Migraine Treatment: CGRP Therapies, Gepants, Botox, and Neuromodulation

Medically reviewed by Anton Ostashko, MD

Overview

Migraine is a disabling neurological disease, not simply a severe headache. It involves altered sensory processing and pain modulation, activation of the trigeminovascular system, and signaling molecules that include calcitonin gene-related peptide (CGRP). In the 2021 Global Burden of Disease analysis summarized by the World Health Organization, migraine ranked third among neurological conditions by age-standardized disability-adjusted life-years.12

Migraine care has changed substantially. Patients now have targeted preventive and acute treatments, including CGRP monoclonal antibodies, gepants, onabotulinumtoxinA (Botox®) for chronic migraine, neuromodulation devices, nerve blocks, and newer self-administered formulations of established drug classes. The most effective plan is usually built around migraine subtype, headache frequency, disability, medication use, prior treatment response, medical comorbidities, and patient goals.

The most important migraine updates are:

  • CGRP-targeting therapies are a first-line preventive option. The 2024 American Headache Society position statement supports initiating a CGRP-targeting preventive without requiring prior failure of older medication classes. This places these treatments alongside other first-line options; it does not mean that every patient should receive one, or that insurance step-therapy requirements have disappeared.4
  • Fremanezumab (Ajovy®) now has a defined pediatric indication. The FDA added prevention of episodic migraine in patients ages 6 through 17 who weigh at least 45 kg in August 2025. A randomized pediatric trial was then published in 2026. The approval therefore occurred in 2025, while the peer-reviewed Phase 3 publication is a 2026 development.56
  • Acute treatment choices continue to expand. Zavegepant nasal spray provides a non-oral acute gepant option. Dihydroergotamine (DHE) is available as Atzumi™ nasal powder and the Brekiya™ single-dose autoinjector, and Symbravo® combines meloxicam with rizatriptan in one tablet. These products have important, product-specific warnings and contraindications; a newer formulation is not automatically safer or appropriate for every patient.891011
  • Botox remains an established preventive for adult chronic migraine. The U.S. label covers adults with at least 15 headache days per month, with headache lasting at least 4 hours per day. Effectiveness has not been established for episodic migraine with 14 or fewer headache days per month.14
  • The emergency-department evidence has been updated. The American Headache Society guideline published in 2026 gives Level A “must offer” recommendations to intravenous prochlorperazine and greater occipital nerve blocks for eligible adults, and a Level A “must not offer” recommendation to intravenous hydromorphone for migraine-related pain relief.7
  • Neck pain and cutaneous allodynia deserve careful evaluation. Neck pain can be part of migraine, a trigger, a separate cervical disorder, or a combination. Pain from normally nonpainful touch can reflect allodynia and sensitization of migraine pain pathways, but light and sound sensitivity are migraine symptoms rather than forms of cutaneous allodynia.1718
  • PACAP is a prominent investigational pathway beyond CGRP. In sponsor-reported Phase 2b data presented in June 2026, one intravenous bocunebart dose group met the PROCEED trial’s primary endpoint. Other tested dose groups did not achieve statistical significance. Bocunebart remains investigational, the conference results have not yet established long-term clinical benefit, and the drug is not FDA approved.2627

Evidence cutoff: This article reflects publicly available evidence through August 9, 2026. Product indications and warnings are based on current U.S. prescribing information available as of that date. Conference findings that have not yet undergone full peer review are identified as preliminary or sponsor-reported.

Understanding Migraine

Migraine is a disorder of the brain’s sensory and pain-processing networks. An attack can involve head pain, nausea, vomiting, sensory sensitivity, cognitive symptoms, dizziness, neck discomfort, and fatigue. Light, sound, smell, motion, sleep disruption, fasting, hormonal change, stress, alcohol, and other exposures can influence attacks, but triggers vary substantially. Some experiences interpreted as triggers—such as food craving, fatigue, or neck stiffness—may sometimes be early prodromal symptoms rather than the cause of the attack.2

A migraine attack may move through several phases. Not every person has every phase, and phases can overlap.

1. Prodrome

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

2. Aura

Aura consists of fully reversible neurological symptoms that usually develop gradually. Visual symptoms are most common and can include flashing lights, zig-zag lines, blind spots, or spreading distortion. Aura can also involve sensory or language symptoms. Typical individual aura symptoms usually last 5 to 60 minutes. New weakness, persistent symptoms, abrupt onset, loss of consciousness, or a pattern that differs substantially from prior aura requires urgent assessment rather than automatic attribution to migraine.29

3. Headache Phase

Migraine pain may be throbbing, pressure-like, unilateral, or bilateral. It is often accompanied by nausea and sensitivity to light and sound, and routine activity may worsen symptoms. A person does not need every textbook feature for the diagnosis.

4. Postdrome

After the most painful phase improves, some patients feel drained, cognitively slowed, dizzy, emotionally sensitive, or “hungover” for hours or longer.

Episodic Migraine vs. Chronic Migraine

Migraine frequency guides treatment. Episodic migraine is commonly used to describe migraine occurring on fewer than 15 headache days per month. Under the International Classification of Headache Disorders, chronic migraine requires headache on at least 15 days per month for more than 3 months, with migraine features, a migraine-specific medication response, or both on at least 8 days per month.3

Patients often undercount because they record only the most disabling attacks. A useful headache diary tracks:

  • Every day with head pain, not only severe days
  • Days with migraine features such as nausea or light and sound sensitivity
  • Acute-medication days and the medication used
  • Aura, dizziness, neck pain, menstrual timing, and other recurring patterns
  • Sleep, meals, hydration, caffeine, alcohol, travel, stress, and possible triggers
  • Disability, including missed work, reduced productivity, canceled activities, or time in bed

A person reporting six “migraine attacks” each month may have substantially more total headache days when milder or partially treated days are included. That distinction can change the diagnosis, preventive-treatment options, and insurance documentation.

The Trigeminovascular System and CGRP

The trigeminovascular system is central to migraine pain. Trigeminal pathways carry sensory information from the face, head, meninges, and cranial blood vessels. During an attack, activation of these pathways can release CGRP and other signaling molecules involved in pain transmission and sensitization.2

CGRP-targeting treatments use different approaches:

  • Preventive monoclonal antibodies: erenumab targets the CGRP receptor; fremanezumab, galcanezumab, and eptinezumab target the CGRP ligand. Eptinezumab is administered intravenously, while the others are given subcutaneously.
  • Gepants: small-molecule CGRP-receptor antagonists. Ubrogepant, rimegepant, and zavegepant have acute-treatment roles; rimegepant also has a preventive indication for episodic migraine, and atogepant is used for prevention.

These treatments are important advances, but they are not interchangeable. Indications, dosing, interactions, age ranges, pregnancy considerations, adverse effects, and insurance coverage differ. Current U.S. labels for several CGRP antagonists include warnings about hypersensitivity, hypertension, and Raynaud’s phenomenon, so product-specific review remains necessary.581213

The Trigeminocervical Pathway: Why Migraine Often Includes Neck Pain

Many patients are told that their headaches are “coming from the neck.” Sometimes a cervical disorder does contribute: joint disease, prior whiplash, muscle dysfunction, occipital neuralgia, or cervicogenic headache may coexist with migraine. Migraine itself can also cause neck discomfort before, during, or between attacks.

The reason is the trigeminocervical pathway. Sensory input from the trigeminal system and upper cervical nerves converges within the trigeminocervical complex in the lower brainstem and upper cervical spinal cord. This shared processing helps explain why upper-neck pain can be perceived in the head and why migraine can be felt in the occipital or cervical region.17

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

That pattern does not, by itself, distinguish migraine from occipital neuralgia or cervicogenic headache. The examination should consider neck range of motion, reproducible pain with movement or pressure, focal nerve tenderness, trauma history, neurological findings, and the full migraine symptom pattern. Physical therapy may help when a genuine cervical or myofascial contributor is present, but neck-directed treatment should not replace migraine treatment when the primary disorder is migraine.

