Editor’s Note:  The original version of the article was edited to reflect that antiepileptic agents divalproex sodium, valproate sodium, and topiramate should be avoided in women of childbearing potential due to the risk of birth defects.

The American Headache Society (AHS) released updated guidance on the use of novel preventive and acute treatments for migraine in adults. These revised recommendations were published in Headache.

The emergence of novel medications, technologies, formulations of established drug therapies, and biologics has created a need for updated guidance on the treatment of migraine. For these updated recommendations, input was elicited from North American and European expert clinicians and researchers who specialize in headache medicine.

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The recommendations for initiating preventive treatment in patients with migraine remain unchanged; patients with migraine should be considered for preventive treatment if migraine attacks interfere with the patients’ daily routines (despite acute treatment), attacks occur on more than 4 headache days each month, acute treatment is either overused or does not alleviate migraine symptoms, adverse events have resulted from the use of acute treatment, or the patient has requested preventive treatment.

Basic principles guiding the initiation, titration, and, if necessary, cessation of preventive treatment for migraine are as follows:

  • Use evidence-based preventive treatments. These include antiepileptic drugs, β-blockers, frovatriptan, and onabotulinumtoxinA. Antiepileptic agents divalproex sodium, valproate sodium, and topiramate should be avoided in women of childbearing potential due to the risk of birth defects.
  • Start low and titrate. Clinicians should commence oral treatments at a low dose and titrate slowly until the target response develops, the maximum or target dose is reached, or tolerability issues emerge.
  • Reach a therapeutic dose. After an initial target dose is prescribed, advise patients to discontinue titration if the maximum dose is reached, when efficacy is optimal, or when adverse events become intolerable.
  • Give an adequate trial. An adequate trial time of ≥8 weeks at a target or usual effective dose is advised for oral preventive treatments to optimize the possibility of a therapeutic response.
  • Establish realistic expectations. Patients should be involved in the treatment process to help establish individual expectations and for patients to understand  about potential treatment latencies. Patients should also be informed of the frequency and severity of common adverse events.
  • Optimize drug selection. Preventive treatment should be selected based on evidence for efficacy, provider experience, tolerability, patient preference, headache subtype, comorbid and coexistent illnesses, concomitant medications, psychological factors such as heart rate and blood pressure, body habitus, and pregnancy (or the potential for pregnancy).
  • Maximize adherence. Currently, long-term adherence to oral preventive treatment for migraine is poor. Treatment adherence can be improved by providing patient education about dose adjustments, treatment expectations, and adverse events.

Of note, newer injectable prevention therapies may not need gradual dose escalation as they provide rapid onset of therapeutic benefits and are associated with a favorable tolerability profile. For emerging preventive options such as erenumab, fremanezumab, galcanezumab, and eptinezumab, measuring the response should be patient- and clinician dependent and should follow the same outcome metrics for other preventive treatments.

For acute migraine treatment, goals include rapid and consistent freedom from pain and other symptoms; restored functional ability; minimal need for repeat dosing or emergency medications; optimal self-care and reduced subsequent use of health care resources such as emergency department visits, diagnostic imaging, clinician and ambulatory infusion center visits; and minimal or no adverse events.

The following acute treatment principles may help to improve outcomes in patients with migraine.

  • Use evidence-based treatments. Nonsteroidal anti-inflammatory drugs (NSAIDs), non-opioid analgesics, acetaminophen, or caffeinated analgesic combinations (eg, combined aspirin, acetaminophen, and caffeine) should be considered for mild to moderate attacks. Migraine-specific agents (eg, triptans, dihydroergotamine [DHE]) are advised for moderate to severe attacks and mild to moderate attacks that respond poorly to NSAIDs or caffeinated combinations.
  • Choose a non-oral route of administration for severe nausea or vomiting. Subcutaneous, intranasal, and inhaled powdered formulations of sumatriptan 3 mg, 4 mg, or 6 mg intranasal and intramuscular (IM) formulations of ketorolac should be used in patients whose attacks are associated with severe nausea or vomiting or who have trouble swallowing orally administered medication. Antiemetics such as prochlorperazine suppositories may also be useful for patients who are unable to accommodate oral medication administration.
  • Account for tolerability and safety issues. Certain acute treatments have been associated with side effects in patients with certain coexistent and comorbid illnesses. Failure to account for tolerability and safety issues when prescribing acute therapies may cause patients to limit, delay, or forgo treatment altogether.
  • Consider self-administered rescue. Options for outpatient rescue include subcutaneous sumatriptan, DHE injection or intranasal spray, or corticosteroids (eg, dexamethasone, IM ketorolac). Inpatient options include parenteral formulations of triptans, DHE, antiemetics, NSAIDs (ketorolac), anticonvulsants (eg, valproate sodium and topiramate [except in women of childbearing potential who are not using an appropriate form of contraception]), corticosteroids, and magnesium sulfate.
  • Avoid medication overuse. Acute treatment for migraine in patients who use acute therapies on a regular basis should be limited to approximately 2 headache days per week; preventive treatment should be offered to patients who exceed this limit.

The US Food and Drug Administration has cleared single-pulse transcranial magnetic stimulation for the acute and preventive treatment of migraine, electrical trigeminal nerve stimulation for the acute and preventive treatment of migraine, and noninvasive vagus nerve stimulation for the acute treatment of migraine.

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Cognitive behavioral therapy and biofeedback and relaxation therapies have been shown to be effective in preventing and treating migraine. The goals of this type of therapy include reduced frequency and severity of headache, reduced headache-related disability, reduced reliance on poorly tolerated or unwanted pharmacotherapies, enhanced personal control of migraine, and reduced headache-related distress and psychological symptoms.

Biobehavioral modalities can be used alone or combined with pharmacologic treatments, and greater improvement in migraine has been noted with combined treatment compared with either intervention alone.


American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache. 2018;59(1):1-18.