17 March 2022

Guide to the newest FDA-approved medications for migraine

Written by Dawn Teh

A migraine is characterized by severe throbbing or pain that usually happens to one side of the head. In some instances, it can often also be accompanied by nausea, vomiting, or auras that signal an attack is imminent (such as visual flashes or tingling).¹

For those that suffer from migraines, living with the condition can be extremely disruptive to daily life — especially if they occur without warning. This is why many describe it as being "more than just a headache".

A common condition with not enough research

Despite its debilitating nature (and the fact that it affects approximately  11.1% of the US population and 1 billion people globally), breakthroughs in understanding and effectively treating the condition only started surfacing over the past few decades.² ³

Some experts attribute the lack of research in this area to several factors. Firstly, it's considered a less "glamorous" condition to investigate compared to others that get more limelight from public health or celebrity-led campaigns. Furthermore, with women being 3 times more likely to be affected by migraines than men, historical gender biases often result in clinicians linking symptoms to other conditions.⁴

As a result, migraines have been inaccurately conceptualized throughout the years as being the result of a solely vascular issue relating to blood flow in the brain, as well as a psychosomatic symptom of stress intolerance.

And while treatments have been available, they were all medications used to address other co-morbidities or conditions (like epilepsy and depression). It was only by chance that clinicians realized that they had a secondary benefit in alleviating some migraine symptoms. So while they were somewhat effective, these treatments were not really targeting the true causes of the pain.⁵

The 2 key players in migraines: CGRPs and serotonin

All this has changed recently with pioneering research conducted by Dr. Peter Goadsby, Director of NIHR Clinical Research Facility & Professor of Neurology at King's College London, and his team.

While the exact causes of migraine still remain unclear (everyone has different triggers and predispositions), they discovered a vital part of its underlying biological mechanism that forms the basis of the latest migraine treatments.⁶ ⁴

It turns out that the key to the migraine mystery lies in a neurotransmitter called calcitonin gene-related peptide (CGRP). When the trigeminal nerve in the brain (which controls pain signals) gets irritated by a trigger, it releases CGRPs.

This protein results in inflammation of certain brain cells and ultimately the pain symptoms that characterize migraines.⁷

Another neurotransmitter implicated in migraine development is serotonin (more specifically, the serotonin receptor system around the trigeminal nerve endings).⁸ It's been found that people who experience the condition have higher than usual levels of serotonin between attacks. But at the onset of a migraine, these levels drop.⁹ ¹⁰ ¹¹

The new migraine medications hitting the market

Targeting this neurological cascade of events sparked by CGRPs and serotonin imbalances is now the main goal in migraine treatment. 

Here's a look at how they work:

  1. Gepants (CGRP antagonists): Work by blocking off the brain cell receptors that CGRPs attach to.

  2. Ditans (Serotonin (5-HT)1F receptor agonists): Works by binding to brain cell receptors to stimulate serotonin.¹²

Additionally, they can also be distinguished in terms of the stage at which they act:  

  • Acute migraine medication is used to stop a migraine episode and works best when taken as soon as early symptoms are felt. This course of treatment is usually recommended if the person doesn't have frequent attacks. 

  • Preventive migraine medication is a long-term treatment option for those that experience frequent (4 or more in a month) or severe episodes. They are taken regularly (sometimes daily) and are frequently used together with acute medications.

These medications can also be administered in various ways as oral tablets, intravenous infusions, or injections.

If you're suffering from regular headaches, it is essential to consult a medical professional to explore your treatment option.  

Comparing gepants and ditans for treating migraines

New acute migraine medications¹³ ¹⁴

Gepants (CGRP antagonists)

Ditans (Serotonin (5-HT)1F receptor agonists)

New preventive migraine medications

Some gepants can also be used as longer-term preventive medication. But there is another class of CGRP-targeted medication that is similar to gepants called monoclonal antibody CGRP antagonists.

They’re human-made antibodies and are bigger molecules than gepants.¹³ ¹⁹

It stops the migraine-inducing action of CGRPs by either binding to them or blocking the brain cell receptors that CGRPs usually bind to.

Gepants (CGRP antagonists)¹³ ¹⁴ ²⁰ ²¹

Monoclonal antibody CGRP antagonists²² ²³ ²⁴ ²⁵ ²⁶ ²⁷

How do newer migraine treatments compare with older ones?

Before gepants and ditans came on the scene, here were some of the most common medicines used to treat migraine:²⁸ ¹⁹ ²⁹ ³⁰

The older acute treatments include: 

  • Normal painkillers — such as paracetamol.

  • Anti-inflammatory painkillers — like Ibuprofen and aspirin.

  • Triptans (sumatriptan) that target serotonin pathways in the brain (which is similar to the ways ditans work).

For older preventive treatments, there are:

  • Beta-blockers which are traditionally used to reduce blood pressure. It was thought to be effective in reducing blood vessel dilation that occurs during migraines. 

  • Antidepressants also target serotonin pathways (like ditans) and are usually used to address mental health conditions like depression and anxiety. 

  • Antiseizure medications block electrical impulses in nerves and brain cells. 

  • Botox was used to help reduce pain signals being transmitted to areas like the forehead and scalp.  

  • Anti-sickness medication was used to address nausea symptoms.

