Mechanisms of action and clinical characteristics of three atypical antidepressants: venlafaxine, nefazodone, bupropion

J Affect Disord. 1998 Dec;51(3):237-54. doi: 10.1016/s0165-0327(98)00222-5.


Tricyclic antidepressants have multiple sites of pharmacological actions which are responsible for their tolerability and toxicological problems as well as their efficacy. That fact has prompted the search for antidepressants with fewer sites of action. That search resulted in the serotonin selective reuptake inhibitors (SSRIs), with presumably only one site of action. Although the SSRIs are safer and better tolerated than the TCAs, a significant percentage of patients do not benefit from SSRIs. A group of "atypical antidepressants" including bupropion, nefazodone, and venlafaxine are known to have multiple sites of antidepressant action but do not interact at sites associated with side effects or tolerance. Thus this group of antidepressants present an important alternative to the SSRIs in the pharmacological therapy of depression. The basic pharmacological properties of bupropion, nefazodone, and venlafaxine are presented along with clinical profiles and the role of these three antidepressants in the pharmacotherapy of depression is discussed.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents, Second-Generation / adverse effects
  • Antidepressive Agents, Second-Generation / pharmacology*
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Bupropion / adverse effects
  • Bupropion / pharmacology*
  • Bupropion / therapeutic use*
  • Cyclohexanols / adverse effects
  • Cyclohexanols / pharmacology*
  • Cyclohexanols / therapeutic use*
  • Depressive Disorder / drug therapy*
  • Humans
  • Piperazines
  • Triazoles / adverse effects
  • Triazoles / pharmacology*
  • Triazoles / therapeutic use*
  • Venlafaxine Hydrochloride


  • Antidepressive Agents, Second-Generation
  • Cyclohexanols
  • Piperazines
  • Triazoles
  • Bupropion
  • nefazodone
  • Venlafaxine Hydrochloride