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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Depression is thought to result from a dysfunction in the noradrenergic or serotonergic systems. The noradrenergic system appears to be associated with increased drive, whereas the serotonergic system relates more to changes in mood and it is possible that the different symptoms of depression may benefit from drugs acting mainly on one or other of the neurotransmitter systems. A series of studies has shown that interruption of serotonin synthesis compromises the efficacy of serotonin but not noradrenaline reuptake inhibitors, and interruption of noradrenaline synthesis compromises the efficacy of noradrenaline but not serotonin reuptake inhibitors (SSRIs). This suggests that the two classes of drugs owe their activity to functional changes in different neurotransmitter systems. Reboxetine represents a new class of drugs-the selective noradrenaline reuptake inhibitors (NARIs). It acts specifically at noradrenergic sites unlike the non-selective tricyclic antidepressants (TCAs). NARIs have a role in the treatment of depression, either alone or as adjunctive therapy.
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PMID:Is there a role for a pure noradrenergic drug in the treatment of depression? 916 5

This review reports anatomical studies evaluating central and peripheral alpha 2- and beta-adrenoceptors. The results suggest abnormalities exist in the noradrenergic system in depressed patients. Most animal models involve the use of stress to simulate depression in man. All models that have been developed lead to differential changes in noradrenergic function. We have assessed the effects of reboxetine, a novel, selective noradrenaline-reuptake inhibitor (NARI) in olfactory bulbectomised rats, a procedure that induces significant changes in amygdala function. Reboxetine is an effective antidepressant in the forced swim test and open field test in bulbectomised rats. Unlike the tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), reboxetine is ineffective in the 8-OH-DPAT hypothermia test, indicating that reboxetine is selective for the noradrenergic system. Owing to the abnormalities that occur in depression, it would seem sensible to target the noradrenergic system for treatment of this condition.
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PMID:Noradrenaline in basic models of depression. 916 6

A 6-week, randomised, double-blind, multicentre study in 256 patients with a DSM-III-R diagnosis of major depression was carried out to compare the selective noradrenaline reuptake inhibitor (NARI), reboxetine, with the reference standard tricyclic antidepressant, imipramine. The efficacy of reboxetine, as measured by the extent of improvement of Hamilton Depression Rating Scale. Montgomery and Asberg Depression Rating Scale and the Clinical Global Impression Scale, was similar to that of imipramine. The improvement was observed in the overall population and in severely depressed and melancholic patients. Reboxetine tolerability compared favourably with that of imipramine. Frequency of discontinuation due to adverse events was lower in the reboxetine-treated group (10.0%) than in the imipramine-treated group (14.3%), and the cumulative risk of development (Kaplan-Meier analysis) of dry mouth, hypotension and/or related symptoms and tremor was significantly higher on imipramine than on reboxetine.
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PMID:Efficacy and tolerability of reboxetine compared with imipramine in a double-blind study in patients suffering from major depressive offsodes. 916 9

Reboxetine is a new selective noradrenaline reuptake inhibitor that has been shown to be effective in both the short-(4-8 weeks) and long-term (up to 12 months) treatment of depression. Four positive placebo-controlled studies showed reboxetine to have significant antidepressant efficacy; the response rate (> or = 50% decrease in HAM-D total score) with reboxetine ranging from 56-74%. Comparator-controlled trials showed reboxetine to be at least as efficacious as imipramine and desipramine in both adults and elderly patients. Reboxetine is also as effective as fluoxetine in the overall depressed population. However, subset analysis showed reboxetine to be significantly superior to fluoxetine in severely depressed patients. Reboxetine also showed significant advantages over fluoxetine in terms of social functioning, positively affecting patients' self perception and motivation towards action. The therapeutic effect of reboxetine is maintained for at least up to 1 year. During long-term therapy, 78% of patients receiving reboxetine were in remission at last assessment compared with only 45% of patients in the placebo group. Fewer reboxetine-treated patients relapsed (22%) compared with those receiving placebo (56%). In summary, reboxetine is effective in both the short- and long-term treatment of depression, and is at least as efficacious as traditional tricyclic antidepressant drugs and selective serotonin reuptake inhibitors. The additional benefits offered by reboxetine to the depressed patient include effective long-term treatment, efficacy in all grades of depression (including severe cases) and, importantly, specific advantages on social functioning. These additional benefits make reboxetine a favourable choice in the management of depression.
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PMID:Reboxetine: additional benefits to the depressed patient. 943 28

