Serum leptin levels increase rapidly after initiation of clozapine therapy

Brömel, T.; Blum, WF; Ziegler, Andreas; Schulz, Eberhard; Bender, Matthias; Fleischhaker, Christian; Remschmidt, Helmut; Krieg, J.‐C.; Hebebrand, Johannes

doi:10.1038/sj.mp.4000352

Cited by 160 publications

(113 citation statements)

References 3 publications

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“…Observational preclinical (Thornton-Jones et al, 2002;Ota et al, 2002;Hartfield et al, 2003a;Arjona et al, 2004;Cope et al, 2005) and clinical data suggest that one of the ways SGAs can lead to changes in the patterns of food intake is by increasing appetite (Figure 5b; Bromel et al, 1998;Briffa and Meehan, 1998;Eder et al, 2001;Basson et al, 2001;Kinon et al, 2005) and subsequent consumption of the previously preferred diet (Gothelf et al, 2002;Kane et al, 2004).…”

Section: Effects Of Sgas On Food Intakementioning

confidence: 99%

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Elman

Borsook

Lukas

2006

Neuropsychopharmacol

133

142

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Obesity is highly prevalent among patients with schizophrenia and is associated with detrimental health consequences. Although excessive consumption of fast food and pharmacotherapy with such second-generation antipsychotic agents (SGAs) as clozapine and olanzapine has been implicated in the schizophrenia/obesity comorbidity, the pathophysiology of this link remains unclear. Here, we propose a mechanism based on brain reward function, a relevant etiologic factor in both schizophrenia and overeating. A comprehensive literature search on neurobiology of schizophrenia and of eating behavior was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) energy homeostasis, (2) food reward and hedonics, (3) reward function in schizophrenia, and (4) metabolic effects of the SGAs. A mesolimbic hyperdopaminergic state may render motivational/incentive reward system insensitive to low salience/palatability food. This, together with poor cognitive control from hypofunctional prefrontal cortex and enhanced hedonic impact of food, owing to exaggerated opioidergic drive (clinically manifested as pain insensitivity), may underlie unhealthy eating habits in patients with schizophrenia. Treatment with SGAs purportedly improves dopamine-mediated reward aspects, but at the cost of increased appetite and worsened or at least not improved opiodergic capacity. These effects can further deteriorate eating patterns. Pathophysiological and therapeutic implications of these insights need further validation via prospective clinical trials and neuroimaging studies. INTRODUCTIONObesity has reached pandemic proportions and it is rapidly surpassing smoking as a number one killer in the industrialized world (Sturm, 2002;Skidmore and Yarnell, 2004). Its annual cost to the American society is staggering, and is estimated to be around $117 billion owing to related illnesses and loss of productivity (National Institute of Diabetes and Digestive and Kidney Diseases, 2005).In schizophrenia, obesity is twice as prevalent as in the general public, afflicting over half this patient population (Allison et al, 1999a;Dixon et al, 2000; American Diabetes Association, 2004;Marder et al, 2004;Wirshing, 2004). Besides negative psychosocial impacts (distorted selfesteem and societal stigmatization) and medications noncompliance, schizophrenics appear to be particularly susceptible to the detrimental medical sequelae of obesity such as the 'Metabolic Syndrome', which is a cluster of cardiovascular risk factors, including abdominal adiposity, insulin resistance, impaired, glucose tolerance, dyslipidemia, and hypertension (McKee et al, 1986;Mukherjee et al, 1996;Brown et al, 2000;Haupt and Newcomer, 2002;Ryan and Thakore, 2002;Ryan et al, 2003;Holt et al, 2004;Kohen, 2004;Marder et al, 2004;Lieberman et al, 2005).Excessive body weight gain (BWG) could be attributed to a constellation of endocrine, molecular, genetic, demographic, and lifestyle-related factors. Provided that a common tra...

