REVOLUTIONIZING DEPRESSION TREATMENT: A PARADIGM SHIFT OF KETAMINE THERAPY – A SYSTEMATIC REVIEW

Authors

  • YUVRAJ KAUSHAL Department of Pharmacology, Government Medical College, Patiala, Punjab, India. https://orcid.org/0009-0000-0314-3742
  • PRANAV GOYAL Department of Pharmacology, Government Medical College, Patiala, Punjab, India.
  • ARSHIYA SEHGAL Department of Pharmacology, Government Medical College, Patiala, Punjab, India. https://orcid.org/0000-0001-7293-6156

DOI:

https://doi.org/10.22159/ajpcr.2024v17i8.51360

Keywords:

Ketamine, Treatment-resistant depression, Intranasal ketamine, Depression management

Abstract

Objectives: Primary Objective: (1) The objectives of the study are as follows: assessment of the effectiveness of ketamine-based treatment in known patients of various subtypes of depression and (2) assessment of time of onset and duration along with routes of administration and safety of ketamine therapy. Secondary Objective: The objectives of the study are as follows: (1) evaluate changes in secondary outcomes in scales of depression and anxiety reporting improvement in overall mood and (2) emphasizing the need for extensive research and patient-based data collection for the future.

Methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the literature analysis included fourteen primary clinical studies including randomized controlled trials (RCTs), using electronic databases such as Google Scholar, MEDLINE, or PubMed for our search for relevant literature. RCTs and open-label case reports of adult patients with bipolar illness, major depressive disorder, or postpartum depression receiving ketamine through intravenous infusions or intranasal esketamine were included in the inclusion criteria. Potential review bias and data extraction were done independently by many reviewers with any discrepancies discussed by the team.

Results: MADRS was used as first-order outcomes and other depression and anxiety scales as second-order outcomes. Multiple studies revealed that ketamine therapy reduced the MADRS score, and this reduction occurred 40 min after the infusion and lasted up to 1 week. Moreover, the use of ketamine has proved helpful in addressing anxiety disorders and self-assessed depression, and some studies have demonstrated long-lasting effects of the drug. The safety findings indicated that ketamine was generally safe, as many of the side effects were reported on the same day of administration.

Discussion: This shows that ketamine therapy, especially for patients with treatment-resistant depression (TRD), can be a fast and effective biological treatment for depressive disorders. It could complement or even become a new treatment option due to its immediate onset and prolonged duration of action. Further studies should be conducted to determine the optimal administration intervals, side effects including cognitive impairment, and the frequency of relapses.

Conclusion: Ketamine has emerged as a new class of intervention for the management of depression due to its rapid and sustained antidepressant efficacy with lower risk of side effects. Although it is effective on its own for treating various conditions, there is a need for further research to determine how best to apply it clinically and to establish its side effects in the long run. However, given that ketamine holds the promise of filling the gaps for TRD patients, the substance plays a crucial role in changing the landscape of psychopharmacological management of depression.

Downloads

Download data is not yet available.

References

World Health Organization: Depression Fact Sheet. Available from: https://www.who.int/en/news-room/fact-sheets/detail/depression2020

Ferrari AJ, Charlson FJ, Norman RE, Patten SB, Freedman G, Murray CJ, et al. Burden of depressive disorders by country, sex, age, and year: Findings from the global burden of disease study 2010. PLoS Med. 2013 Nov;10(11):e1001547. doi: 10.1371/journal.pmed.1001547. PMID: 24223526; PMCID: PMC3818162

National Institute of Mental Health. Statistics: Major Depression. Available from: https://www.nimh.nih.gov/health/statistics/major-depression.shtml 2019 [Last accessed on 2021 Apr 27].

Gautam S, Jain A, Gautam M, Vahia VN, Grover S. Clinical practice guidelines for the management of depression. Indian J Psychiatry. 2017 Jan;59(Suppl 1):S34-50. doi: 10.4103/0019-5545.196973. PMID: 28216784; PMC5310101

Nemeroff CB. Prevalence and management of treatment-resistant depression. J Clin Psychiatry. 2007;68 Suppl 8:17-25. PMID: 17640154

Ionescu DF, Rosenbaum JF, Alpert JE. Pharmacological approaches to the challenge of treatment-resistant depression. Dialogues Clin Neurosci. 2015 Jun;17(2):111-26. doi: 10.31887/DCNS.2015.17.2/ dionescu. PMID: 26246787, PMC4518696

Berlim MT, Turecki G. Definition, assessment, and staging of treatment-resistant refractory major depression: A review of current concepts and methods. Can J Psychiatry. 2007 Jan;52(1):46-54. doi: 10.1177/070674370705200108. PMID: 17444078

