Antidepressants

Abstract

Antidepressants, as the name implies, are drugs used to treat depression and are widely used therapeutic agents. They are also some of the most frequently encountered drugs in forensic and clinical toxicology. Antidepressants are often characterized based on when they were developed: first-generation antidepressants, second-generation antidepressants, selective serotonin reuptake inhibitors, and third-generation antidepressants. All of the antidepressants are well absorbed and reach peak serum concentrations within 2–12 h, but there is considerable first-pass metabolism with most of these drugs. They are rather lipophilic and have large volumes of distribution. In general, these drugs are extensively metabolized by cytochrome P450 isoenzymes to demethylated and hydroxylated metabolites, many of which are active. Analysis of these compounds in biological specimens requires specimen preparation either by liquid–liquid extraction or solid-phase extraction. Chromatographic separation by gas or liquid chromatography allows simultaneous analysis of most antidepressants and their major metabolites. First-generation antidepressants are associated with greater toxicity, primarily due to anticholinergic effects, central nervous system effects, and cardiovascular effects. Interpretation of postmortem concentrations of these drugs is complicated by postmortem redistribution; therefore, the use of therapeutic ranges established for antemortem serum is inappropriate.