Article

Efficacy of milnacipran in patients with fibromyalgia

Cypress Biosciences, 4350 Executive Drive, San Diego, CA 92121, USA.
The Journal of Rheumatology (Impact Factor: 3.17). 11/2005; 32(10):1975-85.
Source: PubMed

ABSTRACT Fibromyalgia (FM) is a common musculoskeletal condition characterized by widespread pain, tenderness, and a variety of other somatic symptoms. Current treatments are modestly effective. Arguably, the best studied and most effective compounds are tricyclic antidepressants (TCA). Milnacipran, a nontricyclic compound that inhibits the reuptake of both serotonin and norepinephrine, may provide many of the beneficial effects of TCA with a superior side effect profile.
One hundred twenty-five patients with FM were randomly assigned in a 3:3:2 ratio to receive milnacipran twice daily, milnacipran once daily, or placebo for 3 months in a double-blind dose-escalation trial; 92% of twice-daily and 81% of once-daily participants achieved dose escalation to the target milnacipran dose of 200 mg.
The primary endpoint was reduction of pain. Both the once- and twice-daily groups showed statistically significant improvements in pain, as well as improvements in global well being, fatigue, and other domains. Response rates for patients receiving milnacipran were equal in patients with and without comorbid depression, but placebo response rates were considerably higher in depressed patients, leading to significantly greater overall efficacy in the nondepressed group.
In this Phase II study, milnacipran led to statistically significant improvements in pain and other symptoms of FM. The effect sizes were equal to those previously found with TCA, and the drug was generally well tolerated.

Download full-text

Full-text

Available from: Samuel A Mclean, Jul 05, 2015
0 Followers
 · 
189 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Interventions based on Cognitive Behavioral Therapy (CBT) are widely used to treat chronic pain, but the brain mechanisms responsible for these treatment effects are poorly understood. The aim of this study was to validate the relevance of the cortical control theory in response to an exposure-based form of CBT, Acceptance and Commitment Therapy, in patients with chronic pain. Forty-three female patients diagnosed with fibromyalgia syndrome were enrolled in a randomized, 12-week, waiting-list controlled clinical trial (CBT n=25; controls n=18). CBT was administered in groups of six patients during 12 weekly sessions. Functional magnetic resonance imaging (fMRI) during pressure-evoked pain was assessed before and after treatment or the 12-week period. Self-report questionnaires of depression and anxiety were administered pre- and posttreatment as well as 3 months following end of treatment. Patients treated with CBT reported larger improvement of fibromyalgia on the Patient Global Impression of Change measure, and improved depression and anxiety symptoms, compared to the waiting-list controls. However, there were no effects on clinical pain or pain sensitivity measures. An analysis of fMRI scans revealed that CBT led to increased activations in the ventrolateral prefrontal/lateral orbitofrontal cortex; regions associated with executive cognitive control. We suggest that CBT changes the brain's processing of pain through an altered cerebral loop between pain signals, emotions, and cognitions; leading to increased access to executive regions for reappraisal of pain. Our data thereby support our hypothesis about the activation of a cortical control mechanism in response to CBT treatment in chronic pain.
    Pain 05/2012; 153(7):1495-503. DOI:10.1016/j.pain.2012.04.010 · 5.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fibromyalgia and depression might represent two manifestations of affective spectrum disorder. They share similar pathophysiology and are largely targeted by the same drugs with dual action on serotoninergic and noradrenergic systems. Here, we review evidence for genetic and environmental factors that predispose, precipitate, and perpetuate fibromyalgia and depression and include laboratory findings on the role of depression in fibromyalgia. Further, we comment on several aspects of fibromyalgia which support the development of reactive depression, substantially more so than in other chronic pain syndromes. However, while sharing many features with depression, fibromyalgia is associated with somatic comorbidities and absolutely defined by fluctuating spontaneous widespread pain. Fibromyalgia may, therefore, be more appropriately grouped together with other functional pain disorders, while psychologically distressed subgroups grouped additionally or solely with affective spectrum disorders.
    01/2012; 2012(2090-1542):486590. DOI:10.1155/2012/486590
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fibromyalgia is a condition with widespread muscle pain. Prevalence studies showed that 2% to 7% of the population have fibromyalgia, which affects approximately one million Canadians. Fibromyalgia is most common in women, but it also involves men and children. As with most chronic illnesses, the causes of fibromyalgia are unknown. However, recent research supports underlying abnormalities in the central nervous system, which supports fibromyalgia as a chronic disease state and valid clinical entity. Pain is the primary symptom, often accompanied by overwhelming fatigue, sleep dysfunction and cognitive impairment. In 1990, the American College of Rheumatology developed diagnostic criteria for the diagnosis of fibromyalgia. Lifestyle changes, including pacing of activities and aerobic exercise, are very important in managing fibromyalgia symptoms. Emotional and behavioural therapy can also be helpful. Controlled trials of antidepressants, gabapentinoids, tramadol, zopiclone and sodium oxybate have shown effectiveness in fibromyalgia patients. Pregabalin and duloxetine were recently approved in the United States. Effective management of fibromyalgia is complex and requires a multidisciplinary treatment approach. Response and tolerance of different therapeutic interventions vary from patient to patient. Recent advances in the pathophysiology of fibromyalgia offer hope for new and improved therapies in the management of this disabling condition.
    Pain research & management: the journal of the Canadian Pain Society = journal de la societe canadienne pour le traitement de la douleur 11/2008; 13(6):477-83. · 1.39 Impact Factor