Central Sensitization and Cutaneous Allodynia

Central sensitization describes increased responsiveness within pain-processing pathways. In migraine, it is one proposed mechanism contributing to pain amplification, spread of pain, and cutaneous allodynia—pain caused by a stimulus that is normally not painful.18

Examples of cutaneous allodynia can include pain from:

  • Brushing or washing the hair
  • Wearing glasses, a hat, earrings, or a ponytail
  • Resting the head on a pillow
  • Light touch of the scalp or face

Photophobia, phonophobia, smell sensitivity, and motion sensitivity are common migraine symptoms, but they are not the same as cutaneous allodynia. Fibromyalgia, temporomandibular pain, irritable bowel syndrome, and other pain or sensory disorders can coexist with migraine; their presence does not prove that central sensitization is the sole cause of a patient’s symptoms.

Clinically, frequent attacks or allodynia should prompt attention to preventive treatment, timing and effectiveness of acute treatment, medication overuse, sleep, mood, and cervical or temporomandibular contributors. There is no single routine test that measures all aspects of central sensitization, and treatment cannot guarantee that sensitization will be “reversed.”

Common Migraine Symptoms

Migraine may include moderate or severe head pain; one-sided or bilateral pain; throbbing, pressure, or other pain qualities; nausea or vomiting; light, sound, and smell sensitivity; dizziness or vertigo; visual aura; tingling or numbness; reversible language difficulty during aura; neck pain or stiffness; scalp tenderness; fatigue; cognitive slowing; mood change; and food craving.

Some migraine syndromes can occur with little or no head pain. Examples include typical aura without headache and some episodes of vestibular migraine. These diagnoses still require a characteristic history and careful exclusion of other neurological, ophthalmic, vestibular, cardiovascular, or metabolic causes.

Diagnosing Migraine

Migraine is usually diagnosed clinically through a detailed history and neurological examination. There is no blood test or scan that confirms routine migraine. The evaluation should characterize onset, duration, frequency, associated symptoms, aura, disability, family history, acute-medication use, prior treatments, and red flags for a secondary headache disorder.

A comprehensive assessment may include:

  • A headache diary and review of total headache days, migraine-feature days, and medication-use days
  • Neurological examination and blood-pressure assessment
  • Review of sleep, mood, hormones, caffeine, alcohol, supplements, and prescribed or over-the-counter medications
  • Assessment for medication-overuse headache
  • Evaluation for neck pain, occipital neuralgia, temporomandibular dysfunction, vestibular symptoms, and other comorbidities when relevant
  • Brain MRI, CT, vascular imaging, laboratory testing, eye examination, lumbar puncture, or other testing when the history or examination suggests a secondary cause

For patients with headaches consistent with migraine, a normal neurological examination, and no atypical features or red flags, routine neuroimaging is generally unnecessary. Imaging may be appropriate for a first or worst headache, a substantial pattern change, unusual or prolonged aura, persistent focal findings, side-locked headache, post-traumatic headache, or other concerning features.16

Medication-Overuse Headache

Medication-overuse headache is diagnosed when a person with a pre-existing headache disorder has headache on at least 15 days per month and has regularly overused one or more acute-treatment drugs for more than 3 months. The overuse threshold depends on the medication class.15

Common practical thresholds are:

  • 10 or more days per month: triptans, ergots, opioids, butalbital-containing medications, and combination analgesics
  • 15 or more days per month: simple analgesics such as acetaminophen or a nonsteroidal anti-inflammatory drug when used alone

These thresholds are diagnostic guideposts, not individualized permission to use a drug up to a particular number of days. Cardiovascular, kidney, gastrointestinal, liver, pregnancy, sedation, interaction, and dependence risks may require much stricter limits. Opioids and butalbital are generally avoided for migraine because of limited migraine-specific value and higher risks of overuse, dependence, sedation, and chronification.

Medication overuse is not a moral failing. It usually indicates that the underlying migraine is inadequately controlled. Management may require education, a safer acute plan, withdrawal or tapering of the overused medication, initiation or optimization of prevention, and close follow-up. Abrupt discontinuation is not appropriate for every drug; opioids, barbiturates, and some other medications may require supervised tapering.

