Abbott Laboratories announced that adding Depakote (divalproex sodium) to either Zyprexa (olanzapine) or Risperdal (risperidone) resulted in a decrease or no change in total cholesterol levels, as shown in a recent analysis. The data was presented today at the annual meeting of the American Psychiatric Association in New York.
The results are from a post-hoc analysis of a study involving patients hospitalized for psychosis with schizophrenia and are consistent with the effects of Depakote on cholesterol that have been noted in other preliminary reports in people with bipolar disorder (Zajecka, et al., Journal of Clinical Psychiatry, Dec. 2002). Depakote is currently the most prescribed branded treatment for patients with mania associated with bipolar disorder. Depakote is not approved for the treatment of schizophrenia or as a cholesterol-lowering agent.
"There is a growing concern among physicians, as noted by the recent joint-statement of the American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists and North American Association for the Study of Obesity, that using certain atypical antipsychotics can lead to metabolic issues such as elevated cholesterol levels," said Daniel Casey, M.D., lead investigator and professor of psychiatry and neurology at Oregon Health & Science University. "It is encouraging that this analysis shows combining Depakote with these atypical antipsychotics has no negative effects on cholesterol levels and can even help to lower total cholesterol levels in patients taking these drugs."
The data for this analysis was taken from a study that was conducted to investigate the use of Depakote with an antipsychotic agent in patients hospitalized for acute exacerbation of schizophrenia. Patients were randomly assigned to receive Zyprexa or Risperdal monotherapy or Depakote plus Zyprexa or Risperdal. Improvements from baseline were observed at all evaluation points throughout the 28-day treatment period in all therapy groups, with greater improvements seen in the combination groups. Patients in both combination groups experienced a mean decrease in platelet count. Patients in the Zyprexa and Risperdal monotherapy groups experienced a mean increase in the liver enzyme SGOT/AST, and patients in the Risperdal monotherapy group experienced a mean increase in the liver enzyme SGPT/ALT.
Patients treated with a combination of Depakote and Zyprexa experienced a minimal increase in total cholesterol compared to the increase in patients treated with Zyprexa when used as monotherapy:
+26.62 mg/dL for Zyprexa monotherapy (baseline: 193 mg/dL).
+0.87 mg/dL for Depakote plus Zyprexa (baseline: 198 mg/dL).
Patients treated with a combination of Depakote and Risperdal experienced a decrease in total cholesterol compared to Risperdal when used as monotherapy:
+9.64 mg/dL for Risperdal monotherapy (baseline: 188 mg/dL).
-13.44 mg/dL for Depakote plus Risperdal (baseline: 192 mg/dL).
Patients in the Zyprexa monotherapy group had the highest rate of shift from a normal total cholesterol (<200 mg/dL) to a high total cholesterol (>200 mg/dL).
"Depakote is a well-established therapy that has been trusted by physicians for more than twenty years," said Marleen Verlinden, Ph.D., divisional vice president, Global Pharmaceutical Development, Abbott Laboratories. "This study adds to the growing body of literature identifying the effects of Depakote on cholesterol."
The findings were based on a post-hoc analysis of a 28-day, double-blind, randomized, multicenter study assessing the efficacy and safety of Depakote when combined with either Risperdal or Zyprexa in patients hospitalized for psychosis with schizophrenia.