The development of addiction remains poorly understood, but evidence now supports the proposition that opioid addiction has a physiologic basis influenced by both genetics and the environment. Much addiction research has focused on an apparent “reward pathway” of the mesolimbic system, where opioidmediated dopamine pathways help to generate the positive-feedback system that supports species-sustaining activities such as eating and procreation. The central role of endogenous opioids to this system suggests the mechanism by which the drive to administer exogenous opioids can become as intense as the drives for food and sex.

Changes that have been observed in association with chronic administration of opioids include physical atrophy of dopamine-producing neurons in the ventral tegmental area. Such changes may account for some of the aversive symptoms of opioid withdrawal. It is theorized that neuroadaptations to chronic drug exposure may also lead to the long-term anhedonia that many opioid users experience and may explain why sustained abstinence is so difficult for many users.¹

In 1997, a National Institutes of Health (NIH) consensus development panel concluded that methadone maintenance is the most effective treatment for opioid addiction.² Methadone is initiated at 20 to 40 mg and gradually increased until the patient reports clinical comfort and urine screens are free of other opioids. Most studies suggest that patients generally require a methadone dosage of 60 to 120 mg per day to stop using and craving heroin, although some patients respond to lower dosages and others require much higher dosages.³

Methadone maintenance is a long-term therapy. The majority of patients who discontinue methadone relapse to heroin use, and no factors reliably predict which opioid-dependent patients may do well without pharmacotherapy.⁴ Long-term methadone treatment has no major adverse effects. Constipation and increased sweating are the most common side effects, and they tend to diminish over time. Because methadone can be used safely during pregnancy, it is the treatment of choice in opioid-dependent pregnant women.³ Physicians need to be aware of methadone's interactions with other drugs and should be alert for information about possible interactions as new medications are introduced.

Studies have found that persons on methadone maintenance are three to six times less likely to become infected with the human immunodeficiency virus (HIV), even if they continue to use drugs.^5,6 One study compared heroin addicts who were receiving methadone maintenance treatment with heroin addicts who were not receiving this treatment.⁶ Follow-up of HIV-negative patients over 18 months showed seroconversion rates of 3.5 percent among those who remained on methadone versus 22 percent among those who were not treated with methadone. Heroin addicts who are already infected with HIV also benefit from methadone treatment. One study⁵ found that HIV-positive patients with a history of heroin addiction who were receiving methadone maintenance were less likely to be hospitalized than their counterparts who were not taking methadone.⁷

Regulations require frequent attendance at methadone programs, and the number of methadone maintenance spots is highly restricted. Many patients are required to attend six to seven days per week, and only after three years can patients who are considered to be socially rehabilitated decrease their attendance to weekly. Thus, many patients have no access to treatment, and others are deterred by the strict regulations. The NIH Consensus Report stated, “The unnecessary regulations of methadone maintenance therapy and other long-acting opiate agonist treatment programs should be reduced, and coverage for these programs should be a required benefit in public and private insurance programs.”² In March 2001, the federal regulations were modified, allowing more liberal take-home privileges. Each state has the option of adopting these regulations.”⁸

As Krambeer and associates⁹ note in their article on methadone therapy, which appears in this issue of American Family Physician, there is a move toward a greater role for office-based prescribing, also termed “office-based opioid therapy.” In New York City, a highly successful pilot project has been operating for more than 15 years. A federal waiver allows stable patients to participate in “medical maintenance” through monthly visits to a primary care physician, from whom they receive methadone in addition to regular medical care.³

Until office-based prescribing becomes common, primary care physicians can play a supportive role in methadone therapy. Because methadone use is highly stigmatized, opioid addicts may require a great deal of education about the benefits of this treatment. Because misconceptions about methadone are widespread, it may be helpful to include family members in educational efforts. Krambeer and associates⁹ suggest that patients become involved in Narcotics Anonymous (NA); however, NA and other similar programs often consider methadone maintenance to be contrary to recovery. In becoming knowledgeable about methadone as a treatment for opioid dependence, the primary care physician can play an important role in bringing this highly effective modality to its full potential.