II. Indications: Frequent Migraine Headaches

  1. Consider in any patient desiring Migraine Prophylaxis
  2. Headache frequency
    1. Two or more Headaches monthly
    2. Absolutely indicated for 2 Headache days per week
  3. Headache duration
    1. Prolonged Headaches >2 days with Disability
  4. Headache response to Migraine Abortive Treatment
    1. Refractory to current abortive agents
    2. Intolerance to abortive agents
    3. Overuse of abortive agents

III. Protocol

  1. Effective prophylaxis reduces Headache frequency or severity by 50%
  2. Trial of prophylactic agent for 2-3 months
  3. Keep Headache diary
  4. Start prophylaxis at low dose and gradually increase
  5. Consider tapering to lowest effective dose at 6-12 months

IV. Preparations: Most Effective Agents for Migraine Prophylaxis

  1. Propranolol LA: Level A Evidence
    1. Metoprolol and Timolol have similar efficacy to Propranolol in Migraine Prophylaxis (Level A evidence)
    2. First choice unless Beta Blocker contraindication
    3. Propranolol 80 mg PO daily
      1. Gradually increase over 2-3 weeks until effective dose (typically 80 mg twice daily or 160 mg daily)
      2. Maximum: 240 to 320 mg orally daily
      3. May substitute with generic Propranolol (split daily dose into 3-4 divided doses)
    4. Alternatives
      1. Metoprolol 25 mg at bedtime nightly, then increase by 25 mg weekly up to 50-100 mg daily
  2. Amitriptyline (Elavil) or Nortriptyline (Pamelor): Level B Evidence
    1. Effexor has similar efficacy in Migraine Prophylaxis to Tricyclic Antidepressants
    2. Consider in patients with comorbid Tension Headaches
    3. Start: 10 mg orally at bedtime
    4. Increase by 10 mg each week until at least 30 mg, and preferably 50-100 mg at bedtime
  3. Valproic Acid and derivatives: Level A Evidence
    1. Teratogenic (avoid in women at risk for pregnancy)
    2. See description for adverse effects and monitoring
    3. Depakote Extended Release (ER) start 500 mg orally daily
      1. Increase after 1 week to 500 mg orally twice daily
      2. May increase in 250 mg increments if adverse effects
      3. Preferred Valproate form for Migraine Prophylaxis
    4. Other preparations
      1. Divalproex Sodium (Depakote) 250-500 mg orally twice daily
      2. Valproic Acid (Depakene) 250-500 mg twice daily
  4. Topiramate (Topamax): Level A Evidence
    1. Teratogenic (avoid in women at risk for pregnancy)
    2. May blunt cognitive function and cause weight loss
    3. Dosing
      1. Bedtime dosing
        1. Start: 12.5 to 25 mg orally at bedtime
        2. Increase by 12.5 to 25 mg each week, until at 100 mg at bedtime
      2. Alternative twice daily dosing
        1. Start: 12.5 to 25 mg orally at bedtime for 1 week
        2. Next: 25 mg orally twice daily for 1 week
        3. Next: 25 mg orally in AM and 50 mg orally in PM for 1 week
        4. Next: 50 mg orally twice daily
    4. Efficacy
      1. Effective prophylaxis at 100-200 mg per day
      2. Silberstein (2004) Arch Neurol 61:490-5 [PubMed]
      3. Brandes (2004) JAMA 291:965-73 [PubMed]

VI. Preparations: Antihypertensives

  1. Most effective agents - All are Beta Blockers (Level A evidence)
    1. Propranolol (Inderal) long acting 40 to 320 mg PO qd
    2. Timolol 10-15 mg orally two to four times daily
    3. Metoprolol (Lopressor) 100-450 mg PO qd
  2. Probably effective - All are Beta Blockers (Level B evidence)
    1. Atenolol start 25 mg at bedtime
      1. May increase after 1 week to 50 mg at bedtime
      2. Consider divided dosing 50 mg twice daily
    2. Nadolol
      1. Start 40 mg daily
      2. Increase by 40 mg weekly to 120 mg typical dose (maximum 240 mg daily)
  3. Possibly effective (Level C)
    1. Lisinopril
      1. Migraine without Aura associated with high ACE Level
      2. Schrader (2001) BMJ 322:19-23 [PubMed]
    2. Candesartan
    3. Clonidine
    4. Guanfacine
  4. Inadequate evidence
    1. Bisoprolol (Zebeta)
    2. Acetazolamide (Diamox)
    3. Calcium Channel Blockers
      1. Verapamil
      2. Nicardapine
      3. Nifedipine
      4. Nimodipine
  5. Ineffective (avoid)
    1. Acebutolol
    2. Telmisartan (Micardis)

