Comparing Ketamine to Traditional Antidepressants

Medically Reviewed by Mark Hrymoc, M.D., Chief Medical Officer, double-board certified in General & Addiction Psychiatry

At the Ketamine Therapy Center, we are committed to providing innovative treatments for individuals struggling with depression and other mental health disorders. One such treatment is ketamine infusion therapy, recognized for its rapid and effective relief of symptoms, especially in cases where traditional antidepressants have not been successful.

Ketamine Therapy vs. Traditional Antidepressants: A Game-Changer in Mental Health Treatment

Depression is one of the most prevalent mental health disorders globally, yet many individuals do not respond to first-line treatments like SSRIs or SNRIs. In recent years, ketamine therapy has emerged as a powerful and rapid-acting alternative, especially for individuals with treatment-resistant depression (TRD). But how does it stack up against traditional antidepressants?

One of the earliest controlled studies to demonstrate ketamine’s antidepressant potential was conducted by Berman et al. (2000), which showed significant symptom reduction after a single IV dose in depressed patients. Since then, ketamine infusion therapy has gained recognition for its rapid and effective relief of symptoms, especially in cases where traditional medications have failed.

Unlike traditional antidepressants that modulate serotonin, norepinephrine, or dopamine, ketamine acts on the glutamate system, specifically as an NMDA receptor antagonist. This interaction promotes rapid synaptic plasticity and the growth of new neural connections, which are often impaired in people with chronic depression (Zanos & Gould, 2018).

Understanding how ketamine diverges from conventional antidepressants helps explain its remarkable effectiveness and unique role in modern mental health care:

1. Mechanism of Action

Traditional antidepressants (e.g., SSRIs, SNRIs, tricyclics) primarily work by increasing the availability of monoamines—serotonin, norepinephrine, and dopamine—in the brain (Krystal et al., 2019).

Ketamine, in contrast, blocks NMDA receptors and stimulates AMPA receptors, leading to a surge in glutamate release. This action boosts neuroplasticity and fosters the regeneration of synaptic connections, especially in the prefrontal cortex (Zanos & Gould, 2018).

2. Speed of Effect

Antidepressants typically take 2–6 weeks to show any improvement.

Ketamine often works within hours to days, offering rapid relief—especially vital for individuals in crisis or experiencing suicidal ideation (Wilkinson et al., 2018).

3. Treatment-Resistant Depression

Many patients with TRD fail to respond to multiple antidepressant regimens.

Ketamine has shown efficacy in 50–70% of patients with TRD after just a few treatments (Singh et al., 2016; Anand et al., 2023).

4. Duration of Effect

Traditional antidepressants, once effective, can offer long-term symptom stability when taken regularly.

Ketamine's effects are shorter-lived, typically lasting days to weeks, and often require maintenance infusions or doses to sustain results (Short et al., 2018).

5. Administration Method

Traditional antidepressants are taken orally on a daily basis.

Ketamine is delivered via intravenous (IV) infusion, intramuscular injection, or nasal spray (esketamine), generally under clinical supervision.

6. Side Effects Profile

Antidepressants can cause sexual dysfunction, weight gain, insomnia, and emotional blunting.

Ketamine may induce dissociation, dizziness, nausea, and transient increases in blood pressure—though these are typically short-lived and resolve quickly post-treatment (Short et al., 2018).

The Rise of Esketamine

Esketamine, a nasal spray version of ketamine, was FDA-approved in 2019 for TRD. It is designed for in-clinic use under professional supervision, offering a more accessible format for patients who might benefit from ketamine's mechanism without IV infusions (Daly et al., 2019).

Is Ketamine Safe?

Ketamine therapy is generally well-tolerated, but some patients may experience short-term side effects like dizziness, nausea, or dissociation. These effects typically resolve within an hour after treatment (Short et al., 2018). Ongoing treatment plans are closely monitored by medical professionals to minimize risks and ensure patient safety.

Seek Support

The Ketamine Therapy Center in Los Angeles offers ketamine therapy in the forms of IV, IM, and Spravato; we work with highly trained nurses, doctors, and therapists to deliver the best care possible.

Psychiatrists and therapists who work with us specialize in ketamine therapy, ensuring treatments are safe, effective, and tailored to each patient's needs. We adhere to the highest medical standards, providing a supportive environment throughout your treatment journey.

If you're considering ketamine therapy or have questions about our services, reach out to us at 310-601-9999 or visit our website for more information. Our team is here to support you on your path to healing.

References

• Anand, A., Charney, D. S., Oquendo, M. A., et al. (2023). Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. New England Journal of Medicine, 388, 2315–2325. https://doi.org/10.1056/NEJMoa2302399

• Berman, R. M., Cappiello, A., Anand, A., et al. (2000). Antidepressant effects of ketamine in depressed patients. Biological Psychiatry, 47(4), 351–354.

• Berk, M., Dean, O. M., Cotton, S. M., et al. (2014). The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: An open label trial. Journal of Affective Disorders, 157, 24–29.

• Daly, E. J., Trivedi, M. H., Janik, A., et al. (2019). Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant in Treatment-Resistant Depression. JAMA Psychiatry, 76(9), 893–903.

• Grosso, G., Galvano, F., Marventano, S., et al. (2014). Omega-3 fatty acids and depression: Scientific evidence and biological mechanisms. Oxidative Medicine and Cellular Longevity, 2014.

• Krystal, J. H., Abdallah, C. G., Sanacora, G., et al. (2019). Ketamine: A Paradigm Shift for Depression Research and Treatment. Neuron, 101(5), 774–778.

• Short, B., Fong, J., Galvez, V., Shelker, W., & Loo, C. K. (2018). Side-effects associated with ketamine use in depression: A systematic review. The Lancet Psychiatry, 5(1), 65–78.

• Singh, J. B., Fedgchin, M., Daly, E. J., et al. (2016). Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study. Biological Psychiatry, 80(6), 424–431.

• Wilkinson, S. T., Ballard, E. D., Bloch, M. H., et al. (2018). The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis. American Journal of Psychiatry, 175(2), 150–158.

• Zanos, P., & Gould, T. D. (2018). Mechanisms of ketamine action as an antidepressant. Molecular Psychiatry, 23(4), 801–811.