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Wei B, Shi Y, Yu X, Cai Y, Zhao Y, Song Y, Zhao Z, Huo M, Li L, Gao Q, Yu D, Wang B, Sun M. GR/P300 Regulates MKP1 Signaling Pathway and Mediates Depression-like Behavior in Prenatally Stressed Offspring. Mol Neurobiol 2024; 61:10613-10628. [PMID: 38769227 DOI: 10.1007/s12035-024-04244-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 05/07/2024] [Indexed: 05/22/2024]
Abstract
Accumulating evidence suggests that prenatal stress (PNS) increases offspring susceptibility to depression, but the underlying mechanisms remain unclear. We constructed a mouse model of prenatal stress by spatially restraining pregnant mice from 09:00-11:00 daily on Days 5-20 of gestation. In this study, western blot analysis, quantitative real-time PCR (qRT‒PCR), immunofluorescence, immunoprecipitation, chromatin immunoprecipitation (ChIP), and mifepristone rescue assays were used to investigate alterations in the GR/P300-MKP1 and downstream ERK/CREB/TRKB pathways in the brains of prenatally stressed offspring to determine the pathogenesis of the reduced neurogenesis and depression-like behaviors in offspring induced by PNS. We found that prenatal stress leads to reduced hippocampal neurogenesis and depression-like behavior in offspring. Prenatal stress causes high levels of glucocorticoids to enter the fetus and activate the hypothalamic‒pituitary‒adrenal (HPA) axis, resulting in decreased hippocampal glucocorticoid receptor (GR) levels in offspring. Furthermore, the nuclear translocation of GR and P300 (an acetylation modifying enzyme) complex in the hippocampus of PNS offspring increased significantly. This GR/P300 complex upregulates MKP1, which is a negative regulator of the ERK/CREB/TRKB signaling pathway associated with depression. Interestingly, treatment with a GR antagonist (mifepristone, RU486) increased hippocampal GR levels and decreased MKP1 expression, thereby ameliorating abnormal neurogenesis and depression-like behavior in PNS offspring. In conclusion, our study suggested that the regulation of the MKP1 signaling pathway by GR/P300 is involved in depression-like behavior in prenatal stress-exposed offspring and provides new insights and ideas for the fetal hypothesis of mental health.
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Affiliation(s)
- Bin Wei
- Center for Medical Genetics and Prenatal Diagnosis, Key Laboratory of Birth Defect Prevention and Genetic Medicine of Shandong Health Commission, Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250000, Shandong, China
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou City, 215006, Jiangsu, China
| | - Yajun Shi
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou City, 215006, Jiangsu, China
| | - Xi Yu
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou City, 215006, Jiangsu, China
| | - Yongle Cai
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou City, 215006, Jiangsu, China
| | - Yan Zhao
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou City, 215006, Jiangsu, China
| | - Yueyang Song
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou City, 215006, Jiangsu, China
| | - Zejun Zhao
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou City, 215006, Jiangsu, China
| | - Ming Huo
- Reproductive Medicine Center, The First Hospital of Lanzhou University, LanzhouGansu, 730000, China
| | - Lingjun Li
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou City, 215006, Jiangsu, China
| | - Qinqin Gao
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou City, 215006, Jiangsu, China
| | - Dongyi Yu
- Center for Medical Genetics and Prenatal Diagnosis, Key Laboratory of Birth Defect Prevention and Genetic Medicine of Shandong Health Commission, Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250000, Shandong, China
| | - Bin Wang
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou City, 215006, Jiangsu, China.
| | - Miao Sun
- Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou City, 215006, Jiangsu, China.
- McKusick-Zhang Center for Genetic Medicine, State Key Laboratory for Complex Severe and Rare Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking, Union Medical College, Beijing, 100005, China.
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Giménez-Palomo A, Chamdal AK, Gottlieb N, Lotfaliany M, Jokinen T, Bastawy EM, Adlington K, Benachar N, Dodd S, Pacchiarotti I, Vieta E, Berk M, Stokes PRA. Efficacy and tolerability of monoamine oxidase inhibitors for the treatment of depressive episodes in mood disorders: A systematic review and network meta-analysis. Acta Psychiatr Scand 2024; 150:500-515. [PMID: 39001570 DOI: 10.1111/acps.13728] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 06/20/2024] [Accepted: 06/23/2024] [Indexed: 11/05/2024]
Abstract
BACKGROUND Monoamine oxidase inhibitors (MAOIs) are considered third-line treatments for treatment resistant depression; however, they are underused in clinical practice. AIMS This study aimed to assess the efficacy, tolerability, and acceptability of MAOIs for the treatment of depression in comparison with other antidepressant treatments. METHODS A systematic review and network meta-analysis of randomised clinical trials was performed to compare the efficacy, tolerability and acceptability between MAOIs and other antidepressant treatments for the treatment of depressive episodes. RESULTS A total of 83 double-blinded, randomised controlled trials were included in the analysis, with 7765 participants assigned to an active treatment and 1844 assigned to placebo. Several MAOIs, including isocarboxazid, phenelzine, tranylcypromine and moclobemide, showed significantly higher efficacy compared with placebo. The tolerability and acceptability of MAOIs was comparable to other antidepressants. LIMITATIONS A disproportionate number of studies investigating the most commonly used MAOIs, such as moclobemide and phenelzine, and a lack of specific studies focusing on treatment-resistant and atypical depression. CONCLUSIONS MAOIs are similar in efficacy to other antidepressants for the treatment of depression. However, more studies are needed comparing MAOI treatment in people with treatment-resistant, atypical and bipolar depression.
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Affiliation(s)
- Anna Giménez-Palomo
- Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain
- Bipolar and Depressive Disorders Unit, Hospìtal Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Institute of Neurosciences (UBNeuro), Barcelona, Spain
| | - Anjli K Chamdal
- Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
- East Kent University Hospitals NHS Foundation Trust, Kent, UK
| | - Natalie Gottlieb
- Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Mojtaba Lotfaliany
- IMPACT the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University and Barwon Health, Geelong, Victoria, Australia
| | - Tahir Jokinen
- Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Eslam M Bastawy
- IMPACT the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University and Barwon Health, Geelong, Victoria, Australia
- Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Katherine Adlington
- Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Nawal Benachar
- Department of Psychiatry, East and North Hertfordshire NHS Trust, Hertfordshire, UK
- Faculty of Medical Education, Wolfson College, University of Oxford, Oxford, UK
| | - Seetal Dodd
- IMPACT the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University and Barwon Health, Geelong, Victoria, Australia
- Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia
- Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia
| | - Isabella Pacchiarotti
- Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain
- Bipolar and Depressive Disorders Unit, Hospìtal Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Institute of Neurosciences (UBNeuro), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
| | - Eduard Vieta
- Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain
- Bipolar and Depressive Disorders Unit, Hospìtal Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Institute of Neurosciences (UBNeuro), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
| | - Michael Berk
- IMPACT the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University and Barwon Health, Geelong, Victoria, Australia
- Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia
- Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia
- Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia
| | - Paul R A Stokes
- Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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Chen C, Du S, Shao Q, Fu X, Jin L, Zhou S, Li Y. The effects of aerobic exercise for depression: An umbrella review of systematic reviews and meta-analyses. J Bodyw Mov Ther 2024; 40:2161-2172. [PMID: 39593579 DOI: 10.1016/j.jbmt.2024.10.068] [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: 01/08/2024] [Revised: 10/11/2024] [Accepted: 10/22/2024] [Indexed: 11/28/2024]
Abstract
OBJECTIVE This review aims to determine whether aerobic exercise is beneficial in treating depression in adults in general. METHODS Review of systematic reviews and meta-analyses related to RCTs. PubMed, MEDLINE, PsycINFO, Embase, and Cochrane databases of systematic reviews were searched extensively between September 2009 and September 2023. An extensive search was conducted using MeSH terms, including ''depression'', ''depressive disorder'', ''depressive symptoms'', ''exercise'', ''aerobic exercise'', ''aerobic training'', ''walking'', ''running'', ''jogging'', ''bicycling'', ''physical activity'', ''adult (limiters 18-65 years)'', ''meta-analyses'' and ''systematic reviews''. RESULT In the initial search of the titles and abstracts of reviews, 2345 articles were found. 46 full-text reviews were selected for carefully scrutinized. A total of seven reviews were included in the analysis, and two of them were meta-analyses, which included 42 RCTs. The results of four reviews evaluated the effectiveness of aerobic exercise on depression. Moreover, two reviews examined the efficacy of aerobic exercise as an add-on intervention for depression treatment, one of which was a subgroup analysis. According to two reviews, aerobic exercise improved CRF in people with depression and affected people with MDD from a neurobiological standpoint. CONCLUSION This umbrella review systematically evaluated the efficacy of aerobic exercise in treating adult depression, revealing substantial evidence that supports its potential to alleviate depressive symptoms. The positive synthesis of findings advocates for integrating aerobic exercise as a non-pharmacological treatment option. Nevertheless, additional research is essential to confirm these benefits and optimize exercise protocols for depression management.
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Affiliation(s)
- Che Chen
- School of Chinese Medicine, Ningxia Medical University, Yinchuan, 750004, China.
| | - Shaohui Du
- Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, China.
| | - Qianfeng Shao
- Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, China.
| | - XiaoWei Fu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, China.
| | - Lin Jin
- Novogene Co., Ltd. (Headquarters), China.
| | - Sheng Zhou
- Medical Data Analysis Center of Qingdao Ruyi Software Co., Ltd, China.
| | - Yue Li
- Centre for Translational Medicine, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, 518101, China.
