Basic and Clinical Research Based on Clinical Questions: Reduction of Antipsychotic Medication-induced Adverse Events

Antipsychotics are widely used to manage mental illnesses. They have, however, been reported to cause various adverse events. Two studies were conducted to resolve clinical questions related to adverse events caused by antipsychotic medications in clinical practice. The first adverse event studied was clozapine-induced sialorrhea (CIS), a common adverse event. There is no established standard treatment for CIS because the underlying mechanism remains unclear. Therefore, this study aimed to identify the cause of CIS. Results of clinical and basic studies suggest that N-desmethylclozapine (NDMC), the active metabolite of clozapine, is the causative agent of CIS. Furthermore, the action of NDMC on salivary gland cells via muscarinic receptors is one of the proposed mechanisms of CIS. The second adverse event was hyperglycemia. Antipsychotics increase the incidence of hyperglycemia. However, the incidence of antipsychotic-induced hyperglycemia is difficult to predict because many factors are involved. This study aimed to examine the effect of antipsychotic treatment-associated factors on hyperglycemic progression after adjustment for the effect of background factors suggested to be associated with hyperglycemic progression. A national multicenter prospective observational study of 631 newly initiated patients showed that initiation of clozapine and zotepine treatment significantly increased the incidence of hyperglycemia. In addition, obesity has been shown to significantly increase the incidence of antipsychotic-induced hyperglycemia. Because these studies were conducted to resolve questions that arose in actual clinical practice, the study results obtained are considered to have clinical applicability.