Ketamine and Persistent Anxiety

What the evidence shows and what remains uncertain.

By Jerron C. Hill, M.D. — Board-Certified Anesthesiologist, Founder of HILLMED

Anxiety can affect sleep, concentration, relationships, work, and physical well-being. Most people begin with established treatments such as psychotherapy, lifestyle support, and medication. When symptoms continue despite appropriate care, some patients ask whether ketamine might be an option. The short answer is that ketamine is being studied for several anxiety disorders, but the evidence is still limited. It is not an FDA-approved treatment for anxiety and should not replace a complete psychiatric evaluation or standard care.

What Persistent Symptoms Mean

The phrase "treatment-resistant anxiety" appears in medical research, but it is not a separate diagnosis in the Diagnostic and Statistical Manual of Mental Disorders. Researchers have also used inconsistent definitions. In 2024, an international expert panel proposed operational criteria for treatment-resistant anxiety disorders to improve consistency in research and clinical discussion. That consensus is useful, but it does not turn the phrase into a distinct diagnosis.

For patient education, clearer language is often better: anxiety symptoms have persisted despite an adequate trial of evidence-based treatment. Before labeling symptoms as resistant, clinicians should confirm the diagnosis, treatment dose and duration, adherence, coexisting conditions, substance or medication effects, and whether appropriate psychotherapy was tried.

Established Care Comes First

Treatment depends on the specific anxiety disorder and the individual. A plan may include:

• Evidence-based psychotherapy, especially cognitive behavioral therapy and disorder-specific approaches

• Medication when appropriate, commonly an SSRI or SNRI

• Evaluation of sleep problems, medical conditions, substance use, and medications that can worsen anxiety

• Regular physical activity, restorative sleep, nutrition, mindfulness, and practical stress-management skills

These supportive habits can improve overall health and help regulate the stress response, but they should complement — not substitute for — indicated mental health treatment.

What Ketamine Does

Ketamine affects glutamate signaling, including the N-methyl-D-aspartate receptor. This differs from the primary mechanism of SSRIs and SNRIs. Researchers are studying whether ketamine-related changes in brain signaling and synaptic plasticity can reduce anxiety symptoms more rapidly than conventional medications in some patients. The biology is complex, however, and the exact mechanism of any anxiety benefit has not been established.

What the Research Shows

Early studies have reported short-term reductions in symptoms in some people with social anxiety disorder, generalized anxiety disorder, post-traumatic stress disorder, and other anxiety-spectrum conditions. However, many studies are small, use different diagnoses and dosing methods, or follow patients for only a short period.

For example, a randomized crossover study in 18 adults with social anxiety disorder found improvement on one clinician-rated scale after a single IV ketamine infusion, but not on one self-rated anxiety measure. A separate controlled study included only 12 patients with generalized or social anxiety symptoms that had not improved with prior treatment. Systematic reviews describe the overall findings as preliminary and emphasize variation among studies, temporary effects, and unanswered questions about repeated or maintenance treatment.

This evidence supports further research. It does not establish IV ketamine as routine or first-line treatment for anxiety disorders, and it cannot predict whether an individual patient will benefit.

When a Ketamine Evaluation May Be Considered

A clinician may discuss off-label ketamine only after clarifying the diagnosis, reviewing prior treatment, and weighing potential benefits against risks. The decision should involve the patient's psychiatrist or mental health clinician whenever possible, particularly when anxiety occurs with depression, trauma-related symptoms, bipolar disorder, psychosis, substance-use concerns, or suicidal thoughts.

Safety and Medical Supervision

Ketamine can temporarily increase blood pressure and heart rate and may cause nausea, dizziness, sedation, perceptual changes, or dissociation. Misuse and dependence are also concerns. Screening, individualized dosing, physiologic monitoring, recovery assessment, and transportation home are essential parts of care. Some medical or psychiatric conditions may make treatment inappropriate or require additional evaluation.

At HILLMED, IV ketamine is administered in a medically supervised setting after an individual assessment. Patients remain monitored during treatment and must have a responsible adult drive them home. Treatment decisions are coordinated with the patient's other clinicians when appropriate.

