Fibromyalgia (FM) is a complex syndrome characterized by chronic widespread
musculoskeletal pain which is often accompanied by multiple other symptoms, including
fatigue, sleep disturbances, decreased physical functioning, and dyscognition. Due to these multiple symptoms, as well as high rates of comorbidity with other related disorders, patients with FM often report a reduced quality of life. Although the pathophysiology of FM is not completely understood, patients with FM experience
pain differently from the general population, most likely due to dysfunctional
pain processing in the central nervous system leading to both
hyperalgesia and
allodynia. In many patients with FM, this aberrant
pain processing, or central sensitization, appears to involve decreased
pain inhibition within the spinal tract, which is mediated by descending pathways that utilize
serotonin,
norepinephrine, and other
neurotransmitters. The reduced
serotonin and
norepinephrine levels observed in patients with FM suggest that medications which increase the levels of these
neurotransmitters, such as
serotonin and norepinephrine reuptake inhibitors (
SNRIs), may have clinically beneficial effects in FM and other
chronic pain conditions.
Milnacipran is an
SNRI that has been approved for the management of FM. In clinical trials, treatment with
milnacipran for up to 1 year has been found to improve the
pain and other symptoms of FM. Because FM is characterized by multiple symptoms that all contribute to the decreased quality of life and ability to function, the
milnacipran pivotal trials implemented responder analyses. These utilized a single composite endpoint to identify the proportion of patients who reported simultaneous and clinically significant improvements in
pain, global disease status, and physical function. Other domains assessed during the
milnacipran trials include
fatigue, multidimensional functioning, mood, sleep quality, and patient-reported dyscognition. This review article provides information intended to help clinicians make informed decisions about the use of
milnacipran in the clinical management of patients with FM. It draws primarily on results from 2 of the pivotal clinical trials that formed the basis of approval of
milnacipran in the United States by the Food and Drug Administration.