Milnacipran is safe and well tolerated in the treatment of fibromyalgia syndrome

Milnacipran is a norepinephrine and serotonin reuptake inhibitor that has been used extensively and safely in >50 countries worldwide. Recently, milnacipran has been shown to significantly improve the pain and other symptoms associated with fibromyalgia syndrome (FMS). This analysis includes safety data collected from 2209 FMS patients enrolled in 3 double-blind, placebo-controlled trials. Patients were randomized to receive placebo (n=652), milnacipran 100 mg/day (n=623), or milnacipran 200 mg/day (n=934), with the length of treatment ranging from 12 to 29 weeks. The safety of milnacipran was evaluated using MedDRA-coded treatment emergent adverse events (TEAEs). The percentages of patients reporting at least 1 TEAE were similar across treatment groups (placebo, 83%; 100 mg/day, 89%; 200 mg/day, 89%).The most frequently reported TEAEs were nausea (placebo, 19.6%; milnacipran 100 mg/day, 34.5%; milnacipran, 200 mg/day, 39.3%) and headache (placebo, 13.7%; milnacipran 100 mg/day, 18.6%; milnacipran 200 mg/day, 17.2%). TEAEs reported in ≥5% of patients and twice the incidence of placebo in either milnacipran group were nausea, constipation, hot flush, hyperhidrosis, palpitations, vomiting, heart rate increased, dry mouth, and hypertension. Discontinuation rates due to TEAEs were 23% and 26% for milnacipran 100 mg/day and 200 mg/day, respectively, and 12% for placebo. In general, there was no evidence for increased frequency of TEAEs with increased dosage. The only severe TEAEs to occur in ≥2% of patients were nausea, headache, and migraine. Similar to other drugs in this class, milnacipran was associated with heart rate and blood pressure increases. The frequency, magnitude, and severity of these adverse events were low and reversible with discontinuation of treatment. Milnacipran is a safe and well-tolerated medication for the treatment of FMS patients. Supported by Forest Laboratories and Cypress Bioscience.