Ketamine for the treatment of mental illness: how promising is it?

For centuries, we have searched for cures for depression. Some discoveries, such as psychotherapy and drug treatment, are now widely accepted. But they don’t work for everyone. More recently, an unorthodox drug has gained attention as a new possible intervention: ketamine.

A doctor working with a microscope in a laboratory room is doing scientific research.

Depression, classified as a mental health disorder, can also affect physical health, affecting most body systems. Compared to pre-pandemic reports, symptoms of depression among adults in the United States have tripled during the COVID-19 pandemic.

Depression is often treated with pharmaceutical antidepressants, but these have their limitations. Most antidepressants, such as Prozac, are selective serotonin reuptake inhibitors (SSRIs). About 30% of adults with depression do not respond to SSRIs. This is because SSRIs affect less than 20% of the neurotransmitters in the human brain, and the 80% that are left untreated are thought to be responsible for regulating most brain activity, including mood.

It is clear that new pharmaceutical treatments for depression are needed. This is where ketamine appears as a possible candidate. Although it is classified as a Schedule III non-narcotic substance and is generally used only for anesthesia, there are currently medical exceptions to the use of ketamine for mental health diagnosis, and new research shows promise in successfully treating depression and suicidal tendencies, although not without any significant risk.

How it works

Some say that ketamine is a “miracle drug”. So what makes it different from other treatments?

On a clinical level, ketamine works quickly and well.. As a fast-acting antidepressant, users experience same-day relief after infusion with a measurable effect three to four hours after treatment. Low-dose infusions can last five to seven days, and high-dose infusions even longer. Repeated injections have been shown to successfully reduce suicidal ideation by 69%, a revolutionary finding given that suicide remains the leading cause of death in the United States.

On a biological level, ketamine triggers the production of glutamate, allowing the brain to form new neural pathways, including new patterns of positive thinking. Ketamine is also thought to reduce inflammation and promote regeneration of the connections between stress-damaged brain cells, which is associated with mood disorders.

There are two types of ketamine that are used for depression, often in combination with antidepressants. Ketamine can be given as a nasal spray, infusion, intramuscular injection, or sublingual lozenge. With the exception of the lozenge form (much lower dose), ketamine should only be administered under controlled clinical conditions.


Using ketamine to treat depression is not safe. In fact, for some it can be quite risky. Potential side effects highlight the importance of treatment by a trained physician.

Ketamine is a dissociative drug that can distort the user’s experience and increase feelings of detachment from the environment and self. Possible side effects range from nausea and vomiting to catatonic “out of body” experiences, often referred to as “k-holes,” which may include hallucinations and an inability to speak or move. Some research suggests that regular use of ketamine can lead to persistent dissociative and psychotic symptoms. Further research is needed to determine the risks of frequent dissociative experiences, even at clinically appropriate dosages.

There is also a risk of addiction and abuse, especially when administered outside the clinical setting. Fortunately, there is a limit to how much ketamine a person can absorb sublingually, making it almost impossible to overdose when taken in lozenge form.


In light of the promising benefits, and despite the potential risks, demand for ketamine treatment for depression has skyrocketed. When a new ketamine nasal spray hit the market in 2019, more than 6,000 Americans used it within the first year. Demand has also spawned hundreds of new ketamine wellness centers around the country.

For some patients, even pre-measured doses of ketamine are delivered directly to their homes. Mindbloom, a company at the forefront of home care, recently conducted (and sponsored) the largest safety and efficacy assessment to date of ketamine home treatment kits for depression and anxiety, with more than 1,200 participants. Participants experienced the same rapid and significant benefits in amounts consistent with clinical ketamine treatment. At the same time, home treatment kits are largely unsupervised, which is a legitimate concern given the potential risks of ketamine.

The use of ketamine to treat depression and other mental disorders is still in its early stages. While the benefits of ketamine look promising and have been successfully treated by some, the associated risks are significant and need to be better understood. Ketamine is not a cure by itself and should always be part of a comprehensive treatment plan aimed at developing resistance to symptoms. However, this new approach offers hope to those who struggle with depression and feel left out of traditional treatments.

Caroline Emmitt, MSW, is a Policy Analyst and Isabela Sadey, LSW, is a Senior Policy Analyst at the Partner Evidence-Based Policy Resource Center (PEPReC).


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