CLINICAL ACTIONS:

Migraine is a complex neurologic event encompassing moderate to severe headache as well as systemic and neurologic symptoms.  Treatment is aimed at both amelioration of symptoms as well as prevention of attacks.  Dosage below is based on the Lancet (2018) review and International Headache Society (IHS) guidelines but may vary based on a patient’s medical and clinical circumstances.

ACUTE TREATMENT

General principles to manage acute migraine include

• Treat early while pain is mild
• Consider non-oral routes of administration for patients with nausea/vomiting or rapid pain peak (≤30 min)
  • Nasal spray
  • Injection
  • Suppository
  • Combination approach using medications with different mechanisms of action for those who do not obtain quick relief or relapse within 24 – 48 hours
  • Educate patients regarding potential for medication-overuse
  • Minimize use of ‘simple’ analgesics to <15 days per month and triptans, ergots, or combination analgesics to less than 10 days per month (see below for specific meds)

Simple analgesics – Effective for Mild Pain

• NSAIDS
  • Aspirin 975 – 1000 mg
  • Ibuprofen 400 mg
  • Naproxen 500 – 550 mg (up to 825 mg)
  • Diclofenac potassium 50 mg
  • Indomethacin suppositories 50 mg
    • May be cut into 1/2 or 1/3
• Acetaminophen
  • Acetaminophen (Paracetamol) 1000 mg
  • May be combined with NSAIDs and caffeine

Triptans – First Line for Moderate/Severe Pain

• Selective Serotonin 5-HT Receptor Agonists
• Contraindications due to vasoconstriction
  • History of symptomatic peripheral, coronary, and cerebrovascular disease and severe hypertension
• Pregnancy
  • May be associated with pregnancy-related vascular events, but data currently (mostly based on sumatriptan) has not demonstrated an association with birth defects
  • Usually begin with acetaminophen, then aspirin/NSAIDs and use triptans as 3^rd line therapy when indicated
• Triptans have an overall favorable safety profile when not contraindicated and available without subscription in some European countries
• Typical doses and routes
  • Sumatriptan
    • 6 mg subcutaneous
    • 20 mg intranasal
    • 50 mg oral
    • 100 mg oral
  • Zolmitriptan 5 mg intranasal/2.5 mg oral
  • Almotriptan 12.5 mg oral
  • Eletriptan 20-40 mg oral
  • Frovatriptan 2.5 mg oral
  • Naratriptan 2.5 mg oral
• Patients may respond differently to different triptans and patient preference will also play a role (e.g. patients tend to prefer oral medications)

Dihydroergotamine

• Used when triptans are not well tolerated or patient not responding
• Alpha-adrenergic blocker and arterial vasoconstrictor
  • 1 mg nasal spray, subcutaneous or IM
• Contraindications include
  • Pregnant or nursing
  • Cardiac or circulatory disease (similar to triptans)
• Additional contraindications due to life-threatening periperhal ischemia due to coadministration of dihydroergotamine with CYP 3A4 inhibitors
  • Anti-HIV medications (protease inhibitors)
  • Macrolide antibiotic such as troleandomycin, clarithromycin or erythromycin

Opiods/Butalbital Containing Analgesics

• Best to avoid due to high incidence adverse events, habituation, addiction

PREVENTATIVE TREATMENT

• Consider preventative treatment
  • When ≥ 8 headache days/month or ≥4 migraines/month
  • For patients with chronic migraine

Beta Blockers

• Atenolol (B level evidence): 50–200 mg once a day
• Metoprolol (A level evidence): 50–200 mg once a day for long-acting formulation
• Nadolol (B level evidence): 20–160 mg once a day
• Propranolol (A level evidence): 40–240 mg once a day for long-acting formulation

Antidepressants

• Timolol (A level evidence): 20–60 mg once a day
• Amitriptyline (B level evidence): 10–50 mg before bed
• Nortriptyline (no studies available): 10–150 mg before bed
• Venlafaxine (B level evidence): 75–225 mg once a day for long-acting formulation

