Effects of sodium oxybate on sleep physiology and sleep/wake-related symptoms in patients with fibromyalgia syndrome: a double-blind, randomized, placebo-controlled study.
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).


CONCLUSIONS
This large cohort of patients with FM demonstrated that SXB treatment improved EEG sleep physiology and sleep-related FM symptoms.
Moldofsky
Harvey
H
Centre for Sleep and Chronobiology and Toronto Psychiatric Research Foundation, Toronto, Ontario, Canada. h.moldofsky@utoronto.ca
Inhaber
Neil H
NH
Guinta
Diane R
DR
Alvarez-Horine
Sarah B
SB
D000759:Adjuvants, Anesthesia / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005356:Fibromyalgia / Q000150:complications / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000494:pharmacology / Q000627:therapeutic use; D017286:Polysomnography; D012890:Sleep / Q000187:drug effects*; D012893:Sleep Wake Disorders / Q000188:drug therapy / Q000209:etiology; D012978:Sodium Oxybate / Q000494:pharmacology / Q000627:therapeutic use; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D000759:Adjuvants, Anesthesia; D010919:Placebos; D012978:Sodium Oxybate