Treatment of Cluster Headache: The American Headache Society Evidence-Based Guidelines

Headache. 2016 Jul;56(7):1093-106. doi: 10.1111/head.12866.


Background: Cluster headache (CH), the most common trigeminal autonomic cephalalgia, is an extremely debilitating primary headache disorder that is often not optimally treated. New evidence-based treatment guidelines for CH will assist clinicians with identifying and choosing among current treatment options.

Objectives: In this systematic review we appraise the available evidence for the acute and prophylactic treatment of CH, and provide an update of the 2010 American Academy of Neurology (AAN) endorsed systematic review.

Methods: Medline, PubMed, and EMBASE databases were searched for double-blind, randomized controlled trials that investigated treatments of CH in adults. Exclusion and inclusion criteria were identical to those utilized in the 2010 AAN systematic review.

Results and recommendations: For acute treatment, sumatriptan subcutaneous, zolmitriptan nasal spray, and high flow oxygen remain the treatments with a Level A recommendation. Since the 2010 review, a study of sphenopalatine ganglion stimulation was added to the current guideline and has been administered a Level B recommendation for acute treatment. For prophylactic therapy, previously there were no treatments that were administered a Level A recommendation. For the current guidelines, suboccipital steroid injections have emerged as the only treatment to receive a Level A recommendation with the addition of a second Class I study. Other newly evaluated treatments since the 2010 guidelines have been given a Level B recommendation (negative study: deep brain stimulation), a Level C recommendation (positive study: warfarin; negative studies: cimetidine/chlorpheniramine, candesartan), or a Level U recommendation (frovatriptan).

Conclusions: This AHS guideline can be utilized for understanding which therapies have superiority to placebo or sham treatment in the management of CH. In clinical practice, these recommendations should be considered in concert with other variables including safety, side effects, patient preferences, clinician experience, cost, and the invasiveness of the intervention. Given the lack of Class I evidence and Level A recommendations, particularly for a number of commonly used preventive therapies, further studies are warranted to demonstrate safety and efficacy for established and emerging therapies.

Keywords: calcium-channel blockers; chronic; cluster; episodic; evidence-based medicine; guidelines; headache; lithium; neurostimulation; oxygen; sphenopalatine; verapamil.

Publication types

  • Guideline
  • Review
  • Systematic Review

MeSH terms

  • Central Nervous System Agents / therapeutic use
  • Cluster Headache / drug therapy*
  • Cluster Headache / prevention & control
  • Humans


  • Central Nervous System Agents