Can Lexapro (escitalopram) cause liver injury?

Lexapro (Escitalopram) and Liver Injury

Yes, Lexapro (escitalopram) can cause liver injury, though it is rare compared to other antidepressants. While generally considered among the safer antidepressants regarding hepatotoxicity, cases of escitalopram-induced liver injury have been documented, including cholestatic hepatitis.

Epidemiology and Risk

• Antidepressants as a class can cause drug-induced liver injury (DILI) in approximately 0.5%-3% of patients, typically presenting as asymptomatic mild elevation of serum aminotransferases 1
• A disproportionality analysis of the WHO pharmacovigilance database (VigiBase®) found patients treated with escitalopram had an increased risk of:
  • Hepatitis [OR = 1.938 (1.186-3.166)]
  • Cholestasis [OR = 1.866 (1.279-2.724)] 2

Characteristics of Escitalopram-Induced Liver Injury

Timing and Presentation

• Onset typically occurs within days to months after starting treatment
• Median time to onset is approximately 10 ± 7 days after introduction 2
• Presentation can range from asymptomatic liver enzyme elevations to symptomatic hepatitis with jaundice

Clinical Features

• May present with:
  • Elevated liver enzymes (ALT/AST)
  • Jaundice
  • Pruritus
  • Dark urine
  • Cholestatic pattern of injury 2

Mechanism

• Most cases are idiosyncratic (not dose-dependent) 1
• The exact pathophysiological mechanism remains unclear, but likely involves:
  • Individual genetic susceptibility
  • Possible immune-mediated reactions
  • Metabolic idiosyncrasies 3

Monitoring and Management

Monitoring Recommendations

• Baseline liver function tests (LFTs) before initiating therapy in patients with:
  • Pre-existing liver disease
  • Risk factors for hepatotoxicity
  • Concomitant hepatotoxic medications
• Consider periodic monitoring of LFTs during the first 6 months of treatment, particularly in high-risk patients

Management of Suspected Liver Injury

1. Immediate discontinuation of escitalopram if significant liver injury is suspected
2. Monitor liver enzymes until normalization
3. Evaluate for other causes of liver injury
4. Avoid rechallenge with escitalopram if liver injury is confirmed
5. Consider alternative antidepressants with lower hepatotoxicity risk if needed

Comparative Hepatotoxicity Risk Among Antidepressants

• Lower risk: Citalopram, escitalopram, paroxetine, fluvoxamine 1
• Higher risk: Nefazodone, duloxetine, bupropion, trazodone, amitriptyline 1

Recovery and Prognosis

• Most cases resolve completely after drug discontinuation
• In the documented case report, after escitalopram withdrawal:
  • Pruritus resolved within 2 days
  • Clinical jaundice disappeared within 10 days
  • Complete normalization of liver function tests occurred within 7 weeks 2

Clinical Pearls

• Liver injury from escitalopram is rare but potentially serious
• Patients should be educated about symptoms of liver injury (jaundice, dark urine, right upper quadrant pain)
• Elderly patients and those on multiple medications may be at higher risk
• Cross-toxicity between antidepressants can occur, particularly with tricyclic and tetracyclic antidepressants 1
• Consider alternative antidepressants with lower hepatotoxicity risk in patients with pre-existing liver disease

While escitalopram is considered among the safer antidepressants regarding hepatotoxicity, clinicians should remain vigilant about the potential for liver injury, particularly during the first few months of treatment.