Image by Dan Dimmock

Research by Dr. Thomas Swahn

Barriers to Using Ketamine for the Treatment of Depression

Abstract

Depressive disorders are prevalent in the United States. Current treatment paradigms take weeks to reach clinical efficacy and may leave patients at risk for suicide during the initial weeks of treatment. Intravenous (IV) ketamine infusions have shown promise in the rapid relief of depression symptoms, including efficacy in treatment-resistant depression and relief of suicidal ideation. Initial research has shown ketamine therapy to be safe and effective. Despite a plethora of information in support of the safety and efficacy of ketamine, there is reluctance of both patient and provider in utilizing ketamine’s unique potential. We used a grounded-theory approach to perform a meta-analysis literature review exploring the barriers preventing widespread acceptance of ketamine therapy. We found fear or moral objection to psychoactive effects, potential side effects, and history of abuse as a street drug to be inhibiting factors among patients. Among healthcare providers, barriers included lack of accessibility, addictiveness, abuse potential, and refusal of insurance policies to cover treatment. We present arguments to challenge objections and question concerns as the vast benefit of ketamine therapy far outweighs potential harms. We give recommendations for further research and call for a more rational approach to U.S. drug policy with a focus on objective evidence and an elimination of unwarranted restriction of personal freedoms.

Ketamine Therapy Educational Presentation (Length: 9:44)

Effect of Education on Perception of Ketamine in Primary Care and Mental Health Providers

Abstract

Background: Mental illness is a major healthcare problem. Depression is the leading cause of premature death and disability among adults aged 18-44 worldwide. In the United States, 21% of adults are afflicted by a mental illness. Ketamine therapy is a promising treatment for many mood disorders including treatment-resistant depression, yet is underutilized in US healthcare. Purpose: This project aimed to explore the perspectives of primary care providers and mental health providers toward ketamine therapy. Implementation: Surveys and an educational presentation were developed to identify providers’ perspectives of ketamine therapy before and after education. These were distributed to primary care practices and mental health practices from the 84015 ZIP code and surrounding areas. The surveys included open-ended qualitative questions and quantitative questions using Likert scales to evaluate views. Results: A small number of providers participated, limiting generalizability of results. Statistical analysis was performed to evaluate changes in quantitative responses, finding an increased rating of familiarity with ketamine and its psychoactive effects, as well as increased perception of safety, though there was a decreased likelihood to recommend ketamine therapy for patients or to utilize for themselves or loved ones among medical providers. Qualitative analysis was done in an iterative review revealing themes associated with ketamine in participants perspectives, with medical terminology comprising the bulk of initial perspectives and shifting post-education responses toward different themes. Discussion: The findings of this study suggest that medical providers may be less inclined to recommend ketamine therapy after education discussing its psychoactive effects despite evidence of its efficacy, whereas mental health providers show much more openness to both aspects. Future research should aim to clarify factors influencing this discrepancy and to develop more effective educational approaches.

Videos

What Ketamine Actually Does To Your Brain (Length: 4:34)

Ketamine Depression Treatment - Actify Neurotherapies Deep Dive - Steve Levine, MD (Length 39:10)

Ketamine - From Street Drug to Life Saver (Length 13:43)

The Experimental Ketamine Cure for Depression (Length 22:10)

Hamilton’s Pharmacopeia, S2E5, Ketamine: Realms and Realities

Academic Literature

Bahji, A., Vazquez, G. H., & Zarate, C. A. (2021). Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis. Journal of Affective Disorders, 278, 542–555. https://doi.org/10.1016/j.jad.2020.09.071

Dore, J., Turnipseed, B., Dwyer, S., Turnipseed, A., Andries, J., Ascani, G., Monnette, C., Huidekoper, A., Strauss, N., & Wolfson, P. (2019). Ketamine assisted psychotherapy (KAP): Patient demographics, clinical data and outcomes in three large practices administering ketamine with psychotherapy. Journal of Psychoactive Drugs, 51(2), 189-198. https://doi.org/10.1080/02791072.2019.1587556

Dwyer, J. B., Landeros-Weisenberger, A., Johnson, J. A., Londono Tobon, A., Flores, J. M., Nasir, M., Couloures, K., Sanacora, G., & Bloch, M. H. (2021). Efficacy of intravenous ketamine in adolescent treatment-resistant depression: A randomized midazolam-controlled trial. The American Journal of Psychiatry, 178(4), 352–362. https://doi.org/10.1176/appi.ajp.2020.20010018

Feder, A., Costi, S., Rutter, S. B., Collins, A. B., Govindarajulu, U., Jha, M. K., Horn, S. R., Kautz, M., Corniquel, M., Collins, K. A., Bevilacqua, L., Glasgow, A. M., Brallier, J., Pietrzak, R. H., Murrough, J. W., & Charney, D. S. (2021). A randomized controlled trial of repeated ketamine administration for chronic posttraumatic stress disorder. The American Journal of Psychiatry, 178(2), 193–202. https://doi.org/10.1176/appi.ajp.2020.20050596

Feifel D, Dadiomov D, C. Lee K. (2020). Safety of repeated administration of parenteral ketamine for depression. Pharmaceuticals, 13(7),151. https://doi.org/10.3390/ph13070151

Greenway, K. T., Garel, N., Jerome, L., & Feduccia, A. A. (2020). Integrating psychotherapy and psychopharmacology: Psychedelic-assisted psychotherapy and other combined treatments. Expert Review of Clinical Pharmacology, 13(6), 655–670. https://doi.org/10.1080/17512433.2020.1772054

Kim, S., Rush, B.S. & Rice, T.R. (2020). A systematic review of therapeutic ketamine use in children and adolescents with treatment-resistant mood disorders. European Journal of Child & Adolescent Psychiatry. https://doi.org/10.1007/s00787-020-01542-3

Mathai, D., Mathew, S. J., Storch, E. A., & Kosten, T. R. (2018). Revisiting the hallucinogenic potential of ketamine. Psychiatric Times, 35(6). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094990/

Sanacora, G., Frye, M. A., McDonald, W., Mathew, S. J., Turner, M. S., Schatzberg, A. F., Summergrad, P., & Nemeroff, C. B. (2017). A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry, 74(4), 399-405. https://doi.org/10.1001/jamapsychiatry.2017.0080

Wilkinson, S. T., Wright, D., Fasula, M. K., Fenton, L., Griepp, M., Ostroff, R. B., & Sanacora, G. (2017). Cognitive behavior therapy may sustain antidepressant effects of intravenous ketamine in treatment-resistant depression. Psychotherapy and Psychosomatics, 86(3), 162–167. https://doi.org/10.1159/000457960