Differential metabolic effects of antipsychotic treatments

Haupt, Dan

doi:10.1016/j.euroneuro.2006.06.003

Cited by 109 publications

(81 citation statements)

References 10 publications

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“…The well-established adiposity-mediated mechanism plays a central role in atypical antipsychotic-induced insulin resistance (American Diabetes Association, 2004b;Casey et al, 2004;Newcomer, 2005;Haupt, 2006;Haupt et al, 2007). Besides unhealthy eating habits of patients with schizophrenia, treatment with atypical antipsychotics seems to increase appetite and worsen opiodergic capacity, thus further deteriorating eating patterns (Elman et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Hyperinsulinemic-euglycemic clamp represents the gold standard methodology (DeFronzo et al, 1979;Haupt, 2006) for the determination of insulin-sensitivity in vivo. This technique measures the amount of glucose required to maintain euglycemia in the setting of an experimentally increased insulin level.…”

Section: Hyperinsulinemic-euglycemic Clampmentioning

confidence: 99%

“…Despite the welldescribed effects of adiposity on glucose metabolism in the general population (Welch et al, 1990;Karter et al, 1996;Macor et al, 1997;Mayer-Davis et al, 1997), the underlying mechanisms for potential adiposity-independent effects of atypical antipsychotics on insulin sensitivity have not been identified yet. While most studies report an increased risk for the development of metabolic abnormalities like glucose intolerance, insulin-resistance, and consequentially DM2 in rodent (Houseknecht et al, 2005) or dog studies as well as in patients with schizophrenia (Hedenmalm et al, 2002;Koller and Doraiswamy, 2002;Newcomer et al, 2002;Sernyak et al, 2002;Wilson et al, 2003;Kane et al, 2004;Simpson et al, 2004;Henderson et al, 2005, 2006, Haupt et al, 2007, patients with schizoaffective disorder (Wilson et al, 2003;Simpson et al, 2004) or patients with mood disorder (Gianfrancesco et al, 2003) treated with atypical antipsychotics, other studies fail to confirm these correlations for healthy subjects (Sowell et al, 2002(Sowell et al, , 2003 or patients with schizophrenia (Kinon et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Fasting, post-prandial and post-load glucose are significantly driven by insulin secretion and insulin sensitivity. A variety of techniques to measure these two key parameters exist (Haupt, 2006). Whereas estimation of insulin secretion by frequently sampling oral glucose tolerance tests, fasting glucose, and plasma insulin curves cannot reliably relate b-cell response to acute changes in plasma glucose, intravenous glucose tolerance tests, MINMOD calculations (Bergman, 1989), and hyperinsulinemic as well as euglycemic clamps provide a more accurate measure.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Sacher

Mossaheb

Spindelegger

et al. 2007

Neuropsychopharmacol

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Atypical antipsychotics have been linked to a higher risk for glucose intolerance, and consequentially the development of type 2 diabetes mellitus (DM2). We have therefore set out to investigate the acute effects of oral administration of olanzapine and ziprasidone on whole body insulin sensitivity in healthy subjects. Using the standardized hyperinsulinemic euglycemic clamp technique we compared whole body insulin sensitivity of 29 healthy male volunteers after oral intake of either olanzapine 10 mg/day (n ¼ 14) or ziprasidone 80 mg/day (n ¼ 15) for 10 days. A significant decrease (po0.001) in whole body insulin sensitivity from 5.7 ml/h/kg ( ¼ mean, SM ¼ 0.4 ml/h/kg) at baseline to 4.7 ml/h/kg ( ¼ mean, SM ¼ 0.3 ml/h/kg) after oral intake of olanzapine (10 mg/day) for 10 days was observed. The ziprasidone (80 mg/day) group did not show any significant difference (5.2 ± 0.3 ml/h/kg baseline vs 5.1 ± 0.3 ml/h/kg) after 10 days of oral intake. Our main finding demonstrates that oral administration of olanzapine but not ziprasidone leads to a decrease in whole body insulin sensitivity in response to a hyperinsulinemic euglycemic challenge. Our finding is suggestive that not all atypical antipsychotics cause acute direct effects on glucose disposal and that accurate determination of side effect profile should be performed when choosing an atypical antipsychotic.

