Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper investigates if the highly selective norepinephrine reuptake inhibitor reboxetine leads to a dose-dependent cortisol release and if this response depends on personality dimensions related to clinical depression in healthy volunteers. Twenty-four male subjects received placebo, 2 mg, or 4 mg reboxetine in a balanced, randomized cross-over study. Cortisol was measured in saliva at six different time-points according to the kinetics of the drug. Furthermore, several measurements of cardiovascular parameters, emotional states, and possible side-effects were obtained. Subjects were divided into two groups scoring above or below the median of a depressiveness questionnaire scale [n = 11, low (D-); n = 13, high (D+)]. Results clearly demonstrated, that reboxetine stimulates cortisol release. Whereas blood pressure was not affected, heart rate increased after 2 and 4 mg but not dose dependently. Subjects reported more non-specific arousal while the dimensions of tiredness-wakefulness and positive-negative emotional states were not affected by the drug. Somatic complaints were low and only non-specific complaints were statistically elevated but of negligible amount. Subjects classified as D+ can be characterized as high responders to the drug. This is especially true not only for cortisol increases but also for changes in heart rate and some ratings on physical complaints. Hot flushes, sweating and a throbbing sensation in blood vessels in the head were observed in D+ but only with the 4 mg dose. The results clearly demonstrate that reboxetine stimulates cortisol release and heart rate and that this is particularly pronounced in subjects scoring high on depression-related personality dimensions. Reboxetine, therefore, is a promising tool for investigating neuroendocrine response to noradrenergic challenge tests. The question whether increased responses in D+ are due to an up-regulation of receptor sensitivity as a consequence of low norepinephrine supply is discussed.
 ...
PMID:Reboxetine in a neuroendocrine challenge paradigm: evidence for high cortisol responses in healthy volunteers scoring high on subclinical depression. 1134 96

The goal of the present work was to conduct a meta-analysis comparing reboxetine and the selective serotonin reuptake inhibitors (SSRIs) for major depressive disorder (MDD). Medline/Pubmed was searched for double-blind, randomized trials comparing these two agents for MDD. The makers of reboxetine (Pfizer Inc.) were also contacted to provide missing data and/or unpublished studies. 9 trials (n=2641) were combined using a random effects model. Response rates were comparable between the SSRI (63.9%) and reboxetine (59.2%)-treated groups (p=0.118). There was no significant difference in the degree of improvement in psychosocial functioning, as measured by the social adaptation self-evaluation scale, between the two groups. Overall discontinuation rates (25.1% versus 32.0%; p=0.015), and the rate of discontinuation due to intolerance (8.5% versus 12.6%; p=0.007) favored SSRI treatment. The rate of discontinuation due to lack of efficacy did not differ significantly between the two groups. SSRI-treated patients were more likely to experience nausea, hypersomnia, and fatigue. Reboxetine-treated patients were more likely to experience constipation, difficulty urinating, and insomnia. These results suggest that the NRI reboxetine and the SSRIs differ with respect to their side-effect profile and overall tolerability but not their efficacy in treating MDD.
 ...
PMID:A meta-analysis of clinical trials comparing reboxetine, a norepinephrine reuptake inhibitor, with selective serotonin reuptake inhibitors for the treatment of major depressive disorder. 1771 52