To the Editor: Selective serotonin reuptake inhibitors (SSRIs) are currently the mainstay therapy for depression because of their favorable side effect profile and safety in overdose. Only isolated cases of liver injury in association with fluoxetine, paroxetine, sertraline, and fluvoxamine have previously been reported (1). To our knowledge, the following case is the first reported instance of significant liver damage related to the SSRI citalopram.

A causal association between citalopram and hepatocellular injury can confidently be established because there was a temporal relationship between the administration of the drug and the onset of hepatic abnormalities, there was a rapid recovery after stopping the drug, and alternative explanations were ruled out. Of interest, citalopram hepatotoxicity was associated in this patient with nonspecific symptoms. In patients who do not develop jaundice, hepatotoxicity may have an unspecific clinical presentation. This could lead clinicians to attribute these clinical manifestations to worsening depression and to a discontinuation of, or a change in, medication, with subsequent improvement in the patient’s condition that may hinder the diagnosis of hepatotoxicity and explain the scarcity of reports, despite its continuous use.

In experimental animals, citalopram was found to induce a fatty liver. A metabolite generated through its first-pass metabolism has been suggested to be responsible for the liver toxicity (2). Taken together, these findings and the absence of hypersensitivity features suggest that a metabolically mediated mechanism is feasible.

Cross-hepatotoxicity has been reported with tricyclic antidepressants (3). Citalopram possesses a chemical structure unrelated to that of other antidepressants, which is consistent with the lack of cross-reactivity observed in this patient.