Antipsychotic-Induced Obesity: Histamine May Be the Key

Weight gain and onset of the metabolic syndrome associated with effective atypical antipsychotics (clozapine and olanzapine) are major clinical concerns and can lead to drug discontinuation or avoidance. The mechanism for these effects has not been clearly elucidated. Because hypothalamic AMP-kinase (AMPK) regulates food intake through the histamine H₁ receptor, these researchers examined the effect of antipsychotics on this system in a series of mouse experiments.

In vitro, clozapine and olanzapine increased levels of phospho-AMPK, and quetiapine had similar effects. This effect was selective for the hypothalamus and was not seen with risperidone, ziprasidone, haloperidol, or aripiprazole. In intact mice, clozapine increased hypothalamic AM…