Ketoacidosis as a side-effect of clozapine: a case report

Arta Psychiatr Scand 1996: 93: 217-218 Printed in UK - ull rights reserved

Copyright 0 Munksgaard 1996

ACTA PSYCHIATRICA SCANDINAVICA ISSN 0001-69OX

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Ketoacidosis as a side-effect of clozapine: a case report Kostakoglu AE, Yazici KM, Erbas T, Guvener N. Ketoacidosis as a sideeffect of clozapine: a case report. Acta Psychiatr Scand 1996: 93: 217-218. 0 Munksgaard 1996. We report the case of a patient fulfilling DSM-IV criteria for schizophrenia and treated with clozapine who later developed hyperglycemia and ketoacidosis.

A. E. Kostakoglu', K. M. Yazici', T. Erbas*, N. Giivene? 'Department of Psychiatry. Hacettepe University Faculty of Medicine, *Department of Endocrinology, Hacettepe University Faculty of Medicine, Ankara, Turkey

Key words: clozapine; diabetes; hyperglycemia, ketoacidosis

KBzim M. Yazici, Hacettepe Universitesi Tip Fakultesi, Psikiyatri A.B.D (56). Ankara 06100, Turkey

Accepted for publication September 2, 1995

Clozapine is an atypical antipsychotic drug which is shown to be superior to classical neuroleptics in schizophrenic patients with treatment refractory symptoms and negative symptoms. It has lesser extrapyramidal side-effects than standard neuroleptic compounds ( 1 ). Clozapine's actions, not only on D2 receptors but also on D1, D3, D4, 5HT2 and 5HT3 receptors, and its differential affinity for striatal and limbic D2 receptors are hypothesized to be responsible for its unique clinical properties. Regarding its side-effect profile, clozapine has a higher likelihood of causing seizures than other neuroleptics, and is associated with a relatively high rate of agranulocytosis (2). We would like to report on a case of diabetic ketoacidosis associated with clozapine treatment. To our knowledge, two previous reports have documented the development of hyperglycemia ( 3) and diabetic ketoacidosis (4) with the use of clozapine. Case report

Mr. Y, a 42-year-old, obese man weighing 130 kg, has a 9-year history of persistent bizarre delusions of a persecutory nature. Neuroleptic therapy had been of partial benefit. He was admitted to our psychiatric ward because of exacerbation of his psychotic symptoms. His routine blood chemistry examinations were unremarkable, with the exception of a slight increase in serum glucose level

(121 mg/dl). He had no known history of diabetes, although he had a family history of type I1 diabetes. A regimen of clozapine was started, 25 mg per 0s once a day, and the dosage was gradually increased to 200mg per 0s twice a day for 10 days. The patient did not tolerate this medication regimen well. He complained of drowsiness, sialorrhea, increased urinary frequency and urinary incontinence. Clozapine was decreased to a dose of 350 mg/day. Towards the end of the fourth week of the treatment, the patient showed marked improvement in his psychotic symptoms. However, he began complaining of extreme weakness and a bitter taste in his mouth. Within a few days, sweating, anorexia, blurred vision, diplopia and a state of stupor were added to the symptoms. Laboratory examinations revealed a serum glucose level of 447 mg/dl, glucosuria 4 + and ketonuria 4 + . Plasma osmolality was 312 mOsm/kg. Immediately after making the diagnosis of ketoacidosis, intravenous hydration and a regimen of insulin infusion was started. Considering that clozapine might have caused ketoacidosis, its administration was gradually decreased and terminated. Fluphenazine decanoate was started, 25 mg intramuscularly, every 15 days. On the fourth day of the insulin treatment, the patient was switched to subcutaneous regular insulin injections (40 units of isophane, 20 units of regular insulin in the morning and 20 units of isophane, 10 units of regular insulin in the evening). As symptomatic 217

Kostakoglu et al. hypoglycemia episodes appeared after the 15th day of subcutaneous insulin therapy, the insulin treatment was gradually withdrawn. At that time, fasting blood glucose was measured to be 93 mg/dl and 2 h postprandial blood glucose was 108 mg/dl. The level of C-peptide was 1.25 pmol/ml. Oral glucose tolerance test was compatible with impaired glucose tolerance. The patient was discharged on a diabetic diet of 1400 kcal per day and remained metabolically stable.

insulin-dependent hyperglycemia and diabetic ketoacidosis developed. After discontinuation of clozapine, hyperglycemia completely resolved. This case demonstrates that clozapine alone is responsible for the development of diabetic ketoacidosis in a patient who has impaired glucose tolerance. For that reason, we agree with Koval et al. that blood glucose levels should be closely monitored in patients with a family history of diabetes or impaired glucose tolerance.

Discussion

References

Kamran et al. reported the first insulin-dependent hyperglycemia precipitated by clozapin therapy ( 3 ). Their patient had used benztropin and ranitidine in combination with clozapine. Koval et al.’s patient had developed diabetic ketoacidosis associated with concomitant use of clozapine and lithium ( 4 ) . Neither author completely excluded the effects of other medications on impaired glucose metabolism. Unlike the other reported cases, our patient was being treated with clozapine as monotherapy when

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