DeSanty Kevin P, Amabile Celene M
Gaston Memorial Hospital, Gastonia, NC 28054, USA.
Ann Pharmacother. 2007 Jul;41(7):1201-11. doi: 10.1345/aph.1K114. Epub 2007 Jul 3.
To review principles of drug-induced liver injury (DILI), summarize characteristics of antidepressant-mediated liver injury, and provide recommendations for monitoring and management.
A search relating to antidepressant-induced liver injury was performed using MEDLINE (1966-March 2007). Search terms included antidepressant, cholestasis, hepatotoxicity, jaundice, liver injury, toxic hepatitis, and transaminases. Reference citations not identified in the initial database search were also utilized.
All English-language case reports, letters, and review articles identified from the data sources were used. Case reports and letters relating to hepatotoxicity from antidepressant overdose were excluded.
Antidepressant-induced liver injury described in published cases were of the idiopathic type and, by definition, cannot be predicted based on dose or specific risk factors. Paroxetine had the largest number of cases within the selective serotonin-reuptake inhibitor class. Nefazodone, a serotonin-norepinephrine reuptake inhibitor, appeared to have the most serious cases and is the only antidepressant agent that carries a Food and Drug Administration Black Box Warning regarding hepatotoxicity. The tricyclic antidepressants and monoamine oxidase inhibitors are capable of producing hepatotoxicity, but fewer cases with these agents have been reported in the past 15 years, possibly due to a decline in their use. Causality has not been well established in all reports due to the concurrent use of other drugs and/or underlying liver disease.
Most antidepressant agents have the potential to produce idiopathic liver injury. There is no way to prevent idiopathic DILI, but the severity of the reaction may be minimized with prompt recognition and early withdrawal of the agent. The clinician must be careful to provide ongoing therapy of the underlying depressive disorder and be aware of possible drug discontinuation syndromes should potential hepatotoxicity be suspected.
回顾药物性肝损伤（DILI）的原则，总结抗抑郁药所致肝损伤的特点，并提供监测和管理建议。
使用MEDLINE（1966年 - 2007年3月）进行了与抗抑郁药所致肝损伤相关的检索。检索词包括抗抑郁药、胆汁淤积、肝毒性、黄疸、肝损伤、中毒性肝炎和转氨酶。还利用了在初始数据库检索中未识别的参考文献。
使用从数据来源中识别出的所有英文病例报告、信函和综述文章。排除与抗抑郁药过量所致肝毒性相关的病例报告和信函。
已发表病例中描述的抗抑郁药所致肝损伤属于特发性类型，根据定义，无法基于剂量或特定风险因素进行预测。在选择性5-羟色胺再摄取抑制剂类别中，帕罗西汀的病例数最多。去甲肾上腺素能和特异性5-羟色胺能抗抑郁药奈法唑酮似乎有最严重的病例，并且是唯一一种带有美国食品药品监督管理局关于肝毒性黑框警告的抗抑郁药。三环类抗抑郁药和单胺氧化酶抑制剂能够产生肝毒性，但在过去15年中，这些药物的病例报告较少，可能是由于其使用减少。由于同时使用其他药物和/或潜在的肝脏疾病，并非所有报告中的因果关系都已明确确立。
大多数抗抑郁药都有可能导致特发性肝损伤。无法预防特发性DILI，但通过及时识别和早期停用药物，可将反应的严重程度降至最低。临床医生必须谨慎地为潜在的抑郁症提供持续治疗，并在怀疑可能存在肝毒性时，意识到可能的停药综合征。
