PHOENIX – Preliminary data on the off-label use of sodium oxybate suggest that it improved sleep in a randomized, placebo-controlled study of 151 patients with fibromyalgia who completed 8 weeks of treatment at 21 medical centers.
The study enrolled 195 patients who started with a drug washout period and were randomized to continue for 8 weeks on sodium oxybate 4.5 g/day or 6 g/day or placebo. Doses were split; patients took a half-dose at bedtime, then awoke 4 hours later for the other half.
Forty-four patients (23%) withdrew before completion, mostly from the higher-dose group and primarily because of side effects, including headache, dizziness, and nausea, Dr. Harvey Moldofsky reported at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.
Both objective and subjective measures of sleep improved in the drug groups, compared with placebo–for those who finished the study–more so with the 6-g/day dose, said Dr. Moldofsky, president and director of the Centre for Sleep and Chronobiology, Toronto, and emeritus professor of medicine at the University of Toronto.
The study was funded by Jazz Pharmaceuticals, the company that makes sodium oxybate. Dr. Moldofsky is a consultant to and an advisory board member for the company.
Many patients with fibromyalgia have sleep disturbances, he noted.
Sleep polysomnography showed significant objective improvements in the high-dose group in the following areas: amount of time spent sleeping; sleep efficiency (the proportion of time spent sleeping, compared with time in bed); and the amount of deep, or slow-wave, sleep, he reported.
Subjective results from patient self-reports on several scales showed that they experienced improvements with either dose, compared with placebo, in pain and fatigue (Visual Analog Scale), daytime sleepiness (Epworth Sleepiness Scale), impaired sleep (Jenkins Scale), and daytime functioning (Functional Outcome of Sleep Questionnaire, SF-36 Vitality scale, and Fibromyalgia Impact Questionnaire).
The study provides a proof of concept, but more research is needed before the drug is used by patients with fibromyalgia, he said.
Besides headache, dizziness, and nausea, other side effects that occurred more frequently in the drug groups than in the placebo group included vomiting, nasopharyngitis, extremity pain, muscle cramp, nervous system disorders, restlessness, and incontinence or other renal/urinary disorders.
In 2002 sodium oxybate was approved in the United States to reduce cataplexy attacks in patients with narcolepsy, but the drug is under tightly restricted distribution from Jazz Pharmaceuticals alone – not from pharmacies.
The agent, more commonly known as gamma hydroxybutyrate, or GHB, entered the U.S. market as a dietary supplement in the early 1990s. It subsequently gained favor as a party drug, was used to perpetrate date rape because of its intoxicating effects, and caused many serious adverse events and some deaths from its use and misuse.
More research would be needed to determine whether the improvements in sleep seen in the current study were independent of subjective improvements in pain and functionality, Dr. Moldofsky said.