A few days ago, I was filing yet another neurology letter—this one about a 29-year-old patient with chronic migraines. She was on sumatriptan, naproxen, topiramate, and even riboflavin supplements. She had tried acupuncture, dietary changes, sleep hygiene… you name it.
Her migraines were still disabling. She has had to leave work due to the frequency of her symptoms and had been back and forth to the neurologist for a number of years. I’ve seen lots of patients with migraines and this patient was probably the furthest in her treatment cycle.
Towards the end of the letter my interest peaked. The letter mentioned starting a CGRP inhibitor, a new class of medication which has bought a lot of hope to patients with migraines. Currently it can only be prescribed by neurologists but this is likely to change soon.
With the NHS moving toward allowing CGRP inhibitors to be prescribed in primary care, we may finally have a more targeted, tolerable option to offer patients like her without a long wait for neurology.
Let’s take a look at where we’ve been, why migraines are so hard to treat, and how CGRP inhibitors could shift the landscape.
Migraines: Frustrating for Patients—and Clinicians
Migraine is a common neurological condition affecting an estimated 10 million people in the UK. It’s far more than just a bad headache—it can involve hours or days of headache, visual disturbances, nausea/vomiting and sensitivity to light and sound.
If you think about the average patient with migraines, they often cycle through a long list of medications. In primary care, we often reach for:
• Acute therapies like sumatriptan and NSAIDs
• Preventives such as Amitriptyline, Topiramate, Propranolol
• Supplements (e.g. riboflavin, magnesium) and lifestyle advice
But these treatments have their limits. Some take weeks to show benefit, others are poorly tolerated, and many patients end up trialling multiple drugs without lasting relief. It’s not uncommon to feel stuck both as a patient and as a prescriber.
Many patients struggle to function with such headaches. Long periods of sickness and impact on their personal life are common findings in a history, ultimately contributing to poor mental health in a large contingent of such patients. In the end, patients and clinicians can find themselves quite frustrated once we have exhausted the treatment options.
Why Do Migraines Happen, Anyway?
The exact cause of migraines is still being unraveled, but we do know that it involves neurovascular dysregulation. A key player in the process is a protein called CGRP (Calcitonin Gene-Related Peptide).
During a migraine, CGRP is released by the trigeminal nerve, causing widening of blood vessels, Neurogenic inflammation and the amplification of pain signals. Elevated CGRP levels have been consistently detected during migraine attacks, and normalising these levels can reduce or prevent symptoms—this is the basis for CGRP-targeted therapies.
CGRP Inhibitors: What Are They and How Effective Are They?
CGRP inhibitors are monoclonal antibodies or small molecules designed to block CGRP or its receptor. Unlike general-purpose migraine preventives, these drugs target the migraine pathway directly. This is what makes them both unique and incredibly effective.
Currently licensed CGRP monoclonal antibodies include. They each work in a slightly different way and include|:
• Erenumab (Aimovig) – blocks the CGRP receptor
• Fremanezumab (Ajovy) – binds to CGRP
• Galcanezumab (Emgality) – binds to CGRP
• Eptinezumab (Vyepti) – IV CGRP binder (used less commonly)
As of now, NICE recommends CGRP inhibitors for patients with chronic migraine (≥15 headache days/month, ≥8 migraines), who have tried at least three other preventives. As for their effectiveness, I’ll let you be the judge. Here is a summary of the highest quality (method and sample size) studies done on the use of CGRP therapies in patients with migraines:
• Erenumab (STRIVE trial) - NEJM, 2017 – Goadsby et al: Patients with episodic migraine had 3.2 fewer migraine days/month vs 1.8 with placebo.
• Fremanezumab (HALO CM trial) - NEJM, 2018 – Dodick et al: For chronic migraine, monthly injections led to 4.6 fewer headache days vs 2.5 with placebo.
• Galcanezumab (EVOLVE-1 & 2)
Lancet Neurology, 2018 – Skljarevski et al: Over 60% of patients achieved a ≥50% reduction in migraine days.
Eptinezumab (PROMISE-2 trial) - Lancet Neurology, 2020 – Ashina et al: Rapid onset—some patients improved within 24 hours.
Importantly, these drugs have shown benefit in patients who’ve failed multiple other treatments, and most have fewer side effects compared to traditional options like topiramate or valproate.
What This Means for Us in Primary Care
As CGRP inhibitors become available through primary care pathways, we’ll be able to initiate treatment earlier, follow up more consistently, and reduce pressure on specialist services. The specific type of treatment recommended by NICE is Atogepant. Currently in the UK it costs £182.16 for a pack of 28 tablets but this is likely to reduce with NHS procurement discounts. \
Patients like the 29-year-old I mentioned at the start—who’s done everything right, and still suffers—may finally find relief without waiting months for a neurology appointment.
We’ll keep you updated with any updates on any prescribing updates!
Until next time
How To Deal With a Patient Complaint
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