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)

Duloxetine (Cymbalta(R)) is a potent serotonin and noradrenaline (norepinephrine) reuptake inhibitor (SNRI) in the CNS. It is indicated for the treatment of generalized anxiety disorder (GAD) as well as other indications. In patients with GAD of at least moderate severity, oral duloxetine 60-120 mg once daily was effective with regard to improvement from baseline in assessments of anxiety and functional impairment, and numerous other clinical endpoints. Longer-term duloxetine 60-120 mg once daily also demonstrated efficacy in preventing or delaying relapse in responders among patients with GAD. In addition, duloxetine was generally well tolerated, with most adverse events being of mild to moderate severity in patients with GAD in short- and longer-term trials. Additional comparative and pharmacoeconomic studies are required to position duloxetine among other selective serotonin reuptake inhibitors and SNRIs. However, available clinical data, and current treatment guidelines, indicate that duloxetine is an effective first-line treatment option for the management of GAD. Duloxetine is a potent and selective inhibitor of serotonin and noradrenaline transporters, and a weak inhibitor of dopamine transporters. It has a low affinity for neuronal receptors, such as alpha(1)- and alpha(2)-adrenergic, dopamine D(2), histamine H(1), muscarinic, opioid and serotonin receptors, as well as ion channel binding sites and other neurotransmitter transporters, such as choline and GABA transporters. It does not inhibit monoamine oxidase types A or B. The pharmacokinetics of duloxetine in healthy volunteers were dose proportional over the range of 40-120 mg once daily. Steady state was typically reached by day 3 of administration. Duloxetine may be administered without regard to food or time of day. Duloxetine is highly protein bound and is widely distributed throughout tissues. It is rapidly and extensively metabolized in the liver by cytochrome P450 (CYP) 1A2 and 2D6, and its numerous metabolites, which are inactive, are mainly excreted in the urine. The mean elimination half-life of duloxetine is approximately 12 hours. Duloxetine is a substrate for CYP1A2 and CYP2D6 and a moderate inhibitor of CYP2D6. Concomitant use of duloxetine and potent CYP1A2 inhibitors should be avoided and duloxetine should be used with caution in patients receiving drugs that are extensively metabolized by CYP2D6, particularly those with a narrow therapeutic index. Duloxetine was effective in the short-term treatment of patients with primary GAD of at least moderate severity. In four randomized, double-blind, placebo-controlled, multicentre, phase III trials, duloxetine 60-120 mg once daily for 9 or 10 weeks was significantly more effective than placebo with regard to the primary endpoint of mean change in Hamilton Anxiety Rating Scale (HAM-A) total score from baseline to study endpoint. In addition, all other endpoints were generally improved from baseline to a greater extent with duloxetine 60-120 mg once daily than with placebo. Duloxetine also improved patient role functioning (assessed using Sheehan Disability Scale global impairment functioning scores), health-related quality of life and patient well-being compared with placebo. Duloxetine was effective in patients with GAD who were aged >/=65 years. Pooled results of data from the two short-term efficacy trials that also included an active comparator arm showed that the mean change in HAM-A scores with duloxetine relative to placebo were of the same magnitude as those with venlafaxine extended release versus placebo. Duloxetine 60-120 mg once daily was also more effective than placebo in preventing or delaying relapse in responders to duloxetine in a longer-term study. In this study, patients with GAD received duloxetine during a 26-week, open-label, acute treatment phase and responders were then randomized to continue on duloxetine or receive placebo during a 26-week, double-blind, continuation phase. Time to relapse was significantly longer in duloxetine recipients than in placebo recipients. In addition, significantly fewer duloxetine recipients than placebo recipients relapsed during the double-blind phase of the trial and more duloxetine recipients achieved remission. Short- (9-10 weeks) and longer-term (52 weeks) treatment with duloxetine 60-120 mg once daily was generally well tolerated in patients with GAD, with the majority of adverse events being of mild to moderate severity. Nausea, dry mouth, headache, constipation, dizziness and fatigue were among the most common treatment-emergent adverse events. The adverse event profile of duloxetine did not differ with dose or treatment duration. Significantly more patients receiving short-term duloxetine than placebo discontinued treatment because of an adverse event, with nausea being the only event that resulted in significantly more treatment discontinuations in duloxetine recipients than in placebo recipients. Serious adverse events were uncommon with both short- and longer-term duloxetine treatment. Two episodes of attempted suicide and one episode of completed suicide occurred in duloxetine recipients during the 24-week open-label phase of a longer-term trial. No deaths or suicides were reported in any of the short-term trials. Discontinuation-emergent adverse events, most commonly nausea and dizziness, occurred in up to one-third of duloxetine recipients in the short-term trials.
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PMID:Duloxetine: a review of its use in the treatment of generalized anxiety disorder. 1948 Apr 70

