Hyperosmolar Hyperglycemic State in a Patient Taking Risperidone

Sir: The association of neuroleptics with metabolic disturbances has been well described.¹ Several reports have associated atypical antipsychotics with hyperosmolar hyperglycemic state (HHS); however, most cases have involved olanzapine.^2,3 This letter reports a case of HHS associated with risperidone use.

Case report

Mr. A, a 39-year-old man with Asperger disorder, presented to the emergency department in August 2007 complaining of a 1-day history of general malaise, vomiting, polyuria, and polydipsia. His medical history included hypertension, hypercholesterolemia, and a seizure disorder treated with carbamazepine. His other medications included hydrochlorothiazide, ranitidine, and atenolol.

Three years prior to admission, Mr. A was diagnosed with schizophrenia-like psychosis of epilepsy. His carbamazepine dose was increased to 600 mg/day, and he was started on treatment with 4 mg/day of risperidone. At the time, he weighed 102 kg and had not been diagnosed with diabetes. Over the next 10 months, his weight increased to 122 kg. He displayed neither seizure activity nor return of psychosis; however, he did complain of depressed mood. He was started on treatment with 10 mg/day of paroxetine, which relieved some symptoms. His weight increased to 135 kg over 12 weeks.

On examination at the time of the current presentation, Mr. A displayed tachycardia, globally decreased cognitive ability, and intermittent left upper extremity clonus. Laboratory evaluation revealed a serum glucose level of 1179 mg/dL, a creatinine level of 2.7 mg/dL, a blood urea nitrogen level of 42 mg/dL, a potassium level of 4.0 mmol/L, and an anion gap of 22 mEq/L. The patient's blood osmolality was elevated at 378 mOsm/kg water. His carbamazepine level was therapeutic at 6.0 μg/mL. His glycosylated hemoglobin (HbA_1c) level was 14.6%. His cholesterol, triglycerides, and low-density lipoprotein levels were all elevated. Electroencephalogram revealed generalized slowing, and results of computed tomography of the head were within normal limits. Mr. A showed no evidence of infection. He was admitted to the medical intensive care unit for treatment of HHS.

Fluid and electrolyte management, 2 important therapies in HHS treatment, were applied. Regarding the psychotropics, treatment with risperidone was discontinued, paroxetine was tapered, and an appointment was scheduled for outpatient psychiatric care. Mr. A was also discharged with subcutaneous insulin treatment.

This patient experienced a severe alteration in metabolic parameters while taking an atypical antipsychotic. His weight increased with use of risperidone, and then increased at a faster rate with the coadministration of paroxetine. While this patient was obese prior to risperidone therapy, he carried no diagnosis of type 2 diabetes mellitus until this admission. A recent review of schizophrenic patients treated with atypical antipsychotics diagnosed with diabetes presenting as diabetic ketoacidosis revealed only 1 case associated with risperidone use.⁴ The patient's HbA_1c level of 14.6% implies that he had elevated glucose levels, and undiagnosed type 2 diabetes mellitus, for at least several weeks prior to admission. This patient's risk factors for type 2 diabetes mellitus included obesity, hypertension, dyslipidemia, and neuroleptic therapy.

It is appropriate to perform diabetes screening for at-risk patients receiving neuroleptic therapy.⁵ This case demonstrates the metabolic syndrome presenting as HHS in a patient taking risperidone.