Archive
January, 2019 Monthly archive

Tosymra is a product that uses a novel way to deliver sumatriptan through the nasal passages. Unlike other nasal formulations of sumatriptan, Tosymra uses proprietary technology, Intravail, which enhances the absorption of sumatriptan through the nasal mucosa. This allows a dose of 10 mg to achieve similar blood level to that of a 4 mg injection of sumatriptan. Clinical trials have confirmed high efficacy of Tosymra in migraine patients.

Many migraine sufferers experience nausea, which makes oral medications ineffective they take too long to work. Sumatriptan injections can be very effective, but many patients are reluctant to use them and they tend to cause more side effects. Nasal delivery offers a good middle road – better and faster delivery than by mouth without the pain and side effects of an injection.

The regular liquid sumatriptan nasal spray (Imitrex NS) has been on the market for a couple of decades, but it has never become a popular product. This is partly due to the fact that it is not consistently or well absorbed. The spray contains 20 mg of sumatriptan delivered through a relatively large droplets of fluid. Some of it is drips out from the nose, while some is swallowed and gives an already nauseated migraine patient a bad taste in the mouth.

Another formulation of nasal sumatriptan was Onzetra, which delivered powdered sumatriptan through an ingenious device. It required the patient to blow the powder into the nose and it appeared to have good efficacy.  However, it was somewhat cumbersome to use, very expensive (up to $100 a dose) and because of that it never caught on. Onzetra is no longer being sold.

I think that Tosymra is going to be a very useful addition to our lineup of abortive migraine drugs, provided it is reasonably priced and is covered by insurance companies.

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Fluvoxamine (Luvox) is one of the drugs in the selective serotonin reuptake inhibitor (SSRI) class. Unlike other SSRIs, which are approved for the treatment of anxiety and depression, it is approved for the treatment of obsessive-compulsive disorder (OCD), although OCD is often accompanied by anxiety and depression. Fluvoxamine does relieve anxiety and depression as well, but it has been mostly promoted and used for the treatment of OCD.

The SSRIs are not very effective for the prevention of migraines, but a single double-blind study involving 64 patients showed that fluvoxamine is as good as amitriptyline for the prevention of migraines with fewer side effects. It may be best suited for migraine patients who also suffer from OCD, but I would not prescribe it for migraines without OCD.

Fluvoxamine may have more side effects than other SSRIs, such as fluoxetine (Prozac). Potential side effects of fluvoxamine is similar to those of other SSRIs and include nausea, insomnia, somnolence, headache (most drugs have headache as a potential side effect), decreased libido, nervousness, and dizziness. All antidepressants can also increase the risk of suicide.

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Flunarizine (Sibelium) is a calcium channel blocker approved for the preventive treatment of migraines in most countries, except for the US and Japan. In many countries, flunarizine is considered to be a first-line drug for the prevention of migraines.

It is as effective as propranolol (Inderal), a beta blocker which is approved world-wide for migraine prophylaxis (and hypertension). Flunarizine, 10 mg was found to be more effective than 50 mg of topiramate (Topamax), although the average dose of topiramate for migraines is 100 mg. It can take 6 to 8 weeks before flunarizine becomes effective.

Vestibular migraine is characterized by vertigo which can occur with or without headache and is often difficult to treat. One observational study suggested that flunarizine may improve the attacks of vertigo.

The two most common side effects of flunarizine are drowsiness and weight gain, but can also cause nausea, anxiety, depression, insomnia, and dry mouth. I’ve recommended purchasing flunarizine abroad to a few of my patients who exhausted other options. None have remained on it, either because of side effects or lack of efficacy. Clearly, giving it to the most severely affected patients is not a fair way to evaluate a drug, but I’ve stopped recommending it. This is also because of legal and logistical problems in getting flunarizine from outside the US.

In the US, we do have a different calcium channel blocker, verapamil (Calan). It is not FDA-approved for migraines (only for high blood pressure) and it is not as effective as flunarizine for migraines, but is the first-line drug for the prevention of cluster headaches.

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I’ve given myself an injection of Ajovy in November and December with some improvement and without constipation which I had from Aimovig. However, Ajovy did not prevent all of my migraines, especially those caused by red wine, (I received some nice red wine over the holidays) and I still had to take sumatriptan (Imitrex).

