Comparison of Adaptive Pacing Therapy, Cognitive Behaviour Therapy, Graded Exercise Therapy, and Specialist Medical Care for Chronic Fatigue Syndrome (PACE): A Randomised Trial

Study Questions:

Are therapies including cognitive behavior therapy, graded exercise therapy, and adaptive pacing safe and effective for treatment of chronic fatigue syndrome?


This was a randomized trial of patients who had met Oxford criteria for chronic fatigue syndrome. Patients were recruited from six secondary care clinics in the United Kingdom. Subjects were randomly allocated to receive specialist care alone or in combination with adaptive pacing therapy, cognitive behavioral therapy, or graded exercise therapy. The primary outcomes of interest were symptoms of fatigue (measured by Chalder fatigue questionnaire score) and physical function (measured by short form-36 subscale score) up to 52 weeks post-randomization. Safety was assessed primarily by recording all serious adverse events, including serious adverse reactions to trial treatments. Primary outcomes were rated by participants, who were necessarily unmasked to treatment assignment; the statistician was masked to treatment assignment for the analysis of primary outcomes.


A total of 641 patients were enrolled, of which 160 were assigned to the adaptive pacing group, 161 to the cognitive behavior therapy group, 160 to the graded exercise therapy group, and 160 to the specialist medical care (SMC) alone group. Compared with SMC alone, mean fatigue scores at 52 weeks were 3.4 (95% confidence interval [CI], 1.8-5.0) points lower for cognitive behavior therapy (p = 0.0001) and 3.2 (95% CI, 1.7-4.8) points lower for graded exercise therapy (p = 0.0003), but did not differ for adaptive pacing (0.7 [95% CI, –0.9 to 2.3] points lower; p = 0.38). Compared with SMC alone, mean physical function scores were 7.1 (95% CI, 2.0-12.1) points higher for cognitive behavior therapy (p = 0.0068) and 9.4 (95% CI, 4.4-14.4) points higher for graded exercise therapy (p = 0.0005), but did not differ for adaptive pacing (3.4 [95% CI, –1.6 to 8.4] points lower; p = 0.18). Compared with adaptive pacing, cognitive behavior therapy and graded exercise therapy were associated with less fatigue (cognitive behavior therapy, p = 0.0027; graded exercise therapy, p = 0.0059) and better physical function (cognitive behavior therapy, p = 0.0002; graded exercise therapy, p < 0.0001). Serious adverse reactions were recorded in two (1%) of 159 participants in the adaptive pacing group, three (2%) of 161 in the cognitive behavior therapy group, two (1%) of 160 in the graded exercise therapy group, and two (1%) of 160 in the SMC-alone group.


The investigators concluded that cognitive behavior therapy and graded exercise therapy can safely be added to specialist care with moderate improvement in symptoms related to chronic fatigue syndrome. Adaptive pacing was not an effective addition to specialist care.


This study demonstrated that graded exercise and cognitive behavioral therapy are safe and effective for management of chronic fatigue.

Clinical Topics: Prevention, Exercise

Keywords: Secondary Care, Fatigue Syndrome, Chronic, Great Britain, Exercise Therapy, Cognitive Therapy

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