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Farache Trajano L, Hayes JF, Launders N, Davies NM, Osborn DPJ, Richards-Belle A. Co-prescription of metformin and antipsychotics in severe mental illness: a UK primary care cohort study. BMJ MENTAL HEALTH 2025; 28:e301505. [PMID: 40175159 PMCID: PMC11966999 DOI: 10.1136/bmjment-2024-301505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Accepted: 03/22/2025] [Indexed: 04/04/2025]
Abstract
BACKGROUND Metformin is a pharmacological candidate to mitigate second-generation antipsychotic (SGA)-induced weight gain in patients diagnosed with severe mental illnesses (SMI). OBJECTIVE To determine the incidence, prevalence and demographic patterns of metformin co-prescription among patients diagnosed with SMI initiating SGAs. To estimate the impact of metformin co-prescription on weight over 2 years post-SGA initiation. METHODS A cohort study of patients diagnosed with SMI initiating aripiprazole, olanzapine, quetiapine or risperidone in 2005-2019 using primary care data from Clinical Practice Research Datalink. We estimated cumulative incidence and period prevalences of co-prescription and explored prescribing differences by demographic and clinical factors. We compared weight change among patients prescribed an SGA-only versus an SGA plus metformin, accounting for confounders using linear regression. FINDINGS Among 26 537 patients initiating SGAs, 4652 were ever prescribed metformin and 21 885 were not. The two-year incidence of first metformin prescription was 3.3%. The SGA plus metformin group were more ethnically diverse, had greater social deprivation, more comorbidities and higher baseline weight (mean 90.4 vs 76.8 kg). By 2 years post-SGA initiation, mean weight in the SGA-only group had changed by +4.16% (95% CI -1.26 to +9.58) compared with -0.65% (95% CI -4.26 to +2.96) in the SGA plus metformin group. After confounder adjustment, the 2-year mean difference in weight with metformin co-prescription was -1.48 kg (95% CI -4.03 to 1.07) among females and -1.84 kg (95% CI -4.67 to 0.98) among males. CONCLUSION Metformin is infrequently co-prescribed, despite apparent efficacy and guidelines. CLINICAL IMPLICATIONS Primary and secondary care collaboration should be strengthened and barriers to co-prescribing addressed.
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Affiliation(s)
| | - Joseph F Hayes
- Division of Psychiatry, University College London, London, UK
- North London NHS Foundation Trust, London, UK
| | - Naomi Launders
- Division of Psychiatry, University College London, London, UK
| | - Neil M Davies
- Division of Psychiatry, University College London, London, UK
- Department of Statistical Science, University College London, London, UK
| | - David P J Osborn
- Division of Psychiatry, University College London, London, UK
- North London NHS Foundation Trust, London, UK
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Kamath S, Sokolenko E, Collins K, Chan NSL, Mills N, Clark SR, Marques FZ, Joyce P. IUPHAR themed review: The gut microbiome in schizophrenia. Pharmacol Res 2025; 211:107561. [PMID: 39732352 DOI: 10.1016/j.phrs.2024.107561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/11/2024] [Accepted: 12/23/2024] [Indexed: 12/30/2024]
Abstract
Gut microbial dysbiosis or altered gut microbial consortium, in schizophrenia suggests a pathogenic role through the gut-brain axis, influencing neuroinflammatory and neurotransmitter pathways critical to psychotic, affective, and cognitive symptoms. Paradoxically, conventional psychotropic interventions may exacerbate this dysbiosis, with antipsychotics, particularly olanzapine, demonstrating profound effects on microbial architecture through disruption of bacterial phyla ratios, diminished taxonomic diversity, and attenuated short-chain fatty acid synthesis. To address these challenges, novel therapeutic strategies targeting the gut microbiome, encompassing probiotic supplementation, prebiotic compounds, faecal microbiota transplantation, and rationalised co-pharmacotherapy, show promise in attenuating antipsychotic-induced metabolic disruptions while enhancing therapeutic efficacy. Harnessing such insights, precision medicine approaches promise to transform antipsychotic prescribing practices by identifying patients at risk of metabolic side effects based on their microbial profiles. This IUPHAR review collates the current literature landscape of the gut-brain axis and its intricate relationship with schizophrenia while advocating for integrating microbiome assessments and therapeutic management. Such a fundamental shift in proposing microbiome-informed psychotropic prescriptions to optimise therapeutic efficacy and reduce adverse metabolic impacts would align antipsychotic treatments with microbiome safety, prioritising 'gut-neutral' or gut-favourable drugs to safeguard long-term patient outcomes in schizophrenia therapy.
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Affiliation(s)
- Srinivas Kamath
- UniSA Clinical & Health Sciences, University of South Australia, Adelaide, South Australia 5000, Australia
| | - Elysia Sokolenko
- Discipline of Anatomy and Pathology, School of Biomedicine, University of Adelaide, Adelaide, South Australia 5005, Australia
| | - Kate Collins
- UniSA Clinical & Health Sciences, University of South Australia, Adelaide, South Australia 5000, Australia
| | - Nicole S L Chan
- UniSA Clinical & Health Sciences, University of South Australia, Adelaide, South Australia 5000, Australia
| | - Natalie Mills
- Discipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide, South Australia 5000, Australia
| | - Scott R Clark
- Discipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide, South Australia 5000, Australia
| | - Francine Z Marques
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; Hypertension Research Laboratory, School of Biological Sciences and Victorian Heart Institute, Monash University, Melbourne, VIC, Australia
| | - Paul Joyce
- UniSA Clinical & Health Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.
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Peng TR, Chen JA, Lee JA, Hsing CP, Lee MC, Chen SM. The Optimal Dosage and Duration of Metformin for Prevention and Treatment of Antipsychotic-Induced Weight Gain: An Updated Systematic Review and Meta-Analysis. Schizophr Bull 2024:sbae173. [PMID: 39509416 DOI: 10.1093/schbul/sbae173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
BACKGROUND Weight gain and metabolic complications are substantial adverse effects associated with second-generation antipsychotics. However, comprehensive guidelines for managing antipsychotic-induced weight gain are lacking. METHODS This review included all double-blind, placebo-controlled studies investigating metformin's effectiveness in addressing antipsychotic-related weight gain. We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Google Scholar, and ClinicalTrials.gov for relevant studies from the inception to 2024. A random-effects model was used for the meta-analysis. RESULTS This meta-analysis, including 20 studies with 1070 patients, revealed that metformin significantly surpassed placebo in attenuating weight gain in patients receiving antipsychotics. The mean weight change with metformin was -3.32 kg [95% confidence interval (CI): -4.57 to -2.07]. Additionally, metformin use resulted in a marked decrease in body mass index [-1.24 kg/m2 (95% CI: -1.70 to -0.77)]. Metformin could maintain the effects from 12 to 24 weeks. CONCLUSIONS This updated meta-analysis investigated the durations and dosages of metformin use in patients with schizophrenia experiencing antipsychotic-induced weight gain. The findings highlight the need for additional large-scale research to validate our findings.
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Affiliation(s)
- Tzu-Rong Peng
- Department of Pharmacy, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231016, Taiwan
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
| | - Jou-An Chen
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
| | - Jen-Ai Lee
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
| | - Chih-Pin Hsing
- Graduate Institute of Counseling Psychology and Rehabilitation Counseling, National Kaohsiung Normal University, Kaohsiung 80201, Taiwan
| | - Ming-Chia Lee
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
- Department of Pharmacy, New Taipei City Hospital, New Taipei City 24141, Taiwan
- Department of Nursing, Cardinal Tien College of Healthcare and Management, New Taipei City 231038, Taiwan
| | - Shih-Ming Chen
- School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
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Solmi M, Miola A, Capone F, Pallottino S, Højlund M, Firth J, Siskind D, Holt RIG, Corbeil O, Cortese S, Dragioti E, Du Rietz E, Nielsen RE, Nordentoft M, Fusar-Poli P, Hartman CA, Høye A, Koyanagi A, Larsson H, Lehto K, Lindgren P, Manchia M, Skonieczna-Żydecka K, Stubbs B, Vancampfort D, Vieta E, Taipale H, Correll CU. Risk factors, prevention and treatment of weight gain associated with the use of antidepressants and antipsychotics: a state-of-the-art clinical review. Expert Opin Drug Saf 2024; 23:1249-1269. [PMID: 39225182 DOI: 10.1080/14740338.2024.2396396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 06/12/2024] [Accepted: 08/14/2024] [Indexed: 09/04/2024]
Abstract
INTRODUCTION People with severe mental illness have poor cardiometabolic health. Commonly used antidepressants and antipsychotics frequently lead to weight gain, which may further contribute to adverse cardiovascular outcomes. AREAS COVERED We searched MEDLINE up to April 2023 for umbrella reviews, (network-)meta-analyses, trials and cohort studies on risk factors, prevention and treatment strategies of weight gain associated with antidepressants/antipsychotics. We developed 10 clinical recommendations. EXPERT OPINION To prevent, manage, and treat antidepressant/antipsychotic-related weight gain, we recommend i) assessing risk factors for obesity before treatment, ii) monitoring metabolic health at baseline and regularly during follow-up, iii) offering lifestyle interventions including regular exercise and healthy diet based on patient preference to optimize motivation, iv) considering first-line psychotherapy for mild-moderate depression and anxiety disorders, v)choosing medications based on medications' and patient's weight gain risk, vi) choosing medications based on acute vs long-term treatment, vii) using effective, tolerated medications, viii) switching to less weight-inducing antipsychotics/antidepressants where possible, ix) using early weight gain as a predictor of further weight gain to inform the timing of intervention/switch options, and x) considering adding metformin or glucagon-like peptide-1 receptor agonists, or topiramate(second-line due to potential adverse cognitive effects) to antipsychotics, or aripiprazole to clozapine or olanzapine.
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Affiliation(s)
- Marco Solmi
- Department of Psychiatry, University of Ottawa, Ottawa, Ontario, Canada
- Department of Mental Health, The Ottawa Hospital, Ottawa, Ontario, Canada
- Ottawa Hospital Research Institute (OHRI) Clinical Epidemiology Program, University of Ottawa, Ottawa, Ontario, Canada
- Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany
| | | | - Federico Capone
- Department of Medicine (DIMED), Unit of Internal Medicine III, Padua University Hospital, University of Padua, Padova, Italy
- Department of Biomedical Sciences, University of Padova, Padova, Italy
| | | | - Mikkel Højlund
- Department of Psychiatry Aabenraa, Mental Health Services in the Region of Southern Denmark, Aabenraa, Denmark
- Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark
| | - Joseph Firth
- Division of Psychology and Mental Health, University of Manchester, Manchester, UK
- Greater Manchester Mental Health NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | - Dan Siskind
- Metro South Addiction and Mental Health Service, Princess Alexandra Hospital, Brisbane, Qld, Australia
- Physical and Mental Health Research Stream, Queensland Centre for Mental Health Research, School of Clinical Medicine, Brisbane, Qld, Australia
| | - Richard I G Holt
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
- Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Olivier Corbeil
- Faculty of Pharmacy, Université Laval, Québec, Canada
- Department of Pharmacy, Quebec Mental Health University Institute, Québec, Canada
| | - Samuele Cortese
- Developmental EPI (Evidence synthesis, Prediction, Implementation) lab, Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK
- Child and Adolescent Mental Health Service, Solent NHS Trust, Southampton, UK
- Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK
- Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York, NY, USA
- DiMePRe-J-Department of Precision and Regenerative Medicine-Jonic Area, University of Bari 'Aldo Moro', Bari, Italy
| | - Elena Dragioti
- Pain and Rehabilitation Centre, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Research Laboratory Psychology of Patients, Families & Health Professionals, Department of Nursing, School of Health Sciences, University of Ioannina, Ioannina, Greece
| | - Ebba Du Rietz
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - René Ernst Nielsen
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark
| | - Merete Nordentoft
- Mental Health Centre Copenhagen, Department of Clinical Medicine, Copenhagen University Hospital, Glostrup, Denmark
| | - Paolo Fusar-Poli
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
- Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
- Outreach and Support in South-London (OASIS) service, South London and Maudlsey (SLaM) NHS Foundation Trust, London, UK
- Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian-University (LMU), Munich, Germany
| | - Catharina A Hartman
- Interdisciplinary Centre Psychopathology and Emotion regulation, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
| | - Anne Høye
- Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
- Department of Mental Health and Substance Abuse, University Hospital of North Norway, Tromsø, Norway
| | - Ai Koyanagi
- Research and Development Unit, Parc Sanitari Sant Joan de Déu, Barcelona, Spain
| | - Henrik Larsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- School of Medical Sciences, Örebro University, Örebro, Sweden
| | - Kelli Lehto
- Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Peter Lindgren
- Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden
- The Swedish Institute for Health Economics, Lund, Sweden
| | - Mirko Manchia
- Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
- Unit of Clinical Psychiatry, University Hospital Agency of Cagliari, Cagliari, Italy
- Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
| | | | - Brendon Stubbs
- Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK
| | - Davy Vancampfort
- Department of Rehabilitation Sciences, KU Leuven, Leuven, Belgium
- University Psychiatric Centre KU Leuven, Leuven, Belgium
| | - Eduard Vieta
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain
| | - Heidi Taipale
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
- Center for Psychiatry Research, Stockholm City Council, Stockholm, Sweden
- Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland
- School of Pharmacy, University of Eastern Finland, Kuopio, Finland
| | - Christoph U Correll
- Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany
- Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA
- Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
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Hegde NC, Mishra A, Maiti R, Mishra BR, Mohapatra D, Srinivasan A. Pharmacological interventions for antipsychotic-induced weight gain in schizophrenia: A network meta-analysis. Gen Hosp Psychiatry 2024; 90:12-21. [PMID: 38878592 DOI: 10.1016/j.genhosppsych.2024.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 05/08/2024] [Accepted: 06/10/2024] [Indexed: 09/13/2024]
Abstract
OBJECTIVE Antipsychotic-induced weight gain (AIWG) is a significant but frequently neglected adverse effect of first- and second-generation antipsychotic therapy, which may lead to cardiovascular disturbances. The present network meta-analysis (NMA) was conducted to evaluate and compare the effects of available treatment options in antipsychotic-induced weight gain (AIWG). METHODS The data was extracted from 68 relevant clinical trials after a literature search on MEDLINE/PubMed, Embase, Scopus, Cochrane databases and clinical trial registries. Random-effects Bayesian NMA was done to pool the effects across the interventions for the change in body weight from baseline. A network graph was built, a consistency model was run, node split analysis was performed, treatments were ranked as per the SUCRA score and meta-regression was done for the duration of therapy, baseline body weight and treatment strategy as the predictor variables. Finally, the results were sorted based on the certainty of evidence. RESULTS The drugs showing significant reduction in body weight in order of magnitude of effect size include sibutramine 10 mg (-8.0 kg; -16. to -0.21), metformin 750 mg + lifestyle modification (-7.5 kg; -12 to -2.8), topiramate 200 mg (-7 kg; -10 to -3.4), metformin 750 mg (-5.7 kg; -9.3 to -2.1), topiramate 100 mg (-5.7 kg; -8.8 to -2.5), topiramate 50 mg (-5.2 kg; -10 to -0.57), liraglutide 1.8 mg (-5.2 kg; -10., -0.080), sibutramine 15 mg (-4.5 kg; -8.9 to -0.59), nizatidine 300 mg (-3.0 kg; -5.9 to -0.23) and metformin 1000 mg (-2.3 kg; -4.6 to -0.0046). There was no effect of duration of follow-up, baseline body weight and, preventive versus therapeutic strategy on weight reduction in AIWG. CONCLUSION Metformin 750 mg with lifestyle modification was the most effective treatment for AIWG, followed by topiramate 200 mg, metformin 750 mg, and topiramate 100 mg with moderate certainty of evidence.
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Affiliation(s)
- Naveen Chandrashekar Hegde
- Senior Resident, Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India.
| | - Archana Mishra
- Senior Resident, Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India.
| | - Rituparna Maiti
- Professor, Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar.
| | - Biswa Ranjan Mishra
- Professor, Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), Bhubaneswar.
| | - Debadatta Mohapatra
- Associate Professor, Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), Bhubaneswar.
| | - Anand Srinivasan
- Additional Professor, Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar.
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Kang D, Zhang Y, Wu G, Song C, Peng X, Long Y, Yu G, Tang H, Gui Y, Wang Q, Yuan T, Wu R. The Effect of Accelerated Continuous Theta Burst Stimulation on Weight Loss in Overweight Individuals With Schizophrenia: A Double-Blind, Randomized, Sham-Controlled Clinical Trial. Schizophr Bull 2024; 50:589-599. [PMID: 37921353 PMCID: PMC11059792 DOI: 10.1093/schbul/sbad144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2023]
Abstract
BACKGROUND AND HYPOTHESIS Obesity is a common comorbidity in individuals with schizophrenia and is associated with poor clinical outcomes. At present, there are limited effective approaches for addressing this issue. We conducted a double-blind, randomized, sham-controlled clinical trial to investigate the efficacy of noninvasive magnetic stimulation techniques in reducing obesity in individuals with schizophrenia. STUDY DESIGN Forty overweight individuals with schizophrenia were recruited and randomly assigned to receive either the active or sham intervention. The active group received 50 accelerated continuous theta burst stimulation (cTBS) sessions over the left primary motor area (M1), while the sham group received sham stimulation. The primary outcomes were the change in body weight and body mass index (BMI), and the secondary outcomes were the psychiatric symptoms, eating behavior scales, metabolic measures, and electrophysiological to food picture stimuli. STUDY RESULTS The study demonstrated a significant decrease in body weight and BMI after the intervention selectively in the active group (mean = -1.33 kg, P = .002), and this improvement remained at the 1-month follow-up (mean = -2.02 kg, P = .008). The score on the Barratt Impulsivity Scale (mean = -1.78, P = 0.036) decreased in the active group and mediated the effect of accelerated cTBS on body weight. In the food picture cue electroencephalograph task, the late positive potential component, which is related to motivated attention and emotional processing, decreased in frontal brain regions and increased in posterior regions after the active intervention. CONCLUSIONS The accelerated cTBS may offer a promising approach for treating obesity in individuals with schizophrenia. Further research with a larger sample size or individualized stimulation protocol should be promising. TRIAL REGISTRATION Clinical trial registered with clinicaltrials.gov (NCT05086133).
