Migraine Treatment in 2026: CGRP, Prevention & New Therapies

Chronic Migraine Headaches

Migraine and Chronic Migraine: 2026 Update

CGRP, Gepants, Botox, Neuromodulation, Neck Pain, and Central Sensitization

Last updated: April 25, 2026

Spring 2026 Migraine Treatment Updates — Quick Summary

  • Migraine is a neurologic disease, not just a headache. Migraine can include head pain, nausea, light sensitivity, sound sensitivity, smell sensitivity, dizziness, visual aura, brain fog, fatigue, mood changes, and neck pain. The World Health Organization notes that headache disorders are among the most common nervous-system disorders and that migraine ranked third for overall neurological disease burden by age-standardized disability-adjusted life years in 2021.

  • Chronic migraine has a specific definition. Chronic migraine means headache on 15 or more days per month for more than 3 months, with migraine features on at least 8 days per month. This distinction matters because chronic migraine is treated differently from occasional migraine.

  • CGRP-targeting therapies are now first-line preventive options. The American Headache Society has shifted migraine prevention away from a “fail several older medications first” model and now considers CGRP-targeting therapies a first-line option for prevention, based on evidence for efficacy, tolerability, adherence, and real-world clinical experience.

  • Gepants have changed both acute and preventive migraine care. Rimegepant is approved for both acute migraine treatment and preventive treatment of episodic migraine; the 2026 label notes a 75 mg as-needed acute dose, 75 mg every-other-day preventive dosing, and that safety of more than 18 doses in 30 days has not been established. Atogepant is approved for preventive treatment of migraine in adults, including chronic migraine, and AbbVie notes that only the 60 mg dose is approved for chronic migraine prevention.

  • Nasal acute therapies are more important now. Zavegepant nasal spray is an acute CGRP receptor antagonist option for adults with migraine, useful when nausea, vomiting, or delayed stomach absorption makes oral medication difficult. Its label states it is not a preventive treatment. In 2025, the FDA also approved Atzumi, a dihydroergotamine nasal powder, for acute treatment of migraine with or without aura in adults.

  • A new combination acute medication was approved in 2025. The FDA approved Symbravo, a meloxicam/rizatriptan combination tablet, for acute treatment of migraine with or without aura in adults. This gives clinicians another option for patients who benefit from combining a triptan with an anti-inflammatory strategy.

  • Botox remains a cornerstone for chronic migraine. OnabotulinumtoxinA is indicated for prevention of headaches in adults with chronic migraine, defined as 15 or more headache days per month with headaches lasting 4 hours a day or longer. It is not established for episodic migraine with 14 or fewer headache days per month.

  • Emergency migraine care is moving away from opioids. The 2025 American Headache Society emergency department migraine guideline update gives Level A “must offer” recommendations to IV prochlorperazine and greater occipital nerve blocks when appropriate, while strengthening recommendations against opioid therapies; hydromorphone is listed as a Level A “must not offer” treatment.

  • Neck pain is part of migraine for many patients. A 2025 Cephalalgia review emphasizes that neck pain can be a migraine symptom, a trigger, or a coexisting condition, and that migraine-related neck pain is often misdiagnosed as a purely cervical disorder. The review also highlights overlapping neuroanatomical pathways between the neck and trigeminal pain system.

  • Central sensitization explains why migraine can become chronic, widespread, and touch-sensitive. Central sensitization means the nervous system becomes overly responsive to pain signals. It is linked to cutaneous allodynia, where normally non-painful touch — brushing hair, wearing glasses, lying on a pillow — becomes painful. A review in Journal of Pain Research describes central sensitization as involved in both cutaneous allodynia and migraine chronification.

  • The next pipeline target beyond CGRP is PACAP. In February 2026, Lundbeck announced that IV bocunebart, also known as Lu AG09222, an investigational anti-PACAP monoclonal antibody, met the primary endpoint in a Phase IIb migraine prevention trial in patients with prior preventive treatment failures. This remains investigational, but it is one of the most important “beyond CGRP” migraine developments to watch.

Introduction

Migraine is one of the most disabling neurologic conditions worldwide. It is not simply a severe headache. Migraine is a brain-network disorder involving sensory processing, pain modulation, trigeminal nerve activation, neuropeptides such as CGRP and PACAP, and, in some patients, cortical spreading depression related to aura.

