Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The class of serotonin and norepinephrine reuptake inhibitors (SNRIs) now comprises three medications: venlafaxine, milnacipran, and duloxetine. These drugs block the reuptake of both serotonin (5-HT) and norepinephrine with differing selectivity. Whereas milnacipran blocks 5-HT and norepinephrine reuptake with equal affinity, duloxetine has a 10-fold selectivity for 5-HT and venlafaxine a 30-fold selectivity for 5-HT. All three SNRIs are efficacious in treating a variety of anxiety disorders. There is no evidence for major differences between SNRIs and SSRIs in their efficacy in treating anxiety disorders. In contrast to SSRIs, which are generally ineffective in treating chronic pain, all three SNRIs seem to be helpful in relieving chronic pain associated with and independent of depression. Tolerability of an SNRI at therapeutic doses varies within the class. Although no direct comparative data are available, venlafaxine seems to be the least well-tolerated, combining serotonergic adverse effects (nausea, sexual dysfunction, withdrawal problems) with a dose-dependent cardiovascular phenomenon, principally hypertension. Duloxetine and milnacipran appear better tolerated and essentially devoid of cardiovascular toxicity.
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PMID:SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants. 1614 13

Stress Urinary Incontinence is a common symptom among women. The urethral closure is insufficient. Pelvic floor exercise can minish the symptoms, but many women need an operation. Duloxetine, a new drug, is believed to strengthen the contraction of the external urethral sphincter through central neuromodulation, resulting in enhanced urethral closure during the urine storage phase. In controlled studies a significant effect are found in women suffer from Stress Urinary Incontinence. Discontinuate rates for adverse events were high especially nausea and fatigue. The adverse event deminish after 4 weeks.
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PMID:[Duloxetine. A new preparation for patients with urinary incontinence]. 1632 35

Urinary incontinence is a public health problem, as more than three million women in France are concerned by this problem. The prevalence of stress urinary incontinence is about 40% among these women. Duloxetine is a molecule developed for the oral treatment of stress urinary incontinence. It is a serotonin and norepinephrine reuptake inhibitor, which acts by increasing urethral sphincter tone. In several phase III trials, duloxetine administered orally at a high dose of 80 mg per day, significantly reduced episodes of incontinence. Total scores on the Incontinence Quality of Life questionnaire (I-QOL) were more markedly improved by duloxetine than by placebo. Nausea was an adverse effect observed in more than 25% of cases and required discontinuation of treatment in some patients. However, the encouraging preliminary results of duloxetine in this indication must be confirmed during phase IV post-marketing clinical trials.
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PMID:[Place of duloxetine in the treatment of stress urinary incontinence]. 1645 87

