Clonidine doesn't help adolescents with chronic fatigue

By Anne Harding

NEW YORK (Reuters Health) - Clonidine is not an effective treatment for adolescents with chronic fatigue syndrome (CFS), according to a new randomized controlled trial.

While CFS patients who received clonidine showed an attenuation of sympathetic outflow and a reduction in systemic inflammation in comparison to those given placebo, they also had a relative drop in physical activity, Dr. Vegard Bruun Wyller of Akershus University Hospital in Nordbyhagen, Norway, and colleagues found. They report their findings online February 3 in JAMA Pediatrics.

Dr. Wyller and his colleagues have proposed that CFS is due to a persistent stress response or "sustained arousal," possibly precipitated by infection. Clonidine blocks sympathetic nervous system activity and boosts parasympathetic activity, and has also been shown to improve executive function in primates under high arousal conditions, they note.

To investigate whether clonidine might be beneficial in CFS, and to better understand the pathophysiology of the disease, Dr. Wyller and his colleagues enrolled 120 patients with CFS, ages 12 to 18, and 68 healthy controls. The patients were randomized to receive clonidine or placebo for nine weeks, and were then monitored for 30 weeks.

Compared to the healthy controls, the CFS patients initially took fewer steps per day and had a lower digit span backward score and a lower urinary cortisol-to-creatinine ratio. Their fatigue scores, heart rate responsiveness, plasma norepinephrine, and serum C-reactive protein (CRP) were higher than in controls.

During treatment, patients given clonidine averaged 637 fewer steps per day than those on placebo, though the difference was not significant (P=0.07). The clonidine group had significantly lower average plasma norepinephrine and lower serum CRP than the placebo group.

"Low-dose clonidine is not clinically useful in CFS," Dr. Wyller and colleagues conclude.

Dr. Leonard Jason is currently conducting two studies of CFS in adolescents at DePaul University in Chicago. He told Reuters Health, "It's important to find out what doesn't work, and it turns out that clonidine is probably not going to be a treatment approach for kids with what we call ME/CFS." Dr. Jason, who wasn't involved in the new study, noted that CFS is increasingly being referred to as "myalgic encephalomyelitis/chronic fatigue syndrome."

Although the findings were negative, Dr. Jason added, the new study provides useful information about the pathophysiology of the disease. "We are seeing that these kids who are sick seem to have some enhanced sympathetic nervous system activity, they seem to have some low-grade inflammation, attenuated HPA axis, some cognitive impairment, and activity reductions," he said. With treatment, "there was some attenuated sympathetic outflow, there was some systemic inflammation reduction. The fact that even with those pieces there was a negative effect on physical activity suggests that those aren't the primary things that are mediating this illness."

One limitation of the study, according to Dr. Jason, is the fact that patients were not given a thorough psychiatric workup. This means that adolescents with a psychiatric illness that causes symptoms similar to CFS, such as major depressive disorder, could have been mistakenly classified as having chronic fatigue. Also, he pointed out, Dr. Wyller and colleagues mention using the Fukuda case definition of CFS, which is intended for use in adults.

"Just as you need a good medical workup, you need a psychiatric workup," he said. "We need to be very careful about defining cases."

Dr. Wyller did not respond to a request for comments.

This year, Dr. Jason noted, major efforts are underway to improve understanding of ME/CFS. The Institute of Medicine has launched a consensus study to evaluate criteria for diagnosing ME/CFS, and the National Institutes of Health is seeking applications for R01 and R21 grants for investigating the etiology, diagnosis, pathophysiology, and treatment of the disease.

SOURCE: http://bit.ly/N9lVTy

JAMA Pediatr 2014.

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