Managing Migraine, Part 2: Prescription Preventive Therapies to Reduce Migraine Frequency


Preventive medications might be considered in patients with 4 or more migraine days per month.

Pharmacists can be a helpful resource in counseling patients with migraine. In part 1, Sara Crystal, MD, a neurologist and headache specialist and medical director of Cove discussed nonprescription measures that can help prevent migraine. In cases where nonprescription measures are not enough, preventive treatment with prescription medications may be necessary. Patients may have a lot of questions about these medications—especially when a new drug hits the market.

When choosing preventive treatment for her patients, Crystal explained, “The most important [goal] is to establish realistic expectations.” Crystal teachesher patients that complete elimination of headaches is unlikely. “The goal of preventive therapy is a 50% reduction in migraine/headache days per month, in addition to decreasing the severity and duration of attacks and overall disability,” she said. Crystal also cautions patients that it can take weeks to months to notice improvements from oral preventive drugs. “The migraine-specific anti-[calcitonin gene-related peptide]CGRP medications demonstrate faster onset, though,” she said.

Crystal considers turning to preventive medication in patients with 4 or more migraine days per month, or 2 or more migraine days if the headaches are disabling and don’t respond to acute treatments.

There are 3 classes of non-specific migraine preventives—medications developed for other conditions and found to be effective for migraine prevention: blood pressure medications, anti-seizure medications, and antidepressants.

“When choosing a preventive, we take into account the patient’s comorbidities and other medications, as well as side effects. A beta blocker may be a good choice for someone with hypertension and migraine, while a tricyclic antidepressant might be avoided in someone trying to lose weight,” Crystal explained.

Crystal’s rule of thumb in terms of dosing is to start low and go slow. She starts the patient on a low dose and titrates slowly to the dose that is effective for the patient with minimal side effects.

Both the American Headache Society and the American Academy of Neurology recommend drugs with the best evidence.1 Prescription drugs with the best evidence for migraine prevention include:

Beta Blockers1

  • Propranolol, metoprolol, and timolol are considered first-line treatment and have established efficacy.
  • Atenolol and nadolol are considered second-line treatment and are “probably effective.” 
  • Beta blockers are the most common drugs used to prevent migraine. A beta blocker may be a preferred option in a patient with high blood pressure, angina, or ischemic heart disease.
  • Side effects of beta blockers may include bradycardia, depression, fatigue, hypotension, impotence, and lethargy.
  • Beta blockers require heart rate and blood pressure monitoring.


  • Divalproex sodium (Depakote) and topiramate (Topamax) are considered first-line treatment.
  • Divalproex sodiummay be the preferred option in patients with seizure or bipolar disorder. Side effects may include alopecia, asthenia, dizziness, liver failure, nausea, pancreatitis, somnolence, thrombocytopenia, tremors, and weight gain.
  • Topiramate may be the preferred option in patients with seizure disorder. Side effects include paresthesia, appetite loss, fatigue, kidney stones, metabolic acidosis, nausea, and problems with language, memory, and concentration.
  • Patients who are pregnant should not use either divalproex sodiumor topiramate.


  • Amitriptyline(Elavil) has evidence supporting its efficacy. However, because of its side effect profile, amitriptyline is categorized as “probably effective.”
  • Amitriptyline may be a preferred option in a patient with depression or insomnia.
  • Common side effects include sedation and anticholinergic effects, such as blurry vision, constipation, dry mouth, palpitations, tachycardia, urinary retention. Other side effects include cardiac conduction abnormalities, orthostatic hypotension, QT prolongation, and weight gain.
  • Venlafaxine is also considered probably effective for migraine prevention.
  • Venlafaxine may be a preferred option for patients with depression or anxiety.
  • Common side effects of venlafaxine include nausea and vomiting. Venlafaxine may increase blood pressure.


  • Botox is an effective preventive treatment for chronic migraine. Botox is not effective for episodic migraine and is considered probably ineffective for chronic tension headaches.

Parenteral CGRP inhibitors3

Parenteral CGRP inhibitors have established efficacy for migraine prevention. There are 4 parenteral CGRP inhibitors approved for use in the United States:

  • erenumab (Aimovig);subcutaneous injection
  • fremanezumab (Ajovy);subcutaneous injection
  • galcanezumab (Emgality); subcutaneous injection
  • eptinezumab (Vyepti); IV infusion

Oral CGRP inhibitors/gepants

  • Atogepant (Qulipta) is indicated for the preventive treatment of episodic migraine in adults. The most common side effects are nausea, constipation, and fatigue.4
  • Rimegepant (Nurtec ODT)is indicated for preventive treatment of episodic migraine in adults. It is also indicated for acute treatment of migraine with or without aura. The most common side effects of rimegepant are nausea, abdominal pain, and indigestion.5 

Come back tomorrow for Part 3 of this series, a review of a preventive prescription therapy.


  1. Ha H, Gonzalez A. Migraine headache prophylaxis. Am Fam Physician. 2019;99(1):17-24.
  2. Simpson DM, Hallett M, Ashman EJ, et al. Practice guideline update summary: Botulinum neurotoxin for the treatment of blehparospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016;86(19):1818-1826. Doi:10.1212/WNL.0000000000002560
  3. Ailani J, Burch RC, Robbins MS; for the Board of Directors of the American Headache Society. The American Headache Society consensus statement: Update on integrating new migraine treatments into clinical practice. Headache. 2021;61(7):1021-1039. Doi:10.1111/head.14153
  4. Qulipta—atogepant tablet. DailyMed. Updated October 12, 2021. Accessed January 13, 2022.
  5. Nurtec ODT—rimegepant sulfate tablet, orally disintegrating. DailyMed. Updated December 20, 2021. Accessed January 13, 2022. 
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