Neuromodulation for the treatment of primary headache syndromes

ABSTRACT

Introduction: Neuromodulation techniques play an increasing role in the treatment of primary headaches. While initially reserved for refractory cases they are now increasingly taken into consideration in earlier treatment phases and in non-refractory situations. One of the main reasons for this paradigm shift is that most neuromodulation techniques are better tolerated as compared to the majority of pharmacological approaches. However, these techniques have their limitations that should be considered.

Areas covered: The review provides an overview of the available techniques and their therapeutic rationale as well as on the evidence for their efficacy and their limitations. The review covers these aspects for non-invasive vagal nerve stimulation, sphenopalatine ganglion stimulation, external trigeminal nerve stimulation, occipital nerve stimulation as well as single-pulse and repetitive-pulse transcranial magnetic stimulation.

Expert commentary: Most of the evidence is based on open-label studies. Sham devices used in controlled studies remain problematic as they either do not produce the paresthesias perceived during stimulation or induce some degree of stimulation. Invasive techniques require a surgical intervention with all the potential complications that may arise.

In summary, some of the techniques provide an effective expansion of available treatment options but their indication should be thoroughly evaluated before treatment is considered.

KEYWORDS:

• Cluster headache
• external trigeminal nerve stimulation
• headache
• migraine
• neuromodulation
• non-invasive vagal nerve stimulation
• occipital nerve stimulation
• sphenopalatine ganglion stimulation
• transcranial magnetic stimulation

Article highlights

• Neurostimulation techniques expand the therapeutic armamentarium of primary headaches, in particular, migraine and cluster headache.

• Non-invasive vagal nerve stimulation (nVNS) has been proven effective in the acute treatment of cluster headache attacks in episodic cluster headache. Randomized-controlled trials for the acute and preventive treatment failed to prove an efficacy.

• Exploratory studies suggest that nVNS could be effective in the treatment of indomethacin-responsive headaches.

• Sphenopalatine ganglion (SPG) stimulation is effective in the acute and preventive treatment of chronic cluster headache.

• External trigeminal nerve stimulation (eTNS) has been tested in an RCT for the preventive treatment of migraine but failed to be effective when compared to placebo.

• Occipital nerve stimulation (ONS) has been shown to be ineffective in chronic migraine as the RCT failed to meet its primary endpoint (reduction in attack severity by ≥50%). While the authors observed a significant reduction in headache days a new RCT is required until efficacy can be assumed. For its efficacy in cluster headache, many open-label trials but no RCTs exist. A convincing conclusion regarding its clinical efficacy in cluster headache is therefore not possible.

• Single-pulse transcranial magnetic stimulation has been proven effective for the acute treatment of migraine. For its efficacy in the preventive treatment of migraine no sham-controlled RCT exists.

• Repetitive transcranial magnetic stimulation has been proven effective in an RCT if stimulation is provided at a high frequency (10 Hz). In contrast, low-frequency stimulation (1 Hz) has not been proven effective.

Declaration of interest

J Hoffmann is consulting for/has served on advisory boards for Allergan, Autonomic Technologies Inc. (ATI), Chordate Medical AB, Eli Lilly, Hormosan Pharma, Novartis, and Teva. He received honoraria for speaking from Allergan, Autonomic Technologies Inc. (ATI), Chordate Medical AB, Novartis, and Teva. He serves as Associate Editor for Cephalalgia and the Journal of Orofacial Pain and Headache. A May serves as the Editor-in-chief for Cephalalgia. He received unrestricted scientific grants from Electrocore, and Chordate Medical AB paid to the University Medical Center Hamburg-Eppendorf. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has received honorarium from GammaCore and was principal investigator for trials of Theranica, GammaCore, and eNeura. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.