Valproic Acid as a potentiator of metabolic syndrome in institutionalized residents on concomitant antipsychotics: fat chance, or slim to none?

Abstract

Background: Valproic acid (VPA) is one of the most commonly used antiepileptic medications worldwide; it is also a popular mood stabilizer for use in bipolar disorder and dementia. This study assessed whether VPA may potentiate metabolic side effects in patients with psychiatric disorders taking concomitant antipsychotics (APs). VPA alone has been associated with weight gain, dyslipidemia, hypertension, and diabetes. Patients with psychiatric disorders, especially those on second-generation (atypical) APs, appear to be at increased risk of these metabolic effects. A secondary purpose was to determine if a linear dose-response relationship exists between the VPA dose and adverse metabolic effects.

Methods: This cross-sectional study was conducted using data collected on all patients in the four state-operated psychiatric hospitals in Michigan using a comprehensive assessment instrument, the interRAI Mental Health. All patients taking both VPA and APs (n = 200) were compared to a control group of patients taking APs without VPA (n = 426). Patients were assessed for the presence of the following surrogate indicators of metabolic syndrome: weight gain; high body mass index (BMI greater than 30 kg/m(2)); very high BMI (BMI greater than 40 kg/m(2)); a diagnosis of diabetes mellitus; use of a prescribed statin medication; diagnosis of hyperlipidemia or dyslipidemia; hypertension; or the combination of any three of these factors: high BMI, hyperlipidemia or dyslipidemia, diabetes, and hypertension. Analysis also included assessment of the effect of VPA dosage on metabolic side effects.

Results: Patients in the VPA plus APs group were 3.2 kg heavier than those in the APs group (P = 0.05) at baseline. Compared with the APs group, the VPA plus APs group had a higher prevalence of high and very high BMI, diabetes, hypertension, and the combination of any three factors of high BMI, hyperlipidemia/dyslipidemia, diabetes, and hypertension. However, these differences were not statistically significant. Conversely, there was a slight but non-significant reduction in the prevalence of weight gain, prescribed statins, and hyperlipidemia/dyslipidemia in the VPA plus APs group than the APs group. Finally, higher doses of VPA were not found to be associated with a higher incidence of these metabolic side effects.

Conclusion: Although the patients on VPA were slightly more than 3 kg heavier, VPA did not appear to be associated with significant metabolic effects in patients with psychiatric conditions taking typical and atypical APs. These metabolic effects also do not appear to be related to the dose of VPA.

Figure 1

Study Design APs = antipsychotics; VPA = valproic acid