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Query: UMLS:C0016053 (fibromyalgia)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The primary objectives of this study were to assess the efficacy and safety of duloxetine for reducing pain severity in fibromyalgia patients with or without current major depressive disorder. This was a 6-month, multicenter, randomized, double-blind, placebo-controlled study. In total, 520 patients meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to duloxetine (20 mg/day, 60 mg/day, or 120 mg/day) or placebo, administered once daily, for 6 months (after 3 months, the duloxetine 20-mg/day group titrated to 60 mg/day). The co-primary outcome measures were the Brief Pain Inventory (BPI) average pain severity score and Patient Global Impressions of Improvement (PGI-I) score. Safety was assessed via treatment-emergent adverse events, and changes in vital sign, laboratory, and ECG measures. Compared with placebo-treated patients, those patients treated with duloxetine 120 mg/day improved significantly more on the co-primary outcome measures at 3 months (change in BPI score [-2.31 vs -1.39, P<0.001] and PGI-I [2.89 vs 3.39, P=0.004]) and at 6 months (change in BPI [-2.26 vs -1.43, P=0.003] and PGI-I [2.93 vs 3.37, P=0.012]). Compared with placebo, treatment with duloxetine 60 mg/day also significantly improved the co-primary measures at 3 months and BPI at 6 months. Duloxetine was efficacious in patients both with and without major depressive disorder. There were no clinically significant differences between treatment groups in changes in vital signs, laboratory measures, or ECG measures. Study results demonstrated that duloxetine at doses of 60 mg/day and 120 mg/day appears to be safe and efficacious in patients with fibromyalgia.
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PMID:Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or without major depressive disorder: Results from a 6-month, randomized, double-blind, placebo-controlled, fixed-dose trial. 1898 1

Most antidepressants in clinical use are believed to function by enhancing neurotransmission of serotonin [5-hydroxytryptamine (5-HT)] and/or norepinephrine (NE) via inhibition of neurotransmitter reuptake. Agents that affect reuptake of both 5-HT and NE (serotonin-norepinephrine reuptake inhibitors) have been postulated to offer greater efficacy for the treatment of major depressive disorder (MDD). These dual-acting agents also display a broader spectrum of action, including efficacy for MDD and associated painful physical symptoms, diabetic peripheral neuropathic pain, generalized anxiety disorder, and fibromyalgia syndrome. Substantial preclinical evidence shows that duloxetine, an approved drug for the treatment of MDD, generalized anxiety disorder, and the management of diabetic peripheral neuropathic pain, inhibits reuptake of both 5-HT and NE. This paper reviews clinical and neurochemical evidence of duloxetine's effects on 5-HT and NE reuptake inhibition. The clinical evidence supporting duloxetine's effects on NE reuptake inhibition includes indirect measures such as altered excretion of NE metabolites, cardiovascular effects, and treatment-emergent adverse event profiles similar to those for other drugs believed to act through the inhibition of NE reuptake. In summary, the data presented in this report provide clinical evidence of a mechanism for duloxetine involving both 5-HT and NE reuptake inhibition in humans and are consistent with preclinical evidence for 5-HT/NE reuptake inhibition.
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PMID:Clinical evidence for serotonin and norepinephrine reuptake inhibition of duloxetine. 1840 30

This article reviews current findings regarding the pathophysiologic abnormalities that contribute to the enhanced pain responses of individuals with fibromyalgia as well as the relationships between fibromyalgia and commonly co-occurring disorders. Risk factors for fibromyalgia or enhanced pain responses include genetic and family influences, environmental triggers, and abnormal neuroendocrine and autonomic nervous system function. These risk factors also are associated with several disorders that frequently co-occur with fibromyalgia, such as major depressive disorder, migraine, and irritable bowel syndrome. Indeed, fibromyalgia and these co-occurring conditions may be part of a group of affective spectrum disorders that share important common, and perhaps heritable, causal factors. Recent research strongly suggests that alterations in central processing of sensory input also contribute to the cardinal symptoms of fibromyalgia, persistent widespread pain and enhanced pain sensitivity. Exposure to psychosocial and environmental stressors, as well as altered autonomic nervous system and neuroendocrine responses, also may contribute to alterations in pain perception or pain inhibition. Understanding the pathophysiology of fibromyalgia and co-occurring disorders may help clinicians provide the most appropriate treatment to their patients.
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PMID:Pathophysiologic mechanisms of fibromyalgia and its related disorders. 1853 57

