Concise Review Hepatotoxicity of Psychotropic Drugs

Psychotropic drugs with hepatotoxic potential can be classified based on their intended use: 1) antipsychoticsneuroleptics including phenothiazines, butyrophenones, and clozapine; 2) antidepressants including tricyclics, serotonin reuptake inhibitors, and monoamine oxidase (MAO) inhibitors; 3) anti-anxiety drugs such as benzodiazepines; 4) acetylcholinesterase inhibitors such as tacrine; and 5) drugs of abuse including cocaine and ecstasy. Antiseizure drugs represent another class of central nervous system (CNS) drugs, but will not be considered here. Hepatotoxicity of psychotropic drugs occurs in a variable but small proportion of users and therefore can be considered unpredictable or idiosyncratic. When these uncommon adverse events occur in association with rash, eosinophilia, and/or a rapid positive rechallenge, sufficient circumstantial evidence exists to ascribe the mechanism to an immune-mediated hypersensitivity reaction. Acute overt reactions to drugs tend to have clinicopathological features of hepatitis (destruction of liver parenchyma), cholestasis (impaired bile secretion), or both. The hepatotoxic reactions to psychotropic drugs conform to these general patterns. Furthermore, as with most hepatotoxic drugs, individual psychotropic drugs have a characteristic pattern of injury, i.e., cholestatic for some (e.g., chlorpromazine, haloperidol, tricyclics), hepatitic for others (e.g., hydrazines, MAO inhibitors, cocaine, ecstasy) (see Table 1).