Pregabalin (Lyrica) is an epilepsy drug that is also approved by the FDA for the treatment of neuropathic (nerve) pain associated with diabetes, spinal cord injury, shingles (herpes zoster), and fibromyalgia. It is a controlled drug with a low risk of addiction and abuse, although it is often combined with other illicit drugs. Common side effects include dizziness, drowsiness, difficulty thinking clearly, weight gain, sexual dysfunction, and dry mouth. It also has many other less common side effects.

There are no large controlled trials of pregabalin for migraines only case series and anecdotal reports. However, because it does relieve pain and because two other epilepsy drugs, topiramate (Topamax, Trokendi, Qudexi) and divalproex sodium (Depakote) relieve migraines, at least theoretically it should be also effective for migraines. However, despite the few anecdotal reports, it does not appear to be very effective and often does cause side effects. I rarely prescribe it and have very few patients who benefit from it without side effects.

Propranolol (Inderal) belongs to the beta-blocker family of medications and it was approved by the FDA in 1967 for the treatment of high blood pressure. About a decade later it became the first drug to be approved by the FDA for the preventive treatment of migraine headaches. Propranolol is also used for essential tremor, performance anxiety, fast heart beating (tachycardia), angina, and other conditions. In 1988, a British scientist Sir James Black was awarded the Nobel Prize for the discovery of propranolol.

Propranolol is a very effective drug, but because it can lower blood pressure, side effects such as fatigue, lightheadedness, and fainting can occur. Because it slows down the heart rate it can also make it difficult to exercise, which is one of the best ways to prevent migraines. Propranolol can sometimes worsen pre-existing asthma but newer beta-blockers do not have this problem.

If someone along with migraines has a rapid heartbeat, anxiety, or difficulty making public presentations, this drug can provide dual benefits.

A typical starting dose of propranolol is 60 mg of the long-acting formulation. The dose is then increased to 80, 120, and 160 mg, if needed and if tolerated.

Phenelzine (Nardil) is an antidepressant which was approved by the FDA for the treatment of depression in 1961. It belongs to the family of monoamine oxidase (MAO) inhibitors and it is a very effective antidepressant. However, it is rarely used because of its potential to cause side effects and serious drug and food interactions.

There have been no good trials of phenelzine for the treatment of migraines. One small study compared phenelzine with and without a beta blocker, atenolol. Atenolol is known to help migraines and lowers blood pressure, so it could prevent an increase in blood pressure from phenelzine. Phenelzine worked well with and without atenolol. Another report described 11 patients with refractory (not responding to usual drugs) migraines. Ten of the 11 patients had a greater than 50% reduction in the number of headache attacks. Two patients developed low blood pressure and one, high pressure, which was easily controlled. There was also a case report of dramatic improvement in a patient with chronic and treatment-resistant migraines.

Phenelzine can interact with other antidepressants, appetite suppressants, drugs for attention deficit disorder, some epilepsy drugs, muscle relaxants, certain blood pressure medications, some opioid (narcotic) medications, and other. Foods that can interact with phenelzine include aged cheeses, aged/dried/fermented/salted/smoked/pickled/processed meats and fish, fava beans, Italian green beans, broad beans, overripe or spoiled fruits, packaged soups, sauerkraut, red wine, and some other types of alcohol.

An adverse interaction with these drugs and foods can cause a sudden increase in blood pressure or serotonin syndrome, which can be dangerous. However, it does not mean that every drug and food listed above will always cause a serious reaction. Most people will have mild or no reaction at all and if another drug needs to be added to phenelzine, it can be started at a very low dose, and then the dose can be slowly increased.

Besides drug and food interactions, phenelzine has some unpleasant side effects of its own. These include drowsiness, dizziness, constipation, dry mouth, weight gain, sexual dysfunction, and other.

We have many other antidepressants (tricyclics and SNRIs) and other categories of drugs (CGRP drugs, Botox, epilepsy and high blood pressure medications) that are very effective for the prevention of migraines, so phenelzine is almost never used. I prescribe it only after trying many other preventive drugs but it works exceptionally well for a handful of patients for whom no other drug helps.