Ubrogepant (Ubrelvy) is the first oral anti-CGRP drug to be approved by the FDA for the acute treatment of migraine attacks. It was developed by Allergan, manufacturer of Botox, the safest and arguably the most effective preventive treatment for chronic migraines. Allergan took a risk and bought this drug from Merck after Merck ran into problems developing a similar drug, telcagepant. Fortunately, ubrogepant had none of telcagepant’s problems and it was shown to be safe and effective in two large double-blind placebo-controlled trials.

The FDA-approved package insert says that, UBRELVY is a calcitonin gene-related peptide receptor antagonist indicated for the acute treatment of migraine with or without aura in adults. The recommended dose is 50 mg or 100 mg taken as needed. If needed, a second dose may be administered at least 2 hours after the initial dose. The maximum dose in a 24-hour period is 200 mg. It can be taken with or without food. The most common side effects were nausea, seen in 2% of those receiving placebo, 2% of those on 50 mg of ubrogepant and 3% of patients taking 100 mg. The second most common side effect was somnolence, present in 1% of patients taking placebo, 2% of those taking 50 mg and 3% taking 100 mg.

Such a low incidence of side effects is extremely rare with oral drugs, but we also see this with injectable anti-CGRP drugs that are used for the prevention of migraines. The second oral anti-CGRP drug, rimegepant which is awaiting FDA approval, also seems to have very low rates of side effects, which is very reassuring.

The average cost of developing a new drug is $2.6 billion, which means that by necessity new drugs are expensive. This means that insurance companies will require that migraine patients first try and fail generic versions of triptans, such as sumatriptan (Imitrex) or have a contraindication to taking a triptan. Contraindications for the use of triptans include cardiovascular disease (coronary artery disease, strokes, heart attacks, etc.), uncontrolled hypertension, and a few other. Fortunately, ubrogepant can be safely used in such patients.

Oral triptans work well in about 60% of patients, which leaves millions of migraine sufferers without an effective abortive therapy and for these patients, the introduction of ubrogepant could be life-changing.

Metoprolol (Toprol) is one of the beta-blockers, drugs used for the treatment of hypertension and other heart conditions. It is one of the three beta-blockers (the other two are propranolol and timolol) that are included in the American Academy of Neurology guidelines for the preventive treatment of migraines.

A large double-blind study showed that metoprolol (200 mg/day) was more effective than aspirin (300 mg/day) in achieving 50% migraine frequency reduction (45% vs 30%). No significant side effects were reported in either group.

A small study reported that metoprolol (50–150 mg/day) had similar efficacy to nebivolol (another beta-blocker), 5 mg/day in reducing migraine attacks.

Metoprolol, unlike propranolol and timolol, is a selective beta-blocker, which means that it has a much lower chance of triggering an asthma attack in those who suffer from asthma or prone to occasional asthma attacks.

Some of the side effects that can occur with all beta blockers, including metoprolol, are tiredness., dizziness, constipation, blurred vision, chest pain, slowing of the heart rate, which can interfere with aerobic exercise, and other. Migraines are most common in young women many of whom have low blood pressure, which makes them more likely to develop dizziness and tiredness. It can also interfere with the best preventive treatment of migraines – regular exercise.

I reserve beta-blockers for those with normal or high blood pressure, those with rapid heart beat, and anxiety. It helps physical but not mental manifestations of anxiety – sweating, shaky voice, and fast heart rate. Beta-blockers are proven to help and are often taken in small doses for performance anxiety before giving a speech, presentation, or musical performance.

Methylergonovine (Methergine) is used intravenously or in a tablet form after childbirth to help stop bleeding from the uterus. Methylergonovine belongs to the class of drugs known as ergot alkaloids. A drug in this class that is in wide use for the treatment of migraines is dihydroergotamine (DHE). DHE is one of the most effective drugs for the treatment of an acute migraine when given by injection.

Methysergide (Sansert) was another drug in this class and in a tablet form was used for the prevention of migraine and cluster headaches. It was very effective, but because of a very rare but serious side effect was withdrawn from the market. This was unfortunate because a small group of patients for whom other drugs were ineffective were glad to take that risk in exchange for significantly improved quality of life.

After the withdrawal of methysergide, the only oral ergot drug left on the market was methylergonovine and headache specialists continue to use it for their difficult to treat migraine and cluster patients. Methylergonovine was first reported to be effective for the treatment of migraines with medication overuse in an open-label trial of 60 patients in 1993. Of these 60 patients, 44 or 73% improved.

Another uncontrolled trial of methylergonovine in 20 cluster headache patients also showed it to be very effective. Intravenous infusion of this drug given to 125 migraine patients presenting to the emergency room provided pain freedom after one hour in 74%. This was also an uncontrolled, open-label study, which means that placebo effect very likely played a role.

This being an ergot alkaloid, we have to assume that its prolonged use also has the potential to cause serious side effects similar to methysergide. This side effect is fibrosis, or the development of scarring around kidneys, heart, or lungs. Even though it is very rare, this is a greatly feared side effect because it has no treatment and can lead to loss of function in kidneys, heart or lungs. It is speculated, but not proven, that stopping the drug for a month after 3 or 6 months of continuous use may prevent this side effect.

