Sodium oxybate relieves pain and improves function in fibromyalgia syndrome: A randomized, double-blind, placebo-controlled, multicenter clinical trial.

Arthritis Rheum. 2008 Dec 30;60(1):299-309. [Epub ahead of print]
Russell IJ, Perkins AT, Michalek JE; Oxybate SXB-26 Fibromyalgia Syndrome Study Group.
The University of Texas Health Science Center at San Antonio.
PMID: 19116896

OBJECTIVE: To evaluate the safety and efficacy of sodium oxybate for management of the symptoms of fibromyalgia syndrome (FMS).

METHODS: Patients with FMS (according to the American College of Rheumatology 1990 criteria) were randomized, after discontinuing their prestudy medications for FMS, to receive 4.5 gm or 6 gm of sodium oxybate or matching placebo once per night for 8 weeks. The primary outcome variable (POV) was a composite score for changes from baseline in 3 coprimary self-report measures: patient's pain rating (in daily electronic diaries) on a visual analog scale (PVAS), the Fibromyalgia Impact Questionnaire (FIQ) score, and the Patient Global Impression of Change (PGI-C). A beneficial response rate for the POV composite score was defined as >/=20% improvement in the PVAS and FIQ scores plus a rating of "much better" or "very much better" on the PGI-C. Secondary measures included subjective sleep outcomes (on the Jenkins Scale for Sleep) and quality-of-life measures. The analyses were based on an intent-to-treat (ITT) population.

RESULTS: The ITT population included 188 patients with FMS, 78% of whom completed the trial. Significant benefit was observed with both dosages of sodium oxybate, according to changes in the POV and subjective sleep quality. Improvements in the PVAS score were significantly correlated with sleep outcomes. Sodium oxybate was well tolerated overall; dose-related nausea (

CONCLUSION: Sodium oxybate therapy was well tolerated and significantly improved the symptoms of FMS. Further study of sodium oxybate as a novel therapeutic option for FMS is warranted.

Additional information from

WARNING: Central nervous system depressant with abuse potential. Should not be used with alcohol or other CNS depressants.

Sodium oxybate is GHB, a known drug of abuse. Abuse has been associated with some important central nervous system (CNS) adverse events (including death). Even at recommended doses, use has been associated with confusion, depression and other neuropsychiatric events. Reports of respiratory depression occurred in clinical trials. Almost all of the patients who received sodium oxybate during clinical trials were receiving CNS stimulants.

Important CNS adverse events associated with abuse of GHB include seizure, respiratory depression and profound decreases in level of consciousness, with instances of coma and death. For events that occurred outside of clinical trials, in people taking GHB for recreational purposes, the circumstances surrounding the events are often unclear (e.g., dose of GHB taken, the nature and amount of alcohol or any concomitant drugs).

Previous studies

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Center Trial Comparing the Effects of Orally Administered Xyrem® (Sodium Oxybate) with Placebo for the Treatment of Fibromyalgia

Patrick B. Wood, Louisiana State University Health Sciences Center - Shreveport, Shreveport, LA, USA
February 2006

Introduction: The purpose of this study was to evaluate the efficacy of 2 doses of sodium oxybate for the treatment of primary fibromyalgia.

Materials & methods: The study was an 8-week randomized, placebo-controlled, double blind trial comparing 2 doses of sodium oxybate (4.5g/day, n=58; 6.0g/day, n=66) with placebo (n=64) for the treatment of primary fibromyalgia. Primary outcome measure was a composite endpoint of visual analog scale (VAS) for pain, Fibromyalgia Impact Questionnaire (FIQ) total score, and Patient Global Assessment of Change (PGIC). Secondary measures included Tender Point Count (TPC), Tender Point Index (TPI) and as well as measures of sleep efficiency and well-being. Subject screening included polysomnogram to rule out obstructive sleep apnea or parasomnias and to establish baseline sleep parameters. Treatment group differences were evaluated using an ANOVA method and the Fisher's exact test, using an intention to treat analysis. The protocol was approved by local institutional review boards and all subjects signed informed consent prior to evaluation.

Results: Both doses of sodium oxybate resulted in significantly greater improvement in pain VAS (4.5g/day, p=0.04; 6.0g/day, p=0.03), FIQ (4.5g/day, p=0.007; 6.0g/day, p=0.02), and PGIC (4.5g/day, p=0.03; 6.0g/day, p=0.11). Subjects receiving sodium oxybate also demonstrated a strong trend towards significant improvement in TPC (4.5g/day, p=0.08; 6.0g/day, p=0.05) and TPI (4.5g/day, p=0.06; 6.0g/day, p=0.09). Sodium oxybate also resulted in significantly greater improvement in nearly all secondary and health outcome measures, with significantly more subjects receiving active medication classified as responders in comparison with placebo (4.5g/day, p=0.005; 6.0g/day, p=0.05). No significant difference was demonstrated between active treatments and placebo regarding total adverse outcomes (p=0.14). Subjects receiving sodium oxybate 6.0g/day reported more nausea, vomiting, headache and dizziness as compared to placebo or sodium oxybate 4.5g/day.

Conclusions: Sodium oxybate is a well-tolerated and efficacious treatment for primary fibromyalgia at doses of 4.5g/day and 6.0g/day.


The effects of sodium oxybate on clinical symptoms and sleep patterns in patients with fibromyalgia.

J Rheumatol 2003;30(5):1070-4.
Tri-State Sleep Disorders Center, Cincinnati, Ohio, USA

OBJECTIVE: Fibromyalgia (FM) is associated with the sleep phenomenon of alpha intrusion, and with low growth hormone secretion. Sodium oxybate has been shown to increase both slow-wave sleep and growth hormone levels. This double blind, randomized, placebo controlled crossover trial was conducted to evaluate the effects of sodium oxybate on the subjective symptoms of pain, fatigue, and sleep quality and the objective polysomnographic (PSG) sleep variables of alpha intrusion, slow-wave (stage 3/4) sleep, and sleep efficiency in patients with FM.

METHODS: Patients received either 6.0 g/day sodium oxybate or placebo for 1 month, with an intervening 2 week washout period. Efficacy measures included PSG evaluations, tender point index (TPI), and subjective measurements from daily diary entries. Safety measures included clinical laboratory values, vital signs, and adverse events.

RESULTS: Twenty-four female patients were included in the study; 18 completed the trial. TPI was decreased from baseline by 8.5, compared with an increase of 0.4 for placebo (p = 0.0079). Six of the 7 pain/fatigue scores (overall pain, pain at rest, pain during movement, end of day fatigue, overall fatigue, and morning fatigue) were relieved by 29% to 33% with sodium oxybate, compared with 6% to 10% relief with placebo (p < 0.005). Alpha intrusion, sleep latency, and rapid-eye-movement sleep were significantly decreased, while slow-wave (stage 3/4) sleep was significantly increased, compared with placebo (p < 0.005). Two of the 5 subjective sleep related variables were significantly different from placebo: morning alertness (improved by 18% with sodium oxybate, compared with 2% for placebo; p = 0.0033) and quality of sleep (improved by 33% and 10%, respectively; p = 0.0003).

CONCLUSION: Sodium oxybate effectively reduced the symptoms of pain and fatigue in patients with FM, and dramatically reduced the sleep abnormalities (alpha intrusion and decreased slow-wave sleep) associated with the nonrestorative sleep characteristic of this disorder.