The goals of migraine prevention are to reduce the frequency and severity of migraine attacks, improve daily function, and lessen reliance on “as-needed” medications—all while minimizing side effects.

Finding the right preventive treatment can be challenging, especially for those with frequent headaches or chronic migraine. For many years, preventive care relied on medications developed for other conditions, such as antiseizure medications, antidepressants, and blood pressure medications. Although these medications can be a great choice for some, research shows that more than half of people living with migraine discontinue these treatments within three months, often because of limited effectiveness or side effects.

Today, there are migraine-targeted options available. These include anti-CGRP-targeted therapies, nabotulinumtoxinA injections, and neuromodulation devices.

Anti-CGRP Targeted Therapies

In the past seven years, the FDA has approved eight new medications that block the calcitonin gene-related peptide (CGRP) pathway, which plays a key role in migraine pain.

  • Monoclonal antibodies (anti-CGRP mAbs): erenumab, galcanezumab, fremanezumab, and eptinezumab
  • Gepants (oral CGRP receptor blockers): rimegepant, atogepant, ubrogepant, and zavegepant

Six of these are approved for prevention: erenumab, galcanezumab, fremanezumab, eptinezumab, rimegepant, and atogepant. Fremanezumab was also recently approved for children ages 6–17.

Anti-CGRP mAbs are injections or infusions. Some are monthly at-home injections, others quarterly, and one (eptinezumab) is given by IV infusion every three months. Gepants are taken orally. Rimegepant is a dissolving tablet taken every other day, while atogepant is a daily pill.

OnabotulinumtoxinA

Botox® was FDA-approved for migraine prevention in 2010. In addition to weakening muscles, it prevents the release of CGRP and other pain-related molecules from sensory nerves.

Treatment involves 31 injections across the head and neck, given every 12 weeks in a healthcare professional’s office.

Neuromodulation Devices

Five FDA-cleared neuromodulation devices are available for migraine:

  • External trigeminal nerve stimulation (eTNS)
  • External vagal nerve stimulation (eVNS)
  • Single pulse transcranial magnetic stimulation (sTMS)
  • External combined trigeminal and occipital nerve stimulation (eCOT-NS)
  • Remote electrical neurostimulation (REN)

These devices stimulate nerves connected to migraine pathways, altering how pain signals are processed.

Choosing the Right Preventive Treatment

The best choice depends on multiple factors: effectiveness, personal health profile, side effects, preferences, and access.

Effectiveness

According to the American Headache Society, anti-CGRP therapies (monoclonal antibodies and gepants) are first-line options for episodic migraine. For chronic migraine, anti-CGRP therapies and onabotulinumtoxinA can be considered first-line.

Side Effects

Most preventive treatments are well-tolerated.

  • Anti-CGRP mAbs: injection site reactions, constipation, flu-like symptoms, and in some cases hair loss, high blood pressure, or Raynaud phenomenon.
  • Gepants: constipation, nausea, decreased appetite,fatigue, and in rare cases hair loss or Raynaud phenomenon.
  • OnabotulinumtoxinA: local injection site pain, bruising, neck discomfort, or cosmetic effects such as temporary eyelid drooping.
  • Neuromodulation: mild discomfort at the stimulation site.

Special Considerations

  • Pregnancy: The safety of anti-CGRP therapies and Botox® is unknown. Family planning should be discussed before starting. Gepants may be easier to adjust around conception, while neuromodulation may be an option.

  • Other conditions: Neuromodulation is not recommended for people with uncontrolled epilepsy or implanted devices.

Logistics and Coverage

OnabotulinumtoxinA must be administered in-office every three months, which can be challenging for those far from a provider. Most anti-CGRP therapies can be used at home but some require self-injection, or infusion by a healthcare provider. Neuromodulation can be used at home.

Insurance often requires patients to try older medications before covering anti-CGRP therapies or Botox®. Neuromodulation devices are usually not covered, and out-of-pocket costs can be high.

The Bottom Line

The good news is that people living with migraine now have more preventive options than ever before. With treatments that are more targeted and often better tolerated, you and your healthcare professional can work together to find the approach that best fits your needs and helps improve your quality of life.