Ketamine for Teen Suicidal Ideation: First ED Trial

Adolescent suicide is the second leading cause of death among 10- to 19-year-olds in the United States, and emergency departments are increasingly the first point of contact for teens in crisis. Yet until recently, no randomized controlled trial had tested ketamine specifically for adolescent suicidal ideation in an ED setting. That changed in 2026 with the publication of a pilot RCT by Schlegelmilch and colleagues in BMC Psychiatry.

Why This Study Matters

Most of what we know about ketamine and suicidal ideation comes from adult populations. The well-known meta-analyses — including those we covered in our post on ketamine's rapid reduction of suicidal ideation in adults — demonstrated that ketamine can reduce SI scores within hours. But extrapolating adult findings to adolescents raises legitimate questions about safety, dosing, and developmental neurobiology.

Schlegelmilch et al. designed the first RCT to address that gap directly: testing a single sub-anesthetic IV ketamine infusion (0.5 mg/kg over 40 minutes) versus active placebo in adolescents presenting to the ED with acute suicidal ideation.

Study Design

The trial enrolled adolescents aged 13 to 17 who presented to a pediatric emergency department with clinically significant suicidal ideation, measured by the Columbia-Suicide Severity Rating Scale (C-SSRS). Key design features included:

• Randomization to IV ketamine (0.5 mg/kg) or midazolam as active placebo
• Primary outcome: feasibility of recruitment, randomization, and retention in a pediatric ED setting
• Secondary outcomes: change in SI scores at 4 hours, 24 hours, and 72 hours post-infusion
• Safety monitoring: vital signs, dissociative symptoms (via the Clinician-Administered Dissociative States Scale), and adverse events

As a pilot study, it was not powered to detect definitive treatment effects, but rather to determine whether a full-scale trial would be feasible and safe in this population.

Key Findings

The results were encouraging on multiple fronts:

1. Feasibility confirmed. Recruitment and retention rates exceeded pre-specified thresholds. Families and adolescents were willing to participate, which had been a major concern given the acuity of the setting and the age of the patients.

2. Rapid reduction in SI scores. Adolescents in the ketamine arm showed a meaningful decline in C-SSRS scores at both 4 and 24 hours compared to placebo, though the small sample size limits statistical inference.

3. Acceptable safety profile. Transient dissociative symptoms and mild elevations in blood pressure were observed, consistent with what is seen in adult studies and in pediatric anesthesia contexts. No serious adverse events were reported.

4. Parental acceptance. Caregivers reported high satisfaction and willingness to consider ketamine as a treatment option — an important finding for future enrollment in larger trials.

How This Differs from Adult Research

The adult literature on ketamine and suicidal ideation is substantially more developed. Multiple meta-analyses have confirmed rapid anti-suicidal effects in adults across both IV and intranasal routes. The Schlegelmilch trial is notable because:

• It is the first randomized trial in adolescents in an acute care setting
• Adolescents may metabolize ketamine differently, and the developing brain responds to NMDA receptor modulation in ways that are not fully characterized
• The ED context adds complexity — unlike outpatient infusion clinics, emergency departments must manage rapid triage, family dynamics, and discharge planning simultaneously

These differences mean that adult data cannot simply be applied to teens without dedicated trials like this one.

Limitations

The authors are transparent about the study's boundaries:

• Small sample size — the trial was designed as a pilot, not a definitive efficacy study
• Single infusion — the study tested one dose, not repeated administrations
• IV route only — this does not address oral or sublingual ketamine, which is the route used in at-home treatment models
• Short follow-up — 72 hours is not enough to assess durability of benefit or longer-term safety
• Single site — generalizability to other ED populations remains to be established

A larger, multi-site RCT will be needed to determine whether ketamine should become part of standard ED care for adolescent SI.

What This Means for the Future

This pilot trial opens the door to something the field has needed for years: rigorous, adolescent-specific evidence for ketamine in acute suicidal crises. If a larger trial confirms these preliminary findings, ketamine could become a critical tool for emergency physicians managing the pediatric mental health crisis.

For now, ketamine treatment for suicidal ideation remains better established in adults. Isha Health currently treats adults only, and our clinical outcomes reflect that population. You can learn more about our approach to suicidal ideation treatment and review our clinical outcomes data.

Note: Isha Health currently provides treatment for adults (18+) only. If you or a teen you know is in crisis, contact the 988 Suicide and Crisis Lifeline by calling or texting 988.

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Related Articles

• Ketamine's Rapid Reduction of Suicidal Ideation (Adult Meta-Analysis)
• Online Ketamine Therapy at Isha Health
• Isha Health Clinical Outcomes

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