Safety and Tolerability of Duloxetine in the Treatment of Patients with Fibromyalgia: Analysis of 5 Studies

Duloxetine, a serotonin-norepinephrine reuptake inhibitor, has been shown to effectively treat patients with fibromyalgia. The objective of this integrative analysis is to evaluate the safety and tolerability of duloxetine during up to 60 weeks of treatment. Patients (N=1236) from 4 placebo-controlled studies employing doses of 20, 60, and 120mg/day of duloxetine, and one long-term study (N=350) employing doses of 60 and 120mg/day, were used in these analyses. Safety and tolerability were assessed via reasons for discontinuation, treatment-emergent adverse events (TEAEs), discontinuation-emergent adverse events, and changes in vital signs, weight, and laboratory analytes. In the placebo-controlled studies, overall exposure was 264 patient-years for duloxetine and 154 for placebo. The patients were primarily female (95%) and Caucasian (80.4%), with a mean age of 50.1 years. In the long-term study, patients were similar in demography and duloxetine exposure was 285 patient-years. Discontinuations due to adverse events were higher in the duloxetine group (duloxetine, 19.5%; placebo, 11.8%, P<.001), whereas discontinuations due to lack of efficacy were higher in the placebo group (duloxetine, 7.0%; placebo, 13.5%, P<.001). The most common TEAE was nausea (duloxetine, 29.3%; placebo, 11.4%, P<.001). Nausea was reported as mild to moderate and tended to resolve over time. Clinically small, but statistically significant differences (P<.01) in mean changes in pulse (bpm, 1.22, -.42), systolic (mmHg, 0.91, -1.58) and diastolic (mmHg, 1.04, -1.17) blood pressure, and weight (kg, -.43, 0.28) occurred, respectively, in the duloxetine group compared with the placebo group. In the long-term uncontrolled study, mean changes in vitals during up to 60 weeks of treatment with duloxetine were: -0.1 and -0.2 mmHg for supine systolic and diastolic blood pressure, 0.7 kg for weight (P=.005), and 1.9 bpm for pulse (P<.001) The safety and tolerability profile of duloxetine in these fibromyalgia studies was similar to that observed with duloxetine in other indications.