For many patients, migraine becomes chronic. Chronic migraine can affect work, family life, sleep, mood, exercise, and social activities. The Migraine Research Foundation estimates that migraine affects about 39 million people in the United States and 1 billion worldwide, and that more than 4 million people have chronic daily migraine with at least 15 migraine days per month.

The good news is that migraine treatment has changed dramatically. In 2026, patients have more targeted options than ever before: CGRP monoclonal antibodies, gepants, Botox, neuromodulation devices, nerve blocks, improved acute medications, and emerging therapies that target pathways beyond CGRP.

The best migraine care is no longer just “take something when the headache starts.” It is a personalized plan that asks:

What type of migraine is this? How frequent is it? Is there medication overuse? Is the neck or occipital nerve system involved? Is central sensitization present? What acute plan and preventive plan fit this patient’s medical history and goals?

Understanding Migraine

Migraine is a disorder of the brain’s sensory and pain-processing networks. During a migraine attack, the brain becomes more sensitive to internal and external stimuli. Light, sound, smell, motion, touch, hunger, hormonal shifts, sleep disruption, stress letdown, weather changes, alcohol, and certain foods may all become triggers in susceptible patients.

A migraine attack can have several phases:

1. Prodrome

Hours to days before head pain, patients may notice yawning, fatigue, food cravings, neck stiffness, mood change, thirst, frequent urination, or difficulty concentrating.

2. Aura

Some patients experience aura, most commonly visual symptoms such as flashing lights, zig-zag lines, blind spots, shimmering, or spreading visual distortion. Aura can also involve sensory symptoms, speech difficulty, or other neurologic symptoms. Aura is often linked to cortical spreading depression, a wave of altered electrical activity across the cortex.

3. Headache phase

Migraine pain is often throbbing or pulsating and may be one-sided or bilateral. It is commonly associated with nausea, vomiting, light sensitivity, sound sensitivity, smell sensitivity, and worsening with activity.

4. Postdrome

After the pain improves, patients may feel drained, foggy, sore, dizzy, emotionally sensitive, or “hungover” for a day or more.

Episodic Migraine vs. Chronic Migraine

Migraine frequency is important because it guides treatment.

Episodic migraine generally means migraine on fewer than 15 headache days per month.

Chronic migraine means headache on 15 or more days per month for more than 3 months, with at least 8 days per month having migraine features. The International Classification of Headache Disorders uses this definition because chronic migraine is not just “bad migraine”; it is a more persistent state of nervous-system activation.

Patients often undercount headache days because they only count the worst attacks. A headache diary should track:

  • Any head pain day
  • Migraine-feature days
  • Medication-use days
  • Menstrual timing
  • Sleep, stress, alcohol, skipped meals, travel, weather, and other triggers
  • Disability: missed work, reduced productivity, canceled plans, or time in bed

This matters because a patient with 6 “migraine attacks” per month may actually have 18 headache days per month when milder headache days are included.

The Trigeminovascular System and CGRP

Migraine pain is strongly linked to the trigeminovascular system. The trigeminal nerve carries pain signals from the face, head, blood vessels, and meninges. During migraine, trigeminal nerve activation can lead to release of CGRP, a neuropeptide involved in migraine pain signaling, vasodilation, inflammation, and sensitization.

This is why CGRP-targeting medications have been such an important breakthrough. Some medications block the CGRP ligand, some block the CGRP receptor, and some are small-molecule receptor antagonists called gepants.

The current CGRP-targeting options include preventive monoclonal antibodies such as erenumab, fremanezumab, galcanezumab, and eptinezumab, as well as gepants such as ubrogepant, rimegepant, atogepant, and zavegepant. Eptinezumab is an IV CGRP monoclonal antibody indicated for preventive treatment of migraine in adults, with once-every-3-month dosing described in its label.

The Trigeminocervical Pathway: Why Migraine Often Includes Neck Pain

Many migraine patients are told their headaches are “coming from the neck.” Sometimes that is true. Cervical arthritis, muscle spasm, posture, whiplash, occipital neuralgia, and cervicogenic headache can all contribute to head pain.

But migraine itself can also cause neck pain.

