What antidepressants affect the liver? Understanding the risks

October 8, 2025 •

2 min read

While severe drug-induced liver injury (DILI) from antidepressants is rare, occurring in only 1.28–4 cases per 100,000 patient-years for many classes, all antidepressants have the potential to cause liver-related issues. Understanding what antidepressants affect the liver and monitoring for signs of liver dysfunction are crucial parts of patient care.

Quick Summary

This article explores the link between antidepressant use and liver health, detailing which medication classes carry higher or lower risks of hepatotoxicity. It covers the signs of liver injury, identifies common risk factors, and explains the importance of liver function monitoring to ensure patient safety.

Key Points

All antidepressants carry some risk: While overall risk is low, all classes of antidepressants, including newer ones like SSRIs and SNRIs, can potentially cause drug-induced liver injury (DILI).
Risk varies by class: Older antidepressants (MAOIs, TCAs) and certain atypical agents (nefazodone, agomelatine, bupropion) are linked with higher risk, while some SSRIs (citalopram, escitalopram) have a lower probability.
DILI is often unpredictable: Antidepressant-induced liver injury is typically idiosyncratic.
Monitoring is essential for high-risk patients: Regular liver function testing (blood tests) is recommended for patients on high-risk drugs, those with pre-existing liver disease, or those on multiple medications.
Symptoms can indicate a problem: Watch for signs of liver dysfunction like nausea, jaundice, fatigue, or abdominal pain and report them to a doctor immediately.
Discontinuation is the primary treatment: If liver injury is suspected, stopping the offending medication is the standard management.
Be cautious with alcohol: Mixing alcohol with certain antidepressants, like duloxetine, increases the risk of liver damage.

The liver plays a vital role in metabolizing medications, making it susceptible to adverse effects from many drugs, including antidepressants. While significant antidepressant-induced liver injury (DILI) is an uncommon event, a milder, asymptomatic elevation of liver enzymes can occur in a small percentage of patients. It is important for both clinicians and patients to understand the spectrum of risk associated with different antidepressant types.

Antidepressant Classes and Liver Risk

Monoamine Oxidase Inhibitors (MAOIs)

Older MAOIs like phenelzine and iproniazid have been associated with a higher risk of liver injury. Their hepatic metabolism can lead to hepatocellular injury, sometimes severe.

Tricyclic and Tetracyclic Antidepressants (TCAs)

TCAs, such as imipramine and amitriptyline, are known to have a higher potential for hepatotoxicity than modern SSRIs.

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs generally have a lower DILI risk, though rare reactions can occur. Citalopram, escitalopram, and fluvoxamine appear to have the lowest risk. Sertraline and paroxetine have documented rare cases. Injury is typically hepatocellular and reversible upon discontinuation.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs carry a moderate, though still low, risk. Duloxetine has a relatively higher risk, especially with pre-existing liver disease or heavy alcohol use. Venlafaxine has also been linked to liver injury.

Atypical Antidepressants

This class has varied risks. Bupropion is associated with rare but potentially severe hepatotoxicity. Trazodone has rare reports of acute liver injury. Agomelatine has a notable risk of enzyme elevation and hepatotoxicity. Nefazodone has a significantly higher risk of severe hepatotoxicity.

Risk Factors and Monitoring

Increased risk of antidepressant-induced liver injury can be influenced by age, gender, polypharmacy, pre-existing liver conditions, and genetic factors.

Monitoring involves liver function tests (LFTs). A baseline LFT is recommended, especially for high-risk individuals or those with existing liver issues. Follow-up LFTs are needed for higher-risk medications like agomelatine. Early detection of abnormal LFTs or symptoms like jaundice, abdominal pain, nausea, and fatigue is crucial. If significant abnormalities occur, the medication should be stopped.

Comparison of Antidepressant Liver Risk


Antidepressant Class	Example Drugs	Relative Liver Risk	Typical Onset Window
MAOIs	Iproniazid, Phenelzine	High	Weeks to months
TCAs	Imipramine, Amitriptyline	Moderate-High	Weeks to months
SSRIs	Citalopram, Escitalopram, Fluoxetine	Low	1-6 months
SSRIs	Sertraline, Paroxetine	Low-Moderate	2-24 weeks
SNRIs	Venlafaxine	Low-Moderate	10 days to 6 months
SNRIs	Duloxetine	Moderate-High	Weeks to months (higher risk with alcohol/pre-existing liver disease)
Atypicals	Agomelatine, Bupropion, Trazodone	Variable (Bupropion/Agomelatine higher)	Weeks to months
Discontinued	Nefazodone	Very High	4 weeks to 8 months

Conclusion

While all antidepressants pose some risk to the liver, significant injury is uncommon. Older classes (MAOIs, TCAs) carry higher risks, but some newer drugs like duloxetine and bupropion also require caution. Managing risk involves evaluating patient history, considering risk factors, and monitoring liver function, particularly early in treatment. Prompt action for detected abnormalities is vital.

Resources

For more detailed pharmacologic information on drug-induced liver injury, refer to the {Link: LiverTox database National Institutes of Health https://www.ncbi.nlm.nih.gov/books/NBK548836/}.

Frequently Asked Questions

Yes, although the overall risk is low, all classes of antidepressant medication have the potential to cause some degree of liver injury. The risk and severity vary significantly between different drugs and patient factors.

Older antidepressants like monoamine oxidase inhibitors (MAOIs) and tricyclics (TCAs) carry a relatively higher risk. Among newer drugs, duloxetine, bupropion, trazodone, and agomelatine have all been linked to clinically significant liver injury in rare cases.

Early signs can include fatigue, nausea, appetite loss, and abdominal pain. More severe injury can lead to jaundice (yellowing of the skin and eyes). Many cases, however, are asymptomatic and only detected through routine blood tests showing elevated liver enzymes.

Monitoring is done primarily through blood tests known as liver function tests (LFTs), which measure enzymes like ALT and AST. Your doctor may order these tests at baseline and at intervals, particularly if you are on a higher-risk medication or have other risk factors.

Risk factors include advanced age, the presence of other medical conditions (like pre-existing liver disease), heavy alcohol consumption, and taking multiple medications at once (polypharmacy).

The primary treatment is the prompt discontinuation of the suspected medication. For most cases, liver function returns to normal after stopping the drug. Re-challenging with the same antidepressant is generally avoided.

Following a liver injury from one antidepressant, a doctor can safely switch a patient to a medication from a different pharmacological class to minimize the risk of cross-toxicity. Close monitoring is still required, especially initially.