Subcutaneous Esketamine in Adolescents with Severe Depressive Episodes: A Five-Case Series

Objective: To describe the feasibility, acute tolerability, and short-term symptom trajectories of adjunctive subcutaneous esketamine in adolescents with severe depressive episodes treated in specialized outpatient care.

Methods: This observational case series included five adolescents aged 15-17 years with severe depressive symptoms, suicidal ideation and/or behavior, and insufficient response to previous treatments. Patients received eight once-weekly subcutaneous esketamine sessions, starting at 0.5 mg/kg and titrated up to 1.0 mg/kg based on clinical response and tolerability. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). MADRS-rated suicidal ideation and anhedonia-related symptoms were examined descriptively using MADRS Items 10 and 8, respectively; Item 8 was considered an indirect indicator of anhedonia-related symptoms.

Results: All patients completed the eight-session treatment course. Overall, MADRS trajectories were heterogeneous: one patient achieved remission, three presented varying degrees of partial improvement, and one showed no sustained benefit. MADRS Item 10 scores decreased from baseline to endpoint in four patients, and MADRS Item 8 scores decreased in four patients. Acute adverse effects included transient dissociative symptoms with mild agitation in one patient and mild transient elevations in blood pressure in some cases. No severe acute adverse events, emergency interventions, psychiatric hospitalizations, suicide attempts, or clear manic switches were documented during the 8-week protocol.

Conclusions: In this small uncontrolled case series, adjunctive subcutaneous esketamine was feasible under close monitoring and was associated with heterogeneous short-term depressive symptom trajectories. Decreases in MADRS-rated suicidal ideation and MADRS Item 8 scores should be considered hypothesis-generating and do not establish antidepressant efficacy, domain-specific effects, or reduced suicide risk. Controlled pediatric studies with standardized dosing, suicide-specific assessments, systematic safety monitoring, and longer follow-up are needed.