This is not at all surprising; I always tell my patients that even the most effective treatment is not 100% effective – with enough triggers migraine will still occur. It is possible that with continued use of Ajovy my migraines would progressively get better, but my headaches are quickly and completely relieved by sumatriptan. Sumatriptan has a 25 year safety record and for over 10 years has been available without a prescription in most European countries (you may want to read my post on the daily use of triptans – it is by far the most popular with over 250 comments).

My next self-experiment is to try to prevent migraines with transcranial direct current stimulation (tDCS). We are about to begin a double-blind sham-controlled study and I will describe it in in an upcoming post.

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Antidepressants are widely used for the preventive treatment of migraine headaches. However, some types of antidepressants are better for this purpose than other. Fluoxetine (Prozac, Sarafem) was the first drug in the family of selective serotonin reuptake inhibitors (SSRIs) to be introduced in 1986. This category of antidepressants became very popular not because these drugs were more effective than the older antidepressants, but because they had fewer side effects.

Because tricyclic antidepressants were known to relieve pain and prevent migraine headaches, when the SSRIs became available, they were also studied for various painful conditions.

Small studies suggested that fluoxetine and similar drugs may be effective for the prevention of migraines. Here is another such small study. However, larger and scientifically more rigorous trials showed no effect of fluoxetine on migraines.

Despite this lack of scientific evidence, SSRIs (escitalopram, or Lexapro, paroxetine, or Paxil, sertraline, or Zoloft) are often prescribed for migraines and some migraine sufferers report feeling better on these drugs. One possible explanation is the placebo effect, but it is more likely to be due to the relief of anxiety and depression with some secondary improvement of migraine headaches. In case of tricyclic and some other antidepressants, their pain relieving properties are independent of their effect on depression.

While SSRIs have fewer side effects than many other antidepressants, they also can cause nausea, dizziness, insomnia, loss of libido, inability to reach an orgasm, and other unpleasant symptoms.

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Red wine is a common trigger for migraines, although we still don’t know the cause or why red wine is worse than white. I was just interviewed for this article in the WSJ along with my friend Mo Levin of the UCSF headache clinic.

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Estrogen can be an effective agent for the treatment of menstrual migraines. Many women report that their migraines tend to occur before or during their period and sometimes with ovulation. For some women menstruation is the only time they get a migraine. The attacks appear to be triggered by a drop in estrogen levels. A steady estrogen level is why 2 out of 3 women stop having migraines during pregnancy and menopause.

Most women with menstrual migraines respond well to sumatriptan (Imitrex) and other triptans. If triptan alone does not provide sufficient relief, adding a nonsteroidal anti-inflammatory drug (NSAID) such as naproxen (Aleve) or ibuprofen (Advil) to a triptan can be very effective.

When this strategy does not work and the periods are very regular, mini prophylaxis is another approach. This means taking a preventive drug for a week, starting a day or two before the expected migraine attack. Mini prophylaxis can be tried with the usual preventive drugs such as beta blockers and also with a triptan, such as naratriptan (Amerge), which is somewhat longer acting than other triptans. Sumatriptan and other short-acting triptans also prevents migraine attacks and not only menstrual ones. Some of my patients who wake up every morning with a migraine take a triptan in the evening and avert the attack. This is somewhat surprising because the half-life of sumatriptan is only 2.5 hours.

If all these treatments fail, continuous intake (skipping the week of placebo pills) of an estrogen-containing contraceptive such as Lo Loestrin maintains a steady level of estrogen and can prevent occurrence of periods as well menstrual migraines and other period-related problems such as PMS, painful cramping, and excessive bleeding. It is very safe to suppress periods for at least a year. Several contraceptives are designed to be taken continuously for 3 months at a time. Unfortunately, in some women this strategy fails and they have breakthrough periods along with breakthrough migraines.

Exogenous estrogen (in contraceptives and for hormone replacement in menopause) should be avoided in women who have migraines with aura because of a slight increase in the risk of strokes. While this risk is very small, if a woman smokes or has other risk factors for strokes, taking estrogen-containing pills is definitely contraindicated. For contraception, such patients can take progesterone-only minipill containing norethindrone (Camila, Ortho Micronor).

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