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Gahr M. [Metabolic adverse drug reactions related to psychotropic drugs]. FORTSCHRITTE DER NEUROLOGIE-PSYCHIATRIE 2025; 93:95-103. [PMID: 39313203 DOI: 10.1055/a-2405-5087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/25/2024]
Abstract
Metabolic adverse drug reactions (mADR) related to psychotropic drugs have significant health-related effects including weight gain, impaired glucose tolerance, diabetes mellitus and dyslipidemia as well as economic relevance. Nearly all antipsychotics (AP) and many antidepressants (AD) and mood stabilisers may induce weight gain. Weight development in the first weeks or months after the beginning of the therapy is the strongest predictor for weight gain related to AP and AD. The most important risk factors for mADR are antagonistic effects at H1-, 5-HT2C- und M3-receptors and antidopaminergic effects. However, several other systems are also relevant. Systematic monitoring of metabolic parameters is recommended in all patients treated with substances that are associated with an increased risk of mADR. Lifestyle modification, dietary measures, exercise therapy, dose reduction, change and discontinuation of the substance, and additional treatment with metformin and topiramate are evidence-based treatment options for AP-associated weight gain. GLP-1 receptor agonists such as liraglutide are also promising.
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Affiliation(s)
- Maximilian Gahr
- Krankenhaus für Psychiatrie, Psychotherapie und Psychosomatische Medizin, Schloss Werneck, Werneck, Germany
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2
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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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Campforts B, Drukker M, Crins J, van Amelsvoort T, Bak M. Association between antipsychotic medication and clinically relevant weight change: meta-analysis. BJPsych Open 2023; 9:e18. [PMID: 36651070 PMCID: PMC9885350 DOI: 10.1192/bjo.2022.619] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Previous meta-analyses have shown that almost all antipsychotics are associated with weight gain. However, mean weight gain is not informative about clinically relevant weight gain or weight loss. AIMS To provide further insight into the more severe body weight changes associated with antipsychotic use, we assessed the proportion of patients with clinically relevant weight gain (CRWG) and clinically relevant weight loss (CRWL), defined as ≥7% weight gain and ≥7% weight loss. METHOD We searched PubMed, Embase and PsycInfo for randomised controlled trials of antipsychotics that reported CRWG and CRWL in study populations aged 15 years or older. We conducted meta-analyses stratified by antipsychotic and study duration using a random-effects model. We performed meta-regression analyses to assess antipsychotic-naive status and psychiatric diagnosis as modifiers for CRWG. PROSPERO: CRD42020204734. RESULTS We included 202 articles (201 studies). Almost all included antipsychotics were associated with CRWG. For CRWL, available data were too limited to draw firm conclusions. For some antipsychotics, CRWG was more pronounced in individuals who were antipsychotic-naive than in individuals switching to another antipsychotic. Moreover, a longer duration of antipsychotic use was associated with more CRWG, but not CRWL. For some antipsychotics, CRWG was higher in people diagnosed with schizophrenia, but this was inconsistent. CONCLUSIONS Switching antipsychotic medication is associated with both weight gain and weight loss, but the level of CRWG is higher than CRWL in antipsychotic-switch studies. CRWG was more pronounced in antipsychotic-naive patients, highlighting their vulnerability to weight gain. The impact of diagnosis on CRWG remains inconclusive.
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Affiliation(s)
- Bea Campforts
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
| | - Marjan Drukker
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
| | - Joost Crins
- Faculty of Health Medicine and Life Science, Maastricht University, Maastricht, The Netherlands
| | - Therese van Amelsvoort
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
| | - Maarten Bak
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
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Chen X, Liu L, Zeng Y, Li D, Liu X, Hu C. Olanzapine induces weight gain in offspring of prenatally exposed poly I:C rats by reducing brown fat thermogenic activity. Front Pharmacol 2022; 13:1001919. [PMID: 36249777 PMCID: PMC9561095 DOI: 10.3389/fphar.2022.1001919] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Accepted: 09/13/2022] [Indexed: 11/25/2022] Open
Abstract
Background: Olanzapine (OLZ) is an antipsychotic with a high risk of metabolic syndrome, and its induced metabolic disturbance may be related to the thermogenic function of brown adipose tissue (BAT). Of note is that schizophrenia itself appears to be associated with a higher incidence of metabolic syndrome. However, whether OLZ affects metabolic disorders by regulating BAT function and its mechanism in animal models of schizophrenia have not been reported. Methods: We induced maternal immune activation (MIA) in pregnant rodents by injection of synthetic double-stranded RNA-poly I:C (a virus-like substance), and rats were injected with poly I:C, 10 mg/kg) or saline on day 13 of gestation. Rat offspring received OLZ (1 mg/kg, tid) or vehicle from adulthood for 28 days, and body weight and food intake were recorded. Morphological alterations of white adipose tissue (WAT) and BAT were analyzed by HE and oil red staining, and expression of BAT-specific marker proteins/genes was detected by western blot and qRT-PCR. In addition, embryonic stem cells C3H10T1/2 were used to direct differentiation into brown-like adipocytes, and C3H10T1/2 cells were treated with OLZ for the differentiation process. The effects of OLZ on brown-like adipocyte differentiation and activity were analyzed using oil red staining, immunofluorescence and flow cytometry. Results: Compared with the Veh (saline) group, the TG, pWAT weight, adipocyte size and liver weight of the Veh (poly I:C) group were significantly increased, suggesting that the offspring of Poly I:C rats had obvious dyslipidemia and lipid accumulation, which were risk factors for metabolic abnormalities such as obesity. In addition, OLZ treatment resulted in altered WAT and BAT morphology in poly I:C or saline exposed offspring, causing lipid accumulation and weight gain and reducing the expression of the BAT-specific marker molecule UCP1 protein/gene. At the same time, OLZ inhibited the directional differentiation and mitochondrial activity of C3H10T1/2 brown-like adipocytes. Conclusion: Poly I:C-elicited MIA and OLZ differentially inhibited BAT activity and mitochondrial biogenesis, leading to weight gain in adult rats, a process involving PPAR-γ/UCP1-related thermogenic proteins.
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Affiliation(s)
- Xiaoying Chen
- College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China
- The Second Affiliated Hospital, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Lu Liu
- College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China
- Department of Preclinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Yanping Zeng
- College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China
| | - Dejuan Li
- College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China
| | - Xuemei Liu
- College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China
| | - Changhua Hu
- College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China
- *Correspondence: Changhua Hu,
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Alphs L, Brown B, Turkoz I, Baker P, Fu DJ, Nuechterlein KH. The Disease Recovery Evaluation and Modification (DREaM) study: Effectiveness of paliperidone palmitate versus oral antipsychotics in patients with recent-onset schizophrenia or schizophreniform disorder. Schizophr Res 2022; 243:86-97. [PMID: 35247794 DOI: 10.1016/j.schres.2022.02.019] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 01/28/2022] [Accepted: 02/13/2022] [Indexed: 11/27/2022]
Abstract
We report primary results of the Disease Recovery Evaluation and Modification (DREaM) study, a randomized, open-label, delayed-start trial designed to compare the effectiveness of paliperidone palmitate (PP) versus oral antipsychotics (OAP) in delaying time to first treatment failure (TtFTF) in participants with recent-onset schizophrenia or schizophreniform disorder. DREaM included: Part I, 2-month oral run-in; Part II, 9-month disease progression phase (PP or OAP); Part III, 9 months of additional treatment (PP/PP; OAP rerandomized: OAP/OAP or OAP/PP). PP/PP and OAP/OAP comprised the 18-month extended disease progression (EDP) analysis. A total of 235 participants were randomized to PP (n = 78) or OAP (n = 157) in Part II. No statistically significant differences in TF between treatment groups were identified during Part II (PP 29.5%, OAP 24.8%; P = 0.377), Part III (PP/PP 14.3%, OAP/PP 15.8%, OAP/OAP 28.6%; P = 0.067) or the EDP analysis (PP/PP 28.6%, OAP/OAP 44.4%; NNT = 6; P = 0.080). Using a modified definition of TF excluding treatment supplementation with another antipsychotic, a common approach to managing dose adjustments, significant differences were observed between treatment groups in Part III (PP/PP 4.1%, OAP/PP 14.0%, OAP/OAP 27.0%; P = 0.002) and EDP (PP/PP 14.3%, OAP/OAP 42.9%; P = 0.001). Safety results were consistent with the known safety profile of PP. Although significant treatment differences were not observed during the first 9 months of DREaM, numerical differences favoring PP emerged in the last 9 months and significant differences were observed when TF criteria were limited to their most impactful components. These results highlight the potential benefit of initiating PP early in the course of schizophrenia and provide valuable insights for future clinical trials in recent-onset schizophrenia or schizophreniform disorder. Clinicaltrials.gov identifier: NCT02431702.
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Affiliation(s)
- Larry Alphs
- Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USA
| | - Brianne Brown
- Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USA.
| | - Ibrahim Turkoz
- Janssen Research and Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USA.
| | - Pamela Baker
- Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USA.
| | - Dong-Jing Fu
- Janssen Research and Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USA.
| | - Keith H Nuechterlein
- Departments of Psychiatry and Psychology, University of California at Los Angeles, 150 Medical Plaza Driveway, Los Angeles, CA 90095, USA.
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Wannasuphoprasit Y, Andersen SE, Arranz MJ, Catalan R, Jurgens G, Kloosterboer SM, Rasmussen HB, Bhat A, Irizar H, Koller D, Polimanti R, Wang B, Zartaloudi E, Austin-Zimmerman I, Bramon E. CYP2D6 Genetic Variation and Antipsychotic-Induced Weight Gain: A Systematic Review and Meta-Analysis. Front Psychol 2022; 12:768748. [PMID: 35185676 PMCID: PMC8850377 DOI: 10.3389/fpsyg.2021.768748] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 12/07/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Antipsychotic-induced weight gain is a contributing factor in the reduced life expectancy reported amongst people with psychotic disorders. CYP2D6 is a liver enzyme involved in the metabolism of many commonly used antipsychotic medications. We investigated if CYP2D6 genetic variation influenced weight or BMI among people taking antipsychotic treatment. METHODS We conducted a systematic review and a random effects meta-analysis of publications in Pubmed, Embase, PsychInfo, and CENTRAAL that had BMI and/or weight measurements of patients on long-term antipsychotics by their CYP2D6-defined metabolic groups (poor, intermediate, normal/extensive, and ultra-rapid metabolizers, UMs). RESULTS Twelve studies were included in the systematic review. All cohort studies suggested that the presence of reduced-function or non-functional alleles for CYP2D6 was associated with greater antipsychotic-induced weight gain, whereas most cross-sectional studies did not find any significant associations. Seventeen studies were included in the meta-analysis with clinical data of 2,041 patients, including 93 poor metabolizers (PMs), 633 intermediate metabolizers (IMs), 1,272 normal metabolizers (NMs), and 30 UMs. Overall, we did not find associations in any of the comparisons made. The estimated pooled standardized differences for the following comparisons were (i) PM versus NM; weight = -0.07 (95%CI: -0.49 to 0.35, p = 0.74), BMI = 0.40 (95%CI: -0.19 to 0.99, p = 0.19). (ii) IM versus NM; weight = 0.09 (95% CI: -0.04 to 0.22, p = 0.16) and BMI = 0.09 (95% CI: -0.24 to 0.41, p = 0.60). (iii) UM versus EM; weight = 0.01 (95% CI: -0.37 to 0.40, p = 0.94) and BMI = -0.08 (95%CI: -0.57 to 0.42, p = 0.77). CONCLUSION Our systematic review of cohort studies suggested that CYP2D6 poor metabolizers have higher BMI than normal metabolizers, but the data of cross-sectional studies and the meta-analysis did not show this association. Although our review and meta-analysis constitutes one of the largest studies with comprehensively genotyped samples, the literature is still limited by small numbers of participants with genetic variants resulting in poor or UMs status. We need further studies with larger numbers of extreme metabolizers to establish its clinical utility in antipsychotic treatment. CYP2D6 is a key gene for personalized prescribing in mental health.
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Affiliation(s)
| | | | - Maria J Arranz
- Fundació Docència I Recerca, Mútua Terrassa, Barcelona, Spain
- Barcelona Clinic Schizophrenia Unit, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain
| | - Rosa Catalan
- Barcelona Clinic Schizophrenia Unit, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain
- CIBERSAM, Centro de Investigación Biomédica en Red de Salud Mental, Madrid, Spain
| | - Gesche Jurgens
- Clinical Pharmacological Unit, Zealand University Hospital, Roskilde, Denmark
| | - Sanne Maartje Kloosterboer
- Department of Hospital Pharmacy and Child and Adolescent Psychiatry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Henrik Berg Rasmussen
- Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Roskilde, Denmark
- Department of Science and Environment, Roskilde University Center, Roskilde, Denmark
| | - Anjali Bhat
- Division of Psychiatry, University College London, London, United Kingdom
| | - Haritz Irizar
- Division of Psychiatry, University College London, London, United Kingdom
| | - Dora Koller
- Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States
- Veterans Affairs Connecticut Healthcare System, West Haven, CT, United States
| | - Renato Polimanti
- Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States
- Veterans Affairs Connecticut Healthcare System, West Haven, CT, United States
| | - Baihan Wang
- Division of Psychiatry, University College London, London, United Kingdom
| | - Eirini Zartaloudi
- Division of Psychiatry, University College London, London, United Kingdom
| | - Isabelle Austin-Zimmerman
- Division of Psychiatry, University College London, London, United Kingdom
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Elvira Bramon
- Division of Psychiatry, University College London, London, United Kingdom
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
- Institute of Cognitive Neuroscience, University College London, London, United Kingdom
- Camden and Islington NHS Foundation Trust, London, United Kingdom
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7
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Duan C, Jenkins ZM, Castle D. Therapeutic use of melatonin in schizophrenia: A systematic review. World J Psychiatry 2021; 11:463-476. [PMID: 34513608 PMCID: PMC8394692 DOI: 10.5498/wjp.v11.i8.463] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 07/12/2021] [Accepted: 07/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Sleep dysfunction is a common problem in people with schizophrenia, and side effects of treatment often exacerbate metabolic and cardiovascular risk and may induce extrapyramidal side effects. Melatonin (N-acetyl-5-methoxytryptamine) is an endogenously produced hormone which has demonstrated direct and indirect antioxidant and neuroprotective effects. Previous studies have explored the use of exogenous melatonin in improving sleep outcomes in the general population, yet indications for use in schizophrenia are unclear.
