Exploring the Therapeutic Potential of Ketamine and Psilocybin in Comparison to Current Treatment Regimens for Treatment-Resistant Depression, Mood Disorders, and Post-traumatic Stress Disorder in the Pediatric Population: A Narrative Review

Author: mycolabadmin
8/18/2025
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Summary

This review examines two emerging psychiatric treatments—ketamine and psilocybin—for treating hard-to-treat mental health conditions in children and teenagers. Both work by affecting brain chemicals differently than traditional medications and can provide rapid symptom relief, sometimes within hours or days rather than weeks. The study found promising results for depression, anxiety, PTSD, and bipolar disorder, though researchers emphasize that more studies are needed to ensure these treatments are safe for developing brains and that careful ethical guidelines must be established.

Background

The COVID-19 pandemic highlighted the burden of psychiatric disorders in the pediatric population, revealing a need for rapid-onset therapies. Ketamine and psilocybin have emerged as promising alternatives due to their ability to modulate glutamate pathways through distinct mechanisms: ketamine as an NMDA receptor antagonist and psilocybin as a 5-HT2A receptor agonist.

Objective

This narrative review explores the efficacy and therapeutic potential of ketamine and psilocybin compared to current treatment regimens for pediatric treatment-resistant depression (TRD), mood disorders (anxiety and bipolar disorder), and post-traumatic stress disorder (PTSD). The study aimed to assess safety profiles, clinical outcomes, and ethical considerations for these emerging therapies in children and adolescents.

Results

Ketamine demonstrated rapid-onset antidepressant effects in pediatric TRD with 76% response within three days versus 35% for midazolam. Intravenous ketamine proved nearly three times more effective than intranasal administration. Psilocybin-assisted therapy showed 71% marked depressive symptom reduction and 70% clinical remission for anxiety at six months. Both agents showed efficacy for mood disorders and PTSD, with ketamine-assisted psychotherapy producing substantial PTSD symptom reductions and psilocybin enhancing neural plasticity for traumatic memory reframing.

Conclusion

Ketamine and psilocybin show significant promise as rapid-acting treatments for pediatric TRD, mood disorders, and PTSD, with mechanisms distinct from traditional therapies. Further research is needed to establish optimal dosing, long-term safety profiles in developing brains, and standardized treatment protocols. Ethical considerations regarding neuroplasticity changes and informed consent in pediatric populations require careful evaluation before widespread clinical adoption.

Published in:Cureus,
Study Type:Narrative Review,
Source: PMID: 40970030