Rapid Acting Antidepressants: New Treatments, New Hope, and New Insights into the Brain
Presenting Author(s): Dr. John Krystal, MD
Date and time: 23 Mar 2024 from 09:00 to 10:00
Location: Wildrose Salon A/B (Virtual)
Learning Objectives
1. Discuss limitations of traditional antidepressants;
2. Present distinctive scope of ketamine and Esketamine efficacy; and
3. To review mechanisms underlying ketamine efficacy that may guide the next generation of ketamine/Esketamine treatment.
Literature References
1. Krystal JH, Kavalali ET, Monteggia LM. Ketamine and rapid antidepressantaction: new treatments and novel synaptic signaling mechanisms.Neuropsychopharmacology. 2023 Jul 24. doi: 10.1038/s41386-023-01629-w. Epubahead of print. PMID: 37488280.
2. Duek O, Korem N, Li Y, Kelmendi B, Amen S, Gordon C, Milne M, Krystal JH,Levy I, Harpaz-Rotem I. Long term structural and functional neural changesfollowing a single infusion of Ketamine in PTSD. Neuropsychopharmacology. 2023Oct;48(11):1648-1658. doi: 10.1038/s41386-023-01606-3. Epub 2023 Jun 3. PMID:37270621; PMCID: PMC10517133.
3. Fineberg SK, Choi EY, Shapiro-Thompson R, Dhaliwal K, Neustadter E, SakheimM, Null K, Trujillo-Diaz D, Rondeau J, Pittaro GF, Peters JR, Corlett PR,Krystal JH. A pilot randomized controlled trial of ketamine in BorderlinePersonality Disorder. Neuropsychopharmacology. 2023 Jun;48(7):991-999. doi:10.1038/s41386-023-01540-4. Epub 2023 Feb 17. PMID: 36804489; PMCID:PMC10209175.
4. Holmes SE, Finnema SJ, Naganawa M, DellaGioia N, Holden D, Fowles K, Davis M,Ropchan J, Emory P, Ye Y, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, DumanRS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Imaging the effect ofketamine on synaptic density (SV2A) in the living brain. Mol Psychiatry. 2022Apr;27(4):2273-2281. doi: 10.1038/s41380-022-01465-2. Epub 2022 Feb 15. PMID:35165397; PMCID: PMC9133063.
5. Abdallah CG, Roache JD, Gueorguieva R, Averill LA, Young-McCaughan S, ShiromaPR, Purohit P, Brundige A, Murff W, Ahn KH, Sherif MA, Baltutis EJ, RanganathanM, D'Souza D, Martini B, Southwick SM, Petrakis IL, Burson RR, Guthmiller KB,López-Roca AL, Lautenschlager KA, McCallin JP 3rd, Hoch MB, Timchenko A, SouzaSE, Bryant CE, Mintz J, Litz BT, Williamson DE, Keane TM, Peterson AL, KrystalJH. Dose-related effects of ketamine for antidepressant-resistant symptoms ofposttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial.Neuropsychopharmacology. 2022 Jul;47(8):1574-1581. doi:10.1038/s41386-022-01266-9. Epub 2022 Jan 19. Erratum in:Neuropsychopharmacology. 2022 May 11;: PMID: 35046508; PMCID: PMC8767037.
6. Abdallah CG, Averill LA, Gueorguieva R, Goktas S, Purohit P, Ranganathan M,Sherif M, Ahn KH, D'Souza DC, Formica R, Southwick SM, Duman RS, Sanacora G,Krystal JH. Modulation of the antidepressant effects of ketamine by the mTORC1inhibitor rapamycin. Neuropsychopharmacology. 2020 May;45(6):990-997. doi:10.1038/s41386-020-0644-9. Epub 2020 Feb 24. PMID: 32092760; PMCID: PMC7162891.
Abstract
Twenty-five years ago, we first reported ketamine’s rapid and profound antidepressant effects. This presentation will describe the development of ketamine and Esketamine as transformative treatments for antidepressant-resistant symptoms of depression. It will then review emerging insights into ketamine’s mechanisms of action that link its efficacy to the underlying biology of depression and that suggest novel ways to enhance ketamine efficacy.