From the Guidelines
For patients with elevated liver transaminases who require a depot antipsychotic, paliperidone palmitate (Invega Sustenna or Invega Trinza) is generally the best option. Paliperidone is primarily excreted unchanged in the urine with minimal hepatic metabolism, making it safer for those with liver impairment. The recommended starting regimen for Invega Sustenna is 234 mg on day 1 and 156 mg on day 8, both administered as intramuscular injections, followed by monthly maintenance doses typically ranging from 78-234 mg based on efficacy and tolerability. Some key points to consider when prescribing depot antipsychotics to patients with elevated liver enzymes include:
- Monitoring of liver function tests is essential regardless of which medication is chosen
- The safety profile of paliperidone in hepatic impairment is due to its pharmacokinetic properties - as the active metabolite of risperidone, it bypasses first-pass metabolism in the liver, reducing the burden on an already compromised hepatic system and minimizing the risk of further elevating liver enzymes 1
- Atypical antipsychotics, such as risperidone, may produce elevations in hepatic transaminase levels, which are often transient and generally resolve with cessation of the drug 1 Alternatively, aripiprazole monohydrate (Abilify Maintena) might be considered as a second choice, as it undergoes less hepatic metabolism than many other antipsychotics. Key considerations for the use of these medications in patients with elevated liver enzymes include:
- Baseline liver functions should be checked prior to initiating treatment
- Periodic monitoring of liver function tests during ongoing therapy is necessary 1
- The potential for liver enzyme abnormalities and fatty infiltrates associated with certain antipsychotics, such as risperidone, particularly in adolescent males 1
From the Research
Depot Antipsychotics and Elevated Liver Enzymes
- The choice of depot antipsychotic for a patient with elevated liver enzymes (transaminases) should be made with caution, as some antipsychotics have been associated with hepatotoxicity 2, 3.
- A case report described a patient who developed hepatotoxicity during risperidone use, which did not resolve with a switch to paliperidone therapy, suggesting that both risperidone and its metabolite can cause hepatotoxicity 2.
- A systematic review found that all antipsychotics were associated with a higher prevalence of liver function test (LFT) abnormalities than chance, with transaminases being the most commonly elevated 3.
- Chlorpromazine was found to be most commonly associated with acute liver injury 3.
- In patients with elevated LFTs, an algorithmic approach can be taken to narrow the differential diagnosis and ensure appropriate management and evaluation 4, 5.
- If a patient has elevated liver enzymes, it is recommended to reevaluate and consider a specific workup to rule out liver disease 5.
- Haloperidol was found to be a suitable alternative in a case where a patient developed hepatotoxicity with risperidone and paliperidone 2.