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    • How helpful or harmful is ketamine? 5 things to know after Matthew Perry's death

    Matthew Perry appears at the GQ Men of the Year Party in West Hollywood, Calif., on Nov. 17, 2022. (Photo by Willy Sanjuan/Invision/AP, File) Matthew Perry appears at the GQ Men of the Year Party in West Hollywood, Calif., on Nov. 17, 2022. (Photo by Willy Sanjuan/Invision/AP, File)
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    Matthew Perry鈥檚 2023 death from what the Los Angeles County medical examiner鈥檚 office determined were 鈥渢he acute effects of ketamine鈥 cast a shadow over a medication that has been enjoying growing popularity as therapy for depression and other mental health conditions.

    (The report listed drowning as a contributing factor; Perry was found face down in a hot tub at his home.)

    The actor鈥檚 death raised questions about how ketamine is being used 鈥 and possibly misused 鈥 in a largely unregulated landscape that some critics liken to the 鈥淲ild West鈥 due to a proliferation of clinics around the country. Perry, who had struggled for years with drug addiction, had been open about receiving ketamine therapy for depression.

    鈥淢atthew Perry sought treatment for depression and anxiety and went to a local clinic where he became addicted to intravenous ketamine,鈥 Anne Milgram, the Drug Enforcement Administration鈥檚 administrator, said at a recent press conference. 鈥淲hen clinic doctors refused to increase his dosage, he turned to unscrupulous doctors who saw Perry as a way to make quick money.鈥

    Prosecutors said a underground network of drug sellers and suppliers 鈥 including two doctors 鈥 were responsible for distributing the ketamine that killed Perry. Five people have been charged in connection with the death of the 鈥淔riends鈥 actor. Three are cooperating with prosecutors, while two defendants have pleaded not guilty to respective charges that include falsifying medical records and conspiracy to distribute among others.

    To be clear, ketamine is only approved by the U.S. Food and Drug Administration as an anesthetic and not for the treatment of any psychiatric disorder. (The FDA approved a related drug, esketamine, sold as Spravato, in 2019 for people with treatment-resistance depression.)

    But the scientific evidence showing that ketamine can be helpful in patients with treatment-resistant depression and suicidal ideation is strong and goes back at least 20 years.

    Still, the circumstances surrounding Perry鈥檚 death has brought scrutiny to the relatively new and somewhat misunderstood practice.

    鈥淜etamine is such a different type of treatment than traditional treatments, not just for depression, but in medicine in general,鈥 psychiatrist Dr. David Feifel, founder of Kadima Neuropsychiatry Institute, a private clinic in San Diego that administers ketamine therapy to patients, told CNN Chief Medical Correspondent Dr. Sanjay Gupta recently on his podcast Chasing Life.

    鈥淥ne of the major differences is that the actual setting and the patient鈥檚 state of mind when they are receiving the treatment play a big role in the outcome, the therapeutic effect.鈥

    Feifel, a professor emeritus of psychiatry at the University of California, San Diego鈥檚 School of Medicine, was one of the first doctors to use ketamine off-label to treat depression at the school鈥檚 Center for Advanced Treatment of Mood and Anxiety Disorders, according to an article in the journal The Lancet.

    Unlike traditional antidepressants that target the neurotransmitters serotonin and/or norepinephrine, ketamine targets glutamate 鈥 the most abundant chemical messenger in the brain, Feifel said. It also appears to enhance neuroplasticity, stimulating new connections or pathways in the brain.

    Ketamine was originally developed in the 1960s as an anesthetic 鈥 an application for which it is still used today. (It is on the World Health Organization鈥檚 Model List of Essential Medicines.)

    But Feifel said the drug鈥檚 dissociative and hallucinogenic properties 鈥 which made it such a popular party drug 鈥 may hold the key to why it helps some people with depression and other mental health disorders.

    鈥淜etamine treatment is associated with an altered state of thinking, a psychedelic-like state of thinking, for a short period of time. There鈥檚 a substantial amount of evidence that that is part of the therapeutic effect,鈥 Feifel said. 鈥淭his psychedelic-like experience allows people to view things through a different lens that seems to play a role in their improvement.鈥

    But, Feifel noted, it can be emotional and unpleasant for some 鈥 and it leaves patients undergoing treatment vulnerable because they are not fully in control of their faculties. As a result, proper preparation and supervision are essential, he said.

    Feifel said he started treating patients with ketamine because existing treatments don鈥檛 work for everyone.

