Ketamine Treatment and Major Depressive Disorder
Individuals with Major Depressive Disorder (MDD) can experience significant distress and disruption to social, occupational, and health domains. Hasin et al. (2018) conducted a large national survey that helped illuminate the previously under-explored epidemiology of MDD in the U.S. [1]
Around 5% of U.S. adults met criteria for MDD at any given time, while around 10% had met criteria at some point within 12 months prior, and an approximate 20% of Americans have met criteria at some point in their life time.
MDD is more common in women, with 12-month prevalence found in 13.4% of women and 7.4% in men, and lifetime prevalence found in 26.1% of women and 14.7% of men [1]
A related category of depression that is less well defined and studied is Treatment Resistant Depressant (TRD).
Individuals that meet criteria for this fail to see a reduction in depressive symptoms after traditional treatment, such as talk therapy and antidepressant medication. [2]
While not all individuals with MDD experience TRD, the designation of “treatment-resistant” suggests a need for more effective and fast-acting treatments for depression more broadly.
What is Ketamine?
Ketamine is a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, originally used as a field anesthetic by the U.S. military. [3]
While ketamine remains a schedule III substance federally, it is approved for off-label clinical prescription for anxiety and depression.
Additionally, the FDA has approved a specific form of intranasal ketamine known as eskatamine (and called “Spravato” commercially).
Ketamine Treatment and Therapy
Ketamine treatment for anxiety and depression is often explored as an alternative treatment for patients who do not respond well to talk therapy or other medications, like SSRIs and SNRIs.
That said, physicians do not require evidence of these efforts to prescribe ketamine.
There are a variety of ways physicians can prescribe ketamine for administration. Two common routes of administration are intravenous (IV) and intramuscular (IM).
These are typically administered at ketamine clinics by a clinical staff member.
Patients undergo treatment lying down, wearing eyeshades, and listening to ambient music for around three hours.
They are monitored for any medical issues, and they are cleared for dismissal and arranged transportation to their home the same day.
Ketamine Efficacy for Major Depressive Disorder
One of the most commonly cited advantages to ketamine for depression is its swift effects.
A double-blind, randomized controlled trial compared IV ketamine treatment to a placebo, and results showed that antidepressant effects for the experimental group were present and significant for fifteen days. [4]
This and other studies suggest the rapid onset of antidepressant effects, which appear within days and even hours after administration. [3]
This can be especially useful for patients who experience sharp, acute depressive episodes or suicidal ideation.
Recent research has explored ketamine treatment for MDD specifically.
Antidepressant effects in participants with MDD persisted across the days and up to two months following IV ketamine treatment. [5]
In a similar double-blind study, IM ketamine was found to be effective for patients with MDD with more than half of the participants experiencing rapid reductions in anxiety and depression. [6]
Studies also suggest that ketamine is effective for patients with comorbid or dual-diagnoses disorders.
In a 2018 study, Albott et al. (2018) found that repeated ketamine infusions were effective for a participant population of veterans with treatment resistant depression (TRD) and post-traumatic stress disorder (PTSD), with and a response rate of 93.3% for TRD and a remission rate of 80% for PTSD. [7]
Ketamine-Assisted Psychotherapy (KAP)
Medical ketamine treatment can also be paired with psychotherapy, in a process known as Ketamine-Assisted Psychotherapy (KAP).
Ketamine’s neuroplastic properties suggest that there is an ideal window of time for therapeutic progress, so KAP is often done soon before and after medication treatment. [8]
While there is interest in KAP as a supplement to medication alone, there is little research comparing ketamine alone to ketamine with psychotherapy. Larger and more robust scientific inquiry is needed to explore this.
Special and Cultural Considerations
Before a patient can receive ketamine, they must undergo a psychiatric consultation to screen for any contraindications and ensure safety.
Potential issues can occur if an individual has uncontrolled high blood pressure, hyperthyroidism, and hypertension; cardiovascular disease; and certain primary psychotic disorders. [9]
Patients who receive ketamine treatment in person are typically monitored for blood pressure and heart rate, as well as any negative psychiatric reactions, throughout treatment.
At home ketamine use via rapidly dissolving tablets or intranasal eskatmine requires a patient to self-monitor, which includes blood pressure monitoring and reports on dosing that follows prescriptive requirements.
Research projects involving ketamine treatment for participants with depression have historically underrepresented people of color.
Michaels et al. (2022) conducted a systematic analysis of demographics of double-blind ketamine clinical trials between 1993 and 2020. [10]
Out of the ten studies that provided racial demographics, 73.7% of participants were White, 9.2% Black, 5.0% Hispanic/Latinx, and 0.8% Asian.
The authors point out that despite high rates of depressive mood disorders across race and ethnicity, these trials have underrepresented them in their samples. Therefore, findings from ketamine studies might not be applicable to these groups.