AIM To synthesize the evidence from clinical trials investigating prescribed melatonin as an adjunctive therapy in patients with schizophrenia.
METHODS A systematic literature review of MEDLINE (Ovid), Embase, PsychINFO, and PubMed on the 27/08/20; and CINAHL and Cochrane Library databases, was conducted. Inclusion criteria were: a peer-reviewed clinical trial published in English; included a group of patients with schizophrenia; used melatonin as an adjunctive therapy; and reported any outcome of any duration. Exclusion criteria were: neurodegenerative diseases, primary sleep disorders, co-morbid substance use or animal studies.
RESULTS Fifteen studies were included in the current review with the following primary outcomes: sleep (n = 6), metabolic profile (n = 3), tardive dyskinesia (n = 3), cognitive function (n = 2) and benzodiazepine discontinuation (n = 1).
CONCLUSION Adjunctive melatonin therapy has some positive outcomes for sleep, metabolic profile and tardive dyskinesia in patients with schizophrenia. No beneficial effect of melatonin was observed on outcomes of cognition or benzodiazepine discontinuation. Future studies utilizing larger samples and investigations specifically comparing the effect of melatonin as adjunctive therapy with different antipsychotics in patients with schizophrenia are required.
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Affiliation(s)
- Cathy Duan
- Department of Psychiatry, University of Melbourne, Parkville 3010, VIC, Australia
| | - Zoe M Jenkins
- Department of Psychiatry, University of Melbourne, Parkville 3010, VIC, Australia
- Mental Health Service, St. Vincent's Hospital, Melbourne 3065, VIC, Australia
| | - David Castle
- Department of Psychiatry, University of Melbourne, Parkville 3010, VIC, Australia
- Mental Health Service, St. Vincent's Hospital, Melbourne 3065, VIC, Australia
- Centre for Complex Interventions, Centre for Addictions and Mental Health, Toronto ON M6J 1H4, Canada
- Department of Psychiatry, University of Toronto, Toronto ON M5S, Canada
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8
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Liu JH, Chen N, Guo YH, Guan XN, Wang J, Wang D, Xiu MH. Metabolomics-based understanding of the olanzapine-induced weight gain in female first-episode drug-naïve patients with schizophrenia. J Psychiatr Res 2021; 140:409-415. [PMID: 34144444 DOI: 10.1016/j.jpsychires.2021.06.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 05/30/2021] [Accepted: 06/04/2021] [Indexed: 12/22/2022]
Abstract
Previous studies have demonstrated that patients with schizophrenia (SZ) have greater rate of metabolic disorder as compared with the control population, which likely be the consequence of use of atypical antipsychotics. Olanzapine is a widely used antipsychotic, which increases the weight of SZ patients. However, the underlying mechanism remains poorly understood. Here we report the metabolomics-based understanding of the weight gain induced by olanzapine. 57 first-episode drug-naïve patients (FEDN) were recruited, of whom 27 patients completed a 4-week clinical trial. We then profiled the metabolomes of their plasma with the LC-MS-based nontargeted metabolomics approach at the baseline and after olanzapine monotherapy for 4 weeks. We observed that the plasma of the olanzapine-treated patient had significantly higher lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE) and lower carnitine as compared with that of the baseline plasma samples. Moreover, regression analyses indicated that the change of LysoPC(14:0) level was an independent contributor to the olanzapine-induced weight gain. Our study suggests that the metabolomics-based approach may facilitate the identification of biomarkers associated with the metabolic disorder causing by antipsychotic in schizophrenia patients.
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Affiliation(s)
- Jia Hong Liu
- The Affiliated Kangning Hospital of Wenzhou Medical University, Wenzhou, China
| | - Nan Chen
- Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, China
| | - Yan Hong Guo
- Qingdao Mental Health Center, Qingdao University, Qingdao, China
| | - Xiao Ni Guan
- Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, China
| | - Jun Wang
- Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, China
| | - Dong Wang
- Department of Clinical Psychology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
| | - Mei Hong Xiu
- Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, China.
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9
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Association of CNR1 and INSIG2 polymorphisms with antipsychotics-induced weight gain: a prospective nested case-control study. Sci Rep 2021; 11:15304. [PMID: 34315947 PMCID: PMC8316361 DOI: 10.1038/s41598-021-94700-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 07/07/2021] [Indexed: 02/07/2023] Open
Abstract
Weight gain is a frequent and severe adverse reaction in patients taking antipsychotics. The objective was to further investigate in a natural setting influential risk factors associated with clinically significant weight gain. An observational follow-up study was conducted. Patients when initiating treatment with whatever antipsychotic were included; a structured questionnaire was applied at baseline, 3 and 6 months later; a blood sample was obtained. In a nested case-control approach, patients with an increase ≥ 7% of their initial weight were considered as cases, the remaining, as controls. The results showed that, out of 185 patients, 137 completed the 6-month follow-up (cases, 38; controls, 99). Weight gain gradually and significantly increased in cases (baseline, 65.0 kg; 6 months, 74.0 kg) but not in controls (65.6 kg and 65.8 kg, respectively). Age (adjusted OR = 0.97, 95% CI = 0.96-0.99, p = 0.004), olanzapine (adjusted OR = 2.98, 95% CI = 1.13-7.80, p = 0.027) and quetiapine (adjusted OR = 0.25, 95% = 0.07-0.92, p = 0.037) significantly associated with weight gain. An association was also found for the CNR1 (rs1049353) and INSIG2 (rs7566605) polymorphisms. In conclusion, an increased risk of antipsychotics-induced weight gain was observed for younger age and olanzapine, and a relative lower risk for quetiapine. A potential role of CNR1 rs1049353 and INSIG2 rs7566605 polymorphisms is suggested.
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10
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Prakash J, Chatterjee K, Srivastava K, Chauhan VS. First-episode psychosis: How long does it last? A review of evolution and trajectory. Ind Psychiatry J 2021; 30:198-206. [PMID: 35017801 PMCID: PMC8709526 DOI: 10.4103/ipj.ipj_38_21] [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: 02/23/2021] [Revised: 03/13/2021] [Accepted: 03/16/2021] [Indexed: 11/12/2022] Open
Abstract
Study of first-episode psychosis (FEP), an episode of psychotic nature which manifests for the first time in an individual in the longitudinal continuum of his/her illness, has been study matter of research interest in recent years. A comprehensive review of the literature will help us understand the evolution and trajectory of this concept better. A literature review of available articles addressing the concept, phenomenology, evolution, identification, course, and outcome of FEP was done; the same was subsequently divided into broad topics for better clarity and analyzed. FEP constituted a clinical psychotic phenomenon with underlying significant heterogeneity in diagnosis, stability, course, and outcome. The study has attempted to view FEP both as horizontal spectrum across various diagnoses and longitudinally ranging from asymptomatic individual with unknown risk status to attenuated psychosis to multiple relapses/unremitting illness. Many risk and protective factors have been brought out with varying certainty ranging bio-psycho-social spectrum. Efforts have been made to calculate polygenic risk score based on genes involvement/sharing between various psychotic spectrum disorders; as well as biomarker panels to identify people at risk. FEP may prove to be an important concept to understand psychosis in general; without putting things into the diagnostic rubric. It may help understand multiple risk and protective factors for the course and outcome of psychotic illness and may clear the cloud to sharpen the evidence toward commonality and distinctiveness between various psychotic diagnoses in vogue for more comprehensive concept.
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Affiliation(s)
- Jyoti Prakash
- Department of Psychiatry, Armed Forces Medical College, Pune, Maharashtra, India
| | - K. Chatterjee
- Department of Psychiatry, Armed Forces Medical College, Pune, Maharashtra, India
| | - K. Srivastava
- Department of Psychiatry, Armed Forces Medical College, Pune, Maharashtra, India
| | - V. S. Chauhan
- Department of Psychiatry, Armed Forces Medical College, Pune, Maharashtra, India
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11
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Li XR, Xiu MH, Guan XN, Wang YC, Wang J, Leung E, Zhang XY. Altered Antioxidant Defenses in Drug-Naive First Episode Patients with Schizophrenia Are Associated with Poor Treatment Response to Risperidone: 12-Week Results from a Prospective Longitudinal Study. Neurotherapeutics 2021; 18:1316-1324. [PMID: 33791970 PMCID: PMC8423973 DOI: 10.1007/s13311-021-01036-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/09/2021] [Indexed: 12/12/2022] Open
Abstract
Abnormal redox regulation is thought to contribute to schizophrenia (SCZ). Accumulating studies have shown that the plasma antioxidant enzyme activity is closely associated with the course and outcome in antipsychotics-naïve first-episode (ANFE) patients with SCZ. The main purpose of this study was to investigate the effect of risperidone on oxidative stress markers in ANFE patients and the relationship between risperidone response and changes in oxidative stress markers. Plasma activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) enzyme, total antioxidant status (TAS), and malondialdehyde (MDA) levels were measured in 354 ANFE patients and 152 healthy controls. The clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). Patients received risperidone monotherapy for 12 weeks and oxidative stress markers and PANSS were measured at baseline and at follow-up. Compared with healthy controls, the patients exhibited higher activities of SOD, CAT, and TAS levels, but lower MDA levels and GPx activity. A comparison between 168 responders and 50 non-responders at baseline and 12-week follow-up showed that GPx activity decreased in both groups after treatment. Moreover, GPx activity decreased less in responders and was higher in responders than in non-responders at follow-up. These results demonstrate that the redox regulatory system and antioxidant defense enzymes may have predictive value for the response of ANFE patients to risperidone treatment.
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Affiliation(s)
- Xi Rong Li
- Department of Sleep Medicine, Shandong Mental Health Center, Jinan, China
| | - Mei Hong Xiu
- Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Changping District, Beijing, 100096, China.
| | - Xiao Ni Guan
- Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Changping District, Beijing, 100096, China
| | - Yue Chan Wang
- Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Changping District, Beijing, 100096, China
| | - Jun Wang
- Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Changping District, Beijing, 100096, China
| | - Edison Leung
- Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center At Houston, Houston, TX, USA
| | - Xiang Yang Zhang
- CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, 16 Lincui Road, Chaoyang District, Beijing, 100101, China.
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12
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Delacrétaz A, Glatard A, Dubath C, Gholam M, Gamma F, von Gunten A, Conus P, Eap CB. Valproate is associated with early decrease of high-density lipoprotein cholesterol levels in the psychiatric population. Basic Clin Pharmacol Toxicol 2021; 129:26-35. [PMID: 33733594 DOI: 10.1111/bcpt.13580] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 02/08/2021] [Accepted: 03/09/2021] [Indexed: 01/10/2023]
Abstract
Few studies have evaluated the influence of valproate on the deterioration of the lipid profile in psychiatric patients. This observational study aimed to compare the evolution of metabolic parameters in a sample of adult patients starting valproate (n = 39) with a control group (n = 39) of patients starting aripiprazole, a drug associated with a low risk of metabolic deterioration. Data were obtained from a prospective study including psychiatric patients with metabolic parameters monitored during the first year of treatment. During the first month of treatment with valproate (median: 31 days [IQR: 25-36]), mean body mass index increased significantly (from 24.8 kg/m2 at baseline to 25.2 kg/m2 after one month; P = .03) and mean HDL-C levels decreased significantly (from 1.39 mmol/L to 1.27 mmol/L; P = .02). In comparison, these metabolic variables remained stable during the first month of treatment with aripiprazole. The proportion of patients with early (ie during the first month of treatment) HDL-C decrease of ≥ 5% was significantly higher under valproate (54%) than aripiprazole (15%) treatment (P < .001). These findings remind the importance of a prospective metabolic monitoring in patients who initiate valproate treatment. Further research should be conducted on larger samples and should focus on finding effective interventions to prevent such metabolic adverse effects.
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Affiliation(s)
- Aurélie Delacrétaz
- Department of Psychiatry, Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Lausanne University Hospital, University of Lausanne, Prilly, Switzerland.,Les Toises Psychiatry and Psychotherapy Center, Lausanne, Switzerland
| | - Anaïs Glatard
- Department of Psychiatry, Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Lausanne University Hospital, University of Lausanne, Prilly, Switzerland
| | - Céline Dubath
- Department of Psychiatry, Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Lausanne University Hospital, University of Lausanne, Prilly, Switzerland
| | - Mehdi Gholam
- Department of Psychiatry, Centre of Psychiatric Epidemiology and Psychopathology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Franziska Gamma
- Les Toises Psychiatry and Psychotherapy Center, Lausanne, Switzerland
| | - Armin von Gunten
- Department of Psychiatry, Service of Old Age Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Philippe Conus
- Department of Psychiatry, Service of General Psychiatry, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Chin B Eap
- Department of Psychiatry, Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Lausanne University Hospital, University of Lausanne, Prilly, Switzerland.,Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.,School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.,Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland
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13
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Prevalence of obesity and clinical and metabolic correlates in first-episode schizophrenia relative to healthy controls. Psychopharmacology (Berl) 2021; 238:745-753. [PMID: 33241480 DOI: 10.1007/s00213-020-05727-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 11/18/2020] [Indexed: 10/22/2022]
Abstract
OBJECTIVE People with schizophrenia exhibit a high obesity rate. However, little is known about the prevalence of obesity and its relationship with clinical symptoms and metabolic indicators in first-episode drug-naïve (FEDN) schizophrenia. METHODS Demographic and lipid parameters were gathered from 297 FEDN schizophrenia and 325 healthy controls. The patients' symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS). RESULTS The obesity rate of FEDN patients was 10.77%, similar to that of controls (10.5%). The prevalence of overweight plus obesity of patients was 44.8%, significantly higher than that of controls (36.6%). Compared with non-obese patients, obese patients had higher levels of cholesterol (4.81 ± 0.93 vs 4.22 ± 1.00 mmol/L), triglyceride (0.27 ± 0.21 vs 0.14 ± 0.24 mg/dL), low-density lipoprotein (0.48 ± 0.12 vs 0.40 ± 0.12 mg/dL), greater ratio of triglyceride/high-density lipoprotein (2.01 ± 1.23 vs 1.44 ± 1.26), and higher PANSS positive symptom subscale score (29.81 ± 6.29 vs 27.05 ± 6.15), general psychopathology subscale score (70.75 ± 11.74 vs 66.87 ± 11.37), and total score (149.81 ± 21.08 vs 140.64 ± 21.58), but lower high-density lipoprotein level (1.09 ± 0.21 vs 1.27 ± 0.34 mg/dL) (all p < 0.05). Correlation analysis revealed that body mass index (BMI) was positively correlated with triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, triglyceride/high-density lipoprotein ratio, PANSS positive symptoms, general psychopathology, and total scores (all p < 0.05, r = 0.124 ~ 0.335). Multiple regression analysis confirmed that PANSS positive symptoms, total score, and cholesterol level were significantly associated with BMI (all p < 0.05, β: 0.126-0.162). CONCLUSION There was no significant difference in the prevalence of obesity between FEDN patients and the control group. Moreover, BMI was positively associated with positive symptom severity in FEDN patients.
