Methadone is a synthetic opiate used primarily for detoxification and maintenance in patients who are dependent on opiates, mainly heroin, and in the treatment of chronic severe pain. In the United States, physicians can prescribe methadone for analgesia as a schedule II drug. However, its use as a treatment for drug dependence is restricted to practitioners, clinics and pharmacies licensed by the U.S. Food and Drug Administration for this purpose. Anderson and Kearney review current issues regarding methadone use.

Methadone's mechanism of action is well known, as are the risks of physical dependence and tolerance after repeated use. Its pharmacology accounts for its analgesic and antitussive properties, along with adverse effects such as respiratory depression, decreased bowel motility, miotic pupils, nausea and hypotension. Nalaxone can reverse toxic effects of methadone resulting from an overdose. After abrupt discontinuation or administration of an antagonist such as naloxone, an abstinence syndrome can develop, consisting of lacrimation, rhinorrhea, sneezing, nausea, vomiting, fever, chills, tremor and tachycardia.

Methadone is commonly prescribed as maintenance therapy for heroin addicts because its long half-life delays the abstinence syndrome, making its effects less severe, and because it blocks the euphoric effects of and cravings for heroin. In addition, methadone use is linked to decreases in illicit heroin use and in the incidence of infectious disease among addicts. Maintenance therapy usually is started at 10 to 20 mg of methadone (5 mg of parenteral heroin is approximately equivalent to 20 mg of oral methadone) and is increased in 10-mg increments until withdrawal symptoms are controlled. Patients often require 80 to 100 mg daily to minimize illicit intravenous heroin use. Detoxification involves tapering the dosage with the goal of achieving a drug-free state. Withdrawal symptoms must be carefully controlled during detoxification. Unfortunately, the recidivism rate after detoxification remains high.

Methadone is a good alternative to morphine sulfate for pain management, particularly parenteral methadone, which is about twice as potent as oral methadone. Because analgesia is not related to serum half-life, frequent daily dosing usually is needed for pain management. The normal adult dosage for acute severe pain is 2.5 to 10 mg every three to four hours as needed and 5 to 20 mg every six to eight hours for severe chronic pain. Dosing should be individualized to meet the needs of the patient. The relative equivalent analgesic dose of morphine to methadone varies from 1:1 to 14:1 (14 mg of morphine to 1 mg of methadone).

Methadone crosses the placenta and can cause fetal dependence; therefore, its use in pregnant women should be limited to those with opioid dependence. Detoxification is not recommended during pregnancy because fetal distress can occur. However, women who are dependent on opioids do better with methadone than with no treatment. The advantages include longer gestational periods and higher birth weights, as well as a more moderate abstinence syndrome in the neonate.

The potential difficulties associated with methadone therapy include the need for longer observation periods following overdose because of its longer half-life and variations in pharmacokinetics in infants and the elderly. The most serious adverse effect is the potential for apnea, respiratory failure and hypoxia, leading to coma or death. Other adverse effects associated with long-term use of methadone can include increased sweating, constipation, appetite disturbance, sexual dysfunction, abnormal menses, urinary retention, blurred vision, biliary pain, insomnia, gynecomastia and hepatotoxicity.

The authors conclude that long-term methadone use in patients who are dependent on opioids has substantial societal benefits, including decreased transmission of infectious disease, health care costs and criminal activity. Obstacles to methadone treatment include restrictive government regulations, the stigma of opioid addiction and the inadequate number of health care providers and clinics offering this therapy to patients who would benefit.

editor's note: In the United States, methadone can be given for treatment of heroin abuse only by specially certified methadone-maintenance clinics. In England, primary care physicians prescribe methadone for their patients, who often take their regular doses under the supervision of the pharmacist dispensing the medication. The latter system makes methadone treatment more accessible and decreases the stigma associated with maintenance therapy. Currently, a few pilot studies following the same protocol are underway in the United States. In addition, the use of alternative agents, such as buprenophine, is being explored in the primary care setting. Moving the management of heroin addiction into the primary care office can help by increasing access, but appropriate patient support programs must be available, including employment assistance and counseling for alcohol, legal, social and psychiatric problems.—r.s.