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Affiliation(s)
- Dongyu Kang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Yi Zhang
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Guowei Wu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Chuhan Song
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Xinjie Peng
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Yujun Long
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Guo Yu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Hui Tang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Yawei Gui
- Key Laboratory of Spectral Imaging Technology, Xi’an Institute of Optics and Precision Mechanics of the Chinese Academy of Sciences, Xi’an, China
- Key Laboratory of Biomedical Spectroscopy of Xi’an, Xi’an Institute of Optics and Precision Mechanics of the Chinese Academy of Sciences, Xi’an, China
| | - Quan Wang
- Key Laboratory of Spectral Imaging Technology, Xi’an Institute of Optics and Precision Mechanics of the Chinese Academy of Sciences, Xi’an, China
- Key Laboratory of Biomedical Spectroscopy of Xi’an, Xi’an Institute of Optics and Precision Mechanics of the Chinese Academy of Sciences, Xi’an, China
| | - Tifei Yuan
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Renrong Wu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
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Kang D, Song C, Peng X, Yu G, Yang Y, Chen C, Long Y, Shao P, Wu R. The effect of continuous theta burst stimulation on antipsychotic-induced weight gain in first-episode drug-naive individuals with schizophrenia: a double-blind, randomized, sham-controlled feasibility trial. Transl Psychiatry 2024; 14:61. [PMID: 38272892 PMCID: PMC10810827 DOI: 10.1038/s41398-024-02770-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 01/07/2024] [Accepted: 01/10/2024] [Indexed: 01/27/2024] Open
Abstract
Antipsychotic intake may induce weight gain in drug-naive individuals with schizophrenia, leading to poor compliance in clinical management. However, there is still a lack of effective approaches to treat or prevent this side-effect. Therefore, we conducted this pilot study to investigate the effect of continuous theta burst stimulation (cTBS), a non-invasive magnetic stimulation technique, on preventing olanzapine-induced weight gain. Thirty-nine first-episode drug-naive individuals with schizophrenia were randomly assigned to receive either the active or sham cTBS intervention for 25 sessions (5 times per day for 5 consecutive days). The primary outcomes were changes in body weight and body mass index (BMI). Secondary outcomes included psychiatric symptoms, eating behavior scales, behavior tasks, and metabolic measures. For the result, the body weight and BMI increased significantly in the sham group but not in the active group, with a significant group effect. The active group exhibited a selective increase in the cognitive restraint domain in the Three-Factor Eating Questionnaire (TFEQ-CR) and a decrease in stop-signal reaction time compared to the sham group. The effect of cTBS on body weight was mediated by TFEQ-CR. Our findings demonstrated the feasibility that cTBS intervention could be a potential method for preventing olanzapine-induced weight gain in drug-naive first-episode schizophrenia patients through enhancing cognitive restraint to food. Trial registration: clinical trial registered with clinicaltrials.gov (NCT05086133).
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Affiliation(s)
- Dongyu Kang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China
| | - Chuhan Song
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China
| | - Xingjie Peng
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China
| | - Guo Yu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China
| | - Ye Yang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China
| | - Chuwei Chen
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China
| | - Yujun Long
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China
| | - Ping Shao
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China.
| | - Renrong Wu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China.
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Lee J, Xue X, Au E, McIntyre WB, Asgariroozbehani R, Panganiban K, Tseng GC, Papoulias M, Smith E, Monteiro J, Shah D, Maksyutynska K, Cavalier S, Radoncic E, Prasad F, Agarwal SM, Mccullumsmith R, Freyberg Z, Logan RW, Hahn MK. Glucose dysregulation in antipsychotic-naive first-episode psychosis: in silico exploration of gene expression signatures. Transl Psychiatry 2024; 14:19. [PMID: 38199991 PMCID: PMC10781725 DOI: 10.1038/s41398-023-02716-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/10/2023] [Accepted: 12/14/2023] [Indexed: 01/12/2024] Open
Abstract
Antipsychotic (AP)-naive first-episode psychosis (FEP) patients display early dysglycemia, including insulin resistance and prediabetes. Metabolic dysregulation may therefore be intrinsic to psychosis spectrum disorders (PSDs), independent of the metabolic effects of APs. However, the potential biological pathways that overlap between PSDs and dysglycemic states remain to be identified. Using meta-analytic approaches of transcriptomic datasets, we investigated whether AP-naive FEP patients share overlapping gene expression signatures with non-psychiatrically ill early dysglycemia individuals. We meta-analyzed peripheral transcriptomic datasets of AP-naive FEP patients and non-psychiatrically ill early dysglycemia subjects to identify common gene expression signatures. Common signatures underwent pathway enrichment analysis and were then used to identify potential new pharmacological compounds via Integrative Library of Integrated Network-Based Cellular Signatures (iLINCS). Our search results yielded 5 AP-naive FEP studies and 4 early dysglycemia studies which met inclusion criteria. We discovered that AP-naive FEP and non-psychiatrically ill subjects exhibiting early dysglycemia shared 221 common signatures, which were enriched for pathways related to endoplasmic reticulum stress and abnormal brain energetics. Nine FDA-approved drugs were identified as potential drug treatments, of which the antidiabetic metformin, the first-line treatment for type 2 diabetes, has evidence to attenuate metabolic dysfunction in PSDs. Taken together, our findings support shared gene expression changes and biological pathways associating PSDs with dysglycemic disorders. These data suggest that the pathobiology of PSDs overlaps and potentially contributes to dysglycemia. Finally, we find that metformin may be a potential treatment for early metabolic dysfunction intrinsic to PSDs.
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Grants
- R01 DK124219 NIDDK NIH HHS
- R01 HL150432 NHLBI NIH HHS
- R01 MH107487 NIMH NIH HHS
- R01 MH121102 NIMH NIH HHS
- Holds the Meighen Family Chair in Psychosis Prevention, the Cardy Schizophrenia Research Chair, a Danish Diabetes Academy Professorship, a Steno Diabetes Center Fellowship, and a U of T Academic Scholar Award, and is funded by operating grants from the Canadian Institutes of Health Research (CIHR), the Banting and Best Diabetes Center, the Miners Lamp U of T award, CIHR and Canadian Psychiatric Association Glenda MacQueen Memorial Award, and the PSI Foundation.
- Hilda and William Courtney Clayton Paediatric Research Fund and Dr. LG Rao/Industrial Partners Graduate Student Award from the University of Toronto, and Meighen Family Chair in Psychosis Prevention
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
- UofT | Banting and Best Diabetes Centre, University of Toronto (BBDC)
- Canadian Institutes of Health Research (CIHR) Canada Graduate Scholarship-Master’s program
- Cleghorn Award
- University of Toronto (UofT)
- Centre for Addiction and Mental Health (Centre de Toxicomanie et de Santé Mentale)
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
- U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)
- U.S. Department of Defense (United States Department of Defense)
- Commonwealth of Pennsylvania Formula Fund, The Pittsburgh Foundation
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Affiliation(s)
- Jiwon Lee
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Xiangning Xue
- Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Emily Au
- Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
| | - William B McIntyre
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
| | - Roshanak Asgariroozbehani
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Kristoffer Panganiban
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - George C Tseng
- Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | | | - Emily Smith
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Centre for Addiction and Mental Health, Toronto, ON, Canada
| | | | - Divia Shah
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
| | - Kateryna Maksyutynska
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Samantha Cavalier
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
| | - Emril Radoncic
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
| | - Femin Prasad
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Sri Mahavir Agarwal
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Robert Mccullumsmith
- Department of Neurosciences, University of Toledo, Toledo, OH, USA
- ProMedica, Toledo, OH, USA
| | - Zachary Freyberg
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Ryan W Logan
- Department of Neurobiology, University of Massachusetts Chan Medical School, Worcester, MA, USA
- Department of Psychiatry, University of Massachusetts Chan Medical School, Worcester, MA, USA
- Department of Pharmacology, Physiology & Biophysics, Boston University School of Medicine, Boston, MA, USA
| | - Margaret K Hahn
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
- Centre for Addiction and Mental Health, Toronto, ON, Canada.
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
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9
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Abstract
Psychotropic drug-related weight gain (PDWG) is a common occurrence and is highly associated with non-initiation, discontinuation, and dissatisfaction with psychiatric drugs. Moreover, PDWG intersects with the elevated risk for obesity and associated morbidity that has been amply reported in the psychiatric population. Evidence indicates that differential liability for PDWG exists for antipsychotics, antidepressants, and anticonvulsants. During the past two decades, agents within these classes have become available with significantly lower or no liability for PDWG and as such should be prioritized. Although lithium is associated with weight gain, the overall extent of weight gain is significantly lower than previously estimated. The benefit of lifestyle and behavioral modification for obesity and/or PDWG in psychiatric populations is established, with effectiveness similar to that in the general population. Metformin is the most studied pharmacological treatment in the prevention and treatment of PDWG, and promising data are emerging for glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide, exenatide, semaglutide). Most pharmacologic antidotes for PDWG are supported with low-confidence data (e.g., topiramate, histamine-2 receptor antagonists). Future vistas for pharmacologic treatment for PDWG include large, adequately controlled studies with GLP-1 receptor agonists and possibly GLP-1/glucose-dependent insulinotropic polypeptide co-agonists (e.g., tirzepatide) as well as specific dietary modifications.
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Affiliation(s)
- Roger S McIntyre
- Department of Psychiatry (McIntyre, Rosenblat, Mansur) and Department of Pharmacology and Toxicology (McIntyre, Rosenblat, Mansur), University of Toronto, Toronto; Brain and Cognition Discovery Foundation, Toronto (McIntyre, Kwan, Teopiz); Faculty of Medicine, University of Ottawa, Ottawa (Kwan)
| | - Angela T H Kwan
- Department of Psychiatry (McIntyre, Rosenblat, Mansur) and Department of Pharmacology and Toxicology (McIntyre, Rosenblat, Mansur), University of Toronto, Toronto; Brain and Cognition Discovery Foundation, Toronto (McIntyre, Kwan, Teopiz); Faculty of Medicine, University of Ottawa, Ottawa (Kwan)
| | - Joshua D Rosenblat
- Department of Psychiatry (McIntyre, Rosenblat, Mansur) and Department of Pharmacology and Toxicology (McIntyre, Rosenblat, Mansur), University of Toronto, Toronto; Brain and Cognition Discovery Foundation, Toronto (McIntyre, Kwan, Teopiz); Faculty of Medicine, University of Ottawa, Ottawa (Kwan)
| | - Kayla M Teopiz
- Department of Psychiatry (McIntyre, Rosenblat, Mansur) and Department of Pharmacology and Toxicology (McIntyre, Rosenblat, Mansur), University of Toronto, Toronto; Brain and Cognition Discovery Foundation, Toronto (McIntyre, Kwan, Teopiz); Faculty of Medicine, University of Ottawa, Ottawa (Kwan)
| | - Rodrigo B Mansur
- Department of Psychiatry (McIntyre, Rosenblat, Mansur) and Department of Pharmacology and Toxicology (McIntyre, Rosenblat, Mansur), University of Toronto, Toronto; Brain and Cognition Discovery Foundation, Toronto (McIntyre, Kwan, Teopiz); Faculty of Medicine, University of Ottawa, Ottawa (Kwan)
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10
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Lee J, Xue X, Au E, McIntyre WB, Asgariroozbehani R, Tseng GC, Papoulias M, Panganiban K, Agarwal SM, Mccullumsmith R, Freyberg Z, Logan RW, Hahn MK. Central insulin dysregulation in antipsychotic-naïve first-episode psychosis: In silico exploration of gene expression signatures. Psychiatry Res 2024; 331:115636. [PMID: 38104424 PMCID: PMC10984627 DOI: 10.1016/j.psychres.2023.115636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 10/18/2023] [Accepted: 11/25/2023] [Indexed: 12/19/2023]
Abstract
Antipsychotic drug (AP)-naïve first-episode psychosis (FEP) patients display premorbid cognitive dysfunctions and dysglycemia. Brain insulin resistance may link metabolic and cognitive disorders in humans. This suggests that central insulin dysregulation represents a component of the pathophysiology of psychosis spectrum disorders (PSDs). Nonetheless, the links between central insulin dysregulation, dysglycemia, and cognitive deficits in PSDs are poorly understood. We investigated whether AP-naïve FEP patients share overlapping brain gene expression signatures with central insulin perturbation (CIP) in rodent models. We systematically compiled and meta-analyzed peripheral transcriptomic datasets of AP-naïve FEP patients along with hypothalamic and hippocampal datasets of CIP rodent models to identify common transcriptomic signatures. The common signatures were used for pathway analysis and to identify potential drug treatments with discordant (reverse) signatures. AP-naïve FEP and CIP (hypothalamus and hippocampus) shared 111 and 346 common signatures respectively, which were associated with pathways related to inflammation, endoplasmic reticulum stress, and neuroplasticity. Twenty-two potential drug treatments were identified, including antidiabetic agents. The pathobiology of PSDs may include central insulin dysregulation, which contribute to dysglycemia and cognitive dysfunction independently of AP treatment. The identified treatments may be tested in early psychosis patients to determine if dysglycemia and cognitive deficits can be mitigated.
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Affiliation(s)
- Jiwon Lee
- Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
| | - Xiangning Xue
- Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
| | - Emily Au
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
| | - William B McIntyre
- Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
| | - Roshanak Asgariroozbehani
- Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
| | - George C Tseng
- Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
| | - Maria Papoulias
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
| | - Kristoffer Panganiban
- Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
| | - Sri Mahavir Agarwal
- Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
| | - Robert Mccullumsmith
- Department of Neurosciences, University of Toledo, Toledo, Ohio, United States; ProMedica, Toledo, Ohio, United States.
| | - Zachary Freyberg
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, United States; Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
| | - Ryan W Logan
- Department of Psychiatry, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States; Department of Neurobiology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States.
| | - Margaret K Hahn
- Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
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11
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Diniz BS, Seitz-Holland J, Sehgal R, Kasamoto J, Higgins-Chen AT, Lenze E. Geroscience-Centric Perspective for Geriatric Psychiatry: Integrating Aging Biology With Geriatric Mental Health Research. Am J Geriatr Psychiatry 2024; 32:1-16. [PMID: 37845116 PMCID: PMC10841054 DOI: 10.1016/j.jagp.2023.09.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 08/30/2023] [Accepted: 09/14/2023] [Indexed: 10/18/2023]
Abstract
The geroscience hypothesis asserts that physiological aging is caused by a small number of biological pathways. Despite the explosion of geroscience research over the past couple of decades, the research on how serious mental illnesses (SMI) affects the biological aging processes is still in its infancy. In this review, we aim to provide a critical appraisal of the emerging literature focusing on how we measure biological aging systematically, and in the brain and how SMIs affect biological aging measures in older adults. We will also review recent developments in the field of cellular senescence and potential targets for interventions for SMIs in older adults, based on the geroscience hypothesis.
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Affiliation(s)
- Breno S Diniz
- UConn Center on Aging & Department of Psychiatry (BSD), School of Medicine, University of Connecticut Health Center, Farmington, CT.
| | - Johanna Seitz-Holland
- Department of Psychiatry (JSH), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Psychiatry (JSH), Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Raghav Sehgal
- Program in Computational Biology and Bioinformatics (RS, JK), Yale University, New Haven, CT
| | - Jessica Kasamoto
- Program in Computational Biology and Bioinformatics (RS, JK), Yale University, New Haven, CT
| | - Albert T Higgins-Chen
- Department of Psychiatry (ATHC), Yale University School of Medicine, New Haven, CT; Department of Pathology (ATHC), Yale University School of Medicine, New Haven, CT
| | - Eric Lenze
- Department of Psychiatry (EL), School of Medicine, Washington University at St. Louis, St. Louis, MO
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12
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Schmitz SH, Aronne LJ. The Effective Use of Anti-obesity Medications. Gastroenterol Clin North Am 2023; 52:661-680. [PMID: 37919019 DOI: 10.1016/j.gtc.2023.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2023]
Abstract
Obesity is a heterogeneous disease and there is wide patient-to-patient variability in response to all anti-obesity treatments including lifestyle modifications, anti-obesity medications (AOMs), devices, and bariatric surgery. To effectively treat obesity, practitioners must be knowledgeable about all of these treatment modalities including on-label and off-label AOMs. Care should be individualized to the patient taking into consideration their unique challenges with weight loss, their goals, the presence of comorbidities, medication contraindications, and drug-drug interactions. There is currently no way to know which AOM will be most effective for a patient without trial and error; therefore, prescribe AOMs in sequence and consider combination therapy for optimal results. This article reviews the efficacy, safety, prescribing information, and other considerations for all of the currently available AOMs.
