Olanzapine apparently alters the way the brain anticipates food and experiences the reward of eating – changes that might predispose patients taking the drug to rapid weight gain, a study has shown.
Healthy, normal-weight volunteers who took the drug for a week gained a mean of 1 kg – a significant change from baseline. Brain imaging showed altered activity in areas involved with anticipation, reward response, and satiety, Dr. Jose Mathews and his colleagues reported in the August issue of Archives of General Psychiatry (doi:10.1001/archgenpsychiatry.2012.934).
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A recent study explores how olanzapine may alter the way the brain anticipates food and experiences the reward of eating and how that may predispose patients taking the drug to gain weight rapidly.
"Interestingly, subjects’ perception of hunger did not change significantly after olanzapine treatment nor did their perception of the pleasantness," of morning food intake, wrote Dr. Mathews of Washington University in St Louis and his coauthors. "These findings contrast to the actual behavior of the subjects ... as they consumed significantly more breakfast and gained weight after treatment with olanzapine."
The study comprised 19 young people (mean age, 27 years) with a mean body mass index of 25.78 kg/m2. On the first night, they took 5 mg of olanzapine. They took 10 mg each night for the next 6 nights.
Each night, all of the volunteers stayed at the investigation site. Every morning, they had a functional magnetic resonance imaging session during which they saw images of chocolate milk, tomato juice, or water. After identifying which drink they preferred, they received a small portion through a tube, then rated their choices (very pleasant, pleasant, neutral, unpleasant, and very unpleasant) on a 5-point Likert scale.
After the scan, they consumed a breakfast of the liquid they had chosen and were instructed to drink until they were no longer hungry. Then all were rescanned.
A significant increase was found in the mean amount of breakfast consumed, from about 25 ounces at baseline to about 32 ounces by day 7. The subjects gained a mean of 1.1 kg over the course of the 1-week study.
They also showed a significant increase in the disinhibited eating subscale of the Three-Factor Eating Questionnaire. However, no changes were found in their feeling of hunger or in how pleasant they perceived their drink to be.
Brain imaging, however, showed definite changes in regions involved with anticipation and reward, the authors said.
"In the caudate and putamen, activation to the experience of rewarding taste increased after olanzapine treatment while the response to [water] decreased," the investigators wrote. The drug also affected the inferior frontal cortex, striatum, and anterior cingulate. "All these regions showed enhanced responses to cues predicting rewarding liquids after olanzapine, while there was a decrease in activation elicited by the picture of the [water]."
They also observed decreased activity in the lateral orbital frontal cortex, a region involved in satiety. "These fMRI changes suggested an enhanced anticipatory desire for food, an enhanced reward experience of [eating], and a compromised satiety-related mechanism. This pattern of change after treatment with olanzapine provides a plausible set of mechanisms that may contribute to the weight gain commonly associated with this medication."
The investigators cited several limitations of the study. The absence of a placebo control group limited their ability to show conclusively that the observed changes were tied to olanzapine treatment. Also, the subjects’ unmedicated scan always came before the scan with olanzapine, which means "it is possible that habituation effects could be confounded with the olanzapine effects."
Despite these limitations, Dr. Mathews and his colleagues said they think their findings might "pave the way for targeted treatments that may help dial down the enhanced reward value of food while strengthening the inhibitory circuits that control food intake."
The study was sponsored by the National Alliance for Research on Schizophrenia and Depression, and the National Institutes of Health. Dr. Mathews has been on the speakers bureaus of Janssen Pharmaceuticals and Bristol-Myers Squibb, but had no current financial disclosures.