Accessing Ketamine Treatment and Ketamine Assisted Psychotherapy in San Diego, CA
As mentioned, ketamine remains a scheduled substance, but it can be prescribed by a physician for off-label use to treat anxiety and depression.
Ketamine treatment always involves medical assessment and consultation with a physician, though it does not always involve psychological support from a therapist.
Those seeking to pair therapeutic and counseling support with ketamine treatment can seek out KAP specific therapists and psychedelic coaches.
At Pivot Psychedelics, our team provides psychedelic integration coaching and psychedelic therapy for individuals near San Diego, CA.
Individuals can book a free consultation to connect with team member about accessing a prescribing physician and receiving therapeutic support.
References:
Hasin, D. S., Sarvet, A. L., Meyers, J. L., Saha, T. D., Ruan, W. J., Stohl, M., & Grant, B. F. (2018). Epidemiology of adult DSM-5 major depressive disorder and its specifiers in the United States. JAMA psychiatry, 75(4), 336–346. https://doi.org/10.1001/jamapsychiatry.2017.4602
Oliveira-Maia, A. J., Bobrowska, A., Constant, E., Ito, T., Kambarov, Y., Luedke, H., Mulhern-Haughey, S., & von Holt, C. (2024). Treatment-resistant depression in real-world clinical practice: A systematic literature review of data from 2012 to 2022. Advances in therapy, 41(1), 34–64. https://doi.org/10.1007/s12325-023-02700-0
Murrough, J. W., Iosifescu, D. V., Chang, L. C., Al Jurdi, R. K., Green, C. E., Perez, A. M., Iqbal, S., Pillemer, S., Foulkes, A., Shah, A., Charney, D. S., & Mathew, S. J. (2013). Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. The American journal of psychiatry, 170(10), 1134–1142. https://doi.org/10.1176/appi.ajp.2013.13030392
Singh, J. B., Fedgchin, M., Daly, E. J., De Boer, P., Cooper, K., Lim, P., Pinter, C., Murrough, J. W., Sanacora, G., Shelton, R. C., Kurian, B., Winokur, A., Fava, M., Manji, H., Drevets, W. C., & Van Nueten, L. (2016). A double-blind, randomized, placebo-controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depression. The American journal of psychiatry, 173(8), 816–826. https://doi.org/10.1176/appi.ajp.2016.16010037
Zolghadriha, A., Anjomshoaa, A., Jamshidi, M. R., & Taherkhani, F. (2024). Rapid and sustained antidepressant effects of intravenous ketamine in treatment-resistant major depressive disorder and suicidal ideation: a randomized clinical trial. BMC psychiatry, 24(1), 341. https://doi.org/10.1186/s12888-024-05716-0
Glue, P., Neehoff, S., Beaglehole, B., Shadli, S., McNaughton, N., & Hughes-Medlicott, N. J. (2024). Ketamine for treatment-resistant major depressive disorder: Double-blind active-controlled crossover study. Journal of psychopharmacology (Oxford, England), 38(2), 162–167. https://doi.org/10.1177/02698811241227026
Albott, C. S., Lim, K. O., Forbes, M. K., Erbes, C., Tye, S. J., Grabowski, J. G., Thuras, P., Batres-Y-Carr, T. M., Wels, J., & Shiroma, P. R. (2018). Efficacy, safety, and durability of repeated ketamine infusions for comorbid posttraumatic stress disorder and treatment-resistant depression. The journal of clinical psychiatry, 79(3), 17m11634. https://doi.org/10.4088/JCP.17m11634
Yermus, R., Bottos, J., Bryson, N., De Leo, J. A., Earleywine, M., Hackenburg, E., Kennedy, S., Kezemidis, M., Kratina, S., McMaster, R., Medrano, B., Mina, M., Morisano, D., Muench, M., Pillai, S., Scharlach, R., Setlur, V., Verbora, M., Wolfson, E., Zaer, N., … Lo, C. (2024). Ketamine-assisted psychotherapy provides lasting and effective results in the treatment of depression, anxiety, and post-traumatic stress disorder at 3 and 6 months: Findings from a large retrospective effectiveness study. Psychedelic medicine (New Rochelle, N.Y.), 2(2), 87–95. https://doi.org/10.1089/psymed.2023.0021
Sayad, R., Elsaeidy, A. S., Anis, A. M., Atef, M., Hawash, E. A., Saad, H. A., Hamad, K. A. A., & Kohaf, N. A. (2025). Safety considerations and risk mitigation strategies for ketamine use: a comprehensive review. Annals of medicine and surgery (2012), 87(5), 2829–2837. https://doi.org/10.1097/MS9.0000000000003232
Michaels, T. I., Lester, L., de la Salle, S., & Williams, M. T. (2022). Ethnoracial inclusion in clinical trials of ketamine in the treatment of mental health disorders. Journal of studies on alcohol and drugs, 83(4), 596–607
