Preventative (or Prophylactic) Medicines

Introduction

Preventative medicines (also know as prophylactic medicines) are usually taken daily whether or not a headache is present, to reduce the frequency, severity or duration of headaches. They are often borrowed from other areas of medicine.

Experts suggest that if you are experiencing 4 or more migraine attacks per month, then a preventative medicine should be discussed with your physician.

Preventative medicines can come with potential side effects. Your physician will explain these possible risks (and benefits) to you at the time of selecting a preventative medicine.

Some side effects can be beneficial as we see below.

If there is a comorbid condition also present, your Headache Neurologist may choose a preventative medication that treats both conditions. An example would be if a patient was experiencing seizures and migraine at the same time, a preventative anti-seizure medication may be prescribed.

It is also important for migraine sufferers to learn about various migraine lifestyle factors that can also initiate an attack. Examples of complicating lifestyle conditions include: skipping meals, irregular sleep habits (either too much seep, or too little sleep), or experiencing too much stress. Stress has long since been shown to be the #1 lifestyle trigger that migraineurs experience, so reducing your stress level will most certainly help you to better manage your headaches (for example relaxation therapy, biofeedback).

For more on these lifestyle tips to help you better manage your migraines visit the lifestyle & triggers tab,

Migraine prevention (prophylactic therapy) should be considered when the frequency of migraine attacks is such that reliance on acute medications alone puts patients at risk for medication overuse (rebound) headache. Medication overuse is defined as use of opioids, combination analgesics, or triptans on ten days a month or more, or use of simple analgesics (acetaminophen, ASA, NSAIDs) on 15 days a month or more.

Additionally, preventative therapy could be considered if attacks are less frequent but severe and affect daily activities, or if acute medications are not very effective.

The Canadian Headache Society, Prophylactic Guidelines Development Group 1

Categories of Preventative Medicines:

  • Beta-Blockers
  • Antidepressants
  • Calcium Channel Blockers
  • Angiotensin Receptor Blockers
  • Monoamine Oxidase Inhibitors (MAOIs)
  • Anticonvulsants (anti-seizure)
  • Neurotoxins
  • new oral CGRP antagonist Atogeapant

Beta-Blockers

The Beta-Blocker most common to the general public is propanolol (Inderal). Other examples of Beta-blockers include nadolol (Corgard®), metoprolol (Lopressor) and atenolol (Tenormin). Beta-blockers are commonly used for high blood pressure but can also effectively prevent migraines. Their ability to effectively prevent migraines has long been established.

They are suspected of helping to reduce the widening of arteries - but scientists are unclear. This is important as migraineurs are prone to blood vessel dilation, during an attack.

Side effects that Beta-blockers can cause include drowsiness, sleep irregularities, fatigue, depression, memory disturbances, reduced exercise tolerance, low blood pressure (in people who do not have high blood pressure), and more. Physicians generally avoid prescribing them in patients with depression or other mood disorders

Patients who have asthma should avoid Beta-blockers. Be sure to discuss this with your physician.

Antidepressants

One of the most commonly prescribed used medicine for migraine sufferers is the category of antidepressants. Originally designed to treat depression, and other disorders, scientists discovered by accident their ability to effectively treat migraine patients.

The most common type of the “antidepressant family of medicines” is amitriptyline. Amitriptyline is a tricyclic antidepressant. There are other antidepressants used to aid migraine sufferers in preventing migraine attacks, but amitriptyline is the most utilized in the antidepressant family of medications. Other antidepressants used for migraine prevention include nortriptyline (Aventyl), venlafaxine (Effexor; not a tricyclic).

These medications can benefit the patient by also assisting with depression and can control anxiety, however side effects reported include drowsiness, dry mouth, and possible weight gain.

Calcium Channel Blockers

Calcium Channel Blockers are rarely used in the prevention of migraines, however Flunarizine (Sibelium) has been studied and has shown to be effective for the prevention of migraine. It is available in Canada but not the U.S. Side affects that have been reported include depression and weight gain.

Verapamil, a Calcium Chanel blocker has sometimes been prescribed for the prevention of migraine, and also for Cluster Headache. The author has been taking Verapamil, for Cluster Headaches, for 25+ years, and has experienced no side effects. However, each patient responds differently to individual medications. It can cause severe constipation in some people as well as other side effects.

Verapamil was originally designed to lower blood pressure however, researchers accidentally discovered its benefit to help control migraine.

