When faced with the vexatious disorder fibromyalgia -- multiple symptoms, no specific diagnostic test, no clear treatment -- Dr. George T. Griffing offers patients one piece of advice.

"I tell them they're not nuts," says Dr. Griffing, director of the general internal medicine division at the St. Louis University of School of Medicine. "I tell them there's no easy solution. There's no magic bullet."

Dr. Griffing isn't being flippant. Fibromyalgia's mixture of pain, muscle discomfort, fatigue, sleep problems and other symptoms has prompted many physicians in the past -- and present -- to pass off a patient's complaint as emotional or psychological.

One doctor told the husband of Phyllis Talarico "that I was just looking for attention," says the patient assistance coordinator for the National Fibromyalgia Association, a patient-advocacy organization based in Anaheim, Calif. Felled suddenly by pain and a batch of symptoms in 1992, Talarico says a neurologist and radiologist couldn't agree on whether she had a stroke.

"Two years and 17 doctors later, I had a diagnosis," says Talarico, who started a fibromyalgia support group in 2000. She took a strong pain reliever for eight years. Then she tried a drug designed for treating Parkinson's disease and restless leg syndrome, which has provided more relief.

Talarico's experience with doctors and drugs is typical among patients whose symptoms vary considerably. The Food and Drug Administration estimates that 3 million to 6 million Americans have fibromyalgia, most of whom are women and most of whom develop symptoms in early to mid-adulthood.

Until recently, the FDA hadn't approved any drugs specifically for fibromyalgia, leaving doctors to prescribe many types of medications -- antidepressants, painkillers, sleep-disorder drugs, epilepsy treatment -- in hit-or-miss efforts to alleviate the suffering.

This practice, called off-label prescribing, is perfectly legal: Doctors may prescribe a drug for any disease once the FDA has approved the drug for a single condition or disorder.

However, companies cannot market a drug for off-label uses. Thus, the agency's endorsement of a fibromyalgia treatment gives companies a distinct marketing edge in promoting a drug to doctors and advertising it to patients. To get FDA support, companies must conduct successful clinical trials.

THE FDA ACTS

Two companies have completed enough testing to secure FDA approval, and more companies are in hot pursuit.

In June 2007, New York-based Pfizer became the first company to get the FDA's OK for fibromyalgia with Lyrica. Pfizer also has an experimental compound in clinical trials. (Pfizer also has a St. Louis connection: Locally, it employs 1,200 people, focusing on drug research, and is building a new research facility in St. Louis, which will consolidate its research efforts here.)

Before the FDA approval, fibromyalgia patients had been using Lyrica off-label because the FDA had approved it for epilepsy, nerve pain linked to diabetes and pain associated with shingles.

Lyrica isn't a magic bullet. "Consumers should understand that some patients did not experience benefit in clinical trials," a top FDA official said last year after the agency endorsed Lyrica.

In January, the FDA issued an alert about suicidal behavior for 11 epilepsy drugs, including Lyrica, based on a review of clinical trials covering nearly 44,000 patients.

The FDA found the risk of suicidal behavior or suicidal thinking was twice as high among users of epilepsy drugs versus people taking a placebo. Although the absolute risk was small -- 0.43 percent for those using epilepsy drugs to 0.22 percent among placebo-takers -- the FDA says doctors should monitor these patients closely.

In mid-June, Eli Lilly, of Indianapolis, received FDA approval of Cymbalta for fibromyalgia. Cymbalta has been used off label, too, because it already had FDA approval for depression, generalized anxiety disorder and diabetic nerve pain.

Cymbalta carries a black box warning -- the FDA's strongest alert -- that this drug and other antidepressants can increase the risk of suicidal thinking and behavior in children, adolescents and young adults. The warning says "patients of all ages" taking antidepressants should be monitored for "clinical worsening" or unusual changes in behavior.

The next drug on the FDA schedule will be milnacipran from New York-based Forest Laboratories. (The St. Louis-based Forest Pharmaceuticals, a subsidiary of Forest Laboratories, produces prescription drugs for the U.S. market.)

