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Near Fatal Ketoacidosis With Olanzapine Treatment

Key Words: Ketoacidosis • Olanzapine

TO THE EDITOR:The use of atypical antipsychotics has become increasingly popular over the past years. However, significant weight gain, worsening of lipid profiles, and emerging evidence that a number of these medications, most notably clozapine and olanzapine, may be associated with the risk of new-onset diabetes, serum glucose intolerance, and even diabetic ketoacidosis make these drugs potentially dangerous and even life-threatening if not used with caution and close monitoring.

Since there have been only a few cases reported in the literature and presented at psychiatric conferences of olanzapine-induced ketoacidosis,^1–9 we found it significant to report one that recently took place at our institution.

Ms. A, a 44-year-old African American woman with a history of schizophrenia, paranoid type, was admitted to our psychiatric service. She had a history of hepatitis C and a seizure disorder. Substance abuse history included opiate, cocaine, and alcohol dependence in early full remission. She had neither a personal nor family history of diabetes mellitus (coincidentally, however, while Ms. A was at our hospital, her sister was diagnosed with diabetes). Ms. A was receiving haloperidol, 10 mg t.i.d., and olanzapine, 5 mg h.s., when she came to our institution. Olanzapine therapy had been initiated 10 days earlier. Before olanzapine treatment she had been receiving risperidone, 3 mg b.i.d.

On admission Mrs. A's random blood sugar was elevated at 121 mg/dl, and she weighed 136 pounds. Olanzapine was increased to 20 mg/day, and haloperidol was decreased to 7.5 mg b.i.d. Blood sugar levels measured while fasting (155 mg/dl) and by means of finger sticks over 3 days (123, 134, and 144 mg/dl) remained elevated. The patient's hemoglobin A1c was found to be normal: 5.9%. The patient was placed on a diabetic diet. Olanzapine was increased to 25 mg/day, since the patient was taking phenytoin, which is an inducer of cytochrome P450 3A4. Since the patient still had prominent psychosis nearly 1 month later, ECT was initiated.

After the third session of ECT 1 week later, the patient started to have gastrointestinal distress, deterioration in her mental status, and was found to be hypotensive. She had a fever, and her blood sugar was 383 mg/dl. The patient was sent to the emergency room. Her blood sugar was >500 mg/dl and her CO₂ was <10 mmol/liter. A blood gas analysis revealed acidosis (pH=7.04, PCO₂=9 mm Hg, and HCO₃=2). The anion gap was 26. Her WBC count was 24.7 x 10³/µl with a left shift. She was admitted to the ICU with the diagnosis of diabetic ketoacidosis. Infection was ruled out.

Olanzapine was discontinued, and the patient was hydrated and started on an insulin drip.

The patient returned to the psychiatry service on a regimen of NPH insulin. She now weighed 144 pounds. ECT was restarted, she was kept off of olanzapine, and haloperidol was tapered. As blood sugars remained high, NPH was increased and an oral hypoglycemic agent was started following endocrinology consultation. However, because the patient later became hypoglycemic, the oral agent and NPH were discontinued.

The patient received a full course of ECT and was started on a regimen of ziprasidone for maintenance therapy. She was discharged home on a diabetic diet without the need for diabetes medication. Blood sugars remained under 150. She weighed 139.5 pounds. Olanzapine was deemed the most probable cause of the ketoacidosis.

Although, it seems that the most likely cause of ketoacidosis was olanzapine, we cannot discount the fact that our patient had multiple risk factors: she is over 40 years old, is African American, has schizophrenia, was also taking haloperidol, took risperidone shortly before olanzapine, and was receiving ECT when she went into a ketotic state. Although these all make her at greater risk for acquiring diabetes mellitus, the interesting point to note is the dramatic response the patient's blood sugar had once the patient was taken off of olanzapine and that she continued to receive ECT, getting 15 more treatments while blood sugars normalized. Thus, it was strongly believed that olanzapine was the cause for our patient's near fatal episode of ketoacidosis. We, therefore, found it significant to report such a case, especially since such events are occurring at an ever increasing frequency. It is also important to note the rapid onset of glucose intolerance in our patient. At the time of admission, she was receiving olanzapine (5 mg h.s.) and had a blood sugar level of 121 mg/dl. Ketoacidosis ensued approximately 1 month later with the olanzapine dose at 25 mg h.s. We therefore recommend that such patients have their blood glucose levels, lipid profiles, and body weight much more aggressively monitored and controlled.

REFERENCES

1. Wilson DR et al: New onset diabetes and ketoacidosis with atypical antipsychotics, in Proceedings From the International Congress on Schizophrenia Research. Whistler, BC, International Congress on Schizophrenia Research, 2001
2. Goldstein LE, Sporn J, Brown S, Kim H, Finkelstein J, Gaffey GK, Sachs G, Stern TA: New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychosomatics 1999; 40:438-443[Free Full Text]
3. Gatta B, Rigalleau V, Gin H: Diabetic ketoacidosis with olanzapine treatment. Diabetes Care 1999; 22:1002-1003[Medline]
4. Von Hayek D, Huttl V, Reiss J, Schweiger HD, Fuessl HS: Hyperglykamie and Ketoazidose unter olanzapin. Nervenarzt 1999; 70:836-837[CrossRef][Medline]
5. Lindenmayer J-P, Patel R: Olanzapine-induced ketoacidosis with diabetes mellitus. Am J Psychiatry 1999; 156:1471[Free Full Text]
6. Paizis M et al: Acute-onset DKA during olanzapine treatment in a patient without pretreatment obesity or treatment-associated weight gain. Primary Psychiatry 1999; 6:37-38
7. Rigalleau V, Gatta B, Bonnaud S, Masson M, Bourgeois ML, Vergnot V, Gin H: Diabetes as a result of atypical anti-psychotic drugs-a report of three cases. Diabet Med 2000; 17(6):484-486
8. Selva KA, Scott SM: Diabetic ketoacidosis associated with olanzapine in an adolescent patient. J Pediatr 2001; 138(6):936-937
9. Cagliero E, Henderson DC, Nathan DM: Diabetic ketoacidosis in patients with schizophrenic disorders, in 2001 Annual Meeting New Research Program and Abstracts. Washington, DC, American Psychiatric Association, 2001, p 88

This article has been cited by other articles:

				A. R. Fulbright and K. T. Breedlove Complete Resolution of Olanzapine-Induced Diabetic Ketoacidosis Journal of Pharmacy Practice, August 1, 2006; 19(4): 255 - 258. [Abstract] [PDF]

				O. D. Howes and L. Rifkin Diabetic Keto-Acidotic (DKA) Coma following Olanzapine Initiation in a Previously Euglycaemic Woman and Successful Continued Therapy with Olanzapine J Psychopharmacol, September 1, 2004; 18(3): 435 - 437. [Abstract] [PDF]

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