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Findings on Effective Methadone Dosage

Effective Methadone Dosage

— Vincent P. Dole, M.D., Rockefeller University, New York City

Editor's Note: A pioneer in the use of methadone maintenance for treating opiate addiction, Dr. Dole has been a vital force in the field for more than 25 years. With his colleague Dr. Marie Nyswander, Dr. Dole established the first methadone maintenance program in New York City. When we recently asked Dr. Dole for his thoughts regarding methadone dosage, he offered the following comments for TIE Communiqué readers.

Methadone maintenance treatment for narcotic addiction is being used ineffectively in many clinics. Physicians prescribe inadequate or marginally effective doses on the supposition that a low dose facilitates early withdrawal of the medication and improves the patient's long-term chances for drug-free recovery. Although it seems plausible, this reasoning is not supported by experience.

Relation of low minimal dose to patient failure

On the contrary—clinics that are philosophically committed to minimal dosage have the poorest rates of stopping heroin use by patients in treatment and the highest dropout rates. Virtually all patients who drop out of treatment under these conditions soon return to their previous level of heroin use. This isn't the outcome we'd like to see, but it does reflect reality. In the 27 years since methadone maintenance was introduced, many types of "low dose methadone to abstinence" programs have been started. They have consistently failed to produce positive outcomes for the majority of their patients.

To be sure, some patients do quite well on such relatively low doses as 50 mg per day, but there is no simple test to identify these patients in advance. Contrary to popular wisdom, the optimal dose of methadone for maintenance does not depend on the size of the heroin habit before treatment. It depends only on the rate at which methadone is cleared from the blood in the patient. For effective suppression of the pathological craving for narcotics, the methadone level in the blood must be held above a minimum of about 150 ng/ml by a constant daily oral dose.

Because patients differ significantly in the rate at which they clear methadone from their blood, a low dose can be adequate for some patients and inadequate for many others. Indeed, if the activity of hepatic drug-metabolizing enzymes has been accelerated by interacting medications, such as rifampin, or by other factors, even 100 mg per day might be insufficient to sustain the blood level in the therapeutic range for 24 hours. When it falls below a critical level, the patient experiences abstinence symptoms and is strongly tempted to seek relief by use of illicit opiates.

Reasons for avoiding marginal doses

Fortunately, there is no reason to risk failure by use of marginal doses. Patients can be maintained in a normally functional state over long periods of time without significant narcotic effects on doses as high as 200 mg per day. The tolerance mechanism that blocks the narcotic effect of heroin also blocks the narcotic effect of methadone itself. With such a wide therapeutic range, the only reason for prescribing inadequate doses is a misunderstanding of the relevant pharmacology. Much better results could be obtained by prescribing 80 to 100 mg per day for most patients during the first year of treatment.

The AIDS epidemic has added another urgency to the problem of drug abuse. Now we know that a single use of a contaminated needle and syringe can transmit a fatal disease. Under the circumstances, how can an informed physician be indifferent to the consequences of prescribing inadequate doses of methadone to otherwise intractable addicts?