The reason is the trigeminocervical pathway. Pain signals from the trigeminal nerve and the upper cervical nerves converge in the trigeminocervical complex, a pain-processing region in the lower brainstem and upper cervical spinal cord. Because of this shared wiring, pain from the upper neck can be felt in the head, and migraine pain can be felt in the neck or occipital region.

A 2025 review in Cephalalgia emphasizes that neck pain is common in migraine, can occur during all migraine phases and between attacks, and may be a migraine symptom, a trigger, or a coexisting condition. The same review highlights overlapping neuroanatomical pathways between the neck and trigeminal systems.

This is why a patient may say:

“My migraine starts at the base of my skull, then moves to the temple or behind the eye.”

That pattern does not automatically mean the problem is purely cervical. It may be migraine, occipital neuralgia, cervicogenic headache, or a combination.

Central Sensitization and Cutaneous Allodynia

Central sensitization is one of the most important concepts in chronic migraine.

It means that the nervous system becomes more reactive to pain signals. Pain pathways become amplified. The threshold for triggering symptoms becomes lower. Over time, pain may spread, last longer, and respond less reliably to acute medications.

Signs of central sensitization include:

  • Scalp pain when brushing hair
  • Pain from wearing glasses, hats, earrings, or a ponytail
  • Pain from lying on a pillow
  • Sensitivity to light, sound, smell, touch, or motion
  • Headache that spreads from one region to the whole head
  • Neck and shoulder sensitivity
  • Migraine becoming more frequent or harder to stop
  • Coexisting fibromyalgia, irritable bowel syndrome, temporomandibular pain, restless legs, or other sensory sensitivity syndromes

The medical term for pain from normally non-painful touch is cutaneous allodynia. A Frontiers in Neurology review notes that cutaneous allodynia occurs in approximately 60% of patients with migraine and involves sensitization at multiple levels of the trigeminal-thalamic-cortical pain pathway.

This is clinically important because patients with central sensitization often need prevention, not just rescue medications. Treating attacks earlier, reducing medication overuse, improving sleep, addressing neck/occipital input, and lowering overall migraine frequency can help calm the system.

Common Migraine Symptoms

Migraine symptoms may include:

  • Moderate to severe head pain
  • Throbbing, pulsating, pressure, stabbing, or burning pain
  • Pain on one side or both sides
  • Nausea or vomiting
  • Light sensitivity
  • Sound sensitivity
  • Smell sensitivity
  • Dizziness or vertigo
  • Visual aura
  • Tingling or numbness
  • Speech difficulty during aura
  • Neck pain or stiffness
  • Scalp tenderness
  • Brain fog
  • Fatigue
  • Mood changes
  • Food cravings
  • Difficulty concentrating

Migraine can also present without obvious head pain, especially in vestibular migraine, migraine aura without headache, and some post-concussion migraine patterns.

Diagnosing Migraine

Migraine is usually diagnosed clinically, based on history and neurologic examination. The most important diagnostic tool is a careful story: timing, frequency, duration, associated symptoms, triggers, family history, medication use, disability, and neurologic red flags.

A migraine evaluation may include:

  • Detailed headache history
  • Neurologic examination
  • Headache diary review
  • Medication-overuse assessment
  • Sleep, mood, hormone, and lifestyle review
  • Blood pressure assessment
  • Review of caffeine, alcohol, supplements, and medications
  • Screening for neck pain, occipital neuralgia, TMJ dysfunction, and central sensitization
  • MRI brain or other testing when red flags are present

Most stable, typical migraine patients do not need repeated brain imaging. Imaging is considered when the pattern is new, unusual, progressive, associated with neurologic deficits, or concerning for a secondary cause.

Medication-Overuse Headache

Medication-overuse headache is one of the most common reasons migraine becomes chronic.

The International Classification of Headache Disorders defines medication-overuse headache as headache on 15 or more days per month in a person with a pre-existing headache disorder, developing after regular overuse of acute headache medication for more than 3 months. The threshold is 10 or more days per month for some medications and 15 or more days per month for others, depending on the drug class.