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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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Strodl E, Bambling M, Parnam S, Ritchie G, Cramb S, Vitetta L. Probiotics and magnesium orotate for the treatment of major depressive disorder: a randomised double blind controlled trial. Sci Rep 2024; 14:20841. [PMID: 39242786 PMCID: PMC11379959 DOI: 10.1038/s41598-024-71093-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 08/23/2024] [Indexed: 09/09/2024] Open
Abstract
Following on from our pilot studies, this study aimed to test the efficacy of a combination of probiotics (Lactobacillus acidophilus, Bifidobacterium bifidum, Streptococcus thermophilus), magnesium orotate and coenzyme 10 for the treatment of major depressive disorder (MDD) through a double-blind placebo controlled clinical trial. The participants were 120 adults diagnosed with MDD randomised to daily oral administration, over 8 weeks, of either the intervention or placebo, with a 16-week follow-up period. Intent-to-treat analysis found a significantly lower frequency of the presence of a major depressive episode in the intervention group compared with placebo at the end of the 8-week treatment phase, with no difference between the two conditions at 8-week follow-up. Both the categorical and continuous measure of depressive symptoms showed a significant difference between the two conditions at 4 weeks, but not 8 and 16 weeks. The secondary end-point was demonstrated with an overall reduction in self-rated symptoms of anxiety and stress in the active treatment group compared with placebo. These findings suggest that the combination of probiotics, magnesium orotate and coenzyme 10 may be an effective treatment of MDD over an 8-week period.
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Affiliation(s)
- Esben Strodl
- School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia.
| | - Matthew Bambling
- Faculty of Medicine, University of Queensland, Brisbane, Australia
| | - Sophie Parnam
- School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia
| | - Gabrielle Ritchie
- School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia
- Faculty of Medicine, University of Queensland, Brisbane, Australia
| | - Susanna Cramb
- Australian Centre for Health Services Innovation, School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia
| | - Luis Vitetta
- Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
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Ratajczak P, Martyński J, Zięba JK, Świło K, Kopciuch D, Paczkowska A, Zaprutko T, Kus K. Comparative Efficacy of Animal Depression Models and Antidepressant Treatment: A Systematic Review and Meta-Analysis. Pharmaceutics 2024; 16:1144. [PMID: 39339181 PMCID: PMC11435171 DOI: 10.3390/pharmaceutics16091144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 08/24/2024] [Accepted: 08/26/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND Animal models are critical tools in the study of psychiatric disorders; however, none of the current models fully reflect human stress-related disorders, even though most of the knowledge about the mechanisms of depression comes from animal studies. Animal studies are useful in pharmacological research, whereby we can obtain results that translate into patient treatment by controlling environmental factors, especially in behavioural research. The authors systematically reviewed this issue since medical databases provide access to many primary studies. METHODS A systematic review and meta-analysis were conducted based on 25 primary studies. The studies were identified in databases such as PubMed, Embase, and Web of Science (December 2022) according to the inclusion and exclusion criteria established at the beginning of the research and published in the form of a protocol, following the PRISMA and Cochrane Collaboration methodology for secondary studies and CAMARADES (CAMARADES Berlin, QUEST-BIH Charité) for secondary studies on animals. Forest plot analyses were performed (data presented as Mean Difference, Random Model, Inverse Variance), Risk of Bias assessment (Systematic Review Center for Laboratory animal Experimentation (SYRCLE) evaluation), quality assessment of included studies (Animal research: Reporting of In Vivo Experiments (ARRIVE)), and a range of data from source publications were compiled in tabular form. The study analysed the popularity of both animal depression models (ADM) and rat strains used in pharmacological research to test the efficacy of antidepressant drugs based on the immobility time (IT) factor (Forced Swimming Test). The study examined selective serotonin reuptake inhibitors, namely fluoxetine, sertraline, paroxetine, citalopram, and escitalopram. Additionally, the study addressed issues concerning the "data availability statement" because precise IT data analysis was impossible in the case of 212 papers. RESULTS Our data confirm that the Chronic Unpredictable Mild Stress (CUMS) model is the most popular and versatile model used in preclinical depression research, while the two most popular rat strains were Wistar and Sprague-Dawley. The quality of included papers based on the ARRIVE assessment showed a ratio value equal to 0.63, meaning that studies were of intermediate overall quality. The Risk of Bias assessment based on the SYRCLE tool revealed a high risk related to the blinding and the random outcome assessment. In the meta-analysis, the results indicate that all analysed drugs demonstrated efficacy in reducing IT, and the most analysed drug was fluoxetine (confirmed based on 17 studies (19 models)). The analysis of the efficacy of ADMs showed that the most effective models were CUMS, Flinders Sensitive Line (genetic model), Social Isolation, Restraint Stress, and Low-dose Lipopolysaccharide (pharmacological model). Only 2.35% (5 out of 212) of corresponding authors responded to our data request. CONCLUSIONS The study highlights the dominance of the CUMS model and the Wistar and Sprague-Dawley rat strains in preclinical depression research, affirming the efficacy of SSRIs, particularly fluoxetine, in reducing IT. The findings underscore the need for better data availability and methodological improvements despite intermediate overall study quality and notable bias risks. Enhanced transparency and rigorous assessment standards are essential for advancing the reliability of animal models in depression research.
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Affiliation(s)
- Piotr Ratajczak
- Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
| | - Jakub Martyński
- Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
| | - Jan Kazimierz Zięba
- Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznan, Poland
| | - Katarzyna Świło
- Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
| | - Dorota Kopciuch
- Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
| | - Anna Paczkowska
- Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
| | - Tomasz Zaprutko
- Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
| | - Krzysztof Kus
- Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
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Martin J, Gholamali Nezhad F, Rueda A, Lee GH, Charlton CE, Soltanzadeh M, Ladha KS, Krishnan S, Diaconescu AO, Bhat V. Predicting treatment response to ketamine in treatment-resistant depression using auditory mismatch negativity: Study protocol. PLoS One 2024; 19:e0308413. [PMID: 39116153 PMCID: PMC11309493 DOI: 10.1371/journal.pone.0308413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 07/23/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND Ketamine has recently attracted considerable attention for its rapid effects on patients with major depressive disorder, including treatment-resistant depression (TRD). Despite ketamine's promising results in treating depression, a significant number of patients do not respond to the treatment, and predicting who will benefit remains a challenge. Although its antidepressant effects are known to be linked to its action as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, the precise mechanisms that determine why some patients respond and others do not are still unclear. OBJECTIVE This study aims to understand the computational mechanisms underlying changes in the auditory mismatch negativity (MMN) response following treatment with intravenous ketamine. Moreover, we aim to link the computational mechanisms to their underlying neural causes and use the parameters of the neurocomputational model to make individual treatment predictions. METHODS This is a prospective study of 30 patients with TRD who are undergoing intravenous ketamine therapy. Prior to 3 out of 4 ketamine infusions, EEG will be recorded while patients complete the auditory MMN task. Depression, suicidality, and anxiety will be assessed throughout the study and a week after the last ketamine infusion. To translate the effects of ketamine on the MMN to computational mechanisms, we will model changes in the auditory MMN using the hierarchical Gaussian filter, a hierarchical Bayesian model. Furthermore, we will employ a conductance-based neural mass model of the electrophysiological data to link these computational mechanisms to their neural causes. CONCLUSION The findings of this study may improve understanding of the mechanisms underlying response and resistance to ketamine treatment in patients with TRD. The parameters obtained from fitting computational models to EEG recordings may facilitate single-patient treatment predictions, which could provide clinically useful prognostic information. TRIAL REGISTRATION Clinicaltrials.gov NCT05464264. Registered June 24, 2022.
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Affiliation(s)
- Josh Martin
- Interventional Psychiatry Program, St. Michael’s Hospital, Unity Health Toronto, Toronto, Ontario, Canada
| | - Fatemeh Gholamali Nezhad
- Interventional Psychiatry Program, St. Michael’s Hospital, Unity Health Toronto, Toronto, Ontario, Canada
| | - Alice Rueda
- Interventional Psychiatry Program, St. Michael’s Hospital, Unity Health Toronto, Toronto, Ontario, Canada
| | - Gyu Hee Lee
- Interventional Psychiatry Program, St. Michael’s Hospital, Unity Health Toronto, Toronto, Ontario, Canada
| | - Colleen E. Charlton
- Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
| | - Milad Soltanzadeh
- Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Karim S. Ladha
- Department of Anesthesia, St. Michael’s Hospital, Unity Health Toronto, Toronto, Ontario, Canada
| | - Sridhar Krishnan
- Department of Electrical, Computer, and Biomedical Engineering, Toronto Metropolitan University, Toronto, Ontario, Canada
| | - Andreea O. Diaconescu
- Department of Electrical, Computer, and Biomedical Engineering, Toronto Metropolitan University, Toronto, Ontario, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Venkat Bhat
- Interventional Psychiatry Program, St. Michael’s Hospital, Unity Health Toronto, Toronto, Ontario, Canada
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
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8
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McIntyre RS, Agid O, Biesheuvel E, Purushottamahanti P. Effect of venlafaxine on anhedonia and amotivation in patients with major depressive disorder. CNS Spectr 2024; 29:206-214. [PMID: 38685594 DOI: 10.1017/s1092852924000245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/02/2024]
Abstract
OBJECTIVE Serotonin norepinephrine reuptake inhibitors (SNRIs) have been postulated to afford benefits in alleviating anhedonia and amotivation. This post hoc pooled analysis evaluated the effect of venlafaxine XR, an SNRI, on these symptoms in patients with major depressive disorder (MDD). METHODS Data was pooled from five short-term randomized, placebo-controlled studies of venlafaxine XR for the treatment of MDD, comprising 1087 (venlafaxine XR, n = 585; placebo, n = 502) adult subjects. The change from baseline score in the MADRS anhedonia factor (based on items 1 [apparent sadness], 2 [reported sadness], 6 [concentration difficulties], 7 [lassitude], and 8 [inability to feel]) for anhedonia, and in motivational deficits (based on 3 items of HAM-D17: involvement in work and activities, psychomotor retardation, and energy level [ie, general somatic symptoms]) for amotivation, were measured through 8 weeks. Mixed model repeated measures (MMRMs) were used to analyze changes over time and ANCOVA to analyze the change from baseline at week 8 with LOCF employed to handle missing data. RESULTS At the end of 8 weeks, the change from baseline was significantly greater in patients on venlafaxine XR in both anhedonia (mean, 95% CI: -2.73 [-3.63, -1.82], p < 0.0001) and amotivation scores (mean, 95% CI: -0.78 [-1.04, -0.52], p < 0.0001) than those on placebo. For both measures, the between-group separation from baseline was statistically significant starting from week 2 onwards, and it increased over time. CONCLUSION This analysis demonstrates that venlafaxine XR is effective in improving symptoms of anhedonia and motivational deficits in patients with MDD.
