Ketamine is an FDA-approved anesthetic that has gained traction as a treatment for severe depression, but it carries serious risks when used outside medical supervision. A variant called esketamine (brand name Spravato) received FDA approval in 2019 for people with treatment-resistant depression and suicidal thinking. However, the high-profile death of actor Matthew Perry in October 2023 from ketamine toxicity has raised urgent questions about how the drug is being used, who should have access to it, and what safeguards are necessary.

What Happened to Matthew Perry, and Why Does It Matter?

Perry died accidentally from the acute effects of ketamine while in his swimming pool. Medical examiners found ketamine levels in his system similar to those used during general anesthesia. Court records revealed that Perry had been receiving ketamine through both supervised medical treatments for depression and from illegal drug dealers in the weeks before his death. His live-in assistant obtained dozens of vials of ketamine from multiple sources and repeatedly injected Perry, including on the day he died.

Perry's last supervised ketamine treatment had occurred more than a week before his death, yet ketamine typically leaves the body within hours. This indicated that the fatal dose came from a more recent, unsupervised injection. The medical examiner reported that ketamine caused cardiovascular overstimulation and respiratory depression, which likely caused Perry to lose consciousness in the water. Five people, including his dealer and personal assistant, were convicted in connection with his death.

Is Ketamine Actually Effective for Depression?

Yes, when used in safe, supervised settings with medical oversight, ketamine appears to help some people with treatment-resistant depression. Treatment-resistant depression means a person has not responded to at least two antidepressant medications. Esketamine is approved for people with treatment-resistant depression and for some patients with major depression and acute suicidal thinking.

The appeal is clear: there are very few options for people whose depression doesn't respond to standard antidepressants. Esketamine offers an alternative that doesn't require surgery or general anesthesia, making it less invasive than electroconvulsive therapy (ECT), another treatment for severe depression. However, ongoing research is still vital to understand how long ketamine's effects last, how many treatments people need, and which patients are the best candidates.

"We have very few options for treatment-resistant depression. This is one option. Another is electroconvulsive therapy or ECT. It involves anesthesia in a medical setting. It has very strong response rates but also has strong side effects," said Dr. Pat Fehling, a psychiatrist and addiction medicine specialist at the UCHealth Center for Dependency, Addiction and Rehabilitation.

Dr. Pat Fehling, Psychiatrist and Addiction Medicine Specialist at UCHealth Center for Dependency, Addiction and Rehabilitation

What Are the Real Dangers of Ketamine?

Ketamine carries significant risks, especially when used outside medical settings. The drug elevates blood pressure, and blood pressure surges can trigger cardiac arrest. There have been deaths related to drowning while a person is dissociating from ketamine's effects, meaning they lose awareness of their surroundings. Ketamine also tends to make people feel very woozy, can cause nausea, and often produces surreal, dissociative experiences.

The dissociative effects are particularly dangerous in certain environments. Being in water while using ketamine is extremely unsafe because a person may lose awareness of where they are and drown. This is exactly what happened to Perry. Additionally, ketamine's effects can last for several hours, which is why patients cannot drive themselves home after supervised treatment.

How to Use Ketamine Safely if You're Considering It

• Work with a licensed medical provider: Any use of ketamine needs to involve thoughtful, evidence-based collaboration with a medical professional. Reputable clinics that offer ketamine must abide by stringent safety guidelines and have emergency equipment available.
• Seek FDA-approved esketamine in clinical settings: The only FDA-approved ketamine-derived treatment for behavioral health is esketamine, a nasal spray administered in a doctor's office or certified clinic under medical supervision. This is the safest form for depression treatment.
• Avoid unsupervised use and illegal sources: Never obtain ketamine from dealers or use it outside medical supervision. Medical experts actively monitor patients' blood pressure during supervised treatments to ensure safety, and crash carts are available to revive a person who stops breathing or has a cardiac issue.
• Disclose your full medical history: People with a history of heart problems can be at risk when using ketamine, so it's essential to tell your doctor about any cardiovascular conditions before treatment begins.
• Arrange safe transportation: Do not drive yourself home after ketamine treatment since the effects can be strong and last for a few hours. Plan for someone else to pick you up.

What Does Ketamine Actually Do in the Body?

Ketamine is a powerful anesthetic that dates back to the 1960s. Emergency responders have long used it because it's generally safe, fast-acting, and its effects wear off relatively quickly. For example, ski patrol responders often give ketamine to injured skiers because it provides good pain relief and generally protects a person's breathing while making them feel "a little loopy".

Over the past decade, ketamine has gained traction as both a recreational drug and as a treatment for depression and post-traumatic stress disorder. The dissociative properties that make it useful for anesthesia are the same properties that can help some people with severe depression, though researchers are still working to understand exactly why and for whom it works best.

What Should You Know Before Considering Ketamine Treatment?

If you're struggling with treatment-resistant depression, ketamine may be worth discussing with a psychiatrist or mental health professional. However, it's not a first-line treatment, and it's not right for everyone. The drug requires medical supervision, ongoing monitoring, and a commitment to using it only in approved clinical settings.

The Perry case serves as a stark reminder that ketamine is a powerful drug with real dangers. The difference between therapeutic use and fatal overdose can come down to dosage, frequency, medical supervision, and the environment in which it's used. If you or someone you know is struggling with depression or addiction, the safest path forward is to work with licensed medical professionals who can provide evidence-based treatment in a controlled, monitored setting.