Ketamine Safety in 2026: What Psychiatrists Need to Know About Monitoring, Neurotoxicity, and Clinical Guardrails

As ketamine continues to gain interest as a treatment option for patients with difficult-to-treat mood disorders, psychiatrists face a rapidly evolving clinical landscape that demands both enthusiasm for innovation and vigilance around safety.¹

At the 2026 American Society of Clinical Psychopharmacology (ASCP), Benjamin Brody, MD, associate professor of clinical psychiatry at Weill Cornell Medical College, is hosting a panel examining ketamine safety, adverse effects, and best practices for clinical monitoring. The session comes at a time when ketamine use has expanded significantly across psychiatric practice, while public scrutiny has increased following recent reports of ketamine-associated deaths, Brody told Psychiatric Times.

“It's a rapidly changing and expanding environment, and we want clinicians, researchers, and the general community to have a good sense of how do we use this intervention safely, effectively, with appropriate guardrails,” Brody said.

The discussion is based in part on recent scholarly work examining ketamine safety, including Brody's publication How Do We Get Ketamine Safety Right? and a separate review led by Samuel Wilkinson, MD, evaluating evidence for ketamine-related neurotoxicity in both preclinical and human studies.^1,2

From Anesthetic to Psychiatric Treatment: A Rapidly Expanding Evidence Base

Ketamine’s path into psychiatry has been decades in the making, Brody explained. Originally developed and used as a general anesthetic, he said the medication emerged as a potential antidepressant after researchers first demonstrated its rapid antidepressant effects in 2000.

Since then, evidence supporting ketamine's use in treatment-resistant depression and acute suicidality has grown substantially, he added. The field has also witnessed the development of multiple delivery methods and treatment settings, culminating in the approval of esketamine in 2019, a milestone that expanded patient access to glutamatergic-based treatment options.

“There's been an absolute mountain of literature accumulating around ketamine's use in treatment-resistant depression, for acute suicidality in the context of mood disorders, and of course, in other indications as well,” Brody told Psychiatric Times.

Yet he noted the growing body of evidence has been accompanied by new questions regarding long-term safety, optimal monitoring practices, and the risks associated with broader clinical adoption.

Ketamine Monitoring: Revisiting Established Safety Guardrails

A central theme of the ASCP session is to help clinicians understand the safeguards that should accompany ketamine treatment.

Brody noted that many of these recommendations are not new. The American Psychiatric Association's consensus statement, published in 2017, outlined key monitoring considerations that remain highly relevant today.³

He reminded clinicians the safeguards should include monitoring vital signs and conducting in-person observation for dissociative experiences that may become clinically problematic rather than therapeutic.

“Those are some of the acute factors that clinicians need to be aware of when they're administering ketamine,” he told Psychiatric Times.

The focus on monitoring reflects a broader goal of ensuring that ketamine's benefits can be delivered while minimizing preventable adverse events and maintaining patient safety, he added.

Neurotoxicity Highlights Need for Appropriate Dosing, Treatment Intervals

Beyond acute monitoring, the panel will also examine emerging concerns surrounding potential neurotoxic effects associated with ketamine exposure.

According to Brody, current evidence suggests that ketamine's neurological effects may depend heavily on dose and treatment frequency.

“At low doses, with appropriate intervals between administration, ketamine probably has neurotrophic effects,” he explained. “However, if it's dosed at higher doses and without appropriate intervals between dosing—or if it's dosed too frequently—at some point it becomes neurotoxic.”

Brody emphasized that understanding where that threshold lies remains an important area of investigation and will be a major focus of Wilkinson's presentation.

The conversation reflects a growing recognition that ketamine treatment should not be viewed simply as a binary question of efficacy versus inefficacy, but rather as a nuanced intervention requiring thoughtful attention to dosing schedules, cumulative exposure, and long-term outcomes.

Special Populations Present Additional Clinical Questions

Although evidence supporting ketamine in treatment-resistant depression continues to grow, Brody noted that significantly less research exists for many other populations frequently encountered in practice. To address those gaps, the ASCP panel will include a review of ketamine use in several special populations. Topics will include patients with bipolar disorder, individuals with co-occurring borderline personality disorder, geriatric populations, and medically complex patients, including those facing terminal illness.

“We have much less data on ketamine use outside of treatment-resistant depression,” Brody said.

These populations often present unique diagnostic, medical, and treatment challenges that may alter risk-benefit considerations when ketamine is being considered as part of a comprehensive psychiatric treatment plan, he added.

Equipping Clinicians for Safe Ketamine Use

Ultimately, Brody said the goal of the session is to provide psychiatrists with practical, evidence-informed guidance that reflects both the promise and the limitations of ketamine treatment in 2026.

To do so, the panel brings together experts with complementary perspectives on safety, neurobiology, clinical implementation, and special populations, with Christina Kusan, MD, of Massachusetts General Hospital and Harvard Medical School serving as discussant.

“In sum, we want to give the audience a broad range of things to think about as they're encountering [ketamine] in clinical practice to be well-informed to safely and effectively use ketamine in psychiatric contexts,” Brody told Psychiatric Times.

References

1. Brody BD, Popeo DM, Smetana RW, Kanellopoulos D. How Do We Get Ketamine Safety Right? Three Questions From a Clinical Service. J Clin Psychiatry. 2025;86(3):25com15946.

2. Li SW, Kumpf KT, Urrutia J, et al. Ketamine for Depression, but at What Cost? A Review of Ketamine's Neurotoxic Effects From Preclinical and Human Studies. Am J Psychiatry. 2025;182(10):903-912.

3. Sanacora G, Frye MA, McDonald W, et al. American Psychiatric Association (APA) Council of Research Task Force on Novel Biomarkers and Treatments. A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. JAMA Psychiatry. 2017;74(4):399-405