Of all the older medications, triptans were considered the gold standard for treating migraines and it's still being used by clinicians today. But there is a major drawback to this medication.

Triptans target multiple serotonin receptors found on the brain and blood vessels, and one of its side effects was blood vessel constriction. This made it unsuitable for those with conditions like heart or vascular disease.³¹ ³² ³³

In response to this, researchers sought to develop a more streamlined medication that only acts on the brain cell receptors — and this was how ditans were created. However, ditans also have their own set of side effects. It causes drowsiness, and patients aren't allowed to drive 8 hours after taking the medication.

Given the limitations of ditans, this is why triptans still remain highly relevant these days. Some clinicians still use it as the first line of defense and administer it to patients that don't have a history of heart disease or stroke, while ditans may be used as an alternative for those with these comorbidities.

In recent years, triptans have also been updated. Here’s a list of some of the newer ones available now:

New Triptan Medications (Serotonin (5-HT)1F receptor agonists)¹³ ³⁴ ³⁵ ³⁶ ³⁷

4 tips for managing your migraine treatment

Great strides have been made in the treatment of migraines over the past several decades. But getting the right formula for addressing your symptoms must still be tailored to your individual health circumstance and needs.

Here are 4 tips for determining the best course of treatment for your migraine attacks:³⁸

  • Consider seeing a neurologist that specializes in migraines. Sometimes, seeing a GP or family doctor might be enough to help manage your symptoms. But if attacks become more frequent or intense, you might want to consider consulting a doctor that specializes in migraines.

  • Keep track of attacks in a headache journal. This should include information like the frequency, duration, and severity of your attacks. You can even note any other details like what you were doing before the onset of the migraine or what migraine medication you're taking. The more information you have, the better your physician will be able to tailor a treatment to your needs.  

  • Note any rebound headaches (a result of medication overuse). Paradoxically, certain migraine medications like triptans can cause rebound headaches when taken too frequently. But preliminary research suggests that this effect is not seen in gepants. This is why there is such great interest in this class of medication to be used as both an acute and preventive measure.³⁹ ⁴⁰

  • Inform your doctor about other medical conditions. Certain older migraine medications may not be suitable for you if you're at risk of stroke or heart disease because of their side effects.

After decades of being a neglected condition, we finally have a better understanding of migraines. Those who suffer from it can now access better medication that truly addresses the underlying mechanisms of its occurrence.

Sources:
  1. Migraine | Mayo Clinic

  2. Migraine prevalence, disease burden, and the need for preventive therapy (2007)

  3. Global, regional, and national burden of migraine and tension-type headache, 1990–2016: a systematic analysis for the global burden of disease study 2016 (2018)

  4. Can migraines be untangled by new medical thinking? | The Guardian

  5. Scientists who discovered migraine mechanism win £1.1m Brain prize | The Guardian

  6. Causes - migraine | NHS

  7. What is migraine? Your guide to talking about the condition | SingleCare

  8. Serotonin and CGRP in migraine (2012)

  9. What is the role of serotonin in the pathogenesis of migraine? | Medscape

  10. High brain serotonin levels in migraine between attacks: A 5-HT4 receptor binding PET study (2018)

  11. The science of migraines | American Association for the Advancement of Science

  12. Facts about triptans | National Headache Foundation

  13. What are the new drugs for the treatment of migraines? | Drugs.com

  14. Your guide to the newest migraine medications | SingleCare

  15. What is nurtec ODT (rimegepant) used for and how does it work? | Drugs.com

  16. Ubrelvy efficacy results | UBRELVY

  17. Reyvow (lasmiditan) | REYVOW

  18. All about reyvow | Healthline

  19. New drugs that block a brain chemical are game changers for some migraine sufferers (2021)

  20. FDA approves QULIPTA™ (atogepant), the first and only oral CGRP receptor antagonist specifically developed for the preventive treatment of migraine | Abbvie

  21. Qulipta (atogepant): Side effects (2022)

  22. Eptinezumab in episodic migraine: A randomized, double-blind, placebo-controlled study (PROMISE-1) (2020)

  23. Emgality (galcanezumab): Emgality vs other drugs (2019)

  24. Patients experienced significantly more migraine-free days with AJOVY vs placebo in the HALO + Long-Term Extension Studies | AJOVY

  25. Understanding possible side effects | AJOVY

  26. Aimovig (erenumab-aooe): Uses (2021)

  27. What are the possible side effects of Aimovig? | Aimovig

  28. Migraine medication, treatment and prevention | Patient

  29. Migraine: Triptans | Mayo Clinic

  30. Topamax for migraine prevention | Very Well Health

  31. How gepants and ditans complement existing therapies | American Migraine Foundation

  32. Sumatriptan | NHS

  33. Lasmiditan: New first-in-class drug treatment approved for migraine | Harvard Health Publishing

  34. Tosymra | Tosymra

  35. Sumatriptan (Imitrex, Tosymra) nasal spray | Good Rx

  36. Zembrace symtouch | Drugs.com

  37. Onzetra xsail (sumatriptan) nasal powder | Good Rx

  38. Understanding migraine medications | American Migraine Foundation

  39. Stopping the vicious cycle of rebound headaches | Harvard Health Publishing

  40. Gepants (2020)

The author, Dawn Teh, is a health writer and former psychologist who enjoys exploring topics about the mind, body, and what helps humans thrive.

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