title: 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.
authors.affiliation: Clinical Research Group, Department of Child and Adolescent Psychiatry of the University of Marburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Brömel
authors.forename: W F
authors.initials: WF
authors.lastname: Blum
authors.forename: A
authors.initials: A
authors.lastname: Ziegler
authors.forename: E
authors.initials: E
authors.lastname: Schulz
authors.forename: M
authors.initials: M
authors.lastname: Bender
authors.forename: C
authors.initials: C
authors.lastname: Fleischhaker
authors.forename: H
authors.initials: H
authors.lastname: Remschmidt
authors.forename: J C
authors.initials: JC
authors.lastname: Krieg
authors.forename: J
authors.initials: J
authors.lastname: Hebebrand
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001823:Body Composition / Q000187:drug effects; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D020738:Leptin; D011506:Proteins / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D020738:Leptin; D011506:Proteins; D003024:Clozapine