PALM SPRINGS, CA — A study that evaluated the effect of discontinuing long-term treatment with milnacipran on the symptoms of fibromyalgia found that once the agent was withdrawn, time to loss of therapeutic response was significantly shorter than in patients who continued treatment, investigators reported during the 2012 American Academy of Pain Medicine Annual Meeting.
The multicenter, double-blind, placebo-controlled discontinuation study included 150 patients with fibromyalgia who were enrolled for up to 3.25 years (minimum, 17.9 months) in an open-label study of milnacipran, noted Daniel J. Clauw, MD, of the University of Michigan, Ann Arbor, MI, and colleagues.
The patients entered the study directly from a three-year, open-label, flexible-dose follow-up study and continued their previous milnacipran 50–200mg/day dosage for an additional four weeks of open-label treatment. Responders — those on a ≥100mg/day dose who had achieved a ≥50% reduction in pain compared to before milnacipran exposure on a visual analog scale (VAS) — were randomized 2:1 to milnacipran (milnacipran continued; n=100) or placebo (milnacipran withdrawn; n=50) for 12 weeks.
The patient population was predominantly female (96%) and white (95%). Mean VAS pain score at the baseline randomization visit was 17.5, which represented a 73% reduction from the pretreatment baseline mean score of 65.7.
Time to loss of therapeutic response was the primary efficacy parameter, defined as an increase in VAS pain score to <30% reduction from pre-milnacipran exposure or a fibromyalgia that worsened, requiring an alternative treatment.
At 12 weeks, 64% of patients withdrawn from milnacipran met the criteria for loss of therapeutic response compared with 35% of patients who had continued milnacipran. Median time to loss of therapeutic response was 56 days for patients withdrawn from milnacipran and not calculable for those who continued the agent (P=0.0004).
“In patients who have received long-term treatment with milnacipran (1.5 to 4.5 years), the loss of therapeutic response upon discontinuation of treatment provides evidence of long-term efficacy of milnacipran as a treatment for fibromyalgia,” Dr. Clauw and colleagues concluded. No new safety concerns were observed following milnacipran treatment discontinuation.