Acute Migraine Treatment

The goal of acute treatment is to stop or substantially reduce an attack, restore function, minimize recurrence, and avoid medication toxicity and overuse. The best option depends on attack severity and speed, nausea or vomiting, prior response, cardiovascular and gastrointestinal risk, pregnancy status, drug interactions, and patient preference.19

NSAIDs and Acetaminophen

For some mild-to-moderate attacks, an NSAID or acetaminophen can be effective when taken early. Kidney disease, peptic ulcer or gastrointestinal bleeding, anticoagulant use, liver disease, cardiovascular risk, allergy, pregnancy, and concurrent medications can make these drugs inappropriate or require dose limits.

Triptans

Triptans remain effective migraine-specific treatments for many patients and are available as tablets, dissolving tablets, nasal products, and injections. Current U.S. labeling generally contraindicates triptans in patients with ischemic coronary disease, prior stroke or transient ischemic attack, peripheral vascular disease, uncontrolled hypertension, and hemiplegic or brainstem aura. Each product’s label and the patient’s complete medical history must be reviewed rather than assuming that all chest symptoms or vascular risks are equivalent.1119

Gepants

Gepants do not produce therapeutic vasoconstriction and may be useful for some patients who do not respond to or cannot use triptans. Acute options include ubrogepant, rimegepant, and zavegepant nasal spray. Rimegepant also has a separate preventive indication for episodic migraine; zavegepant is approved for acute treatment only.812

“Nonvasoconstrictive” does not mean risk-free. Gepants have product-specific interaction, liver or kidney, hypersensitivity, blood-pressure, and Raynaud warnings or precautions. The correct choice and dose depend on the relevant label and concurrent medications.

Dihydroergotamine (DHE)

DHE can be useful for selected prolonged or recurrent attacks and is available in injectable and nasal formulations. Atzumi is a DHE nasal powder, and Brekiya is a single-dose subcutaneous autoinjector. Both are approved for acute treatment in adults, not prevention.910

DHE has a boxed warning about serious ischemic complications when used with strong CYP3A4 inhibitors and is contraindicated in several vascular conditions, uncontrolled hypertension, pregnancy, severe hepatic or renal impairment, and within 24 hours of a triptan or another ergot-type drug. These restrictions make medication reconciliation and vascular-risk review essential.

Combination Acute Therapy

Some attacks respond better to rational combination treatment, such as a triptan plus an NSAID, when each component is appropriate. Symbravo combines rizatriptan with meloxicam for acute treatment of migraine with or without aura in adults. Its label carries both triptan-related contraindications and boxed NSAID warnings for cardiovascular thrombotic events and serious gastrointestinal bleeding, ulceration, or perforation.11

Antiemetics and Emergency Treatment

Nausea and vomiting can delay or prevent absorption of oral medication. Depending on the setting, clinicians may use metoclopramide, prochlorperazine, or another antiemetic, or select a nasal or injectable migraine therapy. In the 2026 American Headache Society emergency-department guideline, intravenous prochlorperazine and greater occipital nerve blocks received Level A “must offer” recommendations for eligible adults, while intravenous hydromorphone received a Level A “must not offer” recommendation for migraine-related pain relief.7

⚠️ Medication safety: A patient’s acute plan should specify what to take, when to take it, whether a second dose is allowed, which combinations are prohibited, and when to seek emergency care. Triptans and DHE should not be taken within 24 hours of one another, and multiple products may contain overlapping NSAIDs or acetaminophen. Do not combine or repeat treatments based only on a general article.

Preventive Migraine Treatment

Prevention should be considered when migraine is frequent, disabling, prolonged, associated with medication overuse, contraindications to acute therapy, or inadequate response to acute treatment. A successful preventive may reduce monthly migraine days, attack severity, medication use, emergency visits, and disability. A trial must be long enough and taken consistently enough to judge effect, unless adverse effects require earlier discontinuation.19

Traditional Preventive Medications

Options include topiramate, valproate, propranolol, metoprolol, timolol, candesartan, amitriptyline, nortriptyline, and venlafaxine, among others. Some are FDA approved for migraine prevention and others are used off-label. Choice should be matched to comorbidities, side-effect risk, prior response, blood pressure, body weight, sleep, mood, kidney stones, asthma, liver disease, and pregnancy or pregnancy plans.

