Second Line Migraine Prevention Drugs

Timothy C. Hain, M.D. Chicago IL. Page last modified: August 6, 2012

Other links on this site:

• Migraine Prevention drugs
• Migraine approach flowchart (link)
• Migraine in general
• Migraine and vertigo
• Migraine in Women (link)
• Alternative Therapies (link)
• Migraine and Foods (link)

The Migraine approach flowchart outlines a general approach to migraine using 3 main groups of medications - -anticonvulsants and other drugs that work as nerve stabilizers,  antidepressants that probably work mainly through neurotransmitters such as serotonin and dopamine, and medications that act on blood vessels such as verapamil and the beta-blocker family. 

The purpose of this page is to outline secondary agents, that can be used when the first set fails, or if the first set is not tolerated.  We will again organize by mechanism, with the main addition being "mysterious" agents -- usually claimed to work on migraine. Of course, these agents are somewhat suspicious.

In general, in the USA, most of these drugs are FDA approved for other indications than migraine.  Their use is generally "off label".  Some popular migraine drugs are not approved by the FDA (e.g. flunarizine).

• Anticonvulsants and other nerve stabilizers
  • Topiramate (primary) or Zonegran (similar drug)
    • Sodium Valproate or Lamotrigine (Lamictal)
    • Levetiracetam (Keppra)
    • Oxcarbazapine (trileptal)
    • Gabapentin (Neurontin)
  • Tizanidine (Zanaflex, reduces muscle spasms)
  • Botox injections around the head
  • Acupuncture
• Antidepressants and other Neurotransmitter modulators. While these agents are generally highly effective, there may be substantial side effects.
  • venlafaxine
    • desvenlafaxine (if Venlafaxine fails)
  • nortriptyline or amitriptyline
  • aripiprazole (Abilify, atypical antipsychotic with agonist both at D2 and 5HT1A).
  • quetiapine (Seroquel, an atypical antipsychotic, used for bipolar). Serotonin agent and D2 dopamine  blocker
  • nefazodone (Serzone).  Serotonin (5H2 antagonist). 
  • cyproheptadine or Pizotifen (not FDA approved)
  • Agents that we are dubious about
    • lexapro and other pure SSRI's such as paroxetine (Paxil), Luvox, Zoloft, Celexa, wellbutrin, Fluoxetine (Prozac)
• Agents that act on blood vessels
  • Calcium channel blockers -- nearly every calcium channel blocker has some data suggesting it is helpful.
    • Verapamil or Nimodipine (these are L-channel calcium channel blockers)
      • Flunarizine (considerable data supporting use, not FDA approved in the US). Also D2 blocker
      • Avoid calcium channel vasodilators such as procardia
  • Beta blockers
    • Propranolol, atenolol, timonol, nadolol (Corguard)
      • Nebivolol (Bystolic, if generic versions of above are poorly tolerated)
  • Agents that we are dubious about
    • ACE inhibitors (e.g. lisinopril, candesartin)
    • Clonidine, Tenex
• Nonsteroidals (not to be taken every day)
  • Ibuprofen or Naproxen
  • Indomethacin
• Agents of uncertain mechanism (no recommendation in general)
  • Memantine (Namenda)
  • Herbals -- there are an immense number of uncontrolled studies of these drugs, that are generally available in health food stores.
    • Butterbur (Petadolux). 
    • Ginkgolide B
    • Feverfew
    • Tou Feng Yu pill (TFY) -- a traditional Chinese herbal medicine, Radix Angelicae dahuricae (Baizhi), Rhizome Ligustici (Chuanxiong) and Folium Camelliae sinensis (green tea)
    • L. chuanxiong (traditional Chinese herbal)
    • goshuyuto (Japanese herbal for migraine)
    • Xiaoyao Nose Drops (XYND)
  • Supplements
    • Magnesium, 400 to 600 mg/day.
    • Agents that we tend not to recommend due to lack of positive feedback about them.
      • Riboflavin (B2)
      • Co-Q
• Combinations of tolerated agents
  • Nerve stabilizer and antidepressant
    • Example, topiramate and venlafaxine
    • Botox and venlafaxine
  • Nerve stabilizer and blood vessel agent
    • Example, topiramate and verapamil
    • Botox and verapamil
  • Antidepressant and blood vessal agent
    • example: venlafaxine and propranolol

References:

• Dusitanond, P. and W. B. Young (2009). "Neuroleptics and migraine." Cent Nerv Syst Agents Med Chem 9(1): 63-70.
• Louis, P. and E. L. Spierings (1982). "Comparison of flunarizine (Sibelium) and pizotifen (Sandomigran) in migraine treatment: a double-blind study." Cephalalgia 2(4): 197-203.