Duloxetine has demonstrated efficacy for the treatment of major depressive disorder (MDD) at a dose of 60 mg/day (given once daily). Whereas the target dose for the majority of patients is 60 mg/day, higher duloxetine doses (up to 120 mg/day) have been studied using a twice-daily dosing schedule. To further investigate the pharmacological profile of duloxetine within a once-daily dosing regimen at doses above 60 mg, we examined the safety and tolerability of duloxetine during a dose escalation from 60 mg/day to 120 mg/day. This single-arm, non-placebo-controlled study incorporated a 7-week dose escalation phase, in which patients and investigators were blinded as to timing of dose increases, followed by an open-label extension phase of up to 2 years duration. Patients (age >or=18 years) meeting DSM-IV criteria for MDD (n=128) received placebo for 1 week, followed by duloxetine (60 mg/day) titrated after 1 week to 90 mg/day, and after a further week to 120 mg/day. The dose of 120 mg/day was then maintained for 4 weeks. The extension phase comprised an initial 6-week dose stabilization period, during which duloxetine was tapered to the lowest effective dose, followed by continuation therapy at the stabilized dose. We assessed safety using spontaneously reported treatment-emergent adverse events (TEAEs), changes in vital signs, electrocardiograms (ECGs), laboratory analytes, and visual analogue scales (VAS) for gastrointestinal (GI) disturbance. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score, the Clinical Global Impression of Severity (CGI-S) and Patient Global Impression of Improvement (PGI-I) scales, and VAS assessments of pain severity and interference. The rate of discontinuation due to adverse events during the acute phase of the study was 15.6%. The most frequently reported TEAEs were nausea, headache, dry mouth, dizziness, and decreased appetite. The majority of TEAEs were associated with initial duloxetine dosing; further escalations in dose produced few additional adverse events. VAS measures of GI disturbance worsened significantly compared with baseline values after 1 week of duloxetine treatment. Subsequent assessments of GI disturbance, following dose escalation to 90 mg/day and 120 mg/day, showed either no significant difference or a significant improvement from baseline. Significant improvements (P<.001) were observed in all assessed depression efficacy measures, and in five of six VAS pain outcomes, during acute phase treatment. During 2 years of extension phase therapy, the rate of discontinuation due to adverse events was 11.9%, and the only TEAEs reported by >10% of patients were upper respiratory tract infection (13.1%), headache (10.7%), and insomnia (10.7%). Mean changes from baseline to the end of the extension phase in supine systolic and diastolic blood pressure were 3.8 and 0.5 mm Hg, respectively, and there were no reports of sustained hypertension. Mean increase in heart rate was 5.9 bpm, while patients exhibited a mean weight increase of 3.1 kg over 2 years of treatment. Results from this study suggest that rapid dose escalation of duloxetine (60 mg/day --> 90 mg/day --> 120 mg/day) is safe and tolerable. Despite weekly escalation, the majority of adverse events were mild and transient and occurred in the first week of duloxetine dosing (at 60 mg once daily). Long-term treatment at a stabilized duloxetine dose was associated with a relatively low incidence of TEAEs and treatment discontinuation due to adverse events. Time course profiles of body weight and heart rate showed modest increases during 2 years of treatment [ClinicalTrials.gov number, NC T000 42575].
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PMID:Duloxetine for the treatment of major depressive disorder: safety and tolerability associated with dose escalation. 1684 41

Diabetics develop numerous chronic associated diseases, among them sensory polyneuropathy. Diabetic polyneuropathy (DPN) often causes pain of various kinds, degree and duration. There are many pharmacological approaches: antidepressants are also important. Duloxetine is a recently approved dual action serotonin and noradrenaline re-uptake inhibitor that in its analgesic efficacy is comparable to established drugs. Duloxetine, in a dosage of 60 mg x 1 or x 2 daily, significantly reduces, from the first week of administration, the pain of DPN, when compared with a placebo. The most commonly observed side effects have been nausea, sleepiness, constipation and fatigue. On average duloxetine has not shown any clinically relevant increase in blood pressure, pulse rate and weight. It thus offers a new option as part of the treatment of pain caused by DPN. The various drugs should be considered individually in any treatment algorithm, also taking into account their side effects. Psychotherapeutic methods serve to support the overcoming of pain.
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PMID:[Duloxetine, a new therapeutic option for diabetic peripheral neuropathic pain]. 1713 88

Duloxetine (Cymbalta is an antidepressant of the class of serotonin noradrenaline reuptake inhibitors. The efficacy of duloxetine 60 mg/day has been well demonstrated in the acute and long term treatment of major depression. The level of effectiveness of duloxetine is particularly high and associated with a shorter latency of action. Duloxetine also exhibits antinociceptive properties independently of the antidepressant effect. The side-effect profile of duloxetine is particularly good and similar to selective serotonin reuptake inhibitors with mainly nausea. In total, duloxetine represents a real progress in the pharmacological treatment of major depression.
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PMID:[Medication of the month. Duloxetine (Cymbalta)]. 1719 49

Duloxetine is a newly introduced drug. It is being prescribed for the management of diabetic neuropathic pain and major depressive disorder. The most frequently observed adverse events with duloxetine are nausea, dry mouth and somnolence, constipation, diarrhea, decreased appetite, weight loss, feeling of fatigue, dizziness, somnolence, hypohidrosis, decreased libido and erectile dysfunction. One of the patients being prescribed the drug developed bleeding gums on being started with the drug which resolved on stopping it. We hereby report this case.
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PMID:Bleeding gums: duloxetine may be the cause. 1724 71