Practical rules:

  • Try to avoid triptans, ergots, opioids, butalbital combinations, or combination analgesics on 10 or more days per month.
  • Try to avoid NSAIDs or acetaminophen on 15 or more days per month.
  • Avoid opioids and butalbital whenever possible in migraine.
  • Add or optimize prevention when acute medication use is increasing.
  • Track medication days, not just migraine days.

Medication overuse is not a moral failing. It usually means the migraine disease is under-treated.

Acute Migraine Treatment

The goal of acute treatment is to stop an attack early, restore function, and avoid medication overuse.

NSAIDs and acetaminophen

For milder attacks, NSAIDs or acetaminophen may be appropriate if safe for the patient. Contraindications such as kidney disease, ulcers, anticoagulant use, liver disease, pregnancy, and cardiovascular risk must be considered.

Triptans

Triptans remain useful for many patients. Examples include sumatriptan, rizatriptan, eletriptan, zolmitriptan, naratriptan, and frovatriptan. They work best when taken early in the migraine attack. They are generally avoided in patients with certain cardiovascular, cerebrovascular, hemiplegic migraine, or migraine-with-brainstem-aura situations unless a specialist determines otherwise.

Gepants

Gepants are CGRP receptor antagonists. They do not work by vasoconstriction, which makes them useful for some patients who cannot take triptans. Acute gepant options include ubrogepant, rimegepant, and zavegepant nasal spray.

Rimegepant is approved for acute migraine treatment and preventive treatment of episodic migraine in adults. Its 2026 label lists 75 mg as needed for acute treatment, with a maximum of 75 mg in 24 hours and no established safety for more than 18 doses in 30 days.

Zavegepant is a nasal CGRP receptor antagonist for acute migraine treatment in adults. It is not a preventive medication, and its label notes that the safety of treating more than 8 migraines in a 30-day period has not been established.

Dihydroergotamine

Dihydroergotamine, or DHE, can be useful for prolonged attacks, attacks with recurrence, and some patients who do not respond to triptans or gepants. DHE is available in injectable and nasal forms. The FDA approved Atzumi, a DHE nasal powder, in 2025 for acute treatment of migraine with or without aura in adults.

Combination acute therapy

Some patients respond better to rational combination therapy. A common strategy is a triptan plus an NSAID. In 2025, the FDA approved Symbravo, a meloxicam/rizatriptan tablet, for acute treatment of migraine with or without aura in adults.

Antiemetics

Nausea and vomiting are major barriers to treatment. Antiemetics such as metoclopramide, prochlorperazine, or ondansetron may be used depending on the situation. In emergency settings, IV prochlorperazine has strong evidence in the 2025 American Headache Society emergency department update.

Preventive Migraine Treatment

Prevention should be considered when migraine is frequent, disabling, prolonged, associated with medication overuse, or poorly controlled with acute medications.

Preventive treatment goals are realistic:

  • Fewer migraine days
  • Less severe attacks
  • Better response to acute medications
  • Less medication overuse
  • Better function
  • Fewer emergency visits
  • Less central sensitization over time

Traditional preventive medications

Traditional options include topiramate, valproate, propranolol, metoprolol, timolol, candesartan, amitriptyline, nortriptyline, venlafaxine, and others. These can still be very useful, especially when matched to the patient’s comorbidities. For example, a patient with insomnia may benefit from a different medication than a patient with hypertension, obesity, pregnancy plans, kidney stones, asthma, or depression.

CGRP monoclonal antibodies

CGRP monoclonal antibodies are targeted migraine preventives. They include:

  • Erenumab
  • Fremanezumab
  • Galcanezumab
  • Eptinezumab

The American Headache Society now considers CGRP-targeting therapies a first-line option for migraine prevention rather than a last-resort option after multiple older medication failures.

Preventive gepants

Atogepant is a once-daily oral preventive gepant approved for prevention of migraine in adults, including chronic migraine. AbbVie notes that Qulipta is approved across episodic and chronic migraine and that only the 60 mg dose is approved for chronic migraine prevention.

Rimegepant is another gepant option, used every other day for preventive treatment of episodic migraine in adults, while also having an acute-treatment indication.

Botox for chronic migraine

Botox is one of the most established treatments for chronic migraine. It is given approximately every 12 weeks using a standardized injection pattern across head and neck muscle areas. It is indicated for adults with chronic migraine, not for episodic migraine with 14 or fewer headache days per month.

