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.
Keywords: Antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, side effects, first generation antidepressants, second generation antidepressants, Tyramine, obsessive-compulsive disorder (OCD), Insomnia, tamoxifen, citalopram, Venlafaxine, serotoninnorepinephrine reuptake inhibitor, mirtazapine, fluoxetine.
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