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Basic Psychopharmacology of Antidepressants, Part 1: Antidepressants Have Seven Distinct Mechanisms of Action

Stephen M. Stahl, M.D., Ph.D.

Published: February 1, 1998

Article Abstract

Distinct pharmacologic mechanisms allow the antidepressants to be separated into seven differentclasses. These basic pharmacologic concepts can explain not only the therapeutic actions, but also the sideeffects of the wide range of antidepressants currently available. The two classical mechanisms are those oftricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). The most widely prescribedagents are the serotonin selective reuptake inhibitors (SSRIs). Three other classes of antidepressants,like the SSRIs, increase serotonergic neurotransmission, but they also have additional actions,namely dual serotonin and norepinephrine reuptake inhibition (venlafaxine); serotonin-2 antagonism/reuptakeinhibition (nefazodone); and α2 antagonism plus serotonin-2 and -3 antagonism (mirtazapine). Theselective norepinephrine and dopamine reuptake inhibitor bupropion defines a novel class of antidepressantthat has no direct actions on the serotonin system.

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Volume: 59

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