Hepatotoxicity associated with agomelatine and other antidepressants: Disproportionality analysis using pooled pharmacovigilance data from the Uppsala Monitoring Centre
Abstract
Since its marketing approval, the attention to the hepatic side‐effect profile of the antidepressant agomelatine (AGM) has gradually increased. Several cases of severe hepatotoxic adverse drug reactions (ADR) have been reported and the European Medicines Agency has released a safety warning regarding AGM‐associated hepatotoxicity. However, there are insufficient data for an adequate safety assessment of AGM‐related hepatotoxicity. Therefore, we performed a quantitative signal detection analysis using pharmacovigilance data from the Uppsala Monitoring Centre from the WHO that records ADR data from worldwide sources; we calculated reporting odds ratios (ROR) as measures for disproportionality within a case/non‐case approach for AGM and several other antidepressants. AGM was statistically associated with an increased risk of hepatotoxicity (ROR 6.4 [95%CI 5.7–7.2]) as well as both positive controls: amineptine (ROR 38.4 [95%CI 33.8–43.6]) and nefazodone (ROR 3.2 [95%CI 3.0–3.5]). Following amineptine, AGM was associated with the second highest ROR, followed by tianeptine (ROR 4.4 [95%CI 3.6–5.3]), mianserin (ROR 3.6 [95%CI 3.3–3.9]), and nefazodone. These results support the hypothesis that AGM is associated with relevant hepatotoxicity. However, the used data and applied method do not allow a quantitative evaluation of hepatotoxicity or assessment of substance‐specific differences regarding the extent of hepatotoxicity.
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Among TCAs, clomipramine and amitriptyline also had higher hepatotoxicity than SSRIs.
“Among TCAs, clomipramine and amitriptyline also had higher hepatotoxicity than SSRIs.”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [48]
Among second generation antidepressants, duloxetine had a higher risk of causing hepatotoxicity.
“Among second generation antidepressants, duloxetine had a higher risk of causing hepatotoxicity.”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [48]
A quantitative signal detection analysis using pharmacovigilance data from the Uppsala Monitoring Centre from the WHO showed that agomelatine was statistically associated with an increased risk of hepatotoxicity with a reporting odds ratio of 6.4.
“The results showed that agomelatine was statistically associated with an increased risk of hepatotoxicity with a reporting odds ratio of 6.4.”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [48]
SSRIs did not show significant risk compared with other antidepressants.
“Again, SSRIs did not show significant risk compared with other antidepressants (Table 2).”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [48]
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- Authors
- Gahr, M., Zeiss, R., Lang, D., Connemann, B. J., & Schönfeldt‐Lecuona, C.
- Affiliations
- Universität Ulm (DE)
- Corresponding author
- Gahr, Maximilian
- Venue
- The Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2015-03-09
- Volume
- 55
- Issue
- 7
- Pages
- 768-773
- ISSN
- 0021-9754 (ISSN-L)
- 0091-2700
- 1552-4604
- OpenAlex
- W1696796373
- Cited by
- 14
- References
- 26
- Citations by year
- 2026: 1 · 2021: 1 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 2
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
- Keywords
- agomelatine, hepatotoxicity, antidepressants, adverse drug reactions, disproportionality analysis, reporting odds ratio, amineptine, nefazodone, tianeptine, mianserin, drug safety, pharmacovigilance
- MeSH terms
- Acetamides, Antidepressive Agents, Humans, Naphthalenes, Sweden, Adverse Drug Reaction Reporting Systems, Chemical and Drug Induced Liver Injury, Pharmacovigilance
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