Pharmacotherapeutic group: Other Antidepressants, ATC code: NO6A X18
Mechanism of action
Reboxetine is a highly selective and potent inhibitor of noradrenaline reuptake. It has only a weak effect on the 5-HT reuptake and does not affect the uptake of dopamine.
Noradrenaline reuptake inhibition and the consequent increase of noradrenaline availability in the synaptic cleft and modification of noradrenergic transmission, reportedly is among the most relevant mechanisms of action of known antidepressant drugs.
Pharmacodynamic effects
In vitro
, studies have shown that reboxetine has no significant affinity for adrenergic (α
1
, α
2
, β) and muscarinic receptors; antagonism of such receptors has been described to be associated with cardiovascular, anticholinergic and sedative side effects of other antidepressant drugs. Reboxetine is devoid of
in vitro
binding affinity for either α
1
or α
2
adrenoceptors, however, a functional interference with α-adrenoceptors at high doses
in vivo
cannot be excluded.
Clinical efficacy
In a post hoc stratified analysis of data from 11 placebo-controlled trials involving 2400 patients, there was no statistical difference in response rates on the primary endpoint (HAMD 21 item scale) for reboxetine versus placebo patients with mild to moderate severity of depression. Efficacy was only clearly demonstrated in patients with severe or very severe depression. From these trials there are limited efficacy data available in the use of reboxetine in patients with mild to moderate severity of depression.