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Affiliation(s)
- Sarah H Schmitz
- Division of Endocrinology, Diabetes & Metabolism, New York-Presbyterian Hospital/ Weill Cornell Medical College, Comprehensive Weight Control Center, 1305 York Avenue, 4th Floor, New York, NY 10021, USA.
| | - Louis J Aronne
- Division of Endocrinology, Diabetes & Metabolism, New York-Presbyterian Hospital/ Weill Cornell Medical College, Comprehensive Weight Control Center, 1305 York Avenue, 4th Floor, New York, NY 10021, USA
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13
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Shao T, Huang J, Zhao Y, Wang W, Tian X, Hei G, Kang D, Gao Y, Liu F, Zhao J, Liu B, Yuan TF, Wu R. Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex. Transl Psychiatry 2023; 13:315. [PMID: 37821461 PMCID: PMC10567690 DOI: 10.1038/s41398-023-02616-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 09/21/2023] [Accepted: 09/26/2023] [Indexed: 10/13/2023] Open
Abstract
Cognitive impairment is a core feature of schizophrenia, which is aggravated by antipsychotics-induced metabolic disturbance and lacks effective pharmacologic treatments in clinical practice. Our previous study demonstrated the efficiency of metformin in alleviating metabolic disturbance following antipsychotic administration. Here we report that metformin could ameliorate cognitive impairment and improve functional connectivity (FC) in prefrontal regions. This is an open-labeled, evaluator-blinded study. Clinically stable patients with schizophrenia were randomly assigned to receive antipsychotics plus metformin (N = 48) or antipsychotics alone (N = 24) for 24 weeks. The improvement in cognition was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Its association with metabolic measurements, and voxel-wise whole-brain FC with dorsolateral prefrontal cortex (DLPFC) subregions as seeds were evaluated. When compared to the antipsychotics alone group, the addition of metformin resulted in significantly greater improvements in the MCCB composite score, speed of processing, working memory, verbal learning, and visual learning. A significant time × group interaction effect of increased FC between DLPFC and the anterior cingulate cortex (ACC)/middle cingulate cortex (MCC), and between DLPFC subregions were observed after metformin treatment, which was positively correlated with MCCB cognitive performance. Furthermore, the FC between left DLPFC A9/46d to right ACC/MCC significantly mediated metformin-induced speed of processing improvement; the FC between left A46 to right ACC significantly mediated metformin-induced verbal learning improvement. Collectively, these findings demonstrate that metformin can improve cognitive impairments in schizophrenia patients and is partly related to the FC changes in the DLPFC. Trial Registration: The trial was registered with ClinicalTrials.gov (NCT03271866). The full trial protocol is provided in Supplementary Material.
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Affiliation(s)
- Tiannan Shao
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, PR China
| | - Jing Huang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, PR China
| | - Yuxin Zhao
- Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, PR China
- School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, 100049, PR China
| | - Weiyan Wang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, PR China
| | - Xiaohan Tian
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, 100875, PR China
| | - Gangrui Hei
- Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, PR China
| | - Dongyu Kang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, PR China
| | - Yong Gao
- Department of Orthopedics, The First People's Hospital of Changde, Changde Hospital Affiliated to Xiangya Medical College of Central South University, Changde, 415900, PR China
| | - Fangkun Liu
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, PR China
| | - Jingping Zhao
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, PR China
| | - Bing Liu
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, 100875, PR China
| | - Ti-Fei Yuan
- Shanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, PR China
- Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, PR China
- Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, 200434, PR China
| | - Renrong Wu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, PR China.
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14
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Battini V, Cirnigliaro G, Leuzzi R, Rissotto E, Mosini G, Benatti B, Pozzi M, Nobile M, Radice S, Carnovale C, Dell’Osso B, Clementi E. The potential effect of metformin on cognitive and other symptom dimensions in patients with schizophrenia and antipsychotic-induced weight gain: a systematic review, meta-analysis, and meta-regression. Front Psychiatry 2023; 14:1215807. [PMID: 37502816 PMCID: PMC10370497 DOI: 10.3389/fpsyt.2023.1215807] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 06/20/2023] [Indexed: 07/29/2023] Open
Abstract
Introduction Metformin has shown good efficacy in the management of antipsychotic-induced metabolic syndrome (MetS) in patients with schizophrenia or schizoaffective disorders. Its ability to induce antidepressant behavioural effects and improve cognitive functions has also been investigated: yet information has not been systematized. The aim of this study was therefore to investigate the effects of metformin on cognitive and other symptom dimension in schizophrenic patients treated with antipsychotics through a systematic review and meta-analysis. Methods We searched PubMed, ClinicalTrials.Gov, Embase, PsycINFO, and WHO ICTRP database up to February 2022, Randomised Controlled Trials (RCT) evaluating patients diagnosed with schizophrenia and related disorders, who were treated with metformin as add-on therapy to antipsychotics for the treatment of weight gain and in which changes in psychiatric symptoms and cognitive functions were evaluated. Results A total of 19 RCTs met the inclusion criteria. Meta-analysis was performed on 12 eligible studies. We found a positive trend after 24 weeks of treatment in schizophrenic patients with stable conditions [SMD (95%CI) = -0.40 (-0.82;0.01), OR (95%CI) = 0.5 (-2.4;3.4)]. Better performance was detected in the Brief Assessment of Cognition in Schizophrenia and Positive and Negative Syndrome Scale (PANSS) with low heterogeneity among studies. One study reported changes in BACS-verbal memory subdomain in favour of placebo [MD (95%CI) = -16.03 (-23.65;8.42)]. Gastrointestinal disorders, xerostomia, and extrapyramidal syndrome were the most reported adverse effects. Psychiatric adverse events were also described: in particular, symptoms attributable to a relapse of schizophrenia. Conclusion Some degree of efficacy was found for Metformin in improving cognitive and other symptom dimensions in patients with Schizophrenia. Given the clinical relevance of this potential pharmacological effect, longer specific studies using adequate psychometric scales are strongly recommended. Likewise, how metformin acts in this context needs to be evaluated in order to enhance its efficacy or find more efficacious drugs.
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Affiliation(s)
- Vera Battini
- Department of Biomedical and Clinical Sciences, Pharmacovigilance & Clinical Research, International Centre for Pesticides and Health Risk Prevention, ASST Fatebenefratelli-Sacco, Università degli Studi di Milano, Milan, Italy
| | - Giovanna Cirnigliaro
- Department of Biomedical and Clinical Sciences, Psychiatry Unit 2, ASST Fatebenefratelli-Sacco, Università degli Studi di Milano, Milan, Italy
| | - Rodolfo Leuzzi
- Department of Biomedical and Clinical Sciences, Psychiatry Unit 2, ASST Fatebenefratelli-Sacco, Università degli Studi di Milano, Milan, Italy
| | - Eleonora Rissotto
- Department of Biomedical and Clinical Sciences, Psychiatry Unit 2, ASST Fatebenefratelli-Sacco, Università degli Studi di Milano, Milan, Italy
| | - Giulia Mosini
- Department of Biomedical and Clinical Sciences, Pharmacovigilance & Clinical Research, International Centre for Pesticides and Health Risk Prevention, ASST Fatebenefratelli-Sacco, Università degli Studi di Milano, Milan, Italy
| | - Beatrice Benatti
- Department of Biomedical and Clinical Sciences, Psychiatry Unit 2, ASST Fatebenefratelli-Sacco, Università degli Studi di Milano, Milan, Italy
- CRC “Aldo Ravelli” for Neurotechnology & Experimental Brain Therapeutics, Università degli Studi di Milano, Milan, Italy
| | - Marco Pozzi
- Scientific Institute, IRCCS E. Medea, Bosisio Parini, Italy
| | - Maria Nobile
- Scientific Institute, IRCCS E. Medea, Bosisio Parini, Italy
| | - Sonia Radice
- Department of Biomedical and Clinical Sciences, Pharmacovigilance & Clinical Research, International Centre for Pesticides and Health Risk Prevention, ASST Fatebenefratelli-Sacco, Università degli Studi di Milano, Milan, Italy
| | - Carla Carnovale
- Department of Biomedical and Clinical Sciences, Pharmacovigilance & Clinical Research, International Centre for Pesticides and Health Risk Prevention, ASST Fatebenefratelli-Sacco, Università degli Studi di Milano, Milan, Italy
| | - Bernardo Dell’Osso
- Department of Biomedical and Clinical Sciences, Psychiatry Unit 2, ASST Fatebenefratelli-Sacco, Università degli Studi di Milano, Milan, Italy
- CRC “Aldo Ravelli” for Neurotechnology & Experimental Brain Therapeutics, Università degli Studi di Milano, Milan, Italy
- Department of Psychiatry and Behavioral Sciences, Bipolar Disorders Clinic, Stanford Medical School, Stanford University, Stanford, CA, United States
- Centro per lo studio dei meccanismi molecolari alla base delle patologie neuro-psico-geriatriche, Università degli Studi di Milano, Milan, Italy
| | - Emilio Clementi
- Department of Biomedical and Clinical Sciences, Pharmacovigilance & Clinical Research, International Centre for Pesticides and Health Risk Prevention, ASST Fatebenefratelli-Sacco, Università degli Studi di Milano, Milan, Italy
- Scientific Institute, IRCCS E. Medea, Bosisio Parini, Italy
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15
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Singh VK, Muralidhar D, Malo PK, Bhaskarapillai B, Muralidharan K. Effectiveness of Short-Term Lifestyle Modification on Reducing Body- Weight-Related Parameters in Persons with Severe Mental Illness: A Randomized Controlled Trial. Indian J Psychol Med 2023; 45:352-359. [PMID: 37483568 PMCID: PMC10357896 DOI: 10.1177/02537176231155039] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/25/2023] Open
Abstract
Background Persons with severe mental illness (SMI) reportedly have a high mortality rate due to metabolic syndrome (MS). However, lifestyle modification (LM) offers effective management of some components of MS. This study aimed to evaluate the effectiveness of LM in reducing body-weight-related parameters in SMIs. Method Eighty participants with SMI were assigned randomly to either LM (n = 40) or treatment as usual (TAU; n = 40) groups using block randomization (eight blocks of n = 10). The LM group and their caregivers received a structured LM package that included nutrition counselling, recommendations on a balanced diet, and physical activity. The two groups were assessed on body weight, body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and quality of life (QOL) at baseline and after three months. Thirty-one LM and 33 TAU participants completed the study. Results The LM and TAU groups were comparable on sociodemographic and clinical characteristics and baseline variables of body weight, BMI, WC, and WHR (all P > 0.08). Repeated-measures analysis of variance (RM ANOVA) showed that the LM group had significantly reduced body weight, BMI, WC, and WHR (all P < 0.001) than the TAU group. Similarly, the LM group also showed improvement in their QOL (P < 0.001), whereas TAU showed no improvement. Conclusions LM is an effective way to reduce body-weight-related parameters of MS and improves the QOL among persons with SMI in the short term. The caregivers' inclusion during LM contributed to the weight reduction. However, the long-term effect of the intervention could not be assessed.
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Affiliation(s)
- Vinit Kumar Singh
- Dept. of Psychiatric Social Work, National Institute of Mental Health and Neurosciences (INI), Bengaluru, Karnataka, India
| | - Daliboina Muralidhar
- Dept. of Psychiatric Social Work, National Institute of Mental Health and Neurosciences (INI), Bengaluru, Karnataka, India
| | - Palash Kumar Malo
- Dept. of Biostatistics, National Institute of Mental Health and Neurosciences (INI), Bengaluru, Karnataka, India
| | - Binukumar Bhaskarapillai
- Dept. of Biostatistics, National Institute of Mental Health and Neurosciences (INI), Bengaluru, Karnataka, India
| | - Kesavan Muralidharan
- Dept. of Psychiatry, National Institute of Mental Health and Neurosciences (INI), Bengaluru, Karnataka, India
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16
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Cai J, Li L, Shao T, Sun M, Wang W, Xie P, Wang X, Yang Y, Long Y, Kang D, Xiao J, Su Y, Peng X, Huang Y, Gao M, Wu Q, Song C, Liu F, Shao P, Ou J, Shen Y, Huang J, Wu R. Relapse in patients with schizophrenia and amisulpride-induced hyperprolactinemia or olanzapine-induced metabolic disturbance after switching to other antipsychotics. Psychiatry Res 2023; 322:115138. [PMID: 36871411 DOI: 10.1016/j.psychres.2023.115138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 02/21/2023] [Accepted: 02/25/2023] [Indexed: 03/07/2023]
Abstract
Hyperprolactinemia and metabolic disturbance are common side effects of antipsychotics that cause intolerance. Despite its potential influence on relapse, there are no established guidelines for antipsychotic switching. This naturalistic study explored the association between antipsychotic switching, baseline clinical status, metabolic changes, and relapse in patients with schizophrenia. In total, 177 patients with amisulpride-induced hyperprolactinemia and 274 with olanzapine-induced metabolic disturbance were enrolled. Relapse was determined by assessing changes in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to 6 months (increased over 20% or 10% reaching 70). Metabolic indices were measured at baseline and 3 months. Patients with baseline PANSS >60 were more likely to relapse. Further, patients switching to aripiprazole had a higher risk of relapse regardless of their original medication. Participants who originally used amisulpride had reduced prolactin levels following medication change, while switching to olanzapine caused increased weight and blood glucose levels. In patients originally using olanzapine, only switching to aripiprazole reduced insulin resistance. Adverse effects on weight and lipid metabolism were observed in patients who switched to risperidone, while amisulpride improved lipid profiles. Changing schizophrenia treatment requires careful consideration of multiple variables, particularly the choice of substituted drug and the patient's baseline symptoms.
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Affiliation(s)
- Jingda Cai
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Li Li
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Tiannan Shao
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Mengxi Sun
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Weiyan Wang
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Peng Xie
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Xiaoyi Wang
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Ye Yang
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Yujun Long
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Dongyu Kang
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Jingmei Xiao
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Yuhan Su
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Xingjie Peng
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Yuyan Huang
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Menghui Gao
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Qiongqiong Wu
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Chuhan Song
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Furu Liu
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Ping Shao
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Jianjun Ou
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Yidong Shen
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Jing Huang
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Renrong Wu
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China.
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17
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Ye W, Xing J, Yu Z, Hu X, Zhao Y. Mechanism and treatments of antipsychotic-induced weight gain. Int J Obes (Lond) 2023; 47:423-433. [PMID: 36959286 DOI: 10.1038/s41366-023-01291-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 02/26/2023] [Accepted: 02/28/2023] [Indexed: 03/25/2023]
Abstract
The long-term use of antipsychotics (APs) may cause a variety of diseases, such as metabolic syndrome, antipsychotic-induced weight gain (AIWG), and even obesity. This paper reviews the various mechanisms of AIWG and obesity in detail, involving genetics, the central nervous system, the neuroendocrine system, and the gut microbiome. The common drug and non-drug therapies used in clinical practice are also introduced, providing the basis for research on the molecular mechanisms and the future selection of treatments.
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Affiliation(s)
- Wujie Ye
- School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Jingyu Xing
- School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Zekai Yu
- School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Xingang Hu
- Internal encephalopathy of traditional Chinese medicine, Dongfang Hospital of Beijing University of Chinese Medicine, Beijing, 100078, China.
| | - Yan Zhao
- School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
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18
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Claridy MD, Perez NP, Czepiel KS, Acholonu NO, Stanford FC. Association Between Weight Promoting Medication Use and Weight Status Among Children and Adolescents in the United States. Acad Pediatr 2023; 23:102-108. [PMID: 35533966 PMCID: PMC10042467 DOI: 10.1016/j.acap.2022.04.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Revised: 04/15/2022] [Accepted: 04/30/2022] [Indexed: 01/24/2023]
Abstract
OBJECTIVES The objectives of this study were to 1) examine the prevalence of prescription medication use overall and 2) examine the association between weight promoting medication (WPM) use by therapeutic class and weight status among a nationally representative sample of the children and adolescents in the United States. This study also further investigated antidepressant medication use among this population. METHODS This cross-sectional study used data from the National Health and Nutrition Examination Survey from 2013 to 2018. Children and adolescents ages 2 to 19 years were included in this study. RESULTS Of the 68,057,468 derived participants (34,507,154 [50.7%] male; 33,564,059 [49.3%] aged 2-10 years; 34,905,058 [51.3%] non-Hispanic White), 14,895,618 (22.2%) used a prescription medication in the prior 30 days, 21.7% (3,235,323) of which were considered weight promoting. There was no significant difference between weight status and WPM use for overall prescription medication use. Nevertheless, for overall antidepressant medication use, those with obesity were less likely to be prescribed antidepressant WPM when compared to those with normal weight (adjusted odds ratios 0.4; 95% confidence interval 0.2-0.7). CONCLUSIONS These findings suggest that although there was no significant association between WPM use and weight status overall when examining the association by therapeutic class, most children with obesity were not using antidepressant WPM. This is reassuring and potentially an active attempt at avoiding the use of medications that have an exacerbating effect on weight gain. When choosing antidepressant medications, providers, parents, and patients consider the WPM effects and appropriately choose a medication best suited to the child's health status.
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Affiliation(s)
- Mechelle D Claridy
- Department of Epidemiology and Biostatistics, University of Georgia (MD Claridy), Athens, Ga
| | - Numa P Perez
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School (NP Perez), Boston, Mass
| | - Kathryn S Czepiel
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Stanford School of Medicine (KS Czepiel), Stanford, Calif
| | - Nonyerem O Acholonu
- Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School (NO Acholonu), Boston, Mass
| | - Fatima Cody Stanford
- Department of Medicine, Neuroendocrine Unit, Department of Pediatrics, Pediatric Endocrinology, Massachusetts General Hospital and Harvard Medical School (FC Stanford), Boston, Mass.
