Long-Term Milnacipran Treatment for Fibromyalgia

Las Vegas—Patients with fibromyalgia who took milnacipran for >3 years exhibited improvements in pain, global status, and physical functioning, according to a multicenter, open-label, flexible-dose trial. The results were presented at the AAPM meeting during a poster presentation titled A 3-Year, Open-Label Study of Milnacipran for Fibromyalgia Patients. Several previous phase 2 and phase 3 studies found that milnacipran improved pain and multiple fibromyalgia symptoms for up to 12 to 15 months. In this trial, the authors were interested in examining patients who had completed the previous studies to determine the safety and efficacy of milnacipran for up to an additional 3.25 years. Patients were excluded if they had significant psychiatric illness, risk of suicide, Beck Depression Inventory total score >25, active liver disease, renal impairment, or other significant medical conditions. They also could not have taken another experimental drug in the past 30 days or had concomitant therapy with monoamine oxidase inhibitors, dual serotonin/norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, or digitalis. The study began with 1227 patients, of which 585 completed the trial. It consisted of a 2-week washout/run-in phase, a 2-week dose-escalation period to 100 mg/day of milnacipran, and an 8-week period of a stable, 100-mg/day milnacipran dose. For the remainder of the trial, patients took a flexible daily milnacipran dose of 50 to 200 mg depending on their tolerability or the medication’s efficacy. The efficacy analyses were based on the 1220 patients in the intent-to-treat (ITT) population, defined as those receiving ≥1 dose of study drug and having ≥1 post-baseline efficacy assessment. In the ITT population, the mean age was 50.3 years, the mean weight was 82.0 kg, and the mean body mass index was 30.7 kg/m2. In addition, 95.4% of patients were female, and 93.1% were white. The mean dose of milnacipran was 134 mg/day, while the mean duration of milnacipran treatment was 18.5 months. Approximately 18% of patients (n=217) took milnacipran for >3 years. Patients who received long-term milnacipran treatment improved from baseline on the following measures: visual analog scale, brief pain inventory, patient global disease status, Short Form-36 Health Survey Physical Component summary, and Short Form-36 Health Survey Mental Component summary. The safety analyses included all patients who took ≥1 dose of study drug. The authors said the study did not find any new safety concerns. Similar to previous trials, the most common treatment-emergent adverse events (TEAEs) were nausea and headache, although the rates were lower in this study compared with other studies: 25.9% of patients in this study had nausea compared with 37.0% of patients in previous studies who took milnacipran, while 13.4% of patients in this study had nausea compared with 18.0% of patients in previous studies who took milnacipran. However, other TEAEs were higher in this study, including the incidence of hypertension and upper respiratory tract infection. In addition, 9% of patients in this study had serious adverse events compared with 0% to 2% of patients who took milnacipran in the previous placebo-controlled studies. The mean increases from baseline in supine systolic blood pressure (4.0 mm Hg), diastolic blood pressure (3.3 mm Hg), and heart rate (5 bpm) were similar to the previous trials. Furthermore, <1.5% of patients had potentially clinically significant (PCS) increases in supine vital signs, 18% of patients had PCS weight loss (≥7% decrease from baseline), and 13% of patients had PCS weight gain (≥7% increase from baseline). This study was sponsored by Forest Laboratories, Inc, and Cypress Biosciences, Inc.