External stimulation of the trigeminal nerve for the prevention and treatment of episodic and chronic migraine (Cefaly)

Research areas: High tech medicine, Prevention and screening

& Harald Jagos
Duration: April 2018 – August 2018
Suggested by: Main Association of the Austrian Social Security Institutions
Language: English (Executive summary in German)
Publication: Decision Support Document No. 114: https://eprints.aihta.at/1177/

Background:
There are two types of migraine: episodic and chronic. While episodic migraine is defined as <15 headache days per month, patients with chronic migraine have ? 15 headache days per month. In particular, chronic migraine results in high expense to the society mainly due to the reduction of patient’s economic activity and leads to a significant deterioration in quality of life (QoL). Approximately 2% of the world's population are affected. Some of the non-modifiable risk factors for the transformation from episodic to chronic migraine include: female sex, genetic make-up, history of head/neck injury, stressful life events, and others.

Genetic make-up, daily life routine as well as medical comorbidities influence the presence and the development of migraines. While some of the lifestyle interventions include good sleep patterns and sufficient hydration, non-drug interventions such as taking of vitamins, acupuncture, or mindfulness therapy claim to have an impact on migraines as well. The pharmacological interventions include the use of triptan together with either a non-steroidal anti-inflammatory drug (NSAID) or paracetamol to help relieve migraine. For the prevention of migraine, drugs such as topiramate or propranolol are recommended.

External trigeminal nerve stimulation (e-TNS) and supraorbital transcutaneous nerve stimulation (s-TNS) device produced by the manufacturer Cefaly is the intervention at stake. It claims to be the first line treatment for patients having frequent migraine attacks. The mechanism of action is that e-TNS/s-TNS produces a micro-pulse on the upper branch of the trigeminal nerve (suborbital nerve) through an adhesive electrode that is placed on the forehead. The device approved in Europe claims to both prevent as well as treat migraine attacks and thus be an alternative to pharmacological treatment for migraines.

Aims of project:
The aim of the project is to perform a synthesis of evidence on the basis of a systematic literature review regarding effectiveness and safety of the external stimulation of the trigeminal nerve for the prevention and treatment of episodic and chronic migraine.

Research objectives:
Is e-TNS/s-TNS device in comparison to placebo or the standard therapy (triptan together with NSAIDs or paracetamol, topiramate, propranolol) in patients with episodic/chronic migraine more effective or equally effective concerning improvement in migraine episodes, QoL, and satisfaction; and safer regarding the side effects?

Methods:

• Systematic review of published clinical studies/documents regarding the e-TNS/s-TNS device in comparison to controls determined in the PICO question.
• Systematic literature search in:
  • Cochrane (CENTRAL), Centre for Research and Dissemination (CRD), Embase, Medline
  • Handsearch (in references, as appropriate via Scopus), internet-search, contacting manufacturers.

• Data extraction: Three review authors include and exclude studies independently from each other. One author extracts the data and the other controls the extracted data. Disagreements are resolved through discussion and consensus.
• Assessing the risk of bias and the strength of evidence: The risk of bias tool from the Institute of Health Economics and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach are used.
• Use of the EUnetHTA „HTA Core Model 3.0“ as well as EUnetHTA guidelines

PICO-question:

Population	Prophylactic or first line treatment in patients with episodic and chronic migraine.
Intervention	External trigeminal nerve stimulation (e-TNS) Supraorbital transcutaneous nerve stimulation (s-TNS) Product name: Cefaly®
Control	Acute treatment: Triptan + NSAIDs/Paracetamol	Prevention: Propranolol Topiramate
Outcomes
Effectiveness	Clinical endpoint: (Monthly) migraine attacks (Monthly) headache days (Monthly) acute antimigraine drug intake QoL Satisfaction Pain
Safety	Adverse device effects (ADE), serious adverse device effects (SADE): Pain/intolerance to paresthesia (burning sensation) Arousal changes (insomnia, sleepiness/fatigue) Headaches after stimulation Skin allergy
Study design	Effectiveness: Randomised controlled trials Prospective non-randomized controlled trials Safety: Randomised controlled trials Prospective non-randomised controlled trials Prospective single-arm studies (case-series, registries, no individual case reports).

 

Time schedule/ milestones

 

Time frame	Task
End of April 2018	Scoping, precision of PICO-question, identification and contacting of manufacturers, contacting of external experts
May 2018	Systematic literature search, non-systematic hand search, abstract screening, writing of the background
June 2018	Literature selection, data extraction, assessment of the quality of evidence, synthesis and assessment of evidence
July 2018	Drafting of the 1st version of HTA-report, review of co-authors
End of July 2018	Internal review
Beginning of August 2018	External review
Middle of August 2018	Layout