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.

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.

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.

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.

Erenumab (Aimovig) was the first drug in the family of monoclonal antibodies (mAbs) against calcitonin gene-related peptide (CGRP) approved for the prevention of migraine headaches. CGRP is a substance released during a migraine attack. Erenumab was approved in May of this year, followed by approvals of fremanezumab (Ajovy) and galcanezumab (Emgality) in September. Erenumab is an antibody against the CGRP receptor located on a cell, while the other two drugs are antibodies against the molecule of CGRP. They have very similar efficacy and are surprisingly safe with very few side effects. Erenumab has no contraindications or drug interactions.

All these drugs are delivered by an injection and can cause a local injection site reaction or a rash, but erenumab can also cause constipation. It is possible that with the wider use of these drugs other side effects may become apparent. We have seen a handful of patients whose headaches worsened, a couple who developed fatigue and muscle aches, stomach pains and thinning of hair. The number of such patients is small and it is premature to attribute these effects to the drug. Just like our colleagues across the country, we at the New York Headache Center encourage our patients to report all potential side effects to the manufacturer or the FDA.

Erenumab dose is either a single 70 mg injection or two injections for a total of 140 mg. It comes in a prefilled pen-like device which is very easy to self-administer. It provides dramatic relief to about one in five patients and its overall efficacy is about 50% improvement in 50% of patients. About 30% obtain no relief. We do recommend at least two sets of monthly injections before giving up on erenumab.

Unlike Botox, which is approved for the prevention of only chronic migraines (15 or more headache days each month), erenumab is approved for migraines of any frequency. Usually, we consider preventive therapy in patients who have about 4 migraine attacks a month. Many insurance companies require a trial of two oral preventive drugs (which are extremely cheap) before they agree to pay for erenumab. The cost of erenumab is $575 a month, but the manufacturer offers a free trial and free treatment for up to a year if the insurer refuses to pay for it (you do need to get a denial of payment as well as a second denial upon appeal). The one-year free offer is not available to those on Medicaid or Medicare.

Erenumab and the other two CGRP mAbs are truly breakthrough medications which are changing lives of thousands of migraine sufferers. We are cautiously optimistic that their safety profile will remain as good as it appears to be now.

Eletriptan (Relpax) is one of seven triptans approved for the treatment of an acute migraine. While all triptans are similar (but not identical) to each other in their indications, contraindications, side effects and drug interactions, some are more effective than other. Sumatriptan (Imitrex) is the oldest triptan (approved in 1992) and with many companies making generic copies, it is the cheapest. Sumatriptan, rizatriptan (Maxalt), zolmitriptan (Zomig), eletriptan, and almotriptan (Axert) are similar in their efficacy, but many patients prefer one over another. It is not clear why this may be the case because they all work on the same two very specific serotonin receptor subtypes (5HT-1b and 5HT-1d). I do have a fair number of patients who find eletriptan to be significantly better than other triptans. Generic copies of eletriptan came on the market relatively recently and their price is still relatively high – $10 a pill, compared to $1 for sumatriptan. Brand versions of triptans cost anywhere from $40 for a pill of Maxalt (rizatriptan) to $120 for each pill of Zomig (zolmitriptan). A very rare patient of mine finds that the generic copies are significantly less effective than the brand. It is even more rare for an insurance plan to pay for it.

Eletriptan is available in 20 and 40 mg tablets with the maximum FDA-approved daily dose of 80 mg. However, in some European countries eletriptan is sold in 80 mg tablets and the maximum approved daily dose is 160 mg. I see many patients who are warned by their doctors not to exceed the maximum recommended dose on any particular day and not take a triptan on more than two days a week. The first admonition is supposedly due to the immediate danger of these drugs and the second, due to the risk of medication overuse headaches. Neither prohibition is based on good scientific evidence.

The top five triptans listed above has a very short half-life, which means that they are washed out of the body within a few hours. So if a patient calls me and says that she took a tablet the night before, then another one in the morning and by early afternoon the headache returned, I do reassure her of the safety of taking a third dose. Rizatriptan is the only triptan that is approved by the FDA for up to three doses a day. Since there is nothing unique about rizatriptan, clearly there is no risk in taking other short-acting triptans three times a day as well. Also, there is no documented risk of taking double of the maximum recommended dose of any triptan. This is rare, but some of my patients do very well with 80 mg of eletriptan or 200 mg of sumatriptan, while lower doses are ineffective. In many European countries eletriptan and other triptans are sold without a prescription, indicating their excellent long-term safety profile. This is not to say that triptans have no potential to cause serious side effects, but for a young healthy woman who is a typical migraine sufferer, these drugs are extremely safe.