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Why Ketamine Is Being Used As an Antidepressant

Ketamine For Depression
Ketamine For Depression

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While you might not associate ketamine, a psychedelic club drug known for its dissociative effect on users, with legitimate health care, years of scientific research suggests ketamine may be an effective treatment for depression and other mental illnesses. In fact, in 2019 the Food and Drug Administration (FDA) approved a ketamine treatment for people with treatment-resistant depression (TRD) — in other words, depression that hasn't improved after the use of standard interventions, including antidepressants and counseling.

While it's certainly not yet mainstream, using ketamine for depression has garnered increasingly more buzz as of late. A Netflix docuseries released in July 2022, How to Change Your Mind, explores the use of controversial drugs, including ketamine, and their positive effect on those with mental illnesses. You also may have read about some celebrities, including Sharon Osbourne and Lamar Odom, using ketamine for depression and addiction, respectively. However, there's more research to be done, and as with all medications, everyone may react differently to ketamine treatments for mental illnesses.

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Increased attention around ketamine comes as the COVID-19 pandemic has caused a 25 percent spike in depression and anxiety, according to the World Health Organization. "Now, more than ever, the need exists for a rapidly acting antidepressant for those with suicidal ideation," says Rachel J. Dalthorp, M.D., a psychiatrist at LifeStance Health.

Ahead, learn more about what ketamine is, how it's being used for mental health care, and who experts say might benefit from it.

What is ketamine?

Ketamine is a dissociative anesthetic (meaning it distorts sensory perception) originally created as an injectable, short-acting sedative and painkiller for humans and animals. It was approved for medicinal use by the FDA in the 1970s, but some began using it recreationally, taking advantage of its hallucinogenic effects. "[Ketamine] distorts perceptions of sight and sound and makes the user feel disconnected and not in control," according to the U.S. Drug Enforcement Administration (DEA).

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By the 1980s, ketamine made its way onto the party scene and was sold illegally in the form of a white powder, pills, or dissolved into a liquid. The U.S. made ketamine a federally controlled substance in 1999 to combat the misuse of the drug. While the black market availability of ketamine and recreational use of the drug has increased from 2006 to 2019, these days, less than one percent of people in the U.S. use ketamine for non-medical reasons, according to a study published in American Journal of Public Health in 2021.

Why is ketamine being used as a treatment for depression?

Recent research, including a 2021 systematic review of 83 reports, provides evidence that ketamine offers antidepressant and anti-suicidal effects. What's more, ketamine may offer faster relief from depression symptoms, including suicidal thoughts, when compared to traditional antidepressants and counseling, according to a 2019 study published in the journal of Psychiatry and Clinical Neurosciences.

While more research is needed to determine exactly why ketamine works as a treatment for depression, experts are getting closer to the answer. Ketamine is thought to regulate the brain's glutamate system, which is made of glutamate pathways and receptors in the central nervous system, says psychiatrist Harold Hong, M.D., medical director of New Waters Recovery.

"Glutamate is the most abundant neurotransmitter in the brain that's responsible for mediating many of its functions. When there is overactivity in the glutamate system, it can lead to conditions like anxiety, depression, and even addiction," he explains. "Ketamine works by blocking the NMDA [N-methyl-D-aspartate] receptor, one of glutamate's main receptors. This action results in a decrease in glutamate activity and allows for ketamine to produce its therapeutic effects."

Additionally, a 2018 study shows ketamine may increase neuroplasticity, the brain's ability to change and adapt in response to experiences. This may help patients to think more clearly, have better focus, and better manage emotions over time.

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"Ketamine has proven effective in helping people with severe depression, primarily when other treatments and/or drugs haven't worked for them," adds psychiatrist Devin Dunatov, M.D., medical director at Burning Tree Ranch, an addiction treatment center. Ketamine's ability to help those with TRD is noteworthy, as 30 percent of patients "fail to respond to traditional antidepressant therapies," explains Dalthorp, citing a large antidepressant study completed in 2006.