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Affiliation(s)
- Roger S McIntyre
- Department of Psychiatry, University of Toronto, Toronto, Canada
| | - Ofer Agid
- Department of Psychiatry, CAMH and University of Toronto, Toronto, Canada
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9
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Cernat A, Samaan Z, Abelson J, Ramdyal A, Shaikh H, Vanstone M. Patient perspectives on pharmacogenomic (PGx) testing for antidepressant prescribing in primary care: a qualitative description study. J Community Genet 2024; 15:293-309. [PMID: 38587601 PMCID: PMC11217204 DOI: 10.1007/s12687-024-00705-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Accepted: 03/28/2024] [Indexed: 04/09/2024] Open
Abstract
Many patients with major depressive disorder (MDD) try multiple antidepressants before finding one that works well and is tolerable. Pharmacogenomic (PGx) testing was developed to facilitate more efficacious prescribing. This technology has not been robustly implemented clinically. Patient perspectives are critical to policy decisions, but the views of patients with MDD about the use of PGx testing to guide antidepressant prescribing have not been extensively examined, particularly in publicly funded healthcare systems. The purpose of this qualitative description study was to produce actionable patient perspectives evidence to inform future technology assessment of PGx testing. We conducted semi-structured interviews with 21 adults with MDD for which antidepressants were indicated in Ontario, Canada, and used the Ontario Decision Determinants Framework to conduct an unconstrained deductive content analysis. Patients expressed views about the overall clinical benefit of PGx testing in depression care, preferences for deployment of testing, perspectives on ethical considerations, opinions about equity and patient care, and beliefs regarding the feasibility of adopting PGx testing into the healthcare system. They also worried about the possibility of conflicts of interest between PGx test manufacturers and pharmaceutical companies. This study provides policymakers with patient priorities to facilitate the development of patient-centred policies. It highlights that formal adoption of PGx testing into the healthcare system requires a focus on equity of access and health outcomes.
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Affiliation(s)
- Alexandra Cernat
- Department of Family Medicine, McMaster University, 100 Main St W, Hamilton, ON, L8P 1H6, Canada
- Health Policy PhD Program, Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, L8S 4L8, Canada
| | - Zainab Samaan
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, L8S 4L8, Canada
| | - Julia Abelson
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, L8S 4L8, Canada
| | - Amanada Ramdyal
- Department of Family Medicine, McMaster University, 100 Main St W, Hamilton, ON, L8P 1H6, Canada
| | - Hadia Shaikh
- Department of Family Medicine, McMaster University, 100 Main St W, Hamilton, ON, L8P 1H6, Canada
- Biomedical Discovery and Commercialization Program, Faculty of Health Sciences, McMaster University, Hamilton, L8S 4L8, Canada
| | - Meredith Vanstone
- Department of Family Medicine, McMaster University, 100 Main St W, Hamilton, ON, L8P 1H6, Canada.
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10
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Simon GE, Cruz M, Boggs JM, Beck A, Shortreed SM, Coley RY. Predicting Outcomes of Antidepressant Treatment in Community Practice Settings. Psychiatr Serv 2024; 75:419-426. [PMID: 38050444 DOI: 10.1176/appi.ps.20230380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/06/2023]
Abstract
OBJECTIVE The authors examined whether machine-learning models could be used to analyze data from electronic health records (EHRs) to predict patients' responses to antidepressant medications. METHODS EHR data from a Washington State health system identified patients ages ≥13 years who started an antidepressant medication in 2016 in a community practice setting and had a baseline Patient Health Questionnaire-9 (PHQ-9) score of ≥10 and at least one PHQ-9 score recorded 14-180 days later. Potential predictors of a response to antidepressants were extracted from the EHR and included demographic characteristics, psychiatric and substance use diagnoses, past psychiatric medication use, mental health service use, and past PHQ-9 scores. Random-forest and penalized regression analyses were used to build models predicting follow-up PHQ-9 score and a favorable treatment response (≥50% improvement in score). RESULTS Among 2,469 patients starting antidepressant medication treatment, the mean±SD baseline PHQ-9 score was 17.3±4.5, and the mean lowest follow-up score was 9.2±5.9. Outcome data were available for 72% of the patients. About 48% of the patients had a favorable treatment response. The best-fitting random-forest models yielded a correlation between predicted and observed follow-up scores of 0.38 (95% CI=0.32-0.45) and an area under the receiver operating characteristic curve for a favorable response of 0.57 (95% CI=0.52-0.61). Results were similar for penalized regression models and for models predicting last PHQ-9 score during follow-up. CONCLUSIONS Prediction models using EHR data were not accurate enough to inform recommendations for or against starting antidepressant medication. Personalization of depression treatment should instead rely on systematic assessment of early outcomes.
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Affiliation(s)
- Gregory E Simon
- Kaiser Permanente Washington Health Research Institute, Seattle (Simon, Cruz, Shortreed, Coley); Kaiser Permanente Colorado Institute for Health Research, Aurora (Boggs, Beck)
| | - Maricela Cruz
- Kaiser Permanente Washington Health Research Institute, Seattle (Simon, Cruz, Shortreed, Coley); Kaiser Permanente Colorado Institute for Health Research, Aurora (Boggs, Beck)
| | - Jennifer M Boggs
- Kaiser Permanente Washington Health Research Institute, Seattle (Simon, Cruz, Shortreed, Coley); Kaiser Permanente Colorado Institute for Health Research, Aurora (Boggs, Beck)
| | - Arne Beck
- Kaiser Permanente Washington Health Research Institute, Seattle (Simon, Cruz, Shortreed, Coley); Kaiser Permanente Colorado Institute for Health Research, Aurora (Boggs, Beck)
| | - Susan M Shortreed
- Kaiser Permanente Washington Health Research Institute, Seattle (Simon, Cruz, Shortreed, Coley); Kaiser Permanente Colorado Institute for Health Research, Aurora (Boggs, Beck)
| | - R Yates Coley
- Kaiser Permanente Washington Health Research Institute, Seattle (Simon, Cruz, Shortreed, Coley); Kaiser Permanente Colorado Institute for Health Research, Aurora (Boggs, Beck)
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11
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Ran S, Peng R, Guo Q, Cui J, Chen G, Wang Z. Bupleurum in Treatment of Depression Disorder: A Comprehensive Review. Pharmaceuticals (Basel) 2024; 17:512. [PMID: 38675471 PMCID: PMC11054835 DOI: 10.3390/ph17040512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 04/08/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
The incidence of depression has been steadily rising in recent years, making it one of the most prevalent mental illnesses. As the pursuit of novel antidepressant drugs captivates the pharmaceutical field, the therapeutic efficacy of Traditional Chinese Medicine (TCM) has been widely explored. Chaihu (Bupleurum) has been traditionally used for liver conditions such as hepatitis, liver inflammation, liver fibrosis, and liver cancer. It is believed to have hepatoprotective effects, promoting liver cell regeneration and protecting against liver damage. In addition, Bupleurum has also been used as a Jie Yu (depression-relieving) medicine in China, Japan, Republic of Korea, and other Asian countries for centuries. This review article aims to summarize the research conducted on the antidepressant properties and mechanisms of Bupleurum, as well as discuss the potential of TCM formulas containing Bupleurum. This review highlights various antidepressant ingredients isolated from Bupleurum, including saikosaponin A, saikosaponin D, rutin, puerarin, and quercetin, each with distinct mechanisms of action. Additionally, Chinese herb prescriptions and extracts containing Bupleurum, such as Chaihu Shugansan, Xiaoyaosan, and Sinisan, are also included due to their demonstrated antidepressant effects. This review reveals that these Bupleurum compounds exhibit antidepressant effects through the regulation of neurotransmitter mechanisms (such as 5-HT and DA), the NMDA (N-methyl-D-aspartate) system, brain-derived neurotrophic factor (BDNF), and other intracellular signaling pathways. Collectively, this comprehensive review provides insights into the multiple applications of Bupleurum in the treatment of depression and highlights its potential as an alternative or complementary approach to traditional therapies. However, it is essential to consider the potential adverse effects and clinical restrictions of Bupleurum despite its promising potential. Further research is needed to elucidate its specific mechanisms of action and evaluate its effectiveness in human subjects.
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Affiliation(s)
| | | | | | | | - Gang Chen
- Interdisciplinary Institute for Personalized Medicine in Brain Disorders, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China; (S.R.); (R.P.); (Q.G.); (J.C.)
| | - Ziying Wang
- Interdisciplinary Institute for Personalized Medicine in Brain Disorders, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China; (S.R.); (R.P.); (Q.G.); (J.C.)
