There are four medicines commonly used specifically to prevent relapse to substance misuse, these being naltrexone, disulfiram, acamprosate and buproprion (see Section C4, page 25). Naltrexone is only licensed for the prevention of relapse to opiate misuse (in the UK), although there is increasing evidence to suggest that it is also effective in the prevention of relapse to alcohol misuse.Acamprosate and disulfiram are used solely to aid in prevention of relapse to alcohol misuse; buproprion aids in the prevention of relapse to nicotine misuse.

Naltrexone is an opiate receptor antagonist licensed in this country for the prevention of relapse to opioid drug misuse. It works by blocking the opiate mu (µ) receptor, preventing its activation by opioid receptor agonists such as heroin and methadone. Naltrexone is also sometimes used for prevention of relapse to alcohol, but is not licensed for this currently in the UK. It is usually prescribed orally, although a subcutaneous implant preparation is also available; the implant formulation has clear common-sense advantages for compliance, although it has not been researched in depth, and is currently available only in the private sector.A depot formulation is being trialled in the USA.

EFFECTIVENESS

Claims have been made that mean retention on naltrexone treatment is between one and six months (Kleber H, 1985), depending on patient selection and quality of adjunctive services. However, most studies of naltrexone use have shown high dropout rates and high relapse rates to heroin use (Jaffe J, 1995). A study by Bell et al (1999) found progressive attrition over the 3 month follow-up period with only 20% still using naltrexone after 3 months (one third of these admitted to occasional heroin use on-top of naltrexone). However, another 16% were abstinent without naltrexone use. Of the remaining 64%, 1/3 had relapsed to heroin use (23%), and over a half (37%) were on methadone. One patient had died from heroin overdose. Thus overall, despite the high attrition rate, only one quarter of patients were using illicit drugs in a dependent fashion at three months. This figure is lower than the rates of dependent heroin use commonly reported at 3 months following detoxification without naltrexone prescription.

As a rule of thumb, for an unselected population, maybe 20-40% of patients will be compliant with naltrexone at three months or non-compliant but abstinent from illicit substance misuse. Anecdotal evidence suggests that success is more likely if a carer is available to administer naltrexone and ensure compliance.

A recent Cochrane review (Kirchmayer U et al, 2000) concluded that there was not yet 'sufficient evidence to evaluate the efficacy of naltrexone treatment on opioid dependence, and further studies are needed before making a clear decision on whether to go on using it and enlarge its use as far as possible or to stop its use and concentrate on efficacious alternatives'.

SIDE-EFFECT PROFILE

Hepatotoxicity

In a placebo controlled trial using naltrexone doses sixfold that recommended for blockade of opiate receptors (300mg/day), five of 26 subjects developed elevations of ALT three to nineteen times their baseline values after three to eight weeks of treatment. There was no reaction in the placebo group subjects. All liver function tests returned to (or toward) baseline levels within a matter of weeks from cessation of naltrexone. The subjects with elevated liver enzymes were generally asymptomatic (Kleber H, 1985).

A study of naltrexone (at normal doses of 50mg daily) and methadone on 116 parenteral drug users with hepatitis C infection reported that neither methadone nor naltrexone resulted in increased levels of transaminases (Kleber H, 1985).

No cases of hepatic failure due to naltrexone administration have ever been reported.

DOSAGE GUIDANCE IN ABNORMAL LIVER FUNCTION (KLEBER H, 1985)

• All patients receiving naltrexone should have baseline liver function studies and then repeat tests once a month for the first 4 to 6 months. Patients with baseline liver abnormalities should be tested every 2 weeks for up to 6 weeks before going on to a once a month frequency.
• Do not start naltrexone if the AST is greater than approximately two times normal.
• Discontinue naltrexone if the AST rises to greater than 3 times normal unless some other cause is found (eg alcohol misuse).