The Selective Serotonin Reuptake Inhibitor Sertraline: Its Profile and Use in Psychiatric Disorders

The naphthylamine derivative sertraline is a potent and selective inhibitor of serotonin reuptake into presynaptic terminals. Sertraline has a linear pharmacokinetic profile and a half-life of about 26 h. Its major metabolite, desmethylsertraline does not appear to inhibit serotonin reuptake. Sertraline mildly inhibits the CYP2D6 isoform of the cytochrome P450 system but has little effect on CYP1A2, CYP3A3/4, CYP2C9, or CYP2C19. It is, however, highly protein bound and may alter blood levels of other highly protein bound agents. Sertraline is a widely used serotonin reuptake inhibitor that has been shown to have both antidepressant and antianxiety effects. Many clinical trials have demonstrated its efficacy in depression compared with both placebo and other antidepressant drugs. Its efficacy has also been demonstrated in randomized, controlled trials of patients with obsessive-compulsive disorder, panic disorder, social phobia, and premenstrual dysphoric disorder. In short-term, open-label studies it has appeared efficacious and tolerable in children and adolescents and in the elderly, and data are positive for its use in pregnant or lactating women. Typical side effects include gastrointestinal and central nervous system effects as well as treatment-emergent sexual dysfunction; withdrawal reactions may be associated with abrupt discontinuation of the agent. The safety profile of sertraline in overdose is very favorable. Sertraline's efficacy for both mood and anxiety disorders, relatively weak effect on the cytochrome P450 system, and tolerability profile and safety in overdose are factors that contribute to make it a first-line agent for treatment in both primary and tertiary care settings.