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12
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Amendola S, Hengartner MP. Antidepressants use in Italy: an ecological study of national and regional trends and associated factors. Int Clin Psychopharmacol 2024; 39:93-105. [PMID: 37966155 DOI: 10.1097/yic.0000000000000522] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2023]
Abstract
The present study aimed to (1) provide an update on trends in AD consumption both at the national and regional unit of analysis for the period 2000-2020 in Italy and (2) analyze sociodemographic and healthcare system-related factors associated with AD prescribing at the regional-population level between 2000 and 2019. Data were extracted from reports of the Italian Medicines Agency and databases of the Italian National Institute of Statistics. Linear regression and mixed models were applied to analyze trends in AD use (DDD/1000/day) and ecological factors associated with AD prescribing. Between 2000 and 2010 AD prescription rates constantly increased. Thereafter they stabilized until 2017 when a positive trend began again. There was a positive ecological association between AD prescribing and rates of hospital discharge due to affective disorders, antibiotics prescribing, public non-drug healthcare spending per capita, and Northern regions compared to Southern regions. AD consumption increased massively during the 2000s, flattened during the 2010s but thereafter increased again until 2020. The ecological correlation between healthcare provision/spending and AD consumption suggests that health-economic factors may play an important role.
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Affiliation(s)
- Simone Amendola
- Department of Applied Psychology, Zurich University of Applied Sciences, Zurich, Switzerland
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13
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Parente J, Carolyna Gianlorenco A, Rebello-Sanchez I, Kim M, Mario Prati J, Kyung Kim C, Choi H, Song JJ, Fregni F. Neural, Anti-Inflammatory, and Clinical Effects of Transauricular Vagus Nerve Stimulation in Major Depressive Disorder: A Systematic Review. Int J Neuropsychopharmacol 2024; 27:pyad058. [PMID: 37870480 PMCID: PMC10972554 DOI: 10.1093/ijnp/pyad058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 10/22/2023] [Indexed: 10/24/2023] Open
Abstract
BACKGROUND The discovery of effective treatments for major depressive disorder (MDD) may help target different brain pathways. Invasive vagus nerve stimulation (VNS) is an effective neuromodulation technique for the treatment of MDD; however, the effectiveness of the noninvasive technique, transauricular VNS (taVNS), remains unknown. Moreover, a mechanistic understanding of the neural effects behind its biological and therapeutic effects is lacking. This review aimed to evaluate the clinical evidence and the neural and anti-inflammatory effects of taVNS in MDD. METHODS Two searches were conducted using a systematic search strategy reviewed the clinical efficacy and neural connectivity of taVNS in MDD in humans and evaluated the changes in inflammatory markers after taVNS in humans or animal models of depression. A risk of bias assessment was performed in all human studies. RESULTS Only 5 studies evaluated the effects of taVNS in patients with depression. Although the studies demonstrated the efficacy of taVNS in treating depression, they used heterogeneous methodologies and limited data, thus preventing the conduct of pooled quantitative analyses. Pooled analysis could not be performed for studies that investigated the modulation of connectivity between brain areas; of the 6 publications, 5 were based on the same experiment. The animal studies that analyzed the presence of inflammatory markers showed a reduction in the level of pro-inflammatory cytokines or receptor expression. CONCLUSIONS Data on the clinical efficacy of taVNS in the treatment of MDD are limited. Although these studies showed positive results, no conclusions can be drawn regarding this topic considering the heterogeneity of these studies, as in the case of functional connectivity studies. Based on animal studies, the application of taVNS causes a decrease in the level of inflammatory factors in different parts of the brain, which also regulate the immune system. Therefore, further studies are needed to understand the effects of taVNS in patients with MDD.
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Affiliation(s)
- Joao Parente
- Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil
| | | | | | - Minkyung Kim
- Department of Neurology, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Jose Mario Prati
- Department of Physical Therapy, Federal University of Sao Carlos, Sao Paulo, Brazil
| | - Chi Kyung Kim
- Department of Neurology, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Hyuk Choi
- Department of Medical Sciences, Graduate School of Medicine, Korea University, Seoul, Republic of Korea
- Neurive Co., Ltd., Gimhae, Republic of Korea
| | - Jae-Jun Song
- Neurive Co., Ltd., Gimhae, Republic of Korea
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Medical Center, Seoul, Republic of Korea
| | - Felipe Fregni
- Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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14
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Specka M, Bonnet U, Schmidberg L, Wichmann J, Keller M, Scholze C, Scherbaum N. Effectiveness of Medical Cannabis for the Treatment of Depression: A Naturalistic Outpatient Study. PHARMACOPSYCHIATRY 2024; 57:61-68. [PMID: 38211630 DOI: 10.1055/a-2215-6114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2024]
Abstract
BACKGROUND There is a lack of studies on the course and effectiveness of medical cannabis in the treatment of major depressive disorder (MDD). METHODS Retrospective longitudinal (18 weeks) study of n=59 outpatients with MDD, treated with medical cannabis via a telemedical platform. Previous treatment with antidepressant medication was required for inclusion into the study. Standardized data collection was carried out at entry and during monthly consultations. Severity of depression was measured on a 0-10 point rating scale. Side-effects were assessed by a checklist. RESULTS Patients were 20-54 years old; 72.9% were male; one third reported times of regular cannabis consumption within the previous five years. Drop-out rate was 22% after 18 weeks. Mean severity of depression decreased from 6.9 points (SD 1.5) at entry to 3.8 points (2.7) at week 18 (baseline observation carried forward; 95% CI for the mean difference: 2.4 to 3.8; p<0.001). A treatment response (>50% reduction of the initial score) was seen in 50.8% at week 18. One third of patients complained about side effects, none was considered as severe. Concomitant antidepressant medication (31% of patients) was not associated with outcome. CONCLUSIONS Medical cannabis was well tolerated and dropout rate was comparable to those in clinical trials of antidepressant medication. Patients reported a clinically significant reduction of depression severity. Further research on the effectiveness of medical cannabis for MDD seems warranted. Risks of this medication, such as sustaining or inducing a cannabis use disorder, or side effects such as poor concentration, must be taken into consideration.
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Affiliation(s)
- Michael Specka
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, LVR-Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Udo Bonnet
- Department of Psychiatry, Psychotherapy, and Psychosomatic Medicine, Evangelisches Krankenhaus Castrop-Rauxel, Academic Teaching Hospital of the University of Duisburg-Essen, Essen, Germany
| | | | | | - Martin Keller
- Algea Care GmbH, Frankfurt am Main, Germany
- Department of Global Development and Health, The University of Gothenburg, Gothenburg, Sweden
| | | | - Norbert Scherbaum
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, LVR-Hospital Essen, University of Duisburg-Essen, Essen, Germany
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Raspopova NI. [Pathogenetic basis of modern approaches to the therapy of sleep disorders in the clinic of depression]. Zh Nevrol Psikhiatr Im S S Korsakova 2024; 124:69-74. [PMID: 38676680 DOI: 10.17116/jnevro202412404169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/29/2024]
Abstract
Epidemiological studies indicate that about 35% of the world's population periodically suffer from insomnia. Many authors in their studies note sleep disturbances in the clinic of both somatic and mental disorders, often considering sleep disturbances as one of the predictors of these diseases. In psychiatric practice, sleep disorders are most often described in the clinic of depression, which is determined by the general pathophysiological mechanisms of their development due to disruption of the activity of the main neurotransmitter systems of the brain. The results of clinical studies show that the drug of choice in the treatment of sleep disorders in the depression clinic is the antidepressant Mirtazapine, which has a unique profile of pharmacological activity. According to international recommendations, Mirtazapine is a first-line drug in the treatment of anxiety and depressive disorders with sleep disorders and sexual dysfunction caused by taking other antidepressants.
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Affiliation(s)
- N I Raspopova
- Kazakhstan-Russian Medical University, Almaty, Republic of Kazakhstan
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Tang N, Shu W, Wang HN. Accelerated transcranial magnetic stimulation for major depressive disorder: A quick path to relief? WILEY INTERDISCIPLINARY REVIEWS. COGNITIVE SCIENCE 2024; 15:e1666. [PMID: 37779251 DOI: 10.1002/wcs.1666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 08/21/2023] [Accepted: 08/22/2023] [Indexed: 10/03/2023]
Abstract
Transcranial magnetic stimulation (TMS) is a safe, tolerable, and evidence-based intervention for major depressive disorder (MDD). However, even after decades of research, nearly half of the patients with MDD fail to respond to conventional TMS, with responding slowly and requiring daily attendance at the treatment site for 4-6 weeks. To intensify antidepressant efficacy and shorten treatment duration, accelerated TMS protocols, which involve multiple sessions per day over a few days, have been proposed and evaluated for safety and viability. We reviewed and summarized the current knowledge in accelerated TMS, including stimulation parameters, antidepressant efficacy, anti-suicidal efficacy, safety, and adverse effects. Limitations and suggestions for future directions are also addressed, along with a brief discussion on the application of accelerated TMS during the COVID-19 pandemic. This article is categorized under: Neuroscience > Clinical Neuroscience.
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Affiliation(s)
- Nailong Tang
- Department of Psychiatry, First Affiliated Hospital of Air Force Medical University, Xi'an, Shaanxi, China
- Department of Psychiatry, the 907th Hospital of the PLA Joint Logistics Support Force, Nanping, Fujian, China
| | - Wanqing Shu
- Department of Psychiatry, First Affiliated Hospital of Air Force Medical University, Xi'an, Shaanxi, China
| | - Hua-Ning Wang
- Department of Psychiatry, First Affiliated Hospital of Air Force Medical University, Xi'an, Shaanxi, China
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Li X, Feng D, Ma S, Li M, Zhao S, Tang M. Ventral hippocampus is more sensitive to fluoxetine-induced changes in extracellular 5-HT concentration, membrane 5-HT transporter level and immobility times. Neuropharmacology 2024; 242:109766. [PMID: 37858884 DOI: 10.1016/j.neuropharm.2023.109766] [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: 07/06/2023] [Revised: 09/26/2023] [Accepted: 10/15/2023] [Indexed: 10/21/2023]
Abstract
Hippocampal responses to selective 5-HT reuptake inhibitor (SSRI) have long been studied. However, its sub-regional involvements in mediating SSRI's pharmacological effects have not been fully addressed. The current study sought to investigate neurochemical, neurobiological and neurobehavioral changes in response to direct fluoxetine perfusion into the ventral and dorsal sub-regions of the hippocampus in C57BL/6 mice. Following fluoxetine perfusion, time courses of dialysate 5-HT, 5-HT transporter (5-HTT) protein (total, membrane and cytoplasmic fractions), locomotion, and immobility times in the forced swim test (FST) and tail suspension test (TST) were determined. At baseline, 5-HT uptake efficiency assessed by the no-net-flux microdialysis, and 5-HTT protein were measured as well. Results show that fluoxetine dose-dependently increased dialysate 5-HT, lowered membrane 5-HTT protein and increased cytoplasmic fraction without changing the total level, decreased immobility times in both the FST and TST, with greater responses all detected in the ventral sub-region compared to the dorsal sub-region. Fluoxetine didn't affect locomotor activity, ruling out the possibility that fluoxetine's effects on immobility maybe due to alteration in locomotion. Besides, lower 5-HT uptake efficiency and lower membrane 5-HTT protein level were found in the ventral sub-region at baseline. Together, the sub-regional differences at baseline and in responses to fluoxetine added powerful evidence to support the existence of two distinct 5-HT sub-systems in the hippocampus, with greater changes to fluoxetine detected in the ventral sub-system.