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14
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Bak M, Drukker M, Cortenraad S, Vandenberk E, Guloksuz S. Antipsychotics result in more weight gain in antipsychotic naive patients than in patients after antipsychotic switch and weight gain is irrespective of psychiatric diagnosis: A meta-analysis. PLoS One 2021; 16:e0244944. [PMID: 33596211 PMCID: PMC7888647 DOI: 10.1371/journal.pone.0244944] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 12/20/2020] [Indexed: 01/10/2023] Open
Abstract
Introduction Antipsychotics are associated with bodyweight gain and metabolic disturbance. Previous meta-analyses were limited to mainly antipsychotic switch studies in patients with a diagnosis of schizophrenia or psychosis with short follow-up periods. The present meta-analysis aimed to analyse the impact of weight change in antipsychotic-naive and antipsychotics switch patients and whether body weight change depended on diagnosis. Method We performed a meta-analysis of clinical trials of antipsychotics that reported weight change, irrespective of psychiatric diagnosis. Outcome measure was body weight change. Studies were classified into antipsychotic-naive and antipsychotic-switch. Forest plots stratified by antipsychotic and the duration of antipsychotic use were generated and results were summarised in figures. Results In total, 404 articles were included for the quantitative synthesis. 58 articles were on antipsychotic naive patients. In the antipsychotic naive group, all antipsychotics resulted in body weight gain. In the antipsychotic switch group, most antipsychotics likewise resulted in bodyweight gain, with exception of amisulpride, aripiprazole and ziprasidone that showed no body weight gain or even some weight loss after switching antipsychotics. Diagnosis was not a discriminating factor of antipsychotic induced weight change. Conclusion Antipsychotic use resulted in substantial increase in body weight in antipsychotic-naive patients. In antipsychotic-switch patients the weight gain was mild and not present in amisulpride, aripiprazole and ziprasidone. In both groups, weight gain was irrespective of the psychiatric diagnosis.
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Affiliation(s)
- Maarten Bak
- Department of Psychiatry & Neuropsychology, Maastricht University, Maastricht, The Netherlands
- * E-mail:
| | - Marjan Drukker
- Department of Psychiatry & Neuropsychology, Maastricht University, Maastricht, The Netherlands
| | - Shauna Cortenraad
- Department of Psychiatry & Neuropsychology, Maastricht University, Maastricht, The Netherlands
| | - Emma Vandenberk
- Department of Psychiatry & Neuropsychology, Maastricht University, Maastricht, The Netherlands
| | - Sinan Guloksuz
- Department of Psychiatry & Neuropsychology, Maastricht University, Maastricht, The Netherlands
- Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, United States of America
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15
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Cognitive ability and metabolic physical health in first-episode psychosis. SCHIZOPHRENIA RESEARCH-COGNITION 2021; 24:100194. [PMID: 33659191 PMCID: PMC7895837 DOI: 10.1016/j.scog.2021.100194] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 01/14/2021] [Accepted: 01/27/2021] [Indexed: 11/23/2022]
Abstract
Cognitive impairments are a core feature of first-episode psychosis (FEP), arising before illness onset and antipsychotic exposure. Individuals with chronic psychosis experience poorer physical health while taking antipsychotic medication, but health disparities may be evident at FEP onset, prior to antipsychotic exposure. Given the links between cognition and physical health in healthy populations, the aim was to explore whether cognition and physical health are associated in FEP, which could inform early physical health interventions for cognition in FEP. Participants were aged 15 to 25 and included 86 individuals experiencing FEP with limited antipsychotic exposure and duration of untreated psychosis of ≤six months, and 43 age- and sex-matched controls. Individuals with FEP performed significantly poorer than controls in most cognitive domains (Cohen's d = 0.38 to 1.59). Groups were similar in metabolic health measures, excluding a significantly faster heart rate in FEP (d = 0.68). Through hierarchical regression analyses, we found that in the overall sample, BMI was negatively related to current IQ after controlling for education and group (FEP/control). Relationships between BMI and cognition were consistent across the FEP and healthy control groups. In FEP, current IQ and working memory were negatively correlated with lipid profiles. Findings suggest that in FEP, impaired cognition is exhibited earlier than physical health problems, and that compared to controls, similar relationships with cognition are demonstrated. Causal pathways and trajectories of relationships between health and cognition in FEP require investigation, especially as antipsychotic medications are introduced. The findings have implications for cognitive and health interventions.
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16
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Canal-Rivero M, Ruiz-Veguilla M, Labad J, Ayesa-Arriola R, Vázquez-Bourgon J, Mayoral-van Son J, Setién-Suero E, Ortiz-García de la Foz V, Crespo-Facorro B. Predictors of weight acquisition induced by antipsychotic treatment and its relationship with age in a sample of first episode non-affective psychosis patients: A three-year follow-up study. Schizophr Res 2020; 222:462-464. [PMID: 32600780 DOI: 10.1016/j.schres.2020.06.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 06/12/2020] [Accepted: 06/12/2020] [Indexed: 12/16/2022]
Affiliation(s)
- M Canal-Rivero
- Department of Psychiatry, Hospital Universitari Germans Trías I Pujol, Badalona, Spain.
| | - M Ruiz-Veguilla
- Hospital Universitario Virgen del Rocío, Sevilla, Spain; Departament of Psychiatry, Universidad de Sevilla, Instituto de Biomedicina de Sevilla (IBIS), Spain; CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Spain.
| | - J Labad
- CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Spain; Department of Psychiatry, Corporació Sanitària Universitaria Parc Taulí, I3PT, UAB, Sabadell, Spain
| | - R Ayesa-Arriola
- CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Spain; Department of Psychiatry, Marqués de Valdecilla University Hospital, IDIVAL, School of Medicine, University of Cantabria, Santander, Spain
| | - J Vázquez-Bourgon
- CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Spain; Department of Psychiatry, Marqués de Valdecilla University Hospital, IDIVAL, School of Medicine, University of Cantabria, Santander, Spain
| | - J Mayoral-van Son
- Hospital Universitario Virgen del Rocío, Sevilla, Spain; CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Spain
| | - E Setién-Suero
- CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Spain; Department of Psychiatry, Marqués de Valdecilla University Hospital, IDIVAL, School of Medicine, University of Cantabria, Santander, Spain
| | - V Ortiz-García de la Foz
- CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Spain; Department of Psychiatry, Marqués de Valdecilla University Hospital, IDIVAL, School of Medicine, University of Cantabria, Santander, Spain
| | - B Crespo-Facorro
- Hospital Universitario Virgen del Rocío, Sevilla, Spain; Departament of Psychiatry, Universidad de Sevilla, Instituto de Biomedicina de Sevilla (IBIS), Spain; CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Spain; Department of Psychiatry, Marqués de Valdecilla University Hospital, IDIVAL, School of Medicine, University of Cantabria, Santander, Spain
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17
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Barton BB, Zagler A, Engl K, Rihs L, Musil R. Prevalence of obesity, metabolic syndrome, diabetes and risk of cardiovascular disease in a psychiatric inpatient sample: results of the Metabolism in Psychiatry (MiP) Study. Eur Arch Psychiatry Clin Neurosci 2020; 270:597-609. [PMID: 31302731 DOI: 10.1007/s00406-019-01043-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 07/03/2019] [Indexed: 01/20/2023]
Abstract
The information on prevalence of obesity, diabetes, metabolic syndrome (MetS) and cardiovascular risk (CVR) and on sociodemographic variables available in patients with psychiatric diseases about to be treated with weight gain-associated medication (e.g., clozapine, mirtazapine, quetiapine) is limited. In a naturalistic study, psychiatric inpatients (age: 18-75) of all F diagnoses according to ICD-10, who were about to be treated with weight gain-associated medication, were included. Demographic variables were assessed as well as biological parameters to calculate the Body Mass Index (BMI), MetS, diabetes and CVR. A total of 163 inpatients were included (60.1% male; mean age: 39.8 (± 15.1, 18-75 years). The three most common disorders were depression (46.0%), bipolar disorder (20.9%) and drug addiction (20.2%). The three most common pharmacotherapeutic agents prescribed were quetiapine (29.4%), mirtazapine (20.9%) and risperidone (12.9%). Of the included inpatients 30.1% were overweight, 17.2% obese, and 26.9% and 22.4% fulfilled the criteria for a MetS according to the International Diabetes Federation (IDF) and the National Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (NCEP ATP III), respectively, 3.8% had (pre)diabetes and 8.3% had a moderate and 1.9% a high CVR according to the Prospective Cardiovascular Münster (PROCAM) score. Detailed information is reported on all assessed parameters as well as on subgroup analyses concerning sociodemographic variables. The results suggest that psychiatric patients suffer from multiple metabolic disturbances in comparison to the general population. Monitoring weight, waist circumference, blood pressure and cholesterol regularly is, therefore, highly relevant.
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Affiliation(s)
- Barbara B Barton
- Department of Psychiatry and Psychotherapy, University Hospital , LMU Munich, Germany, Nußbaumstraße 7, 80336, Munich, Germany.
| | - Anja Zagler
- Department of Psychiatry and Psychotherapy, University Hospital , LMU Munich, Germany, Nußbaumstraße 7, 80336, Munich, Germany
| | - Katharina Engl
- Department of Psychiatry and Psychotherapy, University Hospital , LMU Munich, Germany, Nußbaumstraße 7, 80336, Munich, Germany
| | - Leonie Rihs
- Department of Psychiatry and Psychotherapy, University Hospital , LMU Munich, Germany, Nußbaumstraße 7, 80336, Munich, Germany
| | - Richard Musil
- Department of Psychiatry and Psychotherapy, University Hospital , LMU Munich, Germany, Nußbaumstraße 7, 80336, Munich, Germany
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18
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Tandon R, Lenderking WR, Weiss C, Shalhoub H, Barbosa CD, Chen J, Greene M, Meehan SR, Duvold LB, Arango C, Agid O, Castle D. The impact on functioning of second-generation antipsychotic medication side effects for patients with schizophrenia: a worldwide, cross-sectional, web-based survey. Ann Gen Psychiatry 2020; 19:42. [PMID: 32684942 PMCID: PMC7359579 DOI: 10.1186/s12991-020-00292-5] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 06/29/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND It is well established that the different antipsychotics used for schizophrenia symptoms differ substantially in their side effects. However, relatively little is known about the impact of these side effects on functioning from the patient's perspective. We aimed to understand how key side effects of second-generation antipsychotics impact the functioning and quality of life (QoL) of patients with schizophrenia. METHODS This is a cross-sectional, web-based survey of patient-reported side effect burden of antipsychotic drugs in adults with schizophrenia. The survey was deployed in the United States, Canada, Australia, Spain, Italy, Norway, and Denmark. It included sociodemographic and clinical questions, the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF), and the Glasgow Antipsychotic Side-Effect Scale (GASS). Eight pre-defined key side effects classified as activating ("Shaky hands or arms," "Restlessness," and "Difficulty sleeping"), sedating ("Sleepy during the day", "Feeling drugged or like a zombie," and "Feeling dizzy/Fainted") or other side effects ("Problems enjoying sex" and "Gaining weight"), and additional questions related to impacts on function and quality of life were asked. RESULTS In total, 435 participants (mean age: 38 years, 53.8% female) were included. The total Q-LES-Q-SF score indicated overall medium satisfaction with their quality of life (score of 44.3; possible range 14-70). The most prevalent side effects were "Sleepy during the day" (83.2%), "Difficulty sleeping" (74.7%), "Dry mouth" (63.9%), "Problems enjoying sex" (53.4%) and "Gaining weight" (52.4%). Women reported the side effects of "Sleepy during the day", "Problems enjoying sex" and "Gaining weight" more frequently than men. Key side effects impacted physical, social, occupational and psychological aspects of functioning. Patients with key side effects often felt frustrated by their experiences. Total Q-LES-Q-SF score showed a significant inverse correlation with the score of pre-defined groups of side effects indicating worse QoL in association with more severe key side effects in these patients. CONCLUSION Stable patients with schizophrenia taking second-generation antipsychotics live with many side effects, including activating and sedating side effects, sexual side effects, and weight gain. Presence of these side effects is associated with substantial impacts across all aspects of daily functioning and lower quality of life and satisfaction.
