Migraine disease affects over 1 billion people worldwide, yet only a small percentage use preventive medications to manage their attacks. Preventive medications are a vital part of migraine management, particularly for those who experience frequent, severe, or debilitating attacks. Despite their importance, the use of these treatments remains low, with only 13% of migraine patients currently using them. (1)
‘The World Health Organization now ranks migraine as the third most prevalent medical condition in the world, and the second most disabling neurological condition. The economic cost of migraine is also considerable and has an estimated worldwide annual cost of $20 billion, relating to healthcare, procedures and loss of productivity.’ (2)
This article provides an in-depth look at the most commonly prescribed migraine preventive medications and treatments, helping you understand your options and how they can fit into your migraine management plan.
** Disclaimer: This is written from the perspective of the patient and patient-advocate. This is not a substitute for medical advice. The information here will help you understand your many options so that you are better prepared for the next conversation you have with your healthcare provider.
When to Consider Migraine Preventive Medications
Migraine preventive medications are suggested when specific criteria are met, indicating that the frequency, severity, or impact of the migraine attacks warrants a proactive approach. These criteria include:
- Frequent Attacks: Experiencing four or more migraine attacks per month or eight or more days of head pain.
- Disabling Attacks: Attacks that significantly impair daily functioning.
- Prolonged Attacks: Attacks lasting longer than three days.
- Ineffectiveness of Acute Medications: When acute treatments fail to provide relief.
- Contraindications to Acute Medications: In cases where triptans are poorly tolerated or contraindicated.
- Frequent Use of Acute Pain Medications: Using acute medications more than three days per week.
If you meet any of these criteria, your healthcare provider may discuss the potential benefits of preventive medications to reduce the frequency and severity of your migraine attacks.
The Goals of Migraine Preventive Therapy
The primary goal of migraine preventive therapy is to reduce the severity and frequency of migraine attacks by at least 50% within the first three months. Additionally, preventive medications can help:
- Shorten the Duration of Attacks: Making migraine attacks more manageable.
- Increase Responsiveness to Acute Medications: Enhancing the effectiveness of treatments used during an attack.
- Decrease Disability: Improving your ability to function in daily life.
- Address Co-Occurring Conditions: Some preventive medications are chosen based on the presence of other conditions like depression, anxiety, insomnia, or high blood pressure.
Starting a Preventive Medication: The Slow and Steady Approach
When starting a preventive medication, it’s crucial to begin at a low dose and increase slowly. This gradual approach can reduce or eliminate side effects, making the medication more tolerable and effective. (3)
This method is especially important for those with vestibular migraine, where slow titration often leads to better outcomes. By starting low and going slow, you increase the likelihood of tolerating the medication and staying on it long enough to see the benefits.
Categories of Migraine Preventive Medications
Migraine preventive medications are diverse, and their effectiveness can vary based on individual needs and co-occurring conditions. Below, we explore the most common categories of preventive medications and their roles in migraine management.
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Beta Blockers for Migraine
Beta blockers, such as propranolol, are often the first line of treatment for migraine prevention, particularly for those with high blood pressure.
One way these medications works is by blocking beta-adrenergic-mediated cerebral vasodilation, which can help reduce the frequency and severity of migraine attacks. (4) Common potential side effects include fatigue, depression, nausea, dizziness, and insomnia, but they are generally well-tolerated. (5)
| Beta Blockers | Brand Name |
| Propanolol | Generic |
| Nadolol | Corgard, Generic |
| Atenolol | Tenormin, Generic |
| Metroprolol | Toprol XR, Lopressor, Generic |
| Timolol | Betim, Generic |
CGRP antagonists for migraine
In recent years, CGRP antagonists have emerged as a powerful tool in migraine prevention. These medications, including monoclonal antibodies and IV treatments, specifically target calcitonin gene-related peptide (CGRP), a molecule that increases during migraine attacks. (6) By targeting the peptide itself or its receptor, CGRP antagonists help reduce the frequency and severity of attacks, providing significant relief for many patients.
The CGRP preventives tend to have a better side effect profile that many of the older, more conventional migraine medications.