Forest has been working with a small U.S. company, Cypress Biosciences, which licensed the drug from a French company. Although milnacipran is sold in more than 50 countriesas an antidepressant by its French developer, it isn't available in the U.S.

Milnacipran's path to a fibromyalgia treatment has been difficult. In 2005, a clinical trial failed to meet its goal of relieving pain. But in November 2007, the companies announced results of two clinical trials that achieved statistically significant improvements in pain relief.

Major side effects for milnacipran were nausea, constipation, hot flushes, increased heart rate, vomiting and hypertension.

Forest and Cypress have asked the FDA to approve the drug, and the agency is expected to decide by October. The independent firm Sagient Research, which tracks pharmaceutical and biotechnology developments, gives milnacipran a better than 80 percent chance of approval. The firm says eight other compounds are in mid- to late-stage clinical testing, adding that FDA action on other drugs is at least two years away.

LOOKING FOR ANSWERS

Companies are testing so many different types of drugs because researchers still can't pinpoint the cause of fibromyalgia.

The National Institutes of Health says the disorder has been linked to traumatic events or stressful events or repetitive injuries.

People with certain diseases -- such as lupus and rheumatoid arthritis -- "may be more likely" to have fibromyalgia, the NIH says. These diseases are linked to the body's immune system.

Researchers believe the key to fibromyalgia lies in how the body processes pain signals. Some scientists believe there's a genetic link, NIH says.

Peruse www.clinicaltrials.gov and you'll find evidence of 126 clinical trials, including more than 35 still recruiting patients. Researchers are looking at drugs that treat depression, narcolepsy, substance abuse, Parkinson's disease and insomnia, among others. They are testing new compounds as well as the expanded use of existing drugs.

They're also investigating acupuncture, tai chi, biofeedback and cognitive therapy. And they're investigating electrical stimulation of a nerve in the brain and the noninvasive use of changing magnetic fields to produce an electrical current that affects the brain.

"The science of fibromyalgia is still in its infancy," says Dr. Patrick Wood, chief medical advisor of the National Fibromyalgia Association. He predicts researchers eventually will determine that there are several types of fibromyalgia and that companies will work on drugs to target specific types of the disorder.

"We're easily three to five years away from making that concrete connection," he says. "Today's drugs take more of a shotgun approach."

In his private practice, Dr. Wood is willing to prescribe some off-label drugs based on different symptoms for different patients. Just because the FDA has approved a drug for fibromyalgia, that doesn't mean it will work. "You have to treat six patients with Lyrica to get one response," he says.

Before the FDA approved Lyrica, he says, some doctors eschewed prescription drugs because "they say it's not really a disease if there's no drug."

He says conservative physicians will only prescribe an FDA-approved medication even if the drug's mechanism of action doesn't address specific symptoms. Others will try different types of off-label drugs.

Because there's no diagnostic test, doctors can be confused by a patient's condition, especially if the patient is also suffering from another disease with overlapping symptoms.

To test for fibromyalgia, physicians check a series of tenderness points on the body -- a diagnostic protocol developed by the American College of Rheumatology (ACR). They also examine symptoms to rule out other diseases. If a patient has a "history of widespread pain" and exhibits pain in least 11 of these 18 tenderness points when touched, that's a sufficient diagnosis of fibromyalgia for ACR.

Because fibromyalgia patients often have other ailments, medical experts warn about taking too many medications at once for fear of dangerous drug interactions. That's true, too, for patients who take a mixture of pharmaceuticals and dietary supplements and for patients who see several doctors.

Shannon Koch, of Columbia, Mo., says her current physician keeps track of her treatments which, in one year, have included vitamin B-12 injections, dietary supplements, Lyrica, an insomnia drug, an antidepressant and strong painkillers -- as well as physical therapy.

She's trying to find the right combination to solve the muscle aches, pain and insomnia that have kept her from working for five years. "I can't stand for too long, and I can't sit for too long," she says.

Like many patients, it took Koch several years, several doctors and several tests -- X-rays, blood tests, an MRI -- before getting the right diagnosis.

"You wake up one morning," she says, "and you find you're not compatible with your body."

Robert W. Steyer, a freelance journalist living in New York, was a business reporter for the St. Louis Post-Dispatch.