A six-month randomized controlled trial of exercise and pyridostigmine in the treatment of fibromyalgia

Abstract

Objective: A subset of fibromyalgia (FM) patients have a dysfunctional hypothalamic-pituitary-insulin-like growth factor 1 (IGF-1) axis, as evidenced by low serum levels of IGF-1 and a reduced growth hormone (GH) response to physiologic stimuli. There is evidence that pyridostigmine (PYD) improves the acute response of GH to exercise in FM patients. The purpose of this study was to evaluate the clinical effectiveness of 6 months of PYD and group exercise on FM symptoms.

Methods: FM patients were randomized to 1 of the following 4 groups: PYD plus exercise, PYD plus diet recall but no exercise, placebo plus exercise, and placebo plus diet recall but no exercise. The primary outcome measures were the visual analog scale (VAS) score for pain, tender point count, and total myalgic score. Secondary outcome measures were the total score on the Fibromyalgia Impact Questionnaire (FIQ) and FIQ VAS scores for individual symptoms (fatigue, poor sleep, stiffness, and anxiety), as well as quality of life (QOL) and physical fitness (lower body strength/endurance, upper and lower body flexibility, balance, and time on the treadmill).

Results: A total of 165 FM patients completed baseline measurements; 154 (93.3%) completed the study. The combination of PYD and exercise did not improve pain scores. PYD groups showed a significant improvement in sleep and anxiety in those who completed the study and in QOL in those who complied with the therapeutic regimen as compared with the placebo groups. Compared with the nonexercise groups, the 2 exercise groups demonstrated improvement in fatigue and fitness. PYD was generally well tolerated.

Conclusion: Neither the combination of PYD plus supervised exercise nor either treatment alone yielded improvement in most FM symptoms. However, PYD did improve anxiety and sleep, and exercise improved fatigue and fitness. We speculate that PYD may have improved vagal tone, thus benefiting sleep and anxiety; this notion warrants further study.

Figure 1

Distribution of the study patients from initial contact to completion of the study. A total of 165 patients with fibromyalgia completed the baseline measurements, and 154 patients completed the study. Patients were assigned to 1 of 4 groups: pyridostigmine plus exercise, pyridostigmine plus diet recall but no exercise, placebo plus exercise, and placebo plus diet recall but no exercise (see Patients and Methods for details). Adapted, with permission, from ref. 22.

Figure 2

Improvement in sleep quality with pyridostigmine therapy in patients with fibromyalgia. Patients were assigned to 1 of 4 groups: placebo plus diet recall but no exercise (placebo/no group exercise), placebo plus exercise (placebo/group exercise), pyridostigmine plus diet recall but no exercise (pyridostigmine/no group exercise), and pyridostigmine plus exercise (pyridostigmine/group exercise). Sleep was assessed using a 0–10-cm visual analog scale, where lower scores indicate better sleep. Values are the adjusted mean.

Figure 3

Improvement in anxiety levels with pyridostigmine therapy in patients with fibromyalgia. Patients were assigned to 1 of 4 groups: placebo plus diet recall but no exercise (placebo/no group exercise), placebo plus exercise (placebo/group exercise), pyridostigmine plus diet recall but no exercise (pyridostigmine/no group exercise), and pyridostigmine plus exercise (pyridostigmine/group exercise). Anxiety symptoms were assessed using a 0–10-cm visual analog scale, where lower scores indicate less anxiety. Values are the adjusted mean.