Bobo WV, Vande Voort JL, Croarkin PE, Leung JG, Tye SJ, Frye MA. Ketamine for treatment-resistant unipolar and bipolar major depression: Critical review and implications for clinical practice. Depress Anxiety. 2016 Aug;33(8):698-710. doi: 10.1002/da.22505. PMID: 27062450

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29;372:n71. doi: 10.1136/bmj.n71. PMID: 33782057, PMC8005924

Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: A two-site randomized controlled trial. Am J Psychiatry. 2013 Oct;170(10):1134-42. doi: 10.1176/appi. ajp.2013.13030392. PMID: 23982301, PMC3992936

Zarate CA Jr., Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A, et al. Replication of ketamine’s antidepressant efficacy in bipolar depression: A randomized controlled add-on trial. Biol Psychiatry. 2012 Jun 1;71(11):939-46. doi: 10.1016/j. biopsych.2011.12.010. PMID: 22297150, PMC3343177

Lapidus KA, Levitch CF, Perez AM, Brallier JW, Parides MK, Soleimani L, et al. A randomized controlled trial of intranasal ketamine in major depressive disorder. Biol Psychiatry. 2014 Dec 15;76(12):970-6. doi: 10.1016/j.biopsych.2014.03.026, PMID: 24821196, PMC4185009

Altinay M, Karne H, Anand A. Administration of sub-anesthetic dose of ketamine and electroconvulsive treatment on alternate week days in patients with treatment resistant depression: A double blind placebo controlled trial. Psychopharmacol Bull. 2019 Feb 15;49(1):8-16. PMID: 30858635, PMC6386425

Fu DJ, Ionescu DF, Li X, Lane R, Lim P, Sanacora G, et al. Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients who have active suicidal ideation with intent: Double-blind, randomized study (ASPIRE I). J Clin Psychiatry. 2020 May 12;81(3):19m13191. doi: 10.4088/JCP.19m13191. PMID: 32412700

Shiroma PR, Thuras P, Wels J, Albott CS, Erbes C, Tye S, et al. A randomized, double-blind, active placebo-controlled study of efficacy, safety, and durability of repeated vs single subanesthetic ketamine for treatment-resistant depression. Transl Psychiatry. 2020 Jun 26;10(1):206. doi: 10.1038/s41398-020-00897-0. PMID: 32591498; PMCID: PMC7319954.

Zou L, Min S, Chen Q, Li X, Ren L. Subanesthetic dose of ketamine for the antidepressant effects and the associated cognitive impairments of electroconvulsive therapy in elderly patients-A randomized, double-blind, controlled clinical study. Brain Behav. 2021 Jan;11(1):e01775. doi: 10.1002/brb3.1775, PMID: 33305900, PMC7821612

Ionescu DF, Fu DJ, Qiu X, Lane R, Lim P, Kasper S, et al. Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide ideation with intent: Results of a phase 3, double-blind, randomized study (ASPIRE II). Int J Neuropsychopharmacol. 2021 Jan 20;24(1):22-31. doi: 10.1093/ijnp/ pyaa068. PMID: 32861217, PMC7816667

Alipoor M, Loripoor M, Kazemi M, Farahbakhsh F, Sarkoohi A. The effect of ketamine on preventing postpartum depression. J Med Life. 2021 Jan-Mar;14(1):87-92. doi: 10.25122/jml-2020-0116. PMID: 33767791, PMC7982256

Canuso CM, Ionescu DF, Li X, Qiu X, Lane R, Turkoz I, et al. Esketamine nasal spray for the rapid reduction of depressive symptoms in major depressive disorder with acute suicidal ideation or behavior. J Clin Psychopharmacol. 2021 Sep-Oct 01;41(5):516-24. doi: 10.1097/ JCP.0000000000001465. PMID: 34412104, PMC8407443

Han Y, Li P, Miao M, Tao Y, Kang X, Zhang J. S-ketamine as an adjuvant in patient-controlled intravenous analgesia for preventing postpartum depression: A randomized controlled trial. BMC Anesthesiol. 2022 Feb 16;22(1):49. doi: 10.1186/s12871-022-01588-7. PMID: 35172727, PMC8848809

Jones RR, Freeman MP, Kornstein SG, Cooper K, Daly EJ, Canuso CM, et al. Efficacy and safety of esketamine nasal spray by sex in patients with treatment-resistant depression: Findings from short-term randomized, controlled trials. Arch Womens Ment Health. 2022 Apr;25(2):313-26. doi: 10.1007/s00737-021-01185-6, PMID: 34973081, PMC8921149

Ochs-Ross R, Wajs E, Daly EJ, Zhang Y, Lane R, Lim P, et al. Comparison of long-term efficacy and safety of esketamine nasal spray plus oral antidepressant in younger versus older patients with treatment-resistant depression: Post-Hoc analysis of SUSTAIN-2, a long-term open-label phase 3 safety and efficacy study. Am J GeriatrPsychiatry. 2022 May;30(5):541-56. doi: 10.1016/j.jagp.2021.09.014, PMID: 34750057

