Ledger, Hoffman And Now Patton Oswalt's Wife Show How Mixing Drugs Can Be Deadly

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    【 This post was originally published on here. 】

    I wasn’t familiar with her name or her work, but I remember feeling sad when I read of the death of Michelle McNamara last April. McNamara, wife of actor and comedian Patton Oswalt, had died suddenly her sleep. She was only 46 and left behind a young daughter, now 7.

    That feeling resurfaced over the weekend when I read about Oswalt’s statement to the Associated Press about why McNamara died. Although the AP quotes the Los Angeles coroner as saying the cause of her death remains listed as pending, Oswalt said McNamara died from a combination of prescription medications and a previously undiagnosed heart condition.

    I flashed back to the accidental deaths of actors Heath Ledger in 2008 and Philip Seymour Hoffman in 2014 from drug combinations. While Ledger had twice as many drugs in his system as McNamara reportedly had, and Hoffman had used illicit as well as prescription drugs, I was struck by the fact that all three had taken both narcotics and tranquilizers. I got back in touch with Cindy Kuhn, a Duke University pharmacology professor whom I’d interviewed after Ledger’s death about polypharmacy, or the use of two or more drugs at the same time. Depending on the drugs and the reasons for which they are prescribed, polypharmacy can either be lifesaving or deadly.

    This 2011 file photo shows actor Patton Oswalt with his wife, Michelle McNamara, who died in her sleep last April at age 46. Oswalt told the Associated Press on Friday that McNamara died from taking a combination of three drugs and an undiagnosed heart condition. (AP Photo/Matt Sayles)

    According to Oswalt, McNamara had taken Adderall, a combination of the stimulants amphetamine and dextroamphetamine that’s used to treat attention deficit/hyperactivity disorder (ADHD); Xanax, a benzodiazepine tranquilizer; and fentanyl, a powerful opioid (narcotic) painkiller that typically is prescribed only after other opioids are no longer enough. Both Xanax and fentanyl can suppress breathing. Although Oswalt’s statement mentioned that on autopsy his wife was found to have heart disease, which to me sounded like atherosclerosis, or coronary artery disease–unusual in a woman that young–he did not mention any conditions for which those drugs are typically prescribed.

    I asked Kuhn about McNamara’s drug cocktail and the possible role of underlying heart disease, and she answered via email:

    Rita Rubin: Besides cancer pain, why might doctors prescribe fentanyl?

    Cindy Kuhn: Fentanyl is used in a number of chronic pain conditions that are severe. According to UpToDate, the reference we ask medical students to use, it can be appropriate in many different conditions, including diabetic neuropathy (nerve pain), sickle cell disease, chronic kidney or liver disease, severe burns, etc.

    Rubin: Is fentanyl a particularly risky opioid?

    Kuhn: The problem with fentanyl is that it is extremely potent (according to the National Institute on Drug Abuse, fentanyl is 50 to 100 times more potent than morphine). That means the difference between an effective dose and a lethal dose is small. Patients who are not advised properly and inexperienced can accidentally get themselves into trouble. For example, if pain relief with one patch is inadequate, it is a natural inclination to put another patch on. With fentanyl, multiple patches can lead to overdose.

    Rubin: Does having heart disease increase the risk of a fentanyl overdose?

    Kuhn: There have been case reports of heart problems after fentanyl in the medical literature, which may be relevant in this situation, since she was reported to have undiagnosed heart disease.

    Rubin: A few months after McNamara died, the Food and Drug Administration announced that it was requiring a “black box” warning–the strongest type of warning–on opioid and benzodiazepine labels about the serious risks of using the two at the same time.  Why would a doctor prescribe both of them to a patient?

    Kuhn: Generally, physicians would try to avoid this combination, as this is a common overdose problem. Unfortunately, people often see multiple doctors, and one doctor could have prescribed something without knowing what the other doctor had prescribed. Or, the person could have used a drug that had not been prescribed for them. Or the benzodiazepine could have been an old prescription, or vice versa. Or this could happen accidentally due to a mistake by the patient. We do not know the details of this case.

    Rubin: It has not been reported that McNamara had ADHD. Why else might someone take the drug?

    Kuhn: Some drug abusers do take stimulants to offset the sedating effects of opioids and/or benzodiazepines. But again, we do not know the details of this case, and it is entirely possible these three drugs were prescribed legally.

    Rubin: Is polypharmacy a bigger problem than ever?

    Kuhn: Certainly, it’s as big as it has ever been. The big change in the last 15 years has been the increased prescription and non-prescription use of opioid analgesics (painkillers), which carry a real risk of overdose, especially, as in this case, when used in combination with other sedative drugs.

    Rubin: How can people avoid lethal drug combinations?

    Kuhn: By using drugs as prescribed. One problem that even well-intended people have is not finishing a prescription and holding on to the last few benzodiazepines or opioids that were prescribed for a valid reason. They then use them later in an emergency without understanding their current medication interactions. People need to understand that prescription medications can be lethal when used improperly, especially opioids for pain.