Effect of milnacipran on body weight in patients with fibromyalgia

Abstract

Background: The purpose of this study was to evaluate the effects of milnacipran on body weight in patients with fibromyalgia.

Methods: ANALYSES WERE CONDUCTED IN THE FOLLOWING GROUPS: patients from three double-blind, placebo-controlled milnacipran trials (3 months, n = 2096; 6 months, n = 1008); 354 patients receiving milnacipran in placebo-controlled trials and double-blind extension studies (total ≥ 12 months of treatment); and 1227 patients in a long-term (up to 3.25 years) open-label milnacipran study.

Results: In placebo-controlled trials, 77% of patients were overweight or obese at baseline (body mass index ≥ 25 kg/m(2)). Mean weight loss was found with milnacipran at 3 months (100 mg/day, -1.14 kg; 200 mg/day, -0.97 kg; placebo, -0.06 kg; P < 0.001) and 6 months (100 mg/day, -1.01 kg; 200 mg/day, -0.71 kg; placebo, -0.04 kg; P < 0.05). Approximately twice as many milnacipran-treated patients had ≥5% weight loss from baseline compared with placebo (3 and 6 months, P < 0.01). In extension studies, mean weight loss in patients receiving ≥12 months of milnacipran was -1.06 kg. In patients receiving ≥3 years of treatment in the open-label study, mean changes at 12, 24, 30, and 36-38 months were -1.16, -0.76, -0.19, and +0.11 kg, respectively. Among milnacipran-treated patients, rates of nausea (the most common adverse event) were lower among patients who lost weight than among those who did not (3 months, P = 0.02).

Conclusion: The majority of patients with fibromyalgia in the milnacipran studies were overweight or obese. Milnacipran was associated with mean weight loss at 3 and 6 months (P < 0.05 versus placebo) and at 12 and 24 months of treatment, with mean changes drifting back to baseline at 30 months (-0.19 kg) and 36-38 months (+0.11 kg, no placebo comparison).

Keywords: body weight; fibromyalgia; milnacipran.

Figure 1

Baseline BMI in patients with fibromyalgia. Notes: Based on World Health Organization classifications, BMI baseline strata were defined as follows: severely underweight (BMI 16 to < 17 kg/m²), underweight (BMI 17 to < 18.5 kg/m²), normal weight (BMI 18.5 to < 25 kg/m²), overweight (BMI 25 to < 30 kg/m²), obese class I (BMI 30 to < 35 kg/m²), obese class II (BMI 35 to < 40 kg/m²), and obese class III (BMI ≥ 40 kg/m²). Analysis includes 3104 patients with available baseline weight data from three studies.– Abbreviation: BMI, body mass index.

Figure 2

Body weight changes with standard errors by study visit among (A) patients in randomized, placebo-controlled studies (baseline, n = 3104; 3 months [12 weeks], n = 2096; 6 months [27 weeks], n = 1008); (B) patients in extension studies receiving ≥12 months of continuous milnacipran treatment (n = 354); and (C) patients receiving ≥3 years of milnacipran treatment in a long-term, open-label study (n = 220). Notes: Analyses are based on observed cases, with least squares mean changes from baseline shown for placebo-controlled trials and mean changes from lead-in study baseline shown for extension studies and the long-term, open-label study. For placebo-controlled trials, data for weeks 0–12 are from three studies– and data for weeks 19–27 are from two studies., The last visit for study 1 was at week 27, and the last visit for study 2 was at week 29. *P < 0.05; **P < 0.01; ***P < 0.001 versus placebo. Abbreviation: LS, least squares.

Figure 3

Percentage of patients with (A) ≥5% weight loss at 3, 6, and ≥12 months; (B) ≥5% weight gain at 3, 6, and ≥12 months; and (C) ≥5% weight loss or gain from lead-in patients who received 3 years of treatment in the long-term, open-label study. Notes: The 3-month analyses (n = 2096) and 6-month analyses (n = 1008) included patients who participated in a placebo-controlled trial of milnacipran. The ≥12-month analyses (n = 354) included patients who received milnacipran during a placebo-controlled trial and extension study, and are based on weight changes from the lead-in study baseline. Analyses for the 3-year cohort (n = 220) are based on weight changes from baseline of the first lead-in study prior to the long-term, open-label study. **P < 0.01; ***P < 0.001 versus placebo.