The number of Americans who died of overdoses of the prescription drug methadone rose 213 percent in the four years between 1999 and 2002, according to a new analysis by researchers at the Centers for Disease Control and Prevention.Methadone accounts for more than one-third of all deaths from opioid drugs, according to the report in the journal Pharmacoepidemiology and Drug Safety.The remaining two-thirds were divided among other opioid painkillers and synthetic narcotics, including codeine, oxycodone, hydrocodone, morphine, hydromorphone, fentanyl and meperidine.Routine surveillance at the CDC showed a recent increase in deaths caused by these drugs, study co-author Leonard Paulozzi said in a telephone interview with the Sunday Gazette-Mail.?We decided to dig deeper into what was causing the increase,? he said.Researchers found that opioid painkillers caused 91 percent more deaths in 2002 than four years before ? far more than heroin or cocaine, according to death certificates.At the same time, doctors were writing more prescriptions for opioid painkillers, and that ?may have inadvertently contributed? to the deaths, the study found.The rise in methadone deaths was more than double that of other opioids and synthetic narcotics.A recent Sunday Gazette-Mail series revealed the same trend: Methadone was involved in the deaths of three times as many Americans in 2003 as in 1999, according to death certificates.The Gazette-Mail also found that methadone sales have increased almost tenfold over the past decade.Traditionally, methadone was used mostly to treat drug abusers, calming their cravings for heroin and other drugs.Recently, doctors have been prescribing it more often to treat pain. It is cheap and effective, but it has unique pharmacologic properties that can be deadly.The jump in methadone deaths rose along with prescriptions for methadone painkillers ? not methadone from drug treatment clinics, the study found. It cited two other studies that found the same thing.Comparing methadone sales with that of other drugs is tricky. A few milligrams of methadone are more powerful than hundreds of milligrams of some other opioid painkillers.So CDC researchers converted the drugs to ?morphine equivalents? ? the number of milligrams of morphine that is the painkilling equivalent of one milligram of each drug ? and then compared sales.Sales of methadone painkillers (not including methadone sold for drug treatment) rose 175 percent, more than any other opioid.And methadone was the only drug category that had more deaths per sale in 2002 than in 1999.The study probably underestimated the number of opioid deaths, researchers said. For example, the researchers didn?t include any deaths that medical examiners attributed to ?unspecified narcotics,? although those narcotics might have been opioids.Government officials and health professionals need to find ways to reduce the numbers of overdose deaths from opioid painkillers without diminishing the quality of care for patients in pain, the study concluded.?The issue is complicated,? Paulozzi told the Gazette-Mail. ?It does involve public health agencies like ourselves,? as well as other federal agencies including the Drug Enforcement Agency.In 2004, the U.S. Food and Drug Administration announced a new prescription-drug safety plan targeted at opioids. But the study noted ?anecdotal evidence from 2005 that the problem of non-medical use of opioids is worsening,? and said ?additional corrective actions may be necessary.?In a 2004 announcement of its new prescription-drug safety plan, the FDA said it ?will ensure that labeling clearly relays conditions for safe and effective use.?But the Gazette-Mail investigation found that the package insert that comes with each bottle of methadone pain pills includes a ?usual adult dosage? that several studies say could be deadly. The FDA approved the package insert.An FDA spokeswoman told the Gazette-Mail that the agency was working with methadone manufacturers to change the labeling. One of the largest methadone manufacturers told the Gazette-Mail it had not been contacted by the FDA on that issue. The FDA has not responded to a Freedom of Information Act request for public information about the actions it has taken to change the methadone labeling.To read the rest of the series, The Killer Cure, go to www.wvgazette.com/section/Series/The Killer Cure. To contact staff writers Scott Finn or Tara Tuckwiller, use e-mail or call 357-4323 or 348-5189.