Can depression/anxiety medications or dementia medications cause elevated liver enzymes?

Depression/Anxiety and Dementia Medications That Commonly Elevate Liver Enzymes

Yes, several depression/anxiety medications and dementia drugs can elevate liver enzymes, with antidepressants showing 0.5-3% incidence of asymptomatic aminotransferase elevation, while most dementia medications have minimal hepatotoxic risk except tacrine, which causes liver enzyme elevation in 40% of patients. 1, 2

Antidepressants with Higher Hepatotoxicity Risk

The following antidepressants are associated with greater risks of hepatotoxicity and should be used cautiously in patients with baseline elevated liver enzymes 1:

• Tricyclic antidepressants (imipramine, amitriptyline) - can cause hepatocellular injury 1
• MAO inhibitors (phenelzine, iproniazid) - associated with significant hepatotoxicity 1
• Nefazodone - requires monitoring for hepatotoxicity; dose reduction or discontinuation if significant enzyme elevation occurs 2, 1
• Duloxetine - higher hepatotoxicity risk 1
• Bupropion - can cause liver enzyme elevation 1
• Trazodone - associated with hepatotoxicity 1
• Agomelatine - known hepatotoxic potential 1

Antidepressants with Lower Hepatotoxicity Risk

The safest antidepressants regarding liver toxicity are citalopram, escitalopram, paroxetine, and fluvoxamine, which have the least potential for hepatotoxicity 1. However, even paroxetine overdose cases have documented symptoms of hepatic dysfunction including hepatic failure, hepatic necrosis, jaundice, hepatitis, and hepatic steatosis 3.

Dementia Medications and Liver Enzymes

Cholinesterase Inhibitors (Preferred Agents)

• Donepezil - not hepatotoxic and does not require liver monitoring 2
• Rivastigmine - no laboratory monitoring required for hepatotoxicity 2
• Galantamine - minimal hepatotoxic concerns 2

Tacrine (Second-Line Agent)

• Tacrine causes elevation of liver enzyme levels in 40% of treated patients 2
• Requires biweekly liver tests during dosage escalations and every three months thereafter 2
• Should be considered a second-line agent due to its hepatotoxic profile 2

Clinical Management Approach

For Your Patient (AST 58, ALT 98)

Given your patient's mildly elevated transaminases (AST 1.5x ULN, ALT 2.5x ULN approximately):

1. If starting antidepressants: Choose citalopram, escitalopram, paroxetine, or fluvoxamine as first-line options 1

2. If starting dementia medications: Donepezil, rivastigmine, or galantamine are safe choices; avoid tacrine 2

3. Monitoring strategy: The interval between treatment initiation and onset of drug-induced liver injury is generally between several days and 6 months 1

4. Threshold for action: If aminotransferases increase to ≥3 times ULN, consider holding the medication and repeating liver function tests within 48-72 hours 4

Important Caveats

• Drug-induced liver disease accounts for 10-50% of adult patients with elevated enzymes, especially in those over age 50 5
• Liver injury from antidepressants is typically idiosyncratic and unpredictable, generally unrelated to drug dosage 1
• The underlying lesions are often hepatocellular type (like your patient's pattern with ALT > AST) and less frequently cholestatic 1
• Cross-toxicity has been described, mainly for tricyclic and tetracyclic antidepressants 1
• More than 30% of elevated transaminases spontaneously normalize during follow-up in asymptomatic patients 6

Monitoring Recommendations

• Aminotransferase surveillance is the most useful tool for detecting drug-induced liver injury 1
• For medications like cariprazine (atypical antipsychotic sometimes used for depression), baseline liver function tests should be obtained with regular monitoring, particularly in the first few weeks of treatment 7
• Prompt discontinuation of the responsible drug is essential if significant hepatotoxicity develops 1