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19
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Bai L, Liang W, Wang Y, Fan N, Zhang Q, Bian Y, Yang F. Effects of Adjunctive Betahistine Therapy on Lipid Metabolism in Patients with Chronic Schizophrenia: A Randomized Double-Blind Placebo-Controlled Study. Neuropsychiatr Dis Treat 2023; 19:453-460. [PMID: 36874957 PMCID: PMC9984272 DOI: 10.2147/ndt.s392770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 01/27/2023] [Indexed: 03/02/2023] Open
Abstract
OBJECTIVE This study aims to explore the ability of betahistine to inhibit weight gain and abnormal lipid metabolism in patients with chronic schizophrenia. METHODS A comparison study of betahistine or placebo therapy was conducted for 4 weeks in 94 patients with chronic schizophrenia, who were randomly divided into two groups. Clinical information and lipid metabolic parameters were collected. Positive and Negative Syndrome Scale (PANSS) was used to assess psychiatric symptoms. Treatment Emergent Symptom Scale (TESS) was used to evaluate treatment-related adverse reactions. The differences in lipid metabolic parameters before and after treatment between the two groups were compared. RESULTS Repeated measures analysis of variance (ANOVA) revealed that after 4 weeks of betahistine/placebo treatment, the interaction effect of time and group was statistically significant on low-density lipoprotein cholesterol (F = 6.453, p = 0.013) and waist-to-hip ratio (F = 4.473, p = 0.037), but did not reveal any significant interaction effect of time and group on weight, body mass index or other lipid metabolic parameters, as well as the time main effect and group main effect (all p > 0.05). Betahistine had no significant impact on PANSS, and no side effects related to betahistine were detected. CONCLUSION Betahistine may delay metabolic abnormalities in patients with chronic schizophrenia. It does not affect the efficacy of the original antipsychotics. Thus, it provides new ideas for the treatment of metabolic syndrome in patients with chronic schizophrenia.
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Affiliation(s)
- Luyuan Bai
- Peking University Huilongguan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, People's Republic of China
| | - Weiye Liang
- Peking University Huilongguan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, People's Republic of China
| | - Yongqian Wang
- Office of Scientific Research, Peking University Health Science Center, Beijing, People's Republic of China
| | - Ning Fan
- Peking University Huilongguan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, People's Republic of China
| | - Qi Zhang
- Department of Psychology, Wuxi Mental Health Center, Wuxi, People's Republic of China
| | - Yun Bian
- Peking University Huilongguan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, People's Republic of China
| | - Fude Yang
- Peking University Huilongguan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, People's Republic of China
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20
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Goel S, Singh R, Singh V, Singh H, Kumari P, Chopra H, Sharma R, Nepovimova E, Valis M, Kuca K, Emran TB. Metformin: Activation of 5′ AMP-activated protein kinase and its emerging potential beyond anti-hyperglycemic action. Front Genet 2022; 13:1022739. [PMID: 36386794 PMCID: PMC9659887 DOI: 10.3389/fgene.2022.1022739] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 09/22/2022] [Indexed: 11/29/2022] Open
Abstract
Metformin is a plant-based drug belonging to the class of biguanides and is known to treat type-2 diabetes mellitus (T2DM). The drug, combined with controlling blood glucose levels, improves the body’s response to insulin. In addition, trials have identified the cardioprotective potential of metformin in the diabetic population receiving the drug. Activation of 5′ AMP-activated protein kinase (AMPK) is the major pathway for these potential beneficial effects of metformin. Historically, much emphasis has been placed on the potential indications of metformin beyond its anti-diabetic use. This review aims to appraise other potential uses of metformin primarily mediated by the activation of AMPK. We also discuss various mechanisms, other than AMPK activation, by which metformin could produce beneficial effects for different conditions. Databases including PubMed/MEDLINE and Embase were searched for literature relevant to the review’s objective. Reports from both research and review articles were considered. We found that metformin has diverse effects on the human body systems. It has been shown to exert anti-inflammatory, antioxidant, cardioprotective, metabolic, neuroprotective, anti-cancer, and antimicrobial effects and has now even been identified as effective against SARS-CoV-2. Above all, the AMPK pathway has been recognized as responsible for metformin’s efficiency and effectiveness. Owing to its extensive potential, it has the capability to become a part of treatment regimens for diseases apart from T2DM.
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Affiliation(s)
- Sanjay Goel
- Government Medical College, Patiala, Punjab, India
| | - Ravinder Singh
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
- *Correspondence: Ravinder Singh, ; Talha Bin Emran,
| | - Varinder Singh
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Harmanjit Singh
- Department of Pharmacology, Government Medical College and Hospital, Chandigarh, India
| | - Pratima Kumari
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Hitesh Chopra
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Rohit Sharma
- Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Eugenie Nepovimova
- Department of Chemistry, Faculty of Science, University of Hradec Králové, Hradec Králové, Czechia
- Neurology Clinic, University Hospital, Hradec Králové, Czechia
| | - Martin Valis
- Department of Neurology, Charles University in Prague, Faculty of Medicine in Hradec Králové and University Hospital, Hradec Králové, Czechia
| | - Kamil Kuca
- Department of Chemistry, Faculty of Science, University of Hradec Králové, Hradec Králové, Czechia
- Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI), University of Granada, Granada, Spain
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, Bangladesh
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
- *Correspondence: Ravinder Singh, ; Talha Bin Emran,
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21
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Mc Namara KP, Alzubaidi H, Murray M, Samorinha C, Dunbar JA, Versace VL, Castle D. Should antidiabetic medicines be considered to reduce cardiometabolic risk in patients with serious mental illness? Med J Aust 2022; 217 Suppl 7:S29-S33. [PMID: 36183318 PMCID: PMC9828708 DOI: 10.5694/mja2.51701] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 06/22/2022] [Accepted: 07/06/2022] [Indexed: 11/05/2022]
Abstract
Substantially reduced life expectancy for people with serious mental illness compared with the general population is primarily driven by physical health issues, of which cardiovascular disease is the leading cause. In this narrative review, we examine the evidence base for use of metformin and other antidiabetic agents as a means for reducing this excess cardiometabolic disease burden. Evidence from randomised controlled trials (RCTs) suggests substantial potential for metformin to prevent or manage weight gain and glycaemic impairment induced by atypical antipsychotic medications, whereas the impact of metformin on other cardiometabolic risk factors is less consistent. Evidence from RCTs also suggests potential benefits from glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly for addressing cardiometabolic risk factors in people using atypical antipsychotic medications, but this is based on a small number of trials and remains an emerging area of research. Trials of both metformin and GLP-1RAs suggest that these medications are associated with a high prevalence of mild-moderate gastrointestinal side effects. The heterogeneous nature of participant eligibility criteria and of antipsychotic and antidiabetic drug regimens, alongside short trial durations, small numbers of participants and paucity of clinical endpoints as trial outcomes, warrants investment in definitive trials to determine clinical benefits for both metformin and GLP-1RAs. Such trials would also help to confirm the safety profile of antidiabetic agents with respect to less common but serious adverse effects. The weight of RCT evidence suggests that an indication for metformin to address antipsychotic-induced weight gain is worth considering in Australia. This would bring us into line with other countries.
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Affiliation(s)
| | - Hamzah Alzubaidi
- Deakin UniversityWarrnamboolVIC,College of PharmacyUniversity of SharjahSharjahUnited Arab Emirates,Sharjah Institute for Medical ResearchUniversity of SharjahSharjahUnited Arab Emirates
| | | | - Catarina Samorinha
- Sharjah Institute for Medical ResearchUniversity of SharjahSharjahUnited Arab Emirates
| | | | | | - David Castle
- Centre for Complex Interventions, Centre for Addiction and Mental HealthTorontoCanada
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22
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Severe psychiatric disorders and general medical comorbidities: inflammation-related mechanisms and therapeutic opportunities. Clin Sci (Lond) 2022; 136:1257-1280. [PMID: 36062418 DOI: 10.1042/cs20211106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 08/16/2022] [Accepted: 08/22/2022] [Indexed: 11/17/2022]
Abstract
Individuals with severe psychiatric disorders, such as mood disorders and schizophrenia, are at increased risk of developing other medical conditions, especially cardiovascular and metabolic diseases. These medical conditions are underdiagnosed and undertreated in these patients contributing to their increased morbidity and mortality. The basis for this increased comorbidity is not well understood, possibly reflecting shared risks factors (e.g. lifestyle risk factors), shared biological mechanisms and/or reciprocal interactions. Among overlapping pathophysiological mechanisms, inflammation and related factors, such as dysbiosis and insulin resistance, stand out. Besides underlying the association between psychiatric disorders and cardiometabolic diseases, these mechanisms provide several potential therapeutic targets.
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23
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Severe Mental Illness and Cardiovascular Disease: JACC State-of-the-Art Review. J Am Coll Cardiol 2022; 80:918-933. [PMID: 36007991 DOI: 10.1016/j.jacc.2022.06.017] [Citation(s) in RCA: 59] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 06/08/2022] [Accepted: 06/21/2022] [Indexed: 11/23/2022]
Abstract
People with severe mental illness, consisting of schizophrenia, bipolar disorder, and major depression, have a high burden of modifiable cardiovascular risk behaviors and conditions and have a cardiovascular mortality rate twice that of the general population. People with acute and chronic cardiovascular disease are at a higher risk of developing mental health symptoms and disease. There is emerging evidence for shared etiological factors between severe mental illness and cardiovascular disease that includes biological, genetic, and behavioral mechanisms. This state-of-the art review will describe the relationship between severe mental illness and cardiovascular disease, explore the factors that lead to poor cardiovascular outcomes in people with severe mental illness, propose strategies to improve the cardiovascular health of people with severe mental illness, and present areas for future research focus.
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24
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Huang PP, Zhu WQ, Xiao JM, Zhang YQ, Li R, Yang Y, Shen L, Luo F, Dai W, Lian PA, Tang YX, Ran JL, Huang XS. Alterations in sorting and secretion of hepatic apoA5 induce hypertriglyceridemia due to short-term use of olanzapine. Front Pharmacol 2022; 13:935362. [PMID: 36034782 PMCID: PMC9411997 DOI: 10.3389/fphar.2022.935362] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 07/07/2022] [Indexed: 11/13/2022] Open
Abstract
Long-term use of olanzapine, an antipsychotic drug, induces hypertriglyceridemia, resulting in a higher risk of cardiovascular disease. However, the effects and underlying mechanisms of short-term use of olanzapine on circulating triglyceride levels remain poorly understood. Here, the role of apolipoprotein A5 (apoA5), a regulator of triglyceride metabolism, was investigated in olanzapine-induced hypertriglyceridemia. Our multi-center clinical study recruited 36 schizophrenia patients who received short-term (8 weeks) of olanzapine. Besides, female C57BL/6J mice were treated with olanzapine (3 mg/kg/day versus 6 mg/kg/day) for 6 weeks. We demonstrated that short-term use of olanzapine increased plasma triglyceride and decreased plasma apoA5 levels in the patients and mice, with a negative correlation between the two factors. However, no obesity was observed in the patients and mice. Interestingly, olanzapine increased hepatic apoA5 protein in the mice, without significant changes in hepatic Apoa5 mRNA. Consistently, in vitro studies indicated that olanzapine increased medium triglyceride levels and decreased medium apoA5 levels in a dose-dependent manner in human HepG2 cells and primary mouse hepatocytes. Whereas the olanzapine treatment increased hepatic apoA5 protein in vitro, without effects on hepatic APOA5 mRNA. Of note, olanzapine increased the co-localization between apoA5 protein and accumulated lipid droplets in hepatocytes, as opposed to at the hepatocellular plasma membrane, in mouse liver as demonstrated by fluorescence staining. Therefore, our study indicated that short-term use of olanzapine induced hypertriglyceridemia due to defects of sorting and secretion of hepatic apoA5.
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Affiliation(s)
- Piao-Piao Huang
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Institute of Blood Lipid and Atherosclerosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Wen-Qiang Zhu
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Institute of Blood Lipid and Atherosclerosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jing-Mei Xiao
- National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Yi-Qi Zhang
- Department of Critical Care Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Rong Li
- Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yang Yang
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Institute of Blood Lipid and Atherosclerosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Li Shen
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Institute of Blood Lipid and Atherosclerosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Fei Luo
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Institute of Blood Lipid and Atherosclerosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States
| | - Wen Dai
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Institute of Blood Lipid and Atherosclerosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Department of Medicine, Columbia University Medical Center, New York, NY, United States
| | - Ping-An Lian
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Institute of Blood Lipid and Atherosclerosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Ya-Xin Tang
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Institute of Blood Lipid and Atherosclerosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Juan-Li Ran
- Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xian-Sheng Huang
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Institute of Blood Lipid and Atherosclerosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- *Correspondence: Xian-Sheng Huang,
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25
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Yang Y, Shen M, Li L, Long Y, Wang L, Lang B, Wu R. Olanzapine Promotes the Occurrence of Metabolic Disorders in Conditional TCF7L2-Knockout Mice. Front Cell Dev Biol 2022; 10:890472. [PMID: 35874808 PMCID: PMC9298277 DOI: 10.3389/fcell.2022.890472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 05/16/2022] [Indexed: 11/29/2022] Open
Abstract
Objectives: Schizophrenia (SCZ) patients display higher incidence of metabolic syndrome (MetS) and comorbidity of type II diabetes. Both atypical antipsychotics and genetic variants are believed to predispose the patients with the risk, but their interplay remains largely unknown. TCF7L2 is one of the most common genes strongly associated with glucose homeostasis which also participates in the pathogenesis of schizophrenia. In this study, we aimed to explore the regulatory roles of TCF7L2 in atypical antipsychotics-induced MetS. Methods: Mice with pancreatic β-cell–specific Tcf7l2 deletion (CKO) were generated. The CKO mice and control littermates were subjected to olanzapine (4 mg/kg/day) or saline gavage for 6 weeks. Metabolic indices, β cell mass, and the expressing levels of TCF7L2 and GLP-1R in the pancreatic tissue were closely monitored. Results: Tcf7l2 CKO mice displayed a spectrum of core features of MetS, which included remarkably increased rate of weight gain, higher fasting insulin, higher values of blood lipids (cholesterol, triglyceride, and low-density lipoprotein), impaired glucose tolerance, and hypertrophy of adipocytes. Notably, these effects could be further exacerbated by olanzapine. In addition, Tcf7l2 CKO mice with the olanzapine group showed significantly decreased expressions of GLP-1R protein and a trend of reduced pancreatic β-cell mass. RT-qPCR revealed that the CKO mice presented a significantly less transcription of Sp5, an important element of the Wnt signaling pathway. Conclusion: Our study illustrates that mice with pancreatic β-cell–targeted Tcf7l2 deletion were more vulnerable to suffer metabolic abnormalities after olanzapine administration. This impairment may be mediated by the reduced expression of GLP-1R.
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Affiliation(s)
- Ye Yang
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Manjun Shen
- Shenzhen Nanshan Center for Chronic Disease Control, Department of Psychiatry, Shenzhen, China
| | - Li Li
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yujun Long
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Lu Wang
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Bing Lang
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China
- *Correspondence: Bing Lang, ; Renrong Wu,
| | - Renrong Wu
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China
- *Correspondence: Bing Lang, ; Renrong Wu,
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26
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Kim J, Lee N, Suh SB, Jang S, Kim S, Kim DG, Park JK, Lee KW, Choi SY, Lee CH. Metformin ameliorates olanzapine-induced disturbances in POMC neuron number, axonal projection, and hypothalamic leptin resistance. BMB Rep 2022. [PMID: 35651327 PMCID: PMC9252891 DOI: 10.5483/bmbrep.2022.55.6.026] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Antipsychotics have been widely accepted as a treatment of choice for psychiatric illnesses such as schizophrenia. While atypical antipsychotics such as aripiprazole are not associated with obesity and diabetes, olanzapine is still widely used based on the anticipation that it is more effective in treating severe schizophrenia than aripiprazole, despite its metabolic side effects. To address metabolic problems, metformin is widely prescribed. Hypothalamic proopiomelanocortin (POMC) neurons have been identified as the main regulator of metabolism and energy expenditure. Although the relation between POMC neurons and metabolic disorders is well established, little is known about the effects of olanzapine and metformin on hypothalamic POMC neurons. In the present study, we investigated the effect of olanzapine and metformin on the hypothalamic POMC neurons in female mice. Olanzapine administration for 5 days significantly decreased Pomc mRNA expression, POMC neuron numbers, POMC projections, and induced leptin resistance before the onset of obesity. It was also observed that coadministration of metformin with olanzapine not only increased POMC neuron numbers and projections but also improved the leptin response of POMC neurons in the olanzapine-treated female mice. These findings suggest that olanzapine-induced hypothalamic POMC neuron abnormality and leptin resistance, which can be ameliorated by metformin administration, are the possible causes of subsequent hyperphagia.
