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)

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 purpose of this study is to explore the psychological efficacy of Xinwei Decoction, a traditional Chinese herbal medicine, to treat functional dyspepsia (FD) accompanied with depression and anxiety. Seventy-three subjects, divided into three groups, had been given herbal medicine (Xinwei Decoction), prokinetic agent (Domperidone) and placebo, respectively for 8 weeks. Before and after treatment, all subjects were examined with FD symptom scale, Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA). As a result, the total scores of the three groups in FD symptom scale, HAMD and HAMA after treatment decreased in different levels, with the decrease in the herbal group more significant than the other two groups (p < 0.01), indicating the efficacy of the herbal medicine. The total effective rates of the herbal, Domperidone and placebo groups were 90%, 67% and 31%, respectively, which indicated significant effect differences between Xinwei Decoction and Domperidone (p < 0.05) and between Xinwei Decoction and placebo (p < 0.01), showing that the efficacy of herbal therapy was superior to that of the other two therapies. Furthermore, there was no one in the Domperidone and placebo groups being cured of depression and anxiety, while the curing rate in the herbal group was about 70%, indicating the efficacy of herbal medicine in comparison to that of Domperidone and placebo for anti-depression and anti-anxiety. The result demonstrated that Xinwei Decoction could not only alleviate FD symptoms but also relieve depression and anxiety.
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PMID:Clinical and psychological assessment on xinwei decoction for treating functional dyspepsia accompanied with depression and anxiety. 1597 84

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

Domperidone, an upper gastrointestinal function regulatory medicine, has recently been evaluated for its clinical usefulness in the treatment of stress and depression. We examined the effects of domperidone on the plasma levels of motilin-immunoreactive substance (IS), somatostatin-IS, gastrin-IS, adrenocorticotropic hormone (ACTH)-IS, and cortisol under stress conditions by repetitive blood sampling. After a single oral administration of domperidone (30 mg), the plasma domperidone level was highest (58.6+/-6.4 ng/ml) in the sample taken 40 min after administration, after which the plasma level fell. Peak plasma motilin-IS levels (23.1+/-1.4 pg/ml) were achieved 40 min after administration of domperidone (p < 0.01 vs. placebo), and returned to baseline levels within a further 40 min. Plasma somatostatin-IS levels (13.0+/-1.2 pg/ml) increased 60 min after administration of domperidone (p < 0.01 vs. placebo). Plasma gastrin-IS levels did not change significantly. These results suggest that the pharmacological effects of domperidone on gastrointestinal functions are closely related to changes in motilin-IS and somatostatin-IS levels. Domperidone significantly suppressed increases in plasma ACTH-IS and cortisol levels compared with the response to a placebo. These modulatory effects might be beneficial in stress-related diseases and suggest that this medicine has clinical pharmacological activity.
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PMID:Effects of domperidone on human plasma levels of motilin, somatostatin, gastrin, adrenocorticotropic hormone and cortisol. 1614 53

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

Chronic pain is among the most common conditions to initiate medical care; 40% of patients victimized by chronic pain are not under the supervision of a physician, and about 70% of patients with severe pain are receiving pain medical care. About dollar 100 billion is an annual estimated cost representing loss of productivity, increased medical costs, and income loss. Major depressive disorder is not infrequently encountered in daily clinical practice often presenting with somatic complaints that include varieties of pain, and these may be so prominent as to direct the treatment to the somatic complaint evaluation to the exclusion of underlying psychopathology. Anxiety disorders and other psychiatric disorders may also present with such a somatization evaluation focus. Serotonin noradrenergic reuptake inhibitors (SNRIs), ie, venlafaxine and duloxetine, offer benefits over tricyclic antidepressants and serotonin reuptake inhibitors. Years of experience with venlafaxine representing a first-line pharmacotherapy for depression and anxiety have benefited patients presenting with somatic symptoms with a robust onset. A more rapid achievement by venlafaxine of remission and a high-quality pharmacokinetic and pharmacodynamic profile lead to patient compliance and facilitate both fewer relapses and recurrences. Duloxetine is broadly discussed, revealing pharmacokinetic, pharmacodynamic, adverse/side effects, cautions with requisite patient-specific selection, and laboratory monitoring. The management of somatic pain complaints of physical and psychiatric origin is discussed.
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PMID:The role of venlafaxine and duloxetine in the treatment of depression with decremental changes in somatic symptoms of pain, chronic pain, and the pharmacokinetics and clinical considerations of duloxetine pharmacotherapy. 1614 29

Antidepressants that inhibit the re-uptake of serotonin and noradrenaline might offer a chance to reduce the multiple symptoms of depression, as both serotonin and noradrenaline seem to be responsible for the emotional and physical symptoms of depression. The potential superiority of a dual mechanism of action has already been demonstrated in a number of clinical trials. Duloxetine, a novel dual acting, selective serotonin and noradrenaline-re-uptake inhibitor, has demonstrated high remission rates and good efficacy on physical symptoms, especially painful physical symptoms of depression. The results from studies in diabetic neuropathic pain provide further evidence of the effect of duloxetine on pain, independent of its effect on depression. Therefore, duloxetine provides an alternative to current therapeutic options in the treatment of the different symptoms of depression.
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PMID:Duloxetine: a new selective and dual-acting antidepressant. 1650 14

Antidepressant drugs represent the principal form of treatment for major depressive disorder. While there are a plethora of medications available for this task, current drugs have many shortcomings. In the face of these deficiencies there is an ongoing search for new agents. The search has been guided, in part, by drug design based on existing agents and their putative mechanism of action. This has been less than fruitful in addressing inadequacies of existing medications as it has not produced compounds which are novel in terms of pharmacological mechanisms. Recent insights from molecular biological approaches hold promise for the discovery of novel compounds, in particular the so-called neurogenesis hypothesis suggests novel therapeutic approaches. Although significantly modified over the years, the monoamine hypothesis of depression and antidepressant drug action still remains an important driving force behind the development of new compounds. Several recently marketed agents and some in early-phase development tend to conform to these existing mechanistic hypotheses. Clearly the place of these agents in the treatment of depression is dependent on issues such as short- and long-term safety and efficacy. Duloxetine has been developed as a dual monoamine re-uptake inhibitor. Agomelatine is a compound with major effects on the circadian system as well as effects on subtypes of the serotonin receptor system. While the mechanism of action of this compound is not certain, recent evidence would suggest that the drug exerts its effects through antagonist actions at serotonin receptors. Compounds based on the hypothalamic pituitary adrenal axis, substance P antagonism and other neuropeptides have potential application for the treatment of depression but require further development before that potential is realized.
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PMID:Prospects for the treatment of depression. 1668 61


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