Metabolic dysregulation in early onset psychiatric disorder before and after exposure to antipsychotic drugs

Antipsychotic Drugs (APDs) are being widely prescribed to treat various disorders, including schizophrenia and bipolar disorder; however, abnormal glucose metabolism and weight gain have been reported with Atypical Anti-Psychotic drugs (AAPDs) that can lead to insulin-resistance and type 2 diabetes mellitus. The study was designed to assess various biochemical parameters including insulin and blood sugar before and after exposure to APDs in order to exclude the involvement of psychiatric disorders and certain other factors in metabolic dysregulations. Fifty seven APDs-naïve patients with first episode psychosis were divided into six groups who received olanzapine, quetiapine, risperidone, aripiprazole, haloperidol or combination of olanzapine with escitalopram and haloperidol. The serum samples were taken before the intake of the first dose and then on follow-up. Decrease in the level of elevated insulin and glucose was observed post-treatment in some patients, while others were observed whose insulin and glucose levels increased post-treatment, yet some patients did not show any disturbance in the insulin and glucose levels. It is concluded that psychiatric disorders by itself, narcotics, cigarette smoking and use of oral snuff may be also be implicated in metabolic dysregulations. The effects of APDs on insulin and glucose in healthy volunteers might be different than in patients with psychiatric disorders.

Comparative evaluation of pancreatic histopathology of rats treated with olanzapine, risperidone and streptozocin

Olanzapine and risperidone are widely prescribed atypical antipsychotics used in the treatment of schizophrenia and various other psychiatric disorders. Both of these drugs have been extensively reported to cause Type 2 diabetes mellitus and pancreatitis, however, the mechanism of olanzapine and risperidone-induced toxicity has not been so far unveiled. We, therefore, compared the streptozocin-induced pancreatic damage with that of pancreas isolated from olanzapine and risperidone treated rats. It was noticed that fibrotic growth, necrosis and derangement of the pancreatic islet cells caused by streptozocin were more pronounced than olanzapine and risperidone.

Short-term oral administration of risperidone induces pancreatic damage and hyperamylasemia in Sprague-dawley rats

Risperidone is an atypical antipsychotic acting mainly as a dopamine D2 and serotonin 5-HT2 receptors antagonist prescribed in the treatment of schizophrenia and various affective disorders. Risperidone has been reported to be associated with weight gain, panreatitis and type 2 diabetes mellitus. Various mechanisms of risperidone-induced toxicities have been reported but the histology of tissues especially pancreas has never been studied. Therefore, the current study was designed to elucidate the toxic effects of chronic administration of risperidone on pancreas, liver and kidneys. Animals (rats) of either gender were divided into two groups, the risperidone and control groups. Risperidone was administered in a dose of 2.5 mg/kg/d for three weeks. The controls received acidified saline only. Both the groups received restricted diet (20 g/12 h). The body weight and level of random blood sugar (RBS) were measured on a weekly basis. The levels of lipase and amylase were determined at the conclusion of the experiment. At the end of the experiment, the tissues were dissected out for histopathological evaluation. Risperidone showed no weight gain, hyperglycemia or rise in the level of lipase (P> 0.05); however, the level of amylase was raised (***P<0.05). Histological examination under light microscope showed no hepatotoxicity, nephrotoxicity but did show damage to the pancreas. The findings of this study indicated that the incidence of adverse effects associated with risperidone could be prevented/alleviated/delayed by allowing restricted diet.