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Affiliation(s)
- Rajiv Tandon
- Western Michigan University Homer Stryker M.D. School of Medicine, 300 Portage Street, Kalamazoo, MI 49007 USA
| | | | - Catherine Weiss
- Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center Drive, Princeton, NJ 08540 USA
| | - Huda Shalhoub
- Evidera, 7101 Wisconsin Avenue, Suite 1400, Bethesda, MD 20814 USA
| | | | - Jun Chen
- Evidera, 7101 Wisconsin Avenue, Suite 1400, Bethesda, MD 20814 USA
| | - Mallik Greene
- Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center Drive, Princeton, NJ 08540 USA
| | | | | | - Celso Arango
- Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM,CIBERSAM, School of Medicine, Universidad Complutense, Calle del Dr. Esquerdo, 46, 28007 Madrid, Spain
| | - Ofer Agid
- Schizophrenia Division, Complex Care & Recovery Program, Centre for Addiction and Mental Health, Toronto, Canada
- Department of Psychiatry and Institute of Medical Science, University of Toronto, 1001 Queen Street West, Toronto, ON M6J 1H4 Canada
| | - David Castle
- St Vincent’s Health and The University of Melbourne, 41 Victoria Parade, Fitzroy, VIC 3065 Australia
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19
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Luckhoff HK, du Plessis S, Kilian S, Asmal L, Scheffler F, Phahladira L, Olivier RM, Emsley R. Hippocampal subfield volumes and change in body mass over 12 months of treatment in first-episode schizophrenia spectrum disorders. Psychiatry Res Neuroimaging 2020; 300:111084. [PMID: 32388386 DOI: 10.1016/j.pscychresns.2020.111084] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 04/01/2020] [Accepted: 04/03/2020] [Indexed: 02/07/2023]
Abstract
In this study, we explored the relationship between baseline hippocampal subfield volumes and change in body mass over 12 months of treatment in 90 first-episode schizophrenia spectrum disorder patients (66 males, 24 females; mean age= 24.7 ± 6.8 years). Body mass index was assessed in patients at baseline, and at months 3, 6, 9 and 12. Hippocampal subfields of interest were assessed at baseline using a segmentation algorithm included in the FreeSurfer 6.0 software program. Linear regression revealed a significant interactive effect between sex and anterior hippocampus size as predictors of change in body mass over 12 months, adjusting for age, substance use, and treatment duration. In an exploratory post-hoc sub-analysis, partial correlations showed a significant association between weight gain and smaller CA1, CA3 and subiculum volumes in females, but not males, adjusting for age and substance use, with similar trends evident for the CA4 and presubiculum subfields. In conclusion, our findings suggest that smaller anterior hippocampal subfields at baseline are associated with the development of weight gain over the course of treatment in first-episode schizophrenia spectrum disorders in a sex-specific fashion. This may be related to the greater increase in body mass evident for female patients in our study.
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Affiliation(s)
- H K Luckhoff
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7500, South Africa.
| | - S du Plessis
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7500, South Africa
| | - S Kilian
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7500, South Africa
| | - L Asmal
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7500, South Africa
| | - F Scheffler
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7500, South Africa
| | - L Phahladira
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7500, South Africa
| | - R M Olivier
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7500, South Africa
| | - R Emsley
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 7500, South Africa
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Chiliza B, Asmal L, Oosthuizen P, van Niekerk E, Erasmus R, Kidd M, Malhotra A, Emsley R. Changes in Body Mass and Metabolic Profiles in Patients with First-Episode Schizophrenia Treated for 12 Months with A First-Generation Antipsychotic. Eur Psychiatry 2020; 30:277-83. [DOI: 10.1016/j.eurpsy.2014.11.013] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2014] [Revised: 11/26/2014] [Accepted: 11/27/2014] [Indexed: 12/11/2022] Open
Abstract
AbstractObjectives:To assess changes in body mass and metabolic profiles in patients with first-episode schizophrenia receiving standardised, assured treatment and to identify predictors and moderators of the effects.Methods:We investigated the changes in body mass, fasting blood glucose and lipids in 107 largely antipsychotic naïve, first-episode schizophrenia patients who were treated according to a standard algorithm with long-acting injectable flupenthixol decanoate over 12 months.Results:Eighty-three (78%) participants completed the 12 months of treatment, and 104 (97%) received 100% of the prescribed injections during their participation. There were significant increases in BMI (P < .0001), waist circumference (P = 0.0006) and triglycerides (P = 0.03) and decrease in HDL (P = 0.005), while systolic (P = 0.7) and diastolic blood pressure (P = 0.8), LDL (P = 0.1), cholesterol (P = 0.3), and glucose (P = 0.9) values did not change over time. The triglyceride: HDL ratio increased by 91%. Change in BMI was only correlated with change in triglycerides (P = .008). The only significant predictor of BMI increase was non-substance abuse (P = .002).Conclusions:The risks of weight gain and metabolic syndrome associated with antipsychotic treatment in first-episode schizophrenia are not restricted to second generation antipsychotics. This is a global problem, and developing communities may be particularly susceptible.
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Shah P, Iwata Y, Caravaggio F, Plitman E, Brown EE, Kim J, Chan N, Hahn M, Remington G, Gerretsen P, Graff-Guerrero A. Alterations in body mass index and waist-to-hip ratio in never and minimally treated patients with psychosis: A systematic review and meta-analysis. Schizophr Res 2019; 208:420-429. [PMID: 30685395 DOI: 10.1016/j.schres.2019.01.005] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 12/30/2018] [Accepted: 01/05/2019] [Indexed: 01/15/2023]
Abstract
BACKGROUND Obesity is up to 4 times higher in patients with schizophrenia than in the general population. However, the link between obesity and schizophrenia in the absence of antipsychotic use is unclear. Therefore, we aimed to examine differences in obesity measures (body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR)) in antipsychotic-naive and minimally treated (up to 2 weeks of lifetime antipsychotic exposure) patients with psychosis compared to healthy controls (HCs). METHODS A systematic search was conducted using Ovid Medline®, PsycINFO, and Embase. Standardized mean differences (SMDs) in obesity measures between groups were calculated. Separate sensitivity analyses were performed to examine the effects of age, sex, and ethnicity; antipsychotic exposure; and schizophrenia-related psychosis on SMDs. RESULTS A total of 23 studies were included in the meta-analysis (BMI = 23, WC = 9, WHR = 5). BMI was lower (SMD = -0.19, 95% CI = -0.34 to -0.05, P = 0.009) and WHR was elevated (SMD = 0.34, 95% CI = 0.14 to 0.55, P = 0.001) in patients. These differences remained after analyses were restricted to patients matched with HCs for age, sex, and ethnicity; to antipsychotic-naive patients; and to patients with schizophrenia-related diagnoses. CONCLUSIONS Differences in BMI and WHR were observed in never and minimally treated patients with psychosis compared to HCs. Future research is warranted to understand these alterations in the context of body fat biomarkers and neuropathology of psychiatric disorders, independent of the effects of antipsychotics.
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Affiliation(s)
- Parita Shah
- Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
| | - Yusuke Iwata
- Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
| | - Fernando Caravaggio
- Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
| | - Eric Plitman
- Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
| | - Eric E Brown
- Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Geriatric Mental Health Division, CAMH, University of Toronto, Toronto, Ontario, Canada
| | - Julia Kim
- Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
| | - Nathan Chan
- Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
| | - Margaret Hahn
- Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, CAMH, University of Toronto, Toronto, Ontario, Canada
| | - Gary Remington
- Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Geriatric Mental Health Division, CAMH, University of Toronto, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, CAMH, University of Toronto, Toronto, Ontario, Canada
| | - Philip Gerretsen
- Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Geriatric Mental Health Division, CAMH, University of Toronto, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, CAMH, University of Toronto, Toronto, Ontario, Canada
| | - Ariel Graff-Guerrero
- Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Geriatric Mental Health Division, CAMH, University of Toronto, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, CAMH, University of Toronto, Toronto, Ontario, Canada.
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Shpigelman CN, HaGani N. The impact of disability type and visibility on self-concept and body image: Implications for mental health nursing. J Psychiatr Ment Health Nurs 2019; 26:77-86. [PMID: 30793457 DOI: 10.1111/jpm.12513] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 01/30/2019] [Accepted: 02/18/2019] [Indexed: 11/30/2022]
Abstract
WHAT IS KNOWN ON THE SUBJECT?: Physical appearance, as in the case of individuals with physical disabilities who use a cane, walker or wheelchair, also influence others' reactions and as a result, may lead to one's negative or positive feelings and thoughts. A disability that is not observable by others, as in the case of individuals with psychiatric disabilities (mental illnesses), may also have a negative impact on one's feelings and thoughts, due to stigma associated with psychiatric disabilities. To date, research has mainly focused on the way persons with a noticeable type of disability think about themselves. It is also important to evaluate the impact of disability type on ones' feelings and thoughts, and compare persons with visible and invisible disabilities. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: We asked 119 adults (over the age of 18 years) with different types of disabilities to complete a set of questionnaires and found that those who had a disability that was not observable by others (a psychiatric disability) felt more negative about themselves and their body than those who had a disability that was observable by others (a physical disability). The study extends the current knowledge on the impact of disability type and its visibility on the way persons with disabilities think about themselves. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The findings suggest that healthcare services should be modified to address the psychological needs of people with different types of disability. Mental health nurses should identify practices in the community that will improve the feelings and thoughts of consumers with disabilities, and especially those who cope with a psychiatric disability. Abstract Introduction Individuals with disabilities often face stigma and discrimination, which may negatively affect their self-concept. To date, research has mainly focused on the psychological implications of living with a noticeable physical disability. Less attention has been given to individuals with invisible psychiatric disabilities as a stigmatized subgroup in the disability community. Aim To evaluate the impact of disability type and its visibility on the self-concept and body image. Method A cross-sectional quantitative study design was implemented to compare the self-concept and body image of individuals with visible physical disabilities and individuals with invisible psychiatric disabilities (n = 119). Pearson correlations, ANOVA and multiple linear regression models were performed. Results Individuals with invisible psychiatric disabilities reported lower levels of self-concept and body image compared to individuals with visible physical disabilities. Gender, family status and the severity level of the disability were found to be associated with self-concept and body image. Discussion The study extends the current knowledge by showing that disability visibility might play a protective role for persons with physical disabilities compared to persons with psychiatric disabilities. Implications for Practice Mental health nurses should apply practices to enhance the self-concept and body image of consumers with invisible psychiatric disabilities.
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Affiliation(s)
- Carmit-Noa Shpigelman
- Department of Community Mental Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel
| | - Neta HaGani
- School of Social Work, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel
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Newcomer JW, Eriksson H, Zhang P, Weiller E, Weiss C. Changes in metabolic parameters and body weight in brexpiprazole-treated patients with acute schizophrenia: pooled analyses of phase 3 clinical studies. Curr Med Res Opin 2018; 34:2197-2205. [PMID: 29985680 DOI: 10.1080/03007995.2018.1498779] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
OBJECTIVE To analyze the effect of brexpiprazole on metabolic parameters and body weight in adults with schizophrenia, including clinically relevant sub-groups of patients, based on data from two pivotal phase 3 studies (NCT01393613; NCT01396421) and a long-term extension study (NCT01397786). METHODS The short-term studies were randomized, double-blind, placebo-controlled, fixed-dose (2 and 4 mg/day), 6-week phase 3 studies. The long-term study was an open-label 52-week study, recruiting de novo patients and those completing either short-term study. Maximum exposure to brexpiprazole was 58 weeks. Fasting metabolic parameters and weight were measured throughout the studies. Metabolic values were characterized as normal, borderline, or high (cholesterol, triglycerides, and glucose) and low or normal (HDL), using commonly reported thresholds. The incidences of all possible shifts in metabolic parameters were measured from baseline to any time post-baseline during the first 6 weeks, first 6 months, and last 6 months of treatment. RESULTS In short-term studies, the proportion of brexpiprazole-treated patients with unfavorable shifts in metabolic parameters was low and like that of placebo-treated patients; the incidence of these shifts was not dose-dependent. During both short- and long-term treatment, the incidence of unfavorable shifts with brexpiprazole was lower than that of favorable shifts. During short-term studies, the mean increase in body weight was 1.2 kg with brexpiprazole treatment and 0.2 kg with placebo. The mean increase in body weight during long-term treatment was 3.2 kg at week 58. CONCLUSIONS Brexpiprazole treatment was associated with moderate weight gain and small changes in metabolic parameters during both short- and long-term treatment.
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Affiliation(s)
- John W Newcomer
- a Charles E. Schmidt College of Medicine , Florida Atlantic University , Boca Raton , FL , USA
| | | | - Peter Zhang
- c Otsuka Pharmaceutical Development & Commercialization Inc. , Princeton , NJ , USA
| | | | - Catherine Weiss
- c Otsuka Pharmaceutical Development & Commercialization Inc. , Princeton , NJ , USA
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24
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Suvisaari J, Mantere O, Keinänen J, Mäntylä T, Rikandi E, Lindgren M, Kieseppä T, Raij TT. Is It Possible to Predict the Future in First-Episode Psychosis? Front Psychiatry 2018; 9:580. [PMID: 30483163 PMCID: PMC6243124 DOI: 10.3389/fpsyt.2018.00580] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Accepted: 10/23/2018] [Indexed: 12/26/2022] Open
Abstract
The outcome of first-episode psychosis (FEP) is highly variable, ranging from early sustained recovery to antipsychotic treatment resistance from the onset of illness. For clinicians, a possibility to predict patient outcomes would be highly valuable for the selection of antipsychotic treatment and in tailoring psychosocial treatments and psychoeducation. This selective review summarizes current knowledge of prognostic markers in FEP. We sought potential outcome predictors from clinical and sociodemographic factors, cognition, brain imaging, genetics, and blood-based biomarkers, and we considered different outcomes, like remission, recovery, physical comorbidities, and suicide risk. Based on the review, it is currently possible to predict the future for FEP patients to some extent. Some clinical features-like the longer duration of untreated psychosis (DUP), poor premorbid adjustment, the insidious mode of onset, the greater severity of negative symptoms, comorbid substance use disorders (SUDs), a history of suicide attempts and suicidal ideation and having non-affective psychosis-are associated with a worse outcome. Of the social and demographic factors, male gender, social disadvantage, neighborhood deprivation, dysfunctional family environment, and ethnicity may be relevant. Treatment non-adherence is a substantial risk factor for relapse, but a small minority of patients with acute onset of FEP and early remission may benefit from antipsychotic discontinuation. Cognitive functioning is associated with functional outcomes. Brain imaging currently has limited utility as an outcome predictor, but this may change with methodological advancements. Polygenic risk scores (PRSs) might be useful as one component of a predictive tool, and pharmacogenetic testing is already available and valuable for patients who have problems in treatment response or with side effects. Most blood-based biomarkers need further validation. None of the currently available predictive markers has adequate sensitivity or specificity used alone. However, personalized treatment of FEP will need predictive tools. We discuss some methodologies, such as machine learning (ML), and tools that could lead to the improved prediction and clinical utility of different prognostic markers in FEP. Combination of different markers in ML models with a user friendly interface, or novel findings from e.g., molecular genetics or neuroimaging, may result in computer-assisted clinical applications in the near future.
