Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016053 (fibromyalgia)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 5-HT3 receptor is a pentameric ligand-gated cation channel which is found in the central and peripheral nervous system and on extraneuronal locations like lymphocytes, monocytes and fetal tissue. Five monomer subtypes, the 5-HT(3A-E) subunits, have been identified which show differences in the amino-terminal and the transmembrane region. The functional relevance of different receptor compositions is not yet clarified. 5-HT3 receptors are located predominantly in CNS regions that are involved in the integration of the vomiting reflex, pain processing, the reward system and anxiety control. The preferential localization on nerve endings is consistent with a physiological role of 5-HT3 receptors in the control of neurotransmitter release such as dopamine, cholecystokinin, glutamate, acetylcholine, GABA, substance P, or serotonin itself. 5-HT3-receptor agonists cause unpleasant effects like nausea and anxiety, and no clinical use has been considered. In contrast, the introduction of 5-HT3-receptor antagonists for chemotherapy-induced vomiting was extremely successful. After development of other gastrointestinal indications like postoperative vomiting and diarrhea-predominant irritable bowel syndrome recent research focuses on rheumatological indications such as fibromyalgia, rheumatoid arthritis and tendinopathies. Positive effects have also been observed for pain syndromes such as chronic neuropathic pain and migraine. These effects seem to be related to substance P-mediated inflammation and hyperalgesia. Furthermore, antiinflammatory and immunomodulatory properties have been observed for 5-HT3-receptor antagonists which might explain promising findings in systemic sclerosis and other immunological conditions. For all of these innovative indications the optimal dosing schedule is a crucial issue, since a bell-shaped dose-response curve has been observed repeatedly for 5-HT3-receptor antagonists, particularly in CNS effects.
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PMID:The neuronal 5-HT3 receptor network after 20 years of research--evolving concepts in management of pain and inflammation. 1731 6

Acupuncture (AP) is effective for the treatment of postoperative and chemotherapy-induced nausea/vomiting and for postoperative dental pain. Several recent randomized trials have provided strong evidence for beneficial AP effects on chronic low-back pain and pain from knee osteoarthritis. For many other chronic pain conditions, including headaches, neck pain, and fibromyalgia, the evidence supporting AP's efficacy is less convincing. AP's effects on experimental pain appear to be mediated by analgesic brain mechanisms through the release of neurohumoral factors, some of which can be inhibited by the opioid antagonist naloxone. In contrast to placebo analgesia, AP-related pain relief takes considerable time to develop and to resolve. Thus, some of the long-term effects of AP analgesia cannot be explained by placebo mechanisms. Furthermore, it appears that some forms of AP are more effective for providing analgesia than others. Particularly, electro-AP seems best to activate powerful opioid and non-opioid analgesic mechanisms.
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PMID:Mechanisms of acupuncture analgesia: effective therapy for musculoskeletal pain? 1817 1

We present a fibromyalgia patient with traumatic cerebrospinal fluid (CSF) leak. A woman was referred because of widespread pain, general fatigue, dizziness, nausea, vomiting, and deterioration of memory after a traffic accident. These signs and symptoms in a sitting or standing position were more deteriorated than in a recumbent position. Although she was diagnosed with fibromyalgia, her widespread pain was unusually severe. She was diagnosed with traumatic CSF leak based on radioisotope cisternography. Her widespread pain was slightly decreased after epidural blood patches, but the nausea completely disappeared and dizziness was eased. A second radioisotope cisternography revealed that the leak of cerebrospinal fluid was discontinued. CSF leak is characterized by headache, nausea, dizziness, and visual impairment. The symptoms and signs resemble Barre-Lieou syndrome. Another characteristic is that these symptoms and signs in a sitting or standing position are more deteriorated than in a recumbent position. Fibromyalgia after trauma is sometimes comorbid with traumatic CSF leak. Radioisotope cisternography is essential for diagnosis. It demonstrates direct findings such as radioisotope leak into the spinal epidural space and indirect findings such as early bladder filling and/or the rapid disappearance of radioisotopes from the CSF space. A beneficial treatment is an epidural blood patch. Patients with fibromyalgia and traumatic CSF leak are likely to suffer more severe signs and symptoms such as increased widespread pain than patients with fibromyalgia alone. Patients with fibromyalgia and traumatic CSF leak are often refractory to treatment.
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PMID:A fibromyalgia patient with traumatic cerebrospinal fluid leak: a case report. 1850 Apr 38

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

This Practice Point commentary discusses the first two trials of long-term drug treatment in fibromyalgia. In Russell et al.'s study, 33% of patients receiving 6-month treatment with 60 mg/day duloxetine responded to therapy; the number needed to treat was seven. In the three treatment arms, 15% (60 mg/day duloxetine), 27% (120 mg/day duloxetine) and 13% (placebo) of patients discontinued treatment because of adverse events (the most common being nausea [24%] and fatigue [14%]). In Crofford et al.'s study, 32% of patients who received pregabalin had loss of therapeutic response, compared with 61% of patients treated with placebo. The discontinuation rate due to adverse events (dizziness in 36% of cases and somnolence in 22%) during the randomized treatment phase was 16% with pregabalin and 7% with placebo. This commentary discusses the implications of these trials for clinical practice and considers areas for future research in the field. In view of the current results, duloxetine and pregabalin could be administered together and as part of multimodal and multidisciplinary therapy, but treatment should 'start low and go slow'.
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PMID:Duloxetine and pregabalin: safe and effective for the long-term treatment of fibromyalgia? 1840 Apr

