Chronic fatigue: try yoga, citalopram, placebo. (Three Studies).

NEW ORLEANS -- Some subgroups of patients with idiopathic chronic fatigue respond to treatment with the antidepressant citalopram, some benefit from yoga, and some demonstrate a significant placebo response, three independent studies have shown.

The hint of promise in these results should be welcome news to physicians stymied by the dearth of known effective therapies for treating chronic fatigue and its associated symptoms, said Dr. Arthur A. Hartz of the University of Iowa, Iowa City.

Patients with chronic fatigue are often given antidepressants based on suspicions that the fatigue may be a symptom of depression. But the effectiveness of such therapy for relieving fatigue symptoms independent of depression is unproved. Anecdotal success may be a function of the select group of patients in which the therapy is attempted--specifically those who exhibit signs and symptoms of depression, Dr. Hartz said at the annual meeting of the North American Primary Care Research Group.

To determine the efficacy of the selective serotonin re-uptake inhibitor (SSRI) citalopram as a fatigue treatment independent of depression, Dr. Hartz and his colleagues compared the response to citalopram treatment (average 20-40 mg/day) in 31 fatigued subjects with that of 76 controls who had similar fatigue symptoms taking a placebo or ginseng (a known ineffective therapy). All of the study subjects had substantial fatigue not related to organic illness or lifestyle behaviors. Patients who met the criteria for depression or who were already taking antidepressants were excluded.

The investigators evaluated the changes that patients experienced during 1- and 2-month periods based on Rand Index of Vitality (RIV) scores, depressive symptom scores, and the presence and degree of associated somatic symptoms, such as headaches and muscle aches.

After 2 months of follow-up, RIV and depression outcomes for all patients taking citalopram did not differ from those of placebo/ginseng patients, although citalopram therapy was associated with improvements in headaches and muscle aches. For two subgroups--those with less severe fatigue at baseline and women with moderate fatigue--RIV and depression scores improved with citalopram therapy.

"The results suggest that SSRIs may be a useful therapy for certain subgroups of patients with idiopathic chronic fatigue," Dr. Hartz noted. They also point to the possibility that chronic fatigue may be caused by neurochemical mechanisms similar to those that cause depression, he said.

In another study, yoga prevailed over many conventional and alternative therapies as an effective fatigue fighter, reported Suzanne Bentler, also of the university.

"Because there are so few tried and true consistent effective treatments for fatigue, patients often experiment with a range of conventional and unconventional therapies. Our goal was to evaluate some of the more common therapies to determine which, if any, should be further evaluated in a randomized controlled trial," Ms. Bentler said.

To this end, Ms. Bentler and her colleagues began a prospective study to evaluate the effectiveness of 39 interventions being used by 199 primary care patients who reported experiencing substantial fatigue for at least 6 months. Only those therapies being used by at least 10 subjects at baseline were considered.

The investigators assessed self-reported interventions in four categories: lifestyle changes, such as exercise and dietary modifications; alternative therapies, including acupuncture and yoga; prescription antidepressant and antianxiety medications; and supplements and herbs, such as calcium and ginseng.

At the end of the 2-year study, yoga was the only therapy linked to a statistically significant positive outcome by linear regression analysis. Of the yoga practitioners, 24% demonstrated a substantial improvement in fatigue, based on a validated scale. Of the remaining patients using other therapies, 7% exhibited similar improvement, but none that could be tied statistically to a specific treatment.

The results suggest that yoga should be evaluated as a fatigue therapy in a randomized, controlled trial, Ms. Bentler said. Physicians "can feel comfortable recommending yoga to their patients with fatigue symptoms" although the results may vary based on the type of yoga practiced, she noted.

Finally, in a study testing the association of patient characteristics and outcome after 1 month for 71 patients with idiopathic chronic fatigue who were treated with placebo, Mary Charlton, R.N., and her colleagues found that patients who believed that their fatigue had a psychological component were more likely than others to demonstrate a placebo response.

Patients on placebo were asked four questions about feelings of fatigue and energy level. The answers were scored on a 6-point scale and evaluated for statistical significance using the Pearson correlation coefficient.

The results suggest two possibilities, said Ms. Charlton, also of the university. Patients who accept the psychological component of their fatigue may respond more to placebo, and patients whose fatigue has more organic causes are less susceptible to placebo. The findings are significant, she said, because a better understanding of patient characteristics that influence placebo response can help physicians enhance the placebo effect of their treatments.