Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BACKGROUND: Duloxetine is a novel antidepressant that is anticipated to be clinically available soon. It exerts simultaneous noradrenergic and serotonergic neurotransmitter effects. Because of these influences, it is postulated to have a role in management of pain. DATA SOURCES: An Index Medicus search from 1997 to 2003 was conducted using the search terms duloxetine, Cymbalta, and pain. DATA ANALYSIS: Preclinical animal studies suggest that duloxetine may have a direct analgesic role. Premarketing studies have emphasized its utility in alleviating somatic, specifically pain, complaints among patients with major depression. CONCLUSION: Although promising, these results cannot be generalized to patients with pain disorders; the reasons for this are discussed herein. While duloxetine may be useful among somatizing depressed patients and possibly chronic pain patients with comorbid depression, its analgesic role has yet to be elucidated in future research.
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PMID:Antidepressant Use in Chronic Pain Management: Is There Evidence of a Role for Duloxetine? 1515 22

BACKGROUND: Depression is underdiagnosed in the primary care setting. Physical symptoms such as aches, pains, and gastrointestinal disturbance are frequently associated with major depressive disorder (MDD) and are often the presenting symptoms. Duloxetine, a dual-reuptake inhibitor of serotonin and norepinephrine, may have a positive effect on physical symptoms in addition to efficacy in treating emotional symptoms of depression. METHOD: Efficacy was evaluated in 6 double-blind, placebo- and/or active comparator-controlled trials of duloxetine for patients with MDD (DSM-IV criteria). Efficacy in depression was determined primarily using the 17-item Hamilton Rating Scale for Depression (HAM-D-17). Secondary efficacy measures included subscales of the HAM-D-17 and assessment of physical symptoms. Safety evaluations included adverse events, vital signs, laboratory analyses, and electrocardiograms. Safety was evaluated by pooling the data from the MDD trials and a study of duloxetine in nondepressed patients. RESULTS: Duloxetine demonstrated significant differences from placebo on core mood symptoms, physical symptoms (e.g., back pain), and global functioning as early as week 1 of treatment. The estimated probabilities of remission in the studies that demonstrated efficacy ranged from 43% to 57%. The most frequently observed adverse events for duloxetine-treated patients included nausea, dizziness, insomnia, fatigue, and somnolence. Duloxetine did not prolong corrected QT intervals, and the rate of sustained elevations of blood pressure did not differ significantly from placebo. CONCLUSION: In these studies, duloxetine was safe and effective in the treatment of both emotional and physical symptoms of MDD. Based on dose assessments, 60 mg q.d. appears to be the optimum starting and therapeutic dose.
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PMID:Duloxetine: A New Treatment for the Emotional and Physical Symptoms of Depression. 1515 43

BACKGROUND: The efficacy and safety of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine at the recommended starting dose, have been demonstrated in the treatment of major depressive disorder (MDD) in men and women and in the treatment of stress urinary incontinence (SUI) in women. Since the mechanism of action of duloxetine in the treatment of SUI is believed to be related to enhanced urethral closure forces, it is important to clarify the risk of acute urinary retention. METHOD: The relationship between duloxetine and obstructive voiding symptoms was examined in 8 double-blind, 8- to 9-week, placebo-controlled studies and 1 open-label study in men and women treated for MDD with duloxetine 40 to 120 mg/day and in 4 double-blind, 12-week, placebo-controlled studies and 4 ongoing open-label studies in women treated for SUI with duloxetine 80 mg/day. RESULTS: In 378 men and 761 women with MDD treated in placebo-controlled trials, 0.4% (4/1139; 3 men and 1 woman) of those treated with active medication reported subjective urinary retention versus none (0/777) of those treated with placebo (p =.15). In 958 women with SUI treated with duloxetine in placebo-controlled trials, none reported subjective urinary retention. Overall, in the duloxetine placebo-controlled clinical studies in the treatment of MDD and SUI, obstructive voiding symptoms (reported either as subjective urinary retention or other obstructive voiding symptoms) occurred more often in patients receiving duloxetine (1.0%, 20/2097) than in patients receiving placebo (0.4%, 6/1732) (p <.05). Of the 4719 MDD and SUI patients treated with duloxetine in placebo-controlled and ongoing open-label studies, 2 men and 1 woman discontinued because of obstructive voiding symptoms. Although such an evaluation was not required by protocol, no cases of objective acute urinary retention with postvoid residual urine verified with a bladder scan or requiring catheterization were reported in patients treated with duloxetine. CONCLUSION: Duloxetine treatment in women and men with depression and in women with SUI was rarely associated with obstructive voiding symptoms, and no subjects had objective acute urinary retention requiring catheterization.
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PMID:Urinary Side Effects of Duloxetine in the Treatment of Depression and Stress Urinary Incontinence. 1525 99

