Long-term safety, tolerability, and efficacy of duloxetine in the treatment of fibromyalgia

Objectives: To assess the long-term safety, tolerability, and efficacy of duloxetine in patients with fibromyalgia. Methods: We report results from the 6-month extension phases of 2 randomized, double-blind, placebo-controlled clinical trials having 6-month placebo-controlled phases. In Study 1, all patients received duloxetine 120 mg/d after 28 weeks on placebo or duloxetine 60 or 120 mg/d. In Study 2, patients taking placebo were titrated to duloxetine 60 mg/d after 27 weeks on treatment, while duloxetine-treated patients remained on their dosages of 60 or 120 mg/d. Safety and tolerability were assessed via discontinuation rates, treatment-emergent adverse events (TEAEs), and changes in vital signs and laboratory measures. The primary efficacy measure was the Brief Pain Inventory average pain severity score. Results: The percentage of patients entering and completing the extension phase was 56% (156/278) for Study 1 and 69% (140/204) for Study 2. Groups titrating from placebo to duloxetine showed the highest discontinuation rates due to an adverse event (Study 1, 25%; Study 2, 19%) and TEAE rates (Study 1, 82%; Study 2, 77%). The most common TEAEs were nausea and dry mouth. No significant within-group changes in blood pressure occurred in any group. Significant within-group mean increases in pulse (bpm) were observed in the placebo/duloxetine 120 mg group in Study 1 (3.7 [SD = 11.2], P ≤ 0.01) and the placebo/duloxetine 60 mg group in Study 2 (4.8 [SD = 10.2], P ≤ 0.001). Most treatment groups showed small mean change improvements in the Brief Pain Inventory average pain severity score. Conclusions: These findings support a positive risk/benefit profile for duloxetine in the long-term treatment of fibromyalgia.