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Affiliation(s)
- Xiang Li
- Department of Pharmacy, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China
| | - Dan Feng
- Department of Clinical Pharmacology, College of Pharmacy, China Medical University, Shenyang, 110122, China
| | - Shenglu Ma
- Department of Clinical Pharmacology, College of Pharmacy, China Medical University, Shenyang, 110122, China
| | - Mingxing Li
- Department of Clinical Pharmacology, College of Pharmacy, China Medical University, Shenyang, 110122, China
| | - Shulei Zhao
- Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA
| | - Man Tang
- Department of Clinical Pharmacology, College of Pharmacy, China Medical University, Shenyang, 110122, China.
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Corral R, Bojórquez E, Cetkovich-Bakmas M, Córdoba R, Chestaro J, Gama C, Bonetto GG, Jaramillo CL, Moreno RA, Ng B, de Leon EP, Risco L, Silva H, Vazquez G. Latin American consensus recommendations for the management and treatment of patients with treatment-resistant depression (TRD). SPANISH JOURNAL OF PSYCHIATRY AND MENTAL HEALTH 2023:S2950-2853(23)00013-3. [PMID: 38592432 DOI: 10.1016/j.sjpmh.2023.06.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 06/08/2023] [Accepted: 06/14/2023] [Indexed: 04/10/2024]
Abstract
Despite the abundance of literature on treatment-resistant depression (TRD), there is no universally accepted definition of TRD, and available treatment pathways for the management of TRD vary across the Latin American region, highlighting the need for a uniform definition and treatment principles to optimize the management of TRD in Latin America. METHODS Following a thematic literature review and pre-meeting survey, a Latin America expert panel comprising 14 psychiatrists with clinical experience in managing patients with TRD convened and utilized the RAND/UCLA appropriateness method to develop consensus-based recommendations on the appropriate definition of TRD and principles for its management. RESULTS The expert panel agreed that 'treatment-resistant depression' (TRD) is defined as 'failure of two drug treatments of adequate doses, for 4-8 weeks duration with adequate adherence, during a major depressive episode'. A stepwise treatment approach should be employed for the management of TRD - treatment strategies can include maximizing dose, switching to a different class, and augmenting or combining treatments. Nonpharmacological treatments, such as electroconvulsive therapy, are also appropriate options for patients with TRD. CONCLUSION These consensus recommendations on the operational definition of TRD and approved treatments for its management can be adapted to local contexts in the Latin American countries but should not replace clinical judgement. Individual circumstances and benefit-risk balance should be carefully considered while determining the most appropriate treatment option for patients with TRD.
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Affiliation(s)
- Ricardo Corral
- Department of Psychiatry, Jose T. Borda Hospital, University of Buenos Aires, Buenos Aires, Argentina
| | | | - Marcelo Cetkovich-Bakmas
- Institute of Cognitive and Translational Neurosciences (INCyT), INECO Foundation, Favaloro University, Buenos Aires, Argentina
| | - Rodrigo Córdoba
- UR Center for Mental Health - CeRSaME, School of Medicine and Health Sciences - EMCS, University of Rosario, Bogotá, Colombia
| | - Julio Chestaro
- Catholic University of Cibao, La Vega, Dominican Republic; Traumatological Hospital Juan Bosch, La Vega, Dominican Republic
| | - Clarissa Gama
- Department of Psychiatry and Legal Medicine, UFRGS, Research Unit, HCPA, Porto Alegre, Brazil
| | | | - Carlos López Jaramillo
- Department of Psychiatry, School of Medicine, University of Antioquia, Medellin, Colombia
| | | | - Bernardo Ng
- Geriatric Center Nuevo Atardecer and Department of Psychiatry, University of California San Diego, Sun Valley Behavioral and Research Centers, California, USA
| | | | - Luis Risco
- Department of Psychiatry, Faculty of Medicine, University of Chile, Santiago, Chile
| | - Hernán Silva
- Department of Psychiatry, Faculty of Medicine, University of Chile, Santiago, Chile
| | - Gustavo Vazquez
- Research Center on Neurosciences, University of Palermo, Buenos Aires, Argentina; Department of Psychiatry, Queen's University, Kingston, Ontario, Canada.
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Fagiolini A, Cardoner N, Pirildar S, Ittsakul P, Ng B, Duailibi K, El Hindy N. Moving from serotonin to serotonin-norepinephrine enhancement with increasing venlafaxine dose: clinical implications and strategies for a successful outcome in major depressive disorder. Expert Opin Pharmacother 2023; 24:1715-1723. [PMID: 37501324 DOI: 10.1080/14656566.2023.2242264] [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: 07/14/2023] [Accepted: 07/25/2023] [Indexed: 07/29/2023]
Abstract
INTRODUCTION Mental health disorders, especially depressive and anxiety disorders, are associated with substantial health-related burden. While the second-generation antidepressants are widely accepted as first-line pharmacological treatment for major depressive disorder (MDD), patient response to such treatment is variable, with more than half failing to achieve complete remission, and residual symptoms are frequently present. AREAS COVERED Here, the pharmacodynamics of venlafaxine XR are reviewed in relation to its role as both a selective serotonin reuptake inhibitor (SSRI) and a serotonin-norepinephrine-reuptake inhibitor (SNRI), and we look at how these pharmacodynamic properties can be harnessed to guide clinical practice, asking the question 'is it possible to develop a symptom-cluster-based approach to the treatment of MDD with comorbid anxiety utilizing venlafaxine XR?.' Additionally, three illustrative clinical cases provide practical examples of the utility of venlafaxine-XR in real-world clinical practice. The place of venlafaxine XR in managing fatigue/low energy, a frequent residual symptom in MDD, is explored using pooled data from clinical trials of venlafaxine XR. EXPERT OPINION Venlafaxine XR should be considered as a first-line treatment for MDD with or without comorbid anxiety, and there are clear pharmacodynamic signals supporting a symptom cluster-based treatment paradigm for venlafaxine XR.
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Affiliation(s)
- Andrea Fagiolini
- Department of Molecular Medicine, University of Siena School of Medicine, Siena, Italy
| | - Narcis Cardoner
- Department of Psychiatry and Legal Medicine, Hospital de la Santa Creu I Sant Pau, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Universitat Autònoma de Barcelona (UAB), CIBERSAM, Carlos III Health Institute, Madrid, Spain
| | - Sebnem Pirildar
- Department of Mental Health and Diseases, Ege University Medical School, Izmir, Turkey
| | - Pichai Ittsakul
- Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Bernardo Ng
- Mexican Consortium of Neuropsychopharmacology, Mexico, Sun Valley Research Center, Imperial, California, USA
| | - Kalil Duailibi
- Department of Psychiatry, Santo Amaro University, São Paulo, Brazil
| | - Nasser El Hindy
- American Center Neurology and Psychiatry, Dubai, United Arab Emirates
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Alruwaili NS, Al-Kuraishy HM, Al-Gareeb AI, Albuhadily AK, Ragab AE, Alenazi AA, Alexiou A, Papadakis M, Batiha GES. Antidepressants and type 2 diabetes: highways to knowns and unknowns. Diabetol Metab Syndr 2023; 15:179. [PMID: 37653558 PMCID: PMC10470155 DOI: 10.1186/s13098-023-01149-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 08/09/2023] [Indexed: 09/02/2023] Open
Abstract
Type 2 diabetes (T2D) is a metabolic disease caused by the development of insulin resistance (IR), relative insulin deficiency, and hyperglycemia. Hyperglycemia-induced neurochemical dysregulation activates the progression of depression in T2D patients. Therefore, management of depression by antidepressant agents improves glucose homeostasis and insulin sensitivity. However, prolong use of antidepressant drugs may increase the risk for the development of T2D. However, there is strong controversy concerning the use of antidepressant drugs in T2D. Therefore, this review try to elucidate the potential effects of antidepressant drugs in T2D regarding their detrimental and beneficial effects.
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Affiliation(s)
- Nahi Sabih Alruwaili
- Eradah Complex of Mental Health -Northern Border Region, Ministry of Health, Al Bahah, Saudi Arabia
| | - Hayder M Al-Kuraishy
- Department of Clinical pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq
| | - Ali I Al-Gareeb
- Department of Clinical pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq
| | - Ali K Albuhadily
- Department of Clinical pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq
| | - Amany E Ragab
- Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
| | | | - Athanasios Alexiou
- Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW, 2770, Australia
- AFNP Med, Wien, 1030, Austria
| | - Marios Papadakis
- Department of Surgery II, University Hospital Witten-Herdecke, Wuppertal, 42283, Germany.
