Compared with placebo, 300 to 450 milligrams daily of pregabalin for 4 weeks led to “statistically significant and meaningful improvements” in sleep as assessed by polysomnography, the researchers say. Patients also reported sleeping longer and better and having less daily pain when taking pregabalin.
Fibromyalgia affects an estimated 5 million Americans, Dr. Thomas Roth, director of the Sleep Disorders and Research Center, Henry Ford Health System in Detroit, Michigan, and colleagues note in their report.
In addition to widespread muscle pain and tenderness, patients with fibromyalgia often report light, disrupted sleep, daytime tiredness and fatigue, perhaps stemming from their pain.
Pregabalin (up to 600 mg/day) is one of three medications currently approved in the United States for fibromyalgia; the other two are duloxetine and milnacipran. While not specifically approved for improving sleep in patients with fibromyalgia, studies have shown a reduction in daytime tiredness and patient-reported sleep disturbance with pregabalin treatment.
However, until now, no study has specifically looked at the effect of the drug on objective measures of sleep in patients with fibromyalgia, Dr. Roth and colleagues say.
Their study included 119 patients with fibromyalgia meeting subjective and objective criteria for disturbed sleep prior to randomization. Most were white women, and had a mean age 48 years. They were randomly assigned to pregabalin (300 to 450 mg/day) or placebo for four weeks, after which they crossed over to the other treatment following a two-week taper and/or washout period.
At screening and at the end of each study period, patients spent two nights in the study center for polysomnographic (PSG) assessment. Patients kept a diary throughout the study in which they rated their pain, level of sleep and tiredness.
Of the 119 patients randomized, 102 (86%) completed both treatment periods. The researchers say treatment with pregabalin for four weeks reduced PSG-recorded wake-after-sleep-onset (WASO), the primary endpoint, by 19 minutes compared with treatment with placebo (51.5 vs 70.7 minutes; p<0.0001).
Compared with placebo, pregabalin also increased PSG-recorded total sleep time by 25 minutes after four weeks and improved several other measures of sleep, including latency to persistent sleep, sleep efficiency, number of awakenings after sleep onset, and slow-wave sleep.
Patients also reported less daily pain when taking pregabalin, as expected, and improvements in ratings of sleep and tiredness.
The researchers say they found “modest (rho<0.3) but significant correlations” between PSG sleep assessments and ratings of pain and sleep quality.
No serious adverse events were reported during the study and no unexpected adverse events with pregabalin. Patients treated with pregabalin had similar patterns of adverse events considered treatment-related compared with placebo, but more patients experienced adverse events with pregabalin than with placebo (51% vs 21%; p<0.01).
The most frequently reported events (pregabalin vs placebo) were dizziness (30% vs 10%), somnolence (21% vs 5%), headache (9% vs 8%).
This study “further raises the need to characterize the nature of sleep disturbance in fibromyalgia,” Dr. Roth noted in an email to Reuters Health.
The study was sponsored by Pfizer Inc. Two of the authors have disclosed financial relationships with Pfizer; the other three are employees of the company.