100 Migraine Drugs, A to Z: onabotulinumtoxinA

OnabotulinumtoxinA (Botox) is a most remarkable medicine. It was first approved by the FDA in 1989 for two eye conditions and since then it received approval for another dozen conditions as varied as excessive sweating, very frequent urination, spasm of muscles, and of course, migraines.

An interesting chain of serendipitous discoveries led to its approval for migraines. A Vancouver ophthalmologist, Dr. Jean Carruthers started using Botox in 1987 to treat blepharospasm (forceful and uncontrollable blinking) and noticed that patients’ wrinkles disappeared. She mentioned this to her husband-dermatologist Dr. Alastair Carruthers who began to inject it for cosmetic reasons. Then a plastic surgeon in California, Dr. William Binder who has been using Botox to treat wrinkles began hearing from his patient that their headaches went away along with their wrinkles.

When Dr. Binder first presented his observation in the early 1990s, he was met with a lot of skepticism. How could Botox, which affects only superficial muscles and nerve endings, help migraine, which begins deep in the brain? And what does a plastic surgeon really know about headaches? I was also a bit skeptical but faced with many patients whose migraines would not respond to usual treatments, I decided to look into this.

I discovered that by weight, Botox is the deadliest poison known to man. At the same time, it is safer than aspirin, ibuprofen, or acetaminophen because obviously any drug can become a poison depending on the amount you ingest. Thousands of people die every year from bleeding ulcers or kidney problems caused by aspirin and ibuprofen and thousands die from liver damage caused by acetaminophen, but deaths from Botox are extremely rare. Last year I visited Allergan’s manufacturing plant in Ireland where all of the world’s supply of cosmetic and medical Botox is manufactured. On our tour of the plant, we were told that one year’s supply of Botox weighs 1 gram. Each 100-unit vial of Botox contains 5 nanograms (0.000000005 gram) of the toxin.

I was the first neurologist in New York to use Botox for migraines and even though I am a headache specialist and not a plastic surgeon, many of my colleagues were disdainful. Others came to learn the technique I developed. Even before the FDA approval, over 200 doctors from around the world visited our center. It took us a few years to convince Allergan to do clinical trials and then quite a few years to conduct these trials, but in 2010 the FDA approved Botox for the treatment of chronic migraines.

I’ve written several blog posts on the various aspects of Botox therapy including its use off-label (without having an FDA approval) for children with migraines, TMJ disorders, trigeminal neuralgia, post-concussion headaches, common avoidable problems seen with the injections, and about underutilization of this remarkable drug for the treatment of migraines.

Incredibly, the chain of serendipitous discoveries continues – patients treated for migraines reported to feel depressed and this was not because their headaches improved since depression also lifted in patients whose migraines did not improve. And so, this 30-year-old drug continues to find new uses.