The introduction is also posted on Spotify as a podcast by “Gerry at The Health Equation”

You can search Spotify for “Gerry at The Health Equation”

Or use the link below

https://podcasters.spotify.com/pod/show/gerrygaj

Below is the specific link

Gerry Gajadharsingh writes:

“For many years the main drugs used for acute or abortive migraine relief tended to be NSAID, Betablockers, anti-depressants and Triptans.

The medications for preventive therapy of migraines had not changed in a long time until now. First-line preventive therapy has traditionally consisted of three classes of agents: beta-blockers, tricyclic antidepressants such as Amitriptyline, and topiramate (anti-epileptic).

The new drugs called CGRP antagonists work by targeting a specific molecule called calcitonin gene-related peptide (CGRP), which plays a significant role in the development of migraines. During a migraine attack, CGRP levels rise, leading to inflammation and dilating blood vessels around the brain. This combination is thought to trigger the pain and other symptoms associated with migraines.

CGRP-targeting drugs fall into two main categories:

  1. Monoclonal Antibodies (MAbs): These drugs (like erenumab, fremanezumab, and galcanezumab) bind to either the CGRP molecule itself or its receptor, blocking its activity. They’re typically used for migraine prevention and are administered monthly or quarterly. These drugs work by reducing the frequency, duration, and severity of migraine attacks over time.
  2. Small Molecule CGRP Receptor Antagonists: Known as “gepants” (e.g., ubrogepant and rimegepant), these drugs directly block CGRP receptors but act more quickly and can be taken as needed. They’re primarily used for acute migraine relief and work quickly to reduce migraine symptoms once a headache has already started.

Both types of CGRP drugs have shown good effectiveness in reducing migraine frequency and severity for many people, and they’re especially useful for those who haven’t had success with more traditional migraine treatments. Plus, they tend to have fewer side effects compared to older migraine medications.

They are however relatively expensive and given that most headache and migraine symptoms are multifactorial and have several contributory factors, it’s worthwhile in the more medium and long-term, trying to explore and treat these factors with an experienced clinician and not to just rely on expensive medication for symptom relief.

CGRP Targeting Migraine Therapies Dose and Costs

Small-molecule CGRP Receptor Antagonists (Gepants)

Rimegepant (Vydura) 75mg orally every other day (8 tabs) £140

Monoclonal Antibodies

Erenumab (Aimovig) 70-140mg subcutaneous injection once a month £400/month

Fremanezumab (Ajovy) 225mg subcutaneous injection once a month £450/month

Based on new evidence, Candesartan — an angiotensin receptor blocker (ARB) — is now also a first-line drug for migraine. The serotonin-noradrenaline reuptake inhibitors (SNRI’s such as venlafaxine and duloxetine) although usually used for generalised anxiety disorder (GAD) are also considered first-line agents for migraine treatment. The cost of these drugs is much lower than CGRP antagonists.”

https://www.thehealthequation.co.uk/headache-migraine-clinic/

Medscape

Neil Skolnik, MD

I’m Dr Neil Skolnik and today we are going to talk about the position statement from the American Headache Society (AHS) ” Calcitonin gene related peptide targeting therapies are a first line option for the prevention of migraine, which is focused on calcitonin gene-related peptide (CGRP)–targeting therapies. This update is of critical importance because about ¾ of people with migraine get their migraine care from a primary care clinician, not from a neurologist or a headache specialist. CGRP-targeting therapies have transformed migraine care at the specialty level, but many of us in primary care are not yet familiar with this class of medicines. Until this new statement was released, CGRPs were not viewed as first-line agents for migraine. That has now changed.

Two main types of therapy for people with migraine headache are: (1) acute or abortive therapy (when a headache develops, it is treated), and (2) preventive therapy. Preventive therapy is typically used when the patient has headaches on 4 or more days a month and is aimed at reducing the frequency and severity of headaches. About 40% of patients with migraine qualify for preventive therapy, but only a minority are receiving it.

The armamentarium for preventive therapy of migraines had not changed in a long time until now. First-line preventive therapy has traditionally consisted of three classes of agents: beta-blockers, tricyclic antidepressants, and topiramate. These medicines were developed for different therapeutic purposes, yet they work for migraines. These drugs may have off-target effects that can make them difficult to tolerate.

Based on new evidence, Candesartan — an angiotensin receptor blocker (ARB) — is now also a first-line drug for migraine. This is good news, because ARBs are a drug class that we have a lot of experience with, are easy to use, and could be an excellent choice for people with concomitant hypertension or chronic kidney disease. The serotonin-norepinephrine reuptake inhibitors (venlafaxine and duloxetine) are also considered first-line agents for migraine treatment.

In the AHS’s new position statement, the two main drug classes are small-molecule CGRP receptor antagonists and monoclonal antibodies. 

The role of the neuropeptide CGRP in migraine was originally discovered after finding that blood levels of CGRP were elevated during migraine attacks. This led to the discovery of agents that blocked CGRP, initially for acute treatment of migraine, and then for preventive therapy. Multiple clinical studies show the CGRP targeting therapies to be as or even more effective than traditional first-line agents at decreasing the number of migraine days per month.

The efficacy and safety of these agents have been demonstrated in both randomized trials and in real-world studies. Other important positive endpoints include fewer days of migraine, reduced acute medication use, and improvements in many quality-of-life outcomes. Studies also have shown that CGRP-targeting therapies are well tolerated and safe, with very few serious adverse events.

Furthermore, studies have shown the CGRP targeting therapies are effective in individuals who have failed multiple other first-line therapies. They fit now both as first-line agents and as agents that can be used in difficult-to-treat patients as well as in patients who struggle with acute medication overuse, which is often very challenging.

To quote from the AHS statement, “The evidence supporting the efficacy, tolerability, and safety of CGRP-targeting therapies for migraine prevention is substantial in its volume, scope, and quality.”

Side effects are uncommon and can include hypertension, constipation, and Raynaud’s phenomenon.

The position statement is strong and is based on a lot of evidence and clinical experience. CGRP-targeting therapies are now first-line agents for the prevention of migraine headache. We should learn more about and begin to feel comfortable using this class of agents because they stand to benefit our patients greatly. I’d suggest looking at the table below and picking one new agent to become familiar with so that you can add that agent to your toolbox.