The relationship of changes in leptin, neuropeptide Y and reproductive hormones to antipsychotic induced weight gain

Hum Psychopharmacol. 2003 Oct;18(7):551-7. doi: 10.1002/hup.519.

Abstract

Objectives: Weight gain is an important side effect of antipsychotic (AP) treatment. Weight is regulated by multiple systems, including leptin, neuropeptide Y (NPY) and gonadal steroids. The aim was to investigate whether AP-induced weight gain was related to leptin and NPY abnormalities and whether these were associated with a disruption of gonadal steroid production.

Methods: Twenty two female patients with schizophrenia receiving standard AP treatment were studied over a 3-month period. Plasma leptin, NPY, gonadal steroids and their regulators were measured along with weight and BMI.

Results: Weight, leptin and testosterone levels increased over time. There were significant relationships between a change in oestrogen levels and both a change in NPY levels and a change in BMI. Change in BMI, weight and leptin all correlated strongly with a change in the testosterone/luteinizing hormone ratio.

Conclusions: AP treatment results in increase in weight over time and this increase is accompanied by increased leptin levels. AP-induced weight gain is also associated with disruption of the hypothalamic-pituitary-gonadal axis. Altered regulation of NPY, either through abnormal leptin control or serotonin blockade, is a possible explanation for the effects of AP medication on both weight and gonadal steroid levels.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adult
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Benzodiazepines
  • Female
  • Gonadal Steroid Hormones / blood*
  • Humans
  • Leptin / blood*
  • Middle Aged
  • Neuropeptide Y / blood*
  • Olanzapine
  • Pirenzepine / adverse effects
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / therapeutic use
  • Radioimmunoassay
  • Risperidone / adverse effects
  • Risperidone / therapeutic use
  • Schizophrenia / drug therapy
  • Time Factors
  • Weight Gain / drug effects*

Substances

  • Antipsychotic Agents
  • Gonadal Steroid Hormones
  • Leptin
  • Neuropeptide Y
  • Benzodiazepines
  • Pirenzepine
  • Risperidone
  • Olanzapine