Guidelines of the American Psychiatric Association for borderline personality disorder (BPD) indicate selective serotonin reuptake inhibitors and the serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine for treating affective dysregulation and impulsive behavioural dyscontrol symptoms. The SNRI duloxetine has been studied in patients with major depression, generalized anxiety disorder and fibromyalgia, showing particular efficacy on somatic complaints. This study investigates duloxetine in the treatment of patients with BPD. Eighteen outpatients with a DSM-IV-TR diagnosis of BPD were treated with open-label duloxetine, 60 mg/day, for 12 weeks. Patients were assessed at baseline, week 4 and 12 with the CGI Severity item, the BPRS, the HAM-D, the HAM-A, the SOFAS, the BPD Severity Index (BPDSI) and the HSCL-90-Somatization Subscale (HSCL-90 SOM). Adverse effects were evaluated using the Dosage Record Treatment Emergent Symptom Scale. Statistics were performed with the analysis of variance. Significant P values were <or=0.05. Fourteen patients completed the study. Four patients (22.2%) discontinued treatment in the first 4 weeks because of non-compliance. A significant change was found for: BPRS, HAM-D, SOFAS, BPDSI total score and items 'impulsivity', 'outbursts of anger' and 'affective instability' and HSCL-90 SOM. Adverse effects were mild headache and nausea. Initial results suggest that duloxetine is an effective and well-tolerated treatment for BPD, with positive effects on somatic symptoms.
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PMID:Efficacy and tolerability of duloxetine in the treatment of patients with borderline personality disorder: a pilot study. 1871 47

Desvenlafaxine (O-desmethylvenlafaxine) is the major active metabolite of venlafaxine. Desvenlafaxine succinate is now undergoing active evaluation for its therapeutic efficacy in a variety of disorders, including major depressive disorder, vasomotor symptoms associated with menopause, fibromyalgia and diabetic neuropathy. Desvenlafaxine is a serotonin and norepinephrine reuptake inhibitor (SNRI) with similar activity to its parent compound venlafaxine, and little affinity for other brain targets, including muscarinic, cholinergic, histamine H(1) and alpha-adrenergic receptors. Desvenlafaxine has linear pharmacokinetics, low protein binding, a half-life of approximately 10 hours and is metabolized primarily via glucuronidation, and to a minor extent through CYP3A4. The desvenlafaxine succinate formulation appears to have good oral bioavailability. Clearance rates are reduced in the elderly, those with severe renal dysfunction and those with moderate to severe hepatic dysfunction, which may require dosage adjustments. Three published clinical trials have shown supportive but mixed results for the efficacy of desvenlafaxine in the treatment of major depressive disorder with daily doses ranging from 100 mg to 400 mg. One published clinical trial has shown mixed results for the efficacy of desvenlafaxine in the treatment of vasomotor symptoms associated with menopause with daily doses ranging from 50 mg to 200 mg. In these four clinical trials, desvenlafaxine was associated with several mild adverse effects, with the most common effect being nausea. Less common, but more serious, adverse effects reported in these trials included hypertension, QTc interval prolongation, exacerbation of ischemic cardiac disease, elevated lipids and elevated liver enzymes. The exact nature of these serious adverse effects, including the prevalence, clinical significance and potential risk factors, still needs to be fully elucidated. Desvenlafaxine has a low propensity for pharmacokinetic-based drug interactions, although it has the same potential for pharmacodynamic interactions as other serotonin-norepinephrine reuptake inhibitors. Desvenlafaxine is currently another treatment option for major depressive disorder. The only identified potential advantage of desvenlafaxine over venlafaxine or other antidepressant agents at this time is the apparently reduced risk for pharmacokinetic drug interactions.
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PMID:Desvenlafaxine succinate for major depressive disorder. 1880 99

Previous research has suggested that some fibromyalgia may be part of an "affective spectrum disorder," pathophysiologically related to major depression. To examine the suspected association between fibromyalgia syndrome and depression, we conducted a family history study of depression among the first degree relatives (parents, siblings, and children) of two groups of probands with fibromyalgia, one with and one without a lifetime history of major depressive disorder. We tested the hypothesis that depression in patients with fibromyalgia is associated with a family history of depression. Major psychopathology in the probands was assessed with the Schedule for Affective Disorders and Schizophrenia and diagnosed using the Research Diagnostic Criteria. Forty fibromyalgia probands with and 14 fibromyalgia probands without a lifetime history of depression were interviewed about their parents, siblings, and children using the Family History Research Diagnostic Criteria format. Odds ratios were calculated, comparing the proportions of relatives with a history of depression in the two fibromyalgia proband groups. Lifetime histories of depression were found in 18% (n = 16) of the relatives of the probands with fibromyalgia and depression and in 9% (n = 25) of the relatives of the probands who did not have depression. Probands who had fibromyalgia and a history of major depression had more than twice the odds of having a relative who had depression than did the probands who had fibromyalgia but did not have a history of depression (odds ratio = 2.17 (95% confidence interval = 1.02-4.47)). These results suggest that depression in patients with fibromyalgia is associated with a family history of depression. Thus major depressive disorder in patients with fibromyalgia may be attributed more to their familial predisposition to depression than to a reaction to the pain and disability associated with fibromyalgia.
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PMID:Fibromyalgia: a study of family history of depression. 1907 70

