Beyond chronic migraine: a systematic review and expert opinion on the off-label use of botulinum neurotoxin type-A in other primary headache disorders

ABSTRACT

Introduction: Botulinum neurotoxin type-A (BoNTA) is licensed for the treatment of chronic migraine (CM), but it has been tested off-label as a therapeutic choice in other primary headaches (PHs). We aimed to provide a systematic review and expert opinion on BoNTA use in PHs, beyond CM.

Areas covered: After providing an overview on PHs and mechanism of BoNTA action, we report the results of a systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, of BoNTA therapeutic trials in PHs beyond CM. Studies and results were reviewed and discussed, and levels of evidence were graded. We also collected data on relevant ongoing trials.

Expert opinion: Although there are contradictory findings on PHs other than CM, BoNTA may represent a therapeutic option for patients who do not respond to conventional prophylactic treatments. Based on limited available evidence, BoNTA may be considered in refractory tension-type headache, trigeminal autonomic cephalalgias, primary stabbing headache, nummular headache, hypnic headache, and new daily persistent headache, after the primary nature of cephalalgia has been documented and other drugs have failed. Experienced physicians in BoNTA treatment are required to guide the therapeutic protocol for each patient to optimize good and safe outcomes.

KEYWORDS:

• Primary headache
• episodic migraine
• tension type headache
• trigeminal autonomic cephalalgias
• cluster headache
• suna
• sunct
• hemicrania continua
• nummular headache
• new daily persistent headache
• stabbing headache
• hypnic headache
• botulinum neurotoxin
• treatment

Article highlights

• Botulinum neurotoxin type A (BoNTA) blocks SNARE-mediated synaptic trafficking and inhibits the release of neurotransmitters and neuropeptides, including calcitonin gene-related peptide to control cephalic pain.

• BoNTA may have a preventive role in headache through peripheral and possible central nervous system mechanisms.

• Converging experimental, clinical trials, and real-life evidence supports the use of BoNTA in chronic migraine and trigeminal neuralgia.

• Evidence supporting the use of BoNTA in other primary headaches (PHs) is still preliminary and contradictory.

• BoNTA may be considered in PHs other than CM when more established treatments fail, and after the primary nature of headache has been documented.

• Patients’ preferences along with physicians’ expertise with BoNTA should guide therapeutic decision-making in these cases.

• Future clinical trials, with predictive biomarkers to stratify patients according to their response, and multicenter design for less common conditions, are warranted.

Declaration of interest

The authors have no 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.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.