The purpose of this report is to describe the overall safety profile of both short- and longer-term duloxetine treatment of fibromyalgia. Data from four double-blind, randomized, placebo-controlled studies (two with 6-month open-label extension phases) and a 1-year, open-label safety study were included. Safety measures included treatment-emergent adverse events (TEAEs), adverse events leading to discontinuation, serious adverse events (SAEs), clinical laboratory tests, vital signs, and electrocardiograms. The most common TEAEs for short-term treatment with duloxetine were nausea (29.3%), headache (20.0%), dry mouth (18.2%), insomnia (14.5%), fatigue (13.5%), constipation (14.5%), diarrhea (11.6%), and dizziness (11.0%; all p < 0.05 vs. placebo). Most TEAEs emerged early and were mild to moderate in severity. The profile of adverse events in patients enrolled at least 6 months, and for patients in the 1-year study, was similar to that found in the short-term treatment studies, with no new adverse events emerging at a notable rate. About 20% of patients discontinued due to adverse events in the short-term treatment studies and in the 1-year study. SAEs were uncommon, and none occurred at a significantly higher frequency for duloxetine compared with placebo. Mean changes in vital signs and weight were small. Rates of treatment-emergent potentially clinically significant (PCS) vital sign, laboratory, and electrocardiogram measures were low, with only PCS rates of alanine aminotransferase being significantly higher for duloxetine compared with placebo in the placebo-controlled treatment studies. In the 1-year study, four patients (1.1%) had suicide-related behavior. The data provided here summarize short- and long-term safety from five clinical studies in patients treated with duloxetine for fibromyalgia. In addition, postmarketing surveillance continues for adverse events reported with duloxetine in fibromyalgia, as in other indications.
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PMID:Safety and tolerability of duloxetine in the treatment of patients with fibromyalgia: pooled analysis of data from five clinical trials. 1953 10

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

(1) Fibromyalgia is characterised by a range of symptoms that include muscle pain, fatigue and sleep disorders. Anxiety and depression are often also present. The cause is unknown. More women than men are affected; (2) The following review focuses on differential diagnoses and available treatments for fibromyalgia, based on a review of the literature using the standard Prescrire methodology; (3) Fibromyalgia is mainly diagnosed by excluding other possibilities. The principal differential diagnoses are rheumatic involvement of the spine, systemic inflammatory disorders, and hypothyroidism. Unlike these other conditions, fibromyalgia is not associated with radiological or laboratory abnormalities; (4) Paracetamol has not been compared with other treatments in fibromyalgia. Nonsteroidal antiinflammatory drugs have no specific effect; (5) The only two trials assessing tramadol showed little effect; in one study the average pain score was 53 mm in the tramadol group versus 65 mm in the placebo group, on a scale ranging from 0 to 100 mm. The adverse effects of tramadol are those of opiates in general, mainly nausea and dependence. Tramadol interacts with numerous other drugs; (6) The efficacy of tricyclic antidepressants is also difficult to quantify. Their limited superiority over placebo lasts no more than a few months. The efficacy of selective serotonin reuptake inhibitor antidepressants (fluoxetine, paroxetine and citalopram), serotonin and nonadrenaline reuptake inhibitors (duloxetine and milnacipran) is even less well established. Duloxetine has been tested in four placebo-controlled trials with unconvincing results; (7) Pregabalin and gabapentin, two antiepileptic drugs, appear to be more effective than placebo but have only been tested in short-term trials. In one trial 44% of patients in the pregabalin group said they felt better after 13 weeks versus 35% of patients in the placebo group. However, adverse effects are frequent and sometimes troublesome (drowsiness, dizziness, nausea, weight gain). In clinical trials, 19% to 33% of patients stopped treatment due to adverse effects after 13 weeks, depending on the dose of pregabalin; (8) Assessments of non-drug treatments in this setting are generally mediocre. The best-assessed alternative therapies (acupuncture and physical exercise) only have a limited effect; (9) In practice, when a patient presents with symptoms compatible with fibromyalgia, the first step is to rule out a treatable condition. Quality of life may be improved by first acknowledging that the pain is real, and possibly by providing psychological, medical, social and occupational support. The limited efficacy of available drugs, and their potential adverse effects, should be discussed with the patient.
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PMID:Fibromyalgia: poorly understood; treatments are disappointing. 1974 61

Milnacipran is an orally administered selective serotonin and norepinephrine (noradrenaline) reuptake inhibitor indicated for the management of fibromyalgia in adults. In adults, milnacipran was generally effective in the treatment of fibromyalgia in four well designed trials of 3 or 6 months' duration. Composite responder rates for the treatment of fibromyalgia and fibromyalgia pain (co-primary efficacy variables) were generally higher with milnacipran 100 or 200 mg/day (in two divided doses) than with placebo after 12 weeks of fixed-dose treatment. In one study, the composite responder rate for fibromyalgia pain (co-primary efficacy variable) was also higher with milnacipran 200 mg/day than with placebo after 24 weeks of fixed-dose treatment. Furthermore, the benefits of milnacipran therapy were sustained in a 6-month extension of an initial double-blind trial. Improvements from baseline in mean 24-hour recall pain scores, mean weekly recall pain scores, Patient Global Impression of Change scores and in several items of the Fibromyalgia Impact Questionnaire were observed in patients receiving continuous milnacipran for up to 12 months, as well as in patients who switched from placebo to milnacipran therapy at the start of the extension phase. Milnacipran was generally well tolerated in adults with fibromyalgia, with most adverse events being mild to moderate in severity. Nausea was the most common adverse event reported in milnacipran recipients.
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PMID:Milnacipran: in fibromyalgia. 2003 Apr 28


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