Clinical practice guidelines for treatment of fibromyalgia (FM) emphasize the role of pharmacologic interventions that address multiple symptoms, such as pain, fatigue, and sleep disturbance. Patients with FM may benefit from a combination of medications with complementary mechanisms of action that could yield additive or synergistic effects.
A rational combination therapy approach would be:
• Milnacipran [brand name Savella®], a dual reuptake inhibitor thought to augment norepinephrine and serotonin neurotransmitter signaling in descending pain modulatory neurons,
• Plus pregabalin [brand name Lyrica®), which may inhibit nociceptive signaling in ascending fibers through voltage-gated calcium channels.
This randomized, open-label, controlled study evaluated the efficacy and tolerability of milnacipran 50 mg BID when added to pregabalin 150 mg BID or 225 mg BID in FM patients who had an incomplete response to pregabalin during a 4- to 12-week open-label run-in phase.
Pregabalin incomplete responders (defined as patients with weekly recall VAS pain score 40 or more and 90 or less [0 to 100 scale], Patient Global Impression of Severity score 4 or more [moderately ill], and Patient Global Impression of Change [PGIC] score 3 or more [minimally improved]) were randomized to either pregabalin alone (n=179) or milnacipran with pregabalin (n=184) for 11 weeks.
The primary endpoint was an ITT responder analysis, with responders defined as patients reporting a PGIC score of “1” or “2” at endpoint.
• Significantly more patients receiving combination therapy were PGIC responders than patients receiving pregabalin alone.
• The addition of milnacipran to pregabalin also resulted in significantly greater reductions in mean weekly recall VAS pain scores.
• Approximately one-third of patients discontinued the study,
• With fewer patients discontinuing from the milnacipran with pregabalin combination group than pregabalin alone.
This was the first randomized controlled study to demonstrate that adding milnacipran to pregabalin therapy was tolerable and effective in improving global status and reducing pain in patients with FM. (Supported by Forest Laboratories, Inc. and Cypress Bioscience, Inc.)
Source: Presentation (Abstract #215) at American Pain Society Annual Meeting, May 6-8, 2010. By Farmer M, Dayani N, Trugman J, Wang Y, Gendreau R. Forest Research Institute and Cypress Bioscience, Inc., Jersey City, New Jersey and San Diego, California, USA.