Calcium-Channel Blockers and Anticonvulsants

• Verapamil (U level evidence): 120 – 960 mg in divided doses for long-acting formulation
• Flunarizine (A level evidence): 5 – 10 mg once a day
• Gabapentin (U level evidence): 600 – 3600 mg in two–three divided doses
• Topiramate (A level evidence): 50 – 200 mg twice a day or before bed
  • Pregnancy Risk: FDA category D due to strong association with birth defects
• Valproic acid–divalproex (A level evidence): 500 – 2000 mg once a day or in two divided doses
  • Pregnancy Risk: FDA category D due to strong association with birth defects

Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers

• Lisinopril (C level evidence): 10 – 40 mg once a day
• Candesartan (C level evidence): 16 – 32 mg once a day
  • Pregnancy Risk: FDA category D due to strong association with birth defects
• Cyproheptadine (C level evidence): 4 – 16 mg before bed
• Ibuprofen (B level evidence): 200 mg twice a day
• Fenoprofen (B level evidence): 200 – 600 mg twice a day
• Ketoprofen (B level evidence): 50 mg three times a day
• Naproxen (B level evidence): 500 – 1100 mg once a day
• Naproxen sodium (B level evidence): 550 mg twice a day

Calcitonin Gene-Related Peptide (CGRP-R) Blockers

• Erenumab (First FDA-approved CGRP-R blocker for migraine prevention): 70mg once monthly subcutaneously (self-administered)
  • Some patients may benefit from a dosage of 140mg once monthly administered once monthly as two consecutive injections of 70mg each

Miscellaneous agents

• Feverfew (B level evidence): 50 – 82 mg once a day
• Riboflavin (B level evidence): 400 mg once a day or 200 mg twice a day
• Ubidecarenone (coenzyme Q10) C 300 mg once a day
• Magnesium citrate (B level evidence): 400 – 600 mg once a day
• OnabotulinumtoxinA also called botulinum toxin type A (A level evidence): 155 – 195 mg once every 12 weeks (for chronic migraine)
  • FDA approved for chronic, not episodic migraine

Notes: (Canadian Headache Society Guidelines)

• Level A: drug has been established as effective | Level B: drug is probably effective | Level C: drug is possibly effective (requires at least one class 2 study or two consistent class 3 studies) | Level U: data are inadequate or conflicting, treatment is unproven

SYNOPSIS:

Treatment of migraines is intended to reduce the acute symptoms as well as prevent future events.  A multitude of medical therapies are available to this end. When starting therapy begin with the lowest dose and escalate slowly. A 2-3 month trial is necessary to determine efficacy.  6 months may be needed to achieve maximal result.

KEY POINTS:

• Patient using oral sumatriptan but headache not resolved within 2 hours or returns after transient improvement
  • Second dose may be administered at least 2 hours after the first dose
  • Maximum daily dose is 200 mg in a 24-hour period
• Discuss family planning with all women of childbearing age; review adverse effects on pregnancy prior to initiating treatment
• Emerging treatments include:
  • Lasmiditan, a highly selective 5-HT receptor agonist
  • Monoclonal antibody therapy directed against Calcitonin Gene Related Peptide (CGRP)
  • Neuromodulation devices
  • External trigeminal nerve stimulation
  • Noninvasive vagus nerve stimulation
  • Electrical upper-arm skin stimulation

Learn More – Primary Sources

Lancet: Migraine

Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition (2018).

Mother To Baby: Sumatriptan Fact Sheet

Related ObG Topics:

Is It a Migraine? Risk Factors and Diagnostic Categories

What are the Consequences of Taking Triptan for Migraine During Pregnancy?

Does Acupuncture Decrease Incidence of Migraines?

Hormonal Contraception Benefits – Beyond Pregnancy Prevention

CDC Guidance: Contraception in Women with Medical Conditions

FDA Approves Erenumab –  First Among a New Class of Drugs to Prevent Migraines