This in depth-article about CGRP medications details how these medications work.
| Medication | Brand Name |
| eptinezumab-jjmr (IV infusion) | Vyepti |
| Erenumab (Injection) | Aimovig |
| Fremanezumab (injection) | Ajovy |
| Galcanzumab (Injection) | Emgality |
| Atogepant (daily oral tablet) | Qulipta |
| Rimegepant (every other day oral tablet) | Nurtec |
Botox and nerve blocks
OnabotulinumtoxinA (Botox) is a widely used preventive treatment for chronic migraine. While the exact mechanism by which Botox prevents migraines is not fully understood, it has been shown to reduce the number of headache and migraine days by 8-9 days per month.
Nerve blocks are another option, providing targeted relief by blocking specific nerve pathways involved in migraine attacks.
This review of Botox for migraine is very informative.
| Injection | Brand Name |
| OnabotulinumtoxinA | Botox |
| Greater Occipital Nerve Blocks |
ACE inhibitor and ARB’s
ACE inhibitors and ARBs are effective in preventing migraines by promoting vasoconstriction and reducing pro-inflammatory cytokine levels. Like beta blockers, these are traditionally used to help lower blood pressure but also can be helpful for migraine.
These medications are generally well-tolerated and less expensive than some other preventive options, making them a viable choice for many patients. (7)
| Angiotensin-converting enzyme (ACE) Inhibitors, Angiotensin II receptor blocker (ARB) | Brand Name |
| Candesarten | Atacand, Generic |
| Lisinopril | Zestril, Prinvil, Generic |
Calcium channel blockers for migraine
Calcium channel blockers, such as verapamil, are effective in migraine prevention, though not all are FDA-approved for this use. Verapamil is often used for those with co-occurring conditions like high blood pressure, while flunarizine, available in some European countries, is specifically approved for migraine prevention. (8)
| Calcium Channel Antagonists | Brand Name |
| Flunarazine (not available in the US) | Sibelium |
| Verapamil | Verelan PM, Verelan DR, Calan, CalanSR, Generic |
| Diltiazem | Cardizem |
Antidepressants for migraine
Antidepressants are another category of medications used for migraine prevention. They are particularly beneficial for those with co-occurring depression or anxiety. Tricyclic antidepressants, such as amitriptyline, have been shown to be effective, though they may have side effects like weight gain.
SSRIs and SNRIs can also be helpful, though they are not typically used as standalone treatments for migraine.
Tricyclics
Amitriptyline is the only tricyclic antidepressant that has been shown to be consistently effective for the treatment of migraine and chronic tension-type headache. Sometimes amitriptyline has a side effect profile that patients find unfavorable (specifically weight gain), so nortriptyline is often prescribed instead. The drawback here is that it is not as well studied as amitriptyline as a headache preventive. Even so, many choose nortriptyline over amitriptyline for it’s lower side effect profile. A positive side effect of both is that they can often help with sleep.
| Tricyclic Antidepressants | Brand Name |
| Amitriptyline | Elavil |
| Nortriptyline | Pamelor |
| Protriptyline | |
| Doxepin | Sinequan |
SSRIs & SNRIs
According to a 2011 CNS Neuroscience study, “Migraine and chronic tension-type headache patients are between two and five times more likely to suffer from a depressive or anxiety disorder than are individuals without headache”. (9) Treating co-morbid conditions of depression, anxiety and migraine can benefit by adding an antidepressant to migraine prevention therapy.
While the SSRI’s and SNRI’s can help manage depression and anxiety, in some people it can also increase head pain. (10)
Being aware of this potential positive side effect can help patients and doctors make decisions about which medications (shown below) (11) to use and at what dose to be effective for both migraine and depression and/or anxiety. Most have shown to not be effective as a standalone treatment for migraine AND depression/anxiety.
