The development of paroxetine hydrochloride began in the late 1970s. An abundance of data have been accumulated from clinical investigations demonstrating the efficacy of paroxetine in the treatment of major depression and anxiety disorders. The published literature contains a substantial amount of supportive data documenting the safety, tolerability, and pharmacokinetic and pharmacodynamic properties of paroxetine. The role of paroxetine in clinically significant drug-drug interactions, especially involving metabolic inhibitory effects on the substrates of cytochrome p450 2D6, has long been suspected, but only isolated cases provide any evidence. Published data for widespread patient morbidity from drug interactions with paroxetine are almost nonexistent. Considerations of the pharmacokinetic properties of paroxetine support a rationale for the development of new dosage forms that maintain the efficacy yet improve the tolerability profile of the selective serotonin reuptake inhibitors. Paroxetine controlled-release is an enteric-coated formulation with release features that may enhance clinical outcome by modifying absorption-related pharmacokinetics, improving tolerability, and maintaining therapeutic benefits