List of migraine preventives: classes and mechanism of action
«What’s the best preventive for migraine»?
Sadly, there is no answer to this question.
Many different approaches exist, and it is not possible to predict which one will work for one person in particular.
For each option, there are people who do not improve (non-responders), people who improve partially (30%, 50%, partial responders), and people who improve a lot (75%, super-responders).
The same applies to side effects. They cannot be predicted, some people have them and others don’t. In many cases, side effects will improve or go away with time once your body adjusts to being on the new medication.
Oral preventives (pills taken by mouth), are usually started at a low dose and increased slowly every 1-2 weeks if you are not having any intolerable side effects. These medications will start to work gradually over many weeks to months.
So how do I decide which preventive to try?
- Your physician must check which preventive(s) you cannot use for medical reasons (contra-indications). For example, people with asthma should not use beta-blockers as they could worsen symptoms.
- See if the side effect profile is acceptable for you. For example: if you are overweight, a medication causing weight gain is not ideal. If you have insomnia, a medication causing sleepiness taken at bedtime could be beneficial.
- Check your insurance coverage. Some drugs can be used only as a second or third line, after trying cheaper drugs. Example: In Canada, Botox and CGRP antibodies will not be covered if you have not tried 2 other preventives.
Table of Migraine Preventives
** This table is an overview of options. A more detailed table is also available with doses, contraindications, and common side effects.
| Class | Examples Generic (brand name) | How does it work |
| Anti-hypertensive | Candesartan (Atacand) Propranolol (Inderal) Nadolol (Corgard) Verapamil (Isoptin) |
Unclear. Some decrease the electrical hyperexcitability of the brain. |
| Anti-depressant | Amitriptyline (Elavil) Nortriptyline (Aventyl) Venlafaxine (Effexor) |
Modulate pain networks (serotonin, adrenaline, noradrenaline) |
| Anti-seizure | Topiramate (Topamax) Gabapentin (Neurontin) |
Decrease the hyperexcitability of the brain |
| CGRP antibodies | Erenumab (Aimovig) Galcanezumab (Emgality) Fremanezumab (Ajovy) Eptinezumab (Vyepti) |
Block CGRP that plays a role in the migraine cascade Designed specifically for migraine |
| Supplements | Magnesium Vitamine B2 Coenzyme Q10 Butterbur ** Only preparations show to have chemicals that may damage liver removed |
May influence the energy metabolism of the brain and stabilize nerve cells |
| Injectable toxins | Onabotulinum toxin type A (Botox) | Modifies the function of sensory nerves, and decreases the input to the brain |
| Gepants | Atogepant (Qulipta) Rimegepant (Nurtec) |
Blocks the CGRP receptor which reduces the action of CGRP, a protein involved in the migraine cascade. Designed for migraine |
| Neuromodulation | Transcutaneous stimulation (Cefaly) Vagus nerve stimulation (Gamma Core) Transcranial Magnetic Sitmulation (eNEura, not available in Canada |
Influences the pain networks with electrical currents |
Table: Therapies for which there is no strong evidence that it works more than placebo (more research needed OR strong placebo effect suspected).
| Category | Examples | Hypothetical mechanism (NOT proven) |
| Injections | Acupuncture Nerve blocks Daith piercing Sphenopalatine Ganglion (SPG) Blocks |
Influence of the energy meridians Muscle and nerve modulation Blocking sensory inputs to the brain Modulation of the vagus nerve function (not proven) Modulate the nerve networks passing in this ganglion |
| Cannabinoids | Cannabis(many products available with different THC, CBD content and ratios) | The cannabinoid system influences virtually every system in the brain, including the pain network but also others |
| Surgery | Decompression of nerves Neurostimulation with implants |
Relieve the pressure on nerves Modulate the pain system |
| Opioids | Morphine and others Should NOT be used for migraine prevention due to risks |
Act on opioid receptors in the brain (mu, kappa, delta receptors) |
A warning: should any drug that treats epilepsy, high blood pressure, or depression be used for migraine «just in case it works»?
Some tables online list many other drugs, especially blood pressure and depression medications that some physicians may use but have not been studied specifically for migraine. You should be careful. These very long lists are not medically recommended.
Now, read about a few tips to try preventives!
REFERENCES
Pringsheim T, Davenport W, Mackie G, Worthington I, Aube M, Christie SN, et al. Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci. 2012;39(2 Suppl 2): S1-59.
Rajapakse T, Pringsheim T. Nutraceuticals in Migraine: A Summary of Existing Guidelines for Use. Headache. 2016;56(4):808-16.
McGeeney BE. Cannabinoids and hallucinogens for headache. Headache. 2013;53(3):447-58.
VanderPluym J, Evans RW, Starling AJ. Long -Term Use and Safety of Migraine Preventive Medications. Headache. 2016;56(8):1335-43.
Tepper SJ. History and Review of anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: From Translational Research to Treatment. Headache. 2018;58 Suppl 3:238-75.
Argyriou AA, Mantovani E, Mitsikostas DD, Vikelis M, Tamburin S. A systematic review with expert opinion on the role of gepants for the preventive and abortive treatment of migraine. Expert Rev Neurother. 2022;22(6):469-88.
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