Cluster headache therapies: pharmacology and mode of action

ABSTRACT

Introduction

Cluster headache (CH) is the most common trigeminal autonomic cephalalgia with a significant need for novel treatment options. While the use of most of the acute CH medications is supported by clinical trials and based on a pathophysiological concept for the generation of pain, the scientific evidence for preventive CH medications is very limited.

Areas covered

This article reviews acute and preventive substances for the pharmacological treatment of CH with a focus on the mode of action of these drugs. We also summarized the clinical trial evidence and discuss future research directions.

Expert opinion

Recommendations for current pharmacological CH therapies, in particular for CH prevention, are often based on small open label studies with inconclusive results. Larger trials are missing. A shared pathophysiological mechanism of action of these preventatives does not exist. Future studies with CGRP(R) antibodies and novel substances with specific actions are needed and will thereby help to understanding the pathophysiology of CH.

KEYWORDS:

• Cluster
• pharmacology
• therapies
• pathophysiology
• prevention
• CGRP

Article highlights

• Cluster headache (CH) pathophysiology involves a network comprising the hypothalamus, the trigeminal nerve, and autonomic nervous systems. The identification of targets of established drugs helps to distinguish mechanisms of importance for the disease.

• Study evidence for established acute and preventive CH treatment options and pathophysiological considerations, which can be derived from such pharmacological therapies.

• The proposed mechanisms of action of abortive CH medications such as oxygen, triptans, and ergots show similarities in their ability to inhibit neuropeptide release, to foster vasoconstriction, and the blockade of neuronal transmission.

• The most frequently used preventive drugs: steroids, verapamil, topiramate, and lithium have a multitude of actions and bindings sites inside and outside the CNS.

• The role of CGRP and CGRP blockade in CH prevention has not been clearly established to date.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

U Reuter has received honoraria for the participation in advisory boards, speaker fees from Pharm Allergan, Amgen, Autonomic Technologies, CoLucid, ElectroCore, Eli Lilly, Novartis, STREAMedUP, and TEVA. UR has got research support from Novartis and BMBF.

J Mecklenburg has received honoraria for the participation in advisory boards from Novartis.

M. Sanchez del Rio received honoraria for the participation in advisory boards and speaker fees, oral presentations from Allergan, Eli Lilly, Novartis, and Teva. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded