Subcutaneous Ketamine for Treatment-Resistant Depression: A Case Report from Brazil

Case Report: Subcutaneous Ketamine Yields Rapid Improvement in Treatment-Resistant Depression

A newly published case report from Brazil documents rapid clinical improvement in a patient with treatment-resistant depression (TRD) following subcutaneous administration of ketamine. The patient, who had not responded to multiple pharmacological treatments or electroconvulsive therapy, received five subcutaneous ketamine injections. According to the report, the Beck Depression Inventory (BDI) score dropped from 48 (severe depression) to 29 (moderate depression) after the third injection, with this improvement sustained through the end of the protocol. The report, available via OpenAlex, adds to a small but growing body of literature exploring alternative ketamine delivery methods for psychiatric indications.

Mechanism of Action and Context: Why Subcutaneous Delivery?

Ketamine is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, and its rapid antidepressant effects have been demonstrated in several randomized controlled trials using intravenous (IV) and intranasal routes. Subcutaneous administration, while less studied, offers potential advantages: it is less invasive than IV, requires less clinical infrastructure, and may be more accessible in outpatient or resource-limited settings. The rapid reduction in depressive symptoms observed in this case aligns with ketamine's known pharmacodynamics, but the subcutaneous route's pharmacokinetics and safety profile remain poorly characterized in psychiatric populations.

Policy and Research Implications: A Need for Rigorous Trials

This case report underscores the urgent need for controlled clinical trials evaluating subcutaneous ketamine for TRD. To date, most regulatory attention—including the U.S. Food and Drug Administration's (FDA) approval of esketamine (Spravato) for TRD—has focused on intranasal or IV administration. Subcutaneous ketamine is not currently approved by the FDA, the European Medicines Agency (EMA), or Brazil's Agência Nacional de Vigilância Sanitária (ANVISA) for psychiatric use. The report's findings could inform the design of future phase II or III trials, particularly in settings where IV access is challenging. Importantly, the case highlights a non-obvious implication: subcutaneous protocols may reduce logistical barriers in public health systems, potentially expanding access in underserved regions if efficacy and safety are established.

Risks, Limitations, and Unknowns

The evidence presented is limited to a single patient, which precludes any conclusions about efficacy or safety for broader populations. Known risks of ketamine include dissociation, blood pressure elevation, and potential for misuse or dependence. The subcutaneous route may alter absorption rates, side effect profiles, and abuse potential compared to other delivery methods. There is also a lack of long-term safety data for repeated subcutaneous administration in psychiatric populations. Without randomized, controlled data, clinicians and policymakers should exercise caution in interpreting these findings beyond hypothesis generation.

Looking Forward: Research and Regulatory Pathways

Future research should prioritize randomized controlled trials comparing subcutaneous ketamine to established treatments, with careful monitoring for adverse events and misuse. Policymakers and institutional review boards (IRBs) will need to weigh the potential for expanded access against the risks of off-label use and diversion. For now, subcutaneous ketamine remains an experimental approach, but this case report may catalyze new research protocols and funding initiatives, particularly in jurisdictions seeking scalable solutions for TRD. Researchers designing such studies should consider including pharmacokinetic analyses and patient-reported outcome measures to address both efficacy and real-world feasibility.

How we research: This article was researched and written by Dr. Alex Martins, MD, PhD, with review of the original case report (OpenAlex ID: W7206152927), regulatory documents from FDA and ANVISA, and recent clinical trial registries. Reviewed by Dr. Ana Silva on 2026-09-03.