For centuries, we have sought cures for depression. Some discoveries, such as psychotherapy and medication treatment, are now widely accepted. But they don’t work for everyone. More recently, an unorthodox drug has garnered attention as a new, possible intervention: ketamine.
Classified as a mental health disorder, depression can also affect physical health, negatively impacting most of the body’s systems. Compared to pre-pandemic reporting, depressive symptoms among adults in the United States tripled during the COVID-19 pandemic.
Depression is often treated with pharmaceutical antidepressants, but they have their limitations. Most antidepressants, like Prozac, are selective serotonin reuptake inhibitors (SSRIs). About 30% of adults with depression don’t respond to SSRIs. That’s because SSRIs target less than 20% of the neurotransmitters in a person’s brain, and the 80% that are left untreated are believed to be responsible for regulating most brain activity, including mood.
It’s clear that new pharmaceutical treatments for depression are necessary. This is where ketamine emerges as a possible candidate. While classified as a Schedule III non-narcotic substance and typically only used for anesthesia, there are now medical exemptions for ketamine use for mental health diagnoses, with new research showing promise in successful treatment of depression and suicidality, though not without notable risk.
How it Works
Some say ketamine is a “miracle drug.” So, what makes it different from other treatments?
On a clinical level, ketamine works fast and well. As a rapid acting antidepressant, users experience same-day relief after an infusion, with measurable effects three to four hours after treatment. Low-dose infusions can last five to seven days, with high-dose infusions lasting even longer. Repeated injections have shown to successfully decrease suicidal ideation by 69%, a groundbreaking discovery given that suicide remains a leading cause of death in the United States.
On a biological level, ketamine triggers glutamate production, allowing the brain to forge new neural pathways, including new positive thought patterns. Ketamine is also believed to reduce inflammation and promote the regeneration of connections between brain cells damaged by stress, which has been linked to mood disorders.
There are two types of ketamine used for depression, often administered in conjunction with antidepressants. Ketamine can be administered by nasal spray, infusion, intramuscular shot, or sublingual lozenge. Except when in lozenge form (a much lower dose), ketamine can only be administered in monitored clinical settings.
Using ketamine to treat depression isn’t risk-free. In fact, it can be quite risky for some. The potential side effects emphasize the importance of treatment being administered by a trained clinician.
Ketamine is a dissociative drug that can distort a user’s sensations and increase feelings of detachment from the environment and self. Possible side effects range from nausea and vomiting to “out-of-body” catatonic experiences, often referred to as “k-holes,” which can include hallucinations and the inability to speak or move. Some research suggests that regular ketamine use can lead to ongoing dissociative and psychotic symptoms. Further study is needed to determine the risks of frequent dissociative experiences, even with clinically appropriate dosages.
There is also risk of addiction and abuse, especially when administered outside a clinical setting. Fortunately, there is a limit to how much ketamine an individual can absorb sublingually, making it nearly 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 boomed. When a new ketamine nasal spray went on the market in 2019, over 6,000 Americans used it within the first year. The demand has also resulted in the emergence of hundreds of new ketamine wellness centers across the country.
Some patients even have pre-measured doses of ketamine shipped directly to their homes. Mindbloom, a company at the forefront of at-home services, recently conducted (and sponsored) the largest evaluation to date on the safety and effectiveness of at-home ketamine kits for depression and anxiety, with over 1,200 participants. Participants benefited from the same rapid and significant positive effects at rates consistent with clinically administered ketamine treatment. At the same time, there is little oversight for at-home treatment kits, which introduces warranted concerns considering ketamine’s potential risks.
Using ketamine to treat depression and other mental health conditions is still in its early stages. While the benefits of ketamine look promising and have successfully treated some, the associated risks are significant and need to be better understood. Ketamine itself is not a cure and should always be a part of a comprehensive treatment plan aimed at developing resiliency against symptoms. Nonetheless, this new approach provides hope to those who struggle with depression and feel left behind by conventional treatments.
Caroline Emmitt, MSW, is Policy Analyst and Izabela Sadej, LSW, is Senior Policy Analyst, at Partnered Evidence-Based Policy Resource Center (PEPReC).
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