Reboxetine response

Noradrenaline transporters (NAT) are localized in the presynaptic plasma membrane of adrenergic nerve terminals. They belong to a family of proteins with 12 putative transmembrane proteins which are responsible for recycling of released neurotransmitters (noradrena-line/adrenaline, dopamine, serotonin, amino acid transmitters) back into the presynaptic nerve ending. Noradrenaline transporters can be blocked by a number of different antidepressant drags, including tricyclic antidepressants (e.g. desipramine) and selective noradrenaline reuptake inhibitors (e.g. reboxetine). 

It has low affinity for adrenergic, cholinergic, histaminic, dopaminergic, and serotoninergic receptors ( 176). At a dose of 4 mg twice daily, reboxetine has exerted substantial inhibition of NE uptake in humans as witnessed by abolishment of the tyramine pressor response ( 177). 

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. 

The novel compounds nefazodone and trazodone usually require titration to a minimum therapeutic dose of at least 200 mg/day. Response to reboxetine, venlafaxine and mirtazapine may occur at the starting dose but some dose titration is commonly required. Venlafaxine is licensed for treatment-resistant depression by gradual titration from 75 to 375 mg/day. There is some need for dose titration when using MAOIs although recommended starting doses (e.g. phenelzine 15 mg t.d.s.) may be effective. Unlike other drug classes, reduction to a lower maintenance dose is recommended after a response is achieved. 

Reboxetine selectively inhibits the re-uptake of noradrenaline and is particularly useful in patients with negative symptoms such as withdrawal and flattening of emotional response. 

Reboxetine has a complex hepatic biotransformation in humans, including hydroxylation, 0-dealkylation, and oxidation, followed by glucuronidation and sulfoconjugation. In vitro hepatic experiments have indicated that CYP3A4 is the major enzyme responsible for the metabolism of reboxetine. 

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