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Pharmacokinetics of Antidepressants in Patients with Hepatic Impairment

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Abstract

Appropriate use of antidepressant in patients with hepatic impairment requires careful consideration of how the hepatic illness may affect pharmacokinetics. This review aims to analyze pharmacokinetic profile, plasma level variations so as the metabolism of several antidepressants relating to their use in patients with an hepatic impairment. Due to the lack of data regarding hepatic impairment itself, the review is focused mainly on studies investigating pharmacokinetics in hepatic cirrhosis or alcohol-related conditions. More data on reduced hepatic metabolism can be extrapolated by drug studies conducted in elderly populations. Dose adjustment of antidepressants in these patients is important as most of these drugs are predominantly metabolized by the liver and many of them are associated with dose-dependent adverse reactions. As no surrogate parameter is available to predict hepatic metabolism of drugs, dose adjustment according to pharmacokinetic properties of the drugs is proposed. There is a need for a more balanced assessment of the benefits and risks associated with antidepressants use in patients with hepatic impairment, particularly considering pharmacokinetic profile of the drugs to ensure that patients, who would truly benefit from these agents, are not denied appropriate treatment. In conclusion, kinetic studies for centrally acting drugs including antidepressants with predominant hepatic metabolism should be carried out in patients with liver disease to allow precise dose recommendations for enhanced patient safety.

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No sources of funding were used in the preparation of this review. All authors have no conflicts of interest to declare.

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  1. Clinical Psychiatry, Clinical Neuropsychopharmacology Unit, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy

    Massimo Carlo Mauri, Alessio Fiorentini, Silvia Paletta & Alfredo Carlo Altamura

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  1. Massimo Carlo Mauri
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  2. Alessio Fiorentini
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  4. Alfredo Carlo Altamura
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Mauri, M.C., Fiorentini, A., Paletta, S. et al. Pharmacokinetics of Antidepressants in Patients with Hepatic Impairment. Clin Pharmacokinet 53, 1069–1081 (2014). https://doi.org/10.1007/s40262-014-0187-5

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