Older medications remain reasonable first-line choices for many patients. The availability of CGRP-targeting therapies does not make them obsolete, but it does make a blanket requirement to fail multiple older drugs before discussing a targeted preventive less consistent with the 2024 American Headache Society position.4

CGRP Monoclonal Antibodies

Erenumab, fremanezumab, galcanezumab, and eptinezumab are targeted migraine preventives. The American Headache Society considers CGRP-targeting therapies a first-line preventive option based on evidence for efficacy, tolerability, and safety. Selection still requires individualized review of indication, prior treatment, pregnancy planning, constipation, blood pressure, vascular symptoms, hypersensitivity, route of administration, cost, and coverage.45

Pediatric Fremanezumab: What Changed and When

The FDA added Ajovy for prevention of episodic migraine in patients ages 6 through 17 who weigh at least 45 kg in August 2025. The current label does not establish this pediatric indication for chronic migraine or for children below the weight threshold.5

In the 2026 randomized trial, monthly migraine days decreased by an average of 2.5 days with fremanezumab and 1.4 days with placebo over 3 months. A reduction of at least 50% in monthly migraine days occurred in 47.2% and 27.0%, respectively. Injection-site erythema was more common with fremanezumab. The trial supports efficacy in the studied population, but its 3-month blinded period does not answer every long-term safety or durability question.6

Preventive Gepants

Atogepant is a once-daily preventive for adults with episodic or chronic migraine; under the current U.S. label, only the 60 mg dose is recommended for chronic migraine. Rimegepant is taken every other day for prevention of episodic migraine and also has an acute-treatment indication.1213

Drug interactions, severe kidney or liver impairment, hypersensitivity, hypertension, Raynaud’s phenomenon, nausea, constipation, and fatigue or somnolence may be relevant depending on the agent. Preventive and acute gepant use should follow the product label and a clinician-directed plan.

Botox for Chronic Migraine

OnabotulinumtoxinA is FDA approved to prevent headaches in adults with chronic migraine. The labeled regimen is 155 units divided across 31 injection sites in seven head and neck muscle areas, repeated approximately every 12 weeks. Effectiveness has not been established for episodic migraine with 14 or fewer headache days per month.14

Botox carries a boxed warning that botulinum toxin effects can spread beyond the injection site and cause serious symptoms, including swallowing or breathing difficulty. Treatment should be administered by a trained clinician after review of neuromuscular disorders, infection at proposed injection sites, prior toxin exposure, and other safety considerations.

Combination Prevention

Selected patients with persistent chronic migraine may use combination prevention, such as Botox with a CGRP-targeting treatment or a targeted therapy with a traditional preventive. This practice can be clinically reasonable, but evidence is less complete than for each treatment alone, and some combinations are off-label or difficult to obtain through insurance. Benefit, adverse effects, medication burden, and cost should be reassessed rather than continuing every treatment indefinitely.

Should Prevention Start Earlier?

Recent expert statements argue that prevention should be considered before years of escalating disability or progression to chronic migraine. This is a reasonable clinical direction, particularly when attacks are already disabling or acute medication use is rising. However, it has not been proven that a currently available preventive permanently changes the natural history of migraine or guarantees that chronic migraine will be prevented.28

Chronic-migraine candidates for onabotulinumtoxinA can find the full protocol, evidence, and what a treatment cycle involves on our Botox for chronic migraine page.

Occipital Nerve Blocks and Migraine

Greater occipital nerve blocks can be considered when migraine has prominent posterior head pain, scalp tenderness, occipital-neuralgia features, or a difficult-to-break acute attack. The 2026 American Headache Society emergency-department guideline gives greater occipital nerve blocks a Level A “must offer” recommendation for eligible adults in that setting.7

This recommendation does not mean that every migraine originates in the occipital nerve or that response to a block proves occipital neuralgia. Benefit can be temporary, technique and medication vary, and risks include pain, bleeding, infection, numbness, vasovagal symptoms, and rarely other complications. Anticoagulant use, local infection, anatomy, and the purpose of the procedure should be reviewed beforehand.

