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

Summary & key facts

This paper is a review of previous studies that looked at whether two fast-acting drugs, ketamine and psilocybin, might help children and teens with hard-to-treat depression, mood problems like anxiety or bipolar depression, and post-traumatic stress disorder. The authors used a standard method for picking papers to review what we know so far. They found early evidence that ketamine can produce quick reductions in depressive symptoms in young people and that psilocybin can reduce symptoms in people with long-standing depression. The review also says both drugs seem to work by changing a brain chemical system called glutamate, but the evidence is still limited, ethical questions remain, and more research is needed before these treatments could be widely used in children.

Key facts:

• The authors looked over existing studies using a standard process for reviews to compare ketamine and psilocybin with current treatments for young people with non-psychotic psychiatric problems.
• Ketamine is already used safely by doctors as an anesthetic for children, and some studies show it can give fast relief of depressive symptoms in children and adolescents.
• Psilocybin, the active ingredient in 'magic mushrooms', has been reported to reduce symptoms in people with long-standing or treatment-resistant depression, though much of this evidence is not specific to children.
• Both drugs appear to affect the brain's glutamate system. Ketamine blocks a receptor called NMDA and psilocybin stimulates a serotonin receptor, and both actions are linked to increased glutamate release.
• In studies of young people with mood disorders, ketamine tended to be tolerated reasonably well and showed symptom improvements for anxiety and bipolar depression in some reports.
• For PTSD, some studies reported that ketamine-assisted psychotherapy reduced PTSD symptoms, but results were mixed across different groups of patients.
• Psilocybin may help by increasing brain plasticity, which can make it easier for patients to revisit and reframe difficult memories when used together with therapy.
• The authors highlight ethical concerns about giving dissociative or hallucinogenic drugs to children and call for more research on exact brain targets, safety, and long-term effects before wider pediatric use.

Abstract

The stresses of the Coronavirus Disease of 2019 (COVID-19) pandemic highlighted the burden of psychiatric disorders within the pediatric population, revealing a pre-existing need for rapid-onset therapies that have since driven efforts to expand effective therapeutic interventions. In this narrative review, we utilized the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines to direct our report and study selection. We explored the current-state efficacy and therapeutic potential of ketamine and psilocybin in comparison to current treatment regimens for pediatric non-psychotic disorders, including Treatment-Resistant Depression (TRD), mood disorders like anxiety and bipolar disorder, and Post-Traumatic Stress Disorder (PTSD). We chose these pediatric disorders to eliminate concerns regarding reality orientation and the use of dissociative and/or psychedelic medicines in patients who are experiencing symptoms of psychosis. Also, we briefly discuss ketamine's more widely accepted utilization by medical providers as a pediatric anesthetic, and how this gives credence to further evaluation of ketamine's multifaceted indications in pediatric psychiatry. Recent studies have shed light on the involvement of glutamate pathways in the pathophysiology of TRD, mood disorders, and PTSD, and both ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, and psilocybin, a 5-hydroxytryptamine receptor 2A (5-HT2A) agonist, have emerged as promising options due to their ability to augment glutamate release. Ketamine's use for pediatric TRD demonstrated rapid-onset relief for signs and symptoms of depression in children and adolescents, and psilocybin also decreased symptoms in patients with longstanding or refractory depression. Ketamine has been well tolerated and exhibited symptom improvements for youth with mood disorders such as anxiety and bipolar depression, while psilocybin showed promise in fostering emotional processing. In youth suffering from PTSD, ketamine-assisted psychotherapy (KAP) brought about decreases in PTSD symptom severity, though outcomes varied across populations. Psilocybin enhanced neural plasticity, allowing patients to revisit and reframe memories under therapeutic guidance, especially for those with complex or treatment-resistant PTSD. Ethical considerations are involved in the use of dissociative and hallucinogenic therapies like ketamine and psilocybin in the pediatric population, and we explore some ethical issues regarding their use. Further research exploring specific brain locations and mechanisms of action underlying glutamate modulation by ketamine and psilocybin, and the subsequent rapid-acting relief of psychiatric symptoms offered by these substances, could pave the way for innovative treatments targeting pediatric mental health disorders.

Topics

Chemical synthesis and alkaloids Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Clinical psychology Depression (economics) Economics Environmental health Hallucinogen Intensive care medicine Ketamine Macroeconomics Major depressive disorder Medicine Mood Narrative review Population Posttraumatic stress Psilocybin Psychiatry Psychology Psychotherapist Traumatic stress

Substances

Ketamine Psilocybin

Conditions & symptoms

Anxiety Depression PTSD Anxiety or worry Feeling disconnected from others Sadness or low mood