OBJECTIVE: To provide a preliminary assessment of the efficacy
and safety of fludrocortisone acetate treatment of chronic
DESIGN: A placebo-controlled, double-blind,
random-allocation crossover trial of 6 weeks of
SETTING: An outpatient clinical trials unit.
PATIENTS: Twenty-five participants with chronic fatigue
syndrome (mean age, 40 years; 19 [76%] women; mean duration of
illness, 7.0 years) were recruited from a research and clinic
registry. Five patients withdrew from the trial.
INTERVENTIONS: All participants were scheduled to receive
fludrocortisone acetate (0.1-0.2 mg) or a placebo for 6 weeks
in each treatment.
MAIN OUTCOME MEASURES: Self- administered
questionnaires were completed at the beginning and end of each
treatment arm that asked patients to rate the severity of
their symptoms on a visual analogue scale. The Medical
Outcomes Study 36-Item Short-Form Health Survey, a reaction
time test, and a treadmill exercise test were used to assess
functional status. Blood pressure, heart rate, and plasma
norepinephrine levels were obtained at baseline. Blood
pressure and heart rate were recorded at the end of the
exercise test and monitored at all subsequent visits.
At baseline, the study participants reported symptom severity
greater than 5 for most symptoms, and all had evidence of
marked functional impairments. No improvement was observed in
the severity of any symptom or in any test of function for the
20 participants who completed both arms of the trial. Blood
pressure and heart rate readings were unaffected by treatment,
and plasma norepinephrine levels did not differ from those of
a healthy control group. The incidence of adverse experiences
was similar in the fludrocortisone and placebo arms of the
CONCLUSION: Low-dose fludrocortisone does not provide
sufficient benefit to be evident in a preliminary blinded
trial of unselected patients with chronic fatigue syndrome.