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Section: Discussionmentioning

confidence: 99%

Section: Hyperinsulinemic-euglycemic Clampmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Sacher

Mossaheb

Spindelegger

et al. 2007

Neuropsychopharmacol

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“…Obesity increases these patients' risk for cardiovascular morbidity and mortality. In addition, excessive weight and obesity can have important effects on an individual's adjustment in the community, adherence to prescribed medication, ability to participate in rehabilitation efforts, and self-image (2).…”

Section: Weight Gainmentioning

confidence: 99%

Side effects of atypical antipsychotics: a brief overview

2008

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Patients with schizophrenia suffer from increased rates of multiple medical problems, due to their lifestyle (high smoking prevalence, high-fat diet), inherent neglect of personal care, and barriers to treatment of physical illness (1). A further important contributor to adverse health outcomes is the side effect profile of antipsychotic medications. Since the introduction of the second generation or atypical antipsychotics (AAP), these agents have been widely prescribed for the management of patients with schizophrenia, bipolar disorders, other psychotic disorders or conditions with severe behavioral disturbance. The increasing use of AAP is in part due to their lower propensity to induce extrapyramidal symptoms and tardive dyskinesia compared to typical antipsychotics. Now, more than 15 years after the first atypical antipsychotic entered the market, psychiatrists have gradually come to realize that while extrapyramidal symptoms and tardive dyskinesia occur less frequently with atypical agents, these medications may present a different set of adverse effects. The quality of available evidence for the association of specific antipsychotics with particular side effects varies considerably. In this article, we review the recent findings concerning weight gain, diabetes mellitus (DM), hyperlipidemia, QTc interval prolongation, myocarditis, sexual side effects, extrapyramidal side effects and cataract in patients receiving AAP. WEIGHT GAINForty to sixty-two percent of people with schizophrenia are overweight or obese. Obesity increases these patients' risk for cardiovascular morbidity and mortality. In addition, excessive weight and obesity can have important effects on an individual's adjustment in the community, adherence to prescribed medication, ability to participate in rehabilitation efforts, and self-image (2).Treatment with first-and second-generation antipsychotics can contribute to weight gain (3-5). A meta-analysis by Allison and Casey (4) provided an estimate of the mean weight gain in patients receiving standard doses of antipsychotics over a 10-week period: the mean increases were 4.45 kg with clozapine, 4.15 kg with olanzapine, 2.92 kg with sertindole, 2.10 kg with risperidone, and 0.04 kg with ziprasidone. Data on quetiapine have been variable, but it seems that the weight gain liability on this drug may be similar to that of risperidone (6). Weight gain with olanzapine at the commonly used dose of 15mg/day may exceed 10 kg during the first year of treatment (7). On the other hand, weight gain seems to be dose-dependent: Rondanelli et al (8) reported no change in weight in elderly patients who received 1.4 mg/day risperidone or 4.4 mg/day olanzapine or 75 mg/day quetiapine over a 12-month period.Marder et al (9) recommended that the patient's body mass index (BMI) should be recorded before medication initiation or change and at every visit for the first 6 months. The patient should be weighed (and the BMI recorded) at least quarterly when he stabilizes, and more often if he is overweight. BMI monito...

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A Murine Model of Atypical Antipsychotic‐Induced Weight Gain and Metabolic Dysregulation

Coccurello

Moles

2010

CP Neuroscience

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In comparison with conventional, first-generation antipsychotics (e.g., haloperidol), the administration of atypical antipsychotics (AAPs) has been associated with a higher risk of metabolic derangements, including body weight increase, dysregulation of glucose homeostasis, fat accumulation, and even liability to develop type II diabetes. Since this is a serious clinical problem that may be further exacerbated in overweight schizophrenics, establishing animal models of AAP-induced adverse effects may contribute to clarifying the mechanisms underlying these effects. Here we present three basic protocols by which this problem has been modeled. The three protocols differ in many aspects (routes of administration, extent of the chronic treatment, diets, and dosage regimen), and the pros and cons of each procedure are systematically detailed throughout. It should be noted that several factors (e.g., species, sex, duration, and class of AAPs) could restrict the feasibility of these models, as well as their correspondence to the clinical condition.

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Differential metabolic effects of antipsychotic treatments

Cited by 109 publications

References 10 publications

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Side effects of atypical antipsychotics: a brief overview

A Murine Model of Atypical Antipsychotic‐Induced Weight Gain and Metabolic Dysregulation

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