Effect of pregabalin on sleep in patients with fibromyalgia and sleep maintenance disturbance: A randomized, placebo‐controlled, 2‐way crossover polysomnography study

Abstract Objective To assess the effect of pregabalin on polysomnographic (PSG) measures of sleep and patient‐rated sleep, tiredness, and pain in fibromyalgia patients. Methods We performed a randomized, double‐blind, placebo‐controlled, 2‐period crossover PSG study. Patients ages ≥18 years with fibromyalgia satisfied subjective and objective sleep disturbance criteria prior to randomization. Eligible patients were randomized (1:1) to pregabalin (300–450 mg/day) or placebo for crossover period 1, and vice versa for period 2. Each crossover period comprised a dose‐adjustment and dose‐maintenance phase, with a 2‐week taper/washout between periods. In‐laboratory PSGs were recorded during 2 consecutive nights at screening and at the end of each crossover period. The primary end point was the difference in sleep maintenance defined by PSG‐recorded wake after sleep onset (WASO; minutes) between 4 weeks of treatment with pregabalin and with placebo. Other PSG measures; patient‐rated sleep, tiredness, and pain; and tolerability were assessed. Results Of 119 patients randomized (103 women [86.6%], mean age 48.4 years), 102 (85.7%) completed both periods. Patients treated with pregabalin showed a reduction in PSG‐determined WASO versus treatment with placebo (week 4 difference: −19.2 minutes [95% confidence interval (95% CI) −26.7, −11.6]; P < 0.0001). Pain score improved (decreased) with pregabalin versus placebo treatment at all 4 weeks (week 4 difference: −0.52 [95% CI −0.90, −0.14]; P = 0.0084). Modest (ρ = <0.3) but significant correlations were found between PSG sleep assessments and ratings of pain and sleep quality. Frequently reported all‐causality adverse events (pregabalin versus placebo) were: dizziness (30.4% versus 9.9%), somnolence (20.5% versus 4.5%), and headache (8.9% versus 8.1%). Conclusion Patients with fibromyalgia treated with pregabalin had statistically significant and meaningful improvements in sleep, as assessed by PSG. Patients with fibromyalgia also reported decreased daily pain. Pregabalin was well tolerated.