A combination of methadone and two anti-depressant drugs killed the 20-year-old son of celebrity Anna Nicole Smith, according to a pathologist hired by the family.Daniel Smith died accidentally from the ?cumulative effect? of taking methadone, Zoloft and Lexapro, said Dr. Cyril Wecht, who conducted Smith?s autopsy in September.And contrary to published reports, Smith did not have a ?low level? of methadone in his system at the time of death, Wecht said. He said he did not yet have a copy of the toxicology report and therefore could not give out the exact amounts in Smith?s system.?They found a significant amount,? Wecht said.Methadone is a powerful painkiller that also can be used to treat people addicted to heroin or prescription drugs. Smith?s death is one of a growing number blamed on the drug.Methadone contributes to more deaths nationwide than any other prescription narcotic, and West Virginia?s methadone death rate is the nation?s highest, a recent Gazette-Mail investigation found.Methadone was a factor in the deaths of 2,992 people in 2003, up from 790 in 1999, according to an analysis of death certificates conducted by the National Center for Health Statistics for the Gazette-Mail.The drug was blamed for more deaths than heroin and about 1,500 fewer deaths than all other narcotic painkillers combined, including oxycodone, fentanyl, morphine and hydrocodone.Criminals and addicts are not the only people dying. Some overdose victims took the drug as prescribed and died anyway. A Utah study found that 42 percent of methadone overdose victims had a valid prescription for the drug.It isn?t clear whether Smith had a prescription for methadone, Wecht said. He had complained to friends about back pain, which methadone is sometimes used to treat, he said.Smith had a prescription for at least one of the anti-depressants, Wecht said.On Sept. 9, Smith flew to the Bahamas to see his mother, a former Playboy model and reality-TV star. She was recovering in a hospital after giving birth to a daughter three days earlier.Smith was taken directly from the airport to the hospital and stayed with his mother until he died the next morning, said Howard K. Stern, lawyer and long-time friend of Anna Nicole Smith.?There?s just no way that Daniel would have taken his life,? Stern said during an interview Tuesday on CNN?s ?Larry King Live.? ?I mean he was so, so excited to come here and see his mom and be with his sister.?Stern said Smith helped his mother get to the bathroom several times during the night.?At one point, Daniel said to me, ?How come I?m so tired?? And, in hindsight, I wish that I had seen that as some sort of a signal and seen that something wasn?t right,? Stern said in the Tuesday interview.Smith fell asleep in a chair next to his mother?s bed. Shortly after 9:30 a.m. that morning, Anna Nicole Smith woke up to find her son unresponsive. Hospital staff tried unsuccessfully to revive him.Methadone has a unique ability to kill patients who are not used to strong painkillers, said Chris Terpening, doctor of pharmacy at West Virginia University?s Charleston Division.?Methadone is a classic double-edged sword. It is very different from other opioid drugs, like OxyContin or morphine,? Terpening said. ?It has a very long half-life, which means you don?t need to take it as frequently. The bad news is, the drug can accumulate in your system if you take too much too soon.?Like Smith, most methadone overdose victims had more than one drug in their system at the time of their death, according to studies in West Virginia, Maine, North Carolina and Utah.In 2004, a combination of methadone and cocaine killed 17-year-old Brandi Bragg, granddaughter of West Virginia?s biggest lottery winner, Jack Whittaker. She did not have a prescription for methadone, according to her death certificate.But not all victims had multiple drugs in their system. In West Virginia, one in five methadone overdose victims had no other drug in their system, according to a Gazette-Mail analysis of state toxicology and vital statistics data. Others victims had trace, usually harmless amounts of alcohol or acetaminophen.Methadone can interact in dangerous ways with ?downers? such as alcohol, Valium or Xanax, Terpening said. They combine with methadone to make it harder to breathe.Other drugs can inhibit methadone?s breakdown, which can lead to a toxic buildup. Certain blood pressure medications and even grapefruit juice can have this effect. So can Zoloft, but not usually to a dangerous extent, he said.?It?s a little surprising, but not unheard of, that combination resulting in death,? he said.To be safe, people without a prescription should never take methadone, he said. Doctors who prescribe it should begin patients at low doses until they are used to the drug.?The rule of thumb is, start low, go slow,? Terpening said.To contact staff writer Scott Finn, use e-mail or call 357-4323.