Introduction: Milnacipran has demonstrated efficacy in reducing the pain and multidimensional symptoms associated with fibromyalgia syndrome (FMS). This study was a randomized, double-blind extension trial assessing the long-term safety and durable efficacy response of milnacipran in FMS patients maintained on milnacipran or those patients that crossed over from placebo to active treatment.

Methods: Patients (n=449) who successfully completed a 6-month placebo-controlled lead-in study were maintained at milnacipran 200 mg/day (n=209) or re-randomized (from placebo or 100 mg daily) at a 1:4 ratio to either milnacipran 100 mg/day (n=48) or 200 mg/day (n=192) for an additional 6 months of treatment. Efficacy assessments included change from original baseline on 24-hour and weekly recall of pain (0-100 visual analog scale (VAS), change in Fibromyalgia Impact Questionnaire (FIQ) total score, and Patient Global Impression of Change (PGIC). The study protocol was approved by the IRB at each study center; patients gave written, informed consent.

Results: The continuing 12-month treatment cohort demonstrated persistent drug efficacy over the entire period with 1-year pain scores within 5% of the observed scores at entry into the extension trial. Patients initially assigned to placebo and re-randomized to milnacipran 200 mg/day during this extension study experienced a 47% improvement in mean pain total scores while on drug. Improvements were also reflected in the PGIC and the FIQ total score.

The study completion rate was 67%. Milnacipran treatment was generally well-tolerated. The most commonly reported treatment-emergent adverse event (TEAE) was nausea (22.9%, 100mg/day; 23.9%, 200mg/day). Other TEAEs reported in ≥5% of patients were sinusitis, headache, hypertension, constipation, hyperhidrosis, and dizziness.

Conclusions: These data provide further support that milnacipran is safe and effective in fibromyalgia patients and that multidimensional symptom improvement and 1-year durable efficacy can be achieved. To our knowledge, this is the first demonstration of 1-year sustained efficacy in fibromyalgia.