose.
• More rapid and safer induction onto 'holding dose'.
• Potential for thrice weekly dosage schedule (as compared to daily).
• Less likely to cause gastric irritation.
• Less associated with stigma of drug addiction.

Theoretically Subutex is also:

• Less likely to be associated with use of illicit opiates 'on-top' of prescribed buprenorphine.
• Less likely to be diverted onto the black market due to its potential to induce withdrawal symptoms in opiate users with heavier usage.

However, while this is theoretically the case, it has as yet to be demonstrated in clinical trials. Additionally, buprenorphine has itself been associated with local epidemics (in Scotland) and is widely available on the black market in France (where it is frequently prescribed).

Potential disadvantages of Subutex as compared to methadone.

• If serious overdose with cardio-respiratory depression does occur, then it may be more difficult to reverse this with naloxone.
• High cost in maintenance as compared to methadone.
• May be less suitable for opiate addicts with heavier opiate use (greater than 1/4 g heroin daily).

Despite its excellent theoretical profile, Subutex has yet to prove itself in the clinical situation. Similar to methadone it has been associated with misuse, dependency, continued use of illicit opioids 'on-top' of prescribed buprenorphine and risk of overdose. It also poses a special risk of potentially reduced reversibility of overdose with naloxone. Furthermore, as it is not a generic drug, it remains much more expensive than methadone which greatly reduces its potential costeffectiveness as a valid alternative to methadone in maintenance therapy. Cost is not such a significant factor in detoxification; however the use of lofexidine for opioid detoxification may be preferred, due to the ability to commence naltrexone during the lofexidine detoxification process, which may lead to lower relapse rates.

None of these drugs are licensed for the treatment of opiate dependency. They should only be prescribed by or following documented advice from a specialist.

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The above information is copyright of Dr Bruce Trathen MBBS MRCPsych (2006). ISBN 0-9545164-0-0. The author grants permission for these guidelines to be downloaded, copied and distributed freely, but does not grant permission for their sale.