Gepants for migraine: What are they and who might they be suitable for?
By: Ria Bhola, Headache Nurse Specialist
Migraine is common, painful, debilitating and disruptive to people’s lives. People with migraine rely on effective treatments for relief and to be able to function. Some people need both acute and preventive treatment for migraine.
Acute treatments are the medicines used to stop a migraine attack as early as possible. Preventive treatments are used regularly (daily, alternate days, monthly or quarterly) to reduce the overall number of attacks and their severity.
Currently, the triptans are the most effective acute medication and they work best if used early. Triptans became available in the 1990s. Whilst they have been beneficial and life-changing to many people, there are specific groups of people who have not had this benefit for several reasons:
- Non-responders: People who have not found them beneficial. This is estimated at one-third of people who have tried them.
- Side effects: Some people have intolerable side effects and have to avoid them altogether. Chest tightness, throat pressure, dizziness, nausea, drowsiness and fatigue are amongst the common side effects experienced to varying degrees, by an estimated one-third of people with migraine.
- Attack recurrence: Some people find that the attack returns within 24 hours, after initial relief, rather than stopping completely.
- Contraindications: Triptans tighten blood vessels, and this makes them unsuitable for people with cardiovascular (heart and blood vessel) problems, and they must avoid the medicine.
- Medication overuse headache: If triptans are used on 10 or more days per month, over at least three months, this can lead to more headaches or rebound headache and a dependency develops.
These new treatments have been developed to treat acute migraine and are suitable for people with migraine including those in the five groups above. In addition, some gepants can be used regularly (daily or on alternate days) for a preventive effect.
Gepants are small molecule CGRP receptor antagonists. CGRP is calcitonin gene-related peptide; a substance that is released during a migraine attack, at locations in the nervous system involved in migraine.
Larger molecule CGRP monoclonal antibodies are currently used as monthly or quarterly injections, as a preventive. The four CGRP mAb treatments are erenumab, fremanezumab, galcanezumab and eptinezumab.
Gepants, like other acute treatments, are more effective when attacks are treated in the milder stages regarding both pain and other common migraine symptoms. Similarly, the nasal spray formulation is expected to act faster than tablets.
The longer half-life or longer lasting effect in the body compared to triptans, will likely reduce the chance of attack recurrence. As with all medicines, however, not everyone will experience the desired benefit and we should remain realistic to that possibility.
Overall if approved, gepants will probably be prioritised for the five groups of people above, who are yet to have a safe, reliable acute treatment and once approved, a discussion between the patient and their doctor will determine when they should be used.
The gepant treatments currently developed are listed in the table below. However they are not yet all licenced and available for use in the UK. Licences are granted by the MHRA. The Medicines and Healthcare products Regulatory Agency (MHRA) is the UK body responsible for ensuring that medicines and medical devices work and are safe to use. An MHRA licence will also allow a treatment to be used privately.
|Name||NHS Review/Approval (NICE/SMC)*||MHRA Authorisation**||Route||Use|
|Atogepant||Scotland – preventive and acute
England, Wales, and Northern Ireland – under review
|Rimegepant||England – preventive and acute
Scotland – preventive and acute
Northern Ireland- preventive only
Wales – preventive and acute
|Ubrogepant||No review date yet||Not yet||Tablet||Acute|
|Zavegepant||No review date yet||Not yet||Nasal spray||Acute|
*NICE=National Institute for Health and Care Excellence; SMC= Scottish Medicines Consortium
**The Medicines and Healthcare products Regulatory Agency (MHRA).
The Migraine Trust will continue to publish updates when new treatments get approved and become available on the NHS.
In the meantime, it is helpful to keep a once-daily record in a headache diary that shows the days a migraine or headache occurs and when a treatment is used. This provides a valuable snapshot of the frequency and severity of migraine attacks, how long they last and when an acute treatment is needed or used. It will also provide a valuable baseline to compare the effect of any new treatment.