The Food and Drug Administration has approved the marketing of the selective serotonin reuptake inhibitor paroxetine hydrochloride (Paxil / SmithKline Beecham) for the treatment of depression. It is the third of a new group of antidepressants that are supplanting older drugs. The other two are fluoxetine (Prozac/Lilly) and sertraline (Zoloft/Pfizer). Paroxetine hydrochloride has a chemical structure unrelated to other selective serotonin uptake inhibitors.

Controlled trials with outpatients have demonstrated the efficacy of paroxetine (Paxil) for DSM-III major depressive disorders. The benefits of therapy become apparent within about two weeks. (Claghorn J. Int Clin Psychopharmacol 1992; 6(Suppl 4): 25-30.) Paroxetine (Paxil) has the particular advantage of improving sleep without interfering with psychomotor function and is relatively safe in overdose situations. (Montgomery SA. Int Clin Psychopharmacol 1992; 6 (Suppl 4): 91-100.) Patients’ cognitive functions have been found to improve from the start of therapy. (Hindmarch I. Int Clin Psychopharmacol 1992; 6(Suppl 4): 65-67.) Paroxetine’s antidepressive effect has been maintained for up to one year; however, long-term use requires periodic re-evaluation. Paxil is available in 20- or 30-mg tablets. The manufacturer recommends an initial dose of 20 mg/day; this may be titrated upward in increments of 10 mg/day, at intervals of at least one week, to a maximum of 50 mg/day. Paroxetine (Paxil) concentrations reach a steady state in about 10 days. Under clinical conditions, plasma concentrations of paroxetine are less than 400 ng/mL. Extensive metabolism after oral administration yields primarily the polar and conjugated products of oxidation and methylation. Sixty-four percent of a dose is excreted in the urine and 36% in the feces.

In world-wide clinical trials, 21% of patients withdrew from paroxetine (Paxil) treatment because of adverse effects, which included somnolence and insomnia (depending on the timing of the dose), tremor, anxiety, nausea, vomiting, diarrhea, asthenia, ejaculatory disturbance, and other male genital disorders. Paroxetine (Paxil) should not be administered within two weeks of monoamine oxidase inhibitors. Pregnant and nursing women should take paroxetine only if clearly needed and then only with caution. The safety and efficacy of use by children has not been determined.

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