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Methadone: Handle with Care

Although narcotic abuse is notoriously difficult to manage, with high relapse rates in every setting, methadone maintenance therapy (MMT) has been shown to reduce overall rates of abuse of other drugs, overdose and death, criminal activity, needle sharing, and commercial sex work. Methadone maintenance is a long-term strategy. The drug is provided as a substitute, not a cure, for narcotic abuse. Patients may continue to receive their daily maintenance dose for years. One-year retention rates in several large studies of MMT have ranged from 25% to 60%, while rates of relapse after leaving MMT are high. Stopping methadone use poses the same challenges as quitting any narcotic and should only be done under a doctor’s care.

Methadone is also used to treat heroin withdrawal, an issue for some hospitalized patients. Prescribing methadone for maintenance therapy is limited to federally licensed methadone treatment programs.

A MYSTERIOUS OPIOID

Methadone is a potent synthetic opioid developed in Germany in the late 1930s. It mirrors analgesic effects—and unwanted side effects, such as constipation and respiratory depression—of commonly used opioids such as morphine. But it also has some unique, not fully understood pharmaco-kinetic qualities.

Research at the level of basic science—based on its binding properties to NMDA (n-methyl, d-asparte) receptors in the central nervous system—suggests tantalizing potential for managing hard-to-treat neuropathic pain syndromes. Some experts say, however, that the potential is still largely theoretical and evidence is not yet sufficient to conclusively demonstrate this benefit.2-4

Dosing and equianalgesic conversions are complicated by the fact that methadone’s relative potency, compared with morphine, increases as the volume of analgesic increases. Several studies have recommended a morphine/ methadone ratio of 10:1 for patients taking less than 1,000 mg of oral morphine per day and 15:1 for patients taking more than 1,000 mg of oral morphine.5,6 More recent conversion charts from the End-of-Life/Palliative Education Resource Center at the Medical College of Wisconsin and manufacturer Roxane Laboratories suggest an even greater conversion range: 3:1 or 5:1 for oral morphine doses under 100 mg per day but 20:1 for morphine doses more than 1,000 mg.7

Methadone is more familiar and better tested in the context of treating narcotic withdrawal and dependence. Methadone maintenance therapy (MMT), introduced in 1964, is provided to an estimated 210,000 people with the disease of opioid substance abuse.8 A single daily maintenance dose, administered at one of the country’s 785 federally certified methadone treatment centers, reduces the addict’s appetite for heroin and prevents symptoms of withdrawal, but without heroin’s “high.” The White House Office of National Drug Control Policy calls methadone “a rigorously well-tested medication that is safe and efficacious for the treatment of narcotic withdrawal and dependence.”9 —LB

Complications

There are several critical facets of this drug hospitalists must be aware of:

Unpredictable half-life: Meth­a­­done, relative to other opioids, has high lipid solubility, slow metabolism, and a typical half-life ranging from 15 to 60 hours—although it can be longer. Methadone’s analgesic effect is shorter-lived, so analgesic doses should be given two, three, or four times daily. But the longer half-life means it can take three days or more after the initial dose before the drug’s full effect—on respiration for example—is known. That is why therapeutic doses can build to toxic levels. There is also wide variation in its effects among patients. Guidelines suggest titrating methadone upward for increased analgesic effect should not be attempted until at least three days after the first dose.

Respiratory depression: This is an issue when the drug is initiated in an opioid-naïve patient or is too rapidly titrated. Deaths from methadone have been seen at doses once considered safe. Physicians are cautioned to start patients on low doses while using other, short-acting opioids for breakthrough pain and frequently assessing for signs of overdose or respiratory depression, such as difficulty in breathing, shallow breathing, extreme sleepiness, or inability to think, talk, or walk normally.

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