Download Antidepressants in Hepatic Failure Antidepressants in Renal Failure

Antidepressants in Hepatic Failure
Preferred
Consider with Dosage
Decrease
Citalopram (max dose 20mg)
Escitalopram
Sertraline
SSRIs
Avoid
Comments
Citalopram – Levels are increased ~100% with potent Cyp2D6 inhibitors. Similar or more
significant increases should be anticipated in moderate and severe HF.
Fluoxetine
Paroxetine
Sertraline - Highly protein bound, extensively hepatically metabolized to essentially inactive
metabolites. Expect significant increases in free (active) drug in severe HF.
Fluoxetine - need significant dosage decrease (at least 50%), even in compensated
cirrhosis. Is also potent inhibitor of CYP2D6.
Venlafaxine? (↓ dose 50%)
Duloxetine
SNRIs
Paroxetine – t ½ and AUC doubled in alcoholic cirrhosis, also potent inhibitor of CYP2D6.
Venlafaxine: Studies in CYP2D6 Genetically Poor Metabolizers show decreased efficacy
and increased side effects. This may be true with moderate to severe hepatic failure as
well. SSRIs are likely more predictably efficacious.
Duloxetine: Significant increases in AUC, even in compensated cirrhosis.
Other
If necessary to use, monitor serum concentration. Patients with decreased CYP2D6
(including moderate to severe hepatic failure) will have non-linear kinetics (example, a 10%
increase in dose may cause a 75% increase in serum concentrations). Toxicities include
delirium, seizures, and fatal arrhythmias.
Mirtazepine – Approximate 33% decrease in hepatic clearance with slight increase in t1/2
in cirrhosis, likely insignificant.
Amitriptyline
Desipramine
Nortriptyline
TCAs
Mirtazepine
Antidepressants in Renal Failure
Preferred
SSRIs
SNRIs
Sertraline
Escitalopram?
Citalopram?
Duloxetine*
Consider with Dosage Decrease
Comments
Citalopram/Escitalopram – A small % (10-15%) is excreted unchanged and 10% as
weakly active metabolites. Monitor for side effects in renal failure.
Fluoxetine – Single dose studies show no change in PK. Many references suggest no
change in dose in renal failure. However, would anticipate possible accumulation and
non-linear PK with multiple doses.
Paroxetine – AUC and t½ increase as renal function declines. In eCrCl <30mL/min, start
at 10 mg and increase to max of 30 mg.
Duloxetine – No dose adjustment needed in mild-moderate renal failure
Duloxetine (↓ dose 50% in ESRD)
Venlafaxine? (↓ dose 50%)
Amitriptyline
Desipramine
Nortriptyline
TCAs
Other
Avoid
Fluoxetine?
Paroxetine
Mirtazepine
Bupropion
Hydroxy metabolites of TCAs will accumulate in renal failure. These metabolites are the
most cardiotoxic form of TCAs.
Mirtazepine – Clearance decreased 33% in eCrCl ~30mL/min, 50% in <10ml/min with
single dose studies.
Bupropion – Significant accumulation of active metabolites.
SSRIs – Selective Serotonin Reuptake Inhibitors; PK – Pharmacokinetics; AUC – Area Under the Curve; t ½ - half life; eCrCl – estimated Creatinine Clearance; SNRIs – Serotonin-Norepinephrine Reuptake Inhibitors; ESRD – End-stage Renal Disease; TCAs – Tricyclic
Antidepressants; HF – Hepatic Failure
Author(s): Hartman A; Department: Pharmacy; Date Originated: May 2012
This information has been developed by the authors and department listed above at The Ohio State University Medical Center and is intended for use only within the institution. The information is not meant to be applied rigidly and followed in all cases. Professional
judgment must remain central to the application of this information. All rights reserved, including right of reproduction, in whole or in part, in any form without permission from The Ohio State University Medical Center. Copyright: © 2012 The Ohio State University Medical
Center