Antidepressant-induced hepatotoxicity

Expert Opin Drug Saf. 2003 May;2(3):249-62. doi: 10.1517/14740338.2.3.249.


Depression is a chronic, severe and increasingly prevalent illness associated with substantial morbidity, mortality and healthcare costs. Antidepressant drugs, the cornerstone of depression treatment, are not devoid of adverse effects, including hepatotoxicity. To review the risk of liver toxicity related to major antidepressants, the authors have followed structural criteria focusing on the underlying mechanism presumably involved and the role of particular chemical structures. The clinicopathological expression goes from transient increases in liver enzymes to fulminant liver failure. Classical antidepressants such as monoamine oxidase inhibitors (MAOIs) or tricyclic antidepressants (TCAs) seem to have the highest potential to induce liver damage compared with the newer drugs such as selective serotonin re-uptake inhibitors (SSRIs). The potential for severe hepatotoxicity associated with nefazodone is stressed. Guidelines for therapy and prevention of antidepressant-induced hepatotoxicity are also discussed.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / chemistry
  • Antidepressive Agents / therapeutic use
  • Antidepressive Agents, Second-Generation / adverse effects
  • Antidepressive Agents, Second-Generation / chemistry
  • Antidepressive Agents, Second-Generation / therapeutic use
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / chemistry
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Chemical and Drug Induced Liver Injury / therapy
  • Chemical and Drug Induced Liver Injury, Chronic / etiology
  • Chemical and Drug Induced Liver Injury, Chronic / prevention & control
  • Chemical and Drug Induced Liver Injury, Chronic / therapy
  • Depressive Disorder / drug therapy
  • Depressive Disorder / etiology
  • Humans
  • Monoamine Oxidase Inhibitors / adverse effects
  • Monoamine Oxidase Inhibitors / chemistry
  • Monoamine Oxidase Inhibitors / therapeutic use
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / chemistry
  • Selective Serotonin Reuptake Inhibitors / therapeutic use


  • Antidepressive Agents
  • Antidepressive Agents, Second-Generation
  • Antidepressive Agents, Tricyclic
  • Monoamine Oxidase Inhibitors
  • Serotonin Uptake Inhibitors