Abstract

BackgroundCurrent schizophrenia guidelines recommend that the choice of antipsychotic be made by the patient and physician together with a discussion of the likely benefits and side effects of each medication. Second-generation antipsychotics are commonly prescribed for the treatment of psychotic disorders, however metabolic adverse effects, such as hyperglycemia, are a potential complication of using this class of medications. Current sources indicate that the second-generation antipsychotic aripiprazole does not alter glucose homeostasis and confers low or no risk of developing diabetes. Below, the authors outline a case of significant, prolonged hyperglycemia secondary to the initiation of oral aripiprazole.MethodsSee Results.ResultsCase:An 18-year-old female was admitted involuntarily to hospital after she presented with suicidal ideation, ideas of reference, persecutory delusions and paranoia. She was reportedly a well-controlled Type 1 Diabetic prior to admission and her blood sugars were within normal limits for the first 9 days of hospitalization. Aripiprazole 10mg PO QAM was initiated to control symptoms. Within 9 hours of aripiprazole initiation, her blood sugars became unexpectedly and significantly elevated. After 5 days of therapy, aripiprazole was discontinued due to an inability to adequately control blood glucose. Diabetic ketoacidosis and pancreatitis were ruled out as laboratory results showed normal ketones, amylase and lipase. Blood glucose was taken via the Freestyle Libra device which measures interstitial fluid glucose levels and re-checked using the Accu-Chek Inform II monitor which is approved for use with capillary, venous, and arterial blood. Monitoring device malfunction was thereby ruled out as a cause. Diet and insulin administration techniques were closely monitored by nursing staff. Endocrinology and clinical dietary services were consulted. At their peak, blood sugars were as high as 25.9 mmol/L despite an increase in patient’s daily insulin (total bolus and basal) from 19 units/day to 132 units/day. Patient’s blood sugar and insulin requirements remained elevated over the next 17 days before gradually decreasing and returning to baseline.DiscussionIn this case, the authors are of the opinion that the patient experienced a severe idiosyncratic reaction to aripiprazole manifesting as severe hyperglycemia. Aripiprazole’s half-life of elimination is 75 hours, and dehydro-aripiprazole (Aripiprazole’s active metabolite) is 94 hours; the amount of time for the drug to be essentially removed from the body is 15.6 days and 19.6 days respectively (5 half-lives). This is consistent with the duration of time that passed before blood glucose levels normalized once aripiprazole was discontinued. The manufacturer of aripiprazole (Otsuka) has data regarding increases in blood glucose in adolescents. However, these increases are over a 26 week time frame, occurred in 1.9% of patients, and had a mean increase of 0.12mmol/L in their fasting glucose. This data, and the results of this case, therefore suggest that although increases of blood glucose while on aripiprazole tend to be rare and modest, there may be a subcategory of patients who develop severe hyperglycemia on this medication, and when this severe adverse effect is noted, the provocative agent should be promptly discontinued to reverse the effects.

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