Paroxetine: a review of its pharmacology, pharmacokinetics and utility in the treatment of a variety of psychiatric disorders

Abstract

Paroxetine is a selective serotonin re-uptake inhibitor (SSRI). In vitro studies show that it is able to produce a concentration-dependent competitive inhibition of serotonin uptake into brain synaptosomes. This effect can also be demonstrated following in vivo administration of the compound to animals. Paroxetine is almost completely absorbed following oral administration. However, the drug undergoes extensive first pass metabolism. As a result, less than 50% of a single dose of paroxetine reaches the general circulation. Paroxetine is primarily metabolised by the cytochrome P4502D6 isoenzyme. The compound has also been shown to inhibit the activity of this enzyme. As a result, plasma levels of compounds metabolised by the cytochrome P4502D6 isoenzyme can be increased in patients given paroxetine. Paroxetine has been extensively evaluated in clinical studies in depressed patients. The compound shows efficacy superior to placebo, and similar to that obtained with standard tricyclic or tetracyclic agents. Paroxetine also appears to be as efficacious as other SSRIs. The efficacy seen in short-term studies with paroxetine in the treatment of depression is maintained when the drug is given chronically. More recently, paroxetine has been shown to be efficacious in the treatment of panic disorder, obsessive-compulsive disorder, and social anxiety disorder. Nausea, headache and somnolence are the most common adverse events reported by patients given paroxetine. As with other selective serotonin re-uptake inhibitors, a significant percentage of men under therapy with paroxetine report abnormal ejaculation. Paroxetine is well-tolerated by elderly patients, and appears to be associated with few serious adverse events.