Approximately 28 million Americans older than the age of 12 suffer from migraine headaches. Around 18% of women and 6% of men in the United States suffer from migraine headaches. Around 38% of those with a migraine headache need to be on preventive therapy; whereas, only 3% to 13% of migraine sufferers use preventative therapy.
Prophylactic migraine treatment should be considered in patients with more than 3 migraine headaches per month or at least 8 headache days in one month. Patients with severe debilitating headaches despite appropriate acute treatment or those who are intolerant or have contraindications to acute therapy. Prophylaxis should also be considered in patients with medication overuse headaches, certain migraine subtypes like hemiplegic migraine, basilar migraine, migraine with prolonged aura, or if the patient prefers.
Prophylactic treatment for Migraine Headache
It is important to determine the frequency, duration, and severity of headaches and any triggers that may precipitate the headaches.
All patients with migraine headaches should maintain a headache diary to determine the frequency, severity, and duration of headaches. It also helps identify any triggers that can cause a migraine headache. Some common triggers include environmental factors such as noise, odor, medications (like OCP, HRT, H2 blockers), food (cheese, wine, chocolate), and behavioral factors such as sleep deficit or excessive sleep. If triggers can be identified and modified, preventive drug therapy may not be needed. 
1. Pharmacological therapies for migraine prevention
Various medications are available for migraine prophylaxis and prevention. Choosing the right agent is important. The efficacy, side effects, contraindications, cost, and compliance should be considered when deciding the right agent. It is also crucial to consider comorbid medical conditions and drug interactions. Efficacy of treatment can be assessed only after a 2 to 3-month trial; a full trial may take up to 6 months. Always start at a low dose and titrate up slowly. Monotherapy is preferred as there are no significant benefits of using more than one drug unless indicated for other comorbid conditions. Patients should be re-evaluated, and medications preferably discontinued after 1 year, even if they show improvement in symptoms. Successful therapy is defined as a reduction of migraine attacks by at least 50%.
Migraine attacks are associated with neuronal activation, which is thought to be due to cortical spreading activation (CSD) or a brainstem generator. Preventive medications inhibit CSD through various mechanisms, such as blocking calcium and sodium channels, blocking gap junctions, and inhibiting matrix metalloproteinases.
Propranolol is the most common and one of the most effective first-line medications used for migraine prophylaxis. The starting dose is 40 mg to 160 mg and can go up to 320 mg daily. It may take up to 12 weeks at an adequate dose for therapeutic benefits to become apparent.
Other beta-blockers that can be used are timolol, atenolol, and metoprolol. They should be considered in patients with underlying cardiovascular disease. Common side effects of this group of medications are fatigue, nausea, dizziness, decreased exercise tolerance, and depression. Contraindications include severe asthma, peripheral vascular disease, severe bradycardia, and heart blocks.
Depakote and sodium valproate are two anticonvulsant drugs that are used for migraine prophylaxis. They are amongst the first-line agents used for migraine prevention. They are particularly useful for prolonged and atypical migraines. Common side effects include nausea, drowsiness, hair loss, tremors, and hyperammonemia. They are contraindicated in patients with severe liver disease and pancreatitis. Sodium valproate cannot be used in pregnancy because of teratogenicity.
Topamax is another drug used as a first-line treatment option for migraine prophylaxis. Topamax has comparable efficacy to propranolol for preventing migraine headaches. It should be started at a low dose with 25 mg daily and slowly titrated up to 100 mg twice daily. Patients should continue treatment for at least 2 to 3 months before the treatment efficacy is evaluated. Common side effects include memory and concentration problems, paresthesia, fatigue, nausea, and anorexia. Topamax can cause metabolic acidosis and also precipitate kidney stones, acute myopia, and angle-closure glaucoma.
Gabapentin has little efficacy for migraine prevention. The recommended dose is from 1200 to 2400 mg per day. Common side effects include somnolence and dizziness.
Amitriptyline is shown to have some benefit in migraine prevention. It may be more effective than propranolol in mixed migraine-tension type of a headache. Response to treatment can be seen in up to 4 weeks and is more rapid than with beta-blockers. The dose used is 20 to 75 mg daily.
