Tolerance to methadone

For patients entering treatment from an institution where they have been drug-free, initial daily methadone doses should be no more than 20 mg. Otherwise initial daily doses of 30-40 mg should be sufficient to obtain the necessary balance between withdrawal and narcotic symptoms. Thereafter, stabilization is achieved by gradually increasing the dose. When methadone is given in adequate oral doses (usually 60 mg/day or more), a single dose in a stabilized patient lasts 24-36 hours, without creating euphoria and sedation. Tolerance to methadone seems to remain steady, and patients can be maintained on the same dose, in some cases for more than 20 years. 

Cross-tolerance A condition where an individual who is tolerant to the pharmacological effects of one member of a drug family also shows tolerance to other members of that family. Cross-dependence allows drug substitution during detoxification (e.g., methadone for heroin or clomethiazole for ethanol), so reducing the severity and potential danger of withdrawal symptoms. 

There are two main treatments for the opiate withdrawal syndrome. One is replacement therapy with methadone or other X agonists that have a longer half-life than heroin or morphine, and produce mild stimulation rather than euphoria. They also produce cross-tolerance to heroin, lessening heroin s effect if patients relapse. Withdrawal is also treated with the 0C2 agonist clonidine, which inhibits LC neurons, thus counteracting autonomic effects of opiate withdrawal — such as nausea, vomiting, cramps, sweating, tachycardia and hypertension — that are due in part to loss of opiate inhibition of LC neurons. 

The patient who uses methadone long-term may develop a tolerance to the drug s analgesic effect and physical dependence. 

Another important side effect of all opiates on the central nervous system is respiratory depression. This is caused by an inhibitory effect on the brain stem, which is the part of the brain that controls breathing and other involuntary bodily systems such as heart beat, etc. Like nausea and vomiting, people who take methadone and other opiates normally develop a tolerance to this side effect. However, even people who have taken methadone for a long period of time can develop major respiratory depression. 

Methadone is extensively used in opioid withdrawal and maintenance programs (see Drug tolerance in this monograph), and has been safely used for this purpose in pregnancy, with only mild effects on the offspring (41). However, fetal exposure to methadone in utero can cause a neonatal abstinence syndrome after delivery. 

Tolerance to the narcotic properties of methadone develops within 4—6 weeks, but tolerance to the autonomic effects (for example constipation and sweating) develops more slowly. 

Mercadante S, Casuccio A, Fulfaro F, Groff L, Boffi R, Villari P, Gebbia V, Ripamonti C. Switching from morphine to methadone to improve analgesia and tolerability in cancer patients a prospective study. J Clin Oncol 2001 19(11) 2898—904. 

Doverty M, Somogyi AA, White JM, Bochner F, Beare CH, Menelaou A, Ling W. Methadone maintenance patients are cross-tolerant to the antinociceptive effects of morphine. Pain 2001 93(2) 155-63. 

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