Ketamine Within Whole-Person Care

If ketamine is considered, it should be one part of a broader plan. Psychotherapy helps patients work with thoughts, behaviors, trauma responses, and avoidance patterns. Sleep, movement, nutrition, mindfulness, and stress-management practices support nervous-system health and daily function. Ketamine does not replace these foundations, and symptom relief may be temporary.

Frequently Asked Questions

Is ketamine FDA-approved for anxiety? No. Ketamine treatment for an anxiety disorder is off-label. Evidence is still developing, and an individualized medical and psychiatric assessment is necessary.

Is treatment-resistant anxiety a medical diagnosis? No. It is a research and clinical descriptor, not a separate DSM diagnosis. A 2024 expert consensus proposed criteria for treatment-resistant anxiety disorders, but clinicians still need to identify the specific anxiety disorder and review whether prior treatments were adequate.

Does ketamine work faster than an SSRI? Some small studies found symptom changes within hours or days. That does not mean the response will occur for everyone or last. SSRIs and SNRIs remain established treatments and typically require several weeks to assess.

Does ketamine replace psychotherapy? No. Psychotherapy remains central to anxiety care. Any ketamine treatment should be coordinated with a comprehensive plan.

Will I be unconscious? At low doses used in many outpatient IV protocols, patients generally remain responsive, although sedation, dreamlike sensations, or dissociation can occur. Monitoring and a ride home are required.

A Physician's Perspective

Persistent anxiety deserves a careful assessment, not a quick label or a promise of a rapid cure. Ketamine may be worth discussing for selected patients after established treatments have been reviewed, but the current evidence for anxiety is preliminary. My role is to explain that uncertainty clearly, evaluate safety, and coordinate care so that any treatment decision supports the patient's broader mental health plan.

When to Seek Help

Contact a qualified healthcare professional when anxiety causes significant distress or interferes with sleep, work, relationships, or daily function. If you are in crisis or thinking about harming yourself, call or text 988 in the United States to reach the Suicide and Crisis Lifeline.

Learn More

To learn more or schedule a consultation, visit hillmedstressmanagement.com or call our Plano practice at (972) 212-4341.

Selected References

• Domschke K, et al. The definition of treatment resistance in anxiety disorders: a Delphi method-based consensus guideline. World Psychiatry. 2024;23(1):113-123.

• Bokma WA, et al. Aligning the many definitions of treatment resistance in anxiety disorders: a systematic review. Depression and Anxiety. 2019;36(9):801-812.

• Tully JL, et al. Ketamine treatment for refractory anxiety: a systematic review. British Journal of Clinical Pharmacology. 2022;88(10):4412-4426.

• Whittaker E, et al. Systematic review and meta-analysis of randomized controlled trials of ketamine in refractory anxiety spectrum disorders. Therapeutic Advances in Psychopharmacology. 2021;11.

• Taylor JH, et al. Ketamine for social anxiety disorder: a randomized, placebo-controlled crossover trial. Neuropsychopharmacology. 2018;43(2):325-333.

• Glue P, et al. Effects of ketamine in patients with treatment-refractory generalized anxiety and social anxiety disorders. Journal of Psychopharmacology. 2020;34(3):267-272.

Educational Notice

This article provides general education and is not medical advice. Ketamine for anxiety is an off-label use. It is not a cure, is not appropriate for everyone, and must be considered individually by qualified clinicians. Results vary. Do not start, stop, or change treatment without consulting your healthcare professional.

About the author

Jerron C. Hill, M.D. is a board-certified anesthesiologist and the founder of HILLMED, a physician-led wellness practice in Plano, Texas. Drawing on decades of experience administering intravenous medications and managing complex physiology in the operating room, Dr. Hill brings a rigorous, safety-first approach to IV ketamine therapy, IV vitamin therapy, and physician-formulated CBD. At HILLMED, he pairs advanced, doctor-supervised treatments with the fundamentals of whole-person wellness — nutrition, movement, restorative sleep, and stress management — to help patients function and feel better. To learn more or schedule a consultation, visit hillmedstressmanagement.com or call the Plano practice at (972) 212-4341.