The tolerability of reboxetine was evaluated in 2613 adult (aged 18-65 years) or elderly (aged > 65 years) patients with depressive illness treated with reboxetine, comparator agents or placebo, who entered both short- and long-term, controlled and uncontrolled clinical trials. The reboxetine adverse-event profile in acute depression was established by comparison with placebo in 746 patients. Overall, 69% of 373 patients treated with reboxetine experienced adverse events compared with 57% of 373 patients in the placebo group. The majority of adverse events were moderate in severity, and discontinuation because of adverse events was low and comparable in both the reboxetine (8%) and the placebo (7.5%) group. When compared with imipramine, reboxetine was better tolerated. Most side-effects were less common in the reboxetine than the imipramine cohort, and fewer patients receiving reboxetine (10% in adult patients; 11% in elderly patients) discontinued treatment because of adverse events than those receiving imipramine (14% in adult patients; 16% in elderly patients). Compared with fluoxetine, the total frequency of adverse events was similar in reboxetine-treated patients (67%) and fluoxetine-treated patients (65%). In the fluoxetine group, 7% discontinued because of adverse events compared to 12% in the reboxetine group and 12% in the corresponding placebo group. In a 12-month placebo-controlled study, discontinuation because of adverse events in both groups was low (reboxetine 4%; placebo 1%), and the total frequency of adverse events was only marginally higher with reboxetine (28%) than with placebo (23%). Overall, no consistent changes were found in laboratory tests or electrocardiogram recordings and there was no indication of withdrawal symptoms upon abrupt reboxetine discontinuation. Reboxetine, a novel selective noradrenaline reuptake inhibitor, is well tolerated by adults and the elderly during short- and long-term treatment for depression.
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PMID:Reboxetine: a review of antidepressant tolerability. 943 31

Reboxetine is a unique selective norepinephrine reuptake inhibitor (NRI) with proven antidepressant efficacy in pharmacologic and biochemical tests predictive of antidepressant properties. Comprehensive clinical trials, including 8 placebo-controlled and/or active treatment-controlled studies, plus 4 open studies, have assessed the short-term and long-term efficacy and tolerability of reboxetine in patients with major depressive disorders and dysthymia. Results from a total of 690 patients who entered 5 open or placebo-controlled studies are summarized in this paper. Four hundred forty-nine patients with a diagnosis of either major depressive disorder or dysthymia were treated with reboxetine in these clinical studies of 4 weeks' to 12 months' duration. In a 6-week placebo-controlled study, clinically significant improvement (> or = 50% reduction in Hamilton Rating Scale for Depression total score) was observed at last assessment in 74% of reboxetine-treated patients compared with 20% of patients in the placebo group. Similar results were observed in the 6-week run-in phases of the 3 long-term studies, where the efficacy of reboxetine was maintained over the 12-month study period. Reboxetine was well tolerated; adverse events reported were mainly mild to moderate in severity, and there were no clinically significant changes in vital signs or laboratory parameters. The first in its class, reboxetine, a selective NRI, will provide a valuable addition to the existing armamentarium of agents used in the treatment of depression.
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PMID:Antidepressant efficacy and tolerability of the selective norepinephrine reuptake inhibitor reboxetine: a review. 981 23

