As an addiction psychiatrist specializing in the use of ketamine-assisted psychotherapy, both in patients with mood disorders and substance use disorders, I would like to offer some perspective about limits and possibilities of ketamine and esketamine.
Dr. Wesley Ryan
Single infusions of ketamine targeting unipolar mood symptoms indeed yield initial 24-hour response rates of about 60%-70%, though those rates fall precipitously with time.1 Where single treatments fall short in terms of durability of benefit, a series of multiple treatments – modeled around electroconvulsive therapy and pending a noninferiority study to compare the two2 – provide for more robust and durable results.3
Esketamine nasal spray, recently approved by the Food and Drug Administration for treatment-resistant major depressive disorder, consists of one of the component stereoisomers of ketamine and is administered at first twice weekly and then less frequently with time. It now, like off-label ketamine,4 sees clinical use as monotherapy for MDD, as an alternative for patients who have intolerance or lack of response to first-line treatments such as SSRIs.
Ketamine, while perhaps less directly validated and more stigmatized for psychiatric use, recently has been demonstrated in a rigorous trial as noninferior in terms of antidepressant benefit at 24 hours,5 and a multitude of published case studies document maintenance of benefit with repeat doses over a period of months.6 Ketamine notably enjoys several advantages over esketamine as a treatment option: a cost one to two orders of magnitude lower7 (esketamine nasal spray sees a wholesale price of $600-$900 per dose), greater versatility in dose, and lack of a restrictive REMS program.8 The $1-$2 cost of a dose of ketamine means that the clinical barrier of prior authorizations is largely a nonissue and may in and of itself vastly improve access to this novel and efficacious treatment.
My clinical experience involves providing ketamine as an intramuscular bolus along with contemporaneous psychotherapy; such combination of medication and psychotherapy intervention may be more effective than ketamine alone9 and has seen impressive initial results in the treatment of alcohol use disorder, termed ketamine psychedelic therapy.10 I can affirm these hopeful initial findings in the treatment of both mood and substance use disorders, and have observed maintained response from mood symptoms for a period of 1-4 years in several patients, with such sessions provided approximately monthly.11
I hope these preliminary data inform more rigorous study of long-term ketamine as a treatment for psychiatric indications.
Dr. Ryan is a board-certified psychiatrist and addiction psychiatrist who practices in Los Angeles. He has written several articles and a book chapter on ketamine. Dr. Ryan has no disclosures.
References
1. Murrough JW et al. Am J Psychiatry. 2013;170(10):1134-42.
2. Mathew SJ et al. Contemp Clin Trials. 2019;77:19-26.
3. Singh JB et al. Am J Psychiatry. 2016;173(8):816-26.
4. Calabrese L. Int J Psychiatr Res. 2019; 2(5):1-12.
5. Correia-Melo FS et al. J Affect Disord. 2020;264:527-34.
6. Ryan WC, Marta CJ, Koek RJ. Ketamine and depression, in “The Ketamine Papers: Science, Therapy, and Transformation.” Santa Cruz, Calif.: Multidisciplinary Association for Psychedelic Studies, 2016.
7. Institute for Clinical and Economic Review. “Esketamine for the Treatment of Treatment-Resistant Depression: Effectiveness and Value.” Final report. 2019 Jun 20.
8. Spravato package insert. Titusville, N.J.: Janssen Pharmaceuticals.
9. Dore J et al. J Psychoactive Drugs. 2019;51(2):189-98.
10. Krupitsky EM and Grinenko AY. J Psychoactive Drugs. 1997;29(2):165-83.
11. Ryan WC. Ketamine-assisted psychotherapy: Theory and chart review. KRIYA Ketamine Research Institute Conference. Hillsborough, Calif. 2019. Nov 9.