Double-blind, placebo-controlled clinical trials have evaluated and demonstrated the efficacy of duloxetine as an antidepressant in patients with major depressive disorders. The drug has been noted to be well tolerated and effective in the control of depressive symptoms. In addition, duloxetine has been shown to be better than placebo and as effective as paroxetine as an antidepressant and also better than placebo for reducing pain in both experimental models and patients. Duloxetine is a safe and well-tolerated new treatment option for depression including anxiety and painful physical symptoms. Furthermore, duloxetine has proven robust efficacy in stress urinary incontinence.
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PMID:Duloxetine: a new serotonin/noradrenaline reuptake inhibitor for the treatment of depression. 1553 50

This analysis assessed the effects of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine, on indices of cardiovascular safety, including heart rate, blood pressure (BP), and electrocardiograms (ECGs), in a large group of clinical trial patients with depression. Data were available from 8 double-blind, randomized, placebo-controlled (n = 777), and active comparator-controlled depression trials. Duloxetine (n = 1139) doses ranged from 40 to 120 mg/d, and fluoxetine (n = 70) and paroxetine (n = 359) were administered at a dose of 20 mg/d. Patients were treated for 8 to 9 weeks. There was a significant increase for duloxetine compared with placebo for heart rate (1.6 vs. -0.6 beats per minute) and for systolic BP (1.0 vs. -1.2 mm Hg); the difference for diastolic BP (1.1 vs. 0.3) was not significant. There were no significant differences between duloxetine and placebo treatment groups in the incidence of sustained (at least 3 consecutive visits) elevations in systolic (duloxetine 1.0%, placebo 0.4%), diastolic (duloxetine 0.4%, placebo 0.4%), or either (duloxetine 1.3%, placebo 0.8%) BP. Moreover, the effect of duloxetine on mean changes in supine systolic and diastolic BP was not significantly different from that of fluoxetine or paroxetine. Drug-placebo differences in mean changes in electrocardiograms (eg, QTc, PR, and QRS intervals) were neither statistically nor clinically significant, with the exception that duloxetine 120 mg/d had significant decreases in PR and QRS intervals compared with placebo. These data demonstrate that duloxetine has modest effects on heart rate and BP and no clinically meaningful effect on electrocardiogram profiles in a relatively healthy cohort of clinical trial patients. The cardiovascular effects of duloxetine appear to be comparable with medications considered to be first-line options for depression.
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PMID:Cardiovascular profile of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine. 1573 44

Antidepressants are often applied in the treatment of chronic pain. Analgesic action of tricyclic antidepressants (TCAs) has been extensively studied and proven. TCAs are associated with a number of adverse effects which are inconvenient for patients. The newer antidepressants have fewer side effects and equivalent efficacy on mood disorders. This article reviews the available publications (mainly placebo-controlled trials) concerning the efficacy of these medications in the treatment of chronic pain. The data regarding selective serotonin reuptake inhibitors (SSRI) are conflicting. Trazodone (a serotonin-reuptake inhibitor as well as a postsynaptic serotonin receptor antagonist) does not appear to be effective for the treatment of chronic pain. No placebo-controlled studies are available for noradrenergic and specific serotoninergic antidepressant (NaSSA)--mirtazapine and noradrenaline reuptake inhibitor (NaRI)--reboxetine. Bupropion, a noradrenaline and dopamine-reuptake inhibitor appears to be effective in the treatment of neuropathic pain. Venlafaxine--selective serotonin and noradrenergic reuptake inhibitors (SNRI) was shown to be effective in the treatment of different kinds of pain. Duloxetine (SNRI) is effective in relieving both the emotional and painful physical symptoms of depression. Additional randomized, controlled trials are necessary to fully evaluate the role of new antidepressants in the treatment of chronic pain.
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PMID:[The effectiveness of antidepressants in the treatment of chronic non-cancer pain--a review]. 1577 Nov 51

