Atypical antipsychotics and the neural regulation of food intake and peripheral metabolism

Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA.
Physiology & Behavior (Impact Factor: 3.03). 06/2011; 104(4):590-8. DOI: 10.1016/j.physbeh.2011.05.033
Source: PubMed

ABSTRACT The atypical antipsychotics (AAPs) are associated with weight gain and an increased incidence of metabolic disease including type 2 diabetes mellitus. Epidemiological, cross-sectional and prospective studies suggest that two of the AAPs, olanzapine and clozapine, cause the most dramatic weight gain and metabolic impairments including increased fasting glucose, insulin and triglycerides. Relative to the other AAPs, both olanzapine and clozapine exhibit a particularly high antagonistic affinity for histamine and muscarinic receptors which have been hypothesized as mediators of the reported increase in weight and glucose abnormalities. In this article, we review the current evidence for the AAP associated weight gain and abnormal glucose metabolism. We postulate that the effects of the AAPs on food intake and peripheral metabolism are initially independently regulated but with increasing body adiposity, the early AAP-induced impairments in peripheral metabolism will be exacerbated, thereby establishing a vicious cycle such that the effects of the AAP are magnified by the known pathophysiological consequences of obesity. Furthermore, we examine how inhibition of the histaminergic pathway may mediate increases in food intake and the potential role of the vagus nerve in the reported peripheral metabolic effects.

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    • "There are interrelated hypotheses that have been proposed to explain antipsychotic-induced MetS. One hypothesis is that SGAs cause a dysregulation of hormones that control appetite and food intake such as insulin, leptin , adiponectin, and ghrelin (Sentissi et al., 2008; Teff and Kim, 2011; Stip et al., 2012). Most studies investigating this have focused on just a few metabolic mediators and Address for correspondence: C. "
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    • "AAPDs interact not only with DA but also 5-HT (Miyamoto et al., 2005). One of the side effects of AAPDs is weight gain (Ananth et al., 2004; Newcomer, 2005; Teff and Kim, 2011), which would be a welcomed effect for patients with AN. Current studies show that olanzapine treatment induces a decrease in anxiety and depression in AN patients (Bissada et al., 2008), but a larger scale study is required to determine whether this type of AAPD has any effect on improving food consumption in AN patients. "
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