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Affiliation(s)
- Jaana Suvisaari
- Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland
| | - Outi Mantere
- Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland.,Department of Psychiatry, McGill University, Montreal, QC, Canada.,Bipolar Disorders Clinic, Douglas Mental Health University Institute, Montreal, QC, Canada.,Department of Psychiatry, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Jaakko Keinänen
- Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland.,Department of Psychiatry, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Teemu Mäntylä
- Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland.,Department of Neuroscience and Biomedical Engineering, and Advanced Magnetic Imaging Center, Aalto NeuroImaging, Aalto University School of Science, Espoo, Finland.,Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland
| | - Eva Rikandi
- Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland.,Department of Neuroscience and Biomedical Engineering, and Advanced Magnetic Imaging Center, Aalto NeuroImaging, Aalto University School of Science, Espoo, Finland.,Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland
| | - Maija Lindgren
- Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland
| | - Tuula Kieseppä
- Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland.,Department of Psychiatry, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Tuukka T Raij
- Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland.,Department of Neuroscience and Biomedical Engineering, and Advanced Magnetic Imaging Center, Aalto NeuroImaging, Aalto University School of Science, Espoo, Finland
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Oh E, Song E, Shin J. Individual Factors Affecting Self-esteem, and Relationships Among Self-esteem, Body Mass Index, and Body Image in Patients With Schizophrenia. Arch Psychiatr Nurs 2017; 31:588-595. [PMID: 29179826 DOI: 10.1016/j.apnu.2017.08.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 06/16/2017] [Accepted: 08/18/2017] [Indexed: 10/19/2022]
Abstract
The purposes of this study were to identify correlations between body mass index, body image, and self-esteem in patients with schizophrenia and to analyse the specific factors affecting self-esteem. This study had a descriptive design, utilising a cross-sectional survey. Participants were patients with schizophrenia who were admitted to a mental health facility in South Korea. A total of 180 questionnaires were distributed, and an appropriate total sample size of 167 valid questionnaires was analysed. Self-esteem was significantly correlated with body image, the subscale of appearance orientation, and body areas satisfaction. However, body mass index exhibited no significant correlation with any variable. The variables found to have a significant explanatory power of 21.4% were appearance orientation and body areas satisfaction. The explanatory power of all factors was 33.6%. The self-esteem of patients with schizophrenia was influenced by body mass index and body image. The positive symptoms of schizophrenia can be controlled by medication, whereas negative symptoms can be improved through education and nursing care with medication. Thus, psychiatric nurses should develop education and care programs that contribute to the positive body image and self-esteem of patients with schizophrenia.
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Affiliation(s)
- EunJung Oh
- Department of Nursing, Jeonbuk Science College, Republic of Korea
| | - EunJu Song
- Department of Nursing, Wonkwang University, Republic of Korea.
| | - JungEun Shin
- Department of Nursing, Maeumsarang Hospital, Republic of Korea
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26
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Emsley R, Asmal L, du Plessis S, Chiliza B, Phahladira L, Kilian S. Brain volume changes over the first year of treatment in schizophrenia: relationships to antipsychotic treatment. Psychol Med 2017; 47:2187-2196. [PMID: 28347393 DOI: 10.1017/s0033291717000642] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Progressive brain volume reductions have been described in schizophrenia, and an association with antipsychotic exposure has been reported. METHODS We compared percentage changes in grey and white matter volume from baseline to month 12 in 23 previously antipsychotic-naïve patients with a first episode of schizophrenia or schizophreniform disorder who were treated with the lowest effective dose of flupenthixol decanoate depot formulation, with 53 matched healthy individuals. Total antipsychotic dose was precisely calculated and its relationship with brain volume changes investigated. Relationships between volumetric changes and treatment were further investigated in terms of treatment response (changes in psychopathology and functionality) and treatment-related adverse-events (extrapyramidal symptoms and weight gain). RESULTS Excessive cortical volume reductions were observed in patients [-4.6 (6.6)%] v. controls [-1.12 (4.0)%] (p = 0.009), with no significant group differences for changes in subcortical grey matter and white matter volumes. In a multiple regression model, the only significant predictor of cortical volume change was total antipsychotic dose received (p = 0.04). Cortical volume change was not significantly associated with the changes in psychopathology, functionality, extrapyramidal symptoms and body mass index or age, gender and duration of untreated psychosis. CONCLUSIONS Brain volume reductions associated with antipsychotic treatment are not restricted to poor outcome patients and occur even with the lowest effective dose of antipsychotic. The lack of an association with poor treatment response or treatment-related adverse effects counts against cortical volume reductions reflecting neurotoxicity, at least in the short term. On the other hand, the volume reductions were not linked to the therapeutic benefits of antipsychotics.
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Affiliation(s)
- R Emsley
- Department of Psychiatry, Faculty of Medicine and Health Sciences,Stellenbosch University,Cape Town,South Africa
| | - L Asmal
- Department of Psychiatry, Faculty of Medicine and Health Sciences,Stellenbosch University,Cape Town,South Africa
| | - S du Plessis
- Department of Psychiatry, Faculty of Medicine and Health Sciences,Stellenbosch University,Cape Town,South Africa
| | - B Chiliza
- Department of Psychiatry, Faculty of Medicine and Health Sciences,Stellenbosch University,Cape Town,South Africa
| | - L Phahladira
- Department of Psychiatry, Faculty of Medicine and Health Sciences,Stellenbosch University,Cape Town,South Africa
| | - S Kilian
- Department of Psychiatry, Faculty of Medicine and Health Sciences,Stellenbosch University,Cape Town,South Africa
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Strassnig M, Clarke J, Mann S, Remington G, Ganguli R. Body composition, pre-diabetes and cardiovascular disease risk in early schizophrenia. Early Interv Psychiatry 2017; 11:229-236. [PMID: 25752319 DOI: 10.1111/eip.12225] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Accepted: 12/19/2014] [Indexed: 12/13/2022]
Abstract
AIM This preliminary study examines the relationship between body composition, insulin resistance and NCEP-III-defined cardiovascular disease risk factors in persons early in the course of schizophrenia exposed to commonly prescribed atypical antipsychotic medications. METHODS Subjects underwent modified oral glucose tolerance tests (OGTTs) and DEXA (dual X-ray absorptiometry) scans corrected for relevant sociodemographic data, including activity levels. We used linear multiple regression models to evaluate relationships between body composition and metabolic variables. RESULTS Thirty-six individuals diagnosed with schizophrenia, receiving atypical antipsychotic monotherapy, and within 5 years of illness onset, participated. Average age was 25.1 ± 3.6 years (range, 19-34) and duration of illness was 2.5 years (30 ± 18 months). Mean body mass index (BMI) was 28.3 ± 4.9, with a mean total body fat mass of 28.6 ± 8.4%, suggesting an increase in fat relative to BMI. Ten participants (28%) had pre-diabetes (fasting glucose 100-126 mg dL-1 or 2-h OGTT 140-200 mg dL-1 ), but no participant had diabetes. Insulin resistance (HOMA-IR) was predicted by total body mass (BMI) more so than by body fat mass, with an incremental contribution derived from antipsychotics. Insulin secretion in response to glucose challenge was predicted by BMI, body fat mass and antipsychotic medication. CONCLUSIONS Fat mass relative to BMI was increased in early schizophrenia patients receiving atypical antipsychotics. Body composition accounted for most of the variance in risk for abnormalities in glucose metabolism. Incremental contributions were derived from atypical antipsychotics, in line with their known adipogenicity. If direct fat mass measures are unavailable, frequent BMI measures may be practical proxy markers for metabolic risk.
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Affiliation(s)
- Martin Strassnig
- Department of Psychiatry, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Jennifer Clarke
- Department of Epidemiology and Biostatistics, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Steve Mann
- Department of Psychiatry, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
| | - Gary Remington
- Department of Psychiatry, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
| | - Rohan Ganguli
- Department of Psychiatry, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
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Sušilová L, Češková E, Hampel D, Sušil A, Šimůnek J. Changes in BMI in hospitalized patients during treatment with antipsychotics, depending on gender and other factors. Int J Psychiatry Clin Pract 2017; 21:112-117. [PMID: 28498089 DOI: 10.1080/13651501.2017.1291818] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVE To investigate the differences in body mass index (BMI) changes between men and women during hospitalization. METHODS The retrospective study monitored demographic and clinical data of 462 schizophrenic patients hospitalized 737 times between 2006 and 2011. BMI analysis was performed on patients on antipsychotic medication hospitalized longer than four days. RESULTS Patients with an initial BMI < 25 gained more weight than patients with a BMI > 25 (3.94% vs. 0.23%, men 4.02% vs. 0.69%, women 3.79% vs. -0.52%, always p < 0.001). Greater BMI gains were reported during the first hospitalization than during subsequent ones (3.94% vs. 1.66%, men 3.97% vs. 1.98%, women 3.88% vs. 1.18%, always p < 0.001). The comparison between men and women showed a higher increase in BMI in men 2.36% vs. 1.54%, p = 0.022. Men also gained significantly more weight than women on polytherapy (+2.55% vs. +1.37%) and during subsequent hospitalizations (1.98% vs. 1.18%). For treatment with various atypical antipsychotics (AP), no significant differences were found in weight changes between men and women; during treatment using a combination of multi-receptor AP and metabolically neutral aripiprazole, a significant increase of BMI occurred in men, but not in women (p = 0.018). CONCLUSIONS Men appear to be more prone to weight gain than women.
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Affiliation(s)
- Lenka Sušilová
- a Department of Public Health, Faculty of Medicine , Masaryk University , Brno , Czech Republic
| | - Eva Češková
- b Central European Institute of Technology , Masaryk University (CEITEC MU) , Brno , Czech Republic.,c Department of Psychiatry , Faculty Hospital Brno , Brno , Czech Republic.,d Department of Clinical Studies, Medical Faculty , Ostrava University , Ostrava , Czech Republic.,e Department of Psychiatry , Faculty Hospital Ostrava , Ostrava , Czech Republic
| | - David Hampel
- f Department of Statistics and Operation Analysis , Mendel University in Brno , Brno , Czech Republic
| | - Aleš Sušil
- g Department of Informatics , Central Institute for Supervising and Testing in Agriculture , Brno , Czech Republic
| | - Jan Šimůnek
- a Department of Public Health, Faculty of Medicine , Masaryk University , Brno , Czech Republic
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Crespo-Facorro B, Pelayo-Teran JM, Mayoral-van Son J. Current Data on and Clinical Insights into the Treatment of First Episode Nonaffective Psychosis: A Comprehensive Review. Neurol Ther 2016; 5:105-130. [PMID: 27553839 PMCID: PMC5130917 DOI: 10.1007/s40120-016-0050-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Indexed: 12/15/2022] Open
Abstract
Implementing the most suitable treatment strategies and making appropriate clinical decisions about individuals with a first episode of psychosis (FEP) is a complex and crucial task, with relevant impact in illness outcome. Treatment approaches in the early stages should go beyond choosing the right antipsychotic drug and should also address tractable factors influencing the risk of relapse. Effectiveness and likely metabolic and endocrine disturbances differ among second-generation antipsychotics (SGAs) and should guide the choice of the first-line treatment. Clinicians should be aware of the high risk of cardiovascular morbidity and mortality in schizophrenia patients, and therefore monitoring weight and metabolic changes across time is mandatory. Behavioral and counseling interventions might be partly effective in reducing weight gain and metabolic disturbances. Ziprasidone and aripiprazole have been described to be least commonly associated with weight gain or metabolic changes. In addition, some of the SGAs (risperidone, amisulpride, and paliperidone) have been associated with a significant increase of plasma prolactin levels. Overall, in cases of FEP, there should be a clear recommendation of using lower doses of the antipsychotic medication. If no or minimal clinical improvement is found after 2 weeks of treatment, such patients may benefit from a change or augmentation of treatment. Clinicians should provide accurate information to patients and relatives about the high risk of relapse if antipsychotics are discontinued, even if patients have been symptom free and functionally recovered on antipsychotic treatment for a lengthy period of time.
