Safety and efficacy of esreboxetine in patients with fibromyalgia: A fourteen-week, randomized, double-blind, placebo-controlled, multicenter clinical trial

Objective To evaluate the efficacy, tolerability, and safety of multiple fixed dosages of esreboxetine for the treatment of fibromyalgia. Methods Patients meeting the American College of Rheumatology criteria for fibromyalgia were randomized to receive esreboxetine at dosages of 4 mg/day (n = 277), 8 mg/day (n = 284), or 10 mg/day (n = 283) or matching placebo (n = 278) for 14 weeks. The primary efficacy outcomes were the weekly mean pain score and the Fibromyalgia Impact Questionnaire (FIQ) total score at week 14. Secondary efficacy measures included scores for the Patient's Global Impression of Change (PGIC) scale, the Global Fatigue Index (GFI), and the 36-item Short-Form health survey (SF-36; physical function scale only) at week 14. The safety profile of esreboxetine was evaluated based on adverse events and other safety measures. Results Patients receiving all dosages of esreboxetine demonstrated statistically significant improvements in the pain score (P = 0.025), the FIQ score (P = 0.023), and the PGIC score (P = 0.007) compared with patients in the placebo group. Additionally, patients receiving esreboxetine at dosages of 4 mg/day and 8 mg/day showed statistically significant improvements in the GFI score compared with those receiving placebo (P = 0.001). No significant differences in SF-36 physical function scores were observed between patients receiving esreboxetine (any dosage) and those receiving placebo. Adverse events were mostly mild to moderate in severity; insomnia, constipation, dry mouth, nausea, dizziness, hot flush, headache, hyperhidrosis, and palpitations were reported most frequently. Conclusion Esreboxetine was generally well tolerated and was associated with significant improvements in pain, FIQ, PGIC, and fatigue scores compared with placebo. The lack of a dose-response relationship in both the efficacy and safety analyses suggests that esreboxetine at a dosage of 4 mg/day would offer clinical benefit with the least risk of drug exposure.