What inpatient treatments do we have for acute intractable migraine?

OPTIONS FOR DRUG THERAPY

Antiemetics

Dopamine receptor antagonists are assumed to merely treat nausea in patients with migraine; however, they act independently to abort migraine and thus should be considered, irrespective of the presence of nausea.

The two most commonly used agents are prochlorperazine and metoclopramide. The American Academy of Neurology guidelines recommend prochlorperazine as first-line therapy for acute migraine. Metoclopramide is rated slightly lower and is considered to have moderate benefit.⁴ The Canadian Headache Society cites a high level of evidence supporting prochlorperazine and a moderate level of evidence supporting metoclopramide.⁵ The American Headache Society assessment of parenteral pharmacotherapies gives prochlorperazine and metoclopramide a level B recommendation of “should offer” (a recommendation only additionally assigned to subcutaneous sumatriptan).³ Hence, either agent can be used.

To reduce the risk of posttreatment akathisia, diphenhydramine or benztropine may be given before starting a dopamine receptor antagonist. Diphenhydramine may be independently effective in migraine treatment,^6,7 but  data on this are limited.

Ketorolac, ibuprofen

Ketorolac and ibuprofen are the only available nonsteroidal antiinflammatory drugs (NSAIDs) for IV administration. The Canadian Headache Society guidelines strongly recommend ketorolac for the treatment of migraine in emergency settings.⁵ Doses range from 30 mg to 60 mg.¹ Ibuprofen 400 to 800 mg by IV infusion is an acceptable alternative. These medications should be avoided in patients with renal failure or severe coronary artery disease.

Oral naproxen sodium is a possible alternative in patients with cardiovascular disease, as it has been shown to carry a lower cardiovascular risk than other NSAIDs.⁸

The same concerns in patients with renal dysfunction apply to any NSAID, as the enzyme cyclooxygenase plays a constitutive role in glomerular function.

Antiepileptic drugs

The antiepileptic drugs sodium valproate and levetiracetam are available in IV formulations that have demonstrated efficacy in the treatment of status migrainosus¹ (ie, migraine lasting more than 72 hours). Valproate has the strongest track record, is well tolerated, and is effective in rapidly aborting migraine.⁹

Volume repletion

Although its use is anecdotal and to date no trial has measured its efficacy, IV volume repletion is often used in acute migraine, as most headache experts surmise it to be highly effective, especially in patients with prolonged nausea or vomiting.¹

Magnesium

IV magnesium is effective, particularly for migraine with aura.¹⁰ Hypotension is a common side effect, and pretreatment or concurrent treatment with IV fluids is advised. Doses from 500 mg to 1,000 mg have demonstrated efficacy.¹⁰

Corticosteroids

Corticosteroids can be used in the treatment of status migrainosus. Most studies have shown benefit in preventing recurrences rather than merely aborting migraine.¹¹ A systematic review suggested that recurrent headaches are milder with corticosteroid treatment; 19 of 25 studies indicated favorable benefit, and 6 of 19 studies indicated noninferior outcomes.¹²

Both IV methylprednisolone and IV dexamethasone may be considered.¹² Dexamethasone appears to be particularly effective in preventing headache recurrence when combined with other IV therapies.¹³ It can be given as a single dose of 10 mg, or as repeated doses of 4 mg up to 16 mg/day.¹ Patients with active psychosis or uncontrolled diabetes should be closely monitored for these conditions, which corticosteroids can worsen.

Serotoninergic agents

Serotonin agonists including subcutaneous sumatriptan and IV dihydroergotamine are highly effective, with proven statistical and clinical benefit.⁴ They should be considered in patients with no known history of coronary artery disease or other vaso-occlusive vascular disorder.¹

Ideally, IV dihydroergotamine should be administered after consultation with a neurologist or headache specialist, given the pretreatment and cotreatment requirements often necessary to suppress its side effects. Careful titration is important to prevent transient headache exacerbations during infusion, as well as abdominal cramping, nausea, and diarrhea.

Avoid opioids

Opioids should be avoided. Evidence supporting their use in acute migraine is extremely limited,³ and the risks of migraine becoming chronic and of addiction are high.¹⁴ Safer, more effective alternatives have been detailed above.

A detailed algorithm for the management of patients with acute migraine has been published¹⁴ and is aimed at decreasing acute treatment with opioids and barbiturates.