Questions were swirling on social media Friday about the anesthetic ketamine - its side effects, uses and effectiveness - after the Los Angeles County medical examiner attributed "Friends" actor Matthew Perry's death to acute effects of ketamine.
Contributing factors in Perry's death listed in a report released by the County of Los Angeles Department of Medical Examiner. include drowning, coronary artery disease and the effects of buprenorphine, used to treat opioid use disorder. The manner of death was determined to be an accident.
Perry, 54, was found unresponsive Oct. 28 in the pool at his residence in Los Angeles and was pronounced dead at the scene by paramedics.
The coroner's autopsy report noted that Perry was on ketamine infusion therapy to deal with depression and anxiety, with the most recent therapy "reportedly one and a half weeks before death."
A type of psychedelic drug known as a dissociative, Ketamine is an injectable, short-acting substance for use in humans and animals and as a nasal spray for treatment resistant depression, according to the Drug Enforcement Agency. The hallucinogen distorts the perception of sight and sound, makes the user feel disconnected from their pain and environment and can induce both a state of sedation and amnesia.
Perry's autopsy reported noted that the ketamine found in Perry's system at the time of death "could not be from that infusion therapy, since ketamine's half-life is three to four hours, or less." The report said the method of intake could not be determined, but trace amounts of the drug were found in Perry's stomach.
"At the high levels of ketamine found in his postmortem blood specimens, the main lethal effects would be from both cardiovascular overstimulation and respiratory depression," the autopsy report stated.
Local
A prescription version of ketamine called esketamine, under the brand Spravato, was approved by the Food and Drug Administration for for treatment-resistant depression in 2019. However, it can only be used under the supervision of a health care provider in a certified doctor's office or clinic.
Relief from treatment-resistant depression with ketamine happens rapidly, according to an article from Harvard Medical School.
Feeling out of the loop? We'll catch you up on the Chicago news you need to know. Sign up for the weekly Chicago Catch-Up newsletter.
Instead of waiting for an antidepressant to hopefully provide some relief over the course of weeks, people can start to feel the benefits of ketamine within about 40 minutes. Doctors and the FDA emphasize that it isn't a first-option treatment for depression, and it is generally used only when other, more longstanding treatments, such as medication, haven't been effective.
According to one study, 70 percent of patients with treatment-resistant depression who were started on an oral antidepressant and intranasal esketamine improved, compared to just over half in the group that did not receive the medication.
Side effects of ketamine treatment and long-term benefits remain unknown, as more detailed research is needed regarding its safety and effectiveness.
Ketamine was initially approved by the FDA in 1970, in the form of the injectable Ketalar, as an anesthetic during surgery and is used for a range of medical purposes. While generally considered safe, side effects are possible, including the following: dissociation, intoxication, sedation, high blood pressure, dizziness, headache, blurred vision, anxiety, nausea, and vomiting.
Abuse of the drug, a Schedule III controlled substance, has soared in recent years for its dissociative sensations and hallucinogenic effects, similar to those of PCP, which it is derived from.
Often sold as a colorless, odorless liquid or in a white powder form under street names such as "Kit Kat" and "Special K," Ketamine can be abused by being injected, or mixed with liquids, according to the Drug Enforcement Administration. The powder form of the drug is snorted or pressed into tablets, sometimes in combination with other substances.
The FDA noted in October that there was increased interest in compounded ketamine products for the treatment of psychiatric disorders. While such products have been marketed for depression, anxiety, post-traumatic stress disorders and obsessive-compulsive disorder, the FDA hasn't determined if ketamine is safe and effective for such uses.
In Feb. 2022, the FDA published a compounding risk alert describing the potential risks associated with at-home use of compounded ketamine nasal spray and reports of ensuing psychiatric events, increases in blood pressure, respiratory depression, and lower urinary tract and bladder symptoms.
In addition to the concerns regarding the short-term use of compounded ketamine, the overall benefit-risk profile of ketamine for treatment of psychiatric disorders is unknown, according to federal health officials.
In recent years — even before the approval of Spravato — a new industry of ketamine clinics -- which offer the drug off-label as either an infusion or an injection for a wide variety of mental health problems -- has emerged, according to a previous NBC News article.
With a rise in new ketamine clinics across the country, some doctors are worried that it’s an unregulated industry that’s ripe for danger.
Because the drug has FDA approval, any doctor can prescribe it off-label, meaning the drug hasn't been specifically approved for those conditions. Clinics aren’t regulated federally, but they are subject to the same state laws as other outpatient medical clinics.
“The concern with these clinics’ popping up is that people are getting treatments that haven’t been well-proven, well-studied or following any guidelines,” Dr. Smita Das, an associate professor at Stanford University School of Medicine and chairwoman of the American Psychiatric Association’s Council on Addiction Psychiatry told NBC News. “My concern is that people who need treatment will spend their money and energy in these ketamine clinics that aren’t well-proven.”
Multiple doctors also said they’re concerned that some clinics may be offering the drug without any supervision, which is especially worrying if a patient has a “bad trip.”
Only a few small studies have examined its benefits for other mental health conditions beyond treatment-resistant depression, and the American Psychiatric Association doesn’t provide specific guidelines for its use.
“People can rarely experience paranoia or suicidal ideation,” Das said. “And so many of these clinics don’t have mental health professionals staffing them. When those mental health concerns pop up, they may not be equipped to respond appropriately.”