The metabolic effects of olanzapine and topiramate in rats and humans

Evers, S. S., van Dijk, G., van Vliet, A. & Scheurink, A. J. W., Jul-2011, In : Appetite. 57, Supplement 1, p. S15 1 p.

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In humans the anti-psychotic Olanzapine (OLZ) has negative side effects on metabolism: it causes weight gain and increases the risk of developing type 2 Diabetes. The anti-convulsant Topiramate (TPM) has the opposite effects: it reduces body weight and improves insulin sensitivity. Because of this, it has been proposed
to use TPM to counteract OLZs side effects. The underlying mechanisms by which OLZ and TPM influence metabolism are unknown. To study this, we performed a series of studies in both
rats and humans. In rats we administered OLZ and TPM via a permanent intragastric cannula, to mimic oral drug administration, and found that chronic OLZ treatment stimulates weight gain and causes insulin resistance reflected by increased insulin responses during an intravenous-glucose tolerance test OLZ also
decreased locomotor activity and core temperature, pointing to a reduction in energy expenditure. OLZ also increased weight gain
in humans, accompanied with decreased daily physical activity, reduced body temperature and increased baseline and glucosestimulated
insulin levels during an oral glucose tolerance test. TPM reduced the OLZ-induced overeating and weight gain in both rats and humans combined with an increased postprandial satiety rating (in humans). We conclude that, in both rats and humans, a reduction in energy expenditure may explain, at least in part, the
OLZ effects on weight gain and that the OLZ-induced effects on insulin resistance has a peripheral side of action. We also conclude
that TPM may prevent the negative metabolic side effects induced by OLZ. Supported by: Top Institute Pharma.
Original languageEnglish
Pages (from-to)S15
Number of pages1
Issue numberSupplement 1
Publication statusPublished - Jul-2011
Event19th Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB), Clearwater, Florida, USA -
Duration: 12-Jul-201116-Jul-2011


19th Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB), Clearwater, Florida, USA


Event: Conference

ID: 38603569