Low-dose clozapine and diabetic ketoacidosis

Indications:1 hospital patient with refractory schizophrenia. Coexisting diseases: obesity and polysubstance dependence.; Patients:One 22-year-old female inpatient of Hispanic and Italian origin who dropped-out due to side effect.; TypeofStudy:A case report of a woman who developed diabetic ketoacidosis while taking low dose Leponex.; DosageDuration:Increased in 25 mg/day increments to 125 mg daily over 3 weeks. During the 6th week, increased to 150 mg daily. Duration: 10 weeks.; Results:Urinalyses performed both before and 3 weeks after initiation of Leponex revealed neither abnormal glucose nor ketone levels. During the 6th week of Leponex treatment, the patient had a medroxyprogesterone injection, which she had received previously for birth control, and her Leponex dose was increased to 150 mg/day. She demonstrated a 6-pound (lb) weight loss, from 188 to 182 lb. Risperidone was tapered to 2 mg/day and benztropine to 1 mg/day. During the 9th week of Leponex treatment, the patient reported lethargy, menstrual spotting, cramping, breast tenderness, nausea, and vomiting. These symptoms appeared consistent with the effects of medroxyprogesterone. However, at the end of the 10th week, she acutely developed hyperventilation, shortness of breath, and chest discomfort, and she was transferred to an emergency ward. She was diagnosed with diabetic ketoacidosis (with a serum glucose level of 512 mg/dl, a pH level of 7.27, and ketonuria). Although she had no history of diabetes, her risk factors included obesity, a body mass index of 33 kg/m2 and 2 maternal aunts with noninsulin dependent diabetes mellitus. 1 month before starting Leponex, a random serum glucose measurement was 123 mg/dl. When diabetic ketoacidosis was diagnosed, her glycohemoglobin A1c level was 12.2% (normal range = 3.8%-6.4%). The patient was admitted to an intensive care unit, and Leponex was discontinued. She was treated initially with intravenous insulin, which was followed by use of subcutaneous insulin. Risperidone was reinstituted. Upon discharge from the hospital 5 days later, she required 38 units of isophane insulin twice daily (bid), and 20 units of regular insulin bid. Within 3 weeks of discontinuing Leponex, the patient no longer required insulin. While she was on a diabetic diet, her fasting serum glucose levels were between 80 mg/dl and 110 mg/dl. Her risperidone dose was increased to 5 mg/day, and her psychosis improved significantly.; AdverseEffects:1 patients experienced diabetic ketoacidosis, preceded by nausea, vomiting, hyperventilation, dyspnea and chest discomfort, which led to withdrawal.; AuthorsConclusions:Further research is warranted to learn more about the risk factors for clozapine-associated diabetes, to determine whether the dose of clozapine contributes to the risk for diabetic ketoacidosis, and to establish whether diabetes will resolve upon lowering of the dose or discontinuation of the medication; FreeText:The patient was admitted to the psychiatric unit with disorganized thinking, paranoia, and auditory hallucinations. She was unpredictably violent and injured several staff members. She remained symptomatic while taking risperidone 5 mg daily, and her serum prolactin level increased from 9.3 to 88 ng/ml (normal 0-22 ng/ml for women) thus Leponex was initiated. Concurrent medications included lorazepam (3 mg/day), risperidone (5 mg/day tapered to 2 mg/day), benztropine (2 mg/day tapered to 1 mg/day), a multivitamin, calcium supplements, and medroxyprogesterone (for birth control). Tests: urinalysis for glucose and ketone levels, serum glucose level, pH level, and glycohemoglobin A1c level.