Instead it is recommended “SSRI use should be limited to the treatment of depression or anxiety in the headache patient, but not primarily as headache preventives.” (12) The main SNRI medication that helps those with vestibular migraine is venlafaxine. This is often prescribed as a first line medication along with tricyclic antidepressants. Dr. Timothy Hain talks about treating vestibular migraine with these medications on his website.
| Selective Serontonin Reuptake Inhibitor (SSRI) | Brand Name |
| Citalopram | Celexa |
| Escitalopram | Lexapro |
| Fluoxetine | Prozac |
| Paroxetine | Paxil, Pexeva |
| Sertraline | Zoloft |
| Selective Serotonin/Norepinephrine Reuptake Inhibitor (SNRI) | Brand Name |
| Venlafaxine | Effexor |
| Duloxetine | Cymbalta |
| Desfenlafaxine | Pristiq |
Anticonvulsants for migraine
Anticonvulsants like topiramate, sodium valproate, and gabapentin are effective in reducing the frequency and severity of migraine attacks. Lamotrigine has also been shown to be effective at reducing the severity of aura and the attack frequency for patients who have migraine with aura. (13) However, side effects can make these medications less tolerable for some patients. Starting at a low dose and increasing slowly can help mitigate these side effects, making the medication more manageable.
This review of Topamax for migraine is very helpful in cutting through some of the confusion about this medication found on social media.
Anticonvulsants for migraine, especially topiramate and sodium valproate are commonly prescribed and sometimes required by insurance companies before approval of more expensive medications.
| Anticonvulsants | Brand Name |
| Topiramate, Topiramate XR | Topamax, Topamax XR, Generic |
| Sodium Valproate | Depakote, Epilim, Epilim Chrono, Episenta, Generic |
| Gabapentin | Neurontin |
| Pregabalin | Lyrica |
| Zonisamide | Zonegran |
| Levetiracetam | Keppra |
| Lamotrigine | Lamictal |
Muscle relaxers for migraine
Muscle relaxers are another option for migraine prevention, particularly for those who also struggle with sleep. These medications work on brain mechanisms involved in migraines, providing dual benefits of muscle relaxation and improved sleep. (15)
| Muscle Relaxants | Brand Name |
| Cyclobenzaprine | Flexeril |
| Tizanidine | Zanaflex |
| Baclofen | Lioresal |
NSAIDs and triptans for menstrual migraine
Menstrual migraine can be one of the most difficult to treat. The medications listed below are effective in treating menstrual migraine, however following the dosing schedule requires being able to predict the start of the menstrual cycle. Two days prior to the menstrual cycle starting, the medications can be taken twice daily and continue that dosing schedule for 5-7 days depending on the medication prescribed. Five days for naproxen/naproxen sodium, naratriptan and low dose sumatriptan, six days for frovatriptan and seven days for zolmitriptan. (16)
| NSAIDs and Triptans | Brand Name |
| Naproxen/Naproxen Sodium | Naprosyn/Aleve |
| Frovatriptan | Frova, Generic |
| Naratriptan | Amerge |
| Sumatriptan | Imitrex, Generic |
| Zolmitriptan | Zomig |
Miscellaneous Medications
There are some medications that fall into the miscellaneous category. Acetazolamide has been shown to help with migraine attacks associated with flying and altitude as well as those triggered by barometric pressure fluctuations. (17) Spironolactone has been shown to reduce the frequency and severity of migraine that is co-morbid with fibromyalgia. (18) Memantine also reduces the frequency and severity of migraine and is effective when added on to other therapies. (19)
| Miscellaneous Medications | Brand Name |
| Acetazolamide | Diamox |
| Spironolactone | Aldactone |
| Memantine | Namenda |
Nutraceuticals
Many studies have shown the effectiveness of the nutrients in the following table. All are effective for prevention of migraine. (20) (21) (22)
| Vitamins, Minerals, Supplements and Herbs |
| Butterbur (Petadolex) |
| Feverfew |
| Magnesium |
| Vitamin B2 (Riboflavin) |
| Coenzyme Q10 |
| Ginger |
| Melatonin |
Devices
The sTMS was shown to reduce frequency and severity of migraine attacks when patients followed the recommendation of using the device daily. The company that manufactured this device has filed for bankruptcy, so it is unknown about the availability of this device in the future. (23)
Nerivio is a device worn on the arm and works by descending pain modulation via the brainstem. It is both safe and effective. Having it demonstrated can be helpful in making sure everyone is on the same page and gets best results. (24)
The gammaCore device is well tolerated and can be used in the preventive treatment of migraine and chronic cluster headache. It is placed against the neck and activated to stimulate the vagus nerve. gammaCore is thought to reduce the release of glutamate in the brain during a migraine attack and also to disrupt the cortical spreading depression. (25)
Cefaly has been shown to effectively help treat and reduce episodic migraine attacks. (26)
Migraine Strong interviewed a Dr. Courtney White, headache specialist, about several different migraine devices in this helpful interview.
