Gepants and Ditans
Two new treatments for migraine
Recently there has been a lot to get optimistic about in terms of treatments for migraine. After years of using medicines designed for other conditions, there are now specific preventive treatments developed for migraine. Three calcitonin gene-related peptide (CGRP) monoclonal antibodies have been developed and approved for use on the NHS in the UK.
More new treatments are coming in the form of gepants and ditans. They have also been specifically developed to treat migraine. They have been approved for use in the US and will shortly be considered for use in the UK. They have fewer side effects than some other migraine medicines.
The gepants and ditans come as tablets and can be compared to the triptans in their role to stop a migraine attack. They should be taken at the start of an attack, as early as possible, to treat pain and associated migraine symptoms (e.g. nausea, light/noise/smell sensitivity).
The gepants are also being considered as a preventive treatment option for migraine.
There are currently three gepants – Ubrogepant, Atogepant and Rimegepant, and others in development. They are CGRP receptor antagonists.
As opposed to conventional acute treatments such as triptans, non-steroidal anti-inflammatory drugs (NSAIDs), and other painkillers, the gepants don’t seem to cause rebound headache (medication overuse headache). As such, they may be useful as a preventive treatment when taken regularly. If approved for prevention, they will be among the first oral (tablet) CGRP treatments to prevent migraine.
How do they work?
At the start of the migraine process, CGRP is released by the nerves, and this helps to prolong and sustain the migraine attack. Gepants bind to that CGRP receptor on the trigeminal nerve and block this effect. Triptans on the other hand, suppress the release of CGRP and act on different receptors.
Gepants and triptans bind to the blood vessel. However, gepants (unlike triptans) do not constrict or tighten the blood vessel. They prevent it from dilating.
This makes them safer for people with heart issues and they can be used in people with cardiovascular disease. Gepants will be an acute option for people who can’t take triptans, such as those with heart related risks, those who find triptans ineffective or have had unpleasant side effects.
They are also being considered as a preventive treatment.
What are the side effects?
The most common side effects of the gepants, in clinical trials, have been fatigue and nausea.
Is there a risk of medication overuse or rebound headache?
Early indications suggests that gepants may be the first acute treatment that doesn’t cause medication overuse headache. There is ongoing research looking into gepants as a preventive treatment, as well as an acute treatment.
In the US, rimegepant has been approved as both an acute and preventive treatment, ubrogepant has been approved as an acute treatment, and atogepant is currently being considered as a preventive treatment.
In England and Wales, a National Institute for Health and Care Excellence (NICE) appraisal looking at rimegepant for treating and preventing migraine on the NHS has been proposed. Other gepants are likely to be considered in the near future.
There is currently one ditan – lasmiditan.
How do they work?
Lasmiditan is an acute treatment. It is another new class of medication that is like triptans and gepants, but also different. It might be as effective as a triptan, but it is very different from a triptan in the way it works.
It works by binding to one of the three receptors that triptans bind to. It doesn’t constrict the blood vessels. It will be a useful acute treatment for people who are unable to take a triptan due to issues with the constricting of blood vessels. It will also be an option for those who have not found a triptan effective or had problems with their side effects.
What are the side effects?
Unlike the triptans and gepants, lasmiditan can impair concentration and cause tiredness. For this reason, driving is not allowed up to eight hours after taking it.
Lasmiditan is scheduled to be appraised by NICE, with a decision likely in March 2023. In has been approved in the US as an acute treatment.
Benefits of new treatments
The availability and access to new migraine treatments will make an enormous difference to the lives of so many people affected by the debilitating impact of migraine. It will give doctors more options to prescribe from, especially to people who have other conditions or experience side effects that limit their treatment options. Understanding migraine better and developing precise medicines to target migraine will also help to remove some of the stigma people with migraine face.