Serum ghrelin concentrations in patients receiving olanzapine or risperidone

Togo, Takashi; Hasegawa, Kôichi; Miura, Satoshi; Hosojima, Hideki; Kojima, Katsuo; Shoji, Mika; Kase, Akihiko; Uchikado, Hirotake; Iseki, Eizo; Kosaka, Kenji

doi:10.1007/s00213-003-1642-4

Cited by 56 publications

(39 citation statements)

References 10 publications

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“…30,32 As ghrelin levels are known to be influenced by obesity levels, 33 this indicates that the effect of OLA on ghrelin levels is independent of weight gain. Nevertheless, clinical findings are not entirely consistent, as other authors have reported decreased levels of ghrelin, [34][35][36][37][38] especially after short-term treatment with OLA.…”

Section: Discussionmentioning

confidence: 74%

The acute effects of olanzapine on ghrelin secretion, CCK sensitivity, meal size, locomotor activity and body temperature

et al. 2011

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Objective: Significant weight gain is a problematic side effect of treatment with the antipsychotic drug olanzapine (OLA). Previous studies in rats suggest that one of the contributing factors is an impairment in satiation that results in increased food intake. However, the mechanisms underlying this impairment in satiation remain largely unclear. Methods and results: In this study, we determined the effect of OLA on levels of leptin, insulin, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1, peptide YY and amylin in male rats that had received a fixed amount of food. OLA did not affect the secretion of any of these hormones, except for ghrelin levels, which were increased compared with controls. Furthermore, when ghrelin levels were determined in rats just before they received their meal, OLA caused a significant increase in ghrelin levels compared with controls, whereas OLA failed to affect baseline ghrelin levels. Next, we investigated the effect of OLA on the efficacy of CCK to reduce meal size. With coadministration, OLA pretreatment counteracted the reduction in meal size by CCK, although there was no significant interaction between the treatments. Finally, telemetry measurements revealed that acute OLA treatment causes a temporary decrease in both locomotor activity and body core temperature. Conclusion: Taken together, this study shows that acute injection of OLA selectively increases meal-related ghrelin secretion and this may partially underlie the impairment in satiation by OLA.

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Section: Discussionmentioning

confidence: 74%

The acute effects of olanzapine on ghrelin secretion, CCK sensitivity, meal size, locomotor activity and body temperature

et al. 2011

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“…Similarly, it appears possible that during the night, changes of leptin occur, which remain hidden in the morning. The decline of nocturnal ghrelin levels after mirtazapine resembles the lower ghrelin morning levels in schizophrenic patients who received stable treatment with risperidone or olanzapine (Togo et al, 2004), whereas it differs from the increase of ghrelin morning concentrations after 6 months of olanzapine treatment in patients with schizophrenia (Murashita et al, 2005). These contrasts show that the role of various drugs, diagnosis, duration of treatment, and time of blood sampling in changes of ghrelin needs to be disentangled.…”

Section: Discussionmentioning

confidence: 91%

“…After a 6-month treatment with olanzapine, ghrelin plasma morning levels and body fat percentage increased in patients with schizophrenia, whereas their weight and body mass index (BMI) remained unchanged (Murashita et al, 2005). On the other hand, ghrelin levels in patients with schizophrenia who were under stable doses of olanzapine or risperidone for at least 4 weeks were lower than in normal controls, whereas BMI did not differ between groups (Togo et al, 2004). The effect of treatment with antidepressants, including mirtazapine, on ghrelin levels is unknown so far.…”

Section: Introductionmentioning

confidence: 99%

Changes of Sleep Architecture, Spectral Composition of Sleep EEG, the Nocturnal Secretion of Cortisol, ACTH, GH, Prolactin, Melatonin, Ghrelin, and Leptin, and the DEX-CRH Test in Depressed Patients during Treatment with Mirtazapine

Schmid

Wichniak

Uhr

et al. 2005

Neuropsychopharmacol

146

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The noradrenergic and specific serotoninergic antidepressant mirtazapine improves sleep, modulates hormone secretion including blunting of hypothalamic-pituitary-adrenocortical (HPA) activity, and may prompt increased appetite and weight gain. The simultaneous investigation of sleep electroencephalogram (EEG) and hormone secretion during antidepressive treatment helps to further elucidate these effects. We examined sleep EEG (for later conventional and quantitative analyses) and the nocturnal concentrations of cortisol, adrenocorticotropin (ACTH), growth hormone (GH), prolactin, melatonin and the key factors of energy balance, ghrelin, and leptin before and after 28 days of treatment of depressed patients (seven women, three men, mean age 39.974.2 years) with mirtazapine. In addition, a sleep EEG was recorded at day 2 and the dexamethasone-corticotropin-releasing hormone (DEX-CRH) test was performed to assess HPA activity at days À3 and 26. Psychometry and mirtazapine plasma concentrations were measured weekly. Already at day 2, sleep continuity was improved. This effect persisted at day 28, when slow-wave sleep, low-delta, theta and alpha activity, leptin and (0300-0700) melatonin increased, and cortisol and ghrelin decreased. ACTH and prolactin remained unchanged. The first two specimens of GH collected after the start of quantitative EEG analysis were reduced at day 28. The DEX-CRH test showed, at day 26, a blunting of the overshoot of ACTH and cortisol found at day À3. The Hamilton Depression score decreased from 32.177.3 to 15.576.7 between days À1 and 28. A weight gain of approximately 3 kg was observed. This unique profile of changes is compatible with the action of mirtazapine at 5-HT-2 receptors, at presynaptic adrenergic alpha 2 receptors, at the HPA system, and on ghrelin and leptin.

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“…Increases (Murashita et al, 2005;Palik et al, 2005), decreases (Togo et al, 2004), and no change (Sporn et al, 2005;Theisen et al, 2005;Himmerich et al, 2005) in plasma ghrelin levels were reported in patients treated with SGAs; a consensus regarding clinical significance of these changes has not yet transpired. Likewise, potential contributions to weight gain of norepinephrine (Elman et al, 2002(Elman et al, , 2004 and prolactin (Melkersson, 2005;Mann et al, 2006) increases associated with SGA treatment are still unclear.…”

Section: Putative Mechanisms Of Sgas-induced Weight Gainmentioning

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

138

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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Serum ghrelin concentrations in patients receiving olanzapine or risperidone

Abstract: Our results indicate that ghrelin is not a direct cause of increased food intake and weight gain during treatment with olanzapine or risperidone, whereas ghrelin is associated with metabolic change in patients receiving these agents.

Cited by 56 publications

References 10 publications

The acute effects of olanzapine on ghrelin secretion, CCK sensitivity, meal size, locomotor activity and body temperature

The acute effects of olanzapine on ghrelin secretion, CCK sensitivity, meal size, locomotor activity and body temperature

Changes of Sleep Architecture, Spectral Composition of Sleep EEG, the Nocturnal Secretion of Cortisol, ACTH, GH, Prolactin, Melatonin, Ghrelin, and Leptin, and the DEX-CRH Test in Depressed Patients during Treatment with Mirtazapine

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

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