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Affiliation(s)
- Benedicto Crespo-Facorro
- Department of Psychiatry, IDIVAL, School of Medicine, University Hospital Marqués de Valdecilla. CIBERSAM, Centro de Investigación Biomédica en Red de Salud Mental, Edificio IDIVAL, planta 2 | Avda. Cardenal Herrera Oria, s/n. |, 39011, Santander, Spain.
| | - Jose Maria Pelayo-Teran
- Department of Psychiatry, IDIVAL, School of Medicine, University Hospital Marqués de Valdecilla. CIBERSAM, Centro de Investigación Biomédica en Red de Salud Mental, Edificio IDIVAL, planta 2 | Avda. Cardenal Herrera Oria, s/n. |, 39011, Santander, Spain
| | - Jacqueline Mayoral-van Son
- Department of Psychiatry, IDIVAL, School of Medicine, University Hospital Marqués de Valdecilla. CIBERSAM, Centro de Investigación Biomédica en Red de Salud Mental, Edificio IDIVAL, planta 2 | Avda. Cardenal Herrera Oria, s/n. |, 39011, Santander, Spain
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The role of melatonin and melatonin agonists in counteracting antipsychotic-induced metabolic side effects: a systematic review. Int Clin Psychopharmacol 2016; 31:301-6. [PMID: 27294772 DOI: 10.1097/yic.0000000000000135] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
This systematic review aims to investigate whether melatonin or melatonin agonists significantly attenuate metabolic side effects among psychiatric populations treated with atypical antipsychotics. Four randomized-controlled trials were identified through a comprehensive literature search using MEDLINE, EMBASE, and the Cochrane Library on 22 October 2015. These four trials (including three melatonin studies and one ramelteon study) included 138 patients, of whom 71 were treated with melatonin or ramelteon and 67 were treated with a placebo. Because of high heterogeneity, we did not carry out a meta-analysis. Melatonin was beneficial in lowering blood pressure among bipolar disorder patients; this blood pressure-lowering effect was not prominent among schizophrenic patients. Melatonin appeared to improve lipid profiles and body composition and attenuated weight gain among both schizophrenic and bipolar disorder patients. Ramelteon showed a significant efficacy in lowering total cholesterol level. Despite the few studies included, this systematic review provided promising evidence of the potential benefits of melatonin and its agonists in attenuating one or more components of metabolic syndrome among psychiatric patients using atypical antipsychotics.
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Tek C, Kucukgoncu S, Guloksuz S, Woods SW, Srihari VH, Annamalai A. Antipsychotic-induced weight gain in first-episode psychosis patients: a meta-analysis of differential effects of antipsychotic medications. Early Interv Psychiatry 2016; 10:193-202. [PMID: 25962699 PMCID: PMC5589463 DOI: 10.1111/eip.12251] [Citation(s) in RCA: 120] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2014] [Accepted: 04/12/2015] [Indexed: 12/19/2022]
Abstract
AIM The first-episode psychosis (FEP) represents a critical period to prevent cardiovascular and metabolic morbidity decades later. Antipsychotic (AP)-induced weight gain is one modifiable factor in this period. The purpose of this study is to conduct a meta-analysis of AP-induced weight and body mass index (BMI) change in FEP. METHODS A comprehensive literature search identified 28 articles that reported data on AP-specific weight or BMI change in FEP. We conducted a meta-analysis of short- and long-term mean weight and BMI differences between placebo and AP medications. We also performed subgroup and meta-regression analysis to examine weight, BMI outcomes and their relationship with location (Asian vs. Western), sponsorship and baseline weight and BMIs. RESULTS Compared to placebo, AP-caused mean weight gain was 3.22 kg and 1.4 points BMI in the short-term, and 5.30 kg and 1.86 points BMI in the long term. Clinically significant weight gain risk increased about twofold with AP use. Weight gain was associated with duration of AP use. AP medications were associated with more weight gain in Western samples as opposed to Asian samples. Most AP medications were associated with significant body weight gain and BMI increase in FEP patients, except for ziprasidone. Olanzapine and clozapine caused the highest weight gain compared to placebo. CONCLUSION Except for ziprasidone, most AP medications were associated with body weight gain and BMI increase in FEP patients. Early and continuing effects of various AP medications on weight gain and BMI increase should be taken into consideration by clinicians.
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Affiliation(s)
- Cenk Tek
- Yale University Department of Psychiatry, Connecticut Mental Health Hospital, New Haven, Connecticut, USA
| | - Suat Kucukgoncu
- Yale University Department of Psychiatry, Connecticut Mental Health Hospital, New Haven, Connecticut, USA
| | - Sinan Guloksuz
- Yale University Department of Psychiatry, Connecticut Mental Health Hospital, New Haven, Connecticut, USA
| | - Scott W Woods
- Yale University Department of Psychiatry, Connecticut Mental Health Hospital, New Haven, Connecticut, USA
| | - Vinod H Srihari
- Yale University Department of Psychiatry, Connecticut Mental Health Hospital, New Haven, Connecticut, USA
| | - Aniyizhai Annamalai
- Yale University Department of Psychiatry, Connecticut Mental Health Hospital, New Haven, Connecticut, USA
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Keinänen J, Mantere O, Kieseppä T, Mäntylä T, Torniainen M, Lindgren M, Sundvall J, Suvisaari J. Early insulin resistance predicts weight gain and waist circumference increase in first-episode psychosis--A one year follow-up study. Schizophr Res 2015; 169:458-463. [PMID: 26589392 DOI: 10.1016/j.schres.2015.11.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Revised: 09/03/2015] [Accepted: 11/02/2015] [Indexed: 01/13/2023]
Abstract
First-episode psychosis (FEP) is associated with weight gain during the first year of treatment, and risk of abdominal obesity is particularly increased. To identify early risk markers of weight gain and abdominal obesity, we investigated baseline metabolic differences in 60 FEP patients and 27 controls, and longitudinal changes during the first year of treatment in patients. Compared to controls at baseline, patients had higher low-density lipoprotein, triglyceride and apolipoprotein B levels, and lower levels of high-density lipoprotein and apolipoprotein A-I but no difference in body mass index or waist circumference. At 12-month follow-up, 60.6% of patients were overweight or obese and 58.8% had abdominal obesity. No significant increase during follow-up was seen in markers of glucose and lipid metabolism or blood pressure, but increase in C-reactive protein between baseline and 12-month follow-up was statistically significant. Weight increase was predicted by baseline insulin resistance and olanzapine use, while increase in waist circumference was predicted by baseline insulin resistance only. In conclusion, insulin resistance may be an early marker of increased vulnerability to weight gain and abdominal obesity in young adults with FEP. Olanzapine should be avoided as a first-line treatment in FEP due to the substantial weight increase it causes. In addition, the increase in the prevalence of overweight and abdominal obesity was accompanied by the emergence of low-grade systemic inflammation.
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Affiliation(s)
- Jaakko Keinänen
- Mental Health Unit, National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland.
| | - Outi Mantere
- Mental Health Unit, National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland; University of Helsinki and Helsinki University Hospital, Psychiatry, P.O. Box 590, FIN-00029, HUS, Helsinki, Finland.
| | - Tuula Kieseppä
- Mental Health Unit, National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland; University of Helsinki and Helsinki University Hospital, Psychiatry, P.O. Box 590, FIN-00029, HUS, Helsinki, Finland.
| | - Teemu Mäntylä
- Mental Health Unit, National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland; Department of Neuroscience and Biomedical Engineering and Advanced Magnetic Imaging Centre, Aalto NeuroImaging, Aalto University School of Science; Institute of Behavioural Sciences, University of Helsinki, P.O. Box 9, FI-00014, University of Helsinki, Helsinki, Finland.
| | - Minna Torniainen
- Mental Health Unit, National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland.
| | - Maija Lindgren
- Mental Health Unit, National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland.
| | - Jouko Sundvall
- Genomics and Biomarkers Unit, National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland.
| | - Jaana Suvisaari
- Mental Health Unit, National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland.
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Williamson K, Kilner K, Clibbens N. A comparison of the nutrient intake of a community-dwelling first-episode psychosis cohort, aged 19-64 years, with data from the UK population. J Nutr Sci 2015; 4:e28. [PMID: 26495120 PMCID: PMC4611081 DOI: 10.1017/jns.2015.18] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Revised: 12/21/2014] [Accepted: 06/11/2015] [Indexed: 12/20/2022] Open
Abstract
Psychosis increases the risk of CVD, obesity and type 2 diabetes and reduces life expectancy. There are limited data comparing the dietary habits of community-dwelling first-episode psychosis sufferers - with autonomy over diet - and the general population. The data represent the retrospective evaluation of nutritional data collected between 2007 and 2013 from 143 individuals from the UK population receiving treatment for first-episode psychosis. Differences in mean nutrient intakes between the study cohort and the national sample were tested for statistical significance using independent t tests, incorporating Satterthwaite's correction where required. Mean total energy intake was lower for males (P = 0·049) and higher for females (P = 0·016) in the cohort than in the corresponding subgroups of the national sample. Females in the study cohort consumed 12·9 (95 % CI 4·3, 21·5) g more total fat per d, whilst males consumed 7·7 (95 % CI 0·5, 14·9) g less protein per d than the national sample. Males in the study also showed significantly lower mean intakes than nationally of folate, Fe, Se, vitamin D and Zn, but not vitamin C. The proportion of individuals not meeting the lower reference nutrient intakes, particularly for Se (males 54·0 % and females 57·1 %) and for Fe amongst females (29·6 %), is cause for concern regarding potentially severe deficiencies. Further exploration of dietary habits within first-episode psychosis is warranted to assess whether individuals make beneficial dietary changes for their physical and mental health and wellbeing following dietary change intervention. It would also be pertinent to assess any correlation between diet and mental health symptomology.
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Affiliation(s)
- Kevin Williamson
- Rotherham Early Intervention in Psychosis Service, Rotherham Doncaster and South Humber NHS Foundation Trust, 144A Aughton Road, Swallownest Court, Swallownest, Sheffield S26 4TH, UK
| | - Karen Kilner
- Sheffield Hallam University, P102 Montgomery House, 32 Collegiate Crescent, Sheffield S10 2BP, UK
| | - Nicola Clibbens
- Sheffield Hallam University, 36 Collegiate Crescent, Sheffield S10 2BP, UK
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Gurillo P, Jauhar S, Murray RM, MacCabe JH. Does tobacco use cause psychosis? Systematic review and meta-analysis. Lancet Psychiatry 2015; 2:718-725. [PMID: 26249303 PMCID: PMC4698800 DOI: 10.1016/s2215-0366(15)00152-2] [Citation(s) in RCA: 203] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2014] [Revised: 03/13/2015] [Accepted: 03/19/2015] [Indexed: 12/25/2022]
Abstract
BACKGROUND Although the association between psychotic illness and cigarette smoking is well known, the reasons are unclear why people with psychosis are more likely to smoke than are the general population. We aimed to test several hypotheses. First, that daily tobacco use is associated with an increased risk of psychotic illness in both case-control and prospective studies. Second, that smoking is associated with an earlier age at onset of psychotic illness. Finally, that an earlier age at initiation of smoking is associated with an increased risk of psychosis. We also aimed to derive an estimate of the prevalence of smoking in patients presenting with their first episode of psychosis. METHODS We searched Embase, Medline, and PsycINFO and selected observational studies in which rates of smoking were reported in people with psychotic disorders, compared with controls. We calculated the weighted mean difference for age at onset of psychosis and age at initiation of smoking. For categorical outcomes, we calculated odds ratios from cross-sectional studies and risk ratios from prospective studies. FINDINGS Of 3717 citations retrieved, 61 studies comprising 72 samples met inclusion criteria. The overall sample included 14 555 tobacco users and 273 162 non-users. The prevalence of smoking in patients presenting with their first episode of psychosis was 0·57 (95% CI 0·52-0·62; p<0·0001). In case-control studies, the overall odds ratio for the first episode of psychosis in smokers versus non-smokers was 3·22 (95% CI 1·63-6·33), with some evidence of publication bias (Egger's test p=0·018, Begg's test p=0·007). For prospective studies, we calculated an overall relative risk of new psychotic disorders in daily smokers versus non-smokers of 2·18 (95% CI 1·23-3·85). Daily smokers developed psychotic illness at an earlier age than did non-smokers (weighted mean difference -1·04 years, 95% CI -1·82 to -0·26). Those with psychosis started smoking at a non-significantly earlier age than did healthy controls (-0·44 years, 95% CI -1·21 to 0·34). INTERPRETATION Daily tobacco use is associated with increased risk of psychosis and an earlier age at onset of psychotic illness. The possibility of a causal link between tobacco use and psychosis merits further examination. FUNDING NIHR Maudsley Biomedical Research Centre.
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Affiliation(s)
| | - Sameer Jauhar
- Department of Psychosis Studies, King's College, London, UK.
| | - Robin M Murray
- Department of Psychosis Studies, King's College, London, UK
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Manu P, Dima L, Shulman M, Vancampfort D, De Hert M, Correll CU. Weight gain and obesity in schizophrenia: epidemiology, pathobiology, and management. Acta Psychiatr Scand 2015; 132:97-108. [PMID: 26016380 DOI: 10.1111/acps.12445] [Citation(s) in RCA: 196] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/27/2015] [Indexed: 01/17/2023]
Abstract
OBJECTIVE To review recent advances in the epidemiology, pathobiology, and management of weight gain and obesity in patients with schizophrenia and to evaluate the extent to which they should influence guidelines for clinical practice. METHOD A Medline literature search was performed to identify clinical and experimental studies published in 2005-2014 decade. RESULTS Weight gain and obesity increase the risk of adult-onset diabetes mellitus and cardiovascular disorders, non-adherence with pharmacological interventions, quality of life, and psychiatric readmissions. The etiology includes adverse effects of antipsychotics, pretreatment/premorbid genetic vulnerabilities, psychosocial and socioeconomic risk factors, and unhealthy lifestyle. Patients with schizophrenia have higher intake of calories in the form of high-density food and lower energy expenditure. The inverse relationship between baseline body mass index and antipsychotic-induced weight gain is probably due to previous antipsychotic exposure. In experimental models, the second-generation antipsychotic olanzapine increased the orexigenic stimulation of hypothalamic structures responsible for energy homeostasis. CONCLUSION The management of weight gain and obesity in patients with schizophrenia centers on behavioural interventions using caloric intake reduction, dietary restructuring, and moderate-intensity physical activity. The decision to switch antipsychotics to lower-liability medications should be individualized, and metformin may be considered for adjunctive therapy, given its favorable risk-benefit profile.
