Can elevated liver function tests (LFTs) be related to fluoxetine, atomoxetine, and Seroquel (quetiapine)?

Elevated Liver Function Tests Associated with Fluoxetine, Atomoxetine, and Quetiapine

Yes, elevated liver function tests (LFTs) can be related to fluoxetine, atomoxetine, and quetiapine (Seroquel), with atomoxetine carrying the highest risk of clinically significant hepatotoxicity among these medications.

Medication-Specific Hepatotoxicity Risk

Atomoxetine

• Atomoxetine has been associated with clinically significant hepatotoxicity, including cases of severe liver injury 1
• In clinical trials, 41 of 7961 patients treated with atomoxetine developed hepatobiliary events, mostly mild increases in ALT and AST 1
• Post-marketing surveillance identified three cases of reversible drug-induced liver injury probably related to atomoxetine 1
• Case reports document severe hepatitis after starting atomoxetine therapy in children, including one case suggestive of drug-induced autoimmune hepatitis 2
• Atomoxetine should be discontinued in patients with jaundice or laboratory evidence of liver injury and should not be restarted 1

Quetiapine (Seroquel)

• Atypical antipsychotics like quetiapine commonly cause asymptomatic increases in liver enzymes and serum bilirubin levels 3
• Approximately 27.2% of patients on atypical antipsychotics (including quetiapine) showed asymptomatic increases in ALT, AST, GGT, and serum bilirubin levels in the first month of treatment 3
• After 6 months of treatment, abnormalities in liver function tests were observed in 22.7% of patients on atypical antipsychotics 3
• Serious hepatic toxicity with quetiapine is rare but possible 3

Fluoxetine

• All antidepressants, including fluoxetine, can induce hepatotoxicity, especially in elderly patients and those with polypharmacy 4
• Approximately 0.5%-3% of patients treated with antidepressants may develop asymptomatic mild elevation of serum aminotransferase levels 4
• Fluoxetine is associated with reversible liver injury upon discontinuation of the agent 5
• Among SSRIs, fluoxetine has a moderate hepatotoxicity risk profile compared to citalopram, escitalopram, paroxetine, and fluvoxamine, which have lower hepatotoxicity potential 4

Monitoring Recommendations

General Approach

• Obtain baseline liver function tests before starting these medications 3
• Monitor liver function tests regularly during treatment, especially in patients with risk factors for liver damage 3
• For atomoxetine, monitor LFTs more closely due to higher risk of clinically significant hepatotoxicity 1

Monitoring Schedule

• For quetiapine: Check LFTs at baseline and monitor at least annually 3
• For fluoxetine: Check LFTs at baseline and monitor periodically, especially during the first 6 months of treatment 4
• For atomoxetine: Check LFTs at baseline, within the first 1-2 months of usage, and every 3-4 months thereafter 1

When to Be Concerned

• Liver injury from these medications is typically idiosyncratic and unpredictable, generally unrelated to drug dosage 4
• The interval between treatment initiation and onset of liver injury is generally between several days and 6 months 4
• Signs of concern include:
  • ALT > 3X the upper limit of normal 1
  • Jaundice or other clinical symptoms of liver dysfunction 1
  • Progressive elevation of liver enzymes despite stable dosing 4

Management of Elevated LFTs

• If mild elevation (< 3X upper limit of normal) without symptoms: Consider more frequent monitoring while continuing medication 3
• If moderate to severe elevation (> 3X upper limit of normal) or any elevation with symptoms: Consider discontinuation of the medication 1, 4
• Most cases of drug-induced liver injury are reversible when detected early and the offending agent is discontinued 5
• After discontinuation, monitor LFTs until normalization 1

Important Considerations and Pitfalls

• Cross-toxicity between psychotropic medications can occur, so caution is needed when switching between medications in the same class 4
• Concomitant medications that affect hepatic metabolism may increase the risk of liver injury 5
• Patients with pre-existing liver disease may be at higher risk for medication-induced hepatotoxicity 4
• Liver injury can occur in the absence of identifiable underlying risk factors 5
• Always consider other potential causes of elevated LFTs (viral hepatitis, alcohol use, other medications) 4