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)

Elderly patients are particularly susceptible to the potential side effects of current antidepressants due to agerelated physiologic changes. We report a pilot study to examine the tolerability of increasing doses of reboxetine, a selective noradrenaline reuptake inhibitor (selective NRI), in elderly depressed patients. Twelve elderly female patients (75-87 years) with either major depression or dysthymia received reboxetine titrated to 8 mg/day over a 4-week period. Tolerability was assessed and included the measurement of vital signs. Electrocardiograms were recorded at baseline and on days 14 and 28. Newly emergent signs and symptoms were recorded throughout the study. Efficacy was assessed using four rating scales, including the Clinical Global Impression (CGI) scale and Hamilton Depression Rating Scale (HAM-D). Eleven patients completed the study, nine received the maximal dose of reboxetine 8 mg/day, and two received maximum doses of reboxetine 6 mg/day due to cardiac rhythm changes in week 3. A total of five patients experienced tachycardia (including two with cardiac rhythm changes in week 3). At the end of the study, seven patients were "much" to "very much" improved on the CGI scale with a concomitant decrease in HAM-D total score of 22% to 41%. Reboxetine was well tolerated by the majority of patients and efficacy outweighed side effects in 75% of patients. Reboxetine 4 mg/day, increasing to 6 mg/day on the basis of individual patient tolerability, may be considered as a safe dose range for testing the efficacy and tolerability of reboxetine in long-term controlled clinical trials in elderly patients with depression.
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PMID:Reboxetine in the treatment of depression in the elderly: pilot study. 1061 69

The efficacy and tolerability of reboxetine, a unique selective noradrenaline reuptake inhibitor, were compared with those of placebo in a 6-week, randomized, double-blind study of hospitalized patients with a DSM-III-R diagnosis of major depressive disorder. Fifty-two patients (25 in the placebo group, 27 in the reboxetine group) were included in the efficacy analysis. Sixteen (64%) of those in the placebo group and four (15%) in the reboxetine group were withdrawn during the study because of lack of efficacy. Improvement in the mean Hamilton Rating Scale for Depression (HAM-D) total score at last assessment was significantly greater in the reboxetine group than in the placebo group (p < 0.001). Similarly, the response rate to treatment, defined as > or =50% reduction in HAM-D total score, was 74% for patients who received reboxetine compared with 20% for those who received placebo (p < 0.001). A significantly greater response with reboxetine than with placebo was seen as early as day 10 of treatment (p = 0.006). The therapeutic efficacy of reboxetine was substantiated by improvement in mean scores on the Zung Self-Rating Scale and on the Clinical Global Impression Severity of Illness and Global Improvement scales. Reboxetine was well tolerated, and only one patient in each group withdrew because of adverse events. Dry mouth, insomnia, blurred vision, sweating, and constipation were recorded more frequently in the reboxetine group than in the placebo group. There was a tendency toward orthostatic changes in the systolic blood pressure, but this was not clinically significant. This study demonstrated that reboxetine is significantly more effective than placebo in the treatment of hospitalized patients with severe major depressive disorder and is well tolerated.
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PMID:Double-blind, placebo-controlled study with reboxetine in inpatients with severe major depressive disorder. 1065 5

Reboxetine is a new antidepressant acting by selective inhibition of noradrenaline reuptake (NARI) at the synaptic cleft. The efficacy of reboxetine is similar to other antidepressants such as tricyclic and Selective Serotonin reuptake inhibitors once (SSRI). A faster onset of action (in a mean of 10 days) is suggested by preliminary studies. Reboxetine seems also to improve social adjustment of the treated depressed patients. Due to its selectivity, reboxetine presents a favourable safety profile. Treatment of depression will certainly benefit from this new compound. However, some issues need to be clarified such as the use of reboxetine in combination with other antidepressants.
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PMID:[Reboxetine (Edronax)]. 1067 75

Reboxetine is a new selective norepinephrine reuptake inhibitor (selective NRI) for the short- and long-term treatment of depression that is effective and well tolerated at a dose of 8 to 10 mg/day. This study assessed the pharmacokinetics of reboxetine in volunteers with renal impairment. A single 4 mg dose of reboxetine was administered to a total of 18 volunteers with mild (n = 6), moderate (n = 6), or severe (n = 6) renal impairment (creatinine clearance: 56-64, 26-51, and 9-19 ml/min, respectively), and reboxetine concentrations were measured in plasma by HPLC. Mean AUC infinity increased by 43% (mild vs. severe; p < 0.01) as renal function declined, while renal clearance and total urinary excretion of unchanged reboxetine decreased by 67% and 62%, respectively (mild vs. severe; p < 0.01 for both parameters). tmax and t1/2 were not significantly different between groups. In comparison with historical data from young healthy volunteers, AUC infinity and t1/2 are at least doubled in volunteers with renal impairment, while CLr is halved. This pharmacokinetic study has shown that increasing renal dysfunction leads to increasing systemic exposure to reboxetine, particularly in severe renal insufficiency, although reboxetine was well tolerated by all volunteers. Thus, a reduction of the starting dose of reboxetine to 2 mg twice daily would be prudent in patients with renal dysfunction.
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PMID:Pharmacokinetics of single-dose reboxetine in volunteers with renal insufficiency. 1080 1

