New First-Line Treatments for Migraine Prevention

According to the American Headache Society (AHS) position statement,

“Calcitonin Gene-Related Peptide-Targeting Therapies Are a First-Line Option for the Prevention of Migraine.”

Surprisingly, other first-line treatments include:

• Candesartan
• Venlafaxine, and
• Duloxetine

We all know about candesartan. Like Beta-blockers, it is a blood pressure-lowering medicine. For people with hypertension and concomitant migraine, it can be a good choice to target both conditions with a single drug.

Venlafaxine and Duloxetine are SNRIs (selective serotonin-norepinephrine reuptake inhibitors). These drugs are widely used to treat depression and painful neuropathies such as those with diabetic neuropathy.

Until now, Tricyclic antidepressants (TCAs) like Amitriptyline have been commonly used for migraine prevention. However, these drugs have cardiovascular and gastrointestinal side effects and are usually avoided in older patients.

Venlafaxine and Duloxetine can also cause dry mouth, and dyspepsia, and may cause an elevation in the blood pressure.

But, What are CGRP Antagonists?

CGRP targeting therapies include:

• CGRP antagonists
• Monoclonal antibodies targeting CGRP receptors

Research found that migraine patients have high levels of CGRP (calcitonin gene-related peptides) in their blood, especially during acute migraine episodes.

Subsequently, CGRP-targeting therapies were invented. CGRP antagonists are small molecules used primarily to treat the acute migraine headache. However, Nurtec (Rimegepant has also been approved for migraine prevention.

Here are all the CGRP antagonists currently approved for the treatment of migraine headaches:

• Nurtec (Rimegepant)
• Ubrelvy (Ubrogepant)
• Zavzpret Nasal Spray (Zavegepant)
• Atogepant (Qulipta)

Monoclonal antibodies targeting CGRP receptors are indicated primarily for the prevention of migraine headaches.

These drugs are available as subcutaneous injections administered every two to four weeks.

Here is a list of all the CGRP-targeting monoclonal antibodies currently approved for migraine prevention:

• Erenumab (Aimovig)
• Ajovy (Fremanezumab)
• Emgality (Galcanezumab)

Studies have found that CGRP-targeted therapies are more effective than conventional migraine prevention therapies.

These drugs prevent migraine headaches more effectively by reducing the number of migraine episodes per month, improving the quality of life, and reducing the need to use abortive migraine medications.

In addition, these drugs are much safer than conventional migraine preventive therapies.

CGRP antagonists as first-line migraine prevention treatment:

CGRP-targeted therapies have been approved for migraine prevention. These drugs are best for people who have difficult-to-treat migraine and have failed or are intolerant to multiple first-line therapies.

In addition, these drugs are best for people who overuse acute migraine therapies like NSAIDs which can have negative health outcomes in the long run.

Here are the updated recommendations for migraine prevention [Ref]:

• Abbreviations: AAN, American Academy of Neurology; CGRP, calcitonin gene-related peptide; HIT-6, six-item Headache Impact Test; ICHD-3, International Classification of Headache Disorders, third edition; MMDs/MHDs, monthly migraine/headache days; MIDAS, Migraine Disability Assessment.

In Conclusion:

The AHA statement strongly supports the use of CGRP-targeted therapies because of their enhanced efficacy, fewer side effects, and better tolerability.

Primary physicians need to be aware of the doses, mode of administration, and side effects of these drugs (hypertension, Raynaud’s phenomenon, constipation, and injection-site reactions).