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Affiliation(s)
- Jaedeok Kim
- Department of Biomedical Science, Hallym University, Chuncheon 24252, Korea
| | - Nayoung Lee
- Department of Biomedical Science, Hallym University, Chuncheon 24252, Korea
| | - Sang Bum Suh
- University of Ulsan College of Medicine, Seoul 05505, Korea
| | - Sooyeon Jang
- Department of Biomedical Science, Hallym University, Chuncheon 24252, Korea
| | - Saeha Kim
- Department of Biomedical Science, Hallym University, Chuncheon 24252, Korea
| | - Dong-Gyu Kim
- Department of Biomedical Science, Hallym University, Chuncheon 24252, Korea
| | - Jong Kook Park
- Department of Biomedical Science, Hallym University, Chuncheon 24252, Korea
| | - Keun-Wook Lee
- Department of Biomedical Science, Hallym University, Chuncheon 24252, Korea
| | - Soo Young Choi
- Department of Biomedical Science, Hallym University, Chuncheon 24252, Korea
| | - Chan Hee Lee
- Department of Biomedical Science, Hallym University, Chuncheon 24252, Korea
- Program of Material Science for Medicine and Pharmaceutics, Hallym University, Chuncheon 24252, Korea
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27
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Zavala GA, Todowede O, Mazumdar P, Aslam F, Choudhury AH, Jarde A, Khalid H, Reddy S, Gilbody S, Siddiqi N. Effectiveness of interventions to address obesity and health risk behaviours among people with severe mental illness in low- and middle-income countries (LMICs): a systematic review and meta analysis. Glob Ment Health (Camb) 2022; 9:264-273. [PMID: 36618743 PMCID: PMC9806988 DOI: 10.1017/gmh.2022.21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 02/28/2022] [Accepted: 03/13/2022] [Indexed: 01/11/2023] Open
Abstract
Introduction People with severe mental illness (SMI) are more likely to have obesity and engage in health risk behaviours than the general population. The aims of this study are (1) evaluate the effectiveness of interventions that focus on body weight, smoking cessation, improving sleeping patterns, and alcohol and illicit substance abuse; (2) Compare the number of interventions addressing body weight and health risk behaviours in low- and middle-income countries (LMICs) v. those reported in published systematic reviews focusing on high-income countries (HICs). Methods Intervention studies published up to December 2020 were identified through a structured search in the following database; OVID MEDLINE (1946-December 2020), EMBASE (1974-December 2020), CINAHL (1975-2020), APA PsychoINFO (1806-2020). Two authors independently selected studies, extracted study characteristics and data and assessed the risk of bias. and risk of bias was assessed using the Cochrane risk of bias tool V2. We conducted a narrative synthesis and, in the studies evaluating the effectiveness of interventions to address body weight, we conducted random-effects meta-analysis of mean differences in weight gain. We did a systematic search of systematic reviews looking at cardiometabolic and health risk behaviours in people with SMI. We compared the number of available studies of LMICs with those of HICs. Results We assessed 15 657 records, of which 9 met the study inclusion criteria. Six focused on healthy weight management, one on sleeping patterns and two tested a physical activity intervention to improve quality of life. Interventions to reduce weight in people with SMI are effective, with a pooled mean difference of -4.2 kg (95% CI -6.25 to -2.18, 9 studies, 459 participants, I 2 = 37.8%). The quality and sample size of the studies was not optimal, most were small studies, with inadequate power to evaluate the primary outcome. Only two were assessed as high quality (i.e. scored 'low' in the overall risk of bias assessment). We found 5 reviews assessing the effectiveness of interventions to reduce weight, perform physical activity and address smoking in people with SMI. From the five systematic reviews, we identified 84 unique studies, of which only 6 were performed in LMICs. Conclusion Pharmacological and activity-based interventions are effective to maintain and reduce body weight in people with SMI. There was a very limited number of interventions addressing sleep and physical activity and no interventions addressing smoking, alcohol or harmful drug use. There is a need to test the feasibility and cost-effectiveness of context-appropriate interventions to address health risk behaviours that might help reduce the mortality gap in people with SMI in LMICs.
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Affiliation(s)
| | | | | | - Faiza Aslam
- Institute of Psychiatry (IoP), Benazir Bhutto Hospital, Rawalpindi Medical University, Rawalpindi, Pakistan
| | | | | | - Humaira Khalid
- Institute of Psychiatry (IoP), Benazir Bhutto Hospital, Rawalpindi Medical University, Rawalpindi, Pakistan
| | - Sadananda Reddy
- School of Social Sciences/Psychology, CHRIST (Deemed to be University), Bengaluru, India
| | - Simon Gilbody
- Department of Health Sciences, University of York, York, UK
- Hull York Medical School, York, UK
| | - Najma Siddiqi
- Department of Health Sciences, University of York, York, UK
- Hull York Medical School, York, UK
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28
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Spann G, Austin L, King E. Pharmacists in clozapine clinics improving physical health monitoring. Ment Health Clin 2022; 12:193-198. [PMID: 35801163 PMCID: PMC9190272 DOI: 10.9740/mhc.2022.06.193] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 04/20/2022] [Indexed: 11/13/2022] Open
Abstract
Abstract
Introduction
People living with schizophrenia have a higher rate of comorbid physical health diseases and compared with the general population die earlier due to these diseases. A pharmacist working in an outpatient mental health clinic setting could assist with the management of physical health disease for this population. The aim of this study was to investigate whether having a pharmacist in a community clozapine clinic would improve adherence to physical health monitoring and whether this would have a positive effect on these physical health outcomes.
Methods
This retrospective observational study compared patient data from 2 clozapine clinics; one where a pharmacist engaged in medication reviews and management of medication side effects, and another that did not have a pharmacist. The rates of physical health monitoring and the changes from baseline of physical health outcomes (weight, BMI, BP, HbA1c, and lipids) were compared after the first pharmacist intervention (medication review).
Results
The pharmacist clinic had statistically higher rates of metabolic and ECG monitoring (glucose 48% vs 11%, P < .001; lipids 61% vs 7.1%, P < .001; ECG 15% vs 0%, P = .001). Positive trends in weight were identified in the pharmacist-group, although this failed to reach statistical significance.
Discussion
This study shows that pharmacists providing regular medication reviews improves physical health monitoring for patients receiving clozapine.
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Affiliation(s)
| | - Lewis Austin
- 2 Intern Pharmacist, Princess Alexandra Hospital, Metro South Hospital and Health Service, QLD, Australia
| | - Edward King
- 3 Pharmacist, Caboolture Hospital, Metro North Hospital and Health Service, QLD, Australia
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29
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Huang J, Liu C, Yang Y, Kang D, Xiao J, Long Y, Lang B, Peng X, Wang W, Wang X, Liu F, Zhao J, Shi Z, Yuan TF, Wu R. The effects of probiotics plus dietary fiber on antipsychotic-induced weight gain: a randomized clinical trial. Transl Psychiatry 2022; 12:185. [PMID: 35508529 PMCID: PMC9068806 DOI: 10.1038/s41398-022-01958-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 04/18/2022] [Accepted: 04/25/2022] [Indexed: 12/14/2022] Open
Abstract
Probiotics plus dietary fiber has demonstrated efficacy in improving metabolic abnormalities. However, the efficacy of probiotics and dietary fiber as well as their association with microbiota in attenuating antipsychotic-induced weight gain and metabolic disturbance remains poorly understood. Here we analyzed results from the double-blind, randomized, placebo-controlled study to compare and evaluate the effects of probiotics, dietary fiber, and their combination for antipsychotic-induced weight gain in patients with a severe mental disorder. We found that probiotics plus dietary fiber was significantly superior to probiotics alone, dietary fiber only, and the placebo for weight, BMI, and total cholesterol reduction; insulin resistance was worse in the placebo group, with significant increases during the 12-week treatment; probiotics plus dietary fiber significantly reduced weight and prevented further deterioration of metabolic disturbances; and probiotics or dietary fiber alone can prevent further weight gain. We further performed 16 S ribosomal RNA sequencing revealed an increased abundance of microbiota after probiotics plus dietary fiber treatment. Moreover, logistic regression analyses revealed that the higher richness of microbiota was associated with favorable weight loss. These findings suggested that probiotics and dietary fiber co-administration were safe and effective interventions to reduce weight gain in patients treated with antipsychotic medications.
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Affiliation(s)
- Jing Huang
- grid.452708.c0000 0004 1803 0208Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011 Changsha, Hunan China
| | - Chenchen Liu
- grid.452708.c0000 0004 1803 0208Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011 Changsha, Hunan China
| | - Ye Yang
- grid.452708.c0000 0004 1803 0208Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011 Changsha, Hunan China
| | - Dongyu Kang
- grid.452708.c0000 0004 1803 0208Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011 Changsha, Hunan China
| | - Jingmei Xiao
- grid.452708.c0000 0004 1803 0208Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011 Changsha, Hunan China
| | - Yujun Long
- grid.452708.c0000 0004 1803 0208Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011 Changsha, Hunan China
| | - Bing Lang
- grid.452708.c0000 0004 1803 0208Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011 Changsha, Hunan China
| | - Xingjie Peng
- grid.452708.c0000 0004 1803 0208Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011 Changsha, Hunan China
| | - Weiyan Wang
- grid.452708.c0000 0004 1803 0208Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011 Changsha, Hunan China
| | - Xiaoyi Wang
- grid.452708.c0000 0004 1803 0208Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011 Changsha, Hunan China
| | - Fangkun Liu
- grid.452223.00000 0004 1757 7615Department of Neurosurgery, Xiangya Hospital, Central South University, 410008 Changsha, Hunan China
| | - Jingping Zhao
- grid.452708.c0000 0004 1803 0208Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011 Changsha, Hunan China
| | - Zhe Shi
- grid.452708.c0000 0004 1803 0208Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011 Changsha, Hunan China ,grid.488482.a0000 0004 1765 5169Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, Hunan University of Chinese Medicine, 410208 Changsha, Hunan China ,grid.415630.50000 0004 1782 6212Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ti-Fei Yuan
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. .,Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China. .,Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.
| | - Renrong Wu
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China.
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Zhu W, Ding C, Huang P, Ran J, Lian P, Tang Y, Dai W, Huang X. Metformin Ameliorates Hepatic Steatosis induced by olanzapine through inhibiting LXRα/PCSK9 pathway. Sci Rep 2022; 12:5639. [PMID: 35379885 PMCID: PMC8979948 DOI: 10.1038/s41598-022-09610-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 03/17/2022] [Indexed: 11/09/2022] Open
Abstract
Studies have confirmed that olanzapine, the mainstay treatment for schizophrenia, triggers metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). However, the etiology of olanzapine-induced NAFLD is poorly understood. Proprotein convertase subtilisin kexin type 9 (PCSK9) is involved in NAFLD pathogenesis, and metformin can significantly decrease circulating PCSK9. The purpose of this study was to investigate the role of PCSK9 and explore the therapeutic effect of metformin for olanzapine-associated NAFLD. Olanzapine significantly upregulated PCSK9 and promoted lipid accumulation in mouse livers and HepG2 and AML12 cells. Metformin ameliorated these pathological alterations. PCSK9 upstream regulator liver X receptor α (LXRα) was significantly upregulated in olanzapine-induced NAFLD. LXRα antagonist treatment and LXRα overexpression resulted in a decrease and increase of PCSK9, respectively. Hepatic lipogenesis-associated genes FAS and SCD1 were significantly upregulated in olanzapine-induced NAFLD mice and HepG2 cells overexpressing PCSK9, and genes related to lipid β-oxidation (SCAD and PPARα) were downregulated, while metformin reversed these changes. In addition, we found that LXRα overexpression compromised the effect of metformin on PCSK9 levels and intracellular lipid droplet formation. Taken together, our findings suggest that olanzapine enhances hepatic PCSK9 expression by upregulating LXRα, thereby increasing FAS and SCD1 expression as well as decreasing SCAD and PPARα, and promoting lipid accumulation, and, subsequently, NAFLD, which is ameliorated by metformin.
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Affiliation(s)
- Wenqiang Zhu
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Chen Ding
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Piaopiao Huang
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Juanli Ran
- Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Pingan Lian
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Yaxin Tang
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Wen Dai
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.,Department of Medicine, Columbia University Medical Center, New York, USA
| | - Xiansheng Huang
- Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
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31
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Fitzgerald I, O'Connell J, Keating D, Hynes C, McWilliams S, Crowley EK. Metformin in the management of antipsychotic-induced weight gain in adults with psychosis: development of the first evidence-based guideline using GRADE methodology. EVIDENCE-BASED MENTAL HEALTH 2022; 25:15-22. [PMID: 34588212 PMCID: PMC8788031 DOI: 10.1136/ebmental-2021-300291] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 09/07/2021] [Indexed: 11/04/2022]
Abstract
BACKGROUND Adjunctive metformin is the most well-studied intervention in the pharmacological management of antipsychotic-induced weight gain (AIWG). Although a relatively unaddressed area, among guidelines recommending consideration of metformin, prescribing information that would facilitate its applied use by clinicians, for example, provision of a dose titration schedule is absent. Moreover, recommendations differ regarding metformin's place in the hierarchy of management options. Both represent significant barriers to the applied, evidence-based use of metformin for this indication. OBJECTIVE To produce a guideline solely dedicated to the optimised use of metformin in AIWG management, using internationally endorsed guideline methodology. METHODS A list of guideline key health questions (KHQs) was produced. It was agreed that individual recommendations would be 'adopted or adapted' from current guidelines and/or developed de novo, in the case of unanswered questions. A systematic literature review (2008-2020) was undertaken to identify published guidelines and supporting (or more recent) research evidence. Quality appraisal was undertaken using the Appraisal of Guidelines Research and Evaluation II tool, A Measurement Tool to Assess Systematic Reviews (AMSTAR) assessment,and the Cochrane Risk of Bias 2 tool, where appropriate. Assessment of evidence certainty and recommendation development was undertaken using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. FINDINGS We confirmed that no published guideline-of appropriate quality, solely dedicated to the use of metformin to manage AIWG was available. Recommendations located within other guidelines inadequately addressed our KHQs. CONCLUSION All 11 recommendations and 7 supporting good practice developed here were formulated de novo. CLINICAL IMPLICATIONS These recommendations build on the number and quality of recommendations in this area, and facilitate the optimised use of metformin when managing AIWG.
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Affiliation(s)
- Ita Fitzgerald
- Pharmacy Department, Saint John of God Hospitaller Services, Dublin, Ireland
- School of Pharmacy, University College Cork, Cork, Ireland
| | - Jean O'Connell
- Endocrinology, St Columcille's Hospital, Loughlinstown, Ireland
- Endocrinology, St Vincent's University Hospital, Dublin, Ireland
| | - Dolores Keating
- Pharmacy Department, Saint John of God Hospital, Dublin, Ireland
| | - Caroline Hynes
- Pharmacy, Saint John of God Hospitaller Services, Dublin, Ireland
| | - Stephen McWilliams
- School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland
- Medical, Saint John of God Hospitaller Services, Dublin, Ireland
| | - Erin K Crowley
- Pharmaceutical Care Research Group, University College Cork, Cork, Ireland
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Hakami AY, Felemban R, Ahmad RG, Al-Samadani AH, Salamatullah HK, Baljoon JM, Alghamdi LJ, Ramadani Sindi MH, Ahmed ME. The Association Between Antipsychotics and Weight Gain and the Potential Role of Metformin Concomitant Use: A Retrospective Cohort Study. Front Psychiatry 2022; 13:914165. [PMID: 35686187 PMCID: PMC9170991 DOI: 10.3389/fpsyt.2022.914165] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 05/05/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Obesity and its complications are associated with several adverse effects that may cause a serious impact on health. Antipsychotics-induced weight gain (AIWG) is one of the major, yet often neglected side effects of first and second generations antipsychotics. Importantly, several researches have shown metformin to be effective in managing weight gain especially, with AIWG. This study investigated the effect of antipsychotics use on weight gain and the theory of metformin concomitant use on the prevention of AIWG. METHODS A retrospective cohort review of the medical records of patients from the psychiatry outpatient clinics in the King Abdulaziz Medical city, a tertiary hospital in Jeddah from May 2016 to August 2021. The population of patients in Psychiatry section was 4,141. The sampling technique was a non-random consecutive sampling technique. Moreover, the included patients' records were divided to group 1 (patients on antipsychotics) and group 2 (patients using antipsychotics with Metformin). RESULTS According to the study criteria, 395 patients' records were included. A total of 309 (78%) patients were using antipsychotics without metformin, which in this study were depicted as group 1. In addition, a total of 86 (22%) were using antipsychotics with metformin, which in this study were assigned as group 2. Out of Group 1 patients (n = 309), only 67 patients experienced weight loss (21.68%), 43 remained with no weight change (13.92%), and 199 experienced weight gain (64.4%). Out of Group 2 patients (n = 86), 35 patients experienced weight loss (40.7%), 18 patients remained with no weight change (20.93%), and 33 experienced weight gain (38.37%). In addition, group 1 had a mean weight change of 2.5 kg, whereas group 2 had a mean weight change of -0.04 kg. CONCLUSION Statistical analysis revealed that patients on antipsychotics alone experienced weight gain, whereas the concomitant use of metformin showed reduction in the weight gain tendency. Thus, study outcomes indicate that concomitant use of metformin with antipsychotics might significantly reduce the AIWG.
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Affiliation(s)
- Alqassem Y Hakami
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia.,King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Razaz Felemban
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia.,King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Rami Ghazi Ahmad
- King Abdullah International Medical Research Center, Jeddah, Saudi Arabia.,Psychiatry Section, Department of Medicine, Ministry of National Guard-Health Affairs, Jeddah, Saudi Arabia
| | | | - Hassan K Salamatullah
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Jamil M Baljoon
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Loay J Alghamdi
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Mostafa H Ramadani Sindi
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Mohamed Eldigire Ahmed
- King Abdullah International Medical Research Center, Jeddah, Saudi Arabia.,College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
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33
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Tang C, Chua YC, Abdin E, Subramaniam M, Verma S. Twenty-Four Week, Randomized, Double-Blind, Placebo-Controlled Trial of Metformin for Antipsychotic-Induced Weight Gain in Patients with First-Episode Psychosis: A Pilot Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 19:137. [PMID: 35010394 PMCID: PMC8750805 DOI: 10.3390/ijerph19010137] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 12/21/2021] [Accepted: 12/22/2021] [Indexed: 06/14/2023]
Abstract
Excessive weight gain and cardiometabolic dysfunction are common and clinically relevant side effects of antipsychotic medications. In this pilot study, we aimed to establish the feasibility of using metformin and its effectiveness in managing antipsychotic-induced weight gain in patients with first-episode psychosis (FEP) on follow-up with the Singapore Early Psychosis Intervention Programme in a 24-week, randomized, double-blind, placebo-controlled trial, to ascertain the effects of metformin discontinuation on body weight and evaluate the safety and tolerability of metformin. Participants between the ages of 16 and 40 with FEP assessed as clinically stable and who had gained ≥5% of their pre-drug weight after initiation of the antipsychotic treatment were recruited from outpatient clinics between April 2015 and April 2018. Seventeen participants met all the inclusion criteria and were randomized to receive metformin (n = 8) or the placebo (n = 9) at Week 0, with follow up assessments at Weeks 3, 6, 12, 24, and 36. Metformin was generally well-tolerated. Participants in the metformin arm were able to control their weight better than participants receiving the placebo, an effect that did not persist after discontinuation. Our results support the use of metformin as a safe and tolerable weight control measure in a typical outpatient sample of young people with FEP.