Neuromodulation Devices

Noninvasive neuromodulation uses electrical or magnetic stimulation to influence migraine-related pathways. Examples used in migraine care include external trigeminal nerve stimulation, remote electrical neuromodulation, noninvasive vagus nerve stimulation, and single-pulse transcranial magnetic stimulation. Device indications differ by age, acute versus preventive use, migraine subtype, and country.

The 2025 International Headache Society guideline found supportive evidence for several devices, but many recommendations were conditional and based on low or very low certainty. Neuromodulation can be useful for patients who prefer a nondrug option or need an adjunct, but it should not be presented as uniformly effective, risk-free, or interchangeable across devices.20

Examples available in U.S. practice have included Cefaly, Nerivio, gammaCore, and SAVI Dual. FDA-cleared ages and indications, contraindications for implanted electronic devices or cardiac conditions, pregnancy information, treatment schedules, and costs should be checked for the specific device at the time it is prescribed.

Lifestyle and Behavioral Treatment

Lifestyle care is an adjunct to medical treatment, not an implication that migraine is caused by poor choices. Regularity can reduce avoidable physiological stress on a migraine-prone nervous system. Practical foundations include consistent sleep and wake times, regular meals, adequate hydration, consistent rather than fluctuating caffeine intake, regular aerobic activity as tolerated, and moderation of individually confirmed triggers.23

Behavioral treatments may include cognitive behavioral therapy, relaxation training, biofeedback, mindfulness-based approaches, and treatment of insomnia. A 2025 systematic review found that evidence and effect sizes vary by intervention and outcome; these approaches are best presented as evidence-informed components of a layered plan rather than guaranteed substitutes for medication.24

Physical therapy can be valuable when there is demonstrable cervical, vestibular, postural, or myofascial dysfunction. It should be targeted to the identified impairment and coordinated with migraine treatment rather than assuming that posture or muscle tension explains every attack.

Migraine, Mental Health, and Sleep

Migraine commonly coexists with anxiety, depression, insomnia, trauma-related symptoms, and other chronic pain conditions. These disorders can reinforce disability through poor sleep, anticipatory fear, reduced activity, increased acute-medication use, and heightened sensory distress. Their coexistence does not mean that migraine is psychological.

Screening and treatment for mood and sleep disorders are part of neurological care because they affect quality of life, adherence, treatment selection, and sometimes migraine control. Care may include psychotherapy, sleep-focused behavioral treatment, medication when appropriate, evaluation for sleep apnea, and coordination with mental-health or sleep specialists.

Special Migraine Patterns

Vestibular Migraine

Vestibular migraine causes recurrent vestibular symptoms such as vertigo, motion-provoked dizziness, visual-motion sensitivity, or imbalance in a person with a current or past history of migraine. Formal criteria require at least five qualifying episodes lasting 5 minutes to 72 hours, migraine history, migraine features during at least half of episodes, and exclusion of a better explanation. Headache may be absent during some vestibular episodes, but recurrent dizziness alone is not enough for the diagnosis.21

Menstrual Migraine

Menstrual migraine is a reproducible pattern of attacks around menstruation. A diary over at least three cycles can help distinguish menstrual association from chance clustering. Management may include optimized acute treatment, short-term “mini-prevention” around the expected window, or continuous prevention depending on frequency, predictability, aura status, vascular risk, pregnancy plans, and other medical factors.30

Migraine With Aura

Typical aura symptoms develop gradually, are fully reversible, and usually last 5 to 60 minutes for each symptom. Aura can occur before, during, or without headache. A first aura, abrupt onset, persistent deficit, new motor weakness, major change in pattern, or symptoms concerning for stroke requires prompt or emergency evaluation.29

Post-Traumatic Headache With Migraine Features

After concussion or whiplash, headache may resemble migraine and coexist with neck pain, dizziness, sleep disruption, cognitive symptoms, mood symptoms, or sensory sensitivity. It is classified as post-traumatic headache based on its timing after injury, even when the phenotype is migrainous. Evaluation should also consider cervical injury, vestibular dysfunction, medication overuse, and red flags for structural complications.