Niciu MJ, Luckenbaugh DA, Ionescu DF, Guevara S, Machado-Vieira R, Richards EM, et al. Clinical predictors of ketamine response in treatment-resistant major depression. J Clin Psychiatry. 2014 May;75(5):e417-23. doi: 10.4088/JCP.13m08698. PMID: 24922494, PMC4310499

Daly EJ, Trivedi MH, Janik A, Li H, Zhang Y, Li X, et al. Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: A randomized clinical trial. JAMA Psychiatry. 2019 Sep 1;76(9):893-903. doi: 10.1001/ jamapsychiatry.2019.1189. PMID: 31166571, PMC6551577

Sanacora G, Zarate CA, Krystal JH, Manji HK. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov. 2008 May;7(5):426-37. doi: 10.1038/ nrd2462. PMID: 18425072, PMC2715836

White PF, Way WL, Trevor AJ. Ketamine--its pharmacology and therapeutic uses. Anesthesiology. 1982 Feb;56(2):119-36. doi: 10.1097/00000542-198202000-00007. PMID: 6892475

Schroeder C, Jordan J. Norepinephrine transporter function and human cardiovascular disease. Am J Physiol Heart Circ Physiol. 2012 Dec 1;303(11):H1273-82. doi: 10.1152/ajpheart.00492.2012, PMID: 23023867

Singh B, Bobo WV, Rasmussen KG, Stoppel CJ, Rico JA Jr., Schak KM, et al. The association between body mass index and remission rates in patients with treatment-resistant depression who received intravenous ketamine. J Clin Psychiatry. 2019 Nov 12;80(6):19l12852. doi: 10.4088/ JCP.19l12852, PMID: 31721482

Furman JL, Soyombo A, Czysz AH, Jha MK, Carmody TJ, Mason BL, et al. Adiponectin moderates antidepressant treatment outcome in the combining medications to enhance depression outcomes randomized clinical trial. Pers Med Psychiatry. 2018 Aug-Sep;9-10:1-7. doi: 10.1016/j.pmip.2018.05.001, PMID: 30859144, PMC6408148

Salvadore G, Cornwell BR, Colon-Rosario V, Coppola R, Grillon C, Zarate CA Jr., et al. Increased anterior cingulate cortical activity in response to fearful faces: A neurophysiological biomarker that predicts rapid antidepressant response to ketamine. Biol Psychiatry. 2009 Feb 15;65(4):289-95. doi: 10.1016/j.biopsych.2008.08.014, PMID: 18822408, PMC2643469

Chen CH, Ridler K, Suckling J, Williams S, Fu CH, Merlo-Pich E, et al. Brain imaging correlates of depressive symptom severity and predictors of symptom improvement after antidepressant treatment. Biol Psychiatry. 2007 Sep 1;62(5):407-14. doi: 10.1016/j. biopsych.2006.09.018, PMID: 17217921

Xu Y, Hackett M, Carter G, Loo C, Gálvez V, Glozier N, et al. Effects of low-dose and very low-dose ketamine among patients with major depression: A systematic review and meta-analysis. Int J Neuropsychopharmacol. 2016 Apr 20;19(4):pyv124. doi: 10.1093/ijnp/ pyv124. PMID: 26578082, PMC4851268

Farré M, Camí J. Pharmacokinetic considerations in abuse liability evaluation. Br J Addict. 1991 Dec;86(12):1601-6. doi: 10.1111/j.1360- 0443.1991.tb01754.x, PMID: 1786493

Maeng S, Zarate CA Jr. The role of glutamate in mood disorders: Results from the ketamine in major depression study and the presumed cellular mechanism underlying its antidepressant effects. Curr Psychiatry Rep. 2007 Dec;9(6):467-74. doi: 10.1007/s11920-007- 0063-1, PMID: 18221626

Sapkota A, Khurshid H, Qureshi IA, Jahan N, Went TR, Sultan W, et al. Efficacy and safety of intranasal esketamine in treatment-resistant depression in adults: A systematic review. Cureus. 2021 Aug 21;13(8):e17352. doi: 10.7759/cureus.17352. PMID: 34447651, PMC8381465

Published

07-08-2024

How to Cite

YUVRAJ KAUSHAL, PRANAV GOYAL, and ARSHIYA SEHGAL. “REVOLUTIONIZING DEPRESSION TREATMENT: A PARADIGM SHIFT OF KETAMINE THERAPY – A SYSTEMATIC REVIEW”. Asian Journal of Pharmaceutical and Clinical Research, vol. 17, no. 8, Aug. 2024, pp. 27-35, doi:10.22159/ajpcr.2024v17i8.51360.

Issue

Section

Original Article(s)