The problem of treatment-emergent hyperglycemia or DM in adolescent or adult patients treated with atypical APDs has become a major concern for psychiatrists.1-3 In their study, Lipscombe et al4 extend the scope to elderly patients (mean age, 78 years) with preexistent DM. Their data convincingly show an increased risk for hyperglycemia in different groups of diabetic patients with APDs, thereby adding another risk factor to the use of APDs in this population. Some methodological issues, however, hamper the interpretation of the data. The inclusion criterion of controls is described as follows: “Patients could serve as a control more than once and were eligible to become a case at a later time.”4(p1283) No reason for this design are given nor are its advantages or disadvantages discussed. One exclusion criterion was no use of APDs in the preceding year. The possible impact of antipsychotic treatment during one of the previous 77 years is not discussed, nor are data related to this issue presented. The possible role of the somatic and psychiatric condition that led to the prescription of the APDs is not mentioned, nor are their possible implications for the glucose homeostasis discussed. The dichotomy of APDs is based on the presence of treatment-emergent extrapyramidal symptoms with typical APD use and the relative absence of these symptoms with atypical APD use. The relevance of this dichotomy for the impact of APDs on bodyweight and glucose homeostasis is unclear. An analysis of a large adverse events database on diabetes-related adverse events within the group of atypical APDs—aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone—with the typical APD haloperidol as comparison, did not show a uniform class effect but instead a differential risk of DM across atypical antipsychotic therapies, with haloperidol holding the middle ground.5 For 2 reasons, the design of the study by Lipscombe et al4 could not have detected such in-group differences. First, the included drugs in the atypical group consisted not of the 6 aforementioned drugs but only of 3 drugs (olanzapine, quetiapine, and risperidone). Clozapine,1,2 with a well-established highest risk of treatment-emergent hyperglycemia and DM, was excluded owing to administrative reasons. Two atypical APDs with a more favorable metabolic risk profile, aripiprazole and ziprasidone,1,2 were not included. Second, data on prescription rates, dose, and length of treatment are absent. As long as all these factors are not taken into account, we believe that the phrasing of the main result in the abstract and the conclusion of the study by Lipscombe et al,4 that all APDs are associated with increased risk, is premature. Correspondence: Dr De Hert, Psychotic Disorders, University Psychiatric Centre Catholic University, Leuven, Leuvensesteenweg 517, Kortenberg 3070, Belgium (firstname.lastname@example.org). Financial Disclosure: Dr De Hert has been a consultant for, received grant/research support and honoraria from, and has been on the speakers/advisory boards of AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck JA, Pfizer, and Sanofi. Dr Cohen received honoraria from and has been on the speakers/advisory boards of AstraZeneca, Bristol-Myers Squibb, and Eli Lilly. References 1. Newcomer JW Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs 2005;19 ((suppl 1)) 1- 93PubMedGoogle ScholarCrossref 2. Scheen AJDe Hert MA Abnormal glucose metabolism in patients treated with antipsychotics. Diabetes Metab 2007;33 (3) 169- 175PubMedGoogle ScholarCrossref 3. De Hert MDekker JMWood DKahl KGHolt RIMöller HJ Cardiovascular disease and diabetes in people with severe mental illness position statement from the European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC). Eur Psychiatry 2009;24 (6) 412- 424PubMedGoogle ScholarCrossref 4. Lipscombe LLLévesque LGruneir A et al. Antipsychotic drugs and hyperglycemia in older patients with diabetes. Arch Intern Med 2009;169 (14) 1282- 1289PubMedGoogle ScholarCrossref 5. Baker RAPikalov ATran QVKremenets TArani RBDoraiswamy PM Atypical antipsychotic drugs and diabetes mellitus in the US Food and Drug Administration adverse event database: a systematic bayesian signal detection analysis. Psychopharmacol Bull 2009;42 (1) 11- 31PubMedGoogle Scholar
Archives of Internal Medicine – American Medical Association
Published: Dec 14, 2009
Keywords: hyperglycemia,antipsychotic agents,older adult
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