The selective serotonin reuptake inhibitors (SSRIs) have obtained global attention but have not demonstrated superior efficacy in major depression compared with older tricyclic antidepressants. From a pharmacological viewpoint the noradrenergic system in the brain appears to have a central role in neurotransmitter organization. The importance of noradrenaline in depression is supported by its association with clinical parameters such as vigilance and drive. Reboxetine is a selective noradrenaline reuptake inhibitor--the first in its class to be marketed. In both preclinical and clinical studies reboxetine has been found to be an effective and safe antidepressant. Furthermore, reboxetine restores a patients' social functioning, producing a better quality of remission than fluoxetine.
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PMID:The need for new and better antidepressants: reboxetine a new option. 1090 Nov 53

Depression in the elderly is often not recognised and is frequently under-treated. Reboxetine is a selective noradrenaline reuptake inhibitor (selective NRI) which is effective and well tolerated in the treatment of depressed adult patients. This prospective, uncontrolled, multicentre study was designed to assess the efficacy and tolerability of reboxetine as maintenance therapy for major depressive disorder or dysthymia in 160 elderly patients (aged 65-94 years). One hundred and thirty-nine patients completed the 6-week run-in period and entered the long-term phase; 104 patients completed the 52-week treatment period. The proportion of patients with CGI-global improvement ratings assessed as 'much' and 'very much' improved increased from 15.1% at week 2 to 88.7% at week 6 and to 95.2% at week 52. The mean HAM-D total score showed a reduction from 24.0 at baseline to 10.4 at week 6 and 7.5 at week 52. Twenty-five patients discontinued treatment due to adverse events. The most frequently reported adverse events were nausea (11.9%), insomnia (11.9%), headache (10.0%) and dry mouth (9.1%), and these were of mild or moderate severity. In summary, results from this study show reboxetine to be effective, and well tolerated in both the short- and long-term treatment of elderly depressed or dysthymic patients.
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PMID:Reboxetine in the maintenance therapy of depressive disorder in the elderly: a long-term open study. 1098 24

Controlled trials in patients with bulimia nervosa have demonstrated efficacy of antidepressant medications with serotonergic function (e.g. fluoxetine) as well as noradrenergic function (e.g. desipramine). Seven outpatients with bulimia nervosa according to DSM-IV criteria were treated openly with 8 mg of reboxetine, a selective noradrenaline reuptake inhibitor (NRI) over a 12-week period. The patients were assessed with the Structured Clinical Interview for DSM, Clinical Global Impression, 17-item Hamilton Depression Rating scale (HAM-D), Eating Disorder Inventory, Eating Disorders Questionnaire, daily self-ratings of eating behaviour, and the UKU side-effect rating scale. Three patients dropped out prematurely, one after 6 weeks and two after 4 weeks of reboxetine treatment. The reasons for premature attrition were rapid remission in one patient after 2 weeks and constipation, which led to an increase in episodes of laxative intake in two patients. In the total group, the monthly binge eating frequency showed a reduction of 73% and the frequency of vomiting episodes per month decreased by 67%. Furthermore, there was a concomitant decrease of depression ratings (HAM-D: from 12.2-6.1). Reboxetine seems to be an option for the treatment of bulimia nervosa.
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PMID:Reboxetine in the treatment of bulimia nervosa: a report of seven cases. 1111 11

Changes to the binding properties of cortical N-methyl-D-aspartic acid (NMDA) and beta-adrenergic receptors have both been reported as potential indicators of antidepressant activity. In the present investigation we examined the effects of the noradrenaline reuptake inhibitor, reboxetine, the serotonin reuptake inhibitor, sertraline, alone and in combination on the binding properties of cortical NMDA receptors and cortical beta1-adrenoceptors following 14 days of treatment in the olfactory bulbectomized rat model of depression. A decrease in the potency of glycine to displace the strychnine insensitive glycine antagonist [3H] 5,7 dichlorokynurenic acid (5,7 DCKA) was observed in cortical homogenates of OB rats when compared to sham-operated controls. Similarly, treatment with the combination of reboxetine and sertraline for 14 days produced a decrease in the potency of glycine when compared to vehicle treated controls. By contrast neither olfactory bulbectomy or drug treatment significantly altered basal or glycine enhanced binding of the non-competitive NMDA antagonist [3H] MK-801 in cortical homogenates. Reboxetine alone, and in combination with sertraline, down-regulated [3H]-CGP 12177 (a selective beta-adrenoceptor antagonist) binding in both OB and sham-operated animals. The lack of a bulbectomy effect in the [3H] CGP-12177 binding assay, and the fact that olfactory bulbectomy and antidepressant treatments produce a similar change to the potency of glycine at the NMDA receptor, suggests that these tests do not provide a neurochemical marker for either the behavioral hyperactivity deficit or antidepressant response in the model.
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PMID:Effects of reboxetine and sertraline treatments alone and in combination on the binding properties of cortical NMDA and beta1-adrenergic receptors in an animal model of depression. 1112 11