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Affiliation(s)
- P Manu
- The Zucker Hillside Hospital, New York, NY, USA.,Albert Einstein College of Medicine, New York, NY, USA.,Hofstra North Shore - LIJ School of Medicine, Hempstead, NY, USA
| | - L Dima
- Faculty of Medicine, Transilvania University, Brasov, Romania
| | - M Shulman
- The Zucker Hillside Hospital, New York, NY, USA
| | - D Vancampfort
- KU Leuven Department of Rehabilitation Sciences, Leuven, Belgium
| | - M De Hert
- University Psychiatric Centre KU Leuven, Kortenberg, Belgium
| | - C U Correll
- The Zucker Hillside Hospital, New York, NY, USA.,Albert Einstein College of Medicine, New York, NY, USA.,Hofstra North Shore - LIJ School of Medicine, Hempstead, NY, USA
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Moons T, De Hert M, Kenis G, Viechtbauer W, van Os J, Gohlke H, Claes S, van Winkel R. No association between genetic or epigenetic variation in insulin growth factors and antipsychotic-induced metabolic disturbances in a cross-sectional sample. Pharmacogenomics 2015; 15:951-62. [PMID: 24956249 DOI: 10.2217/pgs.14.46] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
AIM Second-generation antipsychotics (SGA) are known to induce metabolic disturbances. Genetic pathways, such as the IGF pathway could be associated with increased metabolic syndrome (MetS). Additionally, IGF2 methylation varies as a function of environmental influences and is associated with schizophrenia and MetS. The current study aims to evaluate whether genetic and epigenetic variation in genes of the IGF pathway are associated with metabolic disturbances in patients under treatment with SGAs. METHODS Cross-sectional metabolic data from 438 patients with schizophrenia spectrum disorder was analyzed. Using the Sequenom MassARRAY iPLEX(TM) platform, 27 SNPs of the IGF1 and IGF2 genes and the IGF receptors IGF1R and IGF2R were genotyped. Methylation status of seven IGF2 CpG dinucleotides was evaluated using a Sequenom MALDI-TOF spectrometer. RESULTS & CONCLUSION There was a significant association between IGF2 methylation and genotype, but no significant association between genetic or epigenetic variability and metabolic parameters in the present study.
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Affiliation(s)
- Tim Moons
- GRASP Research Unit, University Psychiatric Centre Catholic University Leuven, Herestraat 49, 3000 Leuven, Belgium
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Brissos S, Veguilla MR, Taylor D, Balanzá-Martinez V. The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal. Ther Adv Psychopharmacol 2014; 4:198-219. [PMID: 25360245 PMCID: PMC4212490 DOI: 10.1177/2045125314540297] [Citation(s) in RCA: 212] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Despite their widespread use, long-acting injectable (LAI) antipsychotics (APs) are often regarded with some negativity because of the assumption of punishment, control and insufficient evolution towards psychosocial development of patients. However, LAI APs have proved effective in schizophrenia and other severe psychotic disorders because they assure stable blood levels, leading to a reduction of the risk of relapse. Therapeutic opportunities have also arisen after introduction of newer, second-generation LAI APs in recent years. Newer LAI APs are more readily dosed optimally, may be better tolerated and are better suited to integrated rehabilitation programmes. This review outlines the older and newer LAI APs available for the treatment of schizophrenia, with considerations of past and present pharmacological and therapeutic issues. Traditional, evidence-based approaches to systematic reviews and randomized clinical trials are of limited utility in this area so this paper's blending of experimental trials with observational research is particularly appropriate and effective.
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Affiliation(s)
- Sofia Brissos
- Psychiatrist, Lisbon's Psychiatric Hospitalar Centre, Rua Conde de Redondo, nº 8 3º dt., Lisbon, 1150, Portugal
| | - Miguel Ruiz Veguilla
- Grupo Psicosis y Neurodesarrollo, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio /CSIC/Universidad de Sevilla, Unidad de Hospitalizacion de Salud Mental, Sevilla, Spain
| | - David Taylor
- South London and Maudsley NHS Foundation Trust, Pharmacy Department, Maudsley Hospital, Denmark Hill, London, UK
| | - Vicent Balanzá-Martinez
- Catarroja Mental Health Unit, University Hospital Doctor Peset, FISABIO, Valencia; and Section of Psychiatry, University of Valencia, CIBERSAM, Valencia, Spain
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Trend in rates for deaths with mention of schizophrenia on death certificates of US residents, 1999-2010. Soc Psychiatry Psychiatr Epidemiol 2014; 49:1083-91. [PMID: 24562389 DOI: 10.1007/s00127-014-0846-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2013] [Accepted: 02/03/2014] [Indexed: 01/19/2023]
Abstract
BACKGROUND Trends in mortality rates for schizophrenia using multiple causes of death (including contributory causes) coded on death certificates in the US resident population apparently have not been reported. METHODS Age-standardized rates for deaths per 100,000 in 1999-2010 at age 15+ years (and for 15-64 and 65+ years) with mention of schizophrenia were examined for the US resident population, including variation by age, gender, race (blacks/African Americans and whites) and region. RESULTS Deaths at age 15+ years coded with schizophrenia as underlying cause were only 12 % of all deaths with mention of schizophrenia, for which the rate declined from 1.58 in 1999 (3,407 deaths) to 1.32 in 2010 (3,422 deaths) (percentage change or PC = -16 %). Declines were larger in females than males, in whites than blacks, and occurred in the Northeast, Midwest and South but not the West. The rate increased for age 15-64 years (PC = +28 %) (mainly in males), however, while declining for age 65+ years (PC = -35 %). For deaths at age 15-64 years with schizophrenia coded as other than the underlying cause, the largest continuous increase was for endocrine-metabolic diseases (predominantly diabetes mellitus) as underlying cause, with smaller increases in males for cardiovascular diseases, external causes and neoplasms. CONCLUSION Trends in the US rate for deaths with mention of schizophrenia varied among the sociodemographic groups examined. The lack of decline for age 15-64 years requires further study especially with regard to mediators (e.g., obesity) of excess mortality in schizophrenia identified from cohort studies.
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Jacobowitz W, Derbabian B, Saunders A. The Effect of a Calorie-Restricted Diet on Weight Gain in Short-Term Psychiatric Inpatients Receiving Atypical Antipsychotic Medications. J Psychosoc Nurs Ment Health Serv 2014; 52:30-7. [DOI: 10.3928/02793695-20140421-01] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2013] [Accepted: 04/10/2014] [Indexed: 11/20/2022]
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Modabbernia A, Heidari P, Soleimani R, Sobhani A, Roshan ZA, Taslimi S, Ashrafi M, Modabbernia MJ. Melatonin for prevention of metabolic side-effects of olanzapine in patients with first-episode schizophrenia: randomized double-blind placebo-controlled study. J Psychiatr Res 2014; 53:133-40. [PMID: 24607293 DOI: 10.1016/j.jpsychires.2014.02.013] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2013] [Revised: 12/14/2013] [Accepted: 02/14/2014] [Indexed: 12/12/2022]
Abstract
UNLABELLED We aimed to determine the efficacy of melatonin 3 mg/day in prevention of olanzapine-induced metabolic side-effects. In a randomized double-blind placebo-controlled study, 48 patients with first-episode schizophrenia who were eligible for olanzapine treatment, were randomly assigned to olanzapine plus either melatonin 3 mg/day or matched placebo for eight weeks. Anthropometric and metabolic parameters as well as psychiatric symptoms using The Positive and Negative Syndrome Scale (PANSS) were assessed at baseline, week 4, and 8. Primary outcome measure was the change from baseline in weight at week 8. Data were analyzed using t-test, Mann-Whitney U test, and mixed-effects model. Thirty-six patients had at least one post-baseline measurement. At week eight, melatonin was associated with significantly less weight gain [mean difference (MD) = 3.2 kg, P = 0.023], increase in waist circumference [MD = 2.83 cm, P = 0.041] and triglyceride concentration [MD = 62 mg/dl, P = 0.090 (nearly significant)] than the placebo. Changes in cholesterol, insulin, and blood sugar concentrations did not differ significantly between the two groups. Patients in the melatonin group experienced significantly more reduction in their PANSS scores [MD = 12.9 points, P = 0.014] than the placebo group. No serious adverse events were reported. To summarize, in patients treated with olanzapine, short-term melatonin treatment attenuates weight gain, abdominal obesity, and hypertriglyceridemia. It might also provide additional benefit for treatment of psychosis. The study was registered in the ClinicalTrials.gov ( REGISTRATION NUMBER NCT01593774).
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Affiliation(s)
- Amirhossein Modabbernia
- Psychiatry and Psychology Research Center, Department of Psychiatry, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
| | - Parvaneh Heidari
- Department of Psychiatry, Shafa Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Robabeh Soleimani
- Department of Psychiatry, Shafa Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Abdolrasoul Sobhani
- Department of Pharmacology, Guilan University of Medical Sciences, Rasht, Iran
| | - Zahra Atrkar Roshan
- Department of Biostatistics, Guilan University of Medical Sciences, Rasht, Iran
| | - Shervin Taslimi
- Psychiatry and Psychology Research Center, Department of Psychiatry, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran; Department of Biostatistics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mandana Ashrafi
- Psychiatry and Psychology Research Center, Department of Psychiatry, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran
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Volpato AM, Zugno AI, Quevedo J. Recent evidence and potential mechanisms underlying weight gain and insulin resistance due to atypical antipsychotics. BRAZILIAN JOURNAL OF PSYCHIATRY 2014; 35:295-304. [PMID: 24142093 DOI: 10.1590/1516-4446-2012-1052] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/14/2012] [Accepted: 12/20/2012] [Indexed: 12/26/2022]
Abstract
OBJECTIVE Atypical antipsychotics (AAPs) promote obesity and insulin resistance. In this regard, the main objective of this study was to present potential mechanisms and evidence concerning side effects of atypical antipsychotics in humans and rodents. METHOD A systematic review of the literature was performed using the MEDLINE database. We checked the references of selected articles, review articles, and books on the subject. RESULTS This review provides consistent results concerning the side effects of olanzapine (OL) and clozapine (CLZ), whereas we found conflicting results related to other AAPs. Most studies involving humans describe the effects on body weight, adiposity, lipid profile, and blood glucose levels. However, it seems difficult to identify an animal model replicating the wide range of changes observed in humans. Animal lineage, route of administration, dose, and duration of treatment should be carefully chosen for the replication of the findings in humans. CONCLUSIONS Patients undergoing treatment with AAPs are at higher risk of developing adverse metabolic changes. This increased risk must be taken into account when making decisions about treatment. The influence of AAPs on multiple systems is certainly the cause of such effects. Specifically, muscarinic and histaminergic pathways seem to play important roles.
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Affiliation(s)
- Ana Maria Volpato
- Universidade do Extremo Sul Catarinense, Laboratory of Neurosciences, CriciúmaSC, Brazil
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Bak M, Fransen A, Janssen J, van Os J, Drukker M. Almost all antipsychotics result in weight gain: a meta-analysis. PLoS One 2014; 9:e94112. [PMID: 24763306 PMCID: PMC3998960 DOI: 10.1371/journal.pone.0094112] [Citation(s) in RCA: 346] [Impact Index Per Article: 31.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Accepted: 03/12/2014] [Indexed: 02/08/2023] Open
Abstract
Introduction Antipsychotics (AP) induce weight gain. However, reviews and meta-analyses generally are restricted to second generation antipsychotics (SGA) and do not stratify for duration of AP use. It is hypothesised that patients gain more weight if duration of AP use is longer. Method A meta-analysis was conducted of clinical trials of AP that reported weight change. Outcome measures were body weight change, change in BMI and clinically relevant weight change (7% weight gain or loss). Duration of AP-use was stratified as follows: ≤6 weeks, 6–16 weeks, 16–38 weeks and >38 weeks. Forest plots stratified by AP as well as by duration of use were generated and results were summarised in figures. Results 307 articles met inclusion criteria. The majority were AP switch studies. Almost all AP showed a degree of weight gain after prolonged use, except for amisulpride, aripiprazole and ziprasidone, for which prolonged exposure resulted in negligible weight change. The level of weight gain per AP varied from discrete to severe. Contrary to expectations, switch of AP did not result in weight loss for amisulpride, aripiprazole or ziprasidone. In AP-naive patients, weight gain was much more pronounced for all AP. Conclusion Given prolonged exposure, virtually all AP are associated with weight gain. The rational of switching AP to achieve weight reduction may be overrated. In AP-naive patients, weight gain is more pronounced.
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Affiliation(s)
- Maarten Bak
- Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht, The Netherlands
- * E-mail:
| | - Annemarie Fransen
- Maxima Medical Centre Dep. of gynaecology, Veldhoven, The Netherlands
| | - Jouke Janssen
- Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht, The Netherlands
| | - Jim van Os
- Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht, The Netherlands
- King's College London, King's Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, United Kingdom
| | - Marjan Drukker
- Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht, The Netherlands
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Course of weight gain and metabolic abnormalities in first treated episode of psychosis: the first year is a critical period for development of cardiovascular risk factors. Int J Neuropsychopharmacol 2014; 17:41-51. [PMID: 24103107 DOI: 10.1017/s1461145713001053] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Data on the long-term metabolic side-effects associated with antipsychotics are scarce. Prospective longitudinal studies in medication-naive patients with a first episode of psychosis are a valuable source of information as they provide an assessment prior to the antipsychotic exposure and minimize the effect of potential confounding factors. The aim of this study was to assess the course of weight gain and the incidence of metabolic abnormalities during the first 3 yr of antipsychotic treatment. Data were collected from a cohort of 170 first-episode psychosis patients. They were randomly assigned to haloperidol (32%); olanzapine (32%) and risperidone (36%). The dose used was flexible. The initial antipsychotic treatment was changed when required, based on clinical response and tolerability. The results showed that the mean weight gain at 3 yr was 12.1 kg (s.d. = 10.7). It appeared to increase rapidly during the first year (85% of the total mean weight gain) and then stabilized gradually over time. Total cholesterol, LDL-cholesterol and triglyceride levels followed a similar trajectory with a significant increase only during the first year. No significant changes were detected in the mean values of glycaemic parameters. Two patients with a family history of diabetes developed diabetes type II. At short-term the factors positively associated with weight gain were lower body mass index, male gender and olanzapine treatment. At long-term, functional status and clinical response were the main predictors. The results of our study indicate that the first year of antipsychotic treatment is a critical period for weight gain and metabolic changes. Identification of weight gain patterns may help to inform studies that aim to prevent or mitigate the metabolic adverse events associated with antipsychotic therapy.
