Atypical antipsychotic-induced metabolic disturbances in the elderly.

The metabolic side effects of atypical antipsychotics (AAPs) have been widely studied in younger populations, but research investigating these sequelae in the elderly is lacking. This article reviews the available literature examining the use of AAPs in the elderly, evaluating their association with weight gain and changes in blood glucose and lipid parameters. We find a relative paucity of studies in this area; while some data highlight significant, collective changes in metabolic parameters, the majority suggests an apparent low vulnerability to these side effects. We conclude that the risk and clinical implications of unfavorable metabolic changes in the elderly being treated with AAP medications remain largely undetermined, and we caution against drawing firm conclusions based on the available data. The conflicting evidence leaves us recommending that metabolic monitoring be implemented, with regular follow-up as advocated in other populations.

Atypical antipsychotics and effects of adrenergic and serotonergic receptor binding on insulin secretion in-vivo: an animal model.

Atypical antipsychotics (AAPs) are associated with several metabolic sequelae including increased risk of type 2 diabetes. Growing evidence points to a direct drug effect of these compounds on glucose homeostasis, independent of weight gain. While the responsible mechanisms have yet to be elucidated, the heterogeneous binding profiles of AAPs likely include receptors involved in glucose metabolism. This study aimed to clarify weight-gain independent mechanisms of AAP-induced alterations in insulin secretion. Deconstruction of the receptor binding profiles of these agents was done using representative antagonists. Healthy rats were pre-treated with a single subcutaneous dose of prazosin 0.25mg/kg (n = 16), a selective α1 antagonist; idazoxan 0.5mg/kg (n = 10), a selective α2 antagonist; SB242084 0.5mg/kg (n = 10), a selective 5HT2C antagonist; WAY100635 0.1mg/kg (n = 10), a selective 5HT1A antagonist; MDL100907 0.5mg/kg (n = 8), a selective 5HT2A antagonist; or vehicle: 0.9% NaCl saline (n = 8), DMSO (n = 8), or cyclodextrin (n = 5). Hyperglycemic clamps were employed following injection, providing an index of secretory capacity of pancreatic ß-cells. Treatment with prazosin and MDL100907 resulted in significant decreases in both insulin and C-peptide secretion compared to their respective controls, DMSO and saline. These findings were corroborated with decreased glucose infusion rate and disposition index in the prazosin group. Results suggest that α1 and 5HT2A receptor antagonism may be involved in glucose dysregulation with AAP treatment, however, the exact mechanisms involved remain unknown.