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Episodic Migraine Prevention: Comparison of Drugs, Side Effects

A review of existing studies on FDA approved preventive medications for episodic Migraine found there was no statistically significant difference in effectiveness between them. But some drugs were much better tolerated than others.


At first blush it may seem strange that this study focused on preventive options for episodic Migraine. However, it is important to keep in mind that a patient’s Migraines need not be chronic (15 or more headache days a month) to warrant preventive therapies. Preventive therapy is indicated for patients experiencing episodic Migraine attacks at or above a certain level of frequency or intensity, when the Migraine attacks are especially disruptive to the person’s life or when a patient is unable to take or tolerate acute medications.

The goal of preventive therapies for Migraine is 50% or greater reduction in attack frequency without any intolerable side effects. Therefore it is important to know not only which drugs are effective, but also which are more likely than others to cause intolerable side effects that will cause patients to stop taking a drug that may be otherwise helpful.

The researchers noted that previous reviews of studies regarding preventive medication for episodic Migraine focused only on the effectiveness of each specific drug. None compared the effectiveness of each preventive medication to the others. The tolerability of these medications hadn’t been studied before, either.

Reduction in Migraine Attack Frequency:

All medications FDA approved for prevention of episodic Migraine (propranolol, timolol, divalproex sodium and topiramate) were determined to be more effective than placebo at reducing Migraine attack frequency by 50% or more.

Additionally, approved medications improved other aspects of patients’ experiences with Migraine. For example:

  • Topamirate and propanolol were associated with a decrease in use of acute Migraine medications.
  • Divalproex in doses of 1,500 mg/day was associated with a greater than 50% improvement in disruption of the patient’s daily activities and need for medication to treat Migraine symptoms.
  • Topamirate improved patient quality of life as measured by patient scores on the Headache Impact Test, Migraine-Specific Quality of Life Questionnaire and Migraine Disability Assessment. These are popular instruments for assessing the impact of Migraine Disease on the lives of patients.

Side Effects of Migraine Preventives:

The researchers focused on adverse side effects among preventive medications that resulted in discontinuation of treatment. This study marks the first time researchers have done a review of existing studies to compile information that compares side effects between medications.

  • Topamirate (100 and 200 mg/day), propanolol and amitriptyline were the only drugs associated with side effects that lead to discontinuation of the medication more more often than placebo.
  • Topamirate was not associated with side effects leading to discontinuation in patients taking just 50 mg/day.
  • Side effects associated with discontinuation of topamirate included fatigue, taste changes, mood changes, weight loss, nausea, dry mouth and paresthesia (a burning, prickling, tingling or numb sensation that occurs without apparent cause, aka pins & needles).
  • The side effects that most frequently lead to discontinuation of propanolol were diarrhea and nausea.

Do you have questions or thoughts about these research findings? Please share them in the comments.

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.

  1. Tatyana A. Shamliyan, et al. "Preventive Pharmacologic Treatments for Episodic Migraine in Adults." J Gen Intern Med. Published online before print April 17, 2013. doi: 10.1007/s11606-013-2433-1.
  2. Alan Rapaport. "How to Choose a Preventive Medication for Migraine." American Headache Society.
  4. National Institutes of Neurological Disorders and Stroke. "NINDS Paresthesia Information Page." Last updated May 6, 2010. Accessed May 29, 2013.


  • janenez
    6 years ago

    I have never recovered from the brain fog of Topomax. I call it Stupomax. I only took it for 3 months. Went up incrementally in dosage but side effects were too awful at any dose for me. I’m glad to hear it works for some people. Not for me. Going gluten free is the only thing that has helped me as a preventative.

  • peggy875
    6 years ago

    I am surprised there is no mention of the brain fog you get with topamirate. I couldn’t tolerate the fog anymore and it wasn’t reducing my headaches anymore. I took it for several years.

  • Clay Fimmel
    6 years ago

    It doesn’t go into any specifics of the side effects of Toparimate, other than to say once the dosage went past 100 more people were turned off it due to the side effects than the placebo. For sure brain fog is a major factor for many people, myself included, which leads to the frustration with this drug. Others for me were a worsening of my tinnitus and pressure in my head. I was totally out of it once I went up to 100. I was there for a short while and never want to go there again. I had been on 75 for a few years with little effect. It simply wasn’t worth it for me. I had to try other paths.

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