CHICAGO – The antidepressant milnacipran appears to provide sustained pain relief in patients with fibromyalgia.
In a 28-week, randomized blinded extension trial in 449 patients with fibromyalgia, durable pain relief and improved overall well-being was reported after 1 year of use by patients who responded to milnacipran during the trial's lead-in phase, lead investigator Dr. Don Goldenberg and associates reported in a poster at the annual meeting of the American Academy of Neurology. No new safety concerns emerged.
“Milnacipran is safe and effective for long-term use in fibromyalgia patients,” concluded Dr. Goldenberg of Massachusetts General Hospital in Boston, who disclosed receiving personal consulting fees from Forest Laboratories, one of the companies–along with Cypress Bioscience Inc.–that sponsored this trial.
Milnacipran is a dual-reuptake inhibitor that is unique in that it raises levels of the neurotransmitter norepinephrine more than serotonin.
Marketed as Ixel for depression in Europe and Asia for years, milnacipran is not approved for any use in the United States. Despite its lack of Food and Drug Administration approval, word about milnacipran has spread on fibromyalgia patient Web sites.
A new drug application for milnacipran as a fibromyalgia treatment was filed with the FDA in December 2007 by Forest Laboratories Inc. and Cypress Bioscience Inc.
Patients enrolled in the trial had successfully completed a 6-month lead-in trial and were maintained on milnacipran 200 mg/day or rerandomized from placebo or milnacipran 100 mg/day to either milnacipran 100 mg/day or 200 mg/day for an additional 6 months of treatment. Their mean age was 50 years, more than 95% were female, and the mean duration of fibromyalgia was about 5.5 years.
Efficacy was measured as mean change from lead-in baseline to week 55 in pain recall scores, in Patient Global Impression of Change (PGIC) Scale scores, and in total Fibromyalgia Impact Questionnaire (FIQ) scores. No statistical analyses were performed to determine significance for the efficacy outcomes. This is noteworthy, as a pivotal phase III trial in 888 patients with fibromyalgia reported in September 2005 that its primary efficacy assessments failed to demonstrate statistical significance.
The current analyses were based on 147 of 209 patients maintained on milnacipran 200 mg/day for both phases of the study; 63 of 92 patients switched from milnacipran 100 mg/day to 200 mg/day; and 65 of 100 patients who switched from placebo to milnacipran 200 mg/day.
Efficacy data were not available on the 48 patients receiving milnacipran 100 mg in the extension phase.
Patients continuing on milnacipran 200 mg/day in the extension study showed a 46% improvement in mean pain recall scores, the investigators reported.
Patients switched from milnacipran 100 mg/day to 200 mg/day maintained the pain relief achieved in the lead-in trial and showed an additional 12% reduction in pain scores at the higher dose. Overall, their mean pain scores improved 52% from lead-in baseline.
Mean scores on the 7-point PGIC scale were 2.18 for patients continuing on milnacipran 200 mg/day and 1.91 for patients switching from 100 mg/day to 200 mg/day, indicating improvements in both groups after 1 year, according to the investigators. A score of 1 equals “very much improved” and 2 equals “much improved.”
At week 55, the improvement in total FIQ scores was 49% among patients who switched from 100 mg/day to 200 mg/day and 41.5% among those maintained on 200 mg.
Patients switched from placebo to milnacipran 200 mg in the extension trial experienced a 47% improvement in their mean pain total scores after 28 weeks of treatment.
Similar improvements were observed in PGIC and FIQ, according to Dr. Goldenberg, who disclosed that along with fees from Forest Laboratories, he has received personal consulting fees from Eli Lilly & Co. and Merck & Co.
The drug was well tolerated at doses of 100 mg/day and 200 mg/day, and the majority of adverse events were mild to moderate. Data on serious adverse events were not presented in the poster and were not available from the investigators at press time.
The most common newly emergent adverse event during the extension phase in patients continuing on milnacipran was nausea, which was reported in 13% of these patients.