Another antidepressant that is probably effective in migraine prevention is venlafaxine. It is probably as effective as amitriptyline. The dose used is 150 mg daily. Fluoxetine has also been used for migraine prophylaxis. Common side effects include weight gain, drowsiness, dry mouth, and urinary retention. Contraindicated in concurrent use with monoamine oxidase inhibitors (MAOIs).
The efficacy of calcium channel blockers in the preventive treatment of migraine is weak.
Verapamil has shown weak efficacy in preventing migraines. It is used as one of the second-line pharmacological options for migraine prophylaxis.
Flunarizine is a nonspecific CCB that has shown evidence of some efficacy. It is not available in the United States.
- Angiotensin Blockers: ACE-Is/ARBs
Lisinopril and candesartan have some shown some, although weak efficacy for migraine prevention.
They are used for the prevention of menstrual migraine. Start treatment a few days before the anticipated start of the menstrual cycle and continue for the first few days.
Zolmitriptan, frovatriptan, and naratriptan have shown benefits in the short-term prevention of menstrual-related migraines. They are started several days before the expected onset and continued for 5 to 6 days.
- Calcitonin Gene-Related Peptide Therapy
U.S. FDA approved Erenumab for the treatment of migraine prevention in May 2018. It is a monoclonal antibody that mediates transmission of migraine pain by binding to the calcitonin gene-related peptide receptor. It comes as a monthly subcutaneous injection. Common side effects include injection site reaction, constipation, and cramps.
Some other medications that have some but little efficacy for migraine prevention include Magnesium, Vitamin B2, Coenzyme Q10, Botulinum toxin.
Benefits of Botulinum toxin A have not been statistically proven for the treatment of an episodic migraine headache; however, it is proven to be effective for treating chronic headaches.
Methysergide and phenelzine are used as last resorts for severe and refractory cases. Use for more than 6 months can cause cardiac and retroperitoneal fibrosis.
Butterbur and feverfew are two herbal medications available for use for migraine prophylaxis. Studies have failed to prove any substantial benefit with feverfew. Butterbur extract made from underground parts of the plant has been endorsed by the American Academy of Neurology and the American Headache Society to reduce the frequency of migraines.
2. Non-Pharmacological Therapies
Identifying and modifying the trigger if possible. It is important to maintain headache diaries to identify triggers and follow responses when triggers become modified.
Therapies that can help prevent migraines include relaxation, acupuncture, massage, cognitive behavior therapy, and biofeedback techniques.
The FDA approved a transcutaneous electrical nerve stimulation (TENS) device in March 2014 for migraine prevention. More studies are needed to determine its long-term efficacy.
2012 AHS/AAN Guidelines for Migraine Prevention in Adults
Medications are divided into 3 groups:
Level A (medications that have proven effectiveness and should be offered to patients who require migraine prophylaxis): Sodium valproate, valproic acid, propranolol, timolol, topiramate, butterbur.
Level B (medications that are probably effective and should be considered for migraine prevention): Amitriptyline, feverfew, naproxen, fenoprofen, ketoprofen, ibuprofen, magnesium, atenolol, venlafaxine, riboflavin, histamine.
Level C (medications with possible effectiveness and may be considered for migraine prevention): Candesartan, carbamazepine, lisinopril, pindolol, nebivolol, clonidine, cyproheptadine, coenzyme Q10.
Issues of Concern
Migraine Prophylaxis in Children
Propranolol is commonly prescribed for migraine preventive treatment in children, although studies have shown conflicting results. Similarly, topiramate is commonly prescribed for children, but efficacy is questionable.
Data is insufficient for other medications like cyproheptadine, amitriptyline, and valproic acid. Flunarizine is believed to be effective for preventing migraines in children but is not available for use in the United States. 
Migraine Prophylaxis in Pregnancy
It is imperative to maintain a cautious approach. Risks and benefits should be discussed with the patient in detail. Labetalol at a dose of 150 mg twice per day has shown some benefit in pregnant women. Propranolol, topiramate, amitriptyline, fluoxetine, and gabapentin are pregnancy category C drugs. Valproic acid is teratogenic and contraindicated, and the use of lisinopril and candesartan is not recommended for pregnant women.