Treatment-resistant major depression: Systematic review of comparative efficacy of electroconvulsive therapy and ketamine

Graeff Saldanha, Giullia and Locatelli, Leonardo and Miozzo Junior, Izidione Antônio (2025) Treatment-resistant major depression: Systematic review of comparative efficacy of electroconvulsive therapy and ketamine. PHYSIOLOGY INTERNATIONAL, 111 (4). pp. 287-297. ISSN 2498-602X

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Abstract

Depression is the leading cause of disability worldwide. Major Depressive Disorder (MDD) is a condition characterized mostly by low or depressed mood as well as difficulty experiencing emotions, whether positive or negative. Poor adherence has sparked the interest from both physicians and patients in these alternative therapeutic approaches. Ketamine and Electroconvulsive Therapy (ECT) are emerging as promising options. Objective: To evaluate the results related to the efficacy and safety of the therapeutic use of ketamine within its various application methods and ECT in patients with MDD. Method: Systematic review that employed the PubMed database to collect the clinical trials that analyzed and compared the efficacy and safety of intramuscular ketamine, oral ketamine, and ECT in MDD. The files were screened by title and selected by reading the abstracts. The selected files were then read for a complete analysis according to the inclusion and exclusion criteria. Results: Seven randomized clinical trials (RCT) were selected. Ketamine displayed potential in the treatment of MDD due to its rapid-onset effect, but ECT is even more effective in terms of remission. Both treatments are safe, but they involve long-term side effects that require further study. Conclusion: Exploring how the characteristics of individual patients affect the response to ketamine and ECT can propel the development of more personalized treatments. However, the lack of long-term studies on the efficacy and safety of these therapies highlights the need for more RCTs comparing ketamine and ECT in patients with MDD.

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