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Section: Effects Of Sgas On Food Intakementioning

confidence: 99%

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Elman

Borsook

Lukas

2006

Neuropsychopharmacol

133

142

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“…1 Supporting this hypothesis, clozapine has been found to increase serum leptin levels within days after starting treatment. 2 Unfortunately, strict food reduction shows little success indicating that central pathways rather than peripheral actions of atypical neuroleptics or their mediators are involved in weight gain. Evaluation of the body composition revealed an increase in body fat under antipsychotic treatment with atypical antipsychotic drugs, 3 and blockade of serotonin and histamine receptors by these drugs was previously shown to be associated with weight gain.…”

mentioning

confidence: 99%

“…Six degrees of separation: on the prior probability that schizophrenia susceptibility genes converge on synapses, glutamate and NMDA receptors It has been proposed that schizophrenia susceptibility genes converge upon synapses 1,2 and glutamate, [1][2][3][4] impacting particularly on N-methyl-D-aspartate receptor (NMDAR) signalling. 1,2,4 One of the problems with the proposition concerns the prior probability that it is true.…”

mentioning

confidence: 99%

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Clozapine enhances differentiation of adipocyte progenitor cells

et al. 2006

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“…In flu ences on leptin lev els by clo zap ine, ol an zap ine, haloperi dol, and val proic acid have been re ported (41,67,68) (Ta ble 4). Al though leptin in creases may be a prod uct of weight gain, its etio patho genic con tri bu tion and in flu ence on symp tom change re main far from clear and are un der cur rent in ves ti ga tion.…”

Section: Mechanisms Of Weight Gainmentioning

confidence: 99%

Antipsychotic Metabolic Effects: Weight Gain, Diabetes Mellitus, and Lipid Abnormalities

2001

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(Weight clas si fi ca tion by BMI is shown in Ta ble 1.) These preva lence sta tis tics re flect a rapid tra jec tory of change over the past 20 years (4). Obe sity increases the risk for a myr iad of medi cal dis or ders, some forms of can cer, and all-cause mor tal ity (1,5).Re ports of weight gain in duced by con ven tional an tipsy chotics (CAPs, for ex am ple, chlor pro maz ine) be gan to ap pear soon af ter their avail abil ity (6,7). Atypi cal an tipsy chot ics (AAs, for ex am ple, risperi done, ol an zap ine, queti apine, clozap ine) of fer en hanced ef fi cacy in the treat ment of psy chotic dis or ders and are rec om mended as a first-line phar ma cothera peu tic strat egy for schizo phre nia (8). Al though AAs offer an im proved neu ro logi cal side-effect pro file, sev eral AAs ap pear to pos sess greater weight gain li abil ity than CAPs.Antipsychotic-induced weight gain has been de scribed as highly dis tress ing to pa tients, ad versely af fect ing selfesteem, and, al though dif fi cult to quan tify, de creas ing treatment ad her ence (9).The es ti mated preva lence of obe sity among per sons with schizo phre nia con verges with and may ex ceed that of the gen eral popu la tion (10). Fur ther, chronic psy chi at ric pa tients ex hibit high rela tive rates of ad verse health be hav iours (such as smok ing) and sev eral medi cal dis or ders (11).This re view sum ma rizes AA-induced weight gain and the poten tial im pact of these agents on the glu cose ho meo static network and lipid mi lieu. Weight Gain: Comparative LiabilityAntipsychotic-induced weight gain is of ten re ported in an idio syn chra tic man ner. Most authors re port an ab so lute weight change; less re ported, but per haps more clini cally rele vant, are meas ure ments such as weight gain greater than or equal to 7% from base line or pe riph eral ver sus cen tral

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Serum leptin levels increase rapidly after initiation of clozapine therapy

Cited by 160 publications

References 3 publications

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

Clozapine enhances differentiation of adipocyte progenitor cells

Antipsychotic Metabolic Effects: Weight Gain, Diabetes Mellitus, and Lipid Abnormalities

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