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Affiliation(s)
- Charmaine Tang
- Department of Psychosis, Institute of Mental Health, Singapore 539747, Singapore;
| | - Yi Chian Chua
- Department of Psychosis, Institute of Mental Health, Singapore 539747, Singapore;
| | - Edimansyah Abdin
- Research Division, Institute of Mental Health, Singapore 539747, Singapore; (E.A.); (M.S.)
| | - Mythily Subramaniam
- Research Division, Institute of Mental Health, Singapore 539747, Singapore; (E.A.); (M.S.)
| | - Swapna Verma
- Medical Board, Institute of Mental Health, Singapore 539747, Singapore;
- MD Programme Department, Duke-NUS Medical School, Singapore 169857, Singapore
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Zhuo C, Xu Y, Wang H, Zhou C, Liu J, Yu X, Shao H, Tian H, Fang T, Li Q, Chen J, Xu S, Ma X, Yang W, Yao C, Li B, Yang A, Chen Y, Huang G, Lin C. Clozapine induces metformin-resistant prediabetes/diabetes that is associated with poor clinical efficacy in patients with early treatment-resistant schizophrenia. J Affect Disord 2021; 295:163-172. [PMID: 34464878 DOI: 10.1016/j.jad.2021.08.023] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Revised: 08/10/2021] [Accepted: 08/18/2021] [Indexed: 01/07/2023]
Abstract
BACKGROUND Two distinct subtypes of treatment-resistant schizophrenia (TRS) have been recently reported, including early-treatment resistance (E-TR) and late-treatment resistance (L-TR). This study was to assess clozapine-induced metformin-resistant prediabetes/diabetes and its correlation with clinical efficacy in schizophrenia E-TR subtype. METHODS This prospective cohort study enrolled 230 patients with schizophrenia E-TR subtype and they were treated with adequate doses of clozapine for 16 weeks, during which patients with prediabetes/diabetes were assigned to receive add-on metformin. The main outcomes and measures included incidence of clozapine-induced prediabetes/diabetes and metformin-resistant prediabetes/diabetes, and the efficacy of clozapine as assessed by the Positive and Negative Syndrome Scale (PANSS) score. RESULTS Clozapine-induced prediabetes/diabetes occurred in 76.52% of patients (170 prediabetes and 6 diabetes), of which the blood sugar of 43 (24.43%) patients was controlled with metformin. Despite add-on metformin, 47.06% (74/170) of prediabetes patients progressed to diabetes. In total, the incidence of clozapine-induced metformin-resistant prediabetes/diabetes was 75.57% (133/176). On completion of 16-week clozapine treatment, 16.52% (38/230) patients showed clinical improvement with PANSS scores of ≥50% declining. Furthermore, clozapine-induced prediabetes/diabetes was significantly correlated with the poor clinical efficacy of clozapine for schizophrenia E-TR subtype. CONCLUSIONS The incidence of clozapine-induced metformin-resistant prediabetes/diabetes was considerably high in the schizophrenia E-TR subtype. Clozapine-induced metformin-resistant prediabetes/diabetes represents an independent risk factor that adversely affects the clinical efficacy of clozapine for the schizophrenia E-TR subtype. This study provided new evidence for re-evaluating the use of clozapine for TRS, especially E-TR subtype, and the use of metformin for the glycemic control of clozapine-induced prediabetes/diabetes.
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Affiliation(s)
- Chuanjun Zhuo
- Key Laboratory of Multiple Organ Damages of Major Psychoses (MODMP_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; National Center of Endocrine and Metabolic Disease Comprehensive Management (MMC), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key laboratory of Real Time Brain Circuits Tracing of Neurology and Psychiatry (RTBNB_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key Laboratory of Psychiatry Neuroimaging-genetics and Co-morbidity (PNGC_Lab), Tianjin Medical University Clinical Hospital of Mental Health, Tianjin Anding Hospital, Nankai University Affiliated Tianjin Anding Hospital, Tianjin Mental Health Center, Tianjin 300222, China.
| | - Yong Xu
- Department of Psychiatry, First Clinical Medical College, First Hospital of Shanxi Medical University, Taiyuan 030000, China
| | - Haibo Wang
- Peking University Clinical Research Institute, Peking University First Hospital, Beijing, 100191, China
| | - Chunhua Zhou
- Department of Pharmacoloy, The First Hospital of Hebei Medical University, Shijiazhuang 05000, Hebei Province, China
| | - Jian Liu
- Clinical Laboratory, Tianjin Medical University Clinical Hospital of Mental Health, Tianjin Anding Hospital, Nankai University Affiliated Tianjin Anding Hospital, Tianjin Mental Health Center, Tianjin 300222, China
| | - Xiaocui Yu
- National Center of Endocrine and Metabolic Disease Comprehensive Management (MMC), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key laboratory of Real Time Brain Circuits Tracing of Neurology and Psychiatry (RTBNB_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Clinical Laboratory, Tianjin Medical University Clinical Hospital of Mental Health, Tianjin Anding Hospital, Nankai University Affiliated Tianjin Anding Hospital, Tianjin Mental Health Center, Tianjin 300222, China
| | - Hailin Shao
- Key Laboratory of Multiple Organ Damages of Major Psychoses (MODMP_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; National Center of Endocrine and Metabolic Disease Comprehensive Management (MMC), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key laboratory of Real Time Brain Circuits Tracing of Neurology and Psychiatry (RTBNB_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China
| | - Hongjun Tian
- Key Laboratory of Multiple Organ Damages of Major Psychoses (MODMP_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; National Center of Endocrine and Metabolic Disease Comprehensive Management (MMC), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key laboratory of Real Time Brain Circuits Tracing of Neurology and Psychiatry (RTBNB_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China
| | - Tao Fang
- Key Laboratory of Multiple Organ Damages of Major Psychoses (MODMP_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; National Center of Endocrine and Metabolic Disease Comprehensive Management (MMC), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key laboratory of Real Time Brain Circuits Tracing of Neurology and Psychiatry (RTBNB_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China
| | - Qianchen Li
- Department of Pharmacoloy, The First Hospital of Hebei Medical University, Shijiazhuang 05000, Hebei Province, China
| | - Jiayue Chen
- National Center of Endocrine and Metabolic Disease Comprehensive Management (MMC), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key laboratory of Real Time Brain Circuits Tracing of Neurology and Psychiatry (RTBNB_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key Laboratory of Psychiatry Neuroimaging-genetics and Co-morbidity (PNGC_Lab), Tianjin Medical University Clinical Hospital of Mental Health, Tianjin Anding Hospital, Nankai University Affiliated Tianjin Anding Hospital, Tianjin Mental Health Center, Tianjin 300222, China
| | - Shuli Xu
- National Center of Endocrine and Metabolic Disease Comprehensive Management (MMC), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key laboratory of Real Time Brain Circuits Tracing of Neurology and Psychiatry (RTBNB_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key Laboratory of Psychiatry Neuroimaging-genetics and Co-morbidity (PNGC_Lab), Tianjin Medical University Clinical Hospital of Mental Health, Tianjin Anding Hospital, Nankai University Affiliated Tianjin Anding Hospital, Tianjin Mental Health Center, Tianjin 300222, China
| | - Xiaoyan Ma
- National Center of Endocrine and Metabolic Disease Comprehensive Management (MMC), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key laboratory of Real Time Brain Circuits Tracing of Neurology and Psychiatry (RTBNB_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key Laboratory of Psychiatry Neuroimaging-genetics and Co-morbidity (PNGC_Lab), Tianjin Medical University Clinical Hospital of Mental Health, Tianjin Anding Hospital, Nankai University Affiliated Tianjin Anding Hospital, Tianjin Mental Health Center, Tianjin 300222, China
| | - Weiliang Yang
- National Center of Endocrine and Metabolic Disease Comprehensive Management (MMC), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key laboratory of Real Time Brain Circuits Tracing of Neurology and Psychiatry (RTBNB_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key Laboratory of Psychiatry Neuroimaging-genetics and Co-morbidity (PNGC_Lab), Tianjin Medical University Clinical Hospital of Mental Health, Tianjin Anding Hospital, Nankai University Affiliated Tianjin Anding Hospital, Tianjin Mental Health Center, Tianjin 300222, China
| | - Cong Yao
- National Center of Endocrine and Metabolic Disease Comprehensive Management (MMC), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key laboratory of Real Time Brain Circuits Tracing of Neurology and Psychiatry (RTBNB_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key Laboratory of Psychiatry Neuroimaging-genetics and Co-morbidity (PNGC_Lab), Tianjin Medical University Clinical Hospital of Mental Health, Tianjin Anding Hospital, Nankai University Affiliated Tianjin Anding Hospital, Tianjin Mental Health Center, Tianjin 300222, China
| | - Bo Li
- National Center of Endocrine and Metabolic Disease Comprehensive Management (MMC), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key laboratory of Real Time Brain Circuits Tracing of Neurology and Psychiatry (RTBNB_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Department of Psychiatry, Tianjin Kangtai Mental Health Hospital, Tianjin 300014, China
| | - Anqu Yang
- National Center of Endocrine and Metabolic Disease Comprehensive Management (MMC), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key laboratory of Real Time Brain Circuits Tracing of Neurology and Psychiatry (RTBNB_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Department of Psychiatry, Tianjin Kangtai Mental Health Hospital, Tianjin 300014, China
| | - Yuhui Chen
- National Center of Endocrine and Metabolic Disease Comprehensive Management (MMC), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Key laboratory of Real Time Brain Circuits Tracing of Neurology and Psychiatry (RTBNB_Lab), Tianjin fourth center Hospital, Tianjin Medical Affiliated Tianjin Fourth Central Hospital, Nankai University Affiliated Tianjin Fourth Center Hospital, Tianjin 300140, China; Department of Psychiatry, Tianjin Kangtai Mental Health Hospital, Tianjin 300014, China
| | - Guoyong Huang
- Department of Psychiatry, Wenzhou Seventh Peoples Hospital, 325000
| | - Chongguang Lin
- Department of Psychiatry, Wenzhou Seventh Peoples Hospital, 325000
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Chang SC, Goh KK, Lu ML. Metabolic disturbances associated with antipsychotic drug treatment in patients with schizophrenia: State-of-the-art and future perspectives. World J Psychiatry 2021; 11:696-710. [PMID: 34733637 PMCID: PMC8546772 DOI: 10.5498/wjp.v11.i10.696] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/16/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
Metabolic disturbances and obesity are major cardiovascular risk factors in patients with schizophrenia, resulting in a higher mortality rate and shorter life expectancy compared with those in the general population. Although schizophrenia and metabolic disturbances may share certain genetic or pathobiological risks, antipsychotics, particularly those of second generation, may further increase the risk of weight gain and metabolic disturbances in patients with schizophrenia. This review included articles on weight gain and metabolic disturbances related to antipsychotics and their mechanisms, monitoring guidelines, and interventions. Nearly all antipsychotics are associated with weight gain, but the degree of the weight gain varies considerably. Although certain neurotransmitter receptor-binding affinities and hormones are correlated with weight gain and specific metabolic abnormalities, the precise mechanisms underlying antipsychotic-induced weight gain and metabolic disturbances remain unclear. Emerging evidence indicates the role of genetic polymorphisms associated with antipsychotic-induced weight gain and antipsychotic-induced metabolic disturbances. Although many guidelines for screening and monitoring antipsychotic-induced metabolic disturbances have been developed, they are not routinely implemented in clinical care. Numerous studies have also investigated strategies for managing antipsychotic-induced metabolic disturbances. Thus, patients and their caregivers must be educated and motivated to pursue a healthier life through smoking cessation and dietary and physical activity programs. If lifestyle intervention fails, switching to another antipsychotic drug with a lower metabolic risk or adding adjunctive medication to mitigate weight gain should be considered. Antipsychotic medications are essential for schizophrenia treatment, hence clinicians should monitor and manage the resulting weight gain and metabolic disturbances.
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Affiliation(s)
- Shen-Chieh Chang
- Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
| | - Kah Kheng Goh
- Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei 116, Taiwan
| | - Mong-Liang Lu
- Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei 116, Taiwan
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36
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Japanese Society of Neuropsychopharmacology: "Guideline for Pharmacological Therapy of Schizophrenia". Neuropsychopharmacol Rep 2021; 41:266-324. [PMID: 34390232 PMCID: PMC8411321 DOI: 10.1002/npr2.12193] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 06/27/2021] [Indexed: 12/01/2022] Open
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Olanzapine leads to nonalcoholic fatty liver disease through the apolipoprotein A5 pathway. Biomed Pharmacother 2021; 141:111803. [PMID: 34146854 DOI: 10.1016/j.biopha.2021.111803] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 05/17/2021] [Accepted: 06/07/2021] [Indexed: 12/14/2022] Open
Abstract
The antipsychotic drug olanzapine was reported to induce nonalcoholic fatty liver disease (NAFLD), whereas the underlying mechanism remains incompletely understood. This study investigated whether apolipoprotein A5 (apoA5) and sortilin, two interactive factors involved in NAFLD pathogenesis, are implicated in olanzapine-induced NAFLD. In our study, at week 8, olanzapine treatment successfully induced hepatic steatosis in female C57 BL/6 J mice, which was independent of body weight gain. Likewise, olanzapine effectively mediated hepatocyte steatosis in HepG2 cells characterized by substantially elevated intracellular lipid droplets. Increased plasma triglyceride concentration and decreased plasma apoA5 levels were observed in mice treated with 8-week olanzapine. Surprisingly, olanzapine markedly enhanced hepatic apoA5 protein levels in mice, without a significant effect on rodent hepatic ApoA5 mRNA. Our in vitro study showed that olanzapine reduced apoA5 protein levels in the medium and enhanced apoA5 protein levels in hepatocytes, whereas this drug exerted no effect on hepatocyte APOA5 mRNA. By transfecting APOA5 siRNA into HepG2 cells, it was demonstrated that APOA5 knockdown effectively reversed olanzapine-induced hepatocyte steatosis in vitro. In addition, olanzapine drastically increased sortilin mRNA and protein levels in vivo and in vitro. Interestingly, SORT1 knockdown reduced intracellular apoA5 protein levels and increased medium apoA5 protein levels in vitro, without affecting intracellular APOA5 mRNA levels. Furthermore, SORT1 knockdown greatly ameliorated hepatocyte steatosis in vitro. This study provides the first evidence that sortilin inhibits the hepatic apoA5 secretion that is attributable to olanzapine-induced NAFLD, which provides new insight into effective strategies against NAFLD for patients with schizophrenia administered olanzapine.
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Chen Q, Cao T, Li N, Zeng C, Zhang S, Wu X, Zhang B, Cai H. Repurposing of Anti-Diabetic Agents as a New Opportunity to Alleviate Cognitive Impairment in Neurodegenerative and Neuropsychiatric Disorders. Front Pharmacol 2021; 12:667874. [PMID: 34108878 PMCID: PMC8182376 DOI: 10.3389/fphar.2021.667874] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 05/07/2021] [Indexed: 12/16/2022] Open
Abstract
Cognitive impairment is a shared abnormality between type 2 diabetes mellitus (T2DM) and many neurodegenerative and neuropsychiatric disorders, such as Alzheimer’s disease (AD) and schizophrenia. Emerging evidence suggests that brain insulin resistance plays a significant role in cognitive deficits, which provides the possibility of anti-diabetic agents repositioning to alleviate cognitive deficits. Both preclinical and clinical studies have evaluated the potential cognitive enhancement effects of anti-diabetic agents targeting the insulin pathway. Repurposing of anti-diabetic agents is considered to be promising for cognitive deficits prevention or control in these neurodegenerative and neuropsychiatric disorders. This article reviewed the possible relationship between brain insulin resistance and cognitive deficits. In addition, promising therapeutic interventions, especially current advances in anti-diabetic agents targeting the insulin pathway to alleviate cognitive impairment in AD and schizophrenia were also summarized.
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Affiliation(s)
- Qian Chen
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Ting Cao
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - NaNa Li
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Cuirong Zeng
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Shuangyang Zhang
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Xiangxin Wu
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Bikui Zhang
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Hualin Cai
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
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Mbara KC, Mofo Mato PE, Driver C, Nzuza S, Mkhombo NT, Gcwensa SK, Mcobothi EN, Owira PM. Metformin turns 62 in pharmacotherapy: Emergence of non-glycaemic effects and potential novel therapeutic applications. Eur J Pharmacol 2021; 898:173934. [PMID: 33609563 DOI: 10.1016/j.ejphar.2021.173934] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Revised: 01/24/2021] [Accepted: 02/04/2021] [Indexed: 02/07/2023]
Abstract
Metformin is the most commonly prescribed oral antidiabetic medication. Direct/indirect activation of Adenosine Monophosphate-activated protein kinase (AMPK) and non-AMPK pathways, amongst others, are deemed to explain the molecular mechanisms of action of metformin. Metformin is an established insulin receptor sensitising antihyperglycemic agent, is highly affordable, and has superior safety and efficacy profiles. Emerging experimental and clinical evidence suggests that metformin has pleiotropic non-glycemic effects. Metformin appears to have weight stabilising, renoprotective, neuroprotective, cardio-vascular protective, and antineoplastic effects and mitigates polycystic ovarian syndrome. Anti-inflammatory and antioxidant effects of metformin seem to qualify it as an adjunct therapy in treating infectious diseases such as tuberculosis, viral hepatitis, and the current novel Covid-19 infections. So far, metformin is the only prescription medicine relevant to the emerging field of senotherapeutics. Non-glycemic effects of metformin favourable to its repurposing in therapeutic use are hereby discussed.
