title: Retrospective study of hepatic enzyme elevations in children treated with olanzapine, divalproex, and their combination.
abstract: OBJECTIVE
  To evaluate hepatic enzyme elevations during treatment with olanzapine, divalproex, and their combination.
  
  
  METHODS
  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.
authors.affiliation: Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA. joseph.gonzalez-heydrich@tch.harvard.edu
authors.forename: Joseph
authors.initials: J
authors.lastname: Gonzalez-Heydrich
authors.forename: Darcy
authors.initials: D
authors.lastname: Raches
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Wilens
authors.forename: Alan
authors.initials: A
authors.lastname: Leichtner
authors.forename: Enrico
authors.initials: E
authors.lastname: Mezzacappa
mesh_terms: D000293:Adolescent; D000410:Alanine Transaminase / Q000032:analysis / Q000187:drug effects*; D018692:Antimanic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000032:analysis / Q000187:drug effects*; D001569:Benzodiazepines; D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D000077152:Olanzapine; D010195:Pancreatitis / Q000139:chemically induced; D010890:Pirenzepine / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives*; D012189:Retrospective Studies; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D014635:Valproic Acid; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000077152:Olanzapine