A European Multicenter Randomized Double-blind Placebo-controlled Monotherapy Clinical Trial of Milnacipran in Treatment of Fibromyalgia
ABSTRACT This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population.
Outpatients diagnosed with FM according to 1990 American College of Rheumatology criteria (N = 884) were randomized to placebo (n = 449) or milnacipran 200 mg/day (n = 435) for 17 weeks (4-week dose escalation, 12-week stable dose, 9-day down-titration), followed by a 2-week posttreatment period. The primary efficacy criterion was a 2-measure composite responder analysis requiring patients to achieve simultaneous improvements in pain (>or= 30% improvement from baseline in visual analog scale, 24-hour morning recall) and a rating of "very much" or "much" improved on the Patient Global Impression of Change scale. If responder analysis was positive, Fibromyalgia Impact Questionnaire (FIQ) was included as an additional key primary efficacy measure.
At the end of the stable dose period (Week 16), milnacipran 200 mg/day showed significant improvements from baseline relative to placebo in the 2-measure composite responder criteria (p = 0.0003) and FIQ total score (p = 0.015). Significant improvements were also observed in multiple secondary efficacy endpoints, including Short-Form 36 Health Survey (SF-36) Physical Component Summary (p = 0.025), SF-36 Mental Component Summary (p = 0.007), Multidimensional Fatigue Inventory (p = 0.006), and Multiple Ability Self-Report Questionnaire (p = 0.041). Milnacipran was safe and well tolerated; nausea, hyperhidrosis, and headache were the most common adverse events.
Milnacipran is an effective and safe treatment for pain and other predominant symptoms of FM. Registered as trial no. NCT00436033.
- SourceAvailable from: Holger Cramer
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- "While a diagnosis according to the earlier criteria of the American College of Rheumatology required the presence of a specific number of tender points, more recent guidelines did not define tender points but focused on the presence of widespread pain locations  . It was estimated that between 2.9 and 3.8% of the general population in Europe and the US are affected   , with the majority of patients in clinical settings being female . Many patients with fibromyalgia utilize complementary and alternative therapies in addition to conventional medicine. "
ABSTRACT: Objectives. This systematic overview of reviews aimed to summarize evidence and methodological quality from systematic reviews of complementary and alternative medicine (CAM) for the fibromyalgia syndrome (FMS). Methods. The PubMed/MEDLINE, Cochrane Library, and Scopus databases were screened from their inception to Sept 2013 to identify systematic reviews and meta-analyses of CAM interventions for FMS. Methodological quality of reviews was rated using the AMSTAR instrument. Results. Altogether 25 systematic reviews were found; they investigated the evidence of CAM in general, exercised-based CAM therapies, manipulative therapies, Mind/Body therapies, acupuncture, hydrotherapy, phytotherapy, and homeopathy. Methodological quality of reviews ranged from lowest to highest possible quality. Consistently positive results were found for tai chi, yoga, meditation and mindfulness-based interventions, hypnosis or guided imagery, electromyogram (EMG) biofeedback, and balneotherapy/hydrotherapy. Inconsistent results concerned qigong, acupuncture, chiropractic interventions, electroencephalogram (EEG) biofeedback, and nutritional supplements. Inconclusive results were found for homeopathy and phytotherapy. Major methodological flaws included missing details on data extraction process, included or excluded studies, study details, and adaption of conclusions based on quality assessment. Conclusions. Despite a growing body of scientific evidence of CAM therapies for the management of FMS systematic reviews still show methodological flaws limiting definite conclusions about their efficacy and safety.Evidence-based Complementary and Alternative Medicine 01/2015; 2015:610615. DOI:10.1155/2015/610615 · 1.88 Impact Factor
