Migraine Prophylaxis Medications – Comparison Chart

Migraine headaches affect more than one billion individuals per year across the world and are often self-managed by over-the-counter pain relievers such as ibuprofen or aspirin, but sometimes can become debilitating to the point where prescription medications are needed to reduce the frequency and severity of attacks. There are numerous agents that can be used for prophylaxis and we provide a breakdown in our migraine prophylaxis comparison chart below.

Migraines are classified into two subtypes that can be defined by the presence or lack thereof of a visual disturbance called aura. The most common subtype of migraine is without aura which can have symptoms in addition to pain such as irritability, depression, difficulty concentrating, photophobia, or phonophobia. Migraine with aura has similar symptomatology but also is associated with visual manifestations such as flickering lights, spots, lines, and/or sensory numbness or pins/needles. Generally, these aura symptoms are short-lived developing over a period of 5-20 minutes and lasting ≤ 60 minutes.

As I stated earlier, most patients use OTC NSAIDs like ibuprofen or naproxen as first-line for the treatment of migraine headaches. It is guideline recommended that patients attempt to use these medications for mild, self-limiting migraine headaches prior to attempting other medications. If migraines are not self-limiting and symptoms are moderate to severe, or if patients have contraindications to NSAIDs, patients may be prescribed triptans (free comparison chart) for acute abortive treatment. It is important to remember to limit the use of these medications to 2 days per week or less than 10 days per month. If abortive therapy is used more frequently and becomes heavily relied on for even mild migraine headaches, patients may be at risk for further headaches due to medication overuse.

We don’t want to see patients begin to experience medication overuse headaches on top of their debilitating migraines due to relying solely on triptans for relief. If patients are experiencing headaches that cannot be controlled by triptans or are becoming more frequently severe and find themselves using triptans more than prescribed it will be time to consider if prophylaxis is warranted.

Migraine Prophylaxis Comparison Chart

      Drug    Add-On Indication for Use    Contraindications or Cautions    Notable Adverse Effects  
Beta-blockers (propranolol, atenolol, metoprolol, nadolol)Hypertension Angina (chest pain) Cardiac Dysrhythmia (Afib)Asthma, Bradycardia, COPD, HypotensionBradycardia, Depression, Fatigue, Hypotension, Impotence, Lethargy
Divalproex, Divalproex ERBipolar Disorder EpilepsyLiver Disease, PregnancyAlopecia, Asthenia, Dizziness, Hepatic Failure, Nausea (common), Pancreatitis, Somnolence, Thrombocytopenia, Tremors, Weight Gain, Elevated Ammonia
Pregnancy, Kidney Stones, Renal ImpairmentDifficulty with Memory and Concentration, Paresthesia, Decreased Appetite, Fatigue, Kidney Stones, Metabolic Acidosis, Nausea
Chronic Pain  
Do Not Use Within 14 Days of MAOI, Avoid in Acute Myocardial Infarction, Caution in ElderlyBlurry Vision, Constipation, Decreased Seizure Threshold, Dry Mouth, Orthostatic Hypotension, QT Prolongation, Sedation, Tachycardia, Urinary Retention, Confusion
Do Not Use Within 14 Days of MAOIDry Mouth, Hypertension, Insomnia, Mydriasis, Nausea, Nervousness, Seizures
VerapamilHypertension Angina (chest pain) Atrial fibrillationHypotension, Bradycardia, ArrhythmiasHypotension, Constipation, Dizziness, Edema
GabapentinChronic Pain Epilepsy
Renal ImpairmentEdema, Weight Gain, Sedation, Angioedema (rare), Dizziness
Migraine Prophylaxis Medications – Comparison Chart

The above chart talks specifically about what medications are used for prophylactic therapy. The decision of what medication to use generally boils down to comorbid conditions and side-effect profiles. It is important to understand that individual response may vary and the first medication that doctors place you on for prevention may not be effective. Thankfully, there are a few options to choose from, and using these can prevent abortive therapy overuse and further headaches.

If you are looking for more on any of these agents, please check out the Real Life Pharmacology Podcast.

The goal of preventative treatment of migraine headaches is to reduce the severity, frequency, duration, and disability of such headaches. These medications are pursued if the patient’s headaches are significantly disabling, acute treatment is required > 4 days per month, abortive treatment isn’t an option due to contraindications, or if abortive treatment is not effective and overused.  

When reviewing our migraine prophylaxis comparison chart, we don’t list the onset of action. It is important to understand that all of these medications may take time (2-3 months) to show clinical benefit for patients and may become indefinite once migraines are reduced. Another thing to remember is that these medications, although effective, may not eliminate the potential for migraine headaches and effective prevention is considered a 50% reduction in total migraine days.

The choice of prophylactic therapy is often determined by contraindications, potential compelling indications, and the adverse effect profile of each specific medication. The most commonly used agents I see in practice include beta-blockers, topiramate, valproic acid, venlafaxine, and TCAs. CGRP antagonists are a newer class of medication that may be used for this purpose as well and we will cover them in a future post so stay tuned!

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This article was written by Jeff Mueller, PharmD, Candidate in collaboration with Eric Christianson, PharmD, BCPS, BCGP


  1. Silberstein SD. Preventive migraine treatment. Continuum (Minneap Minn). 2015;21(4 Headache):973-989.
  2. Loder E, Burch R, Rizolli P. The 2012 AHS/AAN guidelines for prevention of episodic migraine: a summary and comparison with other recent clinical practice guidelines. Headache. 2012;52(6):930-945.
  3. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society [published correction appears in Neurology. 2013 Feb 26;80(9):871]. Neurology. 2012;78(17):1337-1345. doi:10.1212/WNL.0b013e3182535d20
  4. Becker WJ. Cluster headache: conventional pharmacological management. Headache. 2013;53(7):1191-1196. doi:10.1111/head.12145


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Written By Eric Christianson

November 9, 2022

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