Atypical Antipsychotics and Metabolic Complications

Abstract

Introduction: Second generation antipsychotics (SGA) such as olanzapine are often used for psychotic disorders due to their efficacy and fewer neurological side effects. However, they have been associated with weight gain, prediabetes, diabetes ketoacidosis (DKA), myopathy and rarely rhabdomyolysis. These side effects were reported in individual cases. Our case had both DKA and rhabdomyolysis with chronic olanzapine use of 9 years. Case: A 36 year-old AAM with schizophrenia on olanzapine and risperidone, diet-controlled hyperlipidemia, obesity and prediabetes (HbA1c 6%,) admitted with fatigue, polyuria, polydipsia and confusion. He was diagnosed with DKA with HbA1c 13.7%, rhabdomyolysis (CK 13000 units/L) and acute kidney injury (peak creatinine 12, eGFR<10), requiring insulin infusion, dialysis and mechanical ventilation. Olanzapine was discontinued; his creatinine and glucose improved. His C-peptide was 4.28 ng/ml. Anti-GAD and islet cell antibodies were negative. He was discharged on glargine and risperidone. Two months after discharge, HbA1c was 5.8%, creatinine 1 (eGFR>60) and insulin was stopped. Discussion: This case highlights the importance of monitoring patients on SGA for metabolic complications. Olanzapine’s association with DKA is rare and with rhabdomyolysis is very rare. Several mechanisms for SGA-induced glucose intolerance exist, the most common being the antagonistic effect of olanzapine on serotonin 5HT2C and histamine (H1) receptors in the hypothalamus which leads to increased appetite and weight gain (our patient gained 40 lbs). Additionally, few reports on the association between olanzapine and rhabdomyolysis have been published. The mechanism remains unclear but may be due to drug-related myopathy secondary to high affinity for H1, 5-HT2A and D2 receptors. It is possible that the development of DKA predisposed our patient to developing rhabdomyolysis. Disclosure M. Akunjee: None. S.M. Gandhi: None. E. Nylen: None.

Diabetes Mellitus: An Unrecognized Complication in the Management of Patients With Mental Illness

“…Most of the patients in other studies had elevated HbA1C, suggesting undiagnosed T2DM at least several weeks before psychiatric patients presented to ED with complications [4]. Antipsychotics contribute to glucose intolerance through serotonin receptor (5HT2C) and histamine receptor (H1) antagonism in the hypothalamus resulting in increased appetite, weight gain, and insulin resistance [5]. In our case, the patient presented with an HbA1c of 13.6%, confirming undiagnosed DM.…”

Olanzapine-Induced Diabetic Ketoacidosis: A Reversible Etiology Overlooked in Psychiatric Patients

“…This includes hepatic glucose production through the activation of hypothalamic adenosine 5’-monophsphate-activated protein kinase, which antagonizes serotonin 5HT2C, histamine H1, dopamine D2, and alpha-1 adrenergic receptors. 1 , 10 Olanzapine can directly influence pancreatic beta-cells via apoptosis and/or impairing insulin secretion at an early stage of treatment. 11 It can cause stress on the endoplasmic reticulum in beta-cells, as seen by activation of stress sensor PKR-like endoplasmic reticulum kinase.…”