    鈥淲hen I started in psychiatry, one of the motivations was that I knew mental illness was an incredible scourge of society. The statistics are just unbelievable in terms of rates of depression, anxiety, PTSD (post-traumatic stress disorder) and suicide 鈥 and they are not getting better,鈥 he said. 鈥淎nd after 50 years of medications, they really haven鈥檛 gotten better. So there鈥檚 a huge need.鈥

    Here is what Feifel wants people to know about ketamine, especially if they or someone they know is interested in trying it.

    Ketamine needs appropriate medical supervision

    Ketamine can be a lifeline for certain people who have not responded to common treatments for depression, such as medications and different forms of psychotherapy.

    鈥(It鈥檚) probably the biggest advance in the field of mental health in terms of treatments in many decades,鈥 Feifel said.

    鈥淚t is highly effective when conventional (treatments) are not effective,鈥 he said. 鈥淎nd its rapid effectiveness against suicidal thoughts (is) really important. We鈥檝e never had anything like that where we can give it to somebody 鈥 and it can, sort of, vaporize their suicidal thinking.鈥

    And when done under appropriate medical supervision, ketamine is safe.

    鈥淚t is almost impossible to die from an overdose of ketamine alone,鈥 he said, because it doesn鈥檛 lower respiration rates, 鈥渨hich is very unusual for an anesthetic,鈥 and it has a wide therapeutic range.

    Feifel pointed out Perry鈥檚 death didn鈥檛 happen in a clinic under treatment. 鈥淭here was no medical oversight,鈥 he said. 鈥淭his was not given in anything that resembled a medical context.鈥

    Caveat emptor (buyer beware)

    If you are looking to try ketamine as treatment for depression or another mental health condition, do your homework.

    鈥淚f anybody is considering (ketamine therapy), they have to be somewhat cautious,鈥 Feifel said, 鈥渂ecause currently it鈥檚 a very, unregulated landscape, where there are a lot of, let鈥檚 say, providers that may not be (using it) under the highest standards. And then it can be risky.鈥

    To find an appropriate provider or clinic, start by asking your psychiatrist. 鈥淓ven if they don鈥檛 practice with ketamine themselves, (they) are probably aware of their local colleagues who do so, and the ones who have a good reputation,鈥 he said.

    Look for an expert

    Find a clinic run by a mental health professional.

    鈥淭he problem is many of these providers are not optimal,鈥 Feifel said. You wouldn鈥檛 go to a urology clinic run by a psychiatrist, he noted, so why would you go to a ketamine clinic run by a urologist?

    鈥淚n general, a large proportion of the clinics are not run by mental health professionals, namely psychiatrists.鈥

    Feifel said some clinics may do a good job but many don鈥檛. 鈥淭hey don鈥檛 have the background,鈥 he said, pointing to a psychiatrist鈥檚 years of residency and specialty training, not to mention deep understanding of complex medication regimens.

    鈥淩emember, the people who are coming to this treatment have the most resistant types of depression, the most complex, often with other mental illnesses commingled,鈥 he said.

    Look beyond the infusion

    Seek out a clinic that includes psychotherapy as part of the treatment plan.

    鈥淭he highest standard is to do ketamine treatments in the context of the specialized type of psychotherapy called ketamine-assisted psychotherapy,鈥 Feifel said. 鈥淎 provider that also has a multidisciplinary team that includes licensed therapists who are trained in this 鈥 that鈥檚 a barometer of a very high level of commitment to the best practices in ketamine.鈥

    You don鈥檛 want to walk into a clinic, get an infusion and then be sent on your way without proper follow-up support, he said.

    Steer clear of telehealth providers

    During the height of the pandemic, rules around prescribing controlled medications, such as attention deficit hyperactivity disorder drugs, were relaxed to allow for continuation of therapy. This flexibility of the prescribing rules could spell trouble for someone getting ketamine therapy via telehealth.

    鈥淭here are companies now that will have patients do a quick telemedicine consultation with, let鈥檚 say, a nurse practitioner 鈥 just to check that box that there was a medical assessment, and then they get sent ketamine to their house to do on their own,鈥 Feifel said. 鈥淭hat鈥檚 exactly part of the problem: doing it on your own, unsupervised (and) thinking, 鈥極h, this is fine.鈥欌

    He said people should steer clear of home ketamine, at least initially. 鈥淚 think it鈥檚 a recipe for disaster,鈥 he said.

    Feifel said he believes the public can separate what happened to Perry from the promise of ketamine therapy.

    鈥淭here are people who traffic in drugs and, unfortunately, people who get addicted to drugs, even drugs that are relatively low on the addiction potential scale as ketamine is,鈥 he said. 鈥淪o, I think people in their minds will separate this. 鈥 That is not medical care.鈥

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