Retrospective study of hepatic enzyme elevations in children treated with olanzapine, divalproex, and their combination

Objective: To evaluate hepatic enzyme elevations during treatment with olanzapine, divalproex, and their combination. Method: Fifty-two children, aged 4 to 18 years, with hepatic enzyme levels measured during treatment with olanzapine (n = 17), divalproex (n = 23), or their combination (n = 12), were identified in the computerized records at a pediatric medical center. Clinical characteristics as well as serial alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels were collected. Results: Mean and peak hepatic enzyme levels were significantly higher for the combined treatment group compared to the olanzapine or divalproex groups. All 12 patients who received combined treatment had at least one peak enzyme elevation during the treatment. For 42% of these patients, at least one enzyme level remained elevated during the time for which values were available (mean 8 +/- 6 months). For those treated with divalproex either alone or in combination, the findings were not explained by variations in divalproex plasma levels. Two patients receiving combined treatment had the combination treatment discontinued because of medical complications (pancreatitis in one and steatohepatitis in the other). Conclusions: Combined treatment with olanzapine and divalproex was associated with more elevations of hepatic enzymes than treatment with either agent alone. The long-term significance of this is unknown but warrants study.