USE OF KETAMINE AS A TREATMENT FOR REFRACTORY DEPRESSIVE DISORDER: A NARRATIVE SYSTEMATIC REVIEW
DOI:
https://doi.org/10.56238/revgeov17n3-008Keywords:
Ketamine, Treatment-Resistant Depression, Suicidal Ideation, Treatment, SafetyAbstract
Treatment-resistant depression (TRD) affects up to one-third of patients with major depressive disorder (MDD) and is associated with high rates of morbidity, suicidal ideation, and mortality. In recent years, ketamine and its enantiomer esketamine have emerged as promising therapeutic alternatives due to their rapid antidepressant effect mediated by non-competitive NMDA receptor antagonism. The aim of this systematic review was to evaluate the effectiveness of ketamine in the treatment of TRD, including its impact on suicidal ideation, as well as its safety and tolerability. This review was registered in the PROSPERO platform (CRD420250652857). Searches were conducted in the PubMed, LILACS, Cochrane, and SciELO databases between September 2024 and August 2025. Randomized clinical trials and theses published in Portuguese and English between 2020 and 2025 were included. Two reviewers independently performed screening, data extraction, and risk of bias assessment using the Cochrane Risk of Bias tool. Of the 60 studies initially identified, nine met all inclusion criteria. The results showed that ketamine, administered through different routes (intravenous, intranasal, and intramuscular), significantly reduced depressive symptoms and suicidal ideation compared with placebo or active controls (ECT, midazolam, antidepressants). Clinical response was rapid, sometimes occurring within hours after infusion, although long-term effects remain limited. Reported adverse events were mostly mild and transient, with the most common being dissociative symptoms, headache, and cardiovascular changes. Despite promising evidence, methodological heterogeneity and short follow-up were important limitations. Larger clinical trials with longer follow-up are needed to establish dosing protocols, frequency, and maintenance strategies.
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