Botox.(botulinum toxin – a protein )

Beyond erasing wrinkles, Botox can now help people who spend more than half their lives in headache agony. But is there enough evidence to support treating chronic migraine sufferers with regular shots of the toxin around the head and neck? Doctors are divided

What is Botox?

Botox is the trade name for botulinum
 toxin – a protein produced by the Clostridium botulinum bacterium. By blocking the release of a chemical messenger in the brain, the toxin stops muscles from contracting.

Why try preventing migraines with it?
The story starts around 10 years ago, with some of Hollywood's most revered residents – cosmetic surgeons.

"The plastics people suggested that some of their patients had relief from migraine after Botox treatment," says Peter Goadsby, director of the University of California, San Francisco's Headache Centre.

The idea began to spread and clinicians started giving Botox as an "off-label" treatment – that is, in a way not approved by regulators – to people with migraines.

Allergan, the pharmaceutical company that developed Botox, soon cottoned on and started marketing Botox as a migraine treatment. However, with no proof that the treatment worked, last year the company was fined $375 million for unlawful marketing.

Since then, a number of clinical trials have ruled out any significant reduction in normal tension headaches and non-chronic migraine after Botox treatment.

Chronic migraine differs from ordinary migraines and tension headaches, however. In chronic migraine, the
person has a headache on more than 15 days of each month, at least eight of which are migraines.

What is the evidence for using Botox for chronic migraine, then?

Two clinical trials have investigated this. In both, people with chronic migraine received a series of five 12-weekly rounds of injections of either Botox or a placebo. In each round, individuals were given 31 injections at specific sites around the head and neck.

The first trial concluded that the Botox injections had no effect on the number of headaches experienced by those with chronic migraine, but hinted that the number of days affected by migraine might have been reduced.

When the same team looked at the latter outcome in the second trial, they found a 10 per cent reduction in the number of headache days compared with the placebo group.

How is Botox thought to help chronic migraine?
No one knows. The general consensus is that the blocking of muscle contraction isn't involved in headache relief, says Goadsby. Beyond that, researchers are generally stumped.

How solid is the evidence that Botox works?
Solid enough for the US Food and Drug Administration and the UK Medicines and Healthcare products Regulatory Agency: both bodies approved the therapy for chronic migraine last year.

Others remain unconvinced. Jes Olesen, a neurologist at the University of Copenhagen and chief of the Danish Headache Centre at Glostrup University Hospital in Denmark, has identified a number of faults in the trials, listed in a letter to The Lancet in November. His concerns were echoed in an editorial published in Drug and Therapeutics Bu
lletin this month.

Why is there a dispute?
According to Olesen, over half the trial participants overused pain medication, so the researchers wouldn't have been able to tell whether the participants had chronic migraine or medication overuse headache. What's more, it's impossible to hide the fact that people are receiving Botox, he adds – and that would invalidate the double-blind nature of the experiment. "Their facial expressions change," he says.

Even if you were able to get over those issues, the 10 per cent improvement pales in comparison to the usual 20 to 30 per cent required for most approved drugs, he says. "The FDA has committed one of the biggest blunders in regulatory history."

Sheena Aurora, neurologist at the Swedish Pain and Headache Center in Seattle, Washington, and lead researcher in the clinical trials, says the criticisms are "shocking". People with chronic migraine regularly take painkillers, so the trial represents the real-life situation, she argues.

The placebo group saw a 30 per cent response to the injections, compared with a 40 per cent response from the real injection. This indicates that people weren't looking for changes in their appearance to judge pain relief, either, she adds. And as for the 10 per cent improvement of the Botox group over the placebo group: "Who are we to say 10 per cent isn't enough for these patients?"

Goadsby agrees. "People with chronic migraine are highly disabled and have an unmet need for therapy," he says. "Everyone in clinical practice knows that chronic migraine is very difficult to treat."

While academic criticisms of trials are interesting, Goadsby says, they're not helpful to the millions of migraineurs. "Worrying about a little stone on the road is interesting, but we need to look at the bigger picture."

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