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Affiliation(s)
- Kingsley C Mbara
- Molecular and Clinical Pharmacology Research Laboratory, Department of Pharmacology, Discipline of Pharmaceutical Sciences, University of Kwazulu-Natal, P.O. Box X5401, Durban, South Africa
| | - Pascale E Mofo Mato
- Molecular and Clinical Pharmacology Research Laboratory, Department of Pharmacology, Discipline of Pharmaceutical Sciences, University of Kwazulu-Natal, P.O. Box X5401, Durban, South Africa
| | - Christine Driver
- Molecular and Clinical Pharmacology Research Laboratory, Department of Pharmacology, Discipline of Pharmaceutical Sciences, University of Kwazulu-Natal, P.O. Box X5401, Durban, South Africa
| | - Sanelisiwe Nzuza
- Molecular and Clinical Pharmacology Research Laboratory, Department of Pharmacology, Discipline of Pharmaceutical Sciences, University of Kwazulu-Natal, P.O. Box X5401, Durban, South Africa
| | - Ntokozo T Mkhombo
- Molecular and Clinical Pharmacology Research Laboratory, Department of Pharmacology, Discipline of Pharmaceutical Sciences, University of Kwazulu-Natal, P.O. Box X5401, Durban, South Africa
| | - Senamile Kp Gcwensa
- Molecular and Clinical Pharmacology Research Laboratory, Department of Pharmacology, Discipline of Pharmaceutical Sciences, University of Kwazulu-Natal, P.O. Box X5401, Durban, South Africa
| | - Esethu N Mcobothi
- Molecular and Clinical Pharmacology Research Laboratory, Department of Pharmacology, Discipline of Pharmaceutical Sciences, University of Kwazulu-Natal, P.O. Box X5401, Durban, South Africa
| | - Peter Mo Owira
- Molecular and Clinical Pharmacology Research Laboratory, Department of Pharmacology, Discipline of Pharmaceutical Sciences, University of Kwazulu-Natal, P.O. Box X5401, Durban, South Africa.
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Mishu MP, Uphoff E, Aslam F, Philip S, Wright J, Tirbhowan N, Ajjan RA, Al Azdi Z, Stubbs B, Churchill R, Siddiqi N. Interventions for preventing type 2 diabetes in adults with mental disorders in low- and middle-income countries. Cochrane Database Syst Rev 2021; 2:CD013281. [PMID: 33591592 PMCID: PMC8092639 DOI: 10.1002/14651858.cd013281.pub2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND The prevalence of type 2 diabetes is increased in individuals with mental disorders. Much of the burden of disease falls on the populations of low- and middle-income countries (LMICs). OBJECTIVES To assess the effects of pharmacological, behaviour change, and organisational interventions versus active and non-active comparators in the prevention or delay of type 2 diabetes among people with mental illness in LMICs. SEARCH METHODS We searched the Cochrane Common Mental Disorders Controlled Trials Register, CENTRAL, MEDLINE, Embase and six other databases, as well as three international trials registries. We also searched conference proceedings and checked the reference lists of relevant systematic reviews. Searches are current up to 20 February 2020. SELECTION CRITERIA Randomized controlled trials (RCTs) of pharmacological, behavioural or organisational interventions targeting the prevention or delay of type 2 diabetes in adults with mental disorders in LMICs. DATA COLLECTION AND ANALYSIS Pairs of review authors working independently performed data extraction and risk of bias assessments. We conducted meta-analyses using random-effects models. MAIN RESULTS One hospital-based RCT with 150 participants (99 participants with schizophrenia) addressed our review's primary outcome of prevention or delay of type 2 diabetes onset. Low-certainty evidence from this study did not show a difference between atypical and typical antipsychotics in the development of diabetes at six weeks (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.03 to 7.05) (among a total 99 participants with schizophrenia, 68 were in atypical and 31 were in typical antipsychotic groups; 55 participants without mental illness were not considered in the analysis). An additional 29 RCTs with 2481 participants assessed one or more of the review's secondary outcomes. All studies were conducted in hospital settings and reported on pharmacological interventions. One study, which we could not include in our meta-analysis, included an intervention with pharmacological and behaviour change components. We identified no studies of organisational interventions. Low- to moderate-certainty evidence suggests there may be no difference between the use of atypical and typical antipsychotics for the outcomes of drop-outs from care (RR 1.31, 95% CI 0.63 to 2.69; two studies with 144 participants), and fasting blood glucose levels (mean difference (MD) 0.05 lower, 95% CI 0.10 to 0.00; two studies with 211 participants). Participants who receive typical antipsychotics may have a lower body mass index (BMI) at follow-up than participants who receive atypical antipsychotics (MD 0.57, 95% CI 0.33 to 0.81; two studies with 141 participants; moderate certainty of evidence), and may have lower total cholesterol levels eight weeks after starting treatment (MD 0.35, 95% CI 0.27 to 0.43; one study with 112 participants). There was moderate certainty evidence suggesting no difference between the use of metformin and placebo for the outcomes of drop-outs from care (RR 1.22, 95% CI 0.09 to 16.35; three studies with 158 participants). There was moderate-to-high certainty evidence of no difference between metformin and placebo for fasting blood glucose levels (endpoint data: MD -0.35, 95% CI -0.60 to -0.11; change from baseline data: MD 0.01, 95% CI -0.21 to 0.22; five studies with 264 participants). There was high certainty evidence that BMI was lower for participants receiving metformin compared with those receiving a placebo (MD -1.37, 95% CI -2.04 to -0.70; five studies with 264 participants; high certainty of evidence). There was no difference between metformin and placebo for the outcomes of waist circumference, blood pressure and cholesterol levels. Low-certainty evidence from one study (48 participants) suggests there may be no difference between the use of melatonin and placebo for the outcome of drop-outs from care (RR 1.00, 95% CI 0.38 to 2.66). Fasting blood glucose is probably reduced more in participants treated with melatonin compared with placebo (endpoint data: MD -0.17, 95% CI -0.35 to 0.01; change from baseline data: MD -0.24, 95% CI -0.39 to -0.09; three studies with 202 participants, moderate-certainty evidence). There was no difference between melatonin and placebo for the outcomes of waist circumference, blood pressure and cholesterol levels. Very low-certainty evidence from one study (25 participants) suggests that drop-outs may be higher in participants treated with a tricyclic antidepressant (TCA) compared with those receiving a selective serotonin reuptake inhibitor (SSRI) (RR 0.34, 95% CI 0.11 to 1.01). It is uncertain if there is no difference in fasting blood glucose levels between these groups (MD -0.39, 95% CI -0.88 to 0.10; three studies with 141 participants, moderate-certainty evidence). It is uncertain if there is no difference in BMI and depression between the TCA and SSRI antidepressant groups. AUTHORS' CONCLUSIONS Only one study reported data on our primary outcome of interest, providing low-certainty evidence that there may be no difference in risk between atypical and typical antipsychotics for the outcome of developing type 2 diabetes. We are therefore not able to draw conclusions on the prevention of type 2 diabetes in people with mental disorders in LMICs. For studies reporting on secondary outcomes, there was evidence of risk of bias in the results. There is a need for further studies with participants from LMICs with mental disorders, particularly on behaviour change and on organisational interventions targeting prevention of type 2 diabetes in these populations.
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Affiliation(s)
| | - Eleonora Uphoff
- Cochrane Common Mental Disorders, University of York, York, UK
- Centre for Reviews and Dissemination, University of York, York, UK
| | - Faiza Aslam
- WHO Collaborating Centre for Mental Health & Research, Rawalpindi Medical University, Rawalpindi, Pakistan
| | - Sharad Philip
- Psychiatric Rehabilitation Services Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), An Institute of National Importance, Bangalore, India
| | - Judy Wright
- Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | - Nilesh Tirbhowan
- Department of Health Sciences, Hull York Medical School, University of York, York, UK
| | - Ramzi A Ajjan
- Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK
| | - Zunayed Al Azdi
- Research and Research Uptake Division, ARK Foundation, Dhaka, Bangladesh
| | - Brendon Stubbs
- Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK
- South London and Maudsley NHS Foundation Trust, London, UK
| | - Rachel Churchill
- Cochrane Common Mental Disorders, University of York, York, UK
- Centre for Reviews and Dissemination, University of York, York, UK
| | - Najma Siddiqi
- Department of Health Sciences, University of York, York, UK
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Fernández-Abascal B, Suárez-Pinilla P, Cobo-Corrales C, Crespo-Facorro B, Suárez-Pinilla M. In- and outpatient lifestyle interventions on diet and exercise and their effect on physical and psychological health: a systematic review and meta-analysis of randomised controlled trials in patients with schizophrenia spectrum disorders and first episode of psychosis. Neurosci Biobehav Rev 2021; 125:535-568. [PMID: 33503476 DOI: 10.1016/j.neubiorev.2021.01.005] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Revised: 01/01/2021] [Accepted: 01/04/2021] [Indexed: 12/22/2022]
Abstract
Patients with non-affective psychosis often lead unhealthy lifestyles. We performed a systematic review and meta-analysis on non-pharmacological RCTs for improvement of diet and physical activity in non-affective psychosis patients, including first-episode psychosis. A variety of outcomes was analysed, including metabolic, psychopathology, cognitive, functional and quality of life outcomes. Fifty-nine studies were included. An improvement in anthropometric measurements (BMI, weight, waist circumference) was observed post-intervention, persisting after follow-up. Post-intervention benefit was found also for psychotic symptoms severity (also persisting after follow-up), many cognitive domains and physical and global functioning and quality of life. Conversely, no effect was observed in relation to most blood metabolites, blood pressure and non-psychotic psychopathology and spontaneous physical activity. Improvement was generally larger for interventions including exercise, especially moderate/vigorous aerobic exercise, but follow-up maintenance was greater for psychotherapy interventions. Sensitivity analyses limited to chronic stages of psychosis and low risk of bias studies produced comparable results. Further studies are needed to design optimized interventions in this vulnerable population.
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Affiliation(s)
- Blanca Fernández-Abascal
- Department of Psychiatry, University Hospital Marqués de Valdecilla, IDIVAL, Santander, 39011, Spain.
| | - Paula Suárez-Pinilla
- Department of Psychiatry, University Hospital Marqués de Valdecilla, IDIVAL, Santander, 39011, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, 28029, Spain.
| | | | - Benedicto Crespo-Facorro
- Department of Psychiatry, School of Medicine, University Hospital Virgen del Rocío - IBiS, Sevilla, 41013, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, 28029, Spain
| | - Marta Suárez-Pinilla
- Department of Neurodegenerative Disease, Institute of Neurology, University College of London, London, WC1N 3AX, UK.
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de Boer N, Guloksuz S, van Baal C, Willebrands L, Deenik J, Vinkers CH, Rossum IWV, Zinkstok J, Wilting I, Zantvoord JB, Backx F, Swildens WE, Schouw M, Bogers J, Hulshof F, de Knijff R, Duindam P, Veereschild M, Bak M, Frederix G, de Haan L, van Os J, Cahn W, Luykx JJ. Study protocol of a randomized, double-blind, placebo-controlled, multi-center trial to treat antipsychotic-induced weight gain: the Metformin-Lifestyle in antipsychotic users (MELIA) trial. BMC Psychiatry 2021; 21:4. [PMID: 33402159 PMCID: PMC7783702 DOI: 10.1186/s12888-020-02992-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Accepted: 11/26/2020] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Antipsychotic-induced Weight Gain (AiWG) is a debilitating and common adverse effect of antipsychotics. AiWG negatively impacts life expectancy, quality of life, treatment adherence, likelihood of developing type-2 diabetes and readmission. Treatment of AiWG is currently challenging, and there is no consensus on the optimal management strategy. In this study, we aim to evaluate the use of metformin for the treatment of AiWG by comparing metformin with placebo in those receiving treatment as usual, which includes a lifestyle intervention. METHODS In this randomized, double-blind, multicenter, placebo-controlled, pragmatic trial with a follow-up of 52 weeks, we aim to include 256 overweight participants (Body Mass Index (BMI) > 25 kg/m2) of at least 16 years of age. Patients are eligible if they have been diagnosed with schizophrenia spectrum disorder and if they have been using an antipsychotic for at least three months. Participants will be randomized with a 1:1 allocation to placebo or metformin, and will be treated for a total of 26 weeks. Metformin will be started at 500 mg b.i.d. and escalated to 1000 mg b.i.d. 2 weeks thereafter (up to a maximum of 2000 mg daily). In addition, all participants will undergo a lifestyle intervention as part of the usual treatment consisting of a combination of an exercise program and dietary consultations. The primary outcome measure is difference in body weight as a continuous trait between the two arms from treatment inception until 26 weeks of treatment, compared to baseline. Secondary outcome measures include: 1) Any element of metabolic syndrome (MetS); 2) Response, defined as ≥5% body weight loss at 26 weeks relative to treatment inception; 3) Quality of life; 4) General mental and physical health; and 5) Cost-effectiveness. Finally, we aim to assess whether genetic liability to BMI and MetS may help estimate the amount of weight reduction following initiation of metformin treatment. DISCUSSION The pragmatic design of the current trial allows for a comparison of the efficacy and safety of metformin in combination with a lifestyle intervention in the treatment of AiWG, facilitating the development of guidelines on the interventions for this major health problem. TRIAL REGISTRATION This trial was registered in the Netherlands Trial Register (NTR) at https://www.trialregister.nl/trial/8440 as NTR NL8840 on March 8, 2020.
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Affiliation(s)
- Nini de Boer
- Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508, Utrecht, GA, The Netherlands.
| | - Sinan Guloksuz
- grid.412966.e0000 0004 0480 1382Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands ,grid.47100.320000000419368710Department of Psychiatry, Yale University School of Medicine, New Haven, CT USA
| | - Caroline van Baal
- Department of Biostatistics and Research Support, Julius Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Leonie Willebrands
- Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508 Utrecht, GA The Netherlands
| | - Jeroen Deenik
- Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508 Utrecht, GA The Netherlands ,grid.412966.e0000 0004 0480 1382Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands ,grid.491215.a0000 0004 0468 1456GGz Centraal Mental Health, Amersfoort, The Netherlands
| | - Christiaan H. Vinkers
- grid.7177.60000000084992262Department of Psychiatry and Department of Anatomy and Neuroscience, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands ,GGZinGeest Mental Health, Amsterdam, The Netherlands
| | - Inge Winter-van Rossum
- Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508 Utrecht, GA The Netherlands
| | - Janneke Zinkstok
- Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508 Utrecht, GA The Netherlands
| | - Ingeborg Wilting
- Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Jasper B. Zantvoord
- grid.7177.60000000084992262Department of Psychiatry and Department of Anatomy and Neuroscience, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Frank Backx
- Department of Rehabilitation, Physiotherapy Science & Sport, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Wilma E. Swildens
- grid.413664.2Altrecht Mental Health Care Institute, Utrecht, The Netherlands ,grid.448984.d0000 0003 9872 5642Inholland University of Applied Sciences, Interprofessional Mental Health Care, department Nursing, Amsterdam, The Netherlands
| | - Marieke Schouw
- grid.413664.2Altrecht Mental Health Care Institute, Utrecht, The Netherlands
| | - Jan Bogers
- grid.468622.c0000 0004 0501 8787GGZ Rivierduinen, Oegstgeest, The Netherlands
| | | | | | | | | | - Maarten Bak
- grid.412966.e0000 0004 0480 1382Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands ,Mondriaan Mental Health, Maastricht, The Netherlands
| | - Geert Frederix
- Department of Public Health, Julius Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Lieuwe de Haan
- grid.7177.60000000084992262Department of Psychiatry and Department of Anatomy and Neuroscience, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands ,Arkin GGZ, Amsterdam, The Netherlands
| | - Jim van Os
- Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508 Utrecht, GA The Netherlands ,grid.412966.e0000 0004 0480 1382Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands ,grid.13097.3c0000 0001 2322 6764Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
| | - Wiepke Cahn
- Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508 Utrecht, GA The Netherlands ,grid.413664.2Altrecht Mental Health Care Institute, Utrecht, The Netherlands
| | - Jurjen J. Luykx
- Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, HP A01.126, P.O. Box 85500, 3508 Utrecht, GA The Netherlands ,GGNet Mental Health, Warnsveld, The Netherlands ,Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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Xiao J, Huang J, Long Y, Wang X, Wang Y, Yang Y, Hei G, Sun M, Zhao J, Li L, Shao T, Wang W, Kang D, Liu C, Xie P, Huang Y, Wu R, Zhao J. Optimizing and Individualizing the Pharmacological Treatment of First-Episode Schizophrenic Patients: Study Protocol for a Multicenter Clinical Trial. Front Psychiatry 2021; 12:611070. [PMID: 33716817 PMCID: PMC7947302 DOI: 10.3389/fpsyt.2021.611070] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 01/22/2021] [Indexed: 01/10/2023] Open
Abstract
Introduction: Affecting ~1% of the world population, schizophrenia is known as one of the costliest and most burdensome diseases worldwide. Antipsychotic medications are the main treatment for schizophrenia to control psychotic symptoms and efficiently prevent new crises. However, due to poor compliance, 74% of patients with schizophrenia discontinue medication within 1.5 years, which severely affects recovery and prognosis. Through research on intra and interindividual variability based on a psychopathology-neuropsychology-neuroimage-genetics-physiology-biochemistry model, our main objective is to investigate an optimized and individualized antipsychotic-treatment regimen and precision treatment for first-episode schizophrenic patients. Methods and Analysis: The study is performed in 20 representative hospitals in China. Three subprojects are included. In subproject 1, 1,800 first-episode patients with schizophrenia are randomized into six different antipsychotic monotherapy groups (olanzapine, risperidone, aripiprazole, ziprasidone, amisulpride, and haloperidol) for an 8-week treatment. By identifying a set of potential biomarkers associated with antipsychotic treatment response, we intend to build a prediction model, which includes neuroimaging, epigenetics, environmental stress, neurocognition, eye movement, electrophysiology, and neurological biochemistry indexes. In subproject 2, apart from verifying the prediction model established in subproject 1 based on an independent cohort of 1,800 first-episode patients with schizophrenia, we recruit patients from a verification cohort who did not get an effective response after an 8-week antipsychotic treatment into a randomized double-blind controlled trial with minocycline (200 mg per day) and sulforaphane (3 tables per day) to explore add-on treatment for patients with schizophrenia. Two hundred forty participants are anticipated to be enrolled for each group. In subproject 3, we tend to carry out one trial to construct an intervention strategy for metabolic syndrome induced by antipsychotic treatment and another one to build a prevention strategy for patients at a high risk of metabolic syndrome, which combines metformin and lifestyle intervention. Two hundred participants are anticipated to be enrolled for each group. Ethics and Dissemination: The study protocol has been approved by the Medical Ethics committee of the Second Xiangya Hospital of Central South University (No. 2017027). Results will be disseminated in peer-reviewed journals and at international conferences. Trial Registration: This trial has been registered on Clinicalrials.gov (NCT03451734). The protocol version is V.1.0 (April 23, 2017).