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, AlBeheira, 22511, Egypt
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21
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Treatment and Management of Mental Health Conditions During Pregnancy and Postpartum: ACOG Clinical Practice Guideline No. 5. Obstet Gynecol 2023; 141:1262-1288. [PMID: 37486661 DOI: 10.1097/aog.0000000000005202] [Citation(s) in RCA: 56] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/25/2023]
Abstract
PURPOSE To assess the evidence regarding safety and efficacy of psychiatric medications to treat mental health conditions during pregnancy and lactation. The conditions reviewed include depression, anxiety and anxiety-related disorders, bipolar disorder, and acute psychosis. For information on screening and diagnosis, refer to American College of Obstetricians and Gynecologists (ACOG) Clinical Practice Guideline Number 4, "Screening and Diagnosis of Mental Health Conditions During Pregnancy and Postpartum" (1). TARGET POPULATION Pregnant or postpartum individuals with mental health conditions with onset that may have predated the perinatal period or may have occurred for the first time in pregnancy or the first year postpartum or may have been exacerbated in that time. METHODS This guideline was developed using an a priori protocol in conjunction with a writing team consisting of one specialist in obstetrics and gynecology and one maternal-fetal medicine subspecialist appointed by the ACOG Committee on Clinical Practice Guidelines-Obstetrics and two external subject matter experts. ACOG medical librarians completed a comprehensive literature search for primary literature within Cochrane Library, Cochrane Collaboration Registry of Controlled Trials, EMBASE, PubMed, and MEDLINE. Studies that moved forward to the full-text screening stage were assessed by two authors from the writing team based on standardized inclusion and exclusion criteria. Included studies underwent quality assessment, and a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) evidence-to-decision framework was applied to interpret and translate the evidence into recommendation statements. RECOMMENDATIONS This Clinical Practice Guideline includes recommendations on treatment and management of perinatal mental health conditions including depression, anxiety, bipolar disorders, and acute postpartum psychosis, with a focus on psychopharmacotherapy. Recommendations are classified by strength and evidence quality. Ungraded Good Practice Points are included to provide guidance when a formal recommendation could not be made because of inadequate or nonexistent evidence.
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22
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Li X, Yan D, Liao M, Zhang L, Li Z, Liu B, Chen Y, Zhang Y, Liu J, Li L. Effect of fluvoxamine on plasma interleukin-6 in patients with major depressive disorder: a prospective follow-up study. Front Psychiatry 2023; 14:1163754. [PMID: 37304432 PMCID: PMC10247978 DOI: 10.3389/fpsyt.2023.1163754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Accepted: 05/10/2023] [Indexed: 06/13/2023] Open
Abstract
Introduction Major depressive disorder (MDD) is associated with low-grade inflammation, and anti-inflammatory treatment can help improve depressive symptoms. A recent study found that fluvoxamine (FLV) can reduce Interleukin-6 (IL-6) production via sigma-1 receptor in inflammation models. However, the anti- IL-6 effect of FLV in treating patients with MDD and whether it can contribute to antidepressant effects remain unclear. Methods A total of 65 patients with MDD and 34 healthy controls were recruited at baseline, and 50 patients completed the FLV treatment for 2 months. We assessed depression and anhedonia and collected plasma IL-6 levels at baseline, 1 month, and 2 months after baseline. This study evaluated the changes in clinical measures and IL-6 during treatment and analyzed their association. Further subgroup analyses were conducted in patients with MDD with high, medium, or low IL-6. Results Depression and anhedonia were significantly improved in patients with MDD, while the IL-6 did not significantly change after the FLV treatment. However, IL-6 significantly declined after the FLV treatment among patients with MDD with higher baseline IL-6. No significant associations were found between the changes in depressive symptoms and IL-6. Conclusion Our study provided preliminary evidence suggesting that the anti-IL-6 effect of FLV might not play a vital role in its antidepressant treatment, at least in patients with MDD with low inflammation. However, for patients with MDD with higher IL-6, FLV can help reduce IL-6 significantly in the antidepressant treatment, which may help guide the individual treatment of MDD with higher IL-6 levels. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT04160377, identifier NCT04160377.
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Affiliation(s)
- Xueqin Li
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Mental Health Institute of Central South University, China National Clinical Research Center on Mental Disorders (Xiangya), China National Technology Institute on Mental Disorders, Hunan Technology Institute of Psychiatry, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China
| | - Danfeng Yan
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Mental Health Institute of Central South University, China National Clinical Research Center on Mental Disorders (Xiangya), China National Technology Institute on Mental Disorders, Hunan Technology Institute of Psychiatry, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China
| | - Mei Liao
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Mental Health Institute of Central South University, China National Clinical Research Center on Mental Disorders (Xiangya), China National Technology Institute on Mental Disorders, Hunan Technology Institute of Psychiatry, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China
| | - Li Zhang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Mental Health Institute of Central South University, China National Clinical Research Center on Mental Disorders (Xiangya), China National Technology Institute on Mental Disorders, Hunan Technology Institute of Psychiatry, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China
| | - ZeXuan Li
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Mental Health Institute of Central South University, China National Clinical Research Center on Mental Disorders (Xiangya), China National Technology Institute on Mental Disorders, Hunan Technology Institute of Psychiatry, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China
| | - Bangshan Liu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Mental Health Institute of Central South University, China National Clinical Research Center on Mental Disorders (Xiangya), China National Technology Institute on Mental Disorders, Hunan Technology Institute of Psychiatry, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China
| | - Yanjun Chen
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Mental Health Institute of Central South University, China National Clinical Research Center on Mental Disorders (Xiangya), China National Technology Institute on Mental Disorders, Hunan Technology Institute of Psychiatry, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China
| | - Yan Zhang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Mental Health Institute of Central South University, China National Clinical Research Center on Mental Disorders (Xiangya), China National Technology Institute on Mental Disorders, Hunan Technology Institute of Psychiatry, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China
| | - Jin Liu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Mental Health Institute of Central South University, China National Clinical Research Center on Mental Disorders (Xiangya), China National Technology Institute on Mental Disorders, Hunan Technology Institute of Psychiatry, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China
| | - LingJiang Li
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Mental Health Institute of Central South University, China National Clinical Research Center on Mental Disorders (Xiangya), China National Technology Institute on Mental Disorders, Hunan Technology Institute of Psychiatry, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China
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23
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Zhou Q, Li X, Yang D, Xiong C, Xiong Z. A comprehensive review and meta-analysis of neurological side effects related to second-generation antidepressants in individuals with major depressive disorder. Behav Brain Res 2023; 447:114431. [PMID: 37044221 DOI: 10.1016/j.bbr.2023.114431] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 03/19/2023] [Accepted: 04/07/2023] [Indexed: 04/14/2023]
Abstract
Second-generation antidepressants (SGADs) often cause neurological side effects (SEs). This meta-analysis seeks to quantify the short-term rates of neurological SEs related to routinely used second-generation antidepressants used to treat major depressive disorder (MDD). A search of the PubMed, EMBASE,Cochrane Library databases and Web of Science was done to uncover double-blind, randomized, placebo-controlled studies evaluating the effectiveness of frequently used SGADs medicines in people with MDD. Qualifying studies were required to concentrate on the use of SGADs routinely used in MDD and to uncover data on treatment-emergent neurological SEs occurring within 12 weeks of therapy. Overall, 143 RCT studies containing 188 treatment arms were included in the meta-analyses. Most SGADs increased the risk of neurological SEs compared to placebo. The least tolerated antidepressants on the neurological tract were desvenlafaxine (OR=1.98; CI 0.85-4.65; p-value=0.12) and venlafaxine (OR=1.15; CI 0.96-1.38; p-value=0.13). Agomelatine, bupropion and vortioxetine exhibited reduced neurological SEs, showing diminished risk in insomnia (OR=0.56; CI 0.36-0.88; p-value=0.01), somnolence (OR=0.46; CI 0.27-0.79; p-value=0.01), vision blurred (OR=0.43; CI 0.19-0.96; p-value=0.04), respectively. Most SGADs did not or just marginally increased the risk of headache compared to placebo. In conclusion, frequently used SGADs demonstrated distinct patterns of neurological SEs, which physicians should consider when prescribing antidepressants to promote treatment adherence and favorable outcomes in patients with MDD.
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Affiliation(s)
- Qi Zhou
- Department of Neurology, The First People's Hospital of Fuzhou, Fuzhou, Jiangxi, China.
| | - Xinming Li
- Department of Neurology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
| | - Dejiang Yang
- Department of Neurology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
| | - Chongyu Xiong
- Public relations department, The First People's Hospital of Fuzhou, Fuzhou, Jiangxi, China.
| | - Zhenrong Xiong
- Public relations department, The First People's Hospital of Fuzhou, Fuzhou, Jiangxi, China.
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Hoffmann L, Breitkreutz J, Quodbach J. Investigation of the degradation and in-situ amorphization of the enantiomeric drug escitalopram oxalate during Fused Deposition Modeling (FDM) 3D printing. Eur J Pharm Sci 2023; 185:106423. [PMID: 36918059 DOI: 10.1016/j.ejps.2023.106423] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 03/03/2023] [Accepted: 03/11/2023] [Indexed: 03/14/2023]
Abstract
Hot-melt extrusion (HME) and subsequent FDM 3D printing offer great potential opportunities in the formulation development and production of customized oral dosage forms with poorly soluble drugs. However, thermal stress within these processes can be challenging for thermo-sensitive drugs. In this work, three different formulations were prepared to investigate the degradation and the solid state of the thermo-sensitive and poorly soluble drug escitalopram oxalate (ESC-OX) during the two heat-intensive processes HME and FDM 3D printing. For this purpose, hydroxypropyl methyl cellulose (HPMC) and basic butylated methacrylate copolymer (bPMMA) were chosen as polymers. DSC and XRD measurements revealed that ESC-OX is amorphous in the HPMC based formulations in both, extrudates and 3D printed tablets. In contrast, in-situ amorphization of the drug from crystalline state in bPMMA filaments was observed during FDM 3D printing. With regard to the content, it was found that degradation of ESC-OX in extrudates with bPMMA could be avoided and in 3D printed tablets almost fully reduced. Furthermore, a possible conversion into the R-enantiomer in the formulation with bPMMA could be excluded using a chiral column. Compared to the commercial product Cipralex®, drug release from extrudates and tablets with bPMMA was slower but still qualified as immediate drug release.
