Chronic fatigue syndrome has been controversial ever since 1984, when a cluster of cases in an upscale Nevada resort town attracted national attention.

Now a British study in The Lancet is likely to open another chapter in the medical saga.

Comparing four different treatments for CFS, researchers find that psychotherapy and gradual increases in exercise were clearly better than specialist care or an approach favored by many CFS advocates called "adaptive pacing," which helps patients live within their limits.

The results were quite clear," Dr. Michael Sharpe of the University of Edinburgh told Shots. "When a therapist worked with the patient to help them do better over time, it produced better function and less fatigue." Sharpe is the paper's senior author.

The two therapies that proved superior in the study are:

• Twice-a-week cognitive behavior therapy to change the way CFS patients think about their devastating fatigue, or to reduce their fear of exertion; or
• Similarly frequent sessions that gradually increase a patient's activity level, within the patient's ability.

The 641 patients in the study â€" the largest ever in the treatment of chronic fatigue â€" were randomly assigned to different treatments, got six months of therapy, and then were evaluated for fatigue and level of function six months after that.

In a surprise to the researchers, adaptive pacing â€" teaching CFS patients to live within their energy limits â€" didn't reduce fatigue or improve patients' ability to walk longer distances, climb stairs, or engage in daily activities of life, such as grocery shopping.

"It achieved nothing more than just seeing a doctor," Sharpe says. And just seeing a doctor â€" a specialist in CFS â€" wasn't very effective. For what it's worth, all the patients in the study got specialist care, but only one-quarter of them had no other therapy.

All patients rated their own symptoms and how well they were functioning, which were translated into scientifically validated scores. The researchers say they were careful to screen out candidates who didn't meet accepted definitions of CFS, sometimes called myalgic encephalomyelitis.

Study authors point out that psychotherapy and graded exercise came out on top even though patients were less confident in them at the outset.

"I hope the results of this trial will go some way to reassuring some of those people that if this treatment is done by skilled people in an appropriate way, it actually is safe and can stand a very good chance of benefiting them," Sharpe says. But he acknowledges the findings are sure to be controversial.

"There will be some who will be straightforwardly pleased," Sharpe says. "But I think there will be those who are more concerned and suspicious about it."

It might seem strange that people suffering from a lingering, devastating disease like CFS, whose cause remains unknown, would be upset by results that show some treatments actually work better. But people with CFS have learned from bitter experience that any suggestion their symptoms have a psychological component leads many to leap to the conclusion that it's all in their head.

"If you have a condition that people decry and criticize you for, saying it's not really real, it's just psychological, then someone tells you, 'You need a psychological treatment,' it seems like rubbing it in, that people don't believe they're ill," says Sharpe, a professor of psychological medicine.

And indeed, CFS advocates on this side of the Atlantic immediately raised that concern. "The issue with cognitive behavior therapy and graded exercise therapy...have to do with the impression that if these things are effective then it must mean that the condition is all in my head," Kim McCleary, president of the Chronic Fatigue and Immunodeficiency Syndrome Association of America, told Shots. "If you can make it better by changing my illness beliefs, what you're saying to me that I don't have a real illness or a physical illness."

People with CFS and their advocates are also very wary of "graded exercise therapy" â€" partly, it seems, because it may suggest that people with the disorder could get out of bed and push themselves. But a bigger concern is that CFS patients are afraid the approach can backfire, sending them to bed exhausted by post-exertional malaise.

"Far and away the bigger danger is overdoing," says Bruce Campbell, a CFS sufferer who counsels others with the disease. "The number of patients that I've known who were afraid of activity and did too little, I could count them on the fingers of my hands, and I've known several thousand patients."

The British researchers say the rate of serious adverse reactions, such as worsening of fatigue, was no higher among patients in the study who got graded exercise than in those who were counseled to stay within their limits. And no more people in the exercise group dropped out of the study than those in the adaptive pacing group.

The study was funded by Britain's Medical Research Council, a government agency. The U.K.'s National Health Service favors the use of cognitive behavior therapy and graded exercise for CFS.