Diabetes as a result of atypical anti‐psychotic drugs – a report of three cases

Rigalleau, Vincent; Gatta, Blandine; Bonnaud, Stéphanie; Masson, Michel; Bourgeois, M; Vergnot, V; Gin, H.

doi:10.1046/j.1464-5491.2000.00296.x

Cited by 76 publications

(38 citation statements)

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“…We then compiled a table (Table 1) summarizing the cases contained in these reports, to which we added the results of a further search using the terms "diabetes" and "antipsychotic or clozapine or olanzapine or risperidone or quetiapine or ziprasidone" for publications between January 1999 and January 2002 that had not been cited by the four reviews listed above (33)(34)(35)(36)(37)(38)(39)(40)(41)(42). We included all reported cases in which sufficient detail was given for us to determine that patients had developed either clinically relevant hyperglycemia or diabetes according to internationally recognized criteria.…”

Section: Is There a Link Betweenmentioning

confidence: 99%

Patients on Atypical Antipsychotic Drugs

2003

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-Patients with schizophrenia are more likely than the general population to develop diabetes, which contributes to a high risk of cardiovascular complications; individuals with schizophrenia are two to three times more likely to die from cardiovascular disease than the general population. The risk of diabetes, and hence cardiovascular disease, is particularly increased by some of the new atypical antipsychotic drugs. Individuals taking an atypical antipsychotic drug, particularly younger patients under 40 years of age (odds ratio 1.63, 95% CI 1.23-2.16), represent an underrecognized group at high risk of type 2 diabetes. The mechanisms responsible for antipsychotic-induced diabetes remain unclear. Hypotheses include these drugs' potential to cause weight gain, possibly through antagonism at the H 1 , 5-HT 2A , or 5-HT 2C receptors. Other mechanisms independent of weight gain lead to elevation of serum leptin and insulin resistance. Patients with psychoses have difficulties with diet and lifestyle interventions for diabetes and weight management. If hyperglycemia develops, withdrawal from antipsychotic medication will often be inappropriate, and a change to an atypical antipsychotic drug with lower diabetogenic potential should be considered, especially in younger patients. Management of psychoses should routinely include body weight and blood glucose monitoring and steps to promote exercise and minimize weight gain. Careful collaboration between the psychiatric and diabetology teams is essential to minimize the risk of diabetes in patients taking atypical antipsychotic medication and for effective management when it develops. This collaboration will also help minimize the already high risk of cardiovascular disease in individuals with schizophrenia. Diabetes Care 26:1597-1605, 2003T he number of individuals in the population receiving antipsychotic drugs is surprisingly high. The most common reason is schizophrenia, although antipsychotic drugs are widely used in other psychiatric conditions (e.g., bipolar disorder and Alzheimer's disease). Schizophrenia is far more common than is generally appreciated. For example, as many as 1 in 100 individuals in the population will suffer one or more episodes of schizophrenia in a lifetime, and for at least half of these individuals, the illness will be lifelong, probably requiring long-term medication. Schizophrenia causes social disability and also carries a high mortality-approximately twice as high as in the general population (1). It has a strikingly high suicide rate of 10% (2,3), but the most common cause of death is accelerated heart disease (two to three times that in the general population) (4). Despite its relatively low prevalence, the early age at onset and its chronic nature means that schizophrenia is an expensive medical condition to health care systems and to society in general (5,6).The introduction of chlorpromazine after 1956 transformed the lives of many sufferers. Several major chemical classes of antipsychotic drugs were developed, principall...

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Section: Is There a Link Betweenmentioning

confidence: 99%

Patients on Atypical Antipsychotic Drugs

2003

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“…But regardless of its causality, obesity is a significant public health concern and is a well-documented risk factor for type 2 diabetes as well as other chronic diseases, such as cancer and atherosclerosis (4 -6). Nonetheless, diabetes risk with antipsychotic use has also been reported in the absence of significant weight gain (7)(8)(9).…”

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Metabolic Dysregulation With Atypical Antipsychotics Occurs in the Absence of Underlying Disease A Placebo-Controlled Study of Olanzapine and Risperidone in Dogs