Angiotensin Receptor Blockers (Candesartan)

Candesartan (Atacand) is a drug used for high blood pressure and is in class of drugs called Angiotensin Receptor Blockers (ARBs). It has been shown to be effective in preventing migraine attacks. It has very mild side effects, which can include dizziness and low blood pressure (in people who do not have high blood pressure).

Monoamine Oxidase Inhibitors (MAOIs)

Monoamine Oxidase Inhibitors (MAOIs) are antidepressants that are rarely used in the prevention of migraine. Specialists are concerned about their potential side effects and interactions with food and other drugs, as evidence to support their use is minimal.

Anticonvulsants or Anti-Epileptic or Anti-Seizure Medications

Some of the most common examples of Anticonvulsants include: topiramate (Topamax), Valproic Acid or divalproex sodium, and gabapentin (Neurontin) that also fall under the category on Anticonvulsants.

Topiramate is likely the Anticonvulsant that is most commonly prescribed to migraineurs. It has very good evidence for use as a migraine preventative.

Possible side effects include numbness in the fingers, tremor, or cognitive difficulties such as short term memory, word-finding, or effects on mood. A benefit from this medication is that patients can experience weight loss.

Although valproic acid or divalproex sodium are also very effective as migraine preventatives, they have many side effects (such as weight gain, tremor, hair loss and others), and should not be used by pregnant women due to risk of birth defects (neural tube defects).

Neurotoxins

According to Wikipedia "Neurotoxins are toxins that are destructive to nerve tissue" (causing neurotoxicity). 2

Dr. Joel Saper from the Michigan Headache and Neurological Institute in Ann Arbor, Michigan further adds "Neurotoxins used in medicines are purified neurotoxins from the bacteria that causes botulism; a medical condition characterized by progressive muscle weakness and paralysis, usually the result of food poisoning or a deep wound infection. Small amounts of neurotoxins injected directly into muscles can cause the muscle to be greatly weakened. Neurotoxins are used widely in medical practice for a variety of conditions, most involving the spasm of various muscles throughout the body including glands that rely on muscles to exude their substances. 3

A neurotoxin that has recently emerged for the preventative treatment of chronic migraine (migraine occurring on 15 or more days per month) is onabotulinumtoxinA - more commonly known as Botox ®. Access the complete article on Botox (and its effectiveness in treating chronic migraines), reviewed by a Toronto anaesthesiologist on the next tab entitled Injections Used to Prevent a Migraine.

New Atogeapant ( oral CGRP Antagonist)

Atogepant is an orally-administered CGRP receptor antagonist in development for the prevention of migraine. CGRP and its receptors are expressed in regions of the nervous system associated with migraine pathophysiology. It is chemically distinct from ubrogepant (see acute oral medicines), our investigational orally-administered CGRP receptor antagonist for the acute treatment of migraine, and has demonstrated in preclinical studies to have a higher potency and longer half-life, making it potentially suitable for preventive treatment. 4

Issues to Consider When Taking Preventative Medicines

  • never share medications
  • inform your doctor of any side effects that you experience
  • give the medicine at least 4-6 weeks to work properly (many patients abandon a treatment after a very short period)

Learn more about Anti CGRP Treatments For Migraine here

Written by Brent Lucas B.A. (Psych) - Director, Help for Headaches, London, Ontario

Medical edits courtesy of Irene Worthington, B.Sc.Phm (co-author of Canadian acute and prophylactic migraine guidelines). Pharmacist (retired) Sunnybrook Health Sciences Centre, Toronto, Ontario

Angiotensin Receptor Blockers (ARBs) and Angiotensin-converting Enzyme Inhibitors (ACEIs)

There have been a number of studies on using angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) for the prevention of migraine. ARBs are preferred because of minimal side effects. Examples include losartan (Cozaar), olmesartan (Benicar), and candesartan (Atacand). These may be useful for the patient with hypertension and migraine. Side effects include dizziness, among others, but they are usually well tolerated, with no sedation or weight gain. 5

According to the author Dr. Lawrence Robbins (Illinois headache neurologist) ARBs are preferred because of minimal side effects.

References

  1. The Canadian Headache Society, Prophylactic Guidelines Development Group
  2. Wikipedia, What are neurotoxins?
  3. Neurotoxins, Dr. Joel Saper, Michigan Headache and Neurological Institute, Ann Arbor, ,Michigan
  4. Allergan Canada, Atogeapant
  5. Robbins, L Practical Pain Management, Volume 14, Issue #6, 2019

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