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

This manuscript reviews the pharmacodynamics and pharmacokinetics of duloxetine and its efficacy and safety in women with stress urinary incontinence. Duloxetine is a selective inhibitor of neuronal serotonin and norepinephrine uptake which increases urethral striated muscle activity and bladder capacity. Duloxetine is readily absorbed and extensively metabolized; cytochrome P450 1A2 (CYP1A2) inhibiting drugs can markedly increase duloxetine exposure. The clinical efficacy of duloxetine has consistently been demonstrated in several randomized, double-blind studies in women with moderate-to-severe stress urinary incontinence, but the additional benefit relative to placebo was moderate. Duloxetine treatment is frequently associated with adverse events such as nausea, dry mouth, fatigue, insomnia and constipation, but serious adverse events are rare. Therefore, duloxetine appears suitable for the treatment of stress urinary incontinence.
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PMID:Duloxetine in the treatment of stress urinary incontinence. 1980 76

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 is a balanced and potent serotonin and noradrenaline reuptake inhibitor (SNRI) and has adverse effects that are commonly associated with such drugs, including nausea, dry mouth, constipation, insomnia, and dizziness. Recently, duloxetine-induced liver injury has also been observed in patients with preexisting liver disease or chronic alcohol use. We investigated the effects of duloxetine in a healthy young adult with major depressive disorder (MDD) but no risk factors, and found that his total bilirubin level increased to 3.3 mg/dL and he developed jaundice after 5 months of duloxetine treatment. Discontinuation of duloxetine treatment saw his total bilirubin level decrease to 1.8 mg/dL. Thus, the administration of duloxetine might induce liver injury in a patient with MDD. However, the limitations of this single case report must be acknowledged. Although the cause of hepatic dysfunction in this case remains to be elucidated, clinicians should monitor liver function carefully after duloxetine treatment. Further investigations with a larger sample are needed.
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PMID:Cholestatic jaundice induced by duloxetine in a patient with major depressive disorder. 2092 14

The objective of this prospective study was to assess the efficacy and tolerability of duloxetine in the treatment of in military veterans with posttraumatic stress disorder (PTSD).Twenty subjects were enrolled in this 12-week, open-label trial. Diagnosis and symptom severity were assessed with the Clinician Administered PTSD Scale (CAPS). Depressive symptoms were assessed the Hamilton Depression Rating Scale. All subjects had a CAPS score of at least 60 at baseline. Subjects with lifetime history of psychotic disorders or bipolar illness were excluded. Fifteen participants completed 12 weeks of treatment, five dropped-out from the trial, 3 due to side effects. For patients who discontinued, missing values were estimated using "the last observation carried forward" method. Significant improvements were seen on: CAPS total and all subscales, depression and sleep measures. Most of the improvement was observed by week 2 of treatment. Nine participants (45%) were classified as responders, defined by 20% or greater improvement on CAPS total score. The mean daily dose of duloxetine was 81 mg. The most common side effects were constipation (20%) diarrhea (25%) and nausea (20%). Two subjects developed tachycardia, one withdrew from the trial due to this problem. Duloxetine had a fast onset of action and was effective in about half of the subjects, it was well tolerated in most subjects. These preliminary results in a difficult to treat population warrant the conduction of a double blind, placebo-controlled study of duloxetine in PTSD.
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PMID:Duloxetine in military posttraumatic stress disorder. 2115 Aug 44

