Gregory Chen

Lehigh Valley Health Network, USA

Evaluating Esketamine as a Treatment for Adolescents with Treatment Resistant Depression: A Retrospective Review of Safety, Efficacy, and Psychiatric Comorbidities

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Biography

Abstract

Objective

Evaluate the safety, tolerability, and efficacy of ketamine and esketamine in adolescents (13–21 years) with treatment-resistant mood disorders, including treatment-resistant depression (TRD) and bipolar disorder.

Introduction

Ketamine, traditionally used for sedation and pain management, is gaining attention for its psychiatric applications, but research in pediatric populations remains limited. This review examines ketamine use in hospitalized children, adolescents, and young adults, highlighting the high prevalence of psychiatric conditions like depression and suicidal ideation.

Methods

A systematic review assessed the safety, tolerability, and efficacy of ketamine and esketamine in adolescents (13–21 years) with treatment-resistant mood disorders. Two independent reviewers screened PubMed for relevant studies published in English over the past 10 years, focusing on randomized controlled and clinical trials. Extracted data included study design, sample size, dosing, duration, clinical outcomes (e.g., MADRS scores), and adverse effects. Meta-analysis was conducted where feasible, analyzing depressive symptom reduction, safety profiles, tolerability, and psychiatric comorbidities such as GAD and suicide risk.

Mechanism of Ketamine's Antidepressant Effects:

Disruption: Ketamine blocks NMDA receptors, weakening negative cognitive beliefs and recalibrating neural inferences by enhancing glutamate release. These effects lead to fast-acting antidepressant benefits, often within hours of a single sub-anesthetic dose.

Results

Efficacy: Ketamine significantly reduced depressive symptoms, with an average MADRS score decrease of 15.3 ± 11.2 points over a week compared to 8.8 ± 9.4 for midazolam (p = 0.004) Response rates (>50% reduction in MADRS) were higher for esketamine at 38.5% compared to 20% for midazolam.

Safety and Tolerability:-Adverse effects included transient dissociative symptoms in 87% of patients receiving ketamine (measured via CADSS), hypertension (3%), and somnolence (2%) No serious adverse events or misuse were reported -Subanesthetic doses (0.25–0.5 mg/kg) demonstrated improved processing speed in adolescents with major depressive disorder (p < 0.05), without cognitive declines.

Demographic Insights: Participants had an average age of 15.4 years, with 76% female predominance and high rates of psychiatric comorbidities, including GAD (33%) and prior suicide attempts (47%)

Blue Bars: Mean reduction in MADRS scores (± standard deviation), indicating improvement in depressive symptoms.

Red Bars: Response rates (% of patients with >50% reduction in MADRS scores).

Ketamine: Showed a greater reduction in MADRS scores (15.3 ± 11.2) and a higher response rate (38.5%).

Midazolam: Had a smaller reduction in MADRS scores (8.8 ± 9.4) and a lower response rate (20%).

Conclusion

Efficacy in Treatment-Resistant Depression (TRD): Preliminary evidence suggests that a single dose of intravenous ketamine can reduce depressive symptoms in adolescents with TRD, particularly those with shorter depressive episodes and fewer prior treatment failures.

Side Effect Profile: Common side effects included mild and transient dissociative symptoms such as feeling disconnected or spaced out, as well as delirium, hypertension, and somnolence, with no severe adverse events reported.

Future Research: future studies should explore repeated dosing, neurodevelopmental impacts, and predictors of response to refine ketamine’s role in treating adolescent depression.