Ketamine For Depression: Is it Effective?

Henna Geronimo
December 8, 2023

Depression is a mental health issue affecting millions globally. Traditionally, treatments for depression range from psychotherapy and medication to lifestyle changes. However, for some, especially those with treatment-resistant depression, these conventional methods don't always provide relief. This prompted the exploration of alternative treatments, one of which is the use of ketamine.

Ketamine treatment shows promise in providing rapid relief from hard-to-treat depressive symptoms. In Long Beach and other parts of the world, mental health treatment facilities are beginning to incorporate ketamine therapy into their practice.

This blog delves into the effectiveness of ketamine for depression, exploring its mechanisms of action and the outcomes of patients who have undergone this groundbreaking therapy.

Ketamine treatment
Source: Roots Mental Wellness

What is Ketamine?

Ketamine is a medication primarily known for its use as an anesthetic in medical settings. Developed in the 1960s, it was widely used for its fast-acting anesthetic properties. It is noted for its safety in not depressing breathing or blood pressure.

Over the years, ketamine's use expanded beyond the operating room. Due to its unique properties, it found a place in pain management and veterinary medicine. However, its journey has been subject to controversy.

By the late 20th century, ketamine became known for its recreational misuse, overshadowing its medical benefits for a time. This dual identity has made the path of ketamine legislation and acceptance in medical circles somewhat complicated.

The Transition from Anesthetic to a Depression Treatment Option

The turning point for ketamine came with the discovery of its rapid antidepressant effects. Unlike traditional antidepressants that take time to show effects, ketamine was found to offer relief from depressive symptoms within hours or days. This revelation was particularly significant for patients who had not responded to conventional treatment methods.

The mechanism by which ketamine alleviates depression is still being studied, but it's believed to involve the enhancement of neurotransmitter pathways in the brain that are often impaired in depression. This action is notably different from that of traditional antidepressants, which mainly focus on the serotonin system.

Ketamine's role in mental health treatment has been transformative. Its ability to provide rapid relief in severe cases of depression has made it a valuable tool in the mental health treatment arsenal. However, its use is still regulated, and ketamine treatment is typically considered only after other treatments have failed.

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Ketamine's Mechanism of Action for Depression

How Ketamine Affects the Brain Differently Than Typical Antidepressants

Ketamine operates in the brain in a way that differs from traditional antidepressants, which typically target the serotonin, norepinephrine, or dopamine systems. Instead, ketamine acts on the glutamate system, the most abundant neurotransmitter in the brain, which plays a crucial role in neural activation.

Ketamine is known as an NMDA (N-methyl-D-aspartate) receptor antagonist. By blocking these receptors, it disrupts the normal function of the glutamate pathway, leading to an increase in the release of other neurotransmitters and neuroplastic changes in the brain. This is thought to contribute to mood elevation and cognitive improvement.

The Science Behind Ketamine's Rapid-Acting Relief for Some Patients

One of the most remarkable aspects of ketamine treatment is its rapid action. Ketamine can produce noticeable improvements in mood and outlook within hours or days.

This action can be particularly beneficial for those with severe depression or suicidal ideation who need immediate relief.

This rapid action is believed to be due to ketamine's immediate impact on the brain's neurochemistry. It induces an increase in synaptic connections, which can quickly counteract the synaptic deficits often found in people suffering from depression. This increase in synaptic connectivity is thought to be a key factor in the fast alleviation of depressive symptoms.

Additionally, ketamine seems to activate the brain's prefrontal cortex, an area often associated with mood regulation and decision-making, which can be underactive in people with depression. 

Clinical Evidence Supporting Ketamine Treatment

Recent clinical evidence has shed light on the effectiveness of Spravato (esketamine nasal spray) as a treatment for depression. Two pivotal Phase 3 clinical trials have demonstrated the potential of Spravato in providing rapid relief for depressive symptoms.

These trials revealed that Spravato, in combination with a comprehensive standard of care, led to significant reductions in the Montgomery-Åsberg Depression Rating Scale (MADRS) scores within 24 hours of the first dose, with some patients experiencing relief as early as four hours. This is compared to a lesser reduction in the placebo group, indicating the effectiveness of Spravato in treating depressive symptoms​​.

In another study, the Phase 3b ESCAPE-TRD Study, presented at the European Congress of Psychiatry in 2023, it was found that a significantly higher proportion of participants in the esketamine nasal spray (NS) arm achieved remission from depression at Week 6 and at every subsequent time point through Week 32, compared to the quetiapine XR arm. 

treatment-resistant depression
Source: Roots Mental Wellness

Risks and Consideration

Common side effects of using ketamine include dissociation, dizziness, nausea, sedation, and increased blood pressure, which are typically short-lived.

The FDA has approved Spravato under a Risk Evaluation and Mitigation Strategy (REMS), which includes measures to ensure the drug is taken safely and in a controlled environment. This is to mitigate the risks associated with its use, particularly the potential for abuse and misuse.

Who May Be a Good Candidate for Ketamine Treatment?

Not everyone with depression is a candidate for ketamine treatment. It's usually considered for individuals with treatment-resistant depression, meaning they have not responded to at least two different types of standard antidepressant treatments.

Candidates for Spravato treatment are evaluated case-by-case, considering their medical history, mental health status, and previous treatment responses.

Expanding Access to Innovative Mental Health Treatments

In 2023, a significant legislative development, known as the "Access to Psychedelic-Assisted Therapy Act," was introduced with the goal of expanding access to novel treatments for mental health conditions.

The Act is noteworthy for specifically including psilocybin, MDMA, and ketamine-assisted therapy in its definition of "psychedelic-assisted therapy." This inclusion marks a significant shift in the perception of these substances, historically classified as Schedule I drugs in the United States, indicating a lack of accepted medical use and a high potential for abuse.

mental health treatment Long Beach

In Conclusion

Depression affects many people, and while traditional methods exist, those with treatment-resistant depression face unique challenges. Thankfully, alternative treatments like ketamine therapy exist to offer hope for rapid relief.

If you or a loved one is navigating the challenges of depression, know that help is available. At Roots Mental Wellness, we offer innovative treatments like Ketamine and TMS therapy. Contact us to learn more about treatment options.

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Henna Geronimo
Contributing Writer