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Hasnain M, Vieweg WVR. Weight considerations in psychotropic drug prescribing and switching. Postgrad Med 2013; 125:117-29. [PMID: 24113670 DOI: 10.3810/pgm.2013.09.2706] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Our review describes potential weight-altering effects of psychotropic medications (antipsychotics, antidepressants, anti-anxiety medications, mood stabilizers, sedative-hypnotics, medications for attention-deficit/hyperactivity disorder, and other psychotropic medications) and offers guidance on switching a medication if its weight-altering effect becomes problematic. For second-generation antipsychotics, the risk of weight gain is high with clozapine and olanzapine, low with amisulpride, aripiprazole, and ziprasidone, and medium with other second-generation antipsychotics. Switching from a high-risk antipsychotic to a low-risk antipsychotic usually mitigates or reverses weight gain. For second-generation antidepressants, there may be modest weight loss with bupropion and modest weight gain with mirtazapine and paroxetine. Other second-generation antidepressants are weight neutral but individual variations can occur. If significant change in weight occurs, switching to or adding a low-risk second-generation antidepressant should be considered. Mood stabilizers include lithium, valproate, carbamazepine, lamotrigine, oxcarbazepine, and most second-generation antipsychotics. Risk of weight gain is high with lithium and valproate and low with carbamazepine, lamotrigine, and oxcarbazepine. Given the complexity of bipolar disorder and its management, a switch of a mood stabilizer would be best done by a psychiatrist. Benzodiazepines, non-benzodiazepine and melatonergic hypnotics, doxepin, and trazodone are weight neutral. Diphenhydramine may cause weight-gain and can be switched to a weight-neutral hypnotic if needed. Stimulants can cause varying degrees of weight loss and switching to atomoxetine or bupropion may reverse this problem. If that fails, switching to clonidine or guanfacine can be tried. Switching must be evidence-based and take into account status of the condition being treated, efficacy, side effect profile, potential drug-drug interactions, required laboratory monitoring and cost of the drug(s) being considered, and patient's pregnancy status or plan. Non-pharmacological interventions both for mental disorders and overweight/obesity must be fully availed.
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Teff KL, Rickels MR, Grudziak J, Fuller C, Nguyen HL, Rickels K. Antipsychotic-induced insulin resistance and postprandial hormonal dysregulation independent of weight gain or psychiatric disease. Diabetes 2013; 62:3232-40. [PMID: 23835329 PMCID: PMC3749337 DOI: 10.2337/db13-0430] [Citation(s) in RCA: 148] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Atypical antipsychotic (AAP) medications that have revolutionized the treatment of mental illness have become stigmatized by metabolic side effects, including obesity and diabetes. It remains controversial whether the defects are treatment induced or disease related. Although the mechanisms underlying these metabolic defects are not understood, it is assumed that the initiating pathophysiology is weight gain, secondary to centrally mediated increases in appetite. To determine if the AAPs have detrimental metabolic effects independent of weight gain or psychiatric disease, we administered olanzapine, aripiprazole, or placebo for 9 days to healthy subjects (n = 10, each group) under controlled in-patient conditions while maintaining activity levels. Prior to and after the interventions, we conducted a meal challenge and a euglycemic-hyperinsulinemic clamp to evaluate insulin sensitivity and glucose disposal. We found that olanzapine, an AAP highly associated with weight gain, causes significant elevations in postprandial insulin, glucagon-like peptide 1 (GLP-1), and glucagon coincident with insulin resistance compared with placebo. Aripiprazole, an AAP considered metabolically sparing, induces insulin resistance but has no effect on postprandial hormones. Importantly, the metabolic changes occur in the absence of weight gain, increases in food intake and hunger, or psychiatric disease, suggesting that AAPs exert direct effects on tissues independent of mechanisms regulating eating behavior.
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Affiliation(s)
- Karen L Teff
- Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA.
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Taylor M, Ng KYB. Should long-acting (depot) antipsychotics be used in early schizophrenia? A systematic review. Aust N Z J Psychiatry 2013; 47:624-30. [PMID: 23209308 DOI: 10.1177/0004867412470010] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND The relapse rate after a first episode of schizophrenia is high, often due to non-adherence with medication. Long-acting injections of antipsychotics (LAI) are used to promote adherence to medication. OBJECTIVE To review the literature on the use of LAIs in first-episode and early schizophrenia. METHOD A systematic electronic search of all original data containing peer-reviewed studies published in English using EMBASE, MEDLINE, Cochrane and PsychINFO from the onset of records. Reference lists from retrieved articles were examined for further relevant studies. RESULTS Ten studies were identified: two cohort studies; three randomised controlled trials; and five open studies. These studies, although limited, demonstrated the effectiveness of LAI in early schizophrenia. Seven of the 10 studies had risperidone long-acting injection as the only LAI. CONCLUSION LAIs may be useful in the treatment of early schizophrenia in terms of symptom control and relapse reduction, particularly if chosen by the patient or when medication adherence is a priority. There is a need for a large-scale, randomised controlled trial comparing oral and LAI antipsychotics to assess long-term outcomes.
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Affiliation(s)
- Mark Taylor
- Henderson Unit, Royal Edinburgh Hospital, Edinburgh, Scotland, UK.
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Horne J. Why REM sleep? Clues beyond the laboratory in a more challenging world. Biol Psychol 2013; 92:152-68. [DOI: 10.1016/j.biopsycho.2012.10.010] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2012] [Revised: 09/17/2012] [Accepted: 10/11/2012] [Indexed: 11/16/2022]
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Fang J, Chen S, Tong N, Chen L, An D, Mu J, Zhou D. Metabolic syndrome among Chinese obese patients with epilepsy on sodium valproate. Seizure 2012; 21:578-582. [PMID: 22743100 DOI: 10.1016/j.seizure.2012.06.001] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2011] [Revised: 06/02/2012] [Accepted: 06/02/2012] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Many publications have addressed the problem of weight gain and endocrine abnormalities in patients treated with sodium valproate (VPA). However, the presence of metabolic syndrome (MetS) among obese patients with epilepsy on VPA has received little attention. METHODS Thirty-six patients receiving VPA monotherapy were included in this study to evaluate the presence of MetS. All patients were interviewed and clinically examined. Blood samples were obtained after an overnight fast, and an oral glucose-tolerance test was performed. Twenty-eight subjects who were obese but had no epilepsy and were otherwise well were collected as controls ("simple obesity" group). RESULTS The two study groups were well matched in terms of age, gender and body mass index. Insulin resistance measured via homeostasis model assessment (HOMA) index was more severe among the VPA-treated group (4.91±2.91 vs. 2.00±1.72, P=0.007). The frequency of the MetS was slightly higher in the patients with epilepsy compared to controls (47.2% vs. 32.1%, respectively), but this difference was not statistically significant (P=0.223). Multivariate analysis with stepwise logistic regression revealed low positive correlations between MetS development, HOMA index (P=0.029; r=0.361) and valproic acid dose (P=0.049; r=0.323). These correlations were independent of other clinical parameters. CONCLUSIONS Our preliminary study suggests that obese patients with epilepsy treated with VPA are at higher risk of MetS than individuals who are "simply obese" but otherwise well. Therefore, the HOMA index should be monitored in obese patients who receive VPA therapy, rather than monitoring body weight alone.
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Affiliation(s)
- Jiajia Fang
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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De Hert M, Yu W, Detraux J, Sweers K, van Winkel R, Correll CU. Body weight and metabolic adverse effects of asenapine, iloperidone, lurasidone and paliperidone in the treatment of schizophrenia and bipolar disorder: a systematic review and exploratory meta-analysis. CNS Drugs 2012; 26:733-59. [PMID: 22900950 DOI: 10.2165/11634500-000000000-00000] [Citation(s) in RCA: 117] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND The introduction of second-generation antipsychotics (SGAs) over the past 2 decades generated considerable optimism that better antipsychotic treatments for schizophrenia and bipolar disorder were possible. SGAs offer several tolerability benefits over first-generation antipsychotics (FGAs), particularly with respect to extrapyramidal symptoms. However, SGAs can induce serious metabolic dysregulations, especially in drug-naive, first-episode, and child and adolescent populations, with olanzapine and clozapine having the highest propensity to cause these abnormalities. In this context, newer SGAs were developed to further improve the adverse effect burden of available agents. However, until now, the metabolic risk profile of the newly approved SGAs - asenapine, iloperidone, lurasidone and paliperidone (paliperidone extended release and paliperidone palmitate) - has not been compared. OBJECTIVE The objective of this systematic review and exploratory meta-analysis was to assess the effects of asenapine, iloperidone, lurasidone and paliperidone on body weight and other metabolic parameters (cholesterol, triglycerides and glucose), as this information is relevant to guide clinical decision making. METHOD A systematic literature search (1966-March 2012), using the Cochrane Central Register of Controlled Trials and MEDLINE, CINAHL and EMBASE databases, was conducted for randomized, placebo-controlled and head-to-head clinical trials of asenapine, iloperidone, lurasidone and paliperidone. Published and unpublished data on changes in body weight and glucose and lipid metabolism parameters were extracted. For placebo-controlled, short-term (≤12 weeks) and longer-term (>12 weeks) trials with available data on ≥7% weight increase compared with pre-treatment weight, or mean weight change with standard deviation, a formal meta-analysis was performed, estimating the pooled effect size (represented as relative risk [RR], numbers-needed-to-harm [NNH] and weighted mean difference [WMD]). An exploratory meta-analysis was also performed for the other metabolic variables (cholesterol, triglycerides and glucose). Data from active- and placebo-controlled studies were used for a pooled comparison of simple mean changes in weight, cholesterol, triglyceride and glucose levels. RESULTS Fifty-six trials (n = 21 691) in schizophrenia (N = 49, n = 19 299) or bipolar disorder (N = 7, n = 2392) were identified (asenapine: N = 9, iloperidone: N = 11, lurasidone: N = 8, paliperidone: N = 28). Most of the trials (64.3%) were of ≤12 weeks' duration. In the short-term trials, compared with placebo, a ≥7% weight increase was statistically significantly (p < 0.05) most prevalent for asenapine (5 trials, n = 1360, RR = 4.09, 95% confidence interval [CI] 2.25, 7.43, NNH = 17), followed by iloperidone (4 trials, n = 1931, RR = 3.13, 95% CI 2.08, 4.70, NNH = 11) and paliperidone (12 trials, n = 4087, RR = 2.17, 95% CI 1.64, 2.86, NNH = 20). The effect of lurasidone on body weight (6 trials, n = 1793, RR = 1.42, 95% CI 0.87, 2.29) was not statistically significant. Short-term weight gain was statistically significantly (p < 0.001) greater than placebo with iloperidone (1 trial, n = 300, +2.50 kg, 95% CI 1.92, 3.08), paliperidone (15 trials, n = 3552, +1.24 kg, 95% CI 0.91, 1.57), asenapine (3 trials, n = 751, +1.16 kg, 95% CI 0.83, 1.49), as well as with lurasidone (5 trials, n = 999, +0.49 kg, 95% CI 0.17, 0.81, p < 0.01). Sufficient meta-analysable, longer-term, weight change data were only available for asenapine and paliperidone, showing statistically significantly (p < 0.001) greater weight gain versus placebo for both drugs (asenapine, 3 trials, n = 311, +1.30 kg, 95% CI 0.62, 1.98; paliperidone, 6 trials, n = 1174, +0.50 kg, 95% CI 0.22, 0.78). Although statistically significant, in general, no clinically meaningful differences were observed between the four newly approved SGAs and placebo regarding the mean change from baseline to endpoint in cholesterol levels in short-term trials, with the exception of iloperidone for total cholesterol (1 trial, n = 300, +11.60 mg/dL, 95% CI 4.98, 18.22, p ≤ 0.001), high-density cholesterol (1 trial, n = 300, +3.6 mg/dL, 95% CI 1.58, 5.62, p < 0.001) and low-density cholesterol (1 trial, n = 300, +10.30 mg/dL, 95% CI 4.94, 15.66, p < 0.001) and with the exception of lurasidone for high-density cholesterol (5 trials, n = 1004, +1.50 mg/dL, 95% CI 0.56, 2.44, p < 0.01). Asenapine increased total cholesterol statistically significantly (p < 0.05) during longer-term treatment (1 trial, n = 194, +6.53 mg/dL, 95% CI 1.17, 11.89). Regarding triglycerides, only short-term (3 trials, n = 1152, +1.78 mg/dL, 95% CI 0.40, 3.17, p < 0.01) and longer-term treatment with paliperidone (4 trials, n = 791, -0.20 mg/dL, 95% CI -0.40, -0.01, p < 0.05) had a statistically, but not clinically, significant effect. Statistically significant changes in glucose levels were noticed during short-term treatment with asenapine (2 trials, n = 379, -3.95 mg/dL, 95% CI -7.37, -0.53, p < 0.05) and iloperidone (1 trial, n = 300, +6.90 mg/dL, 95% CI 2.48, 11.32, p < 0.01), and during long-term treatment with paliperidone (6 trials, n = 1022, +3.39 mg/dL, 95% CI 0.42, 6.36, p < 0.05). CONCLUSION While preliminary data suggest the lowest weight gain potential with lurasidone and potentially relevant short-term metabolic effects for asenapine and iloperidone, data are still too sparse to comprehensively evaluate the metabolic safety of the newly approved SGAs. Therefore, there is a clear need for further controlled studies to evaluate whether these agents are less problematic regarding treatment-emergent weight gain and metabolic disturbances than other currently available antipsychotics.
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Affiliation(s)
- Marc De Hert
- University Psychiatric Centre, Catholic University Leuven, Kortenberg, Belgium
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