Atypical Antipsychotics and Metabolic Complications

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.