Duloxetine is a serotonin-norepinephrine reuptake inhibitor approved by the US Food and Drug Administration for the treatment of fibromyalgia and painful diabetic neuropathy at doses of 60 mg daily. Duloxetine has been shown to significantly improve the symptoms of chronic pain associated with these disorders, as measured by the Fibromyalgia Impact Questionnaire, Brief Pain Inventory scores, the Clinical Global Impressions Scale, and other various outcome measures in several placebo-controlled, randomized, double-blind, multicenter studies. Symptom improvement generally began within the first few weeks, and continued for the duration of the study. In addition, the efficacy of duloxetine was found to be due to direct effects on pain symptoms rather than secondary to improvements in depression or anxiety. Adverse events including nausea, constipation, dry mouth, and insomnia, were mild and transient and occurred at relatively low rates. In conclusion, duloxetine, a selective inhibitor for the serotonin and norepinephrine transporters, is efficacious in the treatment of chronic pain associated with fibromyalgia or diabetic neuropathy, and has a predictable tolerability profile, with adverse events generally being mild to moderate.
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PMID:Duloxetine in the treatment of chronic pain due to fibromyalgia and diabetic neuropathy. 2138 50

Diabetic neuropathy affects up to 70% of diabetics, and diabetic peripheral neuropathic pain (DPNP) is the most common and debilitating of the diabetic neuropathies. DPNP significantly reduces quality of life and increases management costs in affected patients. Despite the impact of DPNP, management is poor with one-quarter of patients receiving no treatment and many treated with medications having little or no efficacy in managing DPNP. Duloxetine is one of two drugs approved by the United States Food and Drug Administration for DPNP management. Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) proven safe, effective, and cost-saving in reducing DPNP symptoms at a dose of 60 mg/day. Duloxetine doses greater than 60 mg/day for DPNP management are not recommended since they are no more efficacious and associated with more side effects; addition of pregabalin or gabapentin for these patients may be beneficial. Side effects of duloxetine are generally mild and typical for the SNRI class including nausea, dizziness, somnolence, fatigue, sweating, dry mouth, constipation, and diarrhea. Given its other indications, duloxetine is a particularly good choice for DPNP treatment in patients with coexisting depression, anxiety, fibromyalgia, or chronic musculoskeletal pain. Duloxetine treatment had no clinically significant effect on glycemic control and did not increase the risk of cardiovascular events in diabetes patients. However, duloxetine use should be avoided in patients with hepatic disease or severe renal impairment. Given its safety, efficacy, and tolerability, duloxetine is an excellent choice for DPNP treatment in many patients.
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PMID:Duloxetine in the management of diabetic peripheral neuropathic pain. 2184 34

The efficacy and tolerability of Lu AA21004 at 5 mg/day, a novel multimodal antidepressant, were assessed in elderly patients with recurrent major depressive disorder. Patients were randomly assigned (1:1:1) to Lu AA21004 5 mg/day, duloxetine 60 mg/day (reference) or to placebo in an 8-week double-blind study. The primary efficacy measure was the 24-item Hamilton Depression Scale (HAM-D(24)) total score (analysis of covariance, last observation carried forward). Patients (mean age 70.6 years) had a mean baseline HAM-D(24) score of 29.0. Lu AA21004 showed significantly (P = 0.0011) greater improvement on the primary efficacy endpoint compared with placebo at week 8 (3.3 points). Duloxetine also showed superiority to placebo at week 8, thereby validating the study. HAM-D(24) response (53.2 vs. 35.2%) and HAM-D(17) remission (29.2 vs. 19.3%) rates at endpoint were higher for Lu AA21004 than for placebo. Lu AA21004 showed superiority to placebo in cognition tests of speed of processing, verbal learning and memory. The withdrawal rate due to adverse events was 5.8% (Lu AA21004), 9.9% (duloxetine) and 2.8% (placebo). Whereas nausea was the only adverse event with a significantly higher incidence on treatment with Lu AA21004 (21.8%) compared with placebo (8.3%), the incidence of nausea, constipation, dry mouth, hyperhidrosis and somnolence was higher for duloxetine. In conclusion, Lu AA21004 was efficacious and well tolerated in the treatment of elderly patients with recurrent major depressive disorder.
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PMID:A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder. 2257 89


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