Section - Expert Consultations

02. Managing Ketamine/Esketamine Treatment: Discontinuation, Side Effects, and Clinic Practice

Published on April 21, 2026 Certification expiration date: April 21, 2029 DOI: 10.64239/PI-EC098

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Key Points

When a patient relapses after tapering off ketamine or esketamine, consider restarting an index course (twice weekly for a few weeks, then spread out).
With ketamine or esketamine, dysphoric reactions occur in roughly 1 in 200-300 treatments. Many resolve with supportive care alone; others require a short-acting benzodiazepine such as lorazepam.
For esketamine sessions, have patients fast for two hours beforehand. Manage nausea with low-dose ondansetron, and post-treatment headache with OTC ibuprofen or acetaminophen.

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When and How to Stop Esketamine: Tapering and Maintenance

Flavio Guzmán, M.D.: Once a patient is doing well, we wonder how and when to stop. What do we currently know about managing esketamine discontinuation, and are there any strategies that you’d recommend?

Samuel Wilkinson, M.D.: One of the unresolved issues in this space is the long-term approach. Many patients will need maintenance therapy, and it’s not clear what to do if a patient has achieved good remission and response from ketamine or esketamine and is currently receiving it in an ongoing fashion.

My clinic typically approaches this problem as follows: if we achieve about a six-month or longer period of remission, we have a collaborative discussion with the patient and come to a shared decision about whether to continue or taper off.

I feel better about this if the patient has successfully tapered to a frequency of once every three

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Table of Contents

Learning Objectives:
After completing this activity, the learner will be able to:

Identify appropriate candidates for ketamine or esketamine based on prior treatment failures, severity, substance use history, and relevant contraindications.
Describe strategies for maintenance dosing, tapering, and managing rapid relapse after discontinuation of ketamine or esketamine.
Apply clinic-based approaches to managing acute side effects, including dissociation, dysphoric reactions, nausea, and blood pressure changes.

Original Release Date: April 21, 2026
Expiration Date: April 21, 2029

Expert: Samuel Wilkinson, M.D.
Medical Editors: Flavio Guzmán, M.D.

Relevant Financial Disclosures:
Samuel Wilkinson declares the following interest:
– Neurocrine Biosciences Inc.: Research funding
– Oui Therapeutics: Research funding
– Sooma Medical: Serve on DSMB
– LivaNova: Consulting
– Mind Medicine: Consulting
– MoonLake Immunotherapeutics: Serve on DSMB
– Neumora Therapeutics: Served on DSMB
– Joyous: Consulting

All the relevant financial relationships listed above have been mitigated by Medical Academy and the Psychopharmacology Institute.

None of the other faculty, planners, and reviewers for this educational activity have relevant financial relationships to disclose during the last 24 months with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

Contact Information: For questions regarding the content or access to this activity, contact us at support@psychopharmacologyinstitute.com

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Accreditation Statement
This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education through the joint providership of Medical Academy LLC and the Psychopharmacology Institute. Medical Academy is accredited by the ACCME to provide continuing medical education for physicians.

Credit Designation Statement
Medical Academy designates this enduring activity for a maximum of 0.5 AMA PRA Category 1 credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Artificial Intelligence (AI) Use DisclosureArtificial intelligence (AI) tools may have been used in limited stages of developing this activity (e.g., drafting or language refinement). The specific tool, version, and date of use are documented internally.AI does not determine clinical recommendations. All content is reviewed, verified, and approved by the listed faculty and medical editors, and reflects independent human clinical judgment consistent with ACCME Standards for Integrity and Independence in Accredited Continuing Education.

Samuel Wilkinson, M.D.

Flavio Guzmán, M.D.

Key Points

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When and How to Stop Esketamine: Tapering and Maintenance

CME Information

Unlock up to 155 CME Credits, including 40 SA CME Credits.