Serum leptin levels increase rapidly after initiation of clozapine therapy.
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.
Full-textDOI: · Available from: Juergen Christian Krieg, Jun 27, 2014
- SourceAvailable from: Esther Mutale van der Zwaal
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ABSTRACT: The second-generation antipsychotic drug olanzapine has become a widely prescribed drug in the treatment of schizophrenia and bipolar disorder. Unfortunately, its therapeutic benefits are partly outweighed by significant weight gain and other metabolic side effects, which increase the risk for diabetes and cardiovascular disease. Because olanzapine remains superior to other antipsychotic drugs that show less weight gain liability, insight into the mechanisms responsible for olanzapine-induced weight gain is crucial if it is to be effectively addressed. Over the past few decades, several groups have investigated the effects of olanzapine on energy balance using rat models. Unfortunately, results from different studies have not always been consistent and it remains to be determined which paradigms should be used in order to model olanzapine-induced weight gain most accurately. This review summarizes the effects of olanzapine on energy balance observed in different rat models and discusses some of the factors that appear to contribute to the inconsistencies in observed effects. In addition it compares the effects reported in rats with clinical findings to determine the predictive validity of different paradigms.The International Journal of Neuropsychopharmacology 10/2013; 17(01):1-18. DOI:10.1017/S146114571300093X · 5.26 Impact Factor
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ABSTRACT: Schizophrenia is a chronic and disabling mental illness affecting millions of people worldwide. A greater proportion of people with schizophrenia tends to be overweight. Antipsychotic medications have been considered the primary risk factor for obesity in schizophrenia, although the mechanisms by which they increase weight and produce metabolic disturbances are unclear. Several lines of research indicate that leptin could be a good candidate involved in pathways linking antipsychotic treatment and weight gain. Leptin is a circulating hormone released by adipocytes in response to increased fat deposition to regulate body weight, acting through receptors in the hypothalamus. In this work, we reviewed preclinical, clinical, and genetic data in order to infer the potential role played by leptin in antipsychotic-induced weight gain considering two main hypotheses: (1) leptin is an epiphenomenon of weight gain; (2) leptin is a consequence of antipsychotic-induced "leptin-resistance status," causing weight gain.Journal of obesity 03/2012; 2012:572848. DOI:10.1155/2012/572848