What is the role of ketamine nasal spray in treating migraines?

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Last updated: October 28, 2025View editorial policy

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Ketamine Nasal Spray for Migraine Treatment

Ketamine nasal spray is not recommended as a standard treatment for migraine headaches, as current clinical guidelines explicitly suggest against ketamine for short-term migraine treatment. 1

Standard First-Line Treatments for Migraine

  • NSAIDs (aspirin, ibuprofen, naproxen sodium) are recommended as first-line therapy for most migraine sufferers 2, 3, 1
  • For patients with nausea or vomiting, antiemetics like metoclopramide (10 mg IV or orally) should be added to treat accompanying symptoms and improve gastric motility 4, 3
  • Combination medications containing aspirin-acetaminophen-caffeine are effective for migraine treatment (note that acetaminophen alone is not recommended) 3, 1
  • For patients with significant nausea/vomiting, non-oral routes of administration should be selected 2, 3

Second-Line Treatment Options

  • Triptans (rizatriptan, naratriptan, sumatriptan, zolmitriptan) are recommended for patients who don't respond to NSAIDs 4, 2, 3
  • Dihydroergotamine (DHE) nasal spray has good evidence for efficacy when nausea/vomiting is present early in the attack 3

Current Evidence on Ketamine for Migraine

  • The U.S. Department of Veterans Affairs and Department of Defense Clinical Practice Guideline explicitly suggests against intravenous ketamine for migraine treatment 1
  • A 2018 randomized, double-blinded, placebo-controlled trial found that low-dose ketamine (0.2 mg/kg IV) did not produce greater pain reduction compared to placebo for acute migraine 5
  • Ketamine was associated with significantly greater generalized discomfort at 30 minutes compared to placebo 5

Limited Evidence for Ketamine in Specific Scenarios

  • A 2023 retrospective study of intranasal ketamine for refractory chronic migraine found that 49.1% of patients reported it as "very effective," but 74% experienced at least one adverse event 6
  • Ketamine has shown some benefit in treating severe, disabling auras in familial hemiplegic migraine, with 5 out of 11 patients experiencing reduced severity and duration of neurologic deficits 7
  • For treatment-refractory headaches, a 2017 retrospective review found that subanesthetic ketamine infusions provided short-term benefit in 71.4% of patients, but sustained response was not statistically significant 8

Important Clinical Considerations

  • Ketamine should be reserved only for patients with refractory chronic migraine who have failed other aggressive treatments 6
  • Given the potential for overuse and adverse effects, appropriate safety precautions should be implemented if ketamine is used 6
  • Limiting acute treatments to no more than twice weekly is important to prevent medication overuse headaches 2, 3
  • Consider preventive therapy for patients with frequent or disabling migraine attacks 3, 1

Adverse Effects of Ketamine

  • Common side effects include generalized discomfort and fatigue 5
  • The risk of adverse events must be weighed against potential benefits, especially given the availability of established first-line and second-line treatments 1, 5

References

Guideline

Ketamine's Role in Migraine Treatment

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Initial Treatment Approach for Gastric Migraine

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Migraine Treatment Options Without Opiates or Diphenhydramine

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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