Letter to the Editor: Role of Vitamin E in Olanzapine-Induced Hepatotoxicity

Case Presentation

This letter reports the course of a 15-year-old adolescent with disruptive mood dysregulation disorder, reactive attachment disorder, and posttraumatic stress disorder, as well as intellectual disability. The report is interesting in that when vitamin E was discontinued there was a recrudescence of the transaminases. Patient had prior trials of antipsychotics, stimulants, and mood stabilizers, was stabilized on lithium, clonidine, and olanzapine. At the time of admission, baseline laboratories were within normal limits, including aspartate aminotransferase (AST) (17 U/L) and alanine aminotransferase (ALT) (20 U/L). One month after beginning olanzapine, ALT was increased to 110 U/L and AST to 53 U/L. Having ruled out other etiologies, olanzapine and cetirizine were deemed the most probable causes of the elevated transaminases. Cetirizine was discontinued and vitamin E 100 mg/day was initiated to treat elevated transaminase as documented in a prior single case study (Dönmez et al. 2017). Ten days later ALT dropped to 43 U/L and AST to 28 U/L. Vitamin E was discontinued to determine whether ongoing treatment was necessary. Cetirizine was not restarted. Seven days later his ALT had risen to 62 U/L and his AST to 34 U/L; therefore, vitamin E was restarted and was part of his discharge medication regimen. Four weeks later, he was still taking vitamin E and recheck of transaminases showed, ALT at 20 U/L and AST at 24 U/L.

Discussion

Atypical antipsychotics commonly cause asymptomatic elevated transaminases (Atasoy et al. 2007). Olanzapine has been shown to cause asymptomatic transaminases elevation in ∼27% of patients (Atasoy et al. 2007). Drug-induced hepatic damage can be diagnosed within 2–8 weeks after initiating antipsychotic medications and upon ruling out other etiologies (Gaertner et al. 2001). Vitamin E has potent antioxidant properties by protecting the integrity of membranes by inhibiting lipid peroxidation and other therapeutic effects that can retard hepatic fibrosis and may prevent cirrhosis by modulating inflammatory response, cell injury, cellular signaling, and cellular proliferation (Perumpail et al. 2018). A rat model study has shown that free radicals can cause oxidative damage to the mitochondria leading to hepatic damage, which can be prevented with the use of vitamin E (Eftekhari et al. 2016). The single case study referenced earlier used a dose of 400 mg/day of vitamin E to reverse olanzapine-induced liver damage but due to concerns about vitamin E toxicity, we used 100 mg/day and found a similar reduction in both ALT and AST. As a result of our study, we feel that lower dosages of vitamin E alone may be effective in reducing olanzapine-induced hepatic inflammation.

Limitations of this study include lack of long-term follow-up of transaminases with continued vitamin E supplementation. In addition, many prospective studies have shown that mixed dopamine receptor agonists as well as selective serotonin receptor inhibitors and serotonin–norepinephrine receptor inhibitors can cause fluctuations in transaminases that resolve spontaneously. Additional studies will need to be conducted to provide further support for the beneficial role of vitamin E supplementation in reversing olanzapine-induced hepatic damage, determining how long vitamin E should be continued after normalization of transaminases, and the risks versus benefits of potential vitamin E toxicity versus olanzapine-induced elevated transaminases.