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Risperidone-Associated Diabetic Ketoacidosis

Key Words: Risperidone • Diabetes • Ketoacidosis

TO THE EDITOR: In the July-August issue of Psychosomatics, Croarkin et al.¹ reported what is described as the first case of risperidone-associated diabetic ketoacidosis and what to our knowledge is the first published report of new-onset diabetes associated with risperidone treatment. Multiple case reports have previously described disturbances in glucose metabolism, including diabetic ketoacidosis during the treatment of psychotic disorders with clozapine² and olanzapine,^3,4 including a fatality attributed to diabetic ketoacidosis during olanzapine use.⁵ Conventional antipsychotic medications can also have adverse effects on glucose metabolism. Given the acute and long-term complications of diabetes, it is important to clarify the risk associated with different medications in different patient populations. The report from Croarkin et al. concerned a 42-year-old HIV+ male with a history of chronic major depressive disorder with psychotic features. The interpretation of this adverse event, and the possible contribution of risperidone therapy, is confounded by the presence of major risk factors for diabetes in this particular patient that the authors did not discuss in their report.

Not mentioned is that a major depressive disorder itself approximately doubles the risk of developing diabetes mellitus.⁶ Glucose intolerance and diabetes are also associated with HIV infection,⁷ further increasing this patient's risk for diabetic complications independent of antipsychotic treatment. It was also not mentioned in the report whether this patient was taking a protease inhibitor as part of highly active antiretroviral therapy (HAART). Protease inhibitors are strongly associated with hyperglycemia, glucose intolerance, new-onset diabetes mellitus, and exacerbation of existing diabetes mellitus,⁸ with the Food and Drug Administration issuing an advisory in 1997 on this topic. The interpretation of risperidone's role in this event is thus confounded by the additional major risk factors of depression, HIV infection, and possible protease inhibitor therapy.

Clinicians should be aware that antipsychotic medications, particularly some newer agents, have been associated with hyperglycemia, exacerbation of existing diabetes mellitus, new-onset diabetes mellitus, and diabetic ketoacidosis. However, the magnitude of this effect appears to vary across individual medications, with risperidone appearing to have smaller effects on glucose metabolism than either clozapine or olanzapine.^9,10 At this time the only other published reports involving risperidone describe its uncomplicated use in patients diagnosed with diabetes.^11–13 Although more information concerning possible adverse metabolic effects of antipsychotic medications is needed, it will be most useful when relevant information is analyzed and discussed within the context of other established factors that impact glucose metabolism (e.g., adiposity, ethnicity, concomitant illnesses, and other medication effects). Regarding Croarkin et al.'s comment that blood glucose should be periodically tested in patients on risperidone, we feel that patients taking any antipsychotic medication should undergo periodic evaluation of plasma glucose (e.g., annual fasting glucose, baseline, and serial samples when starting and titrating new medications).

REFERENCES

1. Croarkin PE, Jacobs KM, Bain BK: Diabetic ketoacidosis associated with risperidone treatment? (letter) Psychosomatics 2000; 41:369–370
2. Colli A, Cocciolo M, Francobandiera F, et al: Diabetic ketoacidosis associated with clozapine treatment (letter). Diabetes Care 1999; 2:176–177
3. Paizis M, Cavaleri S, Schwarz ME, et al: Acute-onset ketoacidosis during olanzapine treatment in a patient without pretreatment obesity or treatment-associated weight gain. Primary Psychiatry 1999; 6:37–38
4. Goldstein LE, Sporn J, Brown S, et al: New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychosomatics 1999; 40:438–443[Free Full Text]
5. Von Hayek D, Huttl V, Reiss J, et al: Hyperglycemia and ketoacidosis associated with olanzapine. Nervenarzt 1999; 70:836–837[CrossRef][Medline]
6. Eaton WW, Armenian H, Gallo J, et al: Depression and risk for onset of type II diabetes: a prospective population-based study. Diabetes Care 1996; 19:1097–1102
7. Carr A, Samaras K, Thorisdottir A, et al: Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet 1999; 353:2093–2099
8. Vigouroux C, Gharakhanian S, Salhi Y, et al: Diabetes, insulin resistance and dyslipidaemia in lipodystrophic HIV-infected patients on highly active antiretroviral therapy (HAART). Diabetes Metab 1999; 25:225–232[Medline]
9. Henderson DC, Cagliero E, Borbs CP, et al: Atypical antipsychotic agents and glucose metabolism: Bergman's MINMOD Analysis. NCDEU Poster 2000
10. Selke GJ, Newcomer JW, Fucetola R, et al: Atypical antipsychotic-induced differences in glucose regulation in schizophrenia independent of differences in adiposity. Society for Neuroscience Abstracts 2000; 26:275
11. Wirshing DA, Spellberg BJ, Erhart SM, et al: Novel antipsychotics and new onset diabetes. Biol Psychiatry 1998; 44:778–783[CrossRef][Medline]
12. Melamed Y, Mazeh D, Elizur A: Risperidone treatment for a patient suffering from schizophrenia and IDDM (letter). Can J Psychiatry 1998; 43:956
13. Madhusoodanan S, Brenner R, Araujo L, et al: Efficacy of risperidone treatment for psychoses associated with schizophrenia, schizoaffective disorder, bipolar disorder, or senile dementia in 11 geriatric patients: a case series. J Clin Psychiatry 1995; 56:514–518[Medline]

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