Over 70-90% of opiate substitution in the EU is delivered in the form of methadone. Buprenorphine is gaining popularity in many countries. It is estimated that approximately 300,000 people are on methadone in Europe, 180,000 in the United States and 20,000 in Australia. There are many countries in the world where different forms of drug substitution take place. However, the bulk of methadone treatment to date is still carried out in Europe, North America and Australia. These overall estimates would suggest that around half a million people receive this type of drug substitution globally.

Methadone (methadone hydrochloride) is a synthetic opioid agonist that has an effect similar to those observed with morphine on humans. Methadone is well absorbed from the gastro-intestinal tract, irrespective of formulation type (e.g. syrup vs. tablet). It has very good bio availability of 80 to 95%. The elimination half-life of methadone has been estimated to be 24 to 36 hours, with considerable variation across individuals (10 to 80 hours). The main site in the body for the biotransformation of methadone is the liver. Methadone is eliminated from the body in the form of metabolites resulting from biotransformation and by excretion of the drug itself in urine and faeces (Ward et al., 1998; Humeniuk, 2000). This pharmacological profile makes methadone useful as a substitute opioid medication, because it allows oral administration, single daily dosage and achievement of steady-state plasma levels after repeated administration with no opioid withdrawal during usual one-day dosing interval.

The rate of metabolism of methadone by the CYP3A4 enzyme affects the clearance of methadone from the body. The expression of the CYP enzyme is influenced by genetic and environmental factors and by certain medications. It is highly variable which can result in methadone toxicity and, at the other extreme, in opioid withdrawal. Certain medications interact with the blood level concentration of methadone and special attention has to be given to people using other medications such as HIV medications, antibiotics, some anti-epileptics and medications that treat tuberculosis as well as alcohol and barbiturates (Preston, 1996; Farrell, 1994; Mattick, 1996; Ward, 1998). This means that doses must be individualised, based on the characteristics of the individual patient.

Side effects
Some people experience side effects. The most common side effects include increased perspiration, constipation, and disturbances of sleep, sex drive and concentration as well as a potential for weight gain. Such undesirable side effects generally occur at the beginning of treatment and ameliorate over time. In some people they persist over longer periods of treatment, but mostly remain without medical consequences. In total, these side effects affect less than 20% of methadone clients. (Swiss Methadone Report, 1996; Preston, 1996).
Methadone is a safe medication. Contrary to what is popularly thought, there are no effects on bone, teeth or organs. However, to detoxify from methadone is considered very difficult and long lasting.

Maintenance or detoxification
Historically, methadone maintenance therapy (MMT) was the earliest form and continues to be the most widely used form of opioid substitution (or replacement) therapy in the United States, Australia and Europe. However, over the years, methadone has increasingly been prescribed as part of a detoxification treatment.

Detoxification programmes provide supervised withdrawal from opioid dependence with methadone (and often combined with other medications) in order to minimise the severity of withdrawal symptoms. Methadone is usually given orally, although it in some countries it is also available in injectable form.

RP Mattick et al. (2002) of the Cochrane Collaboration systematically evaluated studies on the effects of methadone maintenance treatment (MMT) compared with treatments that did not involve opioid-replacement therapy for opioid dependence: i.e., detoxification, drug-free rehabilitation, placebo medication, waiting-list controls. Based on a meta-analysis of outcome results, methadone was statistically about 3 times more effective than non-pharmacological approaches in retaining patients in treatment (3 RCTs, RR=3.05; 95% CI: 1.75-5.35) and MMT reduced heroin use by nearly 70% (3 RCTs, RR=0.32; 95% CI: 0.23-0.44). The reviewers concluded that MMT is an effective intervention for the treatment of heroin dependence as it retains patients in treatment and decreases heroin use better than treatments that do not use medication-assisted opioid-replacement therapy (Cochrane Library August 2002).