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Affiliation(s)
- Lena Hoffmann
- Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstraße 1, 40225 Düsseldorf, Germany
| | - Jörg Breitkreutz
- Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstraße 1, 40225 Düsseldorf, Germany
| | - Julian Quodbach
- Department of Pharmaceutics, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, the Netherlands.
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Gartlehner G, Dobrescu A, Chapman A, Toromanova A, Emprechtinger R, Persad E, Affengruber L, Pieh C, Klerings I, Wagner G. Nonpharmacologic and Pharmacologic Treatments of Adult Patients With Major Depressive Disorder: A Systematic Review and Network Meta-analysis for a Clinical Guideline by the American College of Physicians. Ann Intern Med 2023; 176:196-211. [PMID: 36689750 DOI: 10.7326/m22-1845] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND Primary care patients and clinicians may prefer alternative options to second-generation antidepressants for major depressive disorder (MDD). PURPOSE To compare the benefits and harms of nonpharmacologic treatments with second-generation antidepressants as first-step interventions for acute MDD, and to compare second-step treatment strategies for patients who did not achieve remission after an initial attempt with antidepressants. DATA SOURCES English-language studies from several electronic databases from 1 January 1990 to 8 August 2022, trial registries, gray literature databases, and reference lists to identify unpublished research. STUDY SELECTION 2 investigators independently selected randomized trials of at least 6 weeks' duration. DATA EXTRACTION Reviewers abstracted data about study design and conduct, participants, interventions, and outcomes. They dually rated the risk of bias of studies and the certainty of evidence for outcomes of interest. DATA SYNTHESIS 65 randomized trials met the inclusion criteria; eligible data from nonrandomized studies were not found. Meta-analyses and network meta-analyses indicated similar benefits of most nonpharmacologic treatments and antidepressants as first-step treatments. Antidepressants had higher risks for discontinuation because of adverse events than most other treatments. For second-step therapies, different switching and augmentation strategies provided similar symptomatic relief. The certainty of evidence for most comparisons is low; findings should be interpreted cautiously. LIMITATIONS Many studies had methodological limitations or dosing inequalities; publication bias might have affected some comparisons. In some cases, conclusions could not be drawn because of insufficient evidence. CONCLUSION Although benefits seem to be similar among first- and second-step MDD treatments, the certainty of evidence is low for most comparisons. Clinicians and patients should focus on options with the most reliable evidence and take adverse event profiles and patient preferences into consideration. PRIMARY FUNDING SOURCE American College of Physicians. (PROSPERO: CRD42020204703).
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Affiliation(s)
- Gerald Gartlehner
- Cochrane Austria, Department for Evidence-based Medicine and Evaluation, University of Krems, Krems, Austria, and RTI International, Research Triangle Park, North Carolina (G.G.)
| | - Andreea Dobrescu
- Cochrane Austria, Department for Evidence-based Medicine and Evaluation, University of Krems, Krems, Austria (A.D., A.C., A.T., E.P., I.K., G.W.)
| | - Andrea Chapman
- Cochrane Austria, Department for Evidence-based Medicine and Evaluation, University of Krems, Krems, Austria (A.D., A.C., A.T., E.P., I.K., G.W.)
| | - Ana Toromanova
- Cochrane Austria, Department for Evidence-based Medicine and Evaluation, University of Krems, Krems, Austria (A.D., A.C., A.T., E.P., I.K., G.W.)
| | | | - Emma Persad
- Cochrane Austria, Department for Evidence-based Medicine and Evaluation, University of Krems, Krems, Austria (A.D., A.C., A.T., E.P., I.K., G.W.)
| | - Lisa Affengruber
- Cochrane Austria, Department for Evidence-based Medicine and Evaluation, University of Krems, Krems, Austria, and Department of Family Medicine, Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands (L.A.)
| | - Christoph Pieh
- Department for Psychotherapy and Biopsychosocial Health, University of Krems, Krems, Austria (C.P.)
| | - Irma Klerings
- Cochrane Austria, Department for Evidence-based Medicine and Evaluation, University of Krems, Krems, Austria (A.D., A.C., A.T., E.P., I.K., G.W.)
| | - Gernot Wagner
- Cochrane Austria, Department for Evidence-based Medicine and Evaluation, University of Krems, Krems, Austria (A.D., A.C., A.T., E.P., I.K., G.W.)
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Qaseem A, Owens DK, Etxeandia-Ikobaltzeta I, Tufte J, Cross JT, Wilt TJ, Crandall CJ, Balk E, Cooney TG, Fitterman N, Hicks LA, Lin JS, Maroto M, Obley AJ, Tice JA, Yost J. Nonpharmacologic and Pharmacologic Treatments of Adults in the Acute Phase of Major Depressive Disorder: A Living Clinical Guideline From the American College of Physicians. Ann Intern Med 2023; 176:239-252. [PMID: 36689752 DOI: 10.7326/m22-2056] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
DESCRIPTION The purpose of this guideline from the American College of Physicians (ACP) is to present updated clinical recommendations on nonpharmacologic and pharmacologic interventions as initial and second-line treatments during the acute phase of a major depressive disorder (MDD) episode, based on the best available evidence on the comparative benefits and harms, consideration of patient values and preferences, and cost. METHODS The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of the evidence. AUDIENCE AND PATIENT POPULATION The audience for this guideline includes clinicians caring for adult patients in the acute phase of MDD in ambulatory care. The patient population includes adults in the acute phase of MDD. RECOMMENDATION 1A ACP recommends monotherapy with either cognitive behavioral therapy or a second-generation antidepressant as initial treatment in patients in the acute phase of moderate to severe major depressive disorder (strong recommendation; moderate-certainty evidence). RECOMMENDATION 1B ACP suggests combination therapy with cognitive behavioral therapy and a second-generation antidepressant as initial treatment in patients in the acute phase of moderate to severe major depressive disorder (conditional recommendation; low-certainty evidence). The informed decision on the options of monotherapy with cognitive behavioral therapy versus second-generation antidepressants or combination therapy should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients' specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences. RECOMMENDATION 2 ACP suggests monotherapy with cognitive behavioral therapy as initial treatment in patients in the acute phase of mild major depressive disorder (conditional recommendation; low-certainty evidence). RECOMMENDATION 3 ACP suggests one of the following options for patients in the acute phase of moderate to severe major depressive disorder who did not respond to initial treatment with an adequate dose of a second-generation antidepressant: • Switching to or augmenting with cognitive behavioral therapy (conditional recommendation; low-certainty evidence) • Switching to a different second-generation antidepressant or augmenting with a second pharmacologic treatment (see Clinical Considerations) (conditional recommendation; low-certainty evidence) The informed decision on the options should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients' specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences.
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Affiliation(s)
- Amir Qaseem
- American College of Physicians, Philadelphia, Pennsylvania (A.Q., I.E-I.)
| | - Douglas K Owens
- Stanford Health Policy, Stanford University, Stanford, California (D.K.O.)
| | | | | | - J Thomas Cross
- A-Cross Medicine Reviews, Colorado Springs, Colorado (J.T.J.)
| | - Timothy J Wilt
- Minneapolis VA Center for Care Delivery and Outcomes Research, Minneapolis, Minnesota (T.J.W.)
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Petrova NN. [Sexual dysfunction on the background of antidepressant therapy]. Zh Nevrol Psikhiatr Im S S Korsakova 2023; 123:115-121. [PMID: 38127711 DOI: 10.17116/jnevro2023123112115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2023]
Abstract
The review is devoted to the problem of sexual dysfunction caused by taking antidepressants. Sexual dysfunction is widespread, but it is not reported, and its impact on the quality of life and compliance of patients is underestimated. Partly because of its bidirectional association with depression, sexual dysfunction is difficult to diagnose. Possible mechanisms and risk factors associated with sexual dysfunction in patients with depression are considered. The data on the frequency of sexual dysfunction with the use of various antidepressants are given. Therapeutic strategies for sexual dysfunction associated with taking antidepressants are described. The advantages of agomelatin as an antidepressant associated with a low risk of sexual side effects are emphasized.
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Affiliation(s)
- N N Petrova
- Saint Petersburg State University, St. Petersburg, Russia
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28
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Nishi A, Sawada K, Uchida H, Mimura M, Takeuchi H. Antipsychotic Monotherapy for Major Depressive Disorder: A Systematic Review and Meta-Analysis. PHARMACOPSYCHIATRY 2023; 56:5-17. [PMID: 36257518 DOI: 10.1055/a-1934-9856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Although several randomized controlled trials (RCTs) have compared the effectiveness, efficacy, and safety of antipsychotic monotherapy (APM) versus placebo in patients with major depressive disorder (MDD), no meta-analysis has examined this topic. We conducted a systematic literature search using MEDLINE and Embase to identify relevant RCTs and performed a meta-analysis to compare the following outcomes between APM and placebo: response and remission rates, study discontinuation due to all causes, lack of efficacy, and adverse events, changes in total scores on depression severity scales, and individual adverse event rates. A total of 13 studies were identified, with 14 comparisons involving 3,197 participants that met the eligibility criteria. There were significant differences between APM and placebo in response and remission rates and changes in the primary depression severity scale in favor of APM, and study discontinuation due to adverse events and several individual adverse events in favor of placebo. No significant difference was observed in discontinuation due to all causes. APM could have antidepressant effects in the acute phase of MDD, although clinicians should be aware of an increased risk of some adverse events.
