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AI-Generated response:

What's the best treatment for refractory migraines?

Answer generated on June 4, 2024

The AI-generated responses are for illustration purposes only and should not be used for medical purposes.

For refractory migraines, consider using CGRP receptor antagonists, lasmiditan, or dihydroergotamine, depending on the specific patient contraindications and previous treatment failures.

Note that opioids should be avoided except as a last resort due to the risk of dependency and exacerbation of headache disorders.[1-2]

  • CGRP receptor antagonists such as erenumab, fremanezumab, eptinezumab, and galcanezumab have shown efficacy in preventing refractory migraines and are generally well-tolerated.[1-2]

  • Lasmiditan can be used for acute migraine treatment in patients with contraindications to triptans due to its lack of vasoconstrictive side effects, but it is sedating, and driving is contraindicated for at least 90 minutes after administration.[1]

  • Dihydroergotamine, administered subcutaneously or intravenously, is effective for severe attacks but generally requires pre-administration of an antiemetic like promethazine due to its emetic potential.[1]

  • Triptans are effective for acute treatment but are contraindicated in patients with cardiovascular issues due to their vasoconstrictive properties.[1][3]

  • Small molecule CGRP receptor antagonists like rimegepant and ubrogepant are useful for acute treatment when triptans are contraindicated or unsuccessful.[1]

Additional info

When considering treatment options for refractory migraines, it's crucial to evaluate the patient's overall health status, including any comorbid conditions that might influence drug choice. For instance, lasmiditan is a good option for patients who cannot use triptans due to cardiovascular risks, but its sedative effects must be considered, especially regarding the patient's need to drive or operate machinery shortly after taking the medication. CGRP receptor antagonists are a newer class of preventive medications that have been shown to be effective in patients who have not responded well to other treatments, making them a promising option for refractory cases. However, long-term data on their safety and efficacy are still being gathered. Dihydroergotamine is a potent option for severe cases but requires careful management of its side effects, including nausea, which necessitates the use of antiemetics. Triptans remain a mainstay for acute treatment but must be used cautiously in patients with certain cardiovascular conditions. Each treatment option has its specific considerations, and therapy should be tailored to the individual patient's needs and medical history.

References

Reference 1

1.

Digre, Kathleen B. (2024). In Goldman-Cecil Medicine (pp. 2376). DOI: 10.1016/B978-0-323-93038-3.00367-1

Ergotamine given early in the migraine attack can be effective if the associated nausea and peripheral vasoconstriction are tolerable. Lasmitidan (50 to 200mg) is a serotonin receptor agonist that does not have the vasoconstrictive side effects of triptans and that is safe and effective for patients who have contraindications to triptans; however, it is sedating, so driving is contraindicated for at least 90minutes and perhaps up to 8hours after its administration. Small-molecule, calcitonin gene–related peptide receptor antagonists are also helpful for treating migraine attacks. Both rimegepant (75mg orally) or ubrogepant (50 to 100mg) can provide about a 10% absolute increase in pain freedom within 2 hours compared with placebo,,have few side effects, and are useful when triptans are not successful or are contraindicated.Ubrogepant is also effective when taken during a migraine prodrome.Another rapid-acting option is zavegepant (10 mg) nasal spray. Forvery severeattacks, dihydroergotamine (1mg subcutaneously or 0.5 to 1mg intravenously [IV]) is usually effective but generally requires an antiemetic (e.g., promethazine, 25mg) before intravenous use. Ketorolac (60mg intramuscularly [IM] or 30mg IV), prochlorperazine (10 to 25mg IM or 10mg IVdelivered over a 5-minute period), metoclopramide (10mg IV), or celecoxcib solution (120mg orally)is useful for patients who are nonresponsive or have contraindications to vasoactive abortive agents. Opioids should not be used except as a last resort.

Preventive treatment (seeTable 367-3) is often recommended when headaches interfere with activities on 3 or more days per month or when the headaches are severe or prolonged.Prophylactic options include β-adrenergic blockers, calcitonin gene–related peptide antibodies and small-molecule inhibitors, calcium-channel antagonists, NSAIDs, tricyclic antidepressants, valproate, and topiramate. Other alternatives include the serotonergic drug cyproheptadine (4 to 20mg) or the monoamine oxidase inhibitor phenelzine (30 to 60mg). Calcitonin gene–related peptide antibody options for prevention,include erenumab (70 to 140mg subcutaneously monthly),,fremanezumab (225mg subcutaneously monthly or 675mg quarterly),eptinezumab (100to 300mg intravenously at baseline and week 12),and galcanezumab (240mg loading and 120mg monthly).Small-molecule inhibitors include rimegepant (75mg orally every other day) and atogepant (10mg once daily to 60mg once daily).-A19c Acupuncture and biofeedback have been used successfully. OnabotulinumtoxinA injection is also effective for prophylaxis of chronic migraine.FDA-approved devices for the prevention of migraines include vagus nerve stimulation, transcutaneous direct current stimulation,trigeminalnerve stimulation, and transcranial magnetic stimulation.As with acute therapy, these devices should be avoided or used with great caution in patients with cardiac pacemakers.

Treatment of migraineis divided into treatment of the acute headache and prevention of subsequent migraine attacks (seeFig. 367-1andhttps://americanheadachesociety.org/flowchart/). Acute treatment is most effectively accomplished with migraine-specific care: a nonspecific analgesic agent or combination analgesic therapy for milder migraine and, most frequently, aggressive migraine-specific therapy for migraine. Stratification of care, including tailoring the treatment according to the type of headache, results in fewer days of disability and use of medications.Which migraine-specific drug will work for any individual patient depends on the patient. It is important to avoid overuse of analgesic and other medications (especially opiates) because overuse can cause chronic daily headache in susceptible individuals. Prompt treatment improves the outcome of headache when compared with late treatment. Mildattacks can generally be treated successfully with over-the-counter analgesics such as acetaminophen (suggested dose, 650 to 1000mg) or NSAIDs (aspirin, 250mg to 1000mg; ibuprofen, 400 to 600mg; naproxen, 500 to 825mg; diclofenac, 50mg; or ketoprofen, 75mg). Formoderate to severemigraine headaches, patients benefit from migraine-specific triptans (seeTable 367-5), ergotamines (dihydroergotamine 1 to 2 mg intranasally or subcutaneously; ergotamine tartrate, 2mg sublingually or 1 to 2mg orally), the combination of naproxen and a triptan, or a formulary combination of isometheptene (65mg), dichlorphenazone (100mg), and acetaminophen (325mg).Contraindications to use of triptans include uncontrolled hypertension, clinical evidence of ischemic heart disease, and Prinzmetal angina. Ergotamine given early in the migraine attack can be effective if the associated nausea and peripheral vasoconstriction are tolerable.

Reference 2

2.

Fitzek M, Raffaelli B, Reuter U. Expert Opinion on Pharmacotherapy. 2022;23(10):1143-1153. doi:10.1080/14656566.2022.2088281.

Publish date: July 5, 2022.

INTRODUCTION: Refractory migraine is associated with low quality of life and great socioeconomic burden. Despite high need for effective, tolerable preventive therapies, there has been little research on potential therapeutic options. Monoclonal antibodies (mAbs) against Calcitonin Gene-Related Peptide (CGRP) are the first preventive therapeutic approach for migraine based on the underlying pathophysiology. AREAS COVERED: Following a brief introduction into the term 'refractory migraine,' the authors reviewavailable treatment options, focusing on current phase III trials of substances acting on the CGRP pathway. EXPERT OPINION: No uniform definition for refractory migraine is available. The vast majority of proposals recommend treatment failure of 2-4 drug classes as a key diagnostic criterion. Phase III studies on CGRP-(receptor) mAbs demonstrated excellent efficacy and tolerability in patients with chronic and episodic migraine including subjects with multiple unsuccessful conventional therapy attempts. However, more comparator trials showing superiority of mAbs versus oral preventatives, such as the HER-MEs study are needed. In summary, with the CGRP antibodies, a group of drugs has entered the market which will most likely not only significantly improve the quality of life of many individual migraine patients but could also reduce indirect health-care costs associated with migraine by reducing recurrent medical consultations.

Reference 3

3.

Selective Serotonin Agonists (Triptans), Elsevier ClinicalKey Drug Class Overview

Content last updated: January 1, 2012.

* All triptans are indicated for the acute treatment of moderate to severe migraine headache; differences in efficacy, safety, and tolerability are minor. * Triptans are the recommended first-line treatment for moderate to severe migraines and for mild migraines resistant to treatment with nonsteroidal anti-inflammatory drugs or combination analgesics (e.g., acetaminophen, aspirin, and caffeine). * Sumatriptan is the only triptan available for subcutaneous injection (sc); sumatriptan sc is more effective than other formulations of sumatriptan as well as all other triptans, but is associated with higher rates of adverse events. * When used in properly selected patients, triptans are safe and well tolerated; however, they are contraindicated in patients with coronary artery disease, peripheral vascular disease, cerebrovascular disease, and uncontrolled hypertension because of their propensity to cause vasoconstriction. Triptans are also contraindicated for use in patients with basilar or hemiplegic migraine.

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