Metformin (Glucophage, Glumetza) is a drug for the treatment of diabetes and you will not find any scientific articles if you google “metformin and migraine”. However, I’ve been prescribing metformin to some of my migraine patients with some success. In the absence of controlled trials to prove its efficacy, one can argue that those patients who improved are experiencing the placebo effect. However, there are two possible ways by which metformin can help prevent migraines.

Obesity does not predispose one to migraines, but in those who do suffer from migraines increased weight is associated with an increased frequency and severity of migraine attacks. Since metformin is proven to help reduce weight, this could be one of the mechanisms by which it improves migraines. Weight loss due to metformin has been shown to be sustainable for up to 10 years.

The second possible mechanism is metformin’s direct effect on inflammation, which is one of the major mechanisms involved in migraines.

I usually prescribe metformin to patients who are overweight and I prefer metformin to the most popular migraine preventive drug, topiramate (Topamax). Topiramate can cause difficulty with memory, kidney stones, osteoporosis, acute glaucoma and other serious side effects, while metformin only occasionally causes nausea. If nausea does occur, changing to a slow release form of metformin (metformin ER) usually helps. Metformin can also cause a drop in vitamin B12 level, so it is worth prescribing a vitamin B12 supplement along with metformin. Metformin should not be prescribed to patients with impaired kidney function, so a baseline blood test is necessary.

Another group of patients I prescribe metformin to are those who are not obese, but report having migraines due to low blood sugar – either when they are hungry or after eating carbohydrate-rich foods, which can lead to a drop in blood glucose (so called reactive hypoglycemia). They often report feeling less hungry and not needing to eat frequently to avoid migraines. Metformin works by regulating the release of glucose from the liver to maintain a steady level of glucose in the blood. This is why this drug does not cause a drop in blood glucose level like other diabetes medications and can be taken by non-diabetics.

The starting dose of metformin is 500 mg a day and if necessary, it can be increased to 1,000 and up to 2,000 mg a day.

Metformin has another unproven potential benefit – it may make you live longer. For now, it’s been shown to be the case only in mice, fruit flies and worms.

Meloxicam (Mobic) is a non-steroidal anti-inflammatory drug (NSAID) which is approved for the treatment of rheumatoid arthritis and osteoarthritis in adults and juvenile rheumatoid arthritis in children older than 2 years. Meloxicam tends to be better tolerated than some other NSAIDs. The main side effects of NSAIDs are heartburn (reflux), stomach pain, and peptic ulcers.

Although there have been no trials of meloxicam for the acute or prophylactic treatment of migraine headaches, it is probably as effective as other NSAID that have been tested for migraines. One advantage of meloxicam is that the effect of a single dose lasts all day. This makes it particularly suitable for the prevention of migraine attacks. It is also available in a liquid form, which can work faster than a solid tablet and speed of onset can be important when using it for acute therapy since faster acting drugs tend to be more effective. Meloxicam tablets are available in 7.5 and 15 mg strength.

An abstract presented at the recent meeting of the International Headache Society describes a new combination product in development for the acute treatment of migraines, which includes meloxicam, 20 mg with rizatriptan (Maxalt), 10 mg. This is a product similar to the combination of naproxen with sumatriptan (Treximet) and just like Treximet is likely to be more effective than either drug alone. However, being a branded drug it is likely to be much more expensive than generic drugs and not likely to be covered by most insurance plans. The insurers usually require that a patient first tries taking sumatriptan and naproxen as separate tablets and if that does not work, will occasionally pay for Treximet. I do have a small number of patients who respond much better to Treximet than to sumatriptan and naproxen taken as separate pills. This can be due to several factors. Most commonly, certain generics may not dissolve as fast as the branded product. Another possible explanation is that the acidity of NSAIDs such as naproxen or meloxicam facilitates absorption of triptans, which could be more pronounced if they are in close contact.

Mefenamic acid (Ponstel) is one the nonsteroidal antiinflammatory drugs (NSAIDs) and like all other NSAIDs it is being used for the treatment of acute migraine attacks.

Mefenamic acid is popular for the treatment of menstrual migraines, which probably stems from the fact that in addition to the treatment of mild or moderate pain, it is also approved for the treatment of dysmenorrhea, or pain of menstruation. In a small study mefenamic acid was found to be specifically effective for the treatment of menstrual migraines, which can be more severe and more difficult to treat than non-menstrual attacks.

Mefenamic acid was found to be superior to acetaminophen (called paracetamol in Europe), which is no surprise since acetaminophen has little antiinflammatory action and therefore does not reduce inflammation that occurs during a migraine attack.

Ergotamine was the mainstay of migraine treatment before the introduction of triptans in 1992. A study comparing ergotamine with mefenamic acid was found them to be equally effective, but ergotamine caused more side effects, especially nausea, which is a common side effect of ergot derivatives.

A small trial suggests that it can be also used for the prevention of migraines and it is as effective as propranolol.

For the treatment of pain and primary dysmenorrhea, the initial dose is 500 mg, followed by 250 mg every 6 hours, as needed. Just like other NSAIDs, it can cause heartburn, stomach upset, bleeding ulcers, and other side effects.