Green light therapy has been shown to reduce the overall severity of migraine attacks. The Allay lamp is one form of green light therapy that uses the narrow band of green light to help reduce migraine symptoms. (27)
| Devices | Brand Name |
| Vagus Nerve Stimulator | gammaCore |
| External Trigeminal Nerve Stimulator | Cefaly |
| Non-invasive neuromodulation device | Nerivio |
| Single-pulse transcranial magnetic stimulation | sTMS by eNeura |
| Narrow band green light therapy | Allay Lamp |
Other Miscellaneous Preventive Treatments
A course of six sessions of full body acupuncture has been shown to be effective in the prevention of migraine. In 3-6 months, migraine attacks were halved for half of the people participating in the 100 person study. (28)
Biofeedback is “effective in reducing the frequency of migraines with clients using medication resulting in a more favorable outcome (70% experiencing at least a 50% reduction in headaches) than just medications alone (50% experience a 50% reduction)”. (29) Biofeedback can be learned through a trained professional or some apps that are on the market or will be soon.
| Miscellaneous Treatments |
| Acupuncture |
| Biofeedback |
Different Approaches to Preventive Therapy
While looking at all of the medications listed in the tables above can be overwhelming, headache specialists and other doctors interested in migraine can combine those and others not listed to tailor a preventive therapy for each individual patient. Each of the writers for Migraine Strong have different preventive therapies for migraine and they are all effective.
Conclusion
I hope this guide has shown that there are lots of different options out there to help us manage migraine. Chat with your doctor about options and join the Migraine Strong Private Facebook group to talk to others in the same boat.
References:
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640499/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990571/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640499/
- https://www.medscape.com/viewarticle/804034_14
- https://www.medscape.com/viewarticle/804034_14
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990571/
- https://www.neurologyadvisor.com/conference-highlights/aan-2019-conference/ace-inhibitors-arbs-may-be-effective-migraine-prophylactic-treatments/
- https://www.medscape.com/viewarticle/804034_14
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493799/
- https://www.practicalpainmanagement.com/patient/conditions/headache/6-medications-can-make-migraine-worse
- https://www.mayoclinic.org/diseases-conditions/depression/in-depth/ssris/art-20044825
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493799/
- https://jnnp.bmj.com/content/76/12/1730
- https://www.medscape.com/viewarticle/804034_14
- https://www.nyheadache.com/blog/muscle-relaxants-for-migraines/
- https://www.neurologytimes.com/headache-and-migraine/treating-menstrual-migraines
- https://www.nyheadache.com/blog/migraine-drugs-a-to-z-acetazolamide/
- https://pubmed.ncbi.nlm.nih.gov/29913681/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603889/
- https://www.medscape.com/viewarticle/804034_14
- https://americanheadachesociety.org/wp-content/uploads/2018/05/Alan_Rapoport_-_Migraine_Prevention_Medications.pdf
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640499/
- https://www.migrainetrust.org/living-with-migraine/treatments/transcranial-magnetic-stimulation/
- https://www.neurologylive.com/clinical-focus/experts-weigh-in-on-early-clinical-experience-with-nerivio-migra-in-acute-migraine
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970666/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440493/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939697/
- https://www.cochrane.org/CD001218/SYMPT_acupuncture-preventing-migraine-attacks
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826281/
Very comprehensive article. Thank you.