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Reviews and Overviews   |    
Antidepressant-Induced Liver Injury: A Review for Clinicians
Cosmin Sebastian Voican, M.D., Ph.D.; Emmanuelle Corruble, M.D., Ph.D.; Sylvie Naveau, M.D., Ph.D.; Gabriel Perlemuter, M.D., Ph.D.
Am J Psychiatry 2014;171:404-415. doi:10.1176/appi.ajp.2013.13050709
View Author and Article Information

The first two authors contributed equally to this work.

Dr. Corruble has received consulting fees from AstraZeneca, Bristol-Myers Squibb, Eisai, Lundbeck, Otsuka, Sanofi, and Servier. Dr. Naveau has received travel funds from Janssen, Gilead, and Bristol-Myers Squibb. Dr. Perlemuter has received travel funds from Janssen, Gilead, and Roche, consulting fees from Bayer, Biocodex, Physiogenex, and Servier, and royalties from Elsevier-Masson. Dr. Voican reports no financial relationships with commercial interests.

From the Hepatogastroenterology Service, AP-HP (Public Assistance-Hospitals of Paris) Hôpital Antoine Béclère, DHU (university hospital department) Hépatinov, Clamart, France; INSERM (National Institute of Health and Medical Research) U996, IPSIT (Institut Paris-Sud d’Innovation Thérapeutique), Clamart; INSERM U669, CHU (university hospital center) de Bicêtre, Kremlin-Bicêtre, France; the Psychiatric Service, AP-HP Hôpital Bicêtre, Kremlin-Bicêtre; and the Faculty of Medicine, Université Paris-Sud, Kremlin-Bicêtre.

Address correspondence to Dr. Perlemuter (gabriel.perlemuter@abc.aphp.fr).

Copyright © 2014 by the American Psychiatric Association

Received May 31, 2013; Revised October 17, 2013; Accepted October 25, 2013.

Abstract

Objective  Antidepressant drugs can cause drug-induced liver injury (DILI). The authors review clinical data relevant to antidepressant-induced liver injury and provide recommendations for clinical practice.

Method  A PubMed search was conducted for publications from 1965 onward related to antidepressant-induced liver injury. The search terms were “liver injury,” “liver failure,” “DILI,” “hepatitis,” “hepatotoxicity,” “cholestasis,” and “aminotransferase,” cross-referenced with “antidepressant.”

Results  Although data on antidepressant-induced liver injury are scarce, 0.5%−3% of patients treated with antidepressants may develop asymptomatic mild elevation of serum aminotransferase levels. All antidepressants can induce hepatotoxicity, especially in elderly patients and those with polypharmacy. Liver damage is in most cases idiosyncratic and unpredictable, and it is generally unrelated to drug dosage. The interval between treatment initiation and onset of liver injury is generally between several days and 6 months. Life-threatening antidepressant-induced liver injury has been described involving fulminant liver failure or death. The underlying lesions are often of the hepatocellular type and less frequently of the cholestatic and mixed types. The antidepressants associated with greater risks of hepatotoxicity are iproniazid, nefazodone, phenelzine, imipramine, amitriptyline, duloxetine, bupropion, trazodone, tianeptine, and agomelatine. The antidepressants that seem to have the least potential for hepatotoxicity are citalopram, escitalopram, paroxetine, and fluvoxamine. Cross-toxicity has been described, mainly for tricyclic and tetracyclic antidepressants.

Conclusions  Although an infrequent event, DILI from antidepressant drugs may be irreversible, and clinicians should be aware of it. Aminotransferase surveillance is the most useful tool for detecting DILI, and prompt discontinuation of the drug responsible is essential. The results of antidepressant liver toxicity in all phases of clinical trials should be available and published. Further research is needed before any new and rigorously founded recommendations can be made.

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TABLE 1.Potential Antidepressant Drug-Drug Interactionsa
Table Footer Note

a CYP450=cytochrome P450.

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TABLE 2.Hepatotoxicity of the Main Antidepressant Drugsa
Table Footer Note

a DILI=drug-induced liver injury; FDA=U.S. Food and Drug Administration; LFT=liver function tests; LT=liver transplantation; recovery=full recovery; ULN=upper limit of normal; VBDS=vanishing bile duct syndrome.

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