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.

0 Followers
 · 
184 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Antidepressant drugs are commonly used to treat fibromyalgia but there is little knowledge about their mechanisms of action. The aim of this study was to compare the cerebral and behavioral response to positive treatment effects of antidepressants or placebo. Ninety-two fibromyalgia patients participated in a 12-week, double-blind, placebo-controlled, clinical trial with milnacipran; a noradrenalin-serotonin re-uptake inhibitor. Before and after treatment, measures of cerebral pain processing were obtained using functional magnetic resonance imaging. Also, there were stimulus-response assessments of pressure-pain, measures of weekly pain and fibromyalgia impact. Following treatment, milnacipran-responders exhibited significantly higher activity in the posterior cingulum, compared to placebo-responders. The mere exposure to milnacipran did not explain our findings since milnacipran-responders exhibited increased activity also in comparison to milnacipran non-responders. Stimulus-response assessments revealed specific antihyperalgesic effects in milnacipran-responders, which also correlated to reduced clinical pain and to increased activation of the posterior cingulum. A short history of pain predicted positive treatment response to milnacipran. We report segregated neural mechanisms for positive responses to treatment with milnacipran and placebo, reflected in the posterior cingulum. The increase of pain-evoked activation in the posterior cingulum may reflect a normalization of altered default mode network processing; an alteration implicated in fibromyalgia pathophysiology. Perspective The present article presents neural and psychophysical correlates to positive treatment responses in patients with fibromyalgia, treated with either milnacipran or placebo. The comparison between placebo- and milnacipran-responders may shed light on the specific mechanisms involved in antidepressant treatment of chronic pain.
    Journal of Pain 10/2014; 15(12). DOI:10.1016/j.jpain.2014.09.011 · 4.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fibromyalgia patients from a long-term, open-label study of milnacipran (50-200 mg/day) were eligible to participate in a 12-week, randomized, placebo-controlled withdrawal study. The withdrawal study evaluated loss of therapeutic response in patients who achieved ≥50% pain improvements after receiving up to 3.25 years of milnacipran. This post-hoc analysis investigated whether patients who met lower thresholds of pain improvement also experienced worsening of fibromyalgia symptoms upon treatment withdrawal. Among patients who received milnacipran ≥100 mg/day during the long-term study, three subgroups were identified based on percentage of pain reduction at randomization: ≥50% (protocol-defined "responders"; n=150); ≥30% to <50% (patients with clinically meaningful pain improvement; n=61); and <30% (n=110). Efficacy assessments included the visual analog scale (VAS) for pain, Fibromyalgia Impact Questionnaire-Revised (FIQR), 36-Item Short-Form Health Survey Physical Component Summary (SF-36 PCS), and Beck Depression Inventory (BDI). In the ≥30 to <50% subgroup, significant worsening in pain was detected after treatment withdrawal. The difference between placebo and milnacipran in mean VAS score changes for this subgroup (+9.0, P<0.05) was similar to the difference in protocol-defined responders (+9.4, P<0.05). In the <30% subgroup, no worsening in pain was observed in either treatment arm. However, patients in this subgroup experienced significant worsening in FIQR scores after treatment withdrawal (placebo, +6.9; milnacipran, -2.8; P<0.001), as well as worsening in SF-36 PCS and BDI scores. Patients who experienced ≥30% to <50% pain reduction with long-term milnacipran had significant worsening of fibromyalgia symptoms after treatment withdrawal. These results suggest that the conventional ≥30% pain responder cutoff may be adequate to demonstrate efficacy in randomized withdrawal studies of fibromyalgia. Patients in the <30% pain reduction subgroup had worsening scores on the FIQR and other multidimensional measures after treatment withdrawal, indicating the importance of identifying and managing the multiple symptoms of fibromyalgia.
    Journal of Pain Research 01/2014; 7:679-687. DOI:10.2147/JPR.S70200
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Centers for Disease Control criteria for chronic fatigue syndrome (CFS) specifically recognize that patients can have both CFS and depression. The clinician's challenge is to judge for each individual patient whether the complaint of fatigue is primarily depression, physical illness, such as CFS, or a combination of both. This review differentiates CFS and fibromyalgia, discussed as “chronic fatigue syndrome and related immune deficiency syndromes” (CFIDS), from depression in terms of physical signs, symptoms, biological parameters, brain imaging, immunology, and treatment. The review focuses on practical applications of research findings with a further focus on future ability to show clear biologic separation and specific treatment. When depressive symptoms exist with those of CFS, accurate differentiation can usually be accomplished by focusing on diagnostic criteria. Presence of multiple physical signs and symptoms of CFIDS may be of great value. In terms of laboratory testing, a single helpful test may be measuring the plasma cortisol, which is usually high in depression and low in CFS. Future research should focus on the combination of plasma cortisol with an index of serotonin function, which is high in CFIDS and low in depression. Additional research should focus on neuroimaging and immune differentiation. Combination of multiple tests should result in a significant and clinically useful separation between CFIDS and major depressive disorder (MDD). In treating patients with significant depression or MDD with CFIDS, one should think of the noradrenergic approach using bupropion or low-dose tricyclic antidepressants in combination with a selective serotonin reuptake inhibitor, especially sertraline, to aid improvement of global, pain, and immunologic parameters. Alternatively, serotonin norepinephrine reuptake inhibitors (venlafaxine and duloxetine) should be considered. Future treatment research should focus on larger placebo-controlled, double-blind trials of these and other antidepressants as well as the evaluation of psychostimulants, electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS).
    Journal of Chronic Fatigue Syndrome 12/2011; 13(4).

Full-text (2 Sources)

Download
168 Downloads
Available from
May 31, 2014