Reboxetine is a novel selective norepinephrine inhibitor that has been evaluated in the treatment of patients with depression. Reboxetine is a racemic mixture, and the (S,S)-(+)-enantiomer appears to be the more potent inhibitor. However, the ratio of the areas under the concentration-time curves of the (S,S)-(+)- and (R,R)-(-)-enantiomers in vivo is approximately 0.5. There is no evidence for chiral inversion. Differences in the clearances of the 2 enantiomers may be explained by differences in protein binding. The pharmacokinetics of reboxetine are linear following both single and multiple oral doses up to a dosage of 12 mg/day. The plasma concentration-time profile following oral administration is best described by a 1-compartment model, and the mean half-life (approximately 12 hours) is consistent with the recommendation to administer the drug twice daily. Reboxetine is well absorbed after oral administration. The absolute bioavailability is 94.5%, and maximal concentrations are generally achieved within 2 to 4 hours. Food affects the rate, but not the extent, of absorption. The distribution of reboxetine appears to be limited to a fraction of the total body water due to its extensive (>97%) binding to plasma proteins. The primary route of reboxetine elimination appears to be through hepatic metabolism. Less than 10% of the dose is cleared renally. A number of metabolites formed through hepatic oxidation have been identified, but reboxetine is the major circulating species in plasma. In vitro studies show that reboxetine is predominantly metabolised by cytochrome P450 (CYP) 3A4; CYP2D6 is not involved. Reboxetine plasma concentrations are increased in elderly individuals and in those with hepatic or renal dysfunction, probably because of reduced metabolic clearance. In these populations, reboxetine should be used with caution, and a dosage reduction is indicated. Ketoconazole decreases the clearance of reboxetine, so that the dosage of reboxetine may need to be reduced when potent inhibitors of CYP3A4 are coadministered. Quinidine does not affect the in vivo clearance of reboxetine, confirming the lack of involvement of CYP2D6. There is no pharmacokinetic interaction between reboxetine and lorazepam or fluoxetine. Reboxetine at therapeutic concentrations has no effect on the in vitro activity of CYP1A2, 2C9, 2D6, 2E1 or 3A4. The lack of effect of reboxetine on CYP2D6 and CYP3A4 was confirmed by the lack of effect on the metabolism of dextromethorphan and alprazolam in healthy volunteers. Thus, reboxetine is not likely to affect the clearance of other drugs metabolised by CYP isozymes.
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PMID:Clinical pharmacokinetics of reboxetine, a selective norepinephrine reuptake inhibitor for the treatment of patients with depression. 1119 74

Social impairment is a common feature of depressive illness, often causing substantial and clinically meaningful dysfunction. Although the depressive symptoms and social impairment are linked, the naturalistic course and response to treatment of these two aspects of depression do not necessarily correlate. A variety of self-report and clinician-administered assessment scales which are specific for the measurement of social functioning and have good psychometric properties have been developed in the past 40 years. The most recent of these instruments is the Social Adaptation Self-evaluation Scale (SASS), a 21-item scale designed in 1989 to assess patient response to antidepressant treatment. SASS was used in two clinical trials comparing reboxetine, the new selective noradrenaline reuptake inhibitor (selective NRI), with fluoxetine. While no difference in efficacy was detectable by traditional assessments of symptoms, reboxetine proved to be significantly more effective than fluoxetine in improving social functioning in patients with depression. Reboxetine was also more effective than fluoxetine in rectifying social functioning in the subset of patients who remitted from an episode of major depression. Specifically, reboxetine improved patient motivation, energy and self-perception. These results indicate that antidepressant therapy can achieve more than symptom relief in depression. It is speculated that there may be a difference in the roles played by serotonin and noradrenaline in social functioning.
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PMID:Role of serotonin and noradrenaline in social dysfunction: a review of data on reboxetine and the Social Adaptation Self-evaluation Scale (SASS). 1122 52


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