Pharmacokinetics of Antidepressants in Patients with Hepatic Impairment

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.

Dose Recommendations for Common Drugs in Patients with Liver Cirrhosis: A Systematic Literature Review

“…The finally identified 18 publications covered a publication period from 1993 to 2019, with a clustering around the year 2014 (Table 2). Eight of the publications were classified as guidelines [9,10,[20][21][22][23][24][25] and ten were categorised as reviews [11,[26][27][28][29][30][31][32][33][34]. They included a total of 1145 dose recommendations for 481 active substances (see Table 3).…”

Depression in the medically ill

“…Given the propensity for both known and unknown interactions in this population, the general approach of 'start low and go slow' is advisable to minimize the risk of toxic effects. Most antidepressants have not been extensively tested in hepatic or renal impairment so product monographs often lack explicit, evidence-based direction for dose adjustment (Hedayati et al, 2012;Mauri et al, 2014). Therefore, added caution is needed, even in the absence of explicit dose adjustment recommendations from the product monograph.…”