Substitution therapy is defined as the administration of a prescribed daily dosage of opioid medicines with long-lasting effects to patients with opioid dependence under medical supervision. Today, drugs used in substitution therapy are mostly methadone and buprenorphine, with morphine and heroine being prescribed less often. In the developed countries, more than half of the patients with opioid dependence are treated with opioid receptor agonists. In 1959, a Canadian doctor Robert Holiday, and later, in 1963, American practitioners Vincent Dole and Marie Nyswander for the first time used methadone in maintenance therapy. In Europe methadone was first administered in 1967 by a Swedish psychiatrist L. Gunne. It was chosen out of a whole range of opioid medications for its good absorbing effects, as it only requires single-daily usage. Expansion of substitution therapy programmes began in the 80ies and 90ies, when an HIV epidemic started to spread with alarming rates.

Prescription of individual doses of medication effectively suppresses the patient’s craving for heroine, and due to the increased tolerance and occupied opioid receptors it blocks euphoric responses caused by heroine use. Doses of substitution therapy are defined for each patient to provide for their subjective comfort.

Medications used
Methadone is a potent agonist of opioid receptors that has different pharmacokinetic properties in comparison to heroine. For substitution therapy it is usually prescribed in the form of a solution or a syrup, and also as pills. It is used as a racemic drug (D-, L-methadone) or a levoisomer (L-methadone, polamidon) which is twice as active as a racemate. Effects of a single dose of methadone last for 24–36 hours. Methadone is usually prescribed once-daily, with the initial daily dose of 20–30 mg that is later increased. It is recommended that in the early stages of treatment the patients remain under medical supervision for 3–4 hours after they are given their dose. Most methadone programmes’ patients receive 60–120 mg of methadone per 24 hours, but some need higher doses (if a patient is a ‘quick metaboliser’). Overall results of methadone substitution therapy are determined by the daily dosing – in the majority of cases it should be no less than 60 mg. When administered regularly, methadone accumulates in fat tissue, creating a depot, and its concentration in blood varies insignificantly. Methadone’s advantages against other substitution drugs are its low cost, single-daily use and good acceptability. Side effects are registered in about 20% of patients and include sweating, constipation, reduced libido and weakened concentration.

Buprenorphine is an agonist-antagonist of opioid receptors that has been used in drug dependence treatment since 1978. In two European countries – France and Finland – buprenorphine is used more often than methadone. High cost is its main disadvantage. According to existing data, buprenorphine is less likely to cause withdrawal symptoms in newborns in contrast to methadone. Buprenorphine use is also associated with much lower risks of deadly overdose, as in high doses it causes antagonistic effects. Daily dosage is from 8 to 32 mg administered sublingually. Its pharmacological characteristics make it possible to use it once a day or every other day.

Benefits of substitution therapy

Benefits of substitution therapy for the community include the following:

• Significant reduction in criminal activities of the patient: no need to find money for drugs.

• Reduced risks of hemocontact infections for the society in general – Hepatitis B and C, HIV – as the patients decrease or avoid injecting practices.

• Reduced levels of promiscuity and sex work among drug using women.

Benefits for the patients include the following:

• Normalisation of life style and improved social functioning.

• Possibility for causal treatment of HIV, Hepatitis B and C.

• Increased availability for social and psychological support.

• Reduced overdose mortality.

• Discontinued or reduced drug injecting.

• Improved physical and mental health.

• Reduced risks of HIV and Hepatitis.

• Distancing from the community of drug users.

 

[1] Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence, WHO, 2009
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