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Antipsychotic 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
F Scheffler, S Kilian, B Chiliza, L Asmal, L Phahladira, S du Plessis, M Kidd, R M Murray, M Di Forti, S Seedat, R Emsley
While acute cannabis use stimulates appetite, general population studies suggest that chronic use is associated with reduced risk of obesity and other cardiometabolic risk factors. In this study we investigated changes in body mass index (BMI), fasting blood glucose and lipids, and rates of metabolic syndrome risk factors in cannabis users vs. non-users in 109 minimally treated patients with first-episode schizophrenia, schizophreniform or schizo-affective disorder who were treated according to a standardized treatment regime with depot antipsychotic medication over 12 months...
March 6, 2018: Schizophrenia Research
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
Cynthia Shannon Weickert, Debora A Rothmond, Tertia D Purves-Tyson
Schizophrenia is a disabling disease impacting millions of people around the world, for which there is no known cure. Current antipsychotic treatments for schizophrenia mainly target psychotic symptoms, do little to ameliorate social or cognitive deficits, have side-effects that cause weight gain, and diabetes and 30% of people do not respond. Thus, better therapeutics for schizophrenia aimed at the route biologic changes are needed and discovering the underlying neurobiology is key to this quest. Postmortem brain studies provide the most direct and detailed way to determine the pathophysiology of schizophrenia...
2018: Handbook of Clinical Neurology
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
Wei Zheng, Qing-E Zhang, Dong-Bin Cai, Xin-Hu Yang, Gabor S Ungvari, Chee H Ng, Ren-Rong Wu, Yu-Tao Xiang
INTRODUCTION: Weight gain is a common antipsychotic (AP)-related adverse drug reaction (ADR) that can increase the risk of cardiovascular diseases and premature mortality. This meta-analysis examined the efficacy and tolerability of combining metformin and lifestyle intervention for AP-related weight gain in schizophrenia. METHODS: Randomized controlled trials (RCTs) with meta-analyzable data were searched and retrieved by 2 independent investigators. RevMan software (version 5...
February 27, 2018: Pharmacopsychiatry
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
Mikaela K Barker, Carly M Sable, Sarah E Montgomery, Lorrie Chow, Timothy J Green, Constadina Panagiotopoulos, Angela M Devlin
BACKGROUND: Second-generation antipsychotic (SGA) treatment in children is associated with metabolic side effects including weight gain, dyslipidemia, and insulin resistance. The objective of this study is to determine if SGA treatment in children affects dietary intakes and relationship to metabolic side effects. METHODS: Three-day food records assessed dietary energy and macronutrient intakes in a cross-sectional population of SGA-treated (n = 35) and SGA-naïve (n = 29) children...
February 2018: Clinical Nutrition ESPEN
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
Baris Olten, Michael H Bloch
Our objective was to examine the association between antipsychotic receptor binding profiles and the magnitude of common side-effects. We used regression analysis to examine the association between the receptor binding affinities of antipsychotic agents (log Ki) and degree of specific antipsychotic side-effects. Data on magnitude of weight gain, prolactin increase and QTc prolongation (in Standardized Mean Difference) and risk of sedation and extrapyramidal symptoms (in Odds Ratio) between individual antipsychotic medications as compared to placebo was based on a recent network meta-analysis examining the treatment of schizophrenia...
February 1, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
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 previous study, a series of benzamides was identified as potent antipsychotic agents. As a continuation of the program to discover novel antipsychotics, herein we reported the evaluation of a series of pyridinecarboxamide derivatives. The most promising compound 7h not only held good activities on dopamine D2, serotonin 5-HT1A and 5-HT2A receptors, but also exhibited low potency for α1A, H1 and 5-HT2C receptors, indicating a low propensity of side effects like orthostatic hypotension and weight gain. Furthermore, 7h exhibited more potent antipsychotic-like effect than aripiprazole in behavioral studies...
January 30, 2018: Bioorganic & Medicinal Chemistry Letters
Evdokia Anagnostou
PURPOSE OF REVIEW: The purpose of this manuscript is to review the evidence generated by clinical trials of pharmaceuticals in autism spectrum disorder (ASD), describe challenges in the conduct of such trials, and discuss future directions RECENT FINDINGS: Clinical trials in ASD have produced several compounds to adequately support the pharmacological treatment of associated symptom domains: attention deficit hyperactivity disorder (methylphenidate, atomoxetine, and alpha agonists), irritability/aggression (risperidone and aripiprazole), sleep (melatonin), and weight gain associated with atypical antipsychotic use (metformin)...
January 31, 2018: Current Opinion in Neurology
Robin Emsley, Sanja Kilian
The course of schizophrenia is characterized by multiple relapses, incomplete remission of symptoms, enduring cognitive deficits, and social and occupational functional impairments. Nonadherence to antipsychotic medication is a major determinant of this poor outcome. Long-acting injectable antipsychotics were developed specifically to address the nonadherence problem and are increasingly considered as an early treatment option, in an attempt to prevent accruing morbidity. This review focuses on paliperidone palmitate, the long-acting injectable (LAI) formulation of paliperidone...
2018: Neuropsychiatric Disease and Treatment
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
Gül Dikeç, Leyla Baysan Arabaci, Gülçin Bölük Uzunoglu, Selin Demet Mizrak
The current research evaluated metabolic side effects in inpatients (N = 271) using atypical antipsychotic medications in a psychiatric hospital in Turkey between June and December 2016. Data were collected via an information form created after reviewing the literature at the time of patients' hospitalization and discharge. According to the analysis, 73.8% of patients stated they experienced side effects from antipsychotic medications and 20.7% of patients experienced weight gain. A statistical difference was detected among body mass index, waist circumference, diastolic blood pressure, and heart rate during patient hospitalization and discharge...
January 11, 2018: Journal of Psychosocial Nursing and Mental Health Services
Kyle J Burghardt, Berhane Seyoum, Abdullah Mallisho, Paul R Burghardt, Renu A Kowluru, Zhengping Yi
Atypical antipsychotics increase the risk of diabetes and cardiovascular disease through their side effects of insulin resistance and weight gain. The populations for which atypical antipsychotics are used carry a baseline risk of metabolic dysregulation prior to medication which has made it difficult to fully understand whether atypical antipsychotics cause insulin resistance and weight gain directly. The purpose of this work was to conduct a systematic review and meta-analysis of atypical antipsychotic trials in healthy volunteers to better understand their effects on insulin sensitivity and weight gain...
April 20, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
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
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