Abstract
Objective. To determine the effects of sodium oxybate (SXB) on sleep physiology and sleep/wake-related symptoms in patients with fibromyalgia syndrome (FM).
Methods. Of 304 patients with FM (American College of Rheumatology tender point criteria) in the screened study population, 209 underwent polysomnography, 195 were randomized, and 151 completed this 8-week, double-blind, placebo-controlled study of SXB 4.5 g and 6 g/night. We evaluated changes in objective sleep measures and subjective symptoms, including daytime sleepiness [Epworth Sleepiness Scale (ESS)], fatigue visual analog scale (FVAS), sleep [Jenkins Scale for Sleep (JSS)], and daytime functioning [Functional Outcome of Sleep Questionnaire (FOSQ), SF-36 Vitality domain, and Fibromyalgia Impact Questionnaire (FIQ) general and morning tiredness].
Results. Pretreatment screening revealed an elevated incidence of maximum alpha EEG-intrusion > 24 min/hour of sleep (66%), periodic limb movements of sleep (20.1% ≥ 5/hour), and moderate to severe obstructive sleep apnea disorder (15.3% apnea-hypopnea index ≥ 15/hour). Compared with placebo, both doses of SXB achieved statistically significant improvements in ESS, morning FVAS, JSS, FOSQ, SF-36 Vitality, and FIQ general and morning tiredness; both doses also demonstrated decreased rapid eye movement (REM) sleep (all p ≤ 0.040). SXB 6 g/night improved afternoon, evening and overall FVAS, reduced wakefulness after sleep onset, and increased Stage 2, slow-wave, and total non-REM sleep (all p ≤ 0.032) versus placebo. Moderate correlations (≥ 0.40) were noted between changes in subjective sleep and pain measures. Adverse events occurring significantly more frequently with SXB than placebo were nausea, pain in extremity, nervous system disorders, dizziness, restlessness, and renal/urinary disorders (including urinary incontinence).
Conclusion. This large cohort of patients with FM demonstrated that SXB treatment improved EEG sleep physiology and sleep-related FM symptoms.
Footnotes
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Clinical trial registry: ClinicalTrials.gov; clinical trial registration number NCT000875555.
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Supported by Jazz Pharmaceuticals, Inc. Palo Alto, California, USA. Dr. Moldofsky has received research support from Eli Lilly, Krele, Pfizer, Pierre Fabre, Sanofi Aventis, and Schering Plough; acts as a consultant for Boehringer Ingleheim, Eli Lilly, Jazz Pharmaceuticals, Krele, Lundbeck, Merck, Paladin Labs, Pfizer, Pierre Fabre, Sanofi Aventis, Schering Plough, and Valeant; and is on the speaker’s bureau for Pfizer. Dr. Inhaber is a former employee of Jazz Pharmaceuticals, Inc., and owns stock in the company. S.B. Alvarez-Horine and D.R. Guinta are employees of Jazz Pharmaceuticals, Inc., and own stock and stock options in the company. Editorial review and manuscript preparation were by Susanna Grzeschik, PhD, RPh, and Daniel Pardi, MS, former employees of Jazz Pharmaceuticals, Inc., and by Deborah Waxman, MA, as well as statistical support from Efim A. Dynin, PhD, and Chinglin Lai, PhD, all from Jazz Pharmaceuticals, Inc.
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- Accepted for publication May 20, 2010.
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