Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with 
currently approved indications for the treatment of depression, 
obsessive-compulsive disorder, panic disorder and social phobia. It is also used 
in the treatment of generalized anxiety disorder, post traumatic stress 
disorder, premenstrual dysphoric disorder and chronic headache. Paroxetine, a 
phenylpiperidine derivative, is the most potent inhibitor of the reuptake of 
serotonin (5-hydroxytryptamine, 5-HT) of all the currently available 
antidepressants including the class of SSRIs. It is a very weak inhibitor of 
norepinephrine (NE) uptake but it is still more potent at this site than the 
other SSRIs. The selectivity of paroxetine, i.e., the ratio of inhibition of 
uptake of norepinephrine to serotonin (NE/5-HT) is amongst the highest of the 
SSRIs. Paroxetine has little affinity for catecholaminergic, dopaminergic or 
histaminergic systems and by comparison with tricyclic antidepressants (TCAs) 
has, therefore, a reduced propensity to cause central and autonomic side 
effects. Paroxetine exhibits some affinity for the muscarinic cholinergic 
receptor but much less than the TCAs. In addition, the adaptive changes of 
somatodendritic (5-HT(1A)) and terminal (5-HT(1B/1D)) autoreceptors observed 
with paroxetine are different to those observed with TCAs; it also inhibits 
nitric oxide synthase. It is both a substrate and an inhibitor of cytochrome 
isoenzyme P450 2D6. Paroxetine is well absorbed orally and undergoes extensive 
first pass metabolism that is partially saturable. Its metabolites are 
pharmacologically inactive in vivo. Steady state levels are achieved after 4-14 
days and an elimination half-life of 21 h is consistent with once-daily dosing. 
There is wide inter-individual variation in the pharmacokinetics of paroxetine 
in adults as well as in the young and the elderly with higher plasma 
concentrations and slower elimination noted in the latter. Elimination is also 
reduced in severe renal and hepatic impairment. Serious adverse events are, 
however, extremely rare even in overdose. In summary, paroxetine is well 
tolerated and effective in the treatment of both depressive and anxiety 
disorders across the age range.