"What is odd and points to abuse is that he had three different benzos in his system and two opioids," he says. "No doctor would prescribe that cocktail."
Thakkar agrees. "I can't see any appropriate clinical situation where all of these medications should have been given to one person at the same time."
The combination would have had what is known as an additive effect. In short, this means that the depressive effects of each of these medications would have piggy-backed on each other.
Hydrocodone and oxycodone, for example, can depress activity in the area of the brain that tells you to breathe, Zacny says. Diazepam, temazepam and alprazolam in high or combined doses can decrease respiration. On top of this, the sleeping pill Ledger took could have further depressed the systems in his body that kept him breathing.
But how could Ledger have gotten access to all these medications? Fairly easily, Thakkar notes. They may have come through different doctors, or Ledger could have obtained them through illegitimate means.
"People do share or obtain prescription medications illegally or inappropriately," adds Thakkar. "This highlights the point that these medications are not to be taken lightly."
In the shadow of Ledger's death, doctors note that the circumstances of his death may serve as an important warning to those who may not be monitoring their medicines as closely as they should.
"The public health angle is the big story here," says Dr. Alan Ducatman, professor and chair of community medicine at the West Virginia University School of Medicine, in Morgantown. "One man — and not the first such celebrity, and definitely not the only American — has raised questions about how we prescribe, monitor, are affected by prescription drugs in our society."
And the impacts of these questions could be widespread. Thakkar says that there are likely millions of people in the United States taking at least one of the medications that contributed to Ledger's death.
"This shouldn't be a loud warning to anyone who is taking these medicines under a doctor's supervision," he says. "But people need to understand that the more they are taking different medications for a single indication, the more they need to be carefully supervised."
Willis agrees. "The message is that this case isn't about pain relief, it's about drug abuse. Where pain is concerned, let your physician be the judge of which drugs to prescribe."