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

Matthew S. Robbins, MD; Amaal J. Starling, MD; Tamara M. Pringsheim, MD; Werner J. Becker, MD; Todd J. Schwedt, MD


Headache. 2016;56(7):1093-1106. 

In This Article

Abstract and Introduction


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.


Cluster headache (CH), the most common of the family of headache disorders known as the trigeminal autonomic cephalalgias,[1] has a lifetime prevalence exceeding one in 1000.[2] CH is considered among the most severe of the primary headache disorders because of extreme pain, associated autonomic symptoms, and high attack frequency. In addition, a sizeable proportion of patients with CH have chronic CH,[2] which features only brief or no remission periods[1] and may be particularly refractory to medical therapies. Evidence suggests that CH is not easily recognized, leading to diagnostic delay. Furthermore, patients with CH are often suboptimally treated, an especially disappointing fact considering there are effective treatments available for aborting and preventing attacks.[3,4] Treatment of CH in accordance with guidelines is associated with better outcomes.[5]

The objective of this systematic review of the literature is to provide evidence-based guidelines for the abortive and preventive treatment of CH. To do so, we updated the 2010 American Academy of Neurology (AAN) endorsed systematic review.[6] The interval of time that has elapsed since completion of the 2010 literature review necessitates these updated recommendations.[7–9] These American Headache Society (AHS) guidelines provide an updated assessment of available data and also include non-medication treatments. Akin to the AAN endorsed systematic review, these guidelines aim to answer the following clinical questions:

  1. Which treatments are effective for the acute treatment of CH attacks?

  2. Which treatments are effective for reducing the frequency of CH attacks?

These AHS guidelines rate the strength of evidence for CH treatment efficacy. Of course, efficacy must be considered in conjunction with side effects, risks, patient preferences, cost, and other factors when making treatment recommendations.