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Case reports and clinical trials published in English and conducted in humans were identified. All reports and trials evaluating a SNRI for the treatment of CIPN were included; 4 case reports, 1 open-label study, and 2 randomized controlled trials were identified for review.
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In study 1, there was no significant difference in mean desvenlafaxine AUC between the CYP2D6 EMs and PMs (-11%; P=0.641) who were administered desvenlafaxine. However, PMs receiving venlafaxine ER had significantly higher venlafaxine and lower desvenlafaxine AUCs compared with EMs (+350% and -74%, respectively; P<0.001 for each). In studies 2, 4, and 5, the mean increases in desipramine AUC with concomitant administration of desvenlafaxine 100 mg ranged from 17% to 36%; the increase with concomitant administration of desvenlafaxine 400 mg (study 3) was 90%. Paroxetine and duloxetine produced increases in mean desipramine AUC of 419% and 122%, respectively, which were significantly greater than the increases seen with desvenlafaxine 100 mg (P<0.001 for each comparison).
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Data were pooled from 4 randomized, double-blind, placebo-controlled studies of duloxetine in patients with fibromyalgia (FM). Variables included in the analyses were those that assessed symptoms in FM domains of pain, fatigue, sleep, cognitive difficulties, emotional well-being, physical function, and impact on daily living. The association of endpoint PGI-I with changes from baseline in individual variables was assessed using Pearson product-moment correlations (r). Stepwise linear regression was used to identify those variables for which changes from baseline were statistically significant independent predictors of the endpoint PGI-I ratings.
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To determine the effect of duloxetine treatment on cognition in patients with fibromyalgia.
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To determine the efficacy, tolerability, and safety of duloxetine when added to oral nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with osteoarthritis (OA) of the knee with pain of moderate or greater severity.
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To investigate the effect of duloxetine on the pharmacokinetics and tolerability of tolterodine and its active 5-hydroxymethyl metabolite (5-HM).
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Efficacies of bupivacaine and duloxetine applied subcutaneously at the incision site against acute postoperative pain were compared after rat skin incision. Contralateral and intraperitoneal injections were used to assess systemic efficacy of duloxetine. Local anesthetic actions were assayed through functional block of the rat sciatic nerve. Inhibition by duloxetine of neuronal Na channels was characterized in rat GH3 cells.
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Evaluation of the corneal nerve fibre density using CCM in six women with non-length-dependent SFN. The patients were characterised by sensory disturbance involving proximal regions of the limbs, face and trunks, and the diagnosis was confirmed by the findings of decreased intraepidermal nerve fibre density on skin biopsy.
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Here we present the case of a 48-year-old woman carrying a homozygous mutation (p.A899T) in mitochondrial polymerase gamma (POLG) and manifesting with a complex neurological phenotype including Dopamine-agonist responsive Parkinsonism.
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Little evidence is available relevant to the treatment of refractory neuropathic pain despite the clinical need. There is a notable lack of high-quality comparative studies. It is evident that there is a need for future, high quality trials, particularly "gold-standard" RCTs in this refractory patient population.
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Research is still needed to predict which patients are at high risk of developing CIPN during treatment and in whom CIPN will persist after completion of chemotherapy.
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The rat incision plus extension model on the dorsothoracic skin was applied to evoke postoperative mechanoallodynia and hyperalgesia, measured for 5 days postoperatively by local responses to von Frey filaments. R-Duloxetine and N-methyl duloxetine were administered systemically (intraperitoneal) or locally (subcutaneous [SC]) 1 hour before the surgery. The block of Na currents in rat neuronal GH3 cells was determined under the whole-cell configuration.
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In this article we describe a computational method that automatically generates chemically relevant compound ideas from an initial molecule, closely integrated with in silico models, and a probabilistic scoring algorithm to highlight the compound ideas most likely to satisfy a user-defined profile of required properties. The new compound ideas are generated using medicinal chemistry 'transformation rules' taken from examples in the literature. We demonstrate that the set of 206 transformations employed is generally applicable, produces a wide range of new compounds, and is representative of the types of modifications previously made to move from lead-like to drug-like compounds. Furthermore, we show that more than 94% of the compounds generated by transformation of typical drug-like molecules are acceptable to experienced medicinal chemists. Finally, we illustrate an application of our approach to the lead that ultimately led to the discovery of duloxetine, a marketed serotonin reuptake inhibitor.
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Oral administration of duloxetine significantly increased the mean and maximal urethral closure pressures at rest over the proximal and middle third of the urethra. During coughing, duloxetine marginally significantly increased the mean distal urethral pressure and significantly reduced the mean delay in the distal urethral pressure peak relative to the vesical peak. Although duloxetine did not change amplitudes of pressure spikes in response to SMS, this drug significantly lowered the MT in response to TMS.
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Our goal was to evaluate the effectiveness, safety and tolerability of duloxetine in the treatment of children and adolescents with somatoform disorder.
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On 19th November 2013, we searched The Cochrane Neuromuscular Group Specialized Register, CENTRAL, DARE, HTA, NHSEED, MEDLINE, and EMBASE. We searched ClinicalTrials.gov for ongoing trials in April 2013. We also searched the reference lists of identified publications for trials of duloxetine for the treatment of painful peripheral neuropathy or chronic pain.
