Clinical effects of serotonin reuptake inhibitors in the treatment of depressive illness.

The serotonergic hypothesis of depression has stimulated the development of a range of chemically diverse compounds that have an exclusive effect on this neurotransmitter for potential use as antidepressant drugs. The group of serotonin reuptake inhibitors are at various stages of clinical development. The authors review the efficacy, side effect profiles, and toxicity of zimelidine, fluvoxamine, and citalopram in detail and ifoxetine, fluoxetine, indalpine, paroxetine, and sertraline in brief. Evidence suggests that, compared with tricyclic antidepressants, these drugs may cause fewer anticholinergic effects and lower cardiotoxicity in the treatment of major depressive disorders. These advantages need to be weighed against an emerging pattern of gastrointestinal complaints, insomnia, and akathisia. The place of serotonin reuptake inhibitors in therapy can be fully evaluated only after further studies, particularly those involving long-term use. The adverse experience associated with zimelidine suggests that caution and vigilance should be exercised in future studies of agents in this class. These drugs will undoubtedly provide important insights into depressive illness and some anxiety disorders and may fulfill their initial promise.