Paroxetine: a selective serotonin reuptake inhibiting antidepressant

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical investigations, adverse effects, and dosing strategies of paroxetine as a treatment of major depression. DATA SOURCES: Specific paroxetine information was selected from a MEDLINE search using paroxetine as the search term. Other sources included manual searches of pertinent journal article references, meeting abstracts, and the manufacturer. STUDY SELECTION: Clinical investigations with a blind, controlled (placebo and/or active), randomized design were selected. With the exception of treatment-resistant depression, no short-term, open investigations were selected. DATA EXTRACTION: Clinical investigations were evaluated for design, sample size, diagnosis, duration, definition of response, and outcome. Data from all investigations were selected by one author and reviewed by both authors. DATA SYNTHESIS: Paroxetine is a selective serotonin reuptake inhibitor (SSRI) recently approved for the treatment of major depression. It is a potent and selective inhibitor of serotonin reuptake and has weak or no activity on the other monoamines; it is also weakly anticholinergic. Although pharmacokinetic parameters are variable, paroxetine is generally well absorbed, highly protein bound, hepatically cleared, and has no active metabolites. Clinical investigations support paroxetine's effectiveness as an antidepressant in an outpatient population with moderately severe depression. Its effectiveness is superior to that of placebo and is comparable to that of active controls. The majority of investigations have been six weeks in duration. Additional data are required to support paroxetine's promise for longer treatment periods (i.e., > or = 1 y), in the elderly, and for treatment-resistant depression. Adverse effects appear to be similar to those caused by the other SSRIs; some of the most common are nausea, diarrhea, insomnia, dry mouth, and nervousness. Significant drug interactions may occur with the monoamine oxidase inhibitors, phenobarbital, and phenytoin. CONCLUSIONS: Paroxetine is safe and effective for treatment of outpatients with moderately severe depression. Further clinical data and experience are necessary to determine this agent's place in the long-term treatment of major depression.

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