The depressive symptoms are associated with chronic pain in this study. A cross-sectional study was performed. A visual analog scale was used to register pain intensity. Depressive symptoms were measured using the Center of Epidemiological Studies (CES-Dr) scale as modified by Eaton and reviewed for use in the Mexican population. The study included 245 patients, with a mean age of 46 years, 86.1% of whom were female. The prevalence of some degree of depression was 55.1%. Patients with fibromyalgia had the highest prevalence of symptoms of depression (78.38%) and major depression (29.73%). Stepwise multiple regressions indicated that the best model (r2 = 0.26) to predict the CES-Dr score included the global pain score (P < 0.0001) and education level (P < 0.004). The Cronbach's alpha of the CES-Dr was high (alpha = 0.888). There was moderate correlation (r = 0.442), P < 0.0001 of the CES-Dr numeric score with the intensity of global pain.
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PMID:Depression and its correlation with in patients pain in the rheumatology service of a Mexican teaching hospital. 1911 64

Chronic pain is often associated with comorbidities such as anxiety and depression, resulting in a low health-related quality of life. The mechanisms underlying this association are not clear, but a disturbance in the pain control systems from the brain stem has been suggested. Thirty neuropathic pain (NP) patients, 28 patients with fibromyalgia (FM), and 26 pain-free age- and gender-matched controls were included and examined with respect to mental distress (self-rated Symptom Checklist-92), depression (doctor-rated Hamilton Depression Scale and self-rated Major Depression Inventory), and anxiety (doctor-rated Hamilton Anxiety Scale and self-rated Anxiety Inventory). In addition, patients assessed their health-related quality of life (SF-36). Chronic pain patients with FM and NP had significantly more mental distress including depression and anxiety than healthy controls both by self-rating and by a professional rating. However, these scores are low compared to other studies on mental distress in chronic pain patients. Only few chronic pain patients meet the diagnostic criteria for depression (NP 3.3%, FM 7.1%), and associations between pain and mental symptoms were only found in the FM group despite similar pain intensities. The findings suggest that different mechanisms are responsible for the development of mood disorders in the two patient groups.
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PMID:Depression, anxiety, health-related quality of life and pain in patients with chronic fibromyalgia and neuropathic pain. 1947 57

This article synthesizes recent data suggesting that the high rates of comorbidity observed between major depression, fibromyalgia and neuropathic pain likely result from the fact that these disorders share multiple biological and environmental underpinnings. This perspective suggests that these biologically complex conditions result from similar genetic vulnerabilities interacting with environmental adversity. Shared genetic determinants include poorly functional alleles regulating monoaminergic, glutamatergic, neurotrophic, opioid and inflammatory cytokine signaling. Chief among environmental risk factors are psychosocial stress and illness, both of which promote, in vulnerable individuals, relative resistance to glucocorticoids, increased sympathetic/decreased parasympathetic activity and increased production and release of proinflamnmatory mediators. Dysregulation of stress/inflammatory pathways promotes alterations in brain circuitry that modulates mood, pain and the stress response. Over time, these functional changes likely promote disruptions in neurotrophic support and disturbances of glia-neuronal communication. These changes, in turn, have been associated with the related processes of central sensitization in pain disorders and "kindling" in depression, both of which may account for the progressive and self-perpetuating nature of these disorders, especially when inadequately treated.
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PMID:Neurobiology of depression, fibromyalgia and neuropathic pain. 1948 16

Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor available in delayed-release capsules for oral use. Duloxetine 60 mg/day, compared with placebo, was associated with a greater reduction from baseline in the Brief Pain Inventory (BPI) average pain severity score, a greater improvement in the patient-rated global impression of improvement (PGI-I) scale in patients with fibromyalgia, with or without major depressive disorder, in two 12- and 15-week phase III studies. In a 27-week, phase III trial, there was no significant difference between duloxetine (60 or 120 mg/day) and placebo for the least squares mean change from baseline to endpoint in BPI average pain scores and the PGI-I score. The significant improvements in efficacy that occurred in patients with fibromyalgia during 8 weeks of open-label treatment with duloxetine 60 mg/day were generally maintained during 52 weeks of subsequent blinded treatment at the same dosage in a phase III trial. Nonresponders during treatment with open-label duloxetine 60 mg/day, demonstrated no increased ability to respond if the duloxetine dosage was up-titrated to 120 mg/day than those who remained on the same dosage during the subsequent 52-week, double-blind phase. Duloxetine was generally well tolerated in studies of up to 1 year in duration, with nausea being the most frequent adverse event and main cause for discontinuing therapy.
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PMID:Duloxetine: in patients with fibromyalgia. 1953 38


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