Effects of Antipsychotic Medications on Appetite, Weight, and Insulin Resistance

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Key points

  • Although some atypical antipsychotic drugs, particularly olanzapine and clozapine, have more severe weight-gain side effects, all antipsychotics, including typical antipsychotics currently used clinically, may cause some degree of weight gain.

  • There are time-dependent changes in weight gain associated with antipsychotic medication, with development of a 3-stage time course; in particular, rapid weight gain in the initial stage is a good indicator for a long-term outcome of weight gain and

Weight-Gain/Obesity Side Effects: Typical Versus Atypical APDs

It had been reported since the 1950s that treatment with some typical APDs (such as chlorpromazine) is associated with weight gain; however, many psychiatrists still hold believe that atypical APDs are associated with significant weight gain and obesity side effects, whereas typical APDs are not.14 For example, the commonly used typical APD, haloperidol, was once believed to have a minimal weight-gain side effect.14 However, a recent report on the European First-Episode Schizophrenia Trial

Effects of antipsychotic medication on appetite and food intake

Theoretically, gain in body weight results from an imbalance between energy intake and energy expenditure, whereby overeating and/or less energy expenditure (such as decreasing resting metabolism and activity) may contribute to overweight and obesity. Over the past 15 years, accumulated data from both clinical and animal studies suggest that increasing appetite and food intake, as well as delayed satiety signaling, are key behavioral changes related to APD-induced weight gain/obesity.32, 33, 34

Effects of Atypical APDs

Validated evidence over the past 20 years has indicated that APD medication significantly increases the risk of insulin resistance, glucose dysregulation, and the development of T2DM.5, 48, 49 Although patients with psychiatric disorders such as schizophrenia have been observed to have an increased risk of developing diabetes regardless of antipsychotics, suggesting that the disease itself may be a predisposing risk factor,50, 51, 52 APD medication has been widely recognized as a main

Neuropharmacologic mechanisms for APD-induced weight gain and glucometabolic side effects

In contrast to typical APDs (such as haloperidol) that are largely potent and selective D2 antagonists, atypical APDs have binding affinities for various neurotransmitter receptors, such as dopamine D2, serotonin 5-HT2A and 5-HT2C, adrenergic α1-2, muscarinic M1 and M3, and histamine H1 receptors.98 Among these receptors, dopamine D2 and 5-HT2 receptors play critical roles in the therapeutic effects of atypical APDs.99, 100 Accumulated evidence has revealed that the antagonistic properties of

Summary

Over the past 20 years it has been established that treatment with atypical APDs is associated with serious weight gain, obesity, and other metabolic side effects such as insulin resistance, glucose dysregulation, and T2DM; however, the metabolic side effects associated with some typical APDs are possibly underestimated. Emerging evidence over the past 5 to 6 years from the studies in first-episode psychotic and drug-naïve patients show that some commonly used typical APDs (such as haloperidol)

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    Funding Sources: This study was supported by a Project grant (APP1044624) from the National Health and Medical Research Council (NHMRC), Australia.

    Conflicts of Interest: None.

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