Depression reboxetine

Most efficacy trials with reboxetine have so far only been published in review articles ( 178). Most of these articles did not have peer review and do not contain the full details concerning methodology or results. This fact limits the ability to accurately determine its relative efficacy and tolerability. In short-term (4 to 8 weeks), placebo-controlled clinical trials, reboxetine produced a response (defined as at least a 50% reduction in severity scores) in 56% to 74% of patients. These results were statistically superior to placebo in most studies. Reboxetine was also found to be as effective as imipramine and desipramine in four double-blind, randomized, active-controlled (but not placebo-controlled) studies involving more than 800 outpatients or inpatients with major depression. Reboxetine produced equivalent antidepressant response rates compared with fluoxetine in two clinical trials, one of which was also placebo-controlled. However, reboxetine was reported to have improved social motivation and behavior more than fluoxetine as assessed by the newly developed Social Adaptation Self-Evaluation Scale. In all of the studies, reboxetine had a similar time (i.e., 2 to 3 weeks) to onset of the antidepressant efficacy as do other antidepressants. 

Reboxetine is a nontricyclic SNRI in which the propylamine side chain of the TCAs is constrained into a morpholine ring (Fig. 21.8). It is a potent and selective ligand for the NET, with a mechanism of action is similar to that of desipramine. Reboxetine is used for the treatment of major depressive disorders. It is a chiral compound that is marketed as a racemic mixture of R,R- and S,S-reboxetine. The antidepressant activity for reboxetine appears to reside with the S,S-(+)-enantiomer, which has approximately twofold the inhibition potency of the R,R-enantiomer (42). It is well tolerated, with different adverse-event profiles, and it appears to be at least as effective as the SSRIs in the treatment of depressive illness. Currently, it is available only in Europe and is under U.S. FDA review. It preferentially inhibits the reuptake of NE (5-FIT NE ratio, 8). Reboxetine is not metabolized by the polymorphic isoforms, CYP2D6 or CYP2C19, and may offer a valuable alternative to the secondary amine TCAs in the treatment of major depression. Reboxetine is likely to become a promising alternative for patients who have failed treatment with or do not tolerate serotonergic antidepressants. Reboxetine has been shown to be effective and well tolerated in the treatment of panic... 

Scates, A. C. Doraiswamy, P. M. (2000). Reboxetine a selective norepinephrine reuptake inhibitor for the treatment of depression. Ann. Pharmacother., 34, 1302-12. 

Shen, Y. F., Li, H. F., Ma, C. et al. (2005). Comparison of reboxetine with fluoxetine in treatment of depressions randomized double-blind multicenter study. Chinese Journal of New Drugs and Clinical Remedies, 24(8), 619-23. 

These types of antidepressant were introduced around 10 years after the SSRIs. They include the serotonin noradrenaline reuptake inhibitor venlafaxine and the selective noradrenaline reuptake inhibitor reboxetine. Although there are fewer data about these drugs, clinical experience has shown they are well tolerated and, unlike the SSRIs, they are only weak inhibitors of drug metabolism (Kent, 2000). Depression is a common psychiatric disorder seen in the elderly and often remains untreated or inadequately treated (Forsell and Fastbom, 2000). Venlafaxine was shown to improve the mood in a group of 36 older patients without any effect on cognitive function, an important consideration where there is the possibility of the coexistence of mild or undiagnosed dementia (Tsolaki et al., 2000). 

Versiani M, Mehilane L, Gaszner P, Arnaud-Castiglioni R. Reboxetine, a unique selective NRI, prevents relapse and recurrence in long-term treatment of major depressive disorder. J Clin Psychiatry 1999 60 400-406. 

Reboxetine was first introduced to the European market in 1997 for the treatment of depression it is not yet available in the United States. Reboxetine represents a novel antidepressant class, the selective noradrenaline reuptake inhibitors (NRIs). 

There are no current data supporting the use of reboxetine in the child and adolescent population. ITowever, given its noradrenergic profile, it may be useful for ADHD and perhaps for depression, and anxiety. 

Vetsiani, M., Amin, M., and Chouinard, G. (2000) Doubleblind, placebo-controlled study with reboxetine in inpatients with sevete majot depressive disorder. / Clin Psychopharmacol 20 28-34. 

A critical review by Olver et al. (2001) on so-called third-generation antidepressants (venlafaxine, reboxetine, nefazodone, mirtazapine) covered 30 controlled therapeutic trials and a number of relapse prevention studies. Questions addressed were overall efficacy, speed of onset and safety but, according to this review, none of the third-generation antidepressants was specifically tested with respect to its potential effects on cognitive function in depressed patients. 

