Migraine prophylaxis: Prescription treatment options

Check out this Medmastery article on prophylactic prescription medication options for your patients with migraines.
Last update2nd Aug 2022

There are many options when it comes to deciding on the right prophylactic medicine for your headache patient: anti-epileptic (anticonvulsant) drugs, antidepressants, beta-blockers, and calcium channel blockers.

Figure 1. There are many pharmaceutical classes available for prophylaxis for primary headaches including anticonvulsants (anti-epileptics), antidepressants, beta-blockers, and calcium channel blockers.

Using anti-epileptics (anticonvulsants) for headache prophylaxis

Anti-epileptics are some of the most effective drugs for migraine prophylaxis. Anti-epileptics are also often used in post-traumatic headaches and the trigeminal cephalalgias.

Figure 2. Anti-epileptics (anticonvulsants) are often used as prophylaxis for migraines, post-traumatic headaches, trigeminal cephalalgias, cluster headaches, and tension headaches.


Typically you would administer valproate at a dose rate between 500 and 1500 mg per day. It is important to note, that valproate can cause neural tube defects and has been associated with polycystic ovarian syndrome, so its use in women of child-bearing age is limited. Also, it has been noted that hepatotoxicity can occur.


Topiramate can be helpful in patients with cluster headaches. Topiramate is frequently associated with paresthesia and may cause memory issues and weight loss. Rarely, it can cause acute narrow angle glaucoma and nephrolithiasis.


Gabapentin may be effective in tension-type headaches. However, if there are mixed migraine features, gabapentin can be ineffective. In these cases, neurologists often substitute divalproex and topiramate as preventative agents.

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Using antidepressants for headache prophylaxis

Tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin noradrenaline reuptake inhibitors (SNRIs) have all been found to be effective in tension-type headache as well as migraine.

Figure 3. Antidepressants are often used as prophylaxis for tension headaches and migraine headaches.

Tricyclic antidepressants

  • Amitriptyline
  • Nortriptyline

Serotonin noradrenaline reuptake inhibitors (SNRIs)

  • Duloxetine
  • Venlafaxine

Selective serotonin reuptake inhibitors (SSRIs)

  • Citalopram
  • Escitalopram
  • Paroxetine
  • Fluoxetine
  • Sertraline

Similar to when you are treating a patient with depression, several weeks may be needed to assess the efficacy of the treatment, and the dosage may need adjustment.

Using beta-blockers for headache prophylaxis

Beta-blockers (such as propranolol, timolol, nadolol, atenolol, and metoprolol) are often used as a first line treatment when there is comorbid hypertension or anxiety.

Figure 4. Beta-blockers may be used as prophylaxis against migraines, especially when your patient also suffers from hypertension or anxiety.

Treatment may take a few weeks to show an effect and the dosage may need adjustments.

If a beta-blocker is indicated, it is usually prescribed at the following typical dose:

  • Propranolol, 120–240 mg daily
  • Nadolol, 80–240 mg daily
  • Metoprolol, 200 mg daily
  • Atenolol, 100 mg daily

Side effects include exercise intolerance, bradycardia, and erectile dysfunction.

Using calcium channel blockers for headache prophylaxis

Calcium channel blockers (such as verapamil and flunarizine) are also effective prophylactic agents for patients suffering from migraines (however, flunarizine is not available in the US).

It should be noted, however, that these drugs generally require higher doses and can have side effects including cardiac arrythmias, such as atrioventricular block and bradycardia.

That’s it for now. If you want to improve your understanding of key concepts in medicine, and improve your clinical skills, make sure to register for a free trial account, which will give you access to free videos and downloads. We’ll help you make the right decisions for yourself and your patients.

Recommended reading

  • Blumenfeld, AM. 2018. Botox for chronic migraine: Tips and tricks. Practical Neurology17: 27–36. https://practicalneurology.com
  • Halker Singh, RB, Starling, AJ, and VanderPluym, J. 2019. Migraine acute therapies. Practical Neurology17: 63–67. https://practicalneurology.com
  • Krel, R and Mathew, PG. 2019. Procedural treatments for headache disorders. Practical Neurology17: 76–79. https://practicalneurology.com
  • Mauskop, A. 2012. Nonmedication, alternative, and complementary treatments for migraine. Continuum (Minneap Minn)18: 796–806. PMID: 22868542
  • Motwani, M and Kuruvilla, D. 2019. Behavioral and integrative therapies for headache. Practical Neurology17: 85–89. https://practicalneurology.com
  • Natekar, A, Malya, S, Yuan, H, et al. 2019. Migraine preventative therapies in development. Practical Neurology17: 54–57. https://practicalneurology.com
  • Parikh, SK and Silberstein, SD. 2018. Calcitonin gene-related peptide monoclonal antibodies. Practical NeurologyFeb: 20–22. https://practicalneurology.com
  • Rizzoli, PB. 2012. Acute and preventative treatment of migraine. Continuum (Minneap Minn)18: 764–782. PMID: 22868540
  • Tepper, SJ and Tepper, DE. 2018. Neuromodulation and headache. Practical Neurology17: 42–45. https://practicalneurology.com

About the author

Robert Coni, DO EdS
Robert is Neurohospitalist, Medical Director, and Coordinator at the Grand Strand Medical Center, and Clinical Assistant Professor at the University of South Carolina.
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