Emerging Migraine Research: Beyond CGRP

CGRP transformed migraine treatment, but many patients have an incomplete response or cannot use available agents. Research is therefore evaluating other neuropeptides and pain pathways.

PACAP Pathway

Pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in migraine biology through mechanisms that overlap with but are not identical to CGRP signaling. A randomized Phase 2 trial published in 2024 showed that blocking PACAP with the investigational antibody Lu AG09222 reduced monthly migraine days at the tested dose, supporting further study of the pathway.25

In June 2026, Lundbeck presented sponsor-reported primary results from the Phase 2b PROCEED trial of bocunebart, the subsequent name for Lu AG09222. In the intravenous dose-A group, the adjusted change in monthly migraine days over weeks 1 through 12 was −4.24 days, compared with −2.86 days for placebo, an adjusted difference of −1.38 days. Dose A met the primary endpoint; the other reported dose groups showed numerical changes but did not reach statistical significance. The company reported no new safety signal and identified regulatory interactions for a Phase 3 program as the next step.2627

These findings are promising but preliminary. The results were presented by the sponsor, have not yet established durable benefit or rare risks, and do not make bocunebart an approved or clinically available treatment.

Better Phenotyping

Research is moving toward matching treatment to clinically meaningful features: chronic versus episodic migraine, aura, vestibular symptoms, menstrual pattern, allodynia, medication overuse, neck involvement, sleep disturbance, mood disorders, cardiovascular risk, pregnancy plans, prior treatment response, and patient preference. At present, no biomarker reliably selects the best drug for an individual patient, so careful clinical follow-up remains essential.

Earlier and More Ambitious Prevention

The field is also examining whether prevention should begin earlier and whether treatment goals should move beyond a 50% reduction in monthly migraine days toward the lowest achievable residual burden. These are important goals, but claims of disease modification or permanent prevention of chronification require stronger long-term evidence.28

Conditions That Can Mimic or Coexist With Migraine

Not every headache with nausea or light sensitivity is primary migraine. Depending on the history and examination, the differential diagnosis can include:

  • Tension-type headache, cluster headache, and other trigeminal autonomic cephalalgias
  • Medication-overuse headache
  • Occipital neuralgia, cervicogenic headache, temporomandibular disorders, and post-traumatic headache
  • Sinus, dental, ophthalmic, or ear disorders
  • Idiopathic intracranial hypertension or low-CSF-pressure headache
  • Giant cell arteritis
  • Stroke, transient ischemic attack, cerebral venous sinus thrombosis, arterial dissection, or reversible cerebral vasoconstriction syndrome
  • Meningitis, encephalitis, systemic infection, or inflammatory disease
  • Brain tumor, hydrocephalus, or another structural lesion
  • Pregnancy- or postpartum-related vascular and hypertensive disorders

The presence of migraine features does not exclude a second diagnosis. A substantial change from a familiar pattern should be assessed on its own merits.

When to Seek Urgent Medical Care

Red flags do not always indicate a dangerous cause, but they should not be managed by assuming that every severe headache is migraine.22

Call 911 or Seek Emergency Care Now

  • A sudden thunderclap headache that reaches maximum intensity within seconds to a minute
  • New weakness, facial droop, persistent numbness, speech difficulty, confusion, loss of consciousness, seizure, double vision, or sudden loss of vision
  • Severe headache with fever, stiff neck, rash, marked illness, or significant immune suppression
  • A severe new headache during pregnancy or the postpartum period, especially with high blood pressure, visual symptoms, confusion, or neurological deficits
  • Headache after significant trauma with worsening pain, repeated vomiting, confusion, unusual drowsiness, or neurological change
  • A first severe headache associated with exertion, sex, or another abrupt pressure-producing event

