Matthew Perry and the lost promise of ketamine treatment for depression
I’m still upset about Matthew Perry’s death in October 2023. And it’s not just because he died too young, which he did. Or because he was talented or - by all accounts - a sweet guy. I’m upset because I suspect he wasn’t the only casualty that night on his back yard pool deck. People struggling with severe depression that night, who might have been considering Ketamine therapy, might have never pursued treatment out of fear that they’d overdose like Perry. His death gave this potentially life-saving medication a dark and somewhat sleazy association.
I’ll start with the sleazy part. The urgent care clinic operator in Calabasas who sold Matthew Perry $57,000 worth of Ketamine was sentenced to 2 ½ years in prison yesterday. Five people, including Perry’s personal assistant, pled guilty in connection with his death. The actor – who had been public about his addiction struggles for years - was undergoing legitimate Ketamine treatment at a clinic that wouldn’t increase his dosage when he asked. Responsible ketamine providers take ethics around dosing extremely seriously, realizing that the drug has a potential for abuse. So Perry turned to an underground network of dealers and prescribers.
“It’s a gross overstatement to say Ketamine killed Matthew Perry; he asked his assistant to “give me a big one,” and then he got in the hot tub and drowned. ”
what is ketamine?
Ketamine is used to treat severe, treatment-resistant depression, ruminative suicidal ideation, Post Traumatic Stress Disorder, and even obsessive-compulsive disorder. It’s been around since the 1960s with a long track record of clinical safety. Ketamine has been FDA-approved since the 1970s and was used on battlefields and in veterinary clinics, but now is mainly used in hospitals as a children’s anesthetic.
It’s a dissociative anesthetic, but it also has psychedelic properties. Those hallucinatory sensations may be the elements of ketamine therapy that get the most attention, but they’re considered side effects of the drug.
how does ketamine help?
Ketamine helps form new synaptic connections and boost neural circuits that regulate stress and mood. Many patients feel better right away, but studies have shown that the benefits to mood and neurological growth can last up to two weeks after. The therapeutic effects are rapid and sometimes notable after just one session, but they don’t last. That’s why ketamine is most effective when taken over consecutive doses, as part of a treatment protocol that happens over the course of several months.
During these two weeks, there’s an enormous growth of new brain cells, which acts like a reset for your brain. Suddenly networks that don’t usually communicate with each other start to connect and these new connections allow cognitive shifts to take place.
Who is ketamine for?
Ketamine is helpful for people with rigid thinking, people who are depressed, addicted, or who ruminate on the same few thoughts all day. For those taking anti-depressants but not getting relief, it’s effective in the way some of those medicines aren’t, because it works on a different neurotransmitter than they do.
It’s important to note that ketamine doesn’t work for everyone. It’s not a miracle cure — clinical response rates fall roughly between 65% and 75%. That’s higher than many antidepressants and comparable to the success seen in multiple forms of talk therapy, but ask anyone who’s been in talk therapy for years: it’s not uncommon to reach a plateau. Years of sessions with little change, or repeated cycles of partial recovery and relapse. For some of these people, ketamine can catalyze a breakthrough. For clients carrying deep, complex, or early-life trauma, ketamine often makes it possible to access material that feels otherwise too shameful, frightening, or blocked. Under its effects, people frequently report feeling open, less afraid, and less defensive — conditions that can allow them to approach painful memories and emotions with more safety and curiosity.
The most promising outcomes come when ketamine is integrated thoughtfully with psychotherapy. Ketamine-Assisted Psychotherapy (KAP) combines the neurobiological effects of the medicine with deliberate, trauma-informed therapeutic work before, during, and after dosing. This combination can accelerate insight, emotional processing, and behavioral change in ways that medication or therapy alone sometimes do not.
High-profile drug overdoses attract media attention, and my hope is that those stories don’t drown out the careful, evidence-based use of ketamine for healing. With proper screening, clinical oversight, and trauma-informed integration, KAP can be a powerful tool in recovery.