Management of Fibromyalgia 

The efficacy of milnacipran hydrochloride for the management of fibromyalgia was established in two double-blind, placebo-controlled, multicenter studies in adult patients (18 to 74 years of age). Enrolled patients met the American College of Rheumatology (ACR) criteria for fibromyalgia (a history of widespread pain for 3 months and pain present at 11 or more of the 18 specific tender point sites). Approximately 35% of patients had a history of depression. Study 1 was six months in duration and Study 2 was three months in duration. 

A larger proportion of patients treated with milnacipran hydrochloride than with placebo experienced a simultaneous reduction in pain from baseline of at least 30% (VAS) and also rated themselves as much improved or very much improved based on the patient global assessment (PGIC). In addition, a larger proportion of patients treated with milnacipran hydrochloride met the criteria for treatment response, as measured by the composite endpoint that concurrently evaluated improvement in pain (VAS), physical function (SF-36 PCS), and patient global assessment (PGIC), in fibromyalgia as compared to placebo. 

Study 1: This 6-month study compared total daily doses of milnacipran hydrochloride 100 mg and 200 mg to placebo. Patients were enrolled with a minimum mean baseline pain score of ≥ 50 mm on a 100 mm visual analog scale (VAS) ranging from 0 (“no pain”) to 100 (“worst possible pain”). The mean baseline pain score in this trial was 69. The efficacy results for Study 1 are summarized in Figure 1. 

Figure 1 shows the proportion of patients achieving various degrees of improvement in pain from baseline to the 3-month time point and who concurrently rated themselves globally improved (PGIC score of 1 or 2). Patients who did not complete the 3-month assessment were assigned 0% improvement. More patients in the milnacipran hydrochloride treatment arms experienced at least a 30% reduction in pain from baseline (VAS) and considered themselves globally improved (PGIC) than did patients in the placebo arm. Treatment with milnacipran hydrochloride 200 mg/day did not confer greater benefit than treatment with milnacipran hydrochloride 100 mg/day.

Figure 1: Patients Achieving Various Levels of Pain Relief with Concurrent Ratings of Being Much or Very Much Improved on the PGIC - Study 1

Study 2: This 3-month study compared total daily doses of milnacipran hydrochloride 100 mg and 200 mg to placebo. Patients were enrolled with a minimum mean baseline pain score of ≥ 40 mm on a 100-mm VAS ranging from 0 (“no pain”) to 100 (“worst possible pain”). The mean baseline pain score in this trial was 65. The efficacy results for Study 2 are summarized in Figure 2. 

Figure 2 shows the proportion of patients achieving various degrees of improvement in pain from baseline to the 3-month time point and who concurrently rated themselves globally improved (PGIC score of 1 or 2). Patients who did not complete the 3-month assessment were assigned 0% improvement. More patients in the milnacipran hydrochloride treatment arms experienced at least a 30% reduction in pain from baseline (VAS) and considered themselves globally improved (PGIC) than did patients in the placebo arm. Treatment with milnacipran hydrochloride 200 mg/day did not confer greater benefit than treatment with milnacipran hydrochloride 100 mg/day. 

Figure 2: Patients Achieving Various Levels of Pain Relief with Concurrent Ratings of Being Much or Very Much Improved on the PGIC - Study 2

In both studies, some patients who rated themselves as globally “much” or “very much” improved experienced a decrease in pain as early as week 1 of treatment with a stable dose of milnacipran hydrochloride that persisted throughout these studies.