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A total of 3,024 filled prescriptions were recorded of which 2,903 (96%) could be further analyzed, corresponding to 37 users per 100,000 women in the population. Each patient filled a mean of 3.4 prescriptions. The persistence of use was very low from the second quarter itself, and after 1 year only 12.5% of the patients still purchased the drug. Most prescriptions were written by GPs and gynecologists. A prescription database like ours consists of dispensed prescriptions and not drugs taken. We believe that these biases are of little importance for the main results.
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To determine the relative efficacy, costs and cost effectiveness of the first-line treatment options for painful diabetic neuropathy.
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The composite outcome was defined as remission (Montgomery-Åsberg Depression Rating Scale [MADRS] score ≤10) and concurrent absence of an AE. The proportions of remitted patients free of (1) any AEs, (2) moderate-to-severe AEs, and (3) study drug-related AEs were compared between treatment groups at each study visit and longitudinally across study visits common to all trials during the first 8 weeks of treatment.
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The objective was to examine duloxetine 60-120 mg/day treatment for relapse prevention in adults with generalized anxiety disorder (GAD). Adult patients (N=887; mean age=43.3 years; 61.0% female) with DSM-IV-TR-defined GAD diagnosis were treated with duloxetine for 26 weeks. Patients who completed open-label phase and were treatment responders (>or=50% reduction in Hamilton Anxiety Rating Scale total score to or=2-point increase in illness severity ratings or by discontinuation due to lack of efficacy. During the double-blind phase, placebo-treated patients (N=201) relapsed more frequently (41.8%) than duloxetine-treated patients (13.7%, N=204, P
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Serotonin syndrome is a potentially lethal adverse drug reaction that may occur in patients taking proserotoninergic medications. Drug interactions are often responsible for the causation of this syndrome. We report two cases of severe serotonin syndrome induced by the administration of cyclobenzaprine in postoperative patients already receiving another proserotoninergic drug (phenelzine in one case and duloxetine in the other). In both cases, symptoms of autonomic instability and severe agitation started within hours of initiation of cyclobenzaprine and fully resolved within 3 days after discontinuing the proserotoninergic drugs. We conclude that cyclobenzaprine should be used with extreme caution in patients receiving other serotonin-enhancing drugs; these patients should be closely monitored for manifestations of serotonin syndrome.
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Urinary incontinence is the inability to willingly control bladder voiding. Stress urinary incontinence (SUI) is the most frequently occurring type of incontinence in women. No widely accepted or approved drug therapy is yet available for the treatment of stress urinary incontinence. Numerous studies have implicated the neurotransmitters, serotonin and norepinephrine in the central neural control of the lower urinary tract function. The pudendal somatic motor nucleus of the spinal cord is densely innervated by 5HT and NE terminals. Pharmacological studies confirm central modulation of the lower urinary tract activity by 5HT and NE receptor agonists and antagonists. Duloxetine is a combined serotonin/norepinephrine reuptake inhibitor currently under clinical investigation for the treatment of women with stress urinary incontinence. Duloxetine exerts balanced in vivo reuptake inhibition of 5HT and NE and exhibits no appreciable binding affinity for receptors of neurotransmitters. The action of duloxetine in the treatment of stress urinary incontinence is associated with reuptake inhibition of serotonin and norepinephrine at the presynaptic neuron in Onuf's nucleus of the sacral spinal cord. In cats, whose bladder had initially been irritated with acetic acid, a dose-dependent improvement of the bladder capacity (5-fold) and periurethral EMG activity (8-fold) of the striated sphincter muscles was found. In a double blind, randomized, placebo-controlled, clinical trial in women with stress urinary incontinence, there was a significant reduction in urinary incontinence episodes under duloxetine treatment. In summary, the pharmacological effect of duloxetine to increase the activity of the striated urethral sphincter together with clinical results indicate that duloxetine has an interesting therapeutic potential in patients with stress urinary incontinence.
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This retrospective cohort study assessed subsequent opioid utilization and health-care costs among patients with diabetic peripheral neuropathic pain (DPNP) who initiated duloxetine vs. other standard of care (SOC) treatments.
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The main limitation is the use of spontaneously reported DEAEs.
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To evaluate the cost effectiveness of escitalopram versus duloxetine in the treatment of MDD, and to identify key cost drivers.
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Ligation injury of the TASM in rats led to long-lasting and constant mechanical hypersensitivity of myogenic origin. The model will be particularly useful in studying the chronicity of myogenic pain TMJ disorders. The model can also be adapted to other regions of the body for studying pathology of painful tendinopathy seen in sports injury, muscle overuse, and rheumatoid arthritis.
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The efficacy of the combination therapy with two antidepressants from different pharmacological families in patients with treatment-resistant depression has been reported in multiple studies. In this prospective 12-weeks open-label study, we assessed the effectiveness of the addition of reboxetine to 79 depressive outpatients diagnosed with major depressive disorder (MDD) according to the DSM-IV criteria who had previously not responded, or had done so only in a partial way, over 8 weeks of conventional treatment, in monotherapy, with duloxetine. Efficacy was assessed using the 21-item Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression-Improvement (CGI-I). Safety was evaluated by recording spontaneously reported adverse events. Data were analysed on an intent-to-treat basis, using the last-observation-carried-forward method. Mean HDRS reduction was 65.5% (P < 0.0001). The percentages of responders (>or=50% reduction in HDRS) and patients considered benefiting from complete remission (HDRS