Drug-Induced Liver Injury (DILI) in Patients with Depression Treated with Antidepressants: A Retrospective Multicenter Study

Ueberberg, Bianca; Frommberger, Ulrich; Messer, Thomas; Zwanzger, Peter; Kuhn, Jens; Anghelescu, Ion; Ackermann, Kathrin; Assion, Hans‐Jörg

doi:10.1055/a-1071-8028

Cited by 5 publications

(3 citation statements)

References 25 publications

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“… 104 A multicenter retrospective analysis of 329 patients undergoing antidepressant therapy at 6 medical centers in Germany revealed that 5.1% of patients experienced increased serum transaminase levels during treatment, with 3 cases (0.9%) meeting the criteria for definite drug-induced liver injury (ALT level >5 times the upper limit of normal); furthermore, the study indicated that among the cases with a transaminase increase, the most commonly implicated antidepressants were mirtazapine, agomelatine, trazodone, and venlafaxine. 105 …”

Section: Common Liver Injury–causing Drugs Linked To Gut Microbiotamentioning

confidence: 99%

Interplay Between Drug-Induced Liver Injury and Gut Microbiota: A Comprehensive Overview

Li,

Hou,

Zhang

et al. 2024

Cellular and Molecular Gastroenterology and Hepatology

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Section: Common Liver Injury–causing Drugs Linked To Gut Microbiotamentioning

confidence: 99%

Interplay Between Drug-Induced Liver Injury and Gut Microbiota: A Comprehensive Overview

Li,

Hou,

Zhang

et al. 2024

Cellular and Molecular Gastroenterology and Hepatology

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“…Therefore, understanding DILI associated with antidepressants and safety monitoring is essential to optimize antidepressant treatment outcomes. Previous reports were based on retrospective multicenter studies, 12 , 13 case reports, 14 – 17 or case series. 18 To the best of our knowledge, there has been no comprehensive evaluation of the association between individual antidepressant drugs and DILI.…”

Section: Introductionmentioning

confidence: 99%

Adverse event profiles of drug-induced liver injury caused by antidepressant drugs: a disproportionality analysis

Jiang,

Wei,

Zhu

et al. 2024

Therapeutic Advances in Drug Safety

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Background: Antidepressants are widely used to manage depression and other psychiatric diseases. A previous study revealed that hepatotoxicity was the main adverse event related to antidepressants. Therefore, drug-induced liver injury (DILI) caused by antidepressants deserves more attention. Objectives: To investigate DILI adverse events reported due to antidepressant use in the United States Food and Drug Administration Adverse Events Reporting System (FAERS) database. Research design: A disproportionality analysis of spontaneously reported adverse events was conducted to assess the association between antidepressant drugs and DILI. Methods: FAERS data from 1 January 2004 to 31 December 2021 were compiled and analyzed using the reporting odds ratio (ROR) and information component (IC). Results: As per the FAERS database, of the 324,588 cases that were administered antidepressants, 10,355 were identified as cases with DILI. Among the identified 42 antidepressants, nefazodone ( n = 47, ROR = 7.79, IC = 2.91), fluvoxamine ( n = 29, ROR = 4.69, IC = 2.20), and clomipramine ( n = 24, ROR = 3.97, IC = 1.96) had the highest ROR for cholestatic injury; mianserin ( n = 3, ROR = 21.46, IC = 3.99), nefazodone ( n = 264, ROR = 18.67, IC = 3.84), and maprotiline ( n = 15, ROR = 5.65, IC = 2.39) for hepatocellular injury; and nefazodone ( n = 187, ROR = 12.71, IC = 0.48), clomipramine ( n = 35, ROR = 2.07, IC = 0.26), and mirtazapine ( n = 483, ROR = 1.96, IC = 0.94) for severe drug-related hepatic disorders. Only nefazodone elicited hepatic failure signals ( n = 48, ROR = 18.64, IC = 4.16). There are limited reports on the adverse reactions of relatively new antidepressant drugs, such as milnacipran, viloxazine, esketamine, and tianeptine, and those not approved by the Food and Drugs Administration, such as reboxetine and agomelatine. Conclusion: A significant association was observed between DILI and nefazodone. Duloxetine and clomipramine were associated with three DILI categories, except hepatic failure. The disproportionality analysis cannot conclude on a definite causal link between antidepressants and DILI. Additional research is required to assess new-generation antidepressants for their propensity to cause DILI.

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“…When depression and NAFLD are associated, there is an increased likelihood of complications and mortality [ 15 ]. With depression increasing, by up to 50%, the risk of NAFLD [ 16 ] and the antidepressant (AD) treatment often inducing liver injury (DILI) [ 17 , 18 , 19 , 20 ], the need for monitoring the liver function in depressed patients becomes apparent [ 21 , 22 ]. While an elevated value of alanine aminotransferase (ALT) serves as a reliable indicator of hepatocellular damage resulting from NAFLD, especially in males [ 23 ], and the hepatic toxicity induced by ADs [ 24 ], gamma-glutamyl transferase (GGT) levels typically rise in response to excessive alcohol consumption, making it a valuable biomarker for assessing alcohol-related liver damage and monitoring alcohol intake in clinical settings [ 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Moderate Alcohol Consumption Increases the Risk of Clinical Relapse in Male Depressed Patients Treated with Serotonin-Norepinephrine Reuptake Inhibitors

Mușat,

Militaru,

Gheorman

et al. 2024

Diagnostics

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Background: While depression can be associated with multiple comorbidities, the association between depression and liver injury significantly increases the mortality risk. The aim of this study was to evaluate if moderate alcohol intake affects the rate of clinical relapses in patients treated with antidepressants as monotherapy. Methods: We assessed, over a period of 30 months, the clinical records of 254 patients with depressive disorder, of either gender, without additional pathologies, receiving monotherapy treatment with antidepressants. Thirty-three patients with alcohol abuse, alcoholism or significant cognitive impairment were excluded. The medical and psychiatric history, medication and liver enzyme values were collected and analyzed. Results: Out of the 221 patients who met the inclusion criteria, 78 experienced relapses of depression. The rate of relapse did not correlate with the levels of liver enzymes. Alcohol consumption, as objectified based on GGT levels and the AST/ALT ratio, suggested that men had higher alcohol intake compared to women. Patients treated with serotonin-norepinephrine reuptake inhibitors (SNRIs) with elevated AST levels were approximately 9 times more likely to relapse, while the ones with elevated GGT had a 5.34 times higher risk. While GGT levels remained a marker for relapse in men with elevated GGT, ALT and not AST proved to be a better risk indicator for relapses in male patients. Conclusion: The use of SNRIs in depressed male patients with moderate alcohol intake should be carefully considered, as they might be susceptible to higher risks of relapse compared to alternative antidepressant therapies.

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Drug-Induced Liver Injury (DILI) in Patients with Depression Treated with Antidepressants: A Retrospective Multicenter Study

Cited by 5 publications

References 25 publications

Interplay Between Drug-Induced Liver Injury and Gut Microbiota: A Comprehensive Overview

Interplay Between Drug-Induced Liver Injury and Gut Microbiota: A Comprehensive Overview

Adverse event profiles of drug-induced liver injury caused by antidepressant drugs: a disproportionality analysis

Moderate Alcohol Consumption Increases the Risk of Clinical Relapse in Male Depressed Patients Treated with Serotonin-Norepinephrine Reuptake Inhibitors

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