Methadone

Methadone is a synthetic opioid used primarily for substitution therapy in heroin or opiate addiction. It can also be used to treat neuropathic pain.

PharmacodynamicsLike other opioids, methadone binds to µ-opioid receptors. In the context of substitution therapy, this leads on the one hand to suppression of withdrawal symptoms. On the other hand, when oral substitution therapy is administered over a long period of time, tolerance build-up suppresses intoxication effects and reduces cravings for heroin or other opiates. At a dose of about 60 mg and above, opioid blockade is achieved, at which point additional use of other opiates or heroin no longer has any effect. The analgesic effect in neuropathic pain is explained by antagonism at NMDA receptors.

PharmacokineticsWhen taken orally, bioavailability is about 90%, and plasma concentrations peak after two to four hours. In the blood, 85% of the opioid is bound to plasma proteins. The long half-life of 13 to 47 hours makes methadone ideal for long-acting substitution therapy. The drug is metabolized in the liver, followed by excretion in the urine.

InteractionsSimultaneous use of alcohol, antidepressants, benzodiazepines or barbiturates can increase the central attenuation of the opioid and thus trigger serious or even life-threatening side effects.

Side effectsDue to central attenuation, methadone often leads to fatigue, headaches or dizziness. In addition, constipation, urinary dysfunction, and psychological symptoms such as depression, anxiety and panic disorders, or hallucinations may occur. In case of overdose, respiratory arrest may be induced by the respiratory depressant effect, and circulatory failure, shock and convulsions may also occur.

Toxicological dataA median lethal dose of 86 mg/kg was observed in rats when administered orally. In infants, as little as 10 mg and in adults, 40 to 50 mg may be lethal. Patients should therefore be closely monitored for signs of overdose, especially at the beginning of substitution therapy.