Reboxetine efficacy

Massana, J. (1998). Reboxetine versus fluoxetine an overview of efficacy and tolerability. J. Clin. 

Compound 10, representing a series of NRIs structurally similar to reboxetine, has been reported to be a potent and selective inhibitor of NET (K-, — 3.2 nM) [24], In an a-methyl-m-tyrosine (a-MMT)-induced cortical NE depletion model in rats, 10 showed dose-dependent activity after oral administration with a measured ED50 of 18mg/kg. WAY-256805 (11), an NRI, was recently reported to be efficacious in the mouse tail suspension model [25]. 

Reboxetine is the only selective and reasonably potent noradrenaline reuptake inhibitor available clinically at the present time. Reboxetine has a chemical structure not dissimilar from viloxazine, an antidepressant which was of only limited clinical interest in the 1970s because of its weak efficacy and unacceptable side effects (nausea, vomiting and occasionally seizures). Unlike the secondary amine TCA antidepressants, such as maprotiline, desipramine, nortriptyline and protriptyline, reboxetine does not affect any other transporter or receptor system and therefore is largely devoid of TCA and SSRI-like side effects. In clinical trials, reboxetine has been shown to be as effective as the SSRIs in the... 

Taken together, the efficacy of antidepressants covers the spectrum of anxiety disorders, although there are important differences between drugs in the group (Table 3). Several new antidepressants have been marketed since the SS-RIs venlafaxine and mirtazapine are discussed later (Sects. 3.2.1.2 and 3.2.1.4) nefazodone, a serotonin reuptake inhibitor and postsynaptic 5-HT2 blocker showed promise in early studies but was recently withdrawn by its manufacturers reboxetine, a noradrenaline reuptake inhibitor (NARI) showed benefits in panic disorder in one published study (Versiani et al. 2002) and further evidence of its anxiolytic efficacy is awaited. 

Reboxetine is a pure noradrenaline reuptake inhibitor that is licensed as an antidepressant in the United Kingdom. Reboxetine has established efficacy based on placebo-controlled studies both in the short and the long term. Previous noradrenaline reuptake inhibitors, such as desipramine, nortriptyline, and maprotiline, have been relatively selective for noradrenaline compared... 

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. 

Reboxetine is marketed in several countries around the world. However, the FDA has recently rejected its new drug application (NDA) because of insufficient evidence of efficacy. Nevertheless, resubmission is planned after the completion of ongoing studies. 

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. 

Ban TA, Gaszner P, Aguglia E, et al. Clinical efficacy of reboxetine a comparative study with desipramine, with methodological considerations. Hum Psychopharmacoi 1998 13 S29-S39... 

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. 

Newer antidepressants. Although the SSRIs are the only antidepressants formally approved for the treatment of panic disorder, recent evidence suggests that several other antidepressants are promising treatments for panic disorder as well. These include nefazodone, venlafaxine XR, mirtazapine, and reboxetine. Bupropion, however, does not seem to have apparent antipanic actions. Since the documentation of efficacy of these newer antidepressants in panic disorder is still emerging, they tend to be used as second-line therapy after SSRIs foil to improve panic or in patients who cannot tolerate them. 

Novel antidepressants Given the importance of SSRIs in the treatment of panic disorder, other, newer antidepressants are developing an efficacy portfolio for panic disorder (and other anxiety disorders) as well. Thus, venlafaxine XR, nefazodone, and mirtazapine hold promise for the treatment of panic disorder. One early study also suggests that the new antidepressant reboxetine may be effective in panic disorder. 

Several findings support the view that antidepressants that enhance both serotonin and norepinephrine (dual-acting antidepressants) have greater therapeutic efficacy compared with antidepressants that enhance either neurotransmitter alone (e.g. SSRIs enhance mainly serotonin, while reboxetine and desipramine enhance predominantly norepinephrine). It is specifically proposed that the dual-acting SNRIs may display faster onset of action and can be more efficacious in cases of severe depression. There are four new-generation dual-acting antidepressants duloxetine, milnacipran, mirtazapine, and venlafaxine. ... 

Dannon PN, lancu I, Grunhaus L. The efficacy of reboxetine in the treatment of refractory patients with panic disorder an open label study. Hum Psychopharmacol 2002 17 329-333. 

The selectivity ratios (Fig. 21.6) show that the SNRIs, as a group, are potent selective inhibitors of the NET and that the secondary amine TCAs are substantially more potent with regard to their inhibition of NE reuptake in comparison to the SSRIs. Their in vitro affinity for inhibiting the NET essentially mirrors more or less their clinical efficacy as SNRIs (11) desipramine > protriptyline > amitriptyline = nortriptyline > reboxetine > maprotiline > amoxapine > imipramine > paroxetine. The level of affinity of the SNRIs for NET is not predictive for antidepressant activity. 

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