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Affiliation(s)
- Akira Nishi
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Kyosuke Sawada
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Hiroyuki Uchida
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Masaru Mimura
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Hiroyoshi Takeuchi
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
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Jia H, Yiyun C, Zhiguo W, Yousong S, Min Z, Yifan S, Na Z, Feng J, Yiru F, Daihui P. Associations between gastrointestinal symptoms, medication use, and spontaneous drug discontinuation in patients with major depressive disorder in China. J Affect Disord 2022; 319:462-468. [PMID: 36055529 DOI: 10.1016/j.jad.2022.08.116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 03/31/2022] [Accepted: 08/26/2022] [Indexed: 10/14/2022]
Abstract
BACKGROUND The study was designed to investigate the associations between gastrointestinal (GI) symptoms, medication use, and spontaneous drug discontinuation (SDD) in patients with major depressive disorder (MDD). METHODS This cross-sectional study included 3256 MDD patients from the National Survey on Symptomatology of Depression (NSSD). Differences in the sociodemographic factors, clinical characteristics, medication use, and self-reported reasons for SDD were compared in patients with different frequencies of GI symptoms. A multiple logistic regression analysis was employed to assess the contribution of GI symptoms to the risk of spontaneous drug discontinuation. RESULTS MDD patients with a higher frequency of GI symptoms were prone to have higher proportions of mood stabilizer and benzodiazepine uses (ps for trend < 0.001) but a lower proportion of SNRI use (pfor trend < 0.001). With the increase in GI symptoms, patients were prone to report worries about long-term side effects (pfor trend < 0.001), with the patients stating ineffective treatments (pfor trend = 0.002) and intolerance of adverse drug reactions (pfor trend = 0.022) as the reasons for SDD. Compared with those patients without GI symptoms, all of the MDD patients with GI symptom frequencies of several days (OR = 1.317; 95 % CI: 1.045-1.660), more than half of all days (OR = 1.305; 95 % CI: 1.005-1.695), and nearly every day (OR = 1.820; 95 %: 1.309-2.531) had an increased risk of SDD. CONCLUSION GI symptoms are highly associated with drug discontinuation in MDD patients. These findings may have important implications for clinical treatment options, as well as for drug adherence management, in MDD patients.
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Affiliation(s)
- Huang Jia
- Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China
| | - Cai Yiyun
- Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China; Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, PR China
| | - Wu Zhiguo
- Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China
| | - Su Yousong
- Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China
| | - Zhang Min
- Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China
| | - Shi Yifan
- Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China
| | - Zhu Na
- Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China; Shanghai Pudong New Area Mental Health Center, Shanghai 200122, PR China
| | - Jin Feng
- Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China
| | - Fang Yiru
- Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China; Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China.
| | - Peng Daihui
- Division of Mood Disorder, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China.
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30
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Erritzoe D, Godlewska BR, Rizzo G, Searle GE, Agnorelli C, Lewis Y, Ashok AH, Colasanti A, Boura I, Farrell C, Parfitt H, Howes O, Passchier J, Gunn RN, Politis M, Nutt DJ, Cowen PJ, Knudsen GM, Rabiner EA. Brain Serotonin Release Is Reduced in Patients With Depression: A [ 11C]Cimbi-36 Positron Emission Tomography Study With a d-Amphetamine Challenge. Biol Psychiatry 2022:S0006-3223(22)01704-8. [PMID: 36635177 DOI: 10.1016/j.biopsych.2022.10.012] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 10/03/2022] [Accepted: 10/21/2022] [Indexed: 01/14/2023]
Abstract
BACKGROUND The serotonin hypothesis of depression proposes that diminished serotonergic (5-HT) neurotransmission is causal in the pathophysiology of the disorder. Although the hypothesis is over 50 years old, there is no firm in vivo evidence for diminished 5-HT neurotransmission. We recently demonstrated that the 5-HT2A receptor agonist positron emission tomography (PET) radioligand [11C]Cimbi-36 is sensitive to increases in extracellular 5-HT induced by an acute d-amphetamine challenge. Here we applied [11C]Cimbi-36 PET to compare brain 5-HT release capacity in patients experiencing a major depressive episode (MDE) to that of healthy control subjects (HCs) without depression. METHODS Seventeen antidepressant-free patients with MDE (3 female/14 male, mean age 44 ± 13 years, Hamilton Depression Rating Scale score 21 ± 4 [range 16-30]) and 20 HCs (3 female/17 male, mean age 32 ± 9 years) underwent 90-minute dynamic [11C]Cimbi-36 PET before and 3 hours after a 0.5-mg/kg oral dose of d-amphetamine. Frontal cortex (main region of interest) 5-HT2A receptor nondisplaceable binding was calculated from kinetic analysis using the multilinear analysis-1 approach with the cerebellum as the reference region. RESULTS Following d-amphetamine administration, frontal nondisplaceable binding potential (BPND) was significantly reduced in the HC group (1.04 ± 0.31 vs. 0.87 ± 0.24, p < .001) but not in the MDE group (0.97 ± 0.25 vs. 0.92 ± 0.22, not significant). ΔBPND of the MDE group was significantly lower than that of the HC group (HC: 15% ± 14% vs. MDE: 6.5% ± 20%, p = .041). CONCLUSIONS This first direct assessment of 5-HT release capacity in people with depression provides clear evidence for dysfunctional serotonergic neurotransmission in depression by demonstrating reduced 5-HT release capacity in patients experiencing an MDE.
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Affiliation(s)
- David Erritzoe
- Division of Psychiatry, Department of Brain Sciences, Imperial College London, London, United Kingdom.
| | - Beata R Godlewska
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom
| | | | | | - Claudio Agnorelli
- Division of Psychiatry, Department of Brain Sciences, Imperial College London, London, United Kingdom; Department of Molecular Medicine, University of Siena, Siena, Italy
| | | | - Abhishekh H Ashok
- Department of Psychosis Studies, King's College London, London, United Kingdom; Department of Radiology, University of Cambridge & Addenbrooke's Hospital, Cambridge, United Kingdom
| | | | - Iro Boura
- Parkinson Foundation Centre of Excellence, King's College London, London, United Kingdom
| | - Chloe Farrell
- Parkinson Foundation Centre of Excellence, King's College London, London, United Kingdom
| | - Hollie Parfitt
- Division of Psychiatry, Department of Brain Sciences, Imperial College London, London, United Kingdom
| | - Oliver Howes
- Department of Psychosis Studies, King's College London, London, United Kingdom
| | | | | | - Marios Politis
- Neurodegeneration Imaging Group, University of Exeter, Exeter, United Kingdom
| | - David J Nutt
- Division of Psychiatry, Department of Brain Sciences, Imperial College London, London, United Kingdom
| | - Philip J Cowen
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom
| | - Gitte M Knudsen
- Neurobiology Research Unit, University Hospital Rigshospitalet and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Eugenii A Rabiner
- Invicro, London, United Kingdom; Department of Neuroimaging, King's College London, London, United Kingdom
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31
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Fugger G, Bartova L, Fabbri C, Fanelli G, Zanardi R, Dold M, Kautzky A, Rujescu D, Souery D, Mendlewicz J, Zohar J, Montgomery S, Serretti A, Kasper S. The sociodemographic and clinical phenotype of European patients with major depressive disorder undergoing first-line antidepressant treatment with NaSSAs. J Affect Disord 2022; 312:225-234. [PMID: 35691416 DOI: 10.1016/j.jad.2022.06.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 05/27/2022] [Accepted: 06/06/2022] [Indexed: 01/14/2023]
Affiliation(s)
- Gernot Fugger
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy
| | - Lucie Bartova
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy
| | - Chiara Fabbri
- Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy; Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom
| | - Giuseppe Fanelli
- Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy; Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands
| | - Raffaella Zanardi
- Vita-Salute San Raffaele University, Milano, Italy; Mood Disorders Unit, IRCCS Scientific Institute Ospedale San Raffaele, Milano, Italy
| | - Markus Dold
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy
| | - Alexander Kautzky
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Dan Rujescu
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Daniel Souery
- School of Medicine, Free University of Brussels, Brussels, Belgium; Psy Pluriel - European Centre of Psychological Medicine, Brussels, Belgium
| | | | - Joseph Zohar
- Psychiatric Division, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Stuart Montgomery
- Imperial College School of Medicine, University of London, London, United Kingdom
| | - Alessandro Serretti
- Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy
| | - Siegfried Kasper
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Center for Brain Research, Medical University of Vienna, Vienna, Austria.
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32
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Tamayo SM, Wei TH, Chen LY, Ho WC, Ton G, Lee YC. An observational study of acupuncture and complementary treatments for major depression: Case series from a preliminary study of proposed collaborative care model. J Tradit Complement Med 2022; 12:499-504. [PMID: 36081817 PMCID: PMC9446101 DOI: 10.1016/j.jtcme.2022.03.002] [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: 06/25/2021] [Revised: 02/02/2022] [Accepted: 03/06/2022] [Indexed: 11/29/2022] Open
Abstract
Background Major depressive disorder is identified as a mood disorder characterized by episodically recurring and potentially life-threatening negative symptoms. It is currently important for study, as it involves high morbidity, mortality and prevalence, as well as unsatisfactory treatment results. Aim Establish an outpatient model from an integrative approach promoting the diversified development of traditional Chinese and Western medicine cooperation, leading to a holistic intervention for patients with depression. Experimental procedure Fifteen participants with moderate to severe depression were followed up for eight weeks in the Acupuncture Department of the China Medical University Hospital in Taichung, Taiwan, under a collaborative outpatient model that combined Western psychiatry and traditional Chinese medicine (TCM). Interdisciplinary Intervention included manual acupuncture twice a week (16 sessions), tai chi, yoga meditation, and nutritional assessment. Symptomatology was measured with primary outcomes (self-reporting via questionnaires) and secondary outcