Vol. 7, Issue 2, Part E (2025)

Treatment‑resistant depression (TRD) remains a major clinical challenge, defined commonly as failure to respond to two or more adequate antidepressant trials despite adherence. Esketamine (Spravato®), the S‑enantiomer of ketamine delivered via intranasal route, has emerged as a promising rapid‐acting adjunctive option. This review synthesizes evidence on the effectiveness of esketamine nasal spray in reducing depressive symptom severity, the assessment scales used in trials and practice, and regional variations in its adoption. Controlled clinical trials such as TRANSFORM and ESCAPE‑TRD have demonstrated that esketamine plus an oral antidepressant leads to significantly greater reductions in Montgomery–Åsberg Depression Rating Scale (MADRS) scores compared with placebo plus antidepressant, and higher rates of response and remission. Relapse‑prevention studies (e.g. SUSTAIN) suggest that maintenance use of esketamine reduces the risk of relapse relative to discontinuation. Common assessment tools include MADRS (primary), HAM‑D, PHQ‑9 (patient‑reported), CGI, and functional/quality‑of­life scales; MADRS is the most sensitive to change in esketamine trials. Safety profiles indicate primarily transient adverse effects (dissociation, dizziness, nausea, blood pressure rise), with low discontinuation rates. Regional uptake of intranasal esketamine varies: the U.S. has implemented it under a REMS (Risk Evaluation and Mitigation Strategy) framework, Europe uses more centralized or hospital‑based protocols, and adoption in Asia (including India) remains limited due to regulatory, infrastructure, and cost barriers.