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Hepatic disease lowers the first-pass extraction and biotransformation of medications. In the presence of liver failure, there is a greater risk for medication side effects, particularly after oral administration and with drugs that have a narrow therapeutic index (like tricyclic antidepressants [TCAs]). Liver disease affects the ability of medications to bind to proteins and affects the metabolism of most antidepressants, benzodiazepines like diazepam, and neuroleptics including haloperidol. With chronic liver failure, there should be a 25%–50% reduction in dosage because medications that are not bound to protein are more active. In cases of acute hepatic disease, alterations in drug dose are not necessary. When choosing an antidepressant medication, citalopram and fluvoxamine are less protein bound and therefore more effective than other SSRIs. Clinicians should avoid carbamazepine, valproate, nefazodone, and the phenothiazines due to hepatotoxicity. Intravenous drug administration avoids first-pass metabolism by the CYP450 system and may allow medication doses more typical for patients with normal hepatic function (Beliles 2000; Shaw and DeMaso 2006).

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