The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled, Two-Way Crossover Study.

OBJECTIVE

This study examined the effects of milnacipran on polysomnographic (PSG) measures of sleep and subjective complaints in patients with fibromyalgia and disturbed sleep.

METHODS

This was a single-site, double-blind, placebo-controlled, two-period crossover PSG study. Eligible subjects (aged 28-72 y) were randomized (1:1) to milnacipran (100 mg/d) or placebo for crossover period 1, and vice versa for period 2. Each crossover period comprised a dose-escalation and dose-maintenance phase, with a 2-w taper/washout between periods. In-laboratory PSGs were collected at baseline, and at the end of each treatment period. The primary endpoints were the difference in PSG-recorded wake after sleep onset (WASO), number of awakenings after sleep onset (NAASO), and sleep efficiency (SE) between 4 w of maintenance treatment with milnacipran and placebo. Other PSG measures, subject-rated sleep, fatigue, physical functioning, and pain were assessed. Post hoc analysis was performed in subjects showing at least 25% reduction in pain from baseline in the Brief Pain Inventory Score (responders).

RESULTS

Of 19 subjects randomized, 15 completed both periods. Subjects treated with milnacipran showed no significant improvements in WASO and NAASO, but showed reduced SE (p = 0.049). Milnacipran did not show significant improvement in other PSG parameters or subjective endpoints. Two thirds of completers met responder criteria and additionally showed a significant improvement in daily effect of pain (p = 0.043) and subjective sleep quality (p = 0.040).

CONCLUSION

The data suggest that milnacipran is not sedating in most patients with fibromyalgia and improvements in sleep are likely a result of pain improvement.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT01234675.