Paroxetine. An update of its pharmacology and therapeutic use in depression and a review of its use in other disorders.

Abstract

Paroxetine is a potent and selective inhibitor of the neuronal reuptake of serotonin (5-hydroxytryptamine; 5-HT), which was previously reviewed as an antidepressant in Drugs in 1991. Since then, more comparative trials with other antidepressants have become available, and its use in the elderly and as long term maintenance therapy has been investigated. Paroxetine has also been studied in several other disorders with a presumed serotonergic component, primarily obsessive compulsive disorder (OCD) and panic disorder. In short term clinical trials in patients with depression, paroxetine produced clinical improvements that were significantly greater than those with placebo and similar to those achieved with other agents including tricyclic antidepressants (TCAs), maprotiline, nefazodone and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, fluvoxamine and sertraline. Long term data suggest that paroxetine is effective in preventing relapse or recurrence of depression in patients treated for up to 1 year. In the elderly, the overall efficacy of paroxetine was at least as good as that of comparator agents. In short term clinical trials involving patients with OCD or panic disorder, paroxetine was significantly more effective than placebo and of similar efficacy to clomipramine. Limited long term data show that paroxetine is effective in maintaining a therapeutic response over periods of 1 year (OCD) and up to 6 months (panic disorder). Preliminary data suggest that paroxetine has potential in the treatment of social phobia, premenstrual dysphoric disorder and chronic headache. Like the other SSRIs, paroxetine is better tolerated than the TCAs, causing few anticholinergic adverse effects. The most commonly reported adverse event associated with paroxetine treatment is nausea, although this is generally mild and subsides with continued use. Fewer withdrawals from treatment due to adverse effects occurred with paroxetine treatment than with TCAs. The adverse events profile of paroxetine appears to be broadly similar to that of other SSRIs, although data from comparative trials are limited. Serious adverse effects associated with paroxetine are very rare. In conclusion, paroxetine is effective and well tolerated, and suitable as first-line therapy for depression. It also appears to be a useful alternative to other available agents for the treatment of patients with OCD or panic disorder.