PhD Defence 03.04.2017 - Aleksei Rakitin

Aleksei Rakitin will defend his doctoral thesis titled „Metabolic effects of acute and chronic treatment with valproic acid in people with epilepsy“ on 3 April 2017 at 14:00.

Supervisors:
Associate Professor Sulev Haldre (UT Institute of Clinical Medicine)
Professor Sulev Kõks (UT Institute of Biomedicine and Translational Medicine)

Opponent:
Professor Torbjörn Tomson (MD, PhD), Karolinska University Hospital, Stockholm, Sweden

Summary: Valproate (VPA) is one of the most frequently prescribed antiepileptic drugs (AEDs), with more than one million people around the world estimated to be taking VPA every day. One of the most common side effects of VPA treatment is weight gain, which could be associated with important metabolic and endocrine abnormalities. However, only a few studies, with conflicting results, have examined the presence of metabolic syndrome (MS) in VPA-treated patients with epilepsy. The precise pathogenic mechanism underlying VPA-induced weight gain is also still unclear. The aims of the current study were to estimate the prevalence of MS and its components among people with epilepsy treated with VPA, to compare it to the general population, and to the people with epilepsy treated with other AED – carbamazepine (CBZ), as well as to describe the effect of acute intravenous VPA treatment on the blood levels of glucose and the influence of chronic VPA treatment on the gene expression in patients with epilepsy. We found that that the prevalence of MS in patients with epilepsy who received VPA treatment was 25.8%, which did not differ from the Estonian general population and CBZ-treated patients. However, females treated with VPA tended to have a higher risk of MS compared to males. Therefore, in females with a higher risk of cardiovascular diseases, AEDs other than VPA could be considered first. Longer duration of VPA treatment and higher dose also tended to increase the risk of MS. The surprisingly small number of genes, which were differently expressed before and after the start of VPA treatment, is explained by the relatively low doses of VPA that were used. Therefore, to minimize the potential side effects of increased gene expression, it is recommended that the lowest effective dose of VPA be used for treating epilepsy. Intravenous VPA administration decreased glucose levels during oral glucose tolerance test directly following the initial VPA exposure. This finding could explain an increased appetite in VPA-treated patients that results in weight gain. The results of our study provide additional information about the risks related to the VPA treatment, which helps to use this effective AED more safely.