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. 2013 Jun;5(3):113-26.
doi: 10.1177/1759720X13483894.

Milnacipran combined with pregabalin in fibromyalgia: a randomized, open-label study evaluating the safety and efficacy of adding milnacipran in patients with incomplete response to pregabalin

Philip J Mease  1 , Mildred V Farmer, Robert H Palmer, R Michael Gendreau, Joel M Trugman, Yong Wang
Affiliations

Milnacipran combined with pregabalin in fibromyalgia: a randomized, open-label study evaluating the safety and efficacy of adding milnacipran in patients with incomplete response to pregabalin

Philip J Mease et al. Ther Adv Musculoskelet Dis. 2013 Jun.

Abstract

Objective: To evaluate the safety, tolerability, and efficacy of adding milnacipran to pregabalin in patients with fibromyalgia who have experienced an incomplete response to pregabalin.

Methods: In this randomized, multicenter, open-label study, patients received pregabalin 300 or 450 mg/day during a 4- to 12-week run-in period. Patients with weekly recall visual analog scale (VAS) pain score of at least 40 and up to 90, Patient Global Impression of Severity score of at least 4, and Patient Global Impression of Change (PGIC) score of at least 3 were classified as incomplete responders and randomized to continue pregabalin alone (n = 180) or receive milnacipran 100 mg/day added to pregabalin (n = 184). The primary efficacy parameter was responder status based on PGIC score of up to 2. The secondary efficacy parameter was change from randomization in weekly recall VAS pain score. Safety parameters included adverse events (AEs), vital signs, and clinical laboratory tests.

Results: The percentage of PGIC responders was significantly higher with milnacipran added to pregabalin (46.4%) than with pregabalin alone (20.8%; p < 0.001). Mean improvement from randomization in weekly recall VAS pain scores was greater in patients receiving milnacipran added to pregabalin (-20.77) than in patients receiving pregabalin alone (-6.43; p < 0.001). During the run-in period, the most common treatment-emergent AEs with pregabalin were dizziness (22.8%), somnolence (17.3%), and fatigue (9.1%). During the randomized period, the most common treatment-emergent AEs with milnacipran added to pregabalin were nausea (12.5%), fatigue (10.3%), and constipation (9.8%).

Conclusions: In this exploratory, open-label study, adding milnacipran to pregabalin improved global status, pain, and other symptoms in patients with fibromyalgia with an incomplete response to pregabalin treatment.

Keywords: clinical trials; fibromyalgia; milnacipran; pain; pregabalin.

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Conflict of interest statement

Conflict of interest statement: Dr Mease has received research/grant funding, consultation fees, and speaker honoraria from Forest Laboratories, Inc., Cypress Bioscience, Inc., Jazz Pharmaceuticals, Eli Lilly and Company, Pfizer Inc., and UCB, Inc. Dr Farmer has received research/grant funding and consultation fees from Forest Laboratories, Inc. Dr Gendreau was formerly an officer at Cypress Bioscence, Inc., one of the companies involved in the development of milnacipran for the management of fibromyalgia. Drs Palmer, Trugman, and Wang are full-time employees of Forest Research Institute, Inc., a subsidiary of Forest Laboratories, Inc, and own stock in that company.

Figures

Figure 1.
Figure 1.
Flow diagram of study progress. ITT, intent to treat; PGIC, Patient Global Impression of Change.
Figure 2.
Figure 2.
PGIC responder rates, defined as the percentage of patients rating their overall improvement since entering the study as very much or much improved (PGIC score ≤ 2). BOCF, baseline observation carried forward; GLMM, generalized linear mixed model; LOCF, last observation carried forward; MLN + PGN, milnacipran added to pregabalin; mLOCF, modified last observation carried forward; n, number of responders; N, number of patients; OC, observed case; PGIC, Patient Global Impression of Change; PGN, pregabalin alone. *p < 0.001 versus PGN. $Percentages are estimates of treatment group response probabilities from the GLMM.
Figure 3.
Figure 3.
Least squares mean change from randomization in weekly recall VAS pain score (LOCF). LOCF, last observation carried forward; MLN + PGN, milnacipran added to pregabalin; PGN, pregabalin alone; VAS, visual analog scale. *p < 0.001 versus PGN.
See this image and copyright information in PMC

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