ECT vs IV Ketamine- Pilot Clinical Trial from India


Out on PubMed form investigators in India, Australia and England, with Jagadisha Thirthalli as senior author is this study:Antidepressant effects of ketamine and ECT: A pilot comparison.
Sharma RK, Kulkarni G, Kumar CN, Arumugham SS, Sudhir V, Mehta UM, Mitra S, Thanki MV, Thirthalli J.J Affect Disord. 2020 Jul 18;276:260-266. doi: 10.1016/j.jad.2020.07.066. Online ahead of print.PMID: 32697707
The abstract is copied below:

Background: To compare the antidepressant effects and cognitive adverse effects of intravenous ketamine infusion and Electro-convulsive therapy (ECT) in persons with severe depressive episodes.

Methods: This assessor-blinded randomized control trial included 25 patients (either sex; 18-65 years) meeting ICD-10 criteria for severe depression (bipolar or unipolar). Patients received either ECT (n = 13) or intravenous infusions of ketamine hydrochloride (0.5 mg/kg over 45 min; n = 12) for six alternate day sessions over a period of two weeks. Severity of depression was assessed at baseline and on every alternate day of intervention using the Hamilton Depression Rating Scale (HDRS) and self-reported Beck Depression Inventory (BDI).

Results: Baseline socio-demographic and clinical variables including HDRS (ECT: 25.15±6.58; Ketamine: 23.33±4.05, p = 0.418) and BDI (ECT: 37.07±6.58; Ketamine: 33.33±9.29; p = 0.254) were comparable. Repeated-measures analysis of variance revealed that ECT patients showed significantly greater reduction in HDRS (group*time interaction effect; F = 4.79; p<0.001) and BDI scores (group*time interaction effect; F = 3.83; p<0.01). ECT patients had higher response rate than ketamine patients [HDRS: ECT- 13/13(100%) vs ketamine- 8/12 (66.70%); p = 0.04]. This was true for remission as well [ECT- 12/13(92.30%) vs ketamine- 6/12(50%), p = 0.030; both HDRS and BDI]. Performance on Digit Symbol Substitution Test (as part of the Battery for ECT-Related Cognitive Deficits scale) significantly improved in ketamine patients (p = 0.02) while that in ECT patients worsened non significantly (p = 0.30).

Limitations: Relatively small sample size; higher proportion of dropouts in the Ketamine arm.

Conclusion: This study favoured ECT over ketamine for a better efficacy over six treatment sessions in severe depression. The results need to be replicated in larger studies.

This is a small study comparing an acute course of ECT to an acute course of IV ketamine infusions. Although ECT outperformed ketamine, ketamine was shown to be quite effective and relatively well tolerated.  The small sample size and various methodological shortcomings do not allow for definitive conclusions. Also, as an acute study, there is no information about durability of results.

Touted as yet another possible replacement for ECT, it remains to be seen what role ketamine will eventually be shown to have in the toolbox of antidepressant treatments. Ketamine quite clearly has antidepressant activity (very different from the weak signal of rTMS, discussed on 7/23/2020), but its effectiveness in real world clinical populations and safety profile have yet to be established. It seems unlikely that ketamine will significantly diminish the demand for ECT. Ketamine's role as an alternative anesthetic induction agent or supplement in ECT remains important and interesting.

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