Antidepressants: Update on Benefits and Risks

Since the initial discovery of the first antidepressants in the 1950s, at least two generations of these medications have come to market. Following a brief historical introduction, this paper reviews the first- and second-generation (FGA and SGA) antidepressant medications and their class-related and individual side effect profiles. Class-related adverse reactions include dietary interactions of monoamine oxidase inhibitors (MAOIs) with tyramine, cardiovascular toxicities of the FGAs, and the behavioral syndrome and sexual dysfunction produced by selective serotonergic reuptake inhibitors (SSRIs). Adverse effects common to the different classes include discontinuation syndromes, possible cognitive impairment, suicidality, and a variety of cardiovascular, gastrointestinal and motoric disturbances. Recent reports of side effects elicited by specific agents are noted. Current concerns raised by antidepressant use in pregnancy are discussed. Recent criticisms of the effectiveness claims of antidepressants are summarized. These include the significant placebo contribution to antidepressant outcomes and the ongoing debate about the long-term usefulness of psychotropic medications in general. Most relevant to antidepressants is the recently proposed phenomenon of “tardive dysphoria” that may occur after prolonged antidepressant use and promote resistance to further treatment.