NATIONAL HARBOR, MD. – Fibromyalgia patients who failed to respond to pregabalin showed significant symptom improvement when milnacipran was added to their regimen compared with those who continued taking pregabalin alone, a study involving 332 patients has shown.
The open-label study was the first randomized, controlled trial to show the benefits of adding milnacipran (MLN) to existing pregabalin (PGN) therapy in fibromyalgia patients, according to Dr. Mildred Farmer of Meridien Research in St. Petersburg, Fla., and colleagues. Pregabalin was approved for treating patients with fibromyalgia in 2007; milnacipran was approved for the indication in 2009.
The patients, aged 18-70 years, had baseline Visual Analog Scale (VAS) pain scores of 40 or higher, and they failed to improve on PGN alone during a 4- to 12-week PGN run-in period.
After the run-in period, patients were randomized to 300 or 450 mg/day of PGN (which served as the control group) or a PGN treatment plus 100 mg/day of milnacipran.
After 11 weeks, significantly more patients in the MLN group reported their symptoms were "much improved" or "very much improved" compared with the control group, based on Patients’ Global Impression of Change scale scores. Patients in the MLN group also showed significant improvements in physical and mental function, fatigue, and cognition compared with controls, based on scores on the Multiple Ability Self-Report Questionnaire (–3.69 vs. 1.19).
In addition, "patients receiving MLN added to PGN had significantly greater improvements in VAS 1-week recall pain scores than patients treated with PGN alone," Dr. Farmer said at the annual meeting of the American Academy of Pain Medicine.
The incidence of serious adverse events was not significantly different between the MLN and PGN groups (2.7% vs. 3.4%), nor was the rate of discontinuation significantly different between the two groups (15% vs. 9%). The most common treatment-emergent adverse events in the MLN group were nausea (10%), fatigue (10%), and constipation (10%). Overall, the incidence of adverse events was consistent with, or less than, the adverse events listed in the prescribing information for MLN and PGN, the researchers noted.
No patients in either group had clinically significant increases or decreases in systolic blood pressure.
The results were limited by the open-label nature of the study. However, the data suggest that fibromyalgia patients with an incomplete response to PGN alone might benefit from the addition of MLN. "Milnacipran and pregabalin appear to be complementary in their actions in fibromyalgia patients," Dr. Farmer said.
The study was sponsored by Forest Laboratories and Cypress Bioscience. Two of the study coauthors were employed by these companies. Dr. Farmer is the chief principal investigator and medical director of Meridien Research.