Article

Serum leptin levels increase rapidly after initiation of clozapine therapy

Clinical Research Group, Department of Child and Adolescent Psychiatry of the University of Marburg, Germany.
Molecular Psychiatry (Impact Factor: 14.5). 02/1998; 3(1):76-80. DOI: 10.1038/sj.mp.4000352
Source: PubMed

ABSTRACT

Weight gain is a major side-effect of treatment with clozapine. In order to investigate the influence of the atypical neuroleptic clozapine on leptin secretion, serum leptin levels were measured in 12 patients at baseline and for a 10-week period after initiation of treatment. Serum clozapine levels and levels of its metabolites were simultaneously assessed. Alterations of body weight and body composition were determined. During the 10-week observation period leptin levels differed significantly from the levels determined at baseline (P < 0.0001). During the first 2 weeks of treatment serum leptin levels at least doubled in eight of the 12 patients. The maximal relative increase over baseline was 536%. Low doses of clozapine were sufficient to induce this effect. Within a 10-week period mean body weight, mean body mass index, mean fat mass and mean lean body mass all increased. Based on the results we suggest that in predisposed individuals clozapine induces an increased appetite; overeating and weight gain can ensue, which in turn underlie elevated leptin secretion.

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Available from: Juergen Christian Krieg, Jun 27, 2014
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    • "There is a positive correlation between the administration of SGAs and hepatic steatosis in – 12–24 h after i.p. injection in rats [55] and the gene expression of profiles follow a biphasic pattern for PPAR controlled genes that leads to rapid accumulation of triglycerides, phospholipids, and cholesterol in the liver [38]. The obesity induced by clozapine is seemingly affected by genetic polymorphsims and it is followed by an increase in plasma leptin of five folds over baseline [4] [17] [55] [112]. Thus, although few studies argue otherwise [45] [110], the vast majority of published literature [47] [55] [82] [16], including a recent clinical trial [130], supports the hypothesis that, independent of baseline BMI and the presence/absence of MetS, clozapine and olanzapine induce accelerated obesity, hyperglycemia and hypertriglyceridemia [38]. "
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    • "Similiarly, most clinical studies failed to observe significant effects of treatment with second-generation antipsychotics on food choice (Gothelf et al., 2002; Strassnig et al., 2003; Henderson et al., 2006). However, some reported frequent food cravings and higher sweet and snack consumption (Bromel et al., 1998; Kluge et al., 2007). Furthermore, weight gain after olanzapine treatment was associated with 'increased snack consumption' and 'thoughts preoccupied with food' (Treuer et al., 2009). "

    Full-text · Dataset · Mar 2015
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    • "Similiarly, most clinical studies failed to observe significant effects of treatment with second-generation antipsychotics on food choice (Gothelf et al., 2002; Strassnig et al., 2003; Henderson et al., 2006). However, some reported frequent food cravings and higher sweet and snack consumption (Bromel et al., 1998; Kluge et al., 2007). Furthermore, weight gain after olanzapine treatment was associated with 'increased snack consumption' and 'thoughts preoccupied with food' (Treuer et al., 2009). "
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