Botox can be especially useful when migraine is chronic, when neck and scalp tenderness are prominent, when oral preventives are poorly tolerated, or when patients have medication-overuse risk.

Combination prevention

Some chronic migraine patients need combination prevention, such as Botox plus a CGRP-targeting therapy, or a preventive gepant plus another preventive strategy. Combination treatment should be individualized and monitored for benefit, side effects, cost, and insurance coverage.

Occipital Nerve Blocks and Migraine

Occipital nerve blocks can be useful when migraine has prominent posterior head pain, scalp tenderness, occipital neuralgia features, or trigeminocervical sensitization.

A key 2025 update is that greater occipital nerve blocks now appear in the American Headache Society emergency department migraine guideline update as a Level A “must offer” option for appropriate adults with acute migraine in emergency settings.

This does not mean every migraine comes from the occipital nerve. It means the occipital nerves are an important access point into the trigeminocervical pain network. In the right patient, a nerve block can help interrupt the pain cycle.

Neuromodulation Devices

Neuromodulation devices use electrical or magnetic stimulation to modulate migraine-related nerve pathways. They can be helpful for patients who prefer non-drug options, cannot tolerate medications, are trying to reduce acute medication use, or need options during pregnancy planning when medication choices are limited.

Devices used in migraine care include options targeting the trigeminal nerve, vagus nerve, remote electrical neuromodulation pathways, or combined trigeminal/occipital branches. The American Migraine Foundation describes FDA-cleared neuromodulation options including Cefaly, Nerivio, gammaCore, and SAVI Dual for prevention and/or acute treatment depending on the device.

Neuromodulation is not a cure, but it can be a useful part of a layered migraine plan.

Lifestyle and Behavioral Treatment

Lifestyle treatment is not “just lifestyle.” In migraine, regularity stabilizes the nervous system.

Important foundations include:

  • Consistent sleep and wake time
  • Regular meals and hydration
  • Caffeine consistency
  • Regular aerobic exercise as tolerated
  • Avoiding excessive fasting
  • Limiting alcohol when it is a trigger
  • Managing screen brightness and sensory overload
  • Treating sleep apnea when present
  • Addressing anxiety, depression, and trauma when relevant
  • Cognitive behavioral therapy, biofeedback, mindfulness, or relaxation training
  • Physical therapy when neck dysfunction, posture, or myofascial pain contribute

Patients with chronic migraine often need both biologic treatment and nervous-system regulation. The goal is not to blame stress; the goal is to reduce the number of inputs that keep the migraine network activated.

Migraine, Mental Health, and Sleep

Migraine, anxiety, depression, insomnia, and chronic pain frequently reinforce one another. A patient with migraine may become anxious about the next attack, sleep poorly, use more acute medications, reduce exercise, and become more sensitized. That cycle can worsen migraine frequency.

Addressing mental health is therefore part of migraine treatment. Cognitive behavioral therapy, treatment of depression or anxiety, sleep therapy, and relaxation-based approaches can improve quality of life and may improve migraine control.

Special Migraine Patterns

Vestibular migraine

Vestibular migraine can cause dizziness, vertigo, imbalance, motion sensitivity, nausea, visual sensitivity, and brain fog. Head pain may be absent or mild. It is often mistaken for inner-ear disease.

Menstrual migraine

Hormonal migraine often clusters around the menstrual window. Treatment may involve acute therapy, mini-prevention around menses, magnesium, hormonal strategies, or standard prevention depending on frequency and risk factors.

Migraine with aura

Migraine aura is usually visual, but it can also involve sensory, language, or brainstem symptoms. New aura symptoms, prolonged aura, weakness, or aura that is different from the patient’s usual pattern should be evaluated carefully.

Post-traumatic migraine

After concussion or whiplash, migraine may overlap with neck pain, vestibular symptoms, sleep disruption, mood symptoms, and central sensitization. Treatment often needs to address both migraine biology and cervical/vestibular contributors.

Emerging Migraine Research: Beyond CGRP

CGRP changed migraine care, but not every patient responds to CGRP-targeting treatment. The next frontier includes other neuropeptides and pain pathways.

