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J Clin Psychiatry. 1998;59 Suppl 4:5-14.

Basic psychopharmacology of antidepressants, part 1: Antidepressants have seven distinct mechanisms of action.

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  • Clinical Neuroscience Research Center and the Department of Psychiatry, University of California, San Diego 92122, USA.


Distinct pharmacologic mechanisms allow the antidepressants to be separated into seven different classes. These basic pharmacologic concepts can explain not only the therapeutic actions, but also the side effects of the wide range of antidepressants currently available. The two classical mechanisms are those of tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). The most widely prescribed agents 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/reuptake inhibition (nefazodone); and alpha2 antagonism plus serotonin-2 and -3 antagonism (mirtazapine). The selective norepinephrine and dopamine reuptake inhibitor bupropion defines a novel class of antidepressant that has no direct actions on the serotonin system.

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