[Show abstract][Hide abstract]ABSTRACT: In an earlier study, we found a similar frequency of individuals with an abnormal correlation between serum leptin levels and body mass index (BMI) (outliers above or below the 95% confidence interval in the regression line) during treatment with antipsychotic drugs (n=301), other psychotropic drugs (n=65), and drug-free individuals (n=229). In this secondary analysis, we compare the frequency of the metabolic syndrome (International Diabetes Federation), its constituting variables, obesity, (BMI>30 kg/m), leptin and insulin serum levels, and an insulin-resistance index (homeostatic model assessment-insulin resistance) in outliers, nonoutliers distributed in their original treatment groups, and all the nonoutliers controlled by age, sex, and BMI. We identified 28 outliers, 24 above and four below the 95% confidence interval limits. Nine individuals were under antipsychotic treatment, four under other drug treatment, and 15 were drug-free. The outliers had a significantly higher frequency of metabolic syndrome and obesity, and higher values of waist circumference, triglycerides, insulin, and blood diastolic pressure. The outliers in the correlation between leptin and BMI may represent a population at high risk of metabolic dysfunction, irrespective of the specific psychotropic drug treatment administered.
Article · Dec 2010 · International clinical psychopharmacology
[Show abstract][Hide abstract]ABSTRACT: Leptin dysregulation has been implicated in the body weight gain and metabolic dysfunction observed with the second generation antipsychotic drugs (SGAD) olanzapine and clozapine.
This study quantified the frequency of subjects with abnormal correlation between leptin and the body mass index controlling for gender (defined as being out of the upper or lower 95% confidence interval in the regression line when combining each group with the drug-free subjects) after prolonged treatment with olanzapine (n=126), clozapine (n=62), first generation antiypsychotics (n=91), other SGAD (n=22), other psychotropic drugs (n=65) and drug-free subjects (n=229).
None of the analysis was significant (p>0.05). In fact, in 17 out of 20 comparisons, the drug-free group had numerically higher frequencies of outliers than the corresponding treatment group. There were 28 outliers (4.7% of the total sample). In agreement with previous studies, cross-sectional analysis did not report gross alterations in serum leptin levels during olanzapine or clozapine administration.
Longitudinal studies should focus on leptin regulation early on treatment, on the frequency of abnormal leptin receptor sensitivity and/or specific polymorphisms in the leptin allele and on several confounding factors in order to design personalized preventive and therapeutic measures.
[Show abstract][Hide abstract]ABSTRACT: Melkersson proposed leptin dysregulation as a factor in the olanzapine-induced metabolic dysfunction. Their suggestion was based on the absence of the expected positive correlation between serum leptin levels and the BMI, and the loss of the sex-dependent difference in leptin levels, which are higher in women. Although subsequent studies did not confirm that proposal, few of them assessed basal leptin levels and corrected for body fat percentage. Along with these variables, we added a precise definition of participants out of the expected positive correlation in a large sample of schizophrenia patients. Sixty patients (26 women and 34 men) with severe schizophrenia undergoing chronic hospitalization and conventional antipsychotic treatment were switched to olanzapine (10-20 mg/day). We assessed at baseline, and at weeks 8 and 16 of treatment, the percentage of participants with abnormal correlation (out of the 95% confidence interval in the regression line) between leptin levels and the BMI, and the correlation between leptin and insulin, glucose, the insulin resistance index, c-reactive protein (CRP) and treatment response. Leptin levels were higher in women than in men (P<0.01). The positive correlation between leptin levels, BMI and percentage of fat were preserved. After olanzapine, 3.8% of women and 2.9-5.8% of men were out the 95% confidence interval, and the proportion was similar at baseline. Glucose, insulin, the insulin resistance index and the CRP levels significantly increased after olanzapine. The impact of olanzapine on leptin regulation appears discrete and limited to a small number of participants. Additional studies must clarify the features that render them to metabolic dysregulation.
Article · Aug 2007 · International Clinical Psychopharmacology