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.

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