Risk evaluation of diabetic ketoacidosis associated with antipsychotics among patients with schizophrenia in the Japanese adverse event report database

Abstract

Objective: Diabetic ketoacidosis (DKA) is a serious life-threatening condition and can be associated with antipsychotic medication. Asian patients with diabetes exhibit less insulin resistance than Caucasians; however, all previous studies concerning antipsychotic-related DKA have been conducted in Western populations. We analyzed the rank order of the association of antipsychotic agents for schizophrenia with DKA using the Japanese Adverse Drug Event Report database, a spontaneous reporting system database.

Methods: We performed a retrospective pharmacovigilance disproportionality analysis using adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between April 2004 and March 2021. The study population comprised 7435 patients with schizophrenia, and the total number of antipsychotic-related DKA reports was 55.

Results: Among the 55 cases of DKA in patients with schizophrenia, 6% (3/55) patients died after DKA. The signals of DKA were reported after treatment with olanzapine, with a significant adjusted reporting odds ratio (95% CI) of 3.26 (1.87-5.66). In 1399 olanzapine treatment cases, multivariable logistic regression analysis using a forward selection method showed that being male (adjusted RORs 2.72 (1.07-6.90)) was associated with the onset of DKA.

Conclusion: Our study revealed that treatment with olanzapine was associated with the development of DKA among patients with schizophrenia. The results also clarified that male patients were at higher risk for DKA among patients treated with olanzapine. The application of these data will aid in risk monitoring and management that may reduce the occurrence of antipsychotic-related DKA in treatment for schizophrenia.

Keywords: Adverse drug reaction; Antipsychotics; Diabetic ketoacidosis; Schizophrenia.