Effects of long-term treatment with antipsychotics on serum leptin levels

Herrán, Andrés; García‐Unzueta, María Teresa; Amado, J. A.; Maza, María Teresa De La; Álvarez, Carlos Forcadell; Vázquez‐Barquero, José Luís

doi:10.1192/bjp.179.1.59

Cited by 69 publications

(48 citation statements)

References 19 publications

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“…Consistent with the report by Herran et al (2001), these results do not support hypotheses concerning impaired leptin secretion or leptin resistance in treated schizophrenia patients compared to healthy controls. Owing to continuing problem of increased prevalence of overweight and obesity in mental illnesses like schizophrenia, and the known impact of obesity on long-term survival, future studies of satiety signals are needed in order to improve the health of patients with mental illness.…”

Section: Discussionsupporting

confidence: 52%

“…Kraus et al (2001) reported lower plasma leptin levels in schizophrenia patients compared to adiposity-matched healthy controls, using the indirect adiposity measure of body mass index (BMI), arguing against leptin resistance and instead for the possibility of a decrease in leptin secretion or increased leptin clearance in this patient population. In contrast, Herran et al (2001) recently reported no difference in plasma leptin levels between treated schizophrenia patients and age, gender, and BMImatched healthy controls. Recently, Zhang et al (2004) described increases in leptin levels after antipsychotic associated weight gain, but the study was not designed to assess if the observed increases in leptin secretion were appropriate for the amount of adiposity gained during treatment.…”

Section: Introductionmentioning

confidence: 89%

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Plasma Leptin and Adiposity During Antipsychotic Treatment of Schizophrenia

Haupt

Luber

Maeda

et al. 2004

Neuropsychopharmacol

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Alterations in plasma leptin have been reported in schizophrenia patients treated with antipsychotics, suggesting the hypothesis that impairments in leptin secretion or signaling might play a role in antipsychotic-induced weight gain. Plasma leptin was measured in 72 schizophrenia patients chronically treated with olanzapine (n ¼ 27), risperidone (n ¼ 24) or typical antipsychotics (n ¼ 21) and 124 healthy adult control subjects. ANCOVA was used to test effects of adiposity (body mass index kg/m 2 ; BMI), subject group (treated patients vs untreated controls), and treatment group (specific medication groups and untreated controls) on plasma leptin concentrations. Additional analyses were performed in a subset of patients and controls individually matched for BMI to further assess group differences in plasma leptin independent of adiposity. BMI strongly predicted plasma leptin concentrations in the overall sample. In addition, a significant three-way interaction between BMI, subject group, and gender was observed. In the individually BMI-matched sample, modestly reduced plasma leptin levels (effect size 0.4 SD) were observed in treated patients in comparison to the BMI-matched healthy controls, with both groups including males and females. However, no differences in plasma leptin levels were observed in the matched sample when separately comparing male patients vs untreated male controls and female patients vs untreated female controls. Plasma leptin in chronically treated patients with schizophrenia is strongly predicted by adiposity, similar to untreated healthy individuals despite adequate power to detect a difference. The results argue against a role for defective leptin secretion or sensitivity in the weight gain induced by antipsychotic medications.

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Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 89%

Plasma Leptin and Adiposity During Antipsychotic Treatment of Schizophrenia

Haupt

Luber

Maeda

et al. 2004

Neuropsychopharmacol

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“…Given our inability to detect inappropriate plasma leptin levels in antipsychotictreated patients in comparison to adiposity-matched controls, the case for undertaking these subsequent studies is weakened (Haupt et al, 2005). As stated in our paper, along with the recent report by Herran et al, evidence does not currently support the hypothesis that leptin regulation in schizophrenia patients during antipsychotic treatment, as compared to leptin regulation in untreated healthy controls, is due to impaired leptin secretion or leptin resistance (Haupt et al, 2005;Herran et al, 2001).…”

Section: Sircontrasting

confidence: 62%

Reply: Plasma Leptin and Antipsychotic-Induced Body Weight Gain

Haupt

Newcomer

2005

Neuropsychopharmacol

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“…Raised leptin and subsequent downregulation of hypothalamic leptin receptors or altered transport dynamics could explain the weight gain and diabetes in patients taking certain antipsychotics (72). Against this are the results of a study comparing leptin levels in 59 patients with chronic schizophrenia with those from a group of healthy subjects matched for sex, age, and BMI (79). There was no difference between leptin levels in patients taking chronic antipsychotic medication (37 conventional and 17 atypical) and matched control subjects.…”

Section: Leptinmentioning

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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Effects of long-term treatment with antipsychotics on serum leptin levels

Abstract: Elevation of leptin levels induced by chronic antipsychotic treatment can be attributed to weight gain, but other mechanisms could be involved.

Cited by 69 publications

References 19 publications

Plasma Leptin and Adiposity During Antipsychotic Treatment of Schizophrenia

Plasma Leptin and Adiposity During Antipsychotic Treatment of Schizophrenia

Reply: Plasma Leptin and Antipsychotic-Induced Body Weight Gain

Patients on Atypical Antipsychotic Drugs

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