Was Mathew Perry’s death caused by an overdose?
January 19,2024
“Friends” star Mathew Perry (age 54) was found floating face down in a hot tub at his L.A. home last October. The LA county Medical Examiner’s report stated “the acute effects of ketamine” were the cause of death but drowning, CAD, and buprenorphine were contributing factors. His opinion was that the main lethal effects were caused by both CV overstimulation (with CAD exacerbating the effects on the heart) and respiratory depression. He felt that drowning contributed due to the likelihood of submersion into the pool as he lapsed into unconsciousness.
But two toxicologists had other opinions. Dr. Andrew Stolback, medical toxicologist at Johns Hopkins, opined that was no evidence of a MI and the blood concentration of buprenorphine was not toxic.
Buprenorphine, a partial µ opioid agonist competes with the extant opiate for the µ opiate receptor. Used for opiate substitution therapy, it has a safer clinical profile than methadone. At a therapeutic dose, especially with chronic administration, buprenorphine doesn’t impact respiratory drive or mental status. Although buprenorphine has a ceiling effect on respiratory drive, it may cause clinical respiratory depression in overdose.
Dr. Ryan Marino, Med Director of Toxicology and Addiction Med at University Hospitals of Cleveland added that ketamine did not stop Perry from breathing.
Ketamine is a dissociative anesthetic that causes loss of pain perception with little or no depression of airway reflexes. This dissociative analgesic also has hallucinogenic properties. Perry had a blood ketamine concentration of 3,271 ng/mL. Concentrations range from 1,000-6,000 ng/mL when used for general anesthesia. Both toxicologists agree that Perry’s blood ketamine concentration is within the range that causes sedation for a surgical procedure, but it is unlikely that Perry would have died if he had not been in a body of water.
Perry was receiving ketamine infusion therapy for depression, but last treatment had been 10 days earlier, so the ketamine from that treatment could not have remained in his system.
So the answer to the question is no, it was not an overdose, but the combined effects of ketamine and buprenorphine that decreased his mental acuity and made him drowsy. Unfortunately, he was in a hot tub.
Question prepared by Donna Seger MD
Comment: Ketamine-assisted therapy has increased in the last few years with hundreds of clinics popping up across the country and some provide take-home doses. The number of deaths related to ketamine has also increased annually. The drug has a large safety window but if someone is dissociated, the person may unintentionally take dangerous actions. This case could add to the controversy regarding administration of ketamine in unsupervised settings. ds
I am interested in any questions you would like answered in the Question of the Week. Please email me with any suggestions at donna.seger@vumc.org.
Donna Seger, MD
Professor Emerita
Department of Medicine
VUMC