Adjunctive canadian Divalproex Sodium Lowers Cholesterol Elevation with Olanzapine generic

Author: Daniel E. Casey, MD, Department of Psychiatry, Oregon Health Sciences University, Portland, Oregon

Cardiovascular disease is a major cause of morbidity and mortality in patients with schizophrenia. Every 1% increase in total cholesterol levels results in a 2% increase in the risk of coronary artery disease.

The number of patients taking combination therapy with atypical antipsychotic agents and divalproex sodium (DVPX) (Depakote tablet, Abbott) is increasing. Some antipsychotic agents are known to have an adverse effect on weight, serum lipids, and glucose. Preliminary data from patients with bipolar disorder and epilepsy suggest that DVPX lowers cholesterol levels. Limited animal studies suggest that valproic acid modifies cholesterol metabolism by enhancing hepatic peroxisomal beta oxidation and by reducing sterol synthesis from lactate or from 3-hydroxybutyrate. However, a systematic evaluation of cholesterol status has not been conducted in schizophrenic patients receiving antipsychotic agents in combination with DVPX.

Investigators conducted an analysis post hoc of 249 patients in a double-blind, randomized, multicenter trial of DVPX in combination with either olanzapine (OLZ) (Zyprexa medication, Eli Lilly) or canadian risperidone (RSP) (Risperdal generic, Janssen). Patients had been randomly assigned to take OLZ monotherapy (n = 65), RSP monotherapy (n = 60), or DVLP in combination with OLZ (n = 66) or RSP (n = 58). The mean age of the participants ranged from 38 to 40 years, and approximately 24% were women.

Mean doses of antipsychotic agents (days 6-28) were 15.0 mg/day for OLZ, 14.9 mg/day for DVPX + OLZ, 6.0 mg/day for RSP, and 6.0 mg/day for DVPX + RSP. The mean modal daily dose of DVPX (range, 500-3,500 mg/day) was 2,363 mg/day for DVPX + OLZ and 2,258 mg/day for DVPX + RSP. After four weeks, the total cholesterol increased from the baseline value by 26.62 mg/dl in the OLZ group, by 9.64 mg/dl in the RSP group, and by 0.87 mg/dl in the DVPX + OLZ group; it decreased by 13.44 mg/dl in the DVPX + RSP group.

The cholesterol levels of 56% of patients that had been in the normal range at baseline were shifted upward into the abnormal range after OLZ therapy. Adding DVPX cut this rate by about half. Approximately 28% of the cholesterol values in the RSP group became abnormal, and that figure was reduced by 5% with the addition of DVPX.

There were no correlations between baseline weight, body mass index, and total cholesterol changes. Increases in liver enzymes (serum alanine and aspartate transaminases, or AST and ALT) observed in the OLZ and RSP monotherapy groups were ameliorated with the addition of DVPX. There were no increases in the burden of side effects with the addition of DVPX, and there were fewer patient withdrawals from the study in the combination groups than in the monotherapy groups. canadian pharmacy

The investigators concluded that adding DVPX to OLZ or RSP therapy resulted in a decrease or in no change in total cholesterol levels. Further longer-term studies are under way.

Over the long-term, the 10% increase in total cholesterol observed at four weeks with OLZ represents a 20% to 30% increase in cardiovascular risk. The benefit of DVPX in preventing patients’ cholesterol values from being pushed up into the abnormal total range, combined with the improved antipsychotic efficacy of DVPX, is substantial. With combination treatment, it may be possible to reduce the typical length of a hospital stay for schizophrenic patients from 14 to seven days.