Arrange Prompt Medical Evaluation

  • A new headache beginning after age 50
  • A progressive pattern, new daily persistent headache, or major change from the usual migraine pattern
  • Headache with cancer, systemic inflammatory disease, unexplained weight loss, or immune suppression
  • Headache consistently triggered by coughing, straining, standing, or lying flat
  • Jaw pain with chewing, scalp tenderness, fever, or visual symptoms
  • A new side-locked headache, prolonged or unusual aura, or persistent symptoms between attacks

The Best Migraine Care Is Staged and Individualized

  1. Confirm the diagnosis and screen for secondary causes. Characterize the headache and neurological symptoms, examine the patient, and investigate red flags rather than treating every recurrent headache as migraine.
  2. Measure the burden accurately. Count all headache days, migraine-feature days, acute-medication days, and disabled days with a diary.
  3. Build a specific acute plan. Select a treatment that fits attack speed, nausea, medical risk, interactions, and prior response. Clarify repeat dosing, prohibited combinations, and rescue options.
  4. Use prevention when the burden justifies it. Choose among traditional medications, CGRP-targeting therapy, Botox for chronic migraine, neuromodulation, and selected procedures according to the patient’s phenotype, safety profile, preference, and access.
  5. Address perpetuating and coexisting problems. Treat medication overuse, sleep disturbance, mood disorders, neck or temporomandibular dysfunction, vestibular symptoms, and lifestyle irregularity without implying that the disease is the patient’s fault.
  6. Reassess with objective outcomes. Review migraine days, disability, acute-medication use, adverse effects, adherence, cost, and patient-defined goals. Stop or change treatments that do not provide meaningful value.

Bottom line: Migraine is treatable, but the best results come from accurate diagnosis, appropriate acute treatment, timely prevention, and repeated measurement of benefit and harm. Newer therapies have expanded options, but “new” does not automatically mean superior, safer, or suitable for every patient. The goal is fewer disabled days, safer medication use, better function, and a plan the patient can realistically follow.

At Los Altos Neurology, we provide individualized migraine evaluation, acute and preventive treatment planning, Botox for eligible adults with chronic migraine, CGRP-targeting therapies, preventive gepants, selected nerve blocks, and guidance on neuromodulation. Treatment is matched to the patient’s headache pattern, medical history, prior response, safety considerations, and goals.

For the practice’s staged approach to all of this — diagnosis, acute and preventive planning, procedures, and follow-up — see our headache & migraine care page.

References

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  3. Headache Classification Committee of the International Headache Society. 1.3 Chronic migraine. International Classification of Headache Disorders, 3rd edition.
  4. Charles AC, Digre KB, Goadsby PJ, Robbins MS, Hershey A. Calcitonin gene-related peptide-targeting therapies are a first-line option for the prevention of migraine: An American Headache Society position statement update. Headache. 2024;64:333-341. doi:10.1111/head.14692.
  5. U.S. Food and Drug Administration. AJOVY (fremanezumab-vfrm) Prescribing Information. Revised June 2026; pediatric indication added August 2025.
  6. Hershey AD, et al. Fremanezumab in Children and Adolescents with Episodic Migraine. N Engl J Med. 2026;394(3):243-252. doi:10.1056/NEJMoa2504546.
  7. Robblee J, et al. 2025 guideline update to acute treatment of migraine for adults in the emergency department: The American Headache Society evidence assessment of parenteral pharmacotherapies. Headache. 2026;66(1):53-76. doi:10.1111/head.70016.
  8. U.S. Food and Drug Administration. ZAVZPRET (zavegepant) Prescribing Information. 2025.
  9. U.S. Food and Drug Administration. ATZUMI (dihydroergotamine mesylate) nasal powder Prescribing Information. 2025.
  10. U.S. Food and Drug Administration. BREKIYA (dihydroergotamine mesylate) injection Prescribing Information. 2025.
  11. U.S. Food and Drug Administration. SYMBRAVO (meloxicam and rizatriptan) Prescribing Information. 2025.
  12. U.S. Food and Drug Administration. NURTEC ODT (rimegepant) Prescribing Information. 2026.
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