Pfizer Reports Epilepsy Drug Treats Anxiety, Lacks Side Effects

Evidence is growing that epilepsy drugs are useful in treating seemingly unrelated conditions, including anxiety.

Pfizer Inc. just unveiled data showing that its experimental epilepsy medicine, pregabalin, appears to be as effective at treating severe anxiety as several established medicines used for the illness, but doesn't have two of those drugs' biggest drawbacks, addiction and sexual dysfunction.

If that proves to be true after further testing, pregabalin could join a number of drugs that were first developed to control epileptic seizures and are more frequently prescribed to treat a host of seemingly unrelated conditions ranging from bipolar disorder to migraines.

Researchers believe that pregabalin, and perhaps other related drugs, could someday supplant the current medicines used to combat severe anxiety.

"We hope that a drug like pregabalin can replace benzodiazepines," says Karl Rickels, a professor of psychiatry at the University of Pennsylvania, Philadelphia, who led the study. The benzodiazepine class includes well-known tranquilizing drugs such as Xanax. Last year, 30 million prescriptions were filled at retail pharmacies for alprazolam, the generic name for Xanax, making it one of the most prescribed drugs in the country, according to NDCHealth, Atlanta.

Pfizer, which funded the new studies, expects to file for Food and Drug Administration approval of pregabalin as a treatment for epilepsy, generalized anxiety disorder and persistent nerve pain later this year.

Though most unconventional uses of epilepsy drugs haven't yet been approved by regulators, doctors now commonly prescribe anticonvulsant medicines for many other illnesses. For instance, the drugs are used to reduce persistent pain caused by nerve damage. Lately, these drugs have also been used to treat conditions that are even further afield, including obesity and bulimia.

Indeed, when physicians mention the epilepsy drugs as options for patients, about a third of the time it is in relation to epilepsy and a third of the time for bipolar illness, which previously was called manic depression. Migraine prevention and a host of other uses account for roughly another third.

How can a drug for controlling epileptic seizures be useful for bipolar illness, migraines and persistent pain? In general, these other neurological and psychiatric conditions stem at least in part from overstimulated nerve cells, called neurons.

In many of these illnesses, the "neurons need to slow down and take a break," says Stephen Silberstein, a professor of neurology at Thomas Jefferson University in Philadelphia. The antiepileptic drugs are designed to tame the most violent neuronal excess, an epileptic seizure. But they also appear to be able to calm related but less extreme conditions. Dr. Silberstein has performed tests of Johnson & Johnson's epilepsy drug Topamax in the prevention of migraines and regularly prescribes the drug for that use.

In the case of pregabalin, the drug targets a switch on nerve cells that controls the flow of electrically charged calcium in and out of the cells. The drug's principal effect is to calm neurons down when they become overloaded, which happens in epilepsy -- and in anxiety.

The two head-to-head studies being presented by doctors Tuesday show that pregabalin appeared to be more effective than alprazolam, a cousin of now available in generic form, and Effexor, an antidepressant made by Wyeth, in quickly taming generalized anxiety disorder, which affects an estimated 5% of people at some point in their lives.

More than 450 patients with the disorder, which is marked by persistent uncontrollable worry or anxiety for at least six months, randomly received four weeks of treatment with one of three different doses of pregabalin, a placebo or alprazolam. A second study in Europe compared various doses of pregabalin, Effexor and a placebo in 426 patients.

The tests indicate pregabalin works more quickly than the antidepressants, like Effexor, and even the anti-anxiety drug Xanax. Acute side effects with pregabalin, such as nausea and headaches, were similar to the acute side effects with the traditional medicines, except for dizziness, which was the problem most frequently reported by pregabalin patients. About a quarter of pregabalin patients in the comparison with Effexor reported dizziness, while a third of the pregabalin patients were dizzy in the comparison with alprazolam. That was twice the rate of dizziness reported by patients taking either of the other medicines.

Severe dizziness was rare with all the drugs, however, including pregabalin. While some antidepressants, including Effexor and Paxil, are approved to treat anxiety, these medicines take a month or more to provide relief and frequently cause sexual side effects. Alprazolam and other similar tranquilizers can be addictive.

If the results seen so far on pregabalin hold up, Dr. Rickels says, the study leader, the drug would have "a big advantage over benzodiazepines," the established standard for treating severe anxiety. Dr. Rickels, a pioneer in the development of benzodiazepine drugs, cautions that the four-week study needs to be confirmed with longer-term results.

Besides Pfizer, Johnson & Johnson and GlaxoSmithKline PLC are actively testing their epilepsy medicines in large clinical tests to support expanded claims for the medicines.

Scientists have yet to determine precisely how epileptic drugs work on so many different conditions. "The mechanism is still catching up with the observation of clinical application," says Mark Pollack, a psychiatrist at Massachusetts General Hospital who was an investigator on one of the pregabalin anxiety studies.

One puzzle is that the epilepsy drugs don't all act on the same chemical pathways. Some mimic a natural substance called GABA, short for gamma-aminobutyric acid, that inhibits neuron activity. Others may block the effects of a neurotransmitter called glutamate that excites neurons. Pregabalin is thought to constrict pores on the surface of neurons that allow electrically charged atoms to pass in and out of the cells.

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