A Systematic Review of Methodological Approaches in Indian Studies Evaluating Effectiveness of Ketamine Therapy for Psychiatric Disorders: Recommendations for Future Research

A systematic review of Indian studies on ketamine for psychiatric disorders found that while interest is growing, most of the 13 included studies have significant methodological weaknesses. The studies were mostly single-center prospective trials with small sample sizes (median 25 participants). Only five reported randomization, two blinded outcome assessors, and none used a double-blind design. Adverse effects were typically assessed through unstructured observation or self-report rather than systematic tools. The review recommends that future research adopt rigorous designs including proper randomization, control groups, blinding, structured safety monitoring, and adequate sample sizes to improve reliability and generalizability.

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Abstract

Ketamine has emerged as a promising treatment strategy for several psychiatric disorders, with rising number of studies examining its safety and efficacy in Indian settings. However, concerns remain regarding their methodological robustness. To systematically review and evaluate the methodological quality of Indian studies assessing the use of ketamine for treating psychiatric disorders and provide recommendations for improving future research design. Review was conducted in accordance with the PRISMA 2020 guidelines and preregistered protocol on PROSPERO (CRD42025640071). PubMed, Google Scholar, and journals of national and zonal branches of the Indian Psychiatric Society journals were systematically searched to identify eligible studies published till December 2024 as per the predefined criteria. Details related to study methodology and ketamine administration were extracted and synthesized narratively. Thirteen studies were included. Most were single-centered prospective trials with small sample sizes (median: 25). Only five studies reported randomization, two involved blinding of outcome assessors, and none used double-blind design. Efficacy was assessed using standardized psychiatric scales; however, adverse effects were primarily evaluated using unstructured observation or self-report. Allocation concealment, flexible dosing, and systematic safety monitoring were infrequently reported. Although Indian studies demonstrate growing interest in exploring ketamine treatment for psychiatric disorders, especially depression, majority of them suffer from significant methodological limitations. Future research should prioritize adopting a rigorous study design including proper randomization, appropriate control group, blinding of participants, and outcome assessors, using structured tools for assessment of ketamine-related adverse events and adequate sample size to enhance reliability and generalizability of study findings.