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Affiliation(s)
- Jingmei Xiao
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Jing Huang
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yujun Long
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Xiaoyi Wang
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Ying Wang
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Ye Yang
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Gangrui Hei
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Mengxi Sun
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Jin Zhao
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Li Li
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Tiannan Shao
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Weiyan Wang
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Dongyu Kang
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Chenchen Liu
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Peng Xie
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yuyan Huang
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Renrong Wu
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Jingping Zhao
- Department of Psychaitry, National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China
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Gao H, Luo C, Tu SJ, Lu RP, Jiang LN, Qiao HJ, Lin Q, Li NN, Chen JH. The Effect of Yijinjing on the Cognitive Function of Patients With Chronic Schizophrenia. Front Psychiatry 2021; 12:739364. [PMID: 34744830 PMCID: PMC8564041 DOI: 10.3389/fpsyt.2021.739364] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Accepted: 09/13/2021] [Indexed: 01/01/2023] Open
Abstract
Background: Patients with chronic schizophrenia present cognitive impairment, which affects their social function and prevents them from reintegrating into society. Yijinjing is a traditional Chinese aerobic exercise that has a putative psychosomatic effect on improving cognitive function. Methods: From January to May 2021, 40 patients with chronic schizophrenia were recruited and randomly divided into a control group and a Yijinjing group. In the 12-week intervention, the patients in the control group received conventional treatment, whereas patients in the Yijinjing group performed Yijinjing exercise (40 min/session, twice a week) in addition to receiving conventional treatment. The Positive and Negative Syndrome Scale (PANSS), the Insight and Treatment Attitude Questionnaire (ITAQ), the Rosenberg Self-esteem Scale (SES), and the Mini Mental State Examination (MMSE) were used to measure clinical symptoms and cognitive function at 0, 6, and 12 weeks. Results: The demographic information was not significantly different between groups. At baseline, the scores of all the scales were not statistically different between groups. After 12 weeks of intervention, compared to those at baseline, the scores of the negative scale (t = 19.00, p < 0.0001), general psychopathology scale (t = 15.98, p < 0.0001), and total score (t = 15.47, p < 0.0001) of the PANSS and SES (t = 5.378, p < 0.0001) had significantly decreased, and the scores of the ITAQ (t = 7.984, p < 0.0001) and MMSE (t = 6.750, p < 0.0001) had significantly increased in Yijinjing group; the score of the MMSE increased in the control group as well (t = 2.491, p = 0.0222). Compared to the respective scores in the control group, the negative scale score (t = 2.953, p = 0.0054) significantly decreased, and the ITAQ (t = 3.043, p = 0.0042) and MMSE (t = 2.2.68, p = 0.0291) scores significantly increased in the Yijinjing group after 12 weeks of intervention. Conclusion: These results provide a preliminary indication that Yijinjing exercise had the potential to improve cognitive function and negative symptoms in patients with chronic schizophrenia. A larger-scale study to determine the trajectory of change in the longer term should be undertaken.
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Affiliation(s)
- Hui Gao
- Department of Psychiatry, Shanghai No.1 Mental Health Center of Civil Administration, Shanghai, China
| | - Chao Luo
- Shanghai Institute of Traditional Chinese Medicine for Mental Health, Shanghai Clinical Research Center for Mental Health, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Si-Jing Tu
- School of Public Health, Hangzhou Normal University, Hangzhou, China.,School of Public Health and Management, Guangxi University of Chinese Medicine, Nanning, China
| | - Ru-Ping Lu
- Department of Psychiatry, Shanghai No.1 Mental Health Center of Civil Administration, Shanghai, China
| | - Lin-Na Jiang
- Department of Psychiatry, Shanghai No.1 Mental Health Center of Civil Administration, Shanghai, China
| | - Hui-Jun Qiao
- Department of Psychiatry, Shanghai No.1 Mental Health Center of Civil Administration, Shanghai, China
| | - Qu Lin
- Department of Psychiatry, Shanghai No.1 Mental Health Center of Civil Administration, Shanghai, China
| | - Ning-Ning Li
- Shanghai Institute of Traditional Chinese Medicine for Mental Health, Shanghai Clinical Research Center for Mental Health, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jian-Hua Chen
- Shanghai Institute of Traditional Chinese Medicine for Mental Health, Shanghai Clinical Research Center for Mental Health, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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45
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Liao X, Ye H, Si T. A Review of Switching Strategies for Patients with Schizophrenia Comorbid with Metabolic Syndrome or Metabolic Abnormalities. Neuropsychiatr Dis Treat 2021; 17:453-469. [PMID: 33603382 PMCID: PMC7884949 DOI: 10.2147/ndt.s294521] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Accepted: 01/07/2021] [Indexed: 12/31/2022] Open
Abstract
Metabolic syndrome (MetS) in patients with schizophrenia occurs 2-3 times more frequently than in the general population. Antipsychotic medication is a primary risk factor for patients with MetS. In particular, the widely used second-generation antipsychotics can affect glucose and lipid metabolism and can induce insulin resistance and other metabolic abnormalities through various receptors. Notably, the metabolic risks of various antipsychotics may differ because of their different pharmacological affinity to MetS-related receptors. Several previous studies have shown that switching from high to low metabolic risk antipsychotics may improve patients' metabolic parameters. The current review aims to discuss the strategies for switching antipsychotic medications and the impact on metabolic abnormalities in patients with schizophrenia.
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Affiliation(s)
- Xuemei Liao
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, People's Republic of China
| | - Hui Ye
- Medical Department, Sanofi, Shanghai, People's Republic of China
| | - Tianmei Si
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, People's Republic of China
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46
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Luo C, Wang X, Huang HX, Mao XY, Zhou HH, Liu ZQ. Coadministration of metformin prevents olanzapine-induced metabolic dysfunction and regulates the gut-liver axis in rats. Psychopharmacology (Berl) 2021; 238:239-248. [PMID: 33095288 DOI: 10.1007/s00213-020-05677-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 10/05/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Olanzapine is widely prescribed for patients with mental disorders; however, it may induce metabolic dysfunction. Metformin is an efficient adjuvant for preventing olanzapine-induced metabolic dysfunction in clinical practice. Although the mechanism of how metformin prevents this metabolic dysfunction remains unknown, changes in the gut-liver axis are considered a potential explanation. METHODS Forty-eight male rats were gavaged with olanzapine and/or metformin for 35 consecutive days. Body weight, food intake, and water intake were measured daily. Histopathological and biochemical tests were performed to evaluate the metabolic dysfunction. The 16S rRNA obtained from fecal bacterial DNA was assessed. RESULTS Olanzapine treatment increased the body weight, blood glucose and triglyceride levels, and the number of adipocytes in the liver. While coadministration of metformin, there was a dose-dependent reverse of the abnormal changes induced by olanzapine treatment. Both olanzapine and metformin treatments altered the composition of the gut microbiota. Bacteroides acidifaciens and Lactobacillus gasseri were possibly played a positive role in metformin-mediated olanzapine-induced metabolic dysfunction prevention. CONCLUSION Metformin prevented olanzapine-induced metabolic dysfunction and regulated the gut microbiota in a dose-dependent manner.
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Affiliation(s)
- Chao Luo
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.,School of Life Sciences, Central South University, Changsha, 410078, Hunan, China
| | - Xu Wang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China
| | - Han-Xue Huang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China
| | - Xiao-Yuan Mao
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China
| | - Hong-Hao Zhou
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.,Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China
| | - Zhao-Qian Liu
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China. .,Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People's Republic of China.
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47
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Chen X, Wang DD, Li ZP. Time course and dose effect of metformin on weight in patients with different disease states. Expert Rev Clin Pharmacol 2020; 13:1169-1177. [PMID: 32940086 DOI: 10.1080/17512433.2020.1822164] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
OBJECTIVES The present study was to quantitate and compare the efficacy of metformin on weight in different disease states using model-based meta-analysis (MBMA). METHODS Randomized controlled trials (RCT) of metformin effects on weight in different disease states were collected by searching the public databases. The change rate of weight from baseline was selected as the efficacy indicator. RESULTS A total 21 RCTs containing 1885 patients including patients with type 2 diabetes mellitus, patients with antipsychotic induced weight gain, patients with obesity, were included into the present study. After deducting placebo effect, the maximal effect (Emax) of metformin on weight in patients with type 2 diabetes mellitus, patients with antipsychotic induced weight gain, patients with obesity were -6.86%, -8.82%, and -4.14%, respectively. The treatment duration to reach half of the maximal effect (ET50) were 107, 45.5, and 15.1 weeks, respectively. Within the metformin dose range from 21 RCTs, no significant dose-response relationship was observed. However, the time-course relationship is obvious for efficacy of metformin on weight. CONCLUSIONS The present study firstly provided quantitative information for metformin effects on weight in different disease states, including patients with type 2 diabetes mellitus, patients with antipsychotic induced weight gain, patients with obesity.
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Affiliation(s)
- Xiao Chen
- Department of Pharmacy, Children's Hospital of Fudan University , Shanghai, China
| | - Dong-Dong Wang
- Department of Pharmacy, Children's Hospital of Fudan University , Shanghai, China
| | - Zhi-Ping Li
- Department of Pharmacy, Children's Hospital of Fudan University , Shanghai, China
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Fakhari S, Nouri A, Jamzad M, Arab‐Salmanabadi S, Falaki F. Investigation of inclusion complex of metformin into selective cyclic peptides as novel drug delivery system: Structure, electronic properties,
AIM,
and
NBO
study via
DFT. J CHIN CHEM SOC-TAIP 2020. [DOI: 10.1002/jccs.202000304] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Shabnam Fakhari
- Department of Chemistry, Shahr‐e‐Qods Branch Islamic Azad University Tehran Iran
| | - Azita Nouri
- Department of Chemistry, Shahr‐e‐Qods Branch Islamic Azad University Tehran Iran
| | - Mina Jamzad
- Department of Chemistry, Shahr‐e‐Qods Branch Islamic Azad University Tehran Iran
| | | | - Foujan Falaki
- Department of Chemistry, Shahr‐e‐Qods Branch Islamic Azad University Tehran Iran
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Speyer H, Jakobsen AS, Westergaard C, Nørgaard HCB, Jørgensen KB, Pisinger C, Krogh J, Hjorthøj C, Nordentoft M, Gluud C, Correll CU. Lifestyle Interventions for Weight Management in People with Serious Mental Illness: A Systematic Review with Meta-Analysis, Trial Sequential Analysis, and Meta-Regression Analysis Exploring the Mediators and Moderators of Treatment Effects. PSYCHOTHERAPY AND PSYCHOSOMATICS 2020; 88:350-362. [PMID: 31522170 DOI: 10.1159/000502293] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Accepted: 07/19/2019] [Indexed: 11/19/2022]
Abstract
BACKGROUND Serious mental illness (SMI) reduces life expectancy, primarily due to somatic comorbidity linked to obesity. Meta-analyses have found beneficial effects of lifestyle interventions in people with SMI and recommended their implementation to manage obesity. OBJECTIVE The objective of this systematic review was to assess the benefits and harms of individualized lifestyle interventions for weight in people diagnosed with SMI and to explore potential mediators and moderators of the effect. METHODS The protocol was registered at PROSPERO (CRD42016049093). Randomized clinical trials (RCTs) assessing the effect of individualized lifestyle interventions on weight management in people with SMI were included. Primary outcomes were differences in endpoint body mass index (BMI) and the proportion achieving clinically relevant weight loss (≥5%). Secondary outcomes included quality of life, cardiometabolic risk factors, and adverse effects. RESULTS We included 41 RCTs (n = 4,267). All trials were at high risk of bias according to the Cochrane Handbook for Systematic Reviews of Interventions. The experimental interventions reduced the mean difference in BMI by -0.63 kg/m2 (95% confidence interval [CI] = -1.02 to -0.23; p = 0.002; I2 = 70.7%) compared to the control groups. At postintervention follow-up (17 RCTs), the effect size remained similar but was no longer significant (BMI = -0.63 kg/m2; 95% CI = -1.30 to 0.04; p = 0.07; I2 = 48.8%). The risk ratio for losing ≥5% of baseline weight was 1.51 (95% CI = 1.07-2.13; p = 0.02) compared to the control groups. GRADE showed very low or low quality of evidence. CONCLUSION There is a statistically significant, but clinically insignificant, mean effect of individualized lifestyle interventions for weight reduction in people with SMI.
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Affiliation(s)
- Helene Speyer
- Mental Health Center Copenhagen, Copenhagen University Hospital, Hellerup, Denmark,
| | - Ane Storch Jakobsen
- Mental Health Center Copenhagen, Copenhagen University Hospital, Hellerup, Denmark
| | - Casper Westergaard
- Mental Health Center Copenhagen, Copenhagen University Hospital, Hellerup, Denmark
| | | | | | - Charlotta Pisinger
- Research Center for Prevention and Health, Department 84-85, Glostrup University Hospital, Glostrup, Denmark
| | - Jesper Krogh
- Mental Health Center Copenhagen, Copenhagen University Hospital, Hellerup, Denmark
| | - Carsten Hjorthøj
- Mental Health Center Copenhagen, Copenhagen University Hospital, Hellerup, Denmark
| | - Merete Nordentoft
- Mental Health Center Copenhagen, Copenhagen University Hospital, Hellerup, Denmark
| | - Christian Gluud
- The Copenhagen Trial Unit, Center for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Christoph U Correll
- The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, New York, USA.,Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, New York, USA.,Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany
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Huang J, Hei GR, Yang Y, Liu CC, Xiao JM, Long YJ, Peng XJ, Yang Y, Zhao JP, Wu RR. Increased Appetite Plays a Key Role in Olanzapine-Induced Weight Gain in First-Episode Schizophrenia Patients. Front Pharmacol 2020; 11:739. [PMID: 32528286 PMCID: PMC7256453 DOI: 10.3389/fphar.2020.00739] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 05/04/2020] [Indexed: 01/10/2023] Open
Abstract
Weight gain and metabolic disturbances, potentially influenced by increased appetite, are common effects of olanzapine treatment in patients with schizophrenia. In this study, we explored the association between olanzapine-induced weight gain and metabolic effects with increased appetite. Drug-naïve, first-episode schizophrenia patients were treated with olanzapine for 12 weeks. Assessments included time to increased appetite, body weight, body mass index, biochemical indicators of blood glucose and lipids, proportion of patients who gained more than 7% or 10% of their baseline weight upon treatment conclusion, patients who developed dyslipidemia, and Positive and Negative Syndrome Scale scores. In total, 33 patients with schizophrenia receiving olanzapine were enrolled and 31 completed the study. During the 12-week olanzapine treatment, 77.4% (24/31) patients had increased appetite with 58.1% (18/31) patients having increased appetite within the first 4 weeks. The mean time for increased appetite was 20.3 days. More patients in the increased appetite group increased their initial body weight by more than 7% after 12 weeks when compared to patients with unchanged appetite (22/24 [91.7%] vs. 3/7 [42.9%], p = 0.004). Earlier increased appetite led to more weight gain during the following month. Overall, 50% of patients in the increased appetite group had dyslipidemia after 12 weeks. Our results demonstrated that olanzapine induced significantly appetite increase in first-episode patients with schizophrenia and appetite increase played a key role in olanzapine-induced weight gain and dyslipidemia. Clinical Trial Registration NCT03451734. Registered March 2, 2018 (retrospectively registered).
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Affiliation(s)
- Jing Huang
- Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China.,China National Clinical Research Center on Mental Disorders, Changsha, China.,China National Technology Institute on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, China
| | - Gang-Rui Hei
- Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China.,China National Clinical Research Center on Mental Disorders, Changsha, China.,China National Technology Institute on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, China
| | - Ye Yang
- Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China.,China National Clinical Research Center on Mental Disorders, Changsha, China.,China National Technology Institute on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, China
| | - Chen-Chen Liu
- Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China.,China National Clinical Research Center on Mental Disorders, Changsha, China.,China National Technology Institute on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, China
| | - Jing-Mei Xiao
- Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China.,China National Clinical Research Center on Mental Disorders, Changsha, China.,China National Technology Institute on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, China
| | - Yu-Jun Long
- Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China.,China National Clinical Research Center on Mental Disorders, Changsha, China.,China National Technology Institute on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, China
| | - Xing-Jie Peng
- Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China.,China National Clinical Research Center on Mental Disorders, Changsha, China.,China National Technology Institute on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, China
| | - Yi Yang
- Mental Health Institute, Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, China
| | - Jing-Ping Zhao
- Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China.,China National Clinical Research Center on Mental Disorders, Changsha, China.,China National Technology Institute on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, China
| | - Ren-Rong Wu
- Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China.,China National Clinical Research Center on Mental Disorders, Changsha, China.,China National Technology Institute on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, China.,Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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