In a 1-year, double-blind, placebo-controlled, long-term treatment study of 358 depressed patients, 22% of reboxetine-maintained patients relapsed versus 55% of those switched to placebo (276). 

Consistent with its most potent known mechanism of action, bupropion is an indirect dopamine agonist via its inhibition of the neuronal uptake pump for dopamine (503, 504). Hence, bupropion can potentiate the effects of other dopamine agonists. This interaction does not typically cause serious problems and may even be advantageous in specific instances such as patients with Parkinson s disease plus a depressive disorder. Because of its ability to inhibit NE uptake, bupropion would be prone to the same interactions as NSRIs such as desipramine and reboxetine. 

Berzewski H, Van-Moffaert M, Gagiano CA. Efficacy and tolerability of reboxetine compared with imipramine in a double-blind study in patients suffering from major depressive episodes. Eur Neuropsychopharmacoi 1997 7 S37-S47... 

Early indications from the use of reboxetine show that its efficacy is at least comparable to that of the tricyclic antidepressants and the SSRIs. In addition, reboxetine may specifically enhance social functioning, perhaps by converting apathetic responders into full remitters. Furthermore, reboxetine may be useful for severe depression, for depression unresponsive to other antidepressants, and as an adjunct to serotonergic antidepressants when dual neurotransmitter mechanisms are necessary to treat the most difficult cases. 

In addition to reboxetine, which is currently marketed, other selective NRIs are in clinical testing at present for depression or attention deficit disorder. These include... 

Lemke MR. Effect of reboxetine on depression in Parkinson s disease patients. J Clin Psychiatry 2002 63 300-304. 

Lemke MR (2000) Reboxetine treatment of depression in Parkinson s disease. J. Clin. Psychiatry 61 872. 

Reboxetine, was the first antidepressant to be developed to work specifically on noradrenaline (Wong et al., 2000). It is a specific noradrenergic reuptake inhibitor (NARI) and in a clinical study, it was found to improve the psycho-social functioning of depressed patients, as measured by the Social Adaptation Self-evaluation Scale (SASS), more than fluoxetine, a specific serotonergic reuptake inhibitor (SSRI) antidepressant (Dubini, Bose, and Polin, 1997). It has been suggested that social adaptation as measured on the scale used (SASS) is associated with the concept of social motivation (Charles et al., 1999). The improvement, thus, appeared to be associated with enhancement of social motivation which might be important for the therapeutic recovery process (Hirschfeld, et al., 2000). However, the mechanism by which the changes in noradrenaline induced by reboxetine led to improvement on the SASS is unknown. 

These data suggest that antidepressant-induced sexual dysfunction is more likely to be associated with agents that greatly potentiate 5HT neurotransmission. This notion is supported by the results of a 6-week doubleblind study of 24 men with premature ejaculation, in which paroxetine (20 mg/day) increased latency to ejaculation six-fold while mirtazapine (30 mg/day) had minimal effect (4). In a randomized, 8-week, double-blind, placebo-controlled study in 450 patients with major depression, fluoxetine (20 -0 mg/day) significantly impaired sexual function, while the noradrenaline re-uptake inhibitor reboxetine had no effect (5). 

Clayton AH, Zajecka J, Ferguson JM, Filipiak-Reisner JK, Brown MT, Schwartz GE. Lack of sexual dysfunction with the selective noradrenaline reuptake inhibitor reboxetine during treatment for major depressive disorder. Int Clin Psychopharmacol 2003 18 151-6. 

A 72-year-old man with diabetes mellitus and cardiovascular disease developed major depression. He was taking aspirin (100 mg/day), enalapril (20 mg/day), and glibenclamide (5 mg/day). His serum sodium was 133 mmol/1 (reference range 134—146 mmol/1). He started to take reboxetine (4 mg/day) and after 8 days experienced malaise and nausea, at which time his serum sodium had fallen to 118 mmol/1. The reboxetine was withdrawn, and both his symptoms and the low serum sodium remitted over the next 6 days. Rechallenge with reboxetine produced a recurrence of both the low sodium and the accompanying symptoms. 

REBOXETINE ANTI HYPERTENSIVES AND HEART FAILURE DRUGSCENTRALLYACTING ANTI HYPERTENSIVES-methyldopa Methyldopa may i effect of antidepressants Methyldopa can cause depression Methyldopa should be avoided in patients with depression... 

Fieishaker JC. Ciinicai pharmacokinetics of reboxetine, a seiective norepinephrine reuptake inhibitor for the treatment of patients with depression. Ciin Pharmacokinet 2000 39(6) 413-27. 

Tanum L. Reboxetine toierabiiity and safety profiie in patients with major depression. Acta Psychiatr Scand Suppi 2000 402 37-40. 

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