Anxiety is one of the conditions comorbid with migraines – if you have migraines you are 2-3 times more likely to suffer from anxiety as well. The relationship is bidirectional, meaning that if you have anxiety, you are more likely to develop migraines. Antidepressants are proven to relieve anxiety even in the absence of depression and they are a better long-term solution than anxiety drugs such as diazepam (Valium) or alprazolam (Xanax) because they are not addictive and do not lose their efficacy over time. A unique drug that is used only for anxiety and not depression and does not cause addiction, is buspirone (Buspar).

Several studies suggest that buspirone is effective for the treatment of migraines. In a 74-patient randomized, prospective, parallel group, double-blind, placebo-controlled study (the most rigorous type of study) headache frequency showed a 43% reduction in the buspirone-treated group, but only a 10% reduction in the placebo group. This effect was independent of the presence or absence of anxiety. Similarly, antidepressants prevent migraines even if the patient is not depressed.

Buspirone has a favorable side effect profile and it does not cause withdrawal symptoms, which is often a problem with other anxiety drugs and to a lesser extent, antidepressants.

On June 1, I injected myself with erenumab (Aimovig). I still had to take sumatriptan for an incipient migraine on June 2 and June 5. On Thursday, June 7, I had a glass of red wine (pinot noir) with dinner and had no headache. Last night, June 9, I decided to stress-test my response to erenumab and had a beer before dinner and a big glass of sparkling wine with dinner. In the past, this combination had always resulted in a migraine a few hours later. This time, nothing happened!

And here is an excerpt from an email from a patient who was one of the first to receive Aimovig:

“Hello Doctor,
It has been a week now and I wanted to share with you the outcome.
It’s a very important improvement as I was able to stop taking Relpax compared to 40mg a day!
3-4 times I felt the migraine coming but it was like « stopped » and I was feeling ok.
It happened during the day and at night twice.
Overall it’s a fantastic improvement.”

Certainly, this all could be due to the placebo effect, but I doubt it, especially because my migraines did not stop right after the injection. I should stress that erenumab is not going to help everyone. Clinical trials suggest that about 60% of migraine sufferers will benefit, but this is a very high success rate, especially considering the lack of any significant side effects.

Cheers!

Propranolol (Inderal) and other blood pressure medications in the beta blocker family are effective for the prevention of migraines. In a previous post 4 years ago I mentioned a report of 7 patients whose migraines were aborted with beta blocker, timolol, eye drops that are used to treat glaucoma.

The same group of doctors at the University of Missouri, Kansas City conducted a double-blind crossover study of timolol eye drops for the treatment of acute migraines. The results of the trial were published this month in JAMA Neurology. The treatment consisted of 4 drops of 0.5% timolol (this compares with 10 to 30 mg dose taken orally. Ten patients treated almost 200 migraine attacks. Four participants found timolol highly effective compared with placebo and one patients rated placebo as highly effective compared with timolol. No side effects were observed.

Instilling timolol eye drops is not likely to become widely used for the treatment of acute migraines. However, this treatment maybe worth trying in patients who do not respond or do not tolerate triptans and NSAIDs.

Only about 20% of migraine sufferers experience an aura. The most common type of aura is visual and it typically consists of partial obscuration of vision with colorful zigzags and blind spots spreading over half of the visual field of both eyes. Sometimes, the aura consists of gradual narrowing of the visual fields which ends in tunnel vision or complete loss of vision. The typical duration is 20 to 60 minutes and usually the aura itself is not disabling, but the headache that follows can be more severe than during attacks without aura. Migraine aura can occur without a subsequent headache. In some people aura does interfere with normal functioning and can be more disabling than the headache. In rare instances, the visual disturbance persists for days, weeks, and months.

In such cases I do a battery of blood tests, including for RBC magnesium, vitamin B12, homocysteine, CoQ10 levels, and other. If RBC magnesium level is low or at the bottom of normal range, a gram of magnesium sulfate given intravenously can abort the aura. We sometimes give an infusion of magnesium without first doing a blood test.

Amiloride (Midamore) is a potassium-sparing diuretic (water pill), which means that unlike most diuretics, it does not deplete potassium. It is used to treat high blood pressure, heart failure and to remove excess fluid in the body. It has been reported to reduce aura and headache symptoms in 4 of 7 patients with otherwise intractable aura. Potential side effects of amiloride include dizziness, nausea, stomach pain, and diarrhea.

Other diuretics, such as acetazolamide, which is also used for barometric pressure-induced migraines and furosemide have also been reported to stop a prolonged visual aura. Other approaches to treat a persistent aura include the use of preventive migraine medications, such as a blood pressure medication, verapamil (Calan) or one of the epilepsy drugs, such as topiramate (Topamax), divalproex sodium (Depakote), or lamotrigine (Lamictal). An infusion of divalproex sodium derivative, valproic acid (Depakene) can be also tried.

Alpha-lipoic acid is one of the natural supplements included in this list of 100 migraine drugs. According to a study by Magis and colleagues, a daily dose of 600 mg of alpha- lipoic acid (known as thioctic acid in some countries) was significantly better than placebo in reducing the frequency of migraine attacks, headache days and pain severity. No side effects were reported in this 44-patient study. However, some of my patients have complained of upset stomach, which is not surprising since it is an acid. This was a small study and it does not conclusively prove that alpha-lipoic acid relieves migraines.

The use of this supplement is most proven in the treatment of peripheral neuropathies, which suggests that it may work for other neurological conditions such as migraine. Alpha-lipoic is being investigated as a treatment for multiple sclerosis, Alzheimer’s, diabetes, strokes and other conditions.

Last month Allergan reported that their oral CGRP receptor antagonist, ubrogepant was safe and effective in the acute treatment of migraine attacks (see my post). Today, results of a phase 3 trial of a similar drug, rimegepant were reported. Biohaven is the company developing rimegepant, which it licensed from Bristol-Myers Squibb. Rimegepant was shown to be about as effective as ubrogepant with very few side effects, confirming that one of more of these “gepants” will make it to the market. These drugs are expected to be approved some time in 2020.

One piece of information that was not initially released by Allergan is that 5 patients on ubrogepant developed liver function abnormalities on blood tests, compared to only 1 on placebo. None of the patients taking rimogepant had liver function abnormalities. This could spell trouble for the Allergan drug, as it did for the original Merck drug, telcagepant.

Both Allergan and Biohaven have additional oral CGRP antagonists in development for the preventive treatment of migraines.