Generalized anxiety disorder (GAD), a prevalent and chronic illness, is associated with dysregulation in both serotonergic and noradrenergic neurotransmission. Our study examined the efficacy, safety, and tolerability of duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, for short-term treatment of adults with GAD. In a 10-week, double-blind, progressive-titration, flexible-dose trial, 327 adult outpatients with a DSM-IV-defined GAD diagnosis were randomized to duloxetine 60-120 mg (DLX, N=168) or placebo (PLA, N=159) treatment. The primary efficacy measure was mean change from baseline to endpoint in Hamilton Anxiety Scale (HAMA) total score. Secondary outcome measures included response rate (HAMA total score reduction > or =50% from baseline), Clinician Global Impression-Improvement (CGI-I) scores, and Sheehan Disability Scale (SDS) scores. Patients who received duloxetine treatment demonstrated significantly greater improvement in HAMA total scores (P=.02); a higher response rate (P=.03), and greater improvement (P=.04) than patients who received placebo. Duloxetine-treated patients were also significantly more improved than placebo-treated patients on SDS global functional (P<.01) and work, social, and family/home impairment scores (P<.05). The rate of discontinuation due to adverse events (AEs) was higher for the duloxetine group compared with the placebo group (P=.002). The AEs most frequently associated with duloxetine were nausea, dizziness, and somnolence. Duloxetine was an efficacious, safe, and well-tolerated treatment that resulted in clinically significant improvements in symptom severity and functioning for patients with GAD.
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PMID:Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible-dose, progressive-titration, placebo-controlled trial. 1731 3

Apomorphine, a non-ergot derivative, is a potent, directly acting dopamine receptor agonist with high affinity to D4, lower to D2, D3, D5, the lowest to D1-like dopamine receptors as well as to serotonin and adrenoreceptors. Subcutaneous apomorphine is currently used in Parkinson's disease as an add-on to levodopa therapy or monotherapy for management of sudden, unexpected and refractory to levodopa-induced off state and fluctuation in advanced stage of illness. Many clinical trials have shown markedly (about 50-72%) reduced time of off phases. Other indications include the challenge test for determining the dopaminergic responsiveness. Apomorphine is used subcutaneously either as intermittent rescue injections or continuous infusions. Several other routes - transdermal, sublingual, intranasal, rectal and intravenous infusion - have been tried. Oral administration is not recommended. Apomorphine has rapid onset of antiparkinsonian action, qualitatively comparable to that of levodopa, short duration of action and stable efficacy with usually mild adverse events similar to other dopamine agonists. Domperidone or trimethobenzamide should be introduced before starting apomorphine treatment to reduce occurrence of peripheral adverse events (nausea, vomiting, orthostatic hypotension). Dyskinesias, sleep disturbances, hallucinations, delusion, oedema and yawning can occur, but some side effects are connected only with a specific route (for example skin nodules appearing during subcutaneous administration). Despite its long history, apomorphine is registered and used in only a few countries. Apomorphine warrants wider application in treatment of advanced Parkinson disease but the high cost of the drug, the necessity of concomitant treatment for prevention of side effects and subcutaneous administration restrict its use.
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PMID:[Apomorphine in off state--clinical experience]. 1794 58

Stress urinary incontinence (SUI) is the most common form of urinary incontinence and occurs more frequently in women than in men. Duloxetine is a balanced dual serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor and shows no relevant binding affinity for histaminergic, dopaminergic, cholinergic, and adrenergic receptors. The efficacy of duloxetine in SUI is based on the inhibition of the presynaptic reuptake of 5-HT and NE in Onuf's nucleus of the sacral spinal cord, whereby it may increase the concentration of 5-HT and NE in the synaptic cleft. The effectiveness of duloxetine was studied in a cat model of acetic acid-induced bladder irritation. The results showed that in cats with previous irritated bladder function, there was a dosage-dependent improvement of bladder capacity and periurethral electromyography (EMG) activity. In women with SUI, it is assumed that the clinical efficacy of duloxetine is based on stronger urethral contraction and persistent sphincter tone during the storage phase. In clinical trials in women with SUI, duloxetine has demonstrated efficacy in reducing incontinence episodes and increasing quality of life. Nausea was the most common adverse event and the main cause for discontinuation. In summary, duloxetine appears to be a promising new option for the treatment of SUI.
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PMID:Duloxetine in the treatment of stress urinary incontinence. 1836 May 68


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