PACAP pathway

PACAP stands for pituitary adenylate cyclase-activating polypeptide. It is another neuropeptide involved in migraine biology. In February 2026, Lundbeck announced positive Phase IIb top-line results for IV bocunebart, also known as Lu AG09222, an investigational anti-PACAP monoclonal antibody for migraine prevention in patients with prior preventive treatment failures. The company stated that it plans to discuss Phase III design options with regulators.

This is promising, but it is not yet an approved migraine treatment.

Better phenotyping

Migraine care is moving toward matching treatments to clinical phenotype: chronic vs episodic, aura vs no aura, vestibular symptoms, menstrual pattern, allodynia, medication overuse, neck involvement, obesity, insomnia, anxiety, depression, cardiovascular risk, pregnancy plans, and treatment history.

Earlier prevention

The field is increasingly recognizing that prevention should not be delayed until a patient has years of disability. Earlier preventive treatment may reduce progression from episodic to chronic migraine, reduce central sensitization, and improve quality of life.

Conditions That Can Mimic Migraine

A careful diagnosis matters because not every headache is migraine. Conditions that can overlap with or mimic migraine include:

  • Tension-type headache
  • Medication-overuse headache
  • Occipital neuralgia
  • Cervicogenic headache
  • Temporomandibular joint disorder
  • Sinus disease
  • Idiopathic intracranial hypertension
  • Giant cell arteritis
  • Stroke or transient ischemic attack
  • Brain tumor or structural lesion
  • Cerebral venous sinus thrombosis
  • Reversible cerebral vasoconstriction syndrome
  • Post-traumatic headache
  • Cluster headache and other trigeminal autonomic cephalalgias

The presence of migraine features does not exclude another diagnosis, especially when the headache pattern changes.

When to Seek Urgent Medical Care

Seek urgent evaluation for:

  • Sudden “worst headache of life”
  • Thunderclap onset
  • New weakness, numbness, speech difficulty, confusion, fainting, double vision, or loss of vision
  • New headache after age 50
  • Headache with fever, stiff neck, rash, or immune suppression
  • Headache during pregnancy or postpartum
  • Headache after significant trauma
  • New headache with cancer history
  • Headache with jaw pain while chewing, scalp tenderness, or vision changes
  • Headache that is positional, triggered by exertion or sex, or progressively worsening
  • A major change from the patient’s usual migraine pattern

Practical Approach at Los Altos Neurology

At Los Altos Neurology, migraine care is individualized. A modern migraine plan may include:

  • Confirming the diagnosis and migraine subtype
  • Counting headache days and migraine days
  • Screening for medication-overuse headache
  • Reviewing prior medication trials and side effects
  • Identifying comorbid neck pain, occipital neuralgia, TMJ pain, vestibular symptoms, sleep problems, anxiety, depression, and central sensitization
  • Building a stepwise acute treatment plan
  • Choosing prevention based on migraine frequency, medical history, patient preference, and insurance access
  • Considering Botox, CGRP monoclonal antibodies, preventive gepants, neuromodulation, or nerve blocks when appropriate
  • Addressing lifestyle regularity, sleep, exercise, hydration, caffeine, stress physiology, and physical therapy when relevant
  • Reassessing response with a headache diary

The goal is not simply fewer headaches. The goal is better function, fewer disabled days, less fear of the next attack, and a treatment plan that patients can actually follow.

Conclusion

Migraine treatment has changed dramatically since 2023.

By May 2026, the most important updates are:

  • CGRP-targeting therapies are now first-line preventive options.
  • Gepants provide acute and preventive options without relying on vasoconstriction.
  • Botox remains a key treatment for chronic migraine.
  • Zavegepant, Atzumi, and Symbravo have expanded acute treatment choices.
  • Greater occipital nerve blocks now have stronger support in emergency migraine care.
  • Neuromodulation devices are increasingly used as non-drug options.
  • Neck pain and migraine should be understood through the trigeminocervical pathway.
  • Central sensitization and allodynia should be actively assessed and treated.
  • PACAP-targeting therapies may become the next major preventive class if Phase III trials confirm benefit.

Bottom line: migraine is treatable, but the best results come from precision. A successful plan identifies the migraine subtype, reduces attack frequency, avoids medication overuse, treats central sensitization, addresses neck and occipital contributors, and gives the patient both acute and preventive tools.