VII. Preparations: Nonsteroidal Antiinflammatory Drugs (NSAIDS)

  1. Risk of Analgesic Overuse Headache
  2. Probably effective (Level B)
    1. Naproxen
    2. NaproxenSodium (Anaprox) 550 mg twice daily
    3. Fenoprofen
    4. Ketoprofen
    5. Ibuprofen
  3. Possibly effective (Level C)
    1. Flurbiprofen
    2. Mefenamic acid
  4. Unknown Efficacy
    1. Aspirin
    2. Indomethacin
  5. Ineffective
    1. Nabumetone (Relafen)

VIII. Preparations: Antidepressants

  1. Probably effective (Level B evidence)
    1. Amitriptyline (Elavil) 30 to 150 mg PO qd
    2. Nortriptyline (Pamelor)
    3. Vanlafaxine (Effexor)
  2. Inadequate evidence
    1. Fluvoxamine
    2. Protriptyline
    3. Fluoxetine (Prozac) 20-40 mg PO qd
      1. Headache worsens in 30% of cases
      2. Steiner (1998) Cephalalgia 18:283-6 [PubMed]
  3. Ineffective agents (avoid)
    1. Clomipramine (Anafranil)

IX. Preparations: Anticonvulsants

  1. Most effective agents (Level A Evidence)
    1. Valproic Acid (Depakote) 250 to 750 mg orally twice daily
    2. Topiramate (Topamax)
  2. Possibly effective (Level C evidence)
    1. Carbamazepine
  3. Inadequate evidence
    1. Gabapentin
  4. Ineffective (avoid)
    1. Lamotrigine
    2. Oxcarbazepine (Trileptal)

X. Preparations: Vitamin Supplementation

  1. Most effective (Level A)
    1. Petasites hybridus (Butterbur): Petadolex 150 mg/day
      1. May reduce Migraine frequency by 50%
      2. GI intollerance is common
      3. Lipton (2004) Neurology 63:2240-4 [PubMed]
  2. Probably effective (Level B)
    1. Feverfew 50 to 82 mg daily
    2. Vitamin B2 (Riboflavin) 400 mg orally daily
      1. Schoenen (1998) Neurology 50:466-70 [PubMed]
    3. Magnesium Oxide 300 mg/day
      1. May also assist with Migraine medication-induced Constipation
      2. May reduce severity and duration of Migraines
      3. Wang (2004) Headache 43(6):601-10 [PubMed]
  3. Possibly effective (Level C)
    1. Coenzyme Q10 100 mg orally three times daily
      1. Reduces Migraines by a third
      2. Sandor (2005) Neurology 64:713-5 [PubMed]
  4. Inadequate evidence (avoid)
    1. Acupuncture
      1. Early evidence suggests 40% reduction in severity, frequency

XI. Preparations: Miscellaneous

  1. Probably effective (Level B)
    1. N-alpha-methyl Histamine
      1. Dose 1-10 ng twice weekly sq injection
      2. Millan-Guerrero (2006) Can J Neurol 33: 195-99 [PubMed]
    2. Botulinum Toxin A injections
      1. Third-line option after 2-3 failed prophylactic agents
      2. Injection sites
        1. Occiput (Occipitalis muscle)
        2. Posterior Neck (Cervical paraspinal, trapezius muscle)
        3. Parietal, supraauricular (Temporalis muscle)
        4. Frontal forehead (Corrugator, Procerus, Frontalis muscles)
      3. FDA approved for chronic Migraines since 2010
      4. Best effect after 3 cycles of injection
      5. Silberstein (2014) J Neurol Neurosurg Psychiatry [PubMed]
  2. Possibly effective (Level C)
    1. Cyproheptadine (Periactin) 4-16 mg orally daily
      1. Serotonin Agonist
  3. Inadequate evidence
    1. Lithium Carbonate (Lithobid) 300 mg PO bid-tid
    2. Anticoagulants and antiplatelet agents
      1. Cyclandilate
      2. Coumadin
      3. Picotamide
      4. Acenocoumarol
  4. Ineffective (avoid)
    1. Clonazepam
    2. Montelukast

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Ontology: Migraine prophylaxis (C1142085)

Concepts Therapeutic or Preventive Procedure (T061)
SnomedCT 408381007
Italian Profilassi dell'emicrania
Japanese 片頭痛予防, ヘンズツウヨボウ
Czech Prevence migrény
English prophylaxis migraine, migraine prophylaxis, Migraine prophylaxis, Migraine prophylaxis (procedure)
Hungarian Migrén profilaxis
Portuguese Profilaxia da enxaqueca
Spanish Profilaxis de la migraña, profilaxis de la migraña (procedimiento), profilaxis de la migraña
Dutch migraine profylaxe
French Prophylaxie de la migraine
German Migraeneprophylaxe