Once used mainly in addiction treatment centers to replace heroin, methadone is today being given out by family doctors, osteopaths and nurse practitioners for throbbing backs, joint injuries and a host of other severe pains.
But too few doctors, experts say, understand how slowly methadone is metabolized and how greatly patients differ in their responses. Some prescribe too much too fast, allowing methadone to build to dangerous levels; some fail to warn patients of the potential dangers of mixing methadone with alcohol or sedatives, or do not keep in contact during the perilous initial week on the drug. And some patients do not follow the doctor's orders.
From 1998 to 2006, the number of methadone prescriptions increased by 700 percent, according to Drug Enforcement Administration figures, flooding parts of the country where it had rarely been seen, write Eerik Eckholm and Olga Pierce in New York Times.
"This is a wonderful medicine used appropriately, but an unforgiving medicine used inappropriately," Dr. Howard A. Heit, a pain specialist at Georgetown University says. "Many legitimate patients, following the direction of the doctor, have run into trouble with methadone, including death."
It is implicated in more than twice as many deaths as heroin, and is rivaling or surpassing the tolls of painkillers like OxyContin and Vicodin.
Between 1999 and 2005, deaths that had methadone listed as a contributor increased nearly fivefold, to 4,462, a number that federal statisticians say is understated since states do not always specify the drugs in overdoses. Florida alone, which keeps detailed data, listed methadone as a cause in 785 deaths in 2007, up from 367 in 2003. In most cases it was mixed with other drugs like sedatives that increased the risks.
The rise of methadone is in part because of a major change in medical attitudes in the 1990s, as doctors accepted that debilitating pain was often undertreated. Insurance plans embraced methadone as a generic, cheaper alternative to other long-lasting painkillers like OxyContin, and many doctors switched to prescribing it because it seemed less controversial and perhaps less prone to abuse than OxyContin.
Federal regulators acknowledge that they were slow to recognize the dangers of newly widespread methadone prescribing and to confront physician ignorance about the drug.
"Those problems were not soon recognized," said Dr. Bob Rappaport, a division director at the Food and Drug Administration. He added: "Methadone is an extremely difficult drug to use, even for specialists. People were using it rather blithely for several years."
Ironically the F.D.A-approved package insert for methadone for decades recommended starting doses for pain at up to 80 mg per day. "This could unequivocally cause death in patients who have not recently been using narcotics," said Dr. Robert G. Newman, former president of Beth Israel Medical Center in New York and an expert in addiction.
In November 2006, after reports of overdoses and deaths among pain patients multiplied and The Charleston Gazette reported on the dangerous package instructions, the F.D.A. cut the recommended starting limit to no more than 30 mg per day. "As soon as we became aware of deaths due to misprescribing for pain patients, we began the process of instituting label changes," Dr. Rappaport said.
This year the federal government started sponsoring voluntary classes that teach doctors the elaborate precautions they should take with methadone, like inching upward from low starting doses and screening patients for addictive behavior.
Methadone creates dependency and is sometimes sought by abusers who say they experience a special buzz when mixing it with Xanax.
While the greatest numbers of methadone-related deaths have occurred among the middle-aged, the fastest growth an eleven-fold jump between 1999 and 2005, to 615 occurred among those age 14 to 24, which experts say may be mainly a result of pill abuse.
A majority of victims also used large quantities of alcohol or benzodiazepine sedatives but few would have died without an opioid as the primary culprit.
Dr. H. Westley Clark, director of the Center for Substance Abuse Treatment of Substance Abuse and Mental Health Services Administration (SAMHSA), "We know that a significant share of the methadone deaths involve doctors making well-intended prescriptions."
Since April, SAMHSA has sponsored nine voluntary training courses on the safe prescribing of opioids, and many more are planned, though they will only reach a fraction of prescribers. The agency is also contracting with the American Society on Addiction Medicine to set up a mentoring program, through which prescribing physicians can receive expert advice.