Case Presentation: A 26-year-old male with a history of schizophrenia presented with generalized abdominal pain and altered mental status. He has a history of multiple psychiatric admissions, specifically seven times in the past two years, and long-term antipsychotic usage. Most recently, he was discharged on clozapine, divaloproex, and trazodone. Initial physical exam was notable for tachycardia and tachypnea, and the patient arousable to auditory stimuli, but very somnolent. He was found to have metabolic acidosis (pH 7.10) with an anion gap of 27, beta-hydroxybutarate 10.28, and glucose 843. Although his most recent HbA1c was 5.0 and was never previously diagnosed with diabetes mellitus, he was admitted to the ICU for DKA. Repeat HbA1c on this admission was 9.3. Further studies, including C-peptide, insulin antibody, islet cell antibody, and glutamic acid decarboxylase antibody were negative. His antipsychotic medications were held and conventional treatment of DKA was initiated with prompt resolution of anion gap metabolic acidosis and hyperglycemia. On discharge, the patient was continued on clozapine and started on lantus and metformin.
Discussion: SGAs are commonly used in the treatment of schizophrenia, and act by blocking post-synaptic dopamine D2 receptors. Most SGAs are associated with weight gain and glucose intolerance. These agents are also known to impair insulin secretion and sensitivity, and promote apoptosis of pancreatic beta cells. As a result, rates of diabetes mellitus are higher in patients taking antipsychotics compared to the general population, especially with olanzapine and clozapine usage1. DKA is a rare, but fatal, complication associated with SGA use and can be the first sign of antipsychotic medication associated diabetes mellitus2. In the acute treatment of antipsychotic-associated DKA, the medication should be discontinued, and insulin and fluid resuscitation should begin promptly. Post-DKA management addresses both the underlying psychiatric illness and the insulin resistance. Depending on the patient, options include switching to a different antipsychotic medication or reintroducing the same agent. In a literature review of antipsychotic-associated DKA, anti-diabetic treatment was not needed in most cases where the antipsychotic was discontinued after resolution of DKA, however many patients who were reintroduced to the DKA-inducing medication required oral hypoglycemic or insulin therapy on discharge3. Clozapine, one of the most common SGA’s to cause DKA, is a medication only used in patients who have failed multiple other therapies. This presents a difficult decision, as it did in this case as the patient has limited other treatment options.
Conclusions: Increased awareness of the adverse effects of SGAs among clinicians and patients is essential to promote periodic diabetes screening, promptly discontinue offending agents in DKA, and ensure adequate follow up.