TOLERANCE AND ACCEPTABILITY OF INTRAVENOUS KETAMINE THERAPY FOR TREATMENT RESISTANT DEPRESSION: A MIXED METHODS ASSESSMENT
Objectives: This study was conducted to evaluate the response of treatment resistant depression to IV ketamine therapy protocol and explore the perspectives of patients regarding the acceptability of this treatment modality.
Study Design: Mixed methods assessment including Quasi experimental design and Qualitative interviews.
Place and Duration of Study: The study was conducted at Department of Psychiatry, Fauji Foundation Hospital, Rawalpindi from Jan to Jun 2022.
Subjects and Methods: Through purposive sampling, 14 patients of treatment resistant depression were made part of the sample. Hamilton Rating scale for Depression (HAM-D) was used to measure response to 6 Ketamine infusions administered over 2 weeks. Paired t-test was applied to analyze changes in HAM-D scores compared to pretreatment baseline at 1 hour, 2 weeks and 1 month after last dose of ketamine using SPSS 26.0. Semi structured interviews were conducted to explore the attitudes of patients regarding ketamine treatment. Thematic analysis was carried out and data driven themes were identified.
Results: There was a statistically significant improvement in severity of depression scores at 1 hour and 2 weeks after the last dose of ketamine. This effect was not significantly sustained at 1 month after the last dose. Some patients expressed initial hesitation related to safety of this treatment, citing comparisons with General anesthesia. By the end of treatment, most patients were keen to be advocates for the access to Ketamine therapy due to experiencing rapid transformational effects on severe depressive symptoms.
Conclusion: IV Ketamine therapy was found to be a rapid, effective and acceptable tool for treatment resistant depression; however its longer-term effects could not be established.
2. Lépine JP, Briley M. The increasing burden of depression. Neuropsychiatr Dis Treat. 2011; 7(Suppl 1):3-7.
3. Voineskos D, Daskalakis ZJ, Blumberger DM. Management of Treatment-Resistant Depression: Challenges and Strategies. Neuropsychiatr Dis Treat. 2020; 16:221-234.
4. McLachlan G. Treatment resistant depression: what are the options? BMJ: British Medical Journal (Online). 2018; 363.
5. Marcantoni WS, Akoumba BS, Wassef M, Mayrand J, Lai H, Richard-Devantoy S, Beauchamp S. A systematic review and meta-analysis of the efficacy of intravenous ketamine infusion for treatment resistant depression: January 2009 - January 2019. J. Affect. Disord. 2020; 277: 831-841
6. Fond G, Loundou A, Rabu C, Macgregor A, Lançon C, Brittner M, et al. Ketamine administration in depressive disorders: a systematic review and meta analysis. Psychopharmacology. 2014; 231:3663–76. doi: 10.1007/s00213-014-3664-5.
7. Kraus C, Rabl U, Vanicek T, Carlberg L, Popovic A, Spies M, et al. Administration of ketamine for unipolar and bipolar depression. Int J Psychiatry Clin Pract. 2017; 21:2–12. doi: 10.1080/13651501.2016.1254802
8. Kakar M, Mustafa M, Khattak H, Naseer S. Effect of single dose of ketamine in patients of major depressive disorder-a Pakistani perspective. PAFMJ. 2020; 70(5):1332-6.
9. Griffiths C, Walker K, Reid I, da Silva KM and O’Neill-Kerr A. A qualitative study of patients’ experience of ketamine treatment for depression: the ‘ketamine and me’ project. J. Affect Disord. Rep. 2021; 4:100079. doi: 10.1016/j.jadr.2021.100079.
10. Mandal S, Sinha VK, Goyal N. Efficacy of ketamine therapy in the treatment of depression. Indian J Psychiatry. 2019; 61(5):480-485.
11. Kryst J, Kawalec P, Mitoraj AM, Pilc A, Lasoń W, Brzostek T. Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials. Pharmacol Rep. 2020; 72(3):543-562. doi: 10.1007/s43440-020-00097-z.
12. Veraart JKE, Smith-Apeldoorn SY, Spaans H-P, et al. Is ketamine an appropriate alternative to ECT for patients with treatment resistant depression? a systematic review. J Affect Disord. 2021; 281:82–89.
13. Bobo WV, Voort JLV, 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; 33: 698–710. doi: 10.1002/da.22505.
14. Memon RI, Naveed S, Faquih AE, Fida A, Abbas N, Chaudhary AMD, Qayyum Z. Effectiveness and Safety of Ketamine for Unipolar Depression: a Systematic Review. Psychiatr Q. 2020; 91(4):1147-1192. doi: 10.1007/s11126-020-09830-6.
15. Naughton M, Clarke G, O'Leary OF, Cryan JF, Dinan TG. A review of ketamine in affective disorders: current evidence of clinical efficacy, limitations of use and pre-clinical evidence on proposed mechanisms of action. J Affect Disord. 2014; 156:24-35. doi: 10.1016/j.jad.2013.11.014.
16. Kritzer MD, Pae CU, Masand PS. Key considerations for the use of ketamine and esketamine for the treatment of depression: focusing on administration, safety, and tolerability. Expert Opin Drug Saf. 2022; 21(6):725-732. doi: 10.1080/14740338.2022.2069749.
17. Le, TT, Cordero IP, Jawad MY, Swainson J, Di Vincenzo JD, Jaberi S, Phan L, Lui LMW, Ho R, Rosenblat JD, McIntyre RS. The abuse liability of ketamine: a scoping review of preclinical and clinical studies. J. Psychiatr. Res. 2022; 151: 476–496. https://doi.org/10.1016/j.jpsychires.2022.04.035.
18. Van Schalkwyk GI, Wilkinson ST, Davidson L, Silverman WK, Sanacora G. Acute psychoactive effects of intravenous ketamine during treatment of mood disorders: analysis of the clinician administered dissociative state scale. J. Affect. Disord. 2018; 227:11-16.
19. Jilka S, Murray C, Wieczorek A, Griffiths H, Wykes T, McShane R. Exploring patients’ and carers’ views about the clinical use of ketamine to inform policy and practical decisions: mixed-methods study. BJPsych Open. 2019; 5(5): p.e62
20. Grady SE, Marsh TA, Tenhouse A, Klein K. Ketamine for the treatment of major depressive disorder and bipolar depression: a review of the literature. Ment. Health Clin. 2017; 7(1):16-23.
21. Sakurai H, Jain F, Foster S, Pedrelli P, Mischoulon D, Fava M, Cusin C. Long-term outcome in outpatients with depression treated with acute and maintenance intravenous ketamine: a retrospective chart review. J. Affect. Disord. 2020; 276: 660-666.
22. Sumner RL, Chacko E, McMillan R, et al. A qualitative and quantitative account of patient’s experiences of ketamine and its antidepressant properties. Journal of Psychopharmacology. 2021; 35(8):946-961. doi:10.1177/0269881121998321