The burden of mental illness has been underestimated worldwide. Depression was the fourth leading cause of disease burden in the world in 1990 and is projected to be the second leading cause of disability by 2020. It is a leading cause of morbidity and mortality in the United States, costing billions of dollars annually in direct and indirect medical costs and losses in productivity. Patients with major depressive disorder (MDD) may experience both psychological and medical complaints, including somatic sensations or pain. Some antidepressants have been shown to treat chronic pain syndromes, but despite the variety of antidepressants available in the United States, only 65-70% of patients respond to initial antidepressant treatment. Treatments are limited by delayed onset of antidepressant effects, side effects, partial response, and treatment resistance. Duloxetine, approved by the U.S. Food and Drug Administration for the treatment of MDD, is a reuptake inhibitor at serotonergic and noradrenergic neurons and appears to have low affinity for other neurotransmitter systems. In clinical trials, duloxetine was effective for the treatment of MDD and was well tolerated. Further study is needed to compare its efficacy with that of other antidepressants, to clarify effects on somatic symptoms, and to assess potential adverse cardiovascular and sexual side effects. Duloxetine is also approved for the management of diabetic peripheral neuropathic pain and is under investigation for the treatment of stress urinary incontinence in women.
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PMID:Duloxetine: a dual serotonin-norepinephrine reuptake inhibitor for treatment of major depressive disorder. 1584 87

Major depressive disorder (MDD) poses a significant health problem and is estimated to be the third most costly and disabling disorder in the United States. Pharmacotherapy of depression has been successful, but improvements in response rates, remission rates, side effects, compliance and faster onset of therapeutic action have become prime objectives in drug development. There is considerable support for the hypothesis that dysfunctional serotonergic or noradrenergic neurotransmission may be etiological in depressed patients. Duloxetine is a balanced and potent reuptake inhibitor of serotonin (5-HT) and norepinephrine (NE) being studied as an antidepressant medication. In this review, we highlight the preclinical pharmacology, pharmacokinetic profile, and effects of duloxetine in the pharmacotherapy of depression. Evidence for 5-HT and NE reuptake inhibition by duloxetine comes from in vitro and in vivo transporter binding and functional uptake studies. Taken together with efficacy data from in vivo microdialysis, electrophysiological and behavioral studies, it is evident that duloxetine is balanced as a dual serotonin norepinephrine uptake inhibitor in vivo. The clinical efficacy and safety of duloxetine in the treatment of MDD has been studied in 6 multicenter, randomized, double-blind, placebo-controlled trials. In these studies, duloxetine was found to be effective in the treatment of emotional/psychological and painful physical symptoms associated with depression. More importantly, duloxetine appears to have better response rates and remission from depressive symptoms, perhaps due to its ability to treat a wider range of symptoms.
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PMID:The dual transporter inhibitor duloxetine: a review of its preclinical pharmacology, pharmacokinetic profile, and clinical results in depression. 1589 57

The efficacy of duloxetine in the treatment of major depressive disorder in women of approximately perimenopausal age (40-55 years; 62 placebo subjects and 55 subjects taking duloxetine, 60 mg/day) was compared with that observed in cohorts of younger (<40 years, 94 placebo subjects and 85 duloxetine subjects) and older (>55 years, 26 placebo subjects and 25 duloxetine subjects) women. Women (ages 40-55 years) receiving duloxetine demonstrated significantly greater improvement in total scores on the 17-item Hamilton Rating Scale for Depression compared with placebo at the study endpoint (week 9). Significant advantages for duloxetine over placebo were observed on 17-item Hamilton depression scale subscales (core, Maier, anxiety, retardation, and sleep), in addition to the Clinical Global Impression severity and Patient Global Impression of Improvement Scale, the Quality of Life in Depression Scale, and Visual Analog Scales assessing pain severity. The magnitude of duloxetine's treatment effect in women ages 40-55 years was similar to that observed in younger (age <40 years) and older (age >55 years) female patients. In the placebo treatment groups, however, mean changes differed substantially by age group with the smallest placebo responses observed in the 40-55 age group. Duloxetine (60 mg/day) was demonstrated to be an effective treatment for major depressive disorder in this cohort of women ages 40-55 years.
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PMID:Duloxetine for the treatment of major depressive disorder in women ages 40 to 55 years. 1600 Jun 78

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


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