The rapid relief ketamine may provide is paramount for those with suicidal thoughts, according to experts. "Many other antidepressants take a long time to work, but patients can see the impact of ketamine very quickly," says Dunatov. Patients can experience "euphoria and may feel relaxed," after using ketamine, adds Amanda Itzkoff, M.D. psychiatrist and CEO of Curated Mental Health.

How is ketamine used as a treatment for depression?

Quick science lesson: Ketamine consists of two pairs of compounds, R- and S-ketamine. This mixture is known as R, S-ketamine, or racemic ketamine, and it's what the FDA originally approved for use as an anesthetic in the 1970s. This type of ketamine is used for intravenous (IV) ketamine infusion therapy and is injected into the bloodstream. While IV ketamine therapy for mood disorders hasn't yet been approved by the FDA, physicians can prescribe it off-label to patients, reports The New York Times. To prescribe a drug off-label means physicians can prescribe the use of an FDA-approved drug for uses other than what the drug has been explicitly approved for by the FDA.

S-ketamine, also known as esketamine, is more potent than racemic ketamine. Because of esketamine's higher potency, doctors are able to use smaller dosages of it when treating depression and other mental illnesses, limiting its side effects. What's more, a form of esketamine has even been approved by the FDA for those with TRD.

In 2019, the FDA approved a nasal spray medication called Spravato, which is manufactured by Janssen Pharmaceuticals. Spravato is a type of esketamine that's designed to be used in conjunction with an oral antidepressant in those with TRD. Spravato can alter a glutamine imbalance within 24 hours, "leading to a rapid antidepressant effect," says Hong. A 2020 study published in the Journal of Affective Disorders also shows that while IV-administered racemic ketamine is more effective in treating depression, esketamine is less likely to cause hallucinations.

Who is eligible for ketamine treatments for depression?

A fast-acting treatment for depression may sound like a dream to those who suffer from this mental illness, but not everyone meets the criteria to be prescribed ketamine therapy by a health care provider. In most cases, it's a last-resort treatment when everything else has failed, according to Dunatov.

Ketamine should be used for "someone with severe depression who hasn't been responding to other treatment options," says Dunatov. "I only recommend patients [try a] ketamine treatment when other things haven't worked," he explains. "Also it is important to remember that ketamine should be [used] in conjunction with other treatments, such as therapy. It shouldn't be used on its own."

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Ketamine isn't recommended for those who are pregnant, are nursing, have any sort of uncontrolled heart disease issues, have a history of psychosis, or have ongoing substance abuse problems, adds Itzkoff.

What are the potential risks of using ketamine for depression?

"As with all drugs, there are potential side effects associated with ketamine use," says Hong. These may include nausea, vomiting, dizziness, drowsiness, and confusion. Additionally, even minimal doses of Spravato nasal spray may induce psychotic symptoms in schizophrenia patients, he adds, noting that hallucinations are rare but have been reported. Though ketamine has the potential to become addictive, more research is needed to determine the addiction risk of ketamine when its administered in professional medical settings.

It's also important to note that a July 2022 study published in the Journal of Studies on Alcohol and Drugs found clinical trials on ketamine for the treatment of mental health disorders underestimated BIPOC patients. Therefore, existing research may not paint a full picture of the efficacy of ketamine for depression for all groups.

Currently, ketamine is also not generally accessible from a financial standpoint. "While some insurance companies will pay for treatment, many will not," says Dalthorp. "The self-pay cost of six [ketamine] infusions can be more than $3,000, an amount many patients struggling with depression simply can't afford." FTR, Spravato comes at a high price too, costing about $729 for just two units of nasal spray.

However, Dalthorp and her team are working with commercial insurance companies in the hope of getting coverage for ketamine treatments. "We can't just offer ketamine to those with the financial means to pay out of pocket when so many are struggling," she says.

While insurance companies might not be ready to cover such ketamine costs for patients, promising research and treatment plans offer a potentially life-saving way to combat TRD, and everyone should be on board with that.

Fact-checked by Cherisse Harris