Ketamine’s use as a depression treatment began in the early 2000s, after originally being used predominantly as a (very safe) anesthetic since its development in the 1960s.
While its use in anesthesia has been well-established for decades, the discovery of its antidepressant properties has opened new avenues in mental health treatment. For more on ketamine’s development history, you can read our deep dive into ketamine’s timeline here.
In this post, we’ll focus on the history of ketamine’s use in treating depression and its increased popularity in the last few years.
Initial Research in 2000 at Yale: 7 Subjects, 72 Hours
The first indication that ketamine could have antidepressant properties came in the early 2000s. In 2000, a small study conducted at Yale University found that seven patients with major depression experienced significant improvement in their symptoms within 72 hours of receiving ketamine infusions. This research, published in the journal Biological Psychiatry, sparked interest in ketamine’s potential as a rapid-acting antidepressant. The conclusion? “These results suggest a potential role for NMDA receptor-modulating drugs in the treatment of depression.”
The Ketamine Research Continues
Following the initial discovery, researchers at the National Institute of Mental Health (NIMH) conducted a series of studies to further investigate ketamine’s antidepressant effects. A study published in 2006, this time with 17 subjects, demonstrated that a single low dose of intravenous ketamine produced rapid and robust antidepressant effects in patients with treatment-resistant depression.
These early findings were particularly significant because traditional antidepressants typically take weeks to months to show effects, and ketamine showed promise in alleviating depressive symptoms within hours.
Expanding Applications for Ketamine
As news of ketamine’s potential spread among the medical community, research expanded to explore its efficacy in treating various mood disorders. Studies began to investigate ketamine’s effects on bipolar depression (BPD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), suicidal ideation, generalized anxiety, postpartum depression (PPD), and more.
A 2014 study found that ketamine rapidly reduced suicidal thoughts in patients with treatment-resistant depression, independent of its effects on depressive symptoms. This finding highlighted ketamine’s potential as a life-saving intervention for individuals at high risk of suicide.
The Rise of Ketamine Clinics
As evidence supporting ketamine’s antidepressant effects accumulated, off-label use of ketamine for depression began to increase. Meanwhile, the “psychedelic renaissance” was kicking into full swing around the 2010s. While ketamine isn’t a traditional psychedelic (it’s an anesthetic), at sub-anesthetic doses, it creates a psychedelic-like experience.
The rise in ketamine research, coupled with the interest in psychedelics and the fact that ketamine is the only legal psychedelic compound in the United States, led to a substantial rise in the development of ketamine clinics.
The first ketamine clinics in the United States opened in the early 2010s, offering intravenous ketamine infusions for treatment-resistant depression. The number of ketamine clinics has grown significantly since then. According to a report by Grand View Research, the U.S. ketamine clinics market size was estimated at $3.41 billion in 2023 and is expected to grow at a compound annual growth rate (CAGR) of 10.60% from 2024 to 2030.
A Milestone: FDA Approval of Esketamine
A major milestone in ketamine’s journey as a depression treatment came in March 2019 when the U.S. Food and Drug Administration (FDA) approved Spravato (esketamine) nasal spray for treatment-resistant depression. Esketamine, the S-enantiomer of ketamine, became the first FDA-approved ketamine-based antidepressant.
This approval marked a significant shift in the treatment landscape for depression and further legitimized ketamine’s use in mental health care. While ketamine infusions and injections are still off-label (and legal) use, Spravato is the only version of ketamine that is eligible for insurance coverage due to the FDA approval.
Why Is Ketamine Such a Popular Treatment for Depression Now?
Several factors have contributed to the growing popularity of ketamine as a depression treatment:
- Rapid onset of action: Unlike traditional antidepressants, ketamine can provide relief from depressive symptoms within hours or days.
- Efficacy in treatment-resistant cases: Ketamine has shown promise in helping patients who haven’t responded to other treatments.
- Potential for long-lasting effects: Some studies suggest that the benefits of ketamine treatment can persist for weeks or months after administration (especially when paired with integration practices).
- Growing mental health awareness: Increased public awareness of mental health issues has led to greater demand for innovative treatments, especially in a post-COVID world.
As research continues and clinical applications expand, ketamine-assisted therapy is likely to play an increasingly important role in mental health treatment. However, it’s crucial to remember that ketamine should only be administered under the supervision of qualified healthcare professionals and as part of a comprehensive treatment plan.
