Diabetic Ketoacidosis Associated With Aripiprazole

Zaineb H. Makhzoumi, B.S., Leon P. McLean, M.D., M.P.H., Jefferson H. Lee, M.D., and Ada I. Ibe, M.D.

Disclosures

Pharmacotherapy. 2008;28(9):1198-1202. 

In This Article

Abstract and Introduction

Abstract

Metabolic adverse effects such as hyperglycemia, alterations in insulin sensitivity, and weight gain are known to be potential complications of atypical antipsychotic therapy. In certain cases, hyperglycemia may be so profound that diabetic ketoacidosis (DKA) or hyperosmolar coma may result. Aripiprazole, approved by the United States Food and Drug Administration in 2002, appears to have fewer metabolic adverse effects than other atypical antipsychotics. We describe a 44-year-old man with no personal or family history of diabetes mellitus who was prescribed aripiprazole for schizoaffective disorder. Two weeks after starting this therapy, the patient developed DKA, which was corrected with insulin therapy and aggressive hydration. According to the Naranjo adverse drug reaction probability scale, aripiprazole was the probable trigger of his DKA. An exhaustive search for other causes of DKA was unrevealing. Administration of aripiprazole or any other atypical antipsychotic should be terminated when impaired glucose tolerance is suspected. Vigilance regarding the potential adverse effects of this class of drugs, including new agents such as aripiprazole, is crucial to preventing potentially life-threatening complications of hyperglycemia.

Introduction

Over the past several decades, the pharmacologic treatment of schizophrenia has shifted from the conventional antipsychotic agents to the newer atypical antipsychotics.[1,2] Advantages of the atypical antipsychotics include more effective treatment of negative symptoms, improved mood and cognition, fewer extrapyramidal side effects, and reduced hyperprolactinemia.[2–5] Of the atypical agents, aripiprazole's once-daily administration presumably enhances patient compliance compared with agents requiring more frequent administration. Although the atypical antipsychotics are generally considered to be better tolerated than the conventional ones, significant adverse effects do occur. As a class, atypical antipsychotics have been associated with weight gain, hyperglycemia, sedation, and orthostatic hypotension.[2,3] Aripiprazole, however, reportedly causes less dramatic weight gain, dyslipidemia, and hyperglycemia than do the older atypical antipsychotics.[2–4]

Numerous case reports have linked atypical antipsychotics to hyperglycemia and new-onset diabetes mellitus, although the precise mechanism causing this effect has not been well elucidated. Two case reports have linked diabetic ketoacidosis (DKA) to aripiprazole therapy: one in a patient with a previous diagnosis of diabetes, the other in a patient with no known history of diabetes.[6,7] We describe a patient with no personal or family history of diabetes who developed DKA after the start of aripiprazole therapy.

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