Serotonin selective reuptake inhibitors (SSRIs) are widely used to treat depression and offer the advantage of being better tolerated compared with tricyclic antidepressants, which inhibit both serotonin and norepinephrine reuptake. Against this background, 2 clinical studies were conducted comparing the efficacy and tolerability of reboxetine, a selective norepinephrine reuptake inhibitor, with fluoxetine, an SSRI. Both studies were of double-blind, randomized, parallel-group, multicenter design. One included a placebo control group. Five hundred forty-nine patients with major depression, under inpatient care or attending outpatient or day hospital clinics, received reboxetine (8-10 mg/day) or fluoxetine (20-40 mg/day) over 8 weeks. The overall efficacy of reboxetine and fluoxetine was similar, and superior to placebo, as assessed by the mean reduction in Hamilton Rating Scale for Depression total score. Reboxetine demonstrated superior efficacy compared with fluoxetine in severely ill patients and was associated with greater improvement in social functioning, especially in terms of motivation toward action and negative self-perception. Both treatments were well tolerated. In summary, reboxetine is an effective and well-tolerated antidepressant and is superior to fluoxetine in the treatment of severely ill patients and in terms of improving social functioning.
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PMID:Reboxetine versus fluoxetine: an overview of efficacy and tolerability. 981 24

The aim of this study was to compare the efficacy and tolerability of reboxetine, a uniquely selective noradrenaline reuptake inhibitor, with the selective serotonin reuptake inhibitor, fluoxetine. A double-blind, randomized, parallel-group, multicentre design was employed. One hundred and sixty-eight patients with acute major depressive episodes were randomized to receive oral reboxetine (8-10 mg/day) or oral fluoxetine (20-40 mg/day). The treatment period was 8 weeks. Reboxetine and fluoxetine were similarly effective as assessed by the mean reduction in total Hamilton Depression Rating Scale score, the percentage of responders and patients in remission, Clinical Global Impression severity of illness and global improvement scores and Montgomery-Asberg Depression Rating Scale. A sub-analysis of patients with severe depression indicated that reboxetine had superior efficacy compared with fluoxetine. Both treatments resulted in some improvement in Social Adaptation Self-evaluation Scale total scores and this was more evident for those patients treated with reboxetine who achieved remission. Both treatments were well tolerated. The results indicate that reboxetine is an effective and well tolerated antidepressant, being more effective than fluoxetine in patients with severe depression, and more effective in terms of social functioning in those patients who achieved remission.
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PMID:Reboxetine: a double-blind comparison with fluoxetine in major depressive disorder. 1022 Jan 21

For the past decade, the role of noradrenaline in depression has been somewhat neglected in favour of serotonin. This is largely because of the advent of the selective serotonin reuptake inhibitors, which have facilitated clinical and experimental observation of the roles of serotonin. Until now, no such tools have been available to study the noradrenergic system. However, the recent development of reboxetine, the first selective noradrenaline reuptake inhibitor, has allowed clinical investigation of the role of the noradrenergic system in different aspects of depressive disorders. In clinical trials, the use of reboxetine has shown that selective noradrenaline reuptake inhibition is an effective approach to alleviating depression. It is more effective than placebo and at least as effective as desipramine, imipramine and fluoxetine in the short term. In addition, its efficacy is maintained in patients with severe depression and in those receiving long-term maintenance treatment. Reboxetine is very well tolerated, as predicted from its pharmacological profile, having fewer anticholinergic side-effects than imipramine or desipramine. Compared with fluoxetine, patients treated with reboxetine experienced less nausea and sexual dysfunction, adverse events that are common among those taking selective serotonin reuptake inhibitors. Adverse events predicted by the neuroanatomy of the noradrenergic system, such as tremor and cardiovascular effects, occurred less frequently than expected. Clinical experience with reboxetine challenges our current knowledge of the role of noradrenaline in depression and questions existing evidence based on studies with noradrenergic tricyclic antidepressants. Selective noradrenaline reuptake inhibition, as exemplified by reboxetine, therefore offers a significant improvement in antidepressant pharmacotherapy, and an opportunity to increase our understanding of the role of noradrenaline in depression.
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PMID:Predicting response: noradrenaline reuptake inhibition. 1046 25

Reboxetine (Edronax-Pharmacia & Upjohn) is a new antidepressant drug introduced last year for the acute treatment and, in patients who respond, the maintenance treatment of depression. It is marketed as a "new selective noradrenaline reuptake inhibitor" (or 'NARI'). The manufacturer claims that reboxetine "not only lifts depressed mood" but also "helps restore social interaction", with "significantly better outcome in terms of social functioning" than fluoxetine. We assess these claims and consider the place of reboxetine in therapy.
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PMID:Reboxetine--another new antidepressant. 1056 66


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