Matthew Perry: with ketamine, the details matter

At Ember Health, we were deeply saddened to hear of the sudden death of actor Matthew Perry in October, who had bravely and publicly battled lifelong substance use issues. The recent news that he had ketamine in his system at the time of his drowning has understandably raised questions and concerns among our patients and broader community. It feels important to provide context to these events, and to shed light on the imperative of taking a nuanced, thoughtful approach to ketamine care for mental health.

Per his autopsy report, Matthew Perry died while under the influence of anesthetic doses of ketamine, in combination with therapeutic doses of the opioid buprenorphine and two separate benzodiazepines. He was found unsupervised, alone in his pool, with the medical examiner stating that drowning, coronary artery disease, and respiratory depression all contributed to his untimely death. The ketamine in his system at the time of his death was separate from an in-office medical treatment of IV ketamine he had received nearly two weeks prior. At the time of death, his blood levels of ketamine were 18-24 fold higher than dosages used for appropriate treatment of depression.

Ketamine is an extraordinarily versatile drug, used in many settings for different purposes and outcomes. As we often say, “ketamine is not ketamine, is not ketamine”. At Ember Health, we are committed to establishing the gold standard of care for ketamine administration to treat depression. As an evidence-driven and detail-oriented organization, we understand that each decision we make matters to the safety and efficacy of this treatment. Elaborating on these details is critical to the larger public discourse.

The patient profile matters.

In Matthew Perry’s memoirs, he shared that he was among those who sought relief of his depression through ketamine care. The data available to the public would suggest that he was an appropriate candidate for ketamine treatment, and the report states that he had received an infusion of ketamine for this clinical depression approximately two weeks prior to his death. At the same time, his autopsy report specifies:

“the ketamine in his system when he died could not have been from that infusion therapy, since the drug’s half life is three to four hours, or less.”

This suggests that, despite previously seeking care in a medical environment, he had obtained a large quantity of ketamine for at- home use.

At Ember Health, we work exclusively with patients managing Major Depressive Disorder and the depressive state of Bipolar Disorder. There are over 4,000 research papers and over 500 unique clinical trials studying the safe, effective use of ketamine in individuals with these diagnoses. Studies consistently show that 75% of people with these conditions experience relief of their depressive symptoms following IV ketamine treatment.

At Ember, 82% of the patients we’ve treated report relief from their depression, half of whom report full remission of depressive symptoms for a period of time. When compared to the efficacy rate of 30 – 40% of traditional oral antidepressants, with quicker effect, and without the side effect profile, these are stunning results.

Many people navigating depression are also navigating substance use disorder. While the clinical data for using ketamine to treat substance use disorder continues to grow, current medical guidelines reiterate that ketamine treatment should only be administered to people who are also dealing with clinical depression. Ketamine itself can be a drug of abuse, and assessment of treatment fit requires nuanced conversations.

At Ember Health, we’ve established safety parameters that are especially important for individuals who suffer from both depression and substance use disorder. This includes placing limitations on the frequency of treatment visits, requiring that we’re the sole source of ketamine for the people we treat, and ensuring that ongoing care is tailored to the person’s underlying depression rather than the pursuit of an altered state. We partner closely with each patient’s care team to ensure ketamine is received in a safe, supportive, and appropriate context.

The route of administration matters.

During his autopsy, the medical examiner found trace amounts of ketamine in Mr. Perry’s stomach. This suggests that he either ingested ketamine orally, or perhaps intranasally in sufficient quantities to cause some to drip into his stomach.

At Ember Health, we exclusively administer ketamine via intravenous (IV) infusion. 87% of studies on ketamine for depression through 2020 were conducted using IV ketamine. Those studies have shown that IV ketamine has the highest efficacy rate and best long term outcome data among all routes of administration for addressing depression.

From a regulatory perspective, IV infusions and intramuscular injections are the only FDA approved versions of ketamine in the United States. IV infusions are the only route of administration currently supported by the American Psychiatric Association, and the Department of Veterans Affairs and U.S. Department of Defense to treat clinical depression. All other versions of ketamine are subject to the FDA’s October warning against their use, due to a host of safety and efficacy concerns.

The dosage matters.

Matthew Perry died while under the influence of anesthetic doses of ketamine, in combination with therapeutic doses of the opioid buprenorphine, and with two separate benzodiazepines in his system. The blood levels in his body at the time of his death (3540 ng/ml) represent 18-24 times the doses typically administered intravenously for clinical depression (150 to 200 ng/mL).

At Ember Health, we administer ketamine in the dosage window that maximizes the antidepressant potential of the treatment, according to the literature. This ranges from 0.5 – 1.0 mg / kg of body weight, administered over a 40-minute infusion.

We also titrate our doses to the specific individual under our care, and take into consideration any medication interactions that could occur. While ketamine is a sedative, medical emergencies with ketamine almost exclusively occur at anesthetic doses, or when it is mixed with other sedative substances in the human body.

In hospitals, surgery centers, and emergency departments, anesthetic doses of ketamine have been administered safely for over 50 years. Even in the doses that led to Mr. Perry’s death, ketamine is routinely used in a medically monitored and supportive environment.

The setting matters.

Mr. Perry was found unsupervised, alone in his pool, with the medical examiner stating that drowning, coronary artery disease, and respiratory depression all contributed to his untimely death.

A recent meta-review showed that IV ketamine for depression remains exceedingly safe when used with careful medical and psychological screening. In these studies, medical serious adverse events (MSAEs) occurred in fewer than 1 in 1,000 treatment sessions. With medical monitoring, clinical, and psychological support, all of these events resolved without long term consequences. This is why the FDA states that ketamine should only ever be administered in a monitored setting, with medical personnel on hand to address the rare issues that arise.

At Ember Health, we administer ketamine in a medically monitored context, with a 1:1 patient to clinician ratio. All of our Clinical Directors are board-certified Emergency Medicine physicians, who are on site at all times that a patient is in our care. All of our doctors and nurses are experts in IV administration and monitoring, and equipped to intervene in the rare case an emergency arises. We are committed to the clinical and psychological safety of our patients, and we put a premium on creating a calming, focused setting to help people make the most of their care.

The stories matter.

Mr. Perry’s death is tragic, and the role ketamine played in his final moments are an important piece of the larger societal story around ketamine. With that said, his account represents one in a tapestry of stories, many of which have had fundamentally different outcomes.

At Ember Health, one of our goals is to help “shift the narrative” in this space, ensuring that people understand the positive impact that safe, thoughtful administration of ketamine can have for those deeply suffering. In our Ember Chronicles, we tell the stories of remarkable people whose lives are touched through this work.

And yet stigmas around depression and ketamine endure. Much of this is due to the sensationalization of “clickbait” headlines and the challenge of covering the subject with the nuance it requires. This is also due to the irresponsibility of individuals providing ketamine in contexts that are unsafe. The fear and apprehension that result are among the largest barriers to access for people who might realize significant benefits.

This is a space that merits our collective attention and thoughtful consideration. There is no conversation we’re unwilling to have here at Ember, with honesty, facts, and compassion. We understand that the details matter. Our community’s investment in understanding these details will undoubtedly be the difference between lives saved and lost.