What is the likelihood of Paroxetine (Paxil) causing hepatic injury?

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Last updated: May 27, 2025View editorial policy

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From the Guidelines

Paxil (paroxetine) has a low risk of causing liver damage, with 0.5% to 3% of patients experiencing asymptomatic mild elevation in transaminase levels, as reported in a literature review 1. The risk of hepatotoxicity is lower with SSRIs, such as Paxil, compared to other antidepressant classes like TCAs and nefazodone. Key points to consider include:

  • The time to onset of hepatotoxicity is typically within six months of starting the medication 1.
  • Patients with pre-existing liver disease, alcohol use, older age, and those taking multiple medications may be at higher risk for liver problems.
  • Warning signs of liver problems, such as yellowing of the skin or eyes, dark urine, upper right abdominal pain, or unusual fatigue, should prompt immediate medical attention.
  • Regular liver function monitoring is not routinely required for most patients on Paxil unless they have pre-existing liver conditions or other risk factors.
  • The liver metabolizes Paxil, which is why there is some potential for impact, but the medication's overall hepatotoxic profile is considered favorable compared to some other psychiatric medications.

From the FDA Drug Label

Increased plasma concentrations of paroxetine occur in subjects with renal and hepatic impairment. The mean plasma concentrations in patients with creatinine clearance below 30 mL/min. were approximately 4 times greater than seen in normal volunteers. Patients with creatinine clearance of 30 to 60 mL/min and patients with hepatic functional impairment had about a 2-fold increase in plasma concentrations (AUC, Cmax). Other notable signs and symptoms observed with overdoses involving paroxetine (alone or with other substances) include ... symptoms of hepatic dysfunction (including hepatic failure, hepatic necrosis, jaundice, hepatitis, and hepatic steatosis)

The likelihood of Paxil causing liver damage is possible, as indicated by increased plasma concentrations in patients with hepatic impairment and reports of hepatic dysfunction in overdose cases 2 2 2. However, the exact likelihood is not quantified in the provided drug labels. Liver damage is a potential risk, particularly in patients with pre-existing hepatic impairment, and caution is advised when prescribing Paxil to these patients.

From the Research

Liver Damage Associated with Paxil

  • Paxil, also known as paroxetine, is a selective serotonin reuptake inhibitor (SSRI) that has been associated with liver damage in some cases 3, 4.
  • The risk of liver damage with Paxil is considered to be low, but it can occur in rare cases, especially in elderly patients and those with polypharmacy 4.
  • Studies have shown that all antidepressants, including Paxil, can induce hepatotoxicity, which is often idiosyncratic and unpredictable 3, 4.
  • The onset of liver injury can occur anywhere from 5 days to 3 years after starting treatment with Paxil 3.

Mechanism of Liver Damage

  • The exact mechanism of liver damage associated with Paxil is not fully understood, but it is thought to be related to the drug's effect on serotonin levels in the body 5.
  • Elevated serotonin levels have been shown to contribute to hepatic lipid accumulation, which can lead to liver damage 5.
  • However, the relationship between Paxil and liver damage is complex, and more research is needed to fully understand the underlying mechanisms 4.

Monitoring and Prevention

  • Monitoring of liver function tests is recommended for patients taking Paxil, especially those with pre-existing liver disease or risk factors for liver damage 3, 4.
  • Immediate discontinuation of Paxil is recommended if abnormal liver function tests or signs and symptoms of liver dysfunction occur 3, 4.
  • Patients should be aware of the potential risk of liver damage associated with Paxil and report any concerns or symptoms to their healthcare provider promptly.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Liver injury associated with antidepressants.

Current drug safety, 2013

Research

Antidepressant-induced liver injury: a review for clinicians.

The American journal of psychiatry, 2014

Research

Fluoxetine-induced hepatic lipid accumulation is linked to elevated serotonin production.

Canadian journal of physiology and pharmacology, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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