Sertraline was approved by the FDA in December 1991 for the treatment of major depression. Sertraline does not affect norepinephrine as do many tricyclic antidepressants. The precise action of SSRIs is not fully understood, but it is believed that sertraline and related agents inhibit reuptake of serotonin at the neuronal membrane. SSRIs have less sedative, anticholinergic, and cardiovascular effects than do the tricyclic antidepressant drugs due to dramatically decreased binding to histamine, acetylcholine, and norepinephrine receptors. Monoamine oxidase is not inhibited by any of the SSRIs.
Anticholinergic activity is virtually absent.
Metabolism appears to be hepatic, with first-pass metabolism and minimal renal excretion of unchanged drug. Steady-state levels are achieved after 1 week of normal daily dosage. The elimination half-life is approximately 26 hours. Dosage adjustments are recommended for patients with mild, stable cirrhosis due to the half-life increase from 22 to 52 hours following a single dose. Seizures have not been reported during therapy with sertraline, despite overdoses as high as 6,000 mg.