Can Lexapro (escitalopram) cause elevated liver enzymes?

Can Lexapro (Escitalopram) Cause Elevated Liver Enzymes?

Yes, Lexapro (escitalopram) can cause elevated liver enzymes, but this occurs rarely—with an incidence of only 0.01% based on large-scale psychiatric surveillance data, making it one of the safest antidepressants regarding hepatotoxicity. 1

Incidence and Risk Profile

• Escitalopram has the lowest probability of drug-induced liver injury among all antidepressants studied, with an incidence rate of 0.01% compared to other SSRIs like citalopram (0.02%) and fluoxetine (0.02%) 1
• Among 184,234 psychiatric inpatients treated with antidepressants over 18 years, escitalopram demonstrated the most favorable hepatic safety profile of all selective serotonin reuptake inhibitors 1
• The FDA prescribing information notes that escitalopram is extensively metabolized hepatically, and in subjects with hepatic impairment, clearance is decreased and plasma concentrations increase 2

Clinical Presentation When Liver Injury Occurs

When hepatotoxicity does occur with escitalopram (though rare), patients may present with:

• Nausea, fatigue, loss of appetite, and abdominal pain as the most common clinical symptoms 1
• Asymptomatic elevation of transaminases (ALT/AST) detected on routine monitoring 3
• Onset typically ranges from 5 days to 3 years after initiation, though most antidepressant-related liver injury manifests within weeks to months 3

Monitoring Recommendations

• Obtain baseline liver function tests (ALT, AST, alkaline phosphatase, total bilirubin) before initiating escitalopram in patients with pre-existing liver disease or risk factors 4, 5
• For patients with hepatic impairment, the recommended dose is reduced to 10 mg/day (rather than the standard 10-20 mg/day) 2
• Routine monitoring is not required in healthy patients given the extremely low incidence, but check liver enzymes if clinical symptoms develop 1, 3

Management of Elevated Liver Enzymes

If liver enzyme elevation occurs during escitalopram treatment:

• For ALT/AST >3× ULN: Immediately discontinue escitalopram and monitor liver function tests every 1-2 weeks until normalization 4, 5
• For ALT/AST 1-3× ULN: Consider discontinuation, monitor every 1-2 weeks, and evaluate for alternative causes 4, 5
• Most cases are reversible upon discontinuation, with rapid resolution of clinical symptoms and normalization of liver enzymes typically within 2-8 weeks 4, 1, 3
• Document the reaction as a potential drug allergy and avoid rechallenge with escitalopram 4

Comparative Safety Context

• Escitalopram's hepatotoxicity risk is significantly lower than other antidepressants such as mianserine (0.36%), agomelatine (0.33%), clomipramine (0.23%), duloxetine, and tricyclic antidepressants 1, 3
• SSRIs as a class are less likely to precipitate drug-induced liver injury compared to other antidepressant classes, making them preferred agents in patients with pre-existing liver dysfunction 1
• Unlike some antidepressants (nefazodone, trazodone, duloxetine) that have been linked to fatal hepatotoxicity, escitalopram-associated liver injury is typically mild and fully reversible 3

Critical Pitfalls to Avoid

• Do not continue escitalopram if ALT/AST rises above 3× ULN, as this indicates significant hepatocellular injury requiring immediate discontinuation 4, 5
• Do not overlook other causes of elevated liver enzymes including viral hepatitis, alcohol use, metabolic dysfunction-associated steatotic liver disease (MASLD), or concomitant hepatotoxic medications 6, 4, 5
• Do not fail to adjust dosing in patients with known hepatic impairment—the standard dose must be reduced to 10 mg/day in this population 2
• Do not rechallenge with escitalopram after documented hepatotoxicity, as this may result in more severe or rapid recurrence of liver injury 4