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
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ABSTRACT: Objectives We investigated the associations of the LEP-2548A/G and HTR2C-759C/T polymorphisms with long-term clozapine-induced weight changes and baseline BMI in chronic patients with schizophrenia.Materials and methodsA total of 113 patients receiving clozapine for at least 1 year were enrolled. Body weight was measured cross-sectionally and data on body weight just before starting clozapine were retrospectively extracted from medical records.ResultsClozapine-induced change in BMI was correlated inversely with the baseline BMI (P<0.001, =-0.347). The LEP-2548A/G polymorphism was associated significantly with the change in BMI (F=4.380, P=0.015) during clozapine use; those with the AA genotype had the highest BMI gain (1.43.1kg/m(2)), followed by those with the AG (-0.2 +/- 3.3kg/m(2)) and GG (-1.6 +/- 3.4kg/m(2)) genotypes. We also found a significant association between the leptin genotype and BMI at baseline (F=3.499, P=0.034); those with the AA genotype had the lowest baseline BMI (23.4 +/- 4.3kg/m(2)), followed by those with the AG (24.1 +/- 4.4kg/m(2)) and GG (28.8 +/- 7.3kg/m(2)) genotypes. In the case of the HTR2C-759C/T polymorphism, we found a trend in which T alleles were more prevalent in male patients with up to 7% increase in BMI than in those with a greater than 7% increase in BMI [12/54 (22.7%) vs. 1/27 (3.7%); Fisher's exact test: P=0.051].Conclusion This study shows an inverse correlation between the baseline BMI and change in BMI during long-term clozapine use in patients with schizophrenia, and the LEP-2548A/G polymorphism was associated significantly with both these measures.Psychiatric Genetics 10/2014; 24(6). DOI:10.1097/YPG.0000000000000053 · 2.27 Impact Factor
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ABSTRACT: BackgroundTo describe the rates, indications, and adverse effects of psychotropic drug prescription in a specialist tertiary hospital child and adolescent eating disorder service.MethodsRetrospective case note study of all active eating disorder patients (N = 115) over the period of treatment from referral to time of study (M = 2 years), covering patient demographics, clinical characteristics, drug prescriptions, indications, and adverse effects.ResultsPsychotropic drugs were prescribed in 45% of cases, most commonly antidepressants (41%), followed by anxiolytics (29%) and antipsychotics (22%), with 8% initiated before referral to the specialist eating disorder program. Common indications were depressed mood, agitation, anxiety, and insomnia. Patient clinical severity and complexity was associated with prescribing. Adverse effects, mostly minor, were recorded in 23% of antidepressant prescriptions, 39% of antipsychotic prescriptions, and 13% of anxiolytic prescriptions. Second generation antipsychotic prescription was associated with subsequent new onset binge eating, in this preliminary observational study. Self-harm by overdose of psychotropics occurred in 11% of patients prescribed medication.ConclusionsPsychotropic medications were frequently prescribed to adolescent eating disorder patients to treat distressing symptoms. Prospective randomised controlled trials to clarify efficacy and safety are needed. Given the difficulties of conducting clinical trials in this population, services are encouraged to monitor and audit medication safety and efficacy in everyday practice, and to report their findings.International Journal of Eating Disorders 08/2013; 1:27. DOI:10.1186/2050-2974-1-27 · 3.03 Impact Factor