A popular painkiller may be more dangerous than we thought.

First created in the 1937, methadone is most well-known for its role in opiate replacement therapy, helping patients wean themselves off morphine, heroin, or other strong opiates. It can also be used on its own as an effective and relatively inexpensive general painkiller, a trend that has been increasing in the last decade. However, this expansion may come at a high cost. A review of medical data from 2009 showed that a disproportionately high amount of fatal overdoses were linked to the drug. Even though methadone only accounted for roughly 1.7% of opiate prescriptions (roughly one out of every sixty), it was involved in more than 30% of fatal overdoses.

This is more than twice as high as the following drug, morphine.

A combination of factors is blamed. For one, methadone has an extremely variable biological half-life. The average person will metabolize half of the drug dose every 22 hours; however, some people can take up to 190 hours (nearly 8 days). Mutations in the cytochrome enzymes P450 CYP3A4, CYP2B6, and CYP2D6 have all been implicated in this variability, as well as drug-drug interactions.

Human error might also be a cause. Methadone, like all opiates, can be habit forming and patients do not always stick to drug regimens. Methadone clinics combat this by strictly watching their patients and administering the prescriptions in single-day doses. However, alternative uses of methadone are often not as carefully shepherded.

“All of the evidence suggests that the increase in methadone deaths is related to the increased use of methadone to treat [general] pain,” said Dr. Thomas R. Frieden, who heads the CDC. “There are plenty of safer alternatives.”  Greater care and personalization are stressed when prescribing methadone for general use.

Toxicity often manifests as irregular heartbeat and breathing difficulties. Nonmedical abuse and illegal sales are also implicated in the rise of overdoses.

Links: Centers for Disease Control and Prevention