Selective serotonin reuptake inhibitors: pharmacologic profiles and potential therapeutic distinctions

OBJECTIVE: To review the respective pharmacologic profiles of the selective serotonin reuptake inhibitors (SSRIs), with particular emphasis placed on clinically relevant distinctions. DATA SOURCES: A MEDLINE search was conducted to identify English language literature published within the last five years on the four SSRIs (fluoxetine, sertraline, paroxetine, fluvoxamine). Previous review articles were scrutinized for additional citations, and manufacturers provided a contemporary bibliography of more recent material. STUDY SELECTION/DATA EXTRACTION: Studies were selected for specific citation on the basis of comparative research merit and the contribution of this original literature to the pharmacologic profile(s) described. DATA SYNTHESIS: All SSRIs appear to be more efficacious than placebo for the acute treatment of major depressive disorder (MDD). Short-term (six-week) efficacy was comparable with that of tricyclic antidepressants for the amelioration of MDD regarded as moderate in severity. Further comparative trials are clearly indicated to demonstrate the therapeutic benefits of SSRIs in specific populations (e.g., geriatric, severely ill) and to demonstrate sustained benefit with long-term prophylaxis. Other potential indications for SSRIs include obsessive-compulsive disorder, panic disorder, bulimia, and chronic pain syndromes. Pharmacokinetic profiles of the four SSRIs reveal similar parametric values, and most quantitative differences are of limited clinical significance. Adverse effects are common but ordinarily mild and transient, primarily restricted to the gastrointestinal tract and central nervous system. Important differences in the prevalence or severity of these adverse effects await the accumulation of further clinical experience and the completion of additional comparative trials. Similarly, the relative propensity of SSRIs to inhibit the metabolism of other medications is currently under investigation. CONCLUSIONS: The four SSRIs studied appear to be more similar than they are different. Slowly, important distinctions are beginning to emerge with regard to adverse effect profiles and potential drug interactions. Given that the costs of these respective medications are comparable, such differences may ultimately serve to establish the preferential selection of individual agents in specific clinical situations.