Atypical antipsychotic-induced diabetes mellitus: How strong is the evidence?

Psychotic Disorders and Schizophrenia Research Program, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
CNS Drugs (Impact Factor: 5.11). 02/2002; 16(2):77-89.
Source: PubMed


Atypical antipsychotics offer significant improvements over older, conventional antipsychotic agents. However, recently the newer agents have been linked to medical morbidity including hyperglycaemia, diabetes mellitus, bodyweight gain and abnormal lipid levels. Even more concerning, because of a significant risk of death, there have been numerous case reports of patients treated with clozapine or olanzapine developing diabetic ketoacidosis shortly after initiation of the drug. Much of the information concerning the medical morbidity of diabetes mellitus is based on case reports, retrospective chart reviews, naturalistic studies and cross-sectional studies. While definitive studies have yet to be reported, mounting evidence suggests that the atypical antipsychotic agents, particularly clozapine and olanzapine, may significantly impair glucose metabolism and increase the risk of diabetes in patients with schizophrenia. Diabetic ketoacidosis, although it appears to be uncommon, is of great concern secondary to the risk of death. Patients treated with atypical antipsychotic agents should be routinely screened for diabetes and other metabolic abnormalities including raised lipid levels. Patients with risk factors for diabetes should be monitored more closely. Reports and clinical experience suggest that in a case of atypical antipsychotic-associated diabetes or diabetic ketoacidosis, discontinuation of the antipsychotic agent may result in complete resolution of the hyperglycaemia and diabetes.

