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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pain is a common cause of disability in osteoarthritis. Duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), has demonstrated analgesic effects in diabetic peripheral neuropathy and fibromyalgia. Considering its central mechanism of action, duloxetine may be effective in other pain states with evidence of central sensitization. Herein, we report the results of a 13-week, randomized, double-blind, placebo-controlled trial of duloxetine (60-120 mg/day) versus placebo in the treatment of knee pain in 231 patients meeting clinical and radiographic criteria for osteoarthritis of the knee. Duloxetine was superior to placebo on the primary efficacy measure (weekly mean 24-h pain scores) beginning at Week 1 and continuing through the treatment period (P < or = .05). There was also a significant improvement in the WOMAC physical functioning subscale and several other secondary outcomes. Adverse-event rates did not differ significantly between treatment groups (49.5% for duloxetine 60-120 mg/day, and 40.8% for placebo).
Pain 2009 Dec
PMID:Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee pain: a 13-week, randomized, placebo-controlled trial. 2042 3

In this article, we investigate the range of treatments prescribed for fibromyalgia. The data suggest that the majority of those treated, 72 percent, receive only one pharmaceutical. An additional 18 percent of patients were prescribed two products and 10% received three products. Pregabalin (Lyrica(R)) monotherapy was the most commonly prescribed regimen (28% of patients) followed by duloxetine (Cymbalta(R)) monotherapy (6%). From a therapeutic class perspective, fibromyalgia patients received pain therapies (42%), antiepileptics (40%), antidepressants (28%), muscle relaxants (14%), and sleep agents (8%). An expert commentary is also included.
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PMID:Treatment of fibromyalgia. 1972 97

(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 and duloxetine, serotonin/noradrenalin reuptake inhibitors, and pregabalin, a alpha(2)-delta(1) Ca(2+) channel blocker, are efficacious against fibromyalgia, a condition characterized by diffuse chronic pain and associated with stress. We compared these compounds (i.p. route), in rat models of acute/inflammatory pain (2.5% intraplantar formalin) and stress-induced ultrasonic vocalization (USV: 22kHz calls following presentation of a conditioned stimulus previously associated with foot-shocks). In the formalin test, milnacipran dose-dependently attenuated paw elevation and licking (minimal effective dose, MED: 2.5mg/kg for licking/late phase). Duloxetine was slightly more potent (MED=0.63). Pregabalin also reduced paw licking/late phase (MED=0.63), but was inactive up to 160mg/kg for paw elevation (both phases) and paw licking (early phase). Milnacipran dose-dependently reduced USV (MED=10, near total inhibition at 20mg/kg); duloxetine was less potent (MED=20). Pregabalin (2.5-80mg/kg) was only significantly active at 40mg/kg. Milnacipran, duloxetine and pregabalin possess analgesic activity in the formalin test on paw licking/late phase (corresponding to inflammatory pain with a central sensitization component). In the stress-induced USV model, milnacipran was the most potent and efficacious compound. To summarize, reduction of formalin-induced paw licking/late phase might constitute a useful indicator of potential activity against inflammatory/centrally sensitized pain, as might be expressed in fibromyalgia.
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PMID:Comparison of milnacipran, duloxetine and pregabalin in the formalin pain test and in a model of stress-induced ultrasonic vocalizations in rats. 1988 99

Fibromyalgia is a chronic pain disorder characterized by widespread pain, stiffness, insomnia, fatigue and distress. Several randomized controlled trials (RCTs) have shown moderate effectiveness of pharmacological therapies for fibromyalgia pain. Evidence from these trials suggests that pharmacological therapy can not only improve pain but also fatigue, function and well-being in patients with fibromyalgia. Duloxetine and milnacipran, two highly selective serotonin-norepinephrine (noradrenaline) reuptake inhibitors, and the alpha(2)delta agonist pregabalin have been approved by the US FDA for the treatment of fibromyalgia symptoms. In general, about half of all treated patients seem to experience a 30% reduction of symptoms, suggesting that many patients with fibromyalgia will require additional therapies. Thus, other forms of treatment, including exercise, cognitive behavioural therapies and self-management strategies, may be necessary to achieve satisfactory treatment outcomes. Despite promising results of pilot trials, RCTs with dopamine receptor agonists and sodium channel antagonists have so far been disappointing for patients with fibromyalgia. However, new pharmacological approaches for the treatment of fibromyalgia pain and insomnia using sodium oxybate appear to be promising.
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PMID:Pharmacological treatment of fibromyalgia syndrome: new developments. 2003 Apr 22

Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) which is FDA approved for the treatment of generalized anxiety disorder (GAD) in doses of 30 mg to 120 mg daily. Duloxetine has been shown to significantly improve symptoms of GAD as measured through the Hamilton Anxiety Rating Scale (HAMA), the Clinical Global Impressions Scale (CGI-I), and other various outcome measures in several placebo-controlled, randomized, double blind, multi-center studies. Symptom improvement began within the first few weeks, and continued for the duration of the studies. In addition, duloxetine has also been shown to improve outcomes in elderly patients with GAD, and in GAD patients with clinically significant pain symptoms. Duloxetine was noninferior compared with venlafaxine XR. Duloxetine was found to have a good tolerability profile which was predictable and similar to another SNRI, venlafaxine. Adverse events (AEs) such as nausea, constipation, dry mouth, and insomnia were mild and transient, and occurred at relatively low rates. It was found to have a low frequency of drug interactions. In conclusion, duloxetine, a selective inhibitor for the serotonin and norepinephrine transporters, is efficacious in the treatment of GAD, and has a predictable tolerability profile, with AEs generally being mild to moderate.
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PMID:Duloxetine in the treatment of generalized anxiety disorder. 2036 Aug 99

Duloxetine, a dual acting norepinephrine serotonin reuptake inhibitor, is a relatively new pharmacologic agent utilized in the treatment of depression, as well as diabetic neuropathic pain, fibromyalgia, and female stress urinary incontinence. This expanding scope of usage will inevitably lead to its eventual appearance during routine post-mortem toxicologic assays. Currently there is a paucity of post-mortem toxicologic data concerning duloxetine. The current report provides six additional case reports of post-mortem duloxetine levels, along with a review of duloxetine's pharmacokinetics, and the toxicologic manifestations which have been reported in the literature. The post-mortem levels reported, including the highest level recorded to date, are integrated with previously published reports to generate a foundation for a nascent guide to the interpretation of post-mortem duloxetine levels that could be encountered during routine post-mortem toxicologic analyses, and establish a basis upon which the establishment of toxic and lethal thresholds for this compound can be further elucidated with greater clarity.
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PMID:Adverse events, toxicity and post-mortem data on duloxetine: case reports and literature survey. 2038 51

We investigated antidepressant prescriptions and reasons for use. According to our data, the top 10 molecules represent approximately 95% of total antidepressant prescriptions for both primary care physicians (PCPs) and psychiatrists. The primary difference between PCPs and psychiatrists was the increased use of buproprion and tricyclics/tetracyclics by psychiatrists. The selective serotonin reuptake inhibitors (SSRIs) and other newer antidepressants such as venlafaxine (Effexor) and buproprion (Wellbutrin) are used to treat depression, anxiety, and bipolar disorders. The noted exception is duloxetine (Cymbalta), which looks like a blend between the newer agents and the tricyclics where there is use beyond the traditional central nervous system (CNS) disorders into pain and migraine.
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PMID:Use of antidepressants: expansion beyond depression and anxiety. 2043 60

In this article, we investigate the range of treatments prescribed for fibromyalgia. The data suggest that the majority of those treated, 82 percent, receive only one pharmaceutical. An additional 12 percent of patients were prescribed two products and six percent received three products. Pregabalin (Lyrica(R)) monotherapy was the most commonly prescribed regimen (21% of patients) followed by duloxetine (Cymbalta(R)) monotherapy (20%). From a therapeutic class perspective, fibromyalgia patients received antidepressants (46%), antiepileptics (35%), pain therapies (25%), muscle relaxants (8%), and sleep agents (2%). An expert commentary is included.
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PMID:Treatment of fibromyalgia. 2053 53

Major depressive disorder (MDD) is characterized by a constellation of affective, cognitive, and somatic symptoms associated with functional abnormalities in relevant brain systems. Painful stimuli are primarily stressful and can trigger consistent responses in brain regions highly overlapping with the regions altered in MDD patients. Duloxetine has proven to be effective in treating both core emotional symptoms and somatic complaints in depression. This study aimed to assess the effects of duloxetine treatment on brain response to painful stimulation in MDD patients. A total of 13 patients and a reference group of 20 healthy subjects were assessed on three occasions (baseline, treatment week 1, and week 8) with functional magnetic resonance imaging (fMRI) during local application of painful heat stimulation. Treatment with duloxetine was associated with a significant reduction in brain responses to painful stimulation in MDD patients in regions generally showing abnormally enhanced activation at baseline. Clinical improvement was associated with pain-related activation reductions in the pregenual anterior cingulate cortex, right prefrontal cortex, and pons. Pontine changes were specifically related to clinical remission. Increased baseline activations in the right prefrontal cortex and reduced deactivations in the subgenual anterior cingulate cortex predicted treatment responders at week 8. This is the first fMRI study addressed to assess the effect of duloxetine in MDD. As a novel approach, the application of painful stimulation as a basic neural stressor proved to be effective in mapping brain response changes associated with antidepressant treatment and brain correlates of symptom improvement in regions of special relevance to MDD pathophysiology.
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PMID:Effects of duloxetine treatment on brain response to painful stimulation in major depressive disorder. 2066 37


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