Olanzapine shifts the temporal relationship between the daily acrophase of serum prolactin and cortisol concentrations rhythm in healthy men

Abstract

Treatment with the atypical antipsychotic drug olanzapine is frequently associated with development of obesity and insulin resistance. Treatment-induced weight gain has been suggested to be the main contributing factor of diminished insulin sensitivity. This study evaluated the effects of short-term treatment with olanzapine on 12h plasma prolactin and cortisol concentrations in healthy men. The effects of two distinct olanzapine formulations were investigated; the oral standard tablets (OST) and the orally disintegrating tablets (ODT). Recent reports indicate that treatment with the ODT formulation may be less harmful in terms of weight gain than the OST. 12 healthy men (age: 25.1+/-5.5 y) received olanzapine OST (10mg QD, 8 days), olanzapine ODT (10mg QD, 8 days) or no intervention in a randomized cross-over design. On day 8, blood samples were taken every 10min between 0000 and 1200h for determination of cortisol and prolactin concentrations. Treatment with olanzapine OST and ODT similarly increased the 12h mean PRL concentrations and the secreted PRL mass. Both drugs similarly shifted the maximal PRL concentration approximately 3-4h backwards in time. Cortisol secretions rates were lower, but the timing of the cortisol acrophase did not change. Both drugs significantly elevated HOMA index for insulin resistance. In conclusion olanzapine OST and ODT equally elevated the prolactin concentration and significantly shifted its acrophase, thus dissociating PRL and cortisol, while both formulations induced similar insulin resistance as evidenced by the elevated HOMA-IR. Notably, these alterations occurred without a measurable effect on body adiposity.