Paroxetine is a novel phenylpiperidine compound that is a potent and selective serotonin reuptake inhibitor. It has little affinity for alpha-adrenergic, dopamine, histamine, and cholinergic receptors. The pharmacokinetic properties of paroxetine are well suited to clinical use. Its bioavailability is not affected by food or antacids; its mean half-life of about 24 hours is consistent with once-a-day dosing; also, it has no pharmacologically active metabolites. In clinical studies involving over 6,700 patients worldwide, the efficacy of paroxetine has been shown consistently to be superior to placebo and comparable to tricyclic antidepressant agents in the treatment of depression. During these trials, paroxetine was used in a broad range of depressed patients, including the moderately to severely depressed, the elderly, and patients whose depressions were accompanied by symptoms of anxiety. In addition, it has been shown to be effective for the prevention of depressive relapse during long-term treatment. Side effects associated with paroxetine tend to be relatively mild, transient, and easily managed. As with other selective serotonin reuptake inhibitors, the most common side effect associated with paroxetine treatment is nausea, although this effect rarely leads to dose reduction or drug discontinuation. Paroxetine should not be coadministered with monoamine oxidase inhibitors or L-tryptophan. Animal data and limited clinical experience suggest that paroxetine is considerably safer in overdose than are tricyclic antidepressant drugs.