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- "Milnacipran, an SNRI, elicits an antinociceptive or antiallodynic effect in rodent models with neuropathic pain following intrathecal administration (Obata et al., 2005; King et al., 2006; Suzuki et al., 2008; Ikeda et al., 2009; Takeda et al., 2009) or systemic administration (Yokogawa et al., 2002; Önal et al., 2007; Berrocoso et al., 2011). In addition, the effect of milnacipran on patients with fibromyalgia as well as depression has been clinically evaluated (Clauw et al., 2008; Mease et al., 2009; Branco et al., 2010; Matthey et al., 2013). The antiallodynic effects of SNRIs have been mainly evaluated by examining the change of the threshold of the withdrawal response to mechanical stimulation. "
ABSTRACT: Milnacipran, a reuptake inhibitor of noradrenaline (NA) and serotonin (5-HT), elicits an antiallodynic effect in rats with neuropathic pain; however, the role of NA and 5-HT receptors in the induction of the antiallodynic effect of milnacipran remains unclear. Thus, we examined the effects of prazosin as an α1 adrenoceptor antagonist, yohimbine as an α2 adrenoceptor antagonist, metergoline as a 5-HT1, 5-HT2 and 5-HT7 receptor antagonist, cyanopindolol as a 5-HT1A/1B receptor antagonist, ketanserin as a 5-HT2 receptor antagonist, and ondansetoron as a 5-HT3 receptor antagonist on the antiallodynic effect of milnacipran in neuropathic rats with chronic constriction injury (CCI). The CCI rats expressed mechanical and thermal allodynia, which was attenuated by intrathecal injection of milnacipran. Yohimbine, but not prazosin, reversed the milnacipran-induced antiallodynic effect. The antiallodynic effect of milnacipran was also reversed by metergoline, ketanserin and ondansetron, while cyanopindolol reversed the antiallodynic effect on mechanical, but not thermal stimulation. Furthermore, c-Fos expression in lamina I/II of the spinal dorsal horn was enhanced by thermal stimulation and the enhanced expression of c-Fos was suppressed by milnacipran. This effect of milnacipran was reversed by yohimbine, metergoline, katanserin and ondansetron, but not prazosin. These results indicate that the effect of milnacipran on mechanical and thermal allodynia and c-Fos expression is elicited through the α2 adrenoceptor, but not α1 adrenoceptor, and 5-HT2 and 5-HT3 receptors; furthermore, the 5-HT1A/1B receptor is involved in mechanical allodynia, but not thermal allodynia.European Journal of Pharmacology 05/2014; 738. DOI:10.1016/j.ejphar.2014.05.022 · 2.68 Impact Factor
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- "Antidepressants have been found to be effective in reducing pain among individuals with OA and fibromyalgia [12,13]. Although, antidepressants therapy is the major modality of treatment for depression, it may be used to treat both depression and pain as well for individuals with arthritis [4,13]. "
ABSTRACT: Background Arthritis and depression often co-occur; however, studies that describe patterns of depression treatment among individuals with arthritis are scant. The purpose of the study was to examine depression treatment patterns among individuals with osteoarthritis (OA) by predisposing, enabling, need factors, personal health practices and external health environment. Methods Retrospective cross-sectional design was used. Data were obtained from 2008 and 2010 Medical Expenditure Panel Survey (MEPS). The sample consisted of 647adults aged over 21 years with depression and OA. Depression treatment was categorized as: 1) No treatment;2) antidepressant use only and 3) both antidepressants and psychotherapy (combination therapy). Chi- square tests and multinomial logistic regressions were used to describe patterns of depression treatment. All analysis was performed using Statistical Analysis Software (SAS) version 9.3. Results Overall, 13.0% of the study sample reported no depression treatment, 67.8% used antidepressants only and 19.2% used combination therapy. Among individuals with OA significant subgroup differences in depression treatment were observed. For example, African Americans were less likely to report depression treatment compared to whites [antidepressants: AOR=0.33, 95% CI=0.21,0.51; combination therapy: AOR=0.39, 95% CI=0.23, 0.65]. Elderly adults were more likely to receive antidepressants and less likely to receive psychotherapy as compared to younger adults [AOR=0.53, 95% CI= 0.28,0.98]. Adults with anxiety were more likely to report depression treatment compared to those without anxiety [antidepressants: AOR=1.53, 95% CI=1.06, 2.22; combination therapy: AOR=3.52, 95% CI=2.40, 5.15]. Conclusion Future research needs to examine the reason for low rates of combination therapy as well as subgroup differences in combination therapy among individuals with OA.BMC Psychiatry 04/2013; 13(1):121. DOI:10.1186/1471-244X-13-121 · 2.24 Impact Factor