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    • "Clozapine and olanzapine are more capable of inducing insulin resistance in peripheral tissues of animals (Albaugh et al., 2006; Cooper et al., 2005) and humans (Houseknecht et al., 2007; Tulipano et al., 2007) when compared with risperidone and quetiapine (De Hert et al., 2012). Importantly, clozapine and olanzapine appear to induce hyperglycemia (Koller and Doraiswamy, 2002; McIntyre et al., 2001), hyperinsulinemia (Vidarsdottir et al., 2010) and insulin resistance (Henderson, 2002; Lindenmayer et al., 2001; Sowell et al., 2003) shortly after the beginning of treatment (resolved on discontinuation of drug and reappeared with reinstitution of drug) (Koller and Doraiswamy, 2002; McIntyre et al., 2001), independently of body weight and adiposity gain which are normally associated with antipsychotics consumption (see Section 3.1), and even in the presence of weight loss (Gatta et al., 1999). Therefore, weight gain is unlikely to be the sole explanation for the diabetogenic effects of these drugs (Henderson et al., 2000). "
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    ABSTRACT: The use of antipsychotic drugs for the treatment of mood disorders and psychosis has increased dramatically over the last decade. Despite its consumption being associated with beneficial neuropsychiatric effects in patients, atypical antipsychotics (which are the most frequently prescribed antipsychotics) use is accompanied by some secondary adverse metabolic effects such as weight gain, dyslipidemia and glucose intolerance. The molecular mechanisms underlying these adverse effects are not fully understood but have been suggested to involve a dysregulation of adipose tissue homeostasis. As such, the aim of this paper is to review and discuss the role of adipose tissue in the development of secondary adverse metabolic effects induced by atypical antipsychotics. Data analyzed in this article suggest that atypical antipsychotics may increase adipose tissue (particularly visceral adipose tissue) lipogenesis, differentiation/hyperplasia, pro-inflammatory mediator secretion and insulin resistance and decrease adipose tissue lipolysis. Consequently, patients receiving antipsychotic medication could be at risk of developing obesity, type 2 diabetes and cardiovascular disease. A better knowledge of the impact of these drugs on adipose tissue homeostasis may unveil strategies to develop novel antipsychotic drugs with less adverse metabolic effects and to develop adjuvant therapies (e.g. behavioral and nutritional therapies) to neuropsychiatric patients receiving antipsychotic medication. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 12/2014; 25(1). DOI:10.1016/j.euroneuro.2014.11.008 · 4.37 Impact Factor
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    • "When measuring QOL in patients treated with antipsychotics, it is important to acknowledge that a variety of factors may influence a patient's QOL: these include side effects and daily dosage of the antipsychotic, depressive, and negative symptoms, duration of treatment, and subjective tolerability [4]. Obesity, cardiovascular disease, and metabolic syndrome are also factors that impact a patient's life prognosis and QOL [5] [6]. Cook et al. [7] reported that for stable outpatients with schizophrenia in a real-world setting, switching to an atypical antipsychotic can result in sustained, significant improvement in clinical response and QOL, as well as in reduced need for hospitalization and community support. "
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    ABSTRACT: Aim. The purpose of this retrospective study was to evaluate changes in clinical indicators which influence the quality of life (QOL) of patients with schizophrenia treated by antipsychotic therapy before and after switching to aripiprazole. Methods. A retrospective chart review of 27 patients diagnosed with schizophrenia and who were switched from one antipsychotic to aripiprazole was performed. Clinical indicators about the daily dosage of antipsychotics and antiparkinsonian drugs, psychiatric condition, and glucose/lipid metabolism, clinical evaluation by nursing observation were used to measure the responsiveness of subjects to aripiprazole. Results. Of the 27 subjects, 14 responded to the switch to aripiprazole with significant improvement of the Brief Psychiatric Rating Scale (BPRS) score (P = 0.04), significant decrease in dosage of antipsychotics in 71% of patients (P = 0.03), and tendency toward reduction in dosage of antiparkinsonian drugs (P = 0.07) and body mass index (BMI) (P = 0.06). However, 8 of 27 subjects had a significant increase in lipid levels after switching to aripiprazole (P = 0.01). Conclusion. QOL for subjects who responded to the switch to aripiprazole improved as indicated by lower doses of antipsychotic and antiparkinson medications, improvement in BPRS score, and a decrease in BMI. Results indicate little influence on patient's QOL.
    08/2012; 2012(4):454898. DOI:10.5402/2012/454898
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    • "In the last twenty years, the introduction of second-generation antipsychotic drugs has caused substantial somatic consequences, such as weight gain (Tandon and Halbreich, 2003), hyperlipidemia (Meyer and Koro, 2004) and insulin resistance (Nasrallah and Newcomer, 2004; Wu et al., 2006). Furthermore, the use of these drugs is associated with the development of metabolic syndrome (Meyer et al., 2005; Shirzadi and Ghaemi, 2006) and type 2 diabetes (Henderson, 2002; Cohen, 2004; Melkersson and Dahl, 2004; Newcomer, 2005). Older patients using second-generation antipsychotics show a 1.6-to 1.7-fold increase in the risk of death (Schneider et al., 2005), which is at least partly due to sudden cardiac death and cerebrovascular accidents. "
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    ABSTRACT: This study aimed to estimate the incidence and relative risk of stroke and post-stroke all-cause mortality in patients with schizophrenia. This study identified a study population from the National Health Insurance Research Database (NHIRD) between 1999 and 2003 that included 80,569 patients with schizophrenia and 241,707 age- and sex-matched control participants without schizophrenia. The participants were randomly selected from the 23,981,020-participant NHIRD, which consists of 96% Taiwanese participants. Participants who had experienced a stroke between 1999 and 2003 were excluded. Using data from the NHIRD between 2004 and 2008, the incidence of stroke (ICD-9-CM code 430-438) and patient survival after stroke were calculated for both groups. After adjusting for confounding risk factors, a Cox proportional-hazards model was used to compare the five-year stroke-free survival rate to the all-cause mortality rate across the two cohorts. Over five years, 1380 (1.71%) patients with schizophrenia and 2954 (1.22%) controls suffered from strokes. After adjusting for demographic characteristics and comorbid medical conditions, patients with schizophrenia were 1.13 times more likely to have a stroke (95% CI=1.05-1.22; P=0.0006). In addition, 1039 (24%) patients who had a stroke died during the follow-up period. After adjusting for patient, physician and hospital variables, the all-cause mortality hazard ratio for patients with schizophrenia was 1.23 (95% CI=1.06-1.41; P=0.0052). During a five-year follow-up, the likelihood of developing a stroke and the all-cause mortality rate were greater among patients with schizophrenia as compared with the control group.
    Schizophrenia Research 03/2012; 138(1):41-7. DOI:10.1016/j.schres.2012.02.013 · 3.92 Impact Factor
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