Integrating New Migraine Treatments Into Clinical Practice

Posted on January 21, 2019


Migraine is characterized by attacks of throbbing, often unilateral headache that are exacerbated by physical activity and associated with photophobia, phonophobia, nausea, and vomiting. About one third of patients have migraine with an aura and three quarters experience a premonitory phase prior to the onset of headache. Diagnoses of migraine can be refined based on the frequency of monthly migraine days (MMDs) and monthly headache days (MHDs); patients with fewer than 15 MMDs or MHDs have episodic migraine, and those with at least 15 MHDs, of which at least 8 are MMDs, have chronic migraine. The American Headache Society recently published a position statement on integrating new migraine treatments into clinical practice.

All patients with migraine should be offered a trial of acute treatment. Use NSAIDs (including aspirin), nonopioid analgesics, acetaminophen, or caffeinated analgesic combinations (eg, aspirin + acetaminophen + caffeine) for mild-to-moderate attacks and migraine-specific agents (triptans, dihydroergotamine [DHE]) for moderate or severe attacks and mild-to-moderate attacks that respond poorly to other agents. Opioids also have established efficacy for acute treatment. Nonoral routes of administration should be considered in patients who do not respond well to oral treatments.

Patients should be instructed to limit treatment to an average of 2 headache days per week, and those exceeding this should be offered preventive treatment. Patients who have medication overuse despite the use of preventive treatment may require an escalation in dose, a change in preventive therapy, or the addition of another agent.

Emerging agents for acute treatment include the small molecule CGRP receptor antagonists, ubrogepant and rimegepant, and lasmiditan, a selective serotonin (5-HT1F) receptor agonist. These novel treatment options do not constrict blood vessels and may have a special role for those with cardiovascular contraindications to triptans. Patients who have contraindications to the use of triptans or who have failed to respond to or tolerate at least 2 oral triptans are eligible for these agents or a neuromodulation device.

Several noninvasive devices have been developed that modulate pain mechanisms by stimulating the nervous system centrally or peripherally with an electric current or a magnetic field. These include 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. Patients who prefer nondrug therapies and those who have failed to respond to, have contraindications to, or poor tolerability with pharmacotherapy may be candidates for neuromodulation.

Many oral preventive treatments have limited to moderate efficacy, moderate to high rates of adverse events (AEs), contraindications, or interactions that limit use. Few use preventive treatment (3–13%), even though it is believed that nearly 40% of those with episodic migraine, and almost all of those with chronic migraine, would benefit.

Preventive treatment should be considered in any of the following situations: attacks significantly interfering with daily routines despite acute treatment; frequent attacks (≥4 MHDs); patient preference; contraindication to, failure, or overuse of acute treatments, with overuse defined as:

  • 10 or more days per month for ergot derivatives, triptans, opioids, combination analgesics, and a combination of drugs from different classes that are not individually overused
  • 15 or more days per month for nonopioid analgesics, acetaminophen, and nonsteroidal antiinflammatory drugs (NSAIDs [including aspirin])

The following oral treatments have established efficacy and should be offered for migraine prevention: antiepileptic drugs (divalproex sodium, valproate sodium, topiramate); beta-blockers (metoprolol, propranolol, timolol); and frovatriptan (for short-term preventive treatment of menstrual migraine). Valproate sodium and topiramate should be used with caution with women of childbearing potential. The following treatments are probably effective and should be considered for migraine prevention: antidepressants (amitriptyline, venlafaxine); beta-blockers (atenolol, nadolol); and angiotensin receptor blockers (candesartan).

There are 4 injectable preventive therapies for migraine: onabotulinumtoxinA and 3 monoclonal antibodies (mAbs) (fremanezumab, galcanezumab, erenumab). OnabotulinumtoxinA is approved for chronic migraine, and erenumab, fremanezumab, and galcanezumab are approved for episodic and chronic migraine. These agents have favorable tolerability profiles. Indications include inability to tolerate or inadequate response to a 6-week trial of at least 2 of the oral medications listed above.

In general, a significant reduction (eg, 50%) in MHDs is a useful benchmark for effectiveness in practice. Additionally, patient-centric and validated outcome measures that evaluate the effect of treatment on functional capacity, disability, and quality of life are important for determining whether meaningful change has occurred.

Education and lifestyle modification is important in the management of migraine. Minimizing exposure and managing unavoidable triggers, appropriate and individualized nutrition advice, and exercise should be implemented and personalized for each patient. Biobehavioral therapy, including cognitive behavioral therapy (CBT) and biofeedback, and relaxation therapies have been shown to be effective in the acute and preventive treatment of migraine. Evidence suggests that combining biobehavioral

interventions with pharmacotherapy provides greater benefits than either modality alone. 

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