et al. 2005

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Atypical antipsychotics have been linked to weight gain, hyperglycemia, and diabetes. We examined the effects of atypical antipsychotics olanzapine (OLZ) and risperidone (RIS) versus placebo on adiposity, insulin sensitivity (S I ), and pancreatic ␤-cell compensation. Dogs were fed ad libitum and given OLZ (15 mg/day; n ‫؍‬ 10), RIS (5 mg/day; n ‫؍‬ 10), or gelatin capsules (n ‫؍‬ 6) for 4 -6 weeks. OLZ resulted in substantial increases in adiposity: increased total body fat (؉91 ؎ 20%; P ‫؍‬ 0.000001) reflecting marked increases in subcutaneous (؉106 ؎ 24%; P ‫؍‬ 0.0001) and visceral (؉84 ؎ 22%; P ‫؍‬ T he introduction of atypical antipsychotics in psychopharmacology represented a major advance in the treatment of schizophrenia, providing an effective therapy for both positive and negative symptoms of psychosis while minimizing the extrapyramidal effects characteristic of earlier therapeutic options. Indeed, these medications are widely prescribed (ϳ3% of the U.S. population) for treatment of schizophrenia, as well as bipolar disorder, depression, and dementia.In the face of their widespread use, concern has arisen regarding treatment-associated weight gain and apparent increased diabetes risk (1-3). It is unclear whether weight gain is a direct effect of the drug or secondary to behavioral changes, such as increased sedation associated with pharmacotherapy. But regardless of its causality, obesity is a significant public health concern and is a well-documented risk factor for type 2 diabetes as well as other chronic diseases, such as cancer and atherosclerosis (4 -6). Nonetheless, diabetes risk with antipsychotic use has also been reported in the absence of significant weight gain (7-9).Evidence linking atypical antipsychotics to metabolic dysregulation is largely based on case reports and retrospective analyses, which note a disproportionately greater number of patients developing fasting hyperglycemia and new-onset diabetes or exhibiting exacerbation of preexisting diabetes soon after the initiation of atypical antipsychotic treatment (10 -15). Henderson et al. (14) reported that Ͼ30% of schizophrenic patients receiving clozapine developed diabetes within a 5-year follow-up, and those with preexisting diabetes required increased insulin dosing. Federal Drug Administration reports (10), based in part on the Medwatch Surveillance Program, provide further evidence of the excessive occurrence of new-onset diabetes and exacerbation of preexisting disease with clozapine compared with disease incidence in untreated individuals. More recently, olanzapine (OLZ) and risperidone (RIS), which collectively account for Ͼ80% of all drugs prescribed of their class of atypical antipsychotics, have also been associated with metabolic abnormalities, though OLZ is generally linked to greater relative risk for diabetes (11,16) and more marked obesity (3,11,17) compared with RIS (12,13,18).It is indeed challenging to study the actions of antipsy-

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“…Pancreatite aguda é outro efeito relacionado, até o momento, principalmente à clozapina, seguida da olanzapina e risperidona, com relatos de cetoacidose concomitante ao desenvolvimento dessa patologia (40). Em relação ao mecanismo envolvido na cetoacidose diabética, apesar de ainda pouco entendido, parece estar relacionado a um efeito inibitório direto nas células beta pancreáticas, com casos de níveis de peptídeo C entre 0,7 e 0,9 nmol/dL à admissão do paciente, com normalização após retirada da droga, sugerindo uma deficiência temporária de insulina (41).…”

Section: Discussionunclassified

Diabetes mellitus associado com drogas antipsicóticas atípicas: relato de caso e revisão da literatura

Reis

Alvarenga

Rosário

et al. 2007

Arq Bras Endocrinol Metab

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RESUMODesde a introdução das medicações antipsicóticas atípicas, iniciando com a clozapina, em 1990, muitos relatos associam essas drogas ao desenvolvimento de diabetes mellitus, entre outros distúrbios metabólicos, assim como abertura da doença como cetoacidose. Relatamos o caso de um paciente de 28 anos, com esquizofrenia, admitido em cetoacidose diabética 1 mês após início da terapia com clozapina, sem relação com ganho de peso, mantendo-se com níveis satisfatórios de glicemia, sem tratamento, após suspensão da droga. Revisamos o assunto, com outros casos relatados até o momento, incluindo a associação de outros antipsicóticos atípicos igualmente envolvidos em distúrbios endócrinos. Objetivamos, com o relato deste caso, aumentar a atenção dos clínicos envolvidos no tratamento dos pacientes portadores de distúrbios psiquiátricos para a possibilidade do surgimento de diabetes durante a terapia, e enfatizar a necessidade de aumento da vigilância e do acompanhamento metabólico desses pacientes. Since the introduction of atypical antipsychotic medications, starting with clozapine in 1990, many studies have associated these drugs with the development of diabetes among other metabolic disorders, as well as with the onset of the disease as ketoacidosis. We report the case of a 28-yearold patient with schizophrenia who was admitted with diabetic acidosis 1 month after the beginning of clozapine therapy. No weight gain was reported and the patient maintains satisfactory glycemia levels with no treatment required after discontinuation of the drug. The literature on this subject and cases reported so far are reviewed, including the association of other atypical antipsychotic drugs also involved in endocrine disorders. The objective of this report is to raise the awareness of physicians treating psychiatric patients to the possibility of new-onset diabetes during therapy with atypical antipsychotic drugs and to emphasize the necessity for increased vigilance and close metabolic follow-up of these patients. (Arq Bras Endocrinol Metab 2007;51/3:488-493)

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Diabetes as a result of atypical anti‐psychotic drugs – a report of three cases

Abstract: Novel APDs not only induce diabetes as a result of weight gain in predisposed patients, but can also lead to a reversible state of insulin deficiency, and sometimes ketoacidosis.

Cited by 76 publications

References 10 publications

Patients on Atypical Antipsychotic Drugs

Patients on Atypical Antipsychotic Drugs

Metabolic Dysregulation With Atypical Antipsychotics Occurs in the Absence of Underlying Disease A Placebo-Controlled Study of Olanzapine and Risperidone in Dogs

Diabetes mellitus associado com drogas antipsicóticas atípicas: relato de caso e revisão da literatura

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