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Antipsychotic induced weight gain

Amy Chia-Ching Kao, Sonia Spitzer, Daniel C Anthony, Belinda Lennox, Philip W J Burnet
Olanzapine is an effective antipsychotic drug but since it causes significant weight gain, it is not well tolerated by psychosis patients. The prebiotic, B-GOS® , attenuates metabolic dysfunction in obese subjects, and in rodents, alters central NMDA receptors and may affect serotonin receptors that are relevant in psychosis. We have determined whether B-GOS® influenced olanzapine-associated weight gain and central NMDA and serotonin receptors. Circulating acetate, IL-1β, IL-8 and TNFα, liver acetyl-CoA carboxylase (ACC), white adipose tissue (WAT) acetate receptor GPR43, and specific faecal bacteria genera were also measured to provide mechanistic information...
March 15, 2018: Translational Psychiatry
Clement C Zai, Arun K Tiwari, Gwyneth C Zai, Miriam S Maes, James L Kennedy
PURPOSE OF REVIEW: This review highlights recent advances in the investigation of genetic factors for antipsychotic response and side effects. RECENT FINDINGS: Antipsychotics prescribed to treat psychotic symptoms are variable in efficacy and propensity for causing side effects. The major side effects include tardive dyskinesia, antipsychotic-induced weight gain (AIWG), and clozapine-induced agranulocytosis (CIA). Several promising associations of polymorphisms in genes including HSPG2, CNR1, and DPP6 with tardive dyskinesia have been reported...
March 9, 2018: Current Opinion in Psychiatry
Kevin J Li, Ronald J Gurrera, Lynn E Delisi
Clozapine has been shown to be the most efficacious therapy for treatment resistant schizophrenia, estimated at one third of all schizophrenia cases. There is significant morbidity and mortality associated with clozapine including risk of agranulocytosis, aspiration pneumonia, bowel ischemia, myocarditis, seizures, and weight gain. Here we present a case of a 62-year-old man with chronic paranoid schizophrenia refractory to numerous antipsychotics who was started on clozapine therapy during an acute inpatient psychiatric admission...
March 1, 2018: Schizophrenia Research
Ilijana Babic, Ashleigh Gorak, Martin Engel, Dominic Sellers, Paul Else, Ashleigh L Osborne, Nagesh Pai, Xu-Feng Huang, Jessica Nealon, Katrina Weston-Green
BACKGROUND: Antipsychotic drugs (APDs), olanzapine and clozapine, do not effectively address the cognitive symptoms of schizophrenia and can cause serious metabolic side-effects. Liraglutide is a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist with anti-obesity and neuroprotective properties. The aim of this study was to examine whether liraglutide prevents weight gain/hyperglycaemia side-effects and cognitive deficits when co-administered from the commencement of olanzapine and clozapine treatment...
February 1, 2018: Journal of Psychopharmacology
Marina Sagud, Suzana Vlatkovic, Dubravka Svob Strac, Mario Sviben, Maja Zivkovic, Maja Vilibic, Bjanka Vuksan-Cusa, Alma Mihaljevic-Peles, Nela Pivac
BACKGROUND: Previous studies suggested a complex association between Toxoplasma gondii (TG) infection and host lipid metabolism. Both TG infection and metabolic disturbances are very common in patients with schizophrenia, but this relationship is not clear. METHODS: In this cross-sectional study, we evaluated the association between TG seropositivity, serum lipid levels, body mass index (BMI) and metabolic syndrome (MetS) in 210 male inpatients with schizophrenia...
February 12, 2018: Comprehensive Psychiatry
Jacob S Ballon, Utpal B Pajvani, Laurel Es Mayer, Zachary Freyberg, Robin Freyberg, Ignacio Contreras, Michael Rosenbaum, Rudolph L Leibel, Jeffrey A Lieberman
Second generation antipsychotics are prescribed for an increasing number of psychiatric conditions, despite variable associations with weight gain, dyslipidemia, and impaired glucose tolerance. The mechanism(s) of the apparent causal relationships between these medications and metabolic effects have been inadequately defined and are potentially confounded by genetic risk of mental illness, attendant lifestyle, and concomitant medications. Therefore, we conducted a study in which 24 healthy volunteers were randomized to olanzapine (highly weight-gain liability), iloperidone (less weight-gain liability), or placebo treatment for 28 days under double-blind conditions...
February 1, 2018: Journal of Psychopharmacology
Simone Pisano, Giangennaro Coppola, Gennaro Catone, Marco Carotenuto, Raffaella Iuliano, Vittoria D'Esposito, Serena Cabaro, Emanuele Miraglia Del Giudice, Carmela Bravaccio, Pietro Formisano
BACKGROUND: Youth exposed to antipsychotics may experience several metabolic consequences that often limit the effectiveness of this class of drugs. OBJECTIVES: The aim of this study was to compare several metabolic markers between subjects who experienced antipsychotic-induced weight gain and untreated obese patients. METHODS: Nineteen non-diabetic youth (mean age 159 months, mean body mass index z-score 1.81) experiencing antipsychotic-induced weight gain and an age-, sex-, and body mass index-matched group of non-diabetic obese patients with no record of treatment (n = 19, mean age 147 months, mean body mass index z-score 2) were compared for a wide range of metabolic factors using a Bioplex Multiplex system...
February 12, 2018: Clinical Drug Investigation
Michael R Rickels, Elys M Perez, Amy J Peleckis, Erica Alshehabi, Huong-Lan Nguyen, Darko Stefanovski, Karl Rickels, Karen L Teff
Atypical antipsychotic drugs have been associated with the development of obesity and diabetes. In particular, olanzapine can induce peripheral insulin resistance and compensatory hyperinsulinemia independent of weight gain or psychiatric disease. To determine if this compensatory increase in insulin is mediated by parasympathetic muscarinic stimulation, we randomized fifteen healthy subjects 2:1 to receive double-blind olanzapine or placebo for 9 days under diet and activity controlled inpatient conditions...
December 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
Charlotte Schröder, Fabian Czerwensky, Stefan Leucht, Werner Steimer
INTRODUCTION: Weight gain is a limiting and frequent adverse effect of second-generation antipsychotic therapy. Identifying genetic risk factors would significantly improve pharmacotherapy. METHODS: We focused on rs7185735 and rs9939609, 2 common single nucleotide polymorphisms of the fat mass and obesity-associated (FTO) gene reported to be associated with obesity. Three-hundred fifty Caucasian inpatients were included in a naturalistic study. RESULTS: After 4 weeks of treatment, we did not observe any significant association of polymorphisms with weight change in the whole study population (p>0...
January 15, 2018: Pharmacopsychiatry
Mingshuo Xu, Yu Wang, Feipu Yang, Chunhui Wu, Zhen Wang, Bin Ye, Xiangrui Jiang, Qingjie Zhao, Jianfeng Li, Yongjian Liu, Junchi Zhang, Guanghui Tian, Yang He, Jingshan Shen, Hualiang Jiang
In the present study, a series of multi-target N-substituted cyclic imide derivatives which possessed potent dopamine D2, serotonin 5-HT1A and 5-HT2A receptors properties were synthesized and evaluated as potential antipsychotics. Among these compounds, (3aR,4R,7S,7aS)-2-(4-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)butyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione hydrochloride (3d) held a promising pharmacological profile. 3d not only showed potent and balanced in vitro activities on D2/5-HT1A/5-HT2A receptors, but also endowed with low to moderate activities on 5-HT2C, H1, α1A, M3 receptors and hERG channel, suggesting a low liability to induce side effects such as weight gain, orthostatic hypotension and QT prolongation...
January 4, 2018: European Journal of Medicinal Chemistry
Ashish Hanmantrao Chepure, Apurva Karmveer Ungratwar
Olanzapine is a second-generation antipsychotic drug mainly used in the treatment of schizophrenia. It has several side effects including weight gain, hypercholesterolemia, and hyperglycemia, but dermatological side effects are rarely reported. We report a rare case of olanzapine-induced psoriasis.
November 2017: Indian Journal of Psychological Medicine
Norio Sugawara, Toyoaki Sagae, Norio Yasui-Furukori, Manabu Yamazaki, Kazutaka Shimoda, Takao Mori, Takuro Sugai, Hiroshi Matsuda, Yutaro Suzuki, Yuji Ozeki, Kurefu Okamoto, Toshiyuki Someya
OBJECTIVE: Patients with schizophrenia have a higher prevalence of metabolic syndrome (MetS) than the general population. Minimizing weight gain and metabolic abnormalities in a population with an already high prevalence of obesity is of clinical and social importance. This randomized controlled trial investigated the effect of monthly nutritional education on weight change and metabolic abnormalities among patients with schizophrenia in Japan. METHODS: From July 2014 to December 2014, we recruited 265 obese patients who had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder...
February 2018: Journal of Psychiatric Research
Kosuke Okazaki, Kazuhiko Yamamuro, Toshifumi Kishimoto
Aims: Antipsychotics are effective for treating schizophrenia, but atypical antipsychotics can cause several adverse side effects including weight gain, hyperprolactinemia, and extrapyramidal symptoms. Moreover, weight gain increases the risk of metabolic diseases. Methods: We treated a case of olanzapine-induced weight gain in a 41-year-old man with schizophrenia by switching his medication from olanzapine to asenapine. Results: The weight gain improved after switching the medication, from 80...
2017: Neuropsychiatric Disease and Treatment
Mitesh Kumar, Ajeet Sidana
The aim of this study is to highlight the association between the use of clozapine and the early development of hypertriglyceridemia, a condition that substantially increases the risk of cardiovascular events and other medical complications. A 34-year-old female with a background history of schizophrenia presented with acute elevation of serum triglycerides and cholesterol within 2 weeks of starting clozapine. Her metabolic parameters normalized following discontinuation of clozapine. Possible hypotheses for lipid dysregulation with atypical antipsychotics include weight gain, dietary changes, and development of glucose intolerance; however, some other factors may be responsible for this rapid escalation of lipid levels...
September 2017: Indian Journal of Psychological Medicine
Shen Li, Ying Gao, Hao Lv, Miaomiao Zhang, Lili Wang, Rui Jiang, Chengai Xu, Xueshi Wang, Ming Gao, Yukun He, Jie Li, Wei-Dong Li
Second-generation antipsychotic agents (SGAs) cause serious metabolic side effects, including weight gain, dyslipidemia, and glucose metabolism abnormalities, which occur by unknown mechanisms. Therefore, the search for prospective markers for antipsychotic-induced weight gain (AIWG) has been of major interest. So far, predictive factors predisposing patients to the develop obesity and related metabolic disturbances induced by SGAs have been relatively less studied among large samples of Chinese schizophrenic patients...
February 2018: Psychoneuroendocrinology
Bernard L Silverman, William Martin, Asli Memisoglu, Lauren DiPetrillo, Christoph U Correll, John M Kane
Antipsychotic medications are associated with weight gain and adverse metabolic effects that complicate the treatment and management of schizophrenia. Olanzapine (OLZ) in particular is associated with significant weight gain and adverse metabolic effects. The present Phase 1, proof of concept, multicenter, randomized, double-blind, placebo-controlled study investigated the safety and effect on weight of a combination of OLZ (10mg) and the opioid modulator samidorphan (SAM; 5mg) in comparison to OLZ alone in healthy, male normal weight volunteers...
November 17, 2017: Schizophrenia Research
X-F Huang, K Weston-Green, Y Yu
Second generation antipsychotics (SGAs), notably atypical antipsychotics including olanzapine, clozapine and risperidone, can cause weight gain and obesity side effects. Antagonism of serotonin 2c receptors (5-HT2cR) and activation of ghrelin receptor type 1a (GHSR1a) signalling have been identified as a main cause of SGA induced obesity. Here we review the pivotal regulatory role of the 5-HT2cR in ghrelin-mediated appetite signalling. The 5-HT2cR dimerizes with GHSR1a to inhibit orexigenic signalling, while 5-HT2cR antagonism reduces dimerization and increases GHSR1a-induced food intake...
November 9, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Chantel Kowalchuk, Celine Teo, Virginia Wilson, Araba Chintoh, Loretta Lam, Sri Mahavir Agarwal, Adria Giacca, Gary J Remington, Margaret K Hahn
BACKGROUND: Insulin receptors are widely expressed in the brain and may represent a crossroad between metabolic and cognitive disorders. Although antipsychotics, such as olanzapine, are the cornerstone treatment for schizophrenia, they are associated with high rates of type 2 diabetes and lack efficacy for illness-related cognitive deficits. Historically, this risk of diabetes was attributed to the weight gain propensity of antipsychotics, but recent work suggests antipsychotics can have weight-independent diabetogenic effects involving unknown brain-mediated mechanisms...
November 2017: Journal of Psychiatry & Neuroscience: JPN
Chantel Kowalchuk, Celine Teo, Virginia Wilson, Araba Chintoh, Loretta Lam, Sri Mahavir Agarwal, Adria Giacca, Gary J Remington, Margaret K Hahn
BACKGROUND: Insulin receptors are widely expressed in the brain and may represent a crossroad between metabolic and cognitive disorders. Although antipsychotics, such as olanzapine, are the cornerstone treatment for schizophrenia, they are associated with high rates of type 2 diabetes and lack efficacy for illness-related cognitive deficits. Historically, this risk of diabetes was attributed to the weight gain propensity of antipsychotics, but recent work suggests antipsychotics can have weight-independent diabetogenic effects involving unknown brain-mediated mechanisms...
October 16, 2017: Journal of Psychiatry & Neuroscience: JPN
Florent Auger, Françoise Martin, Olivier Pétrault, Jennifer Samaillie, Thierry Hennebelle, Mohamed-Sami Trabelsi, François Bailleul, Bart Staels, Régis Bordet, Patrick Duriez
Antipsychotics, such as risperidone, increase food intake and induce alteration in glucose and lipid metabolism concomitantly with overweight and body fat increase, these biological abnormalities belong to the metabolic syndrome definition (high visceral adiposity, hypertriglyceridemia, hyperglycemia, low HDL-cholesterol and high blood pressure). Curcumin is a major component of traditional turmeric (Curcuma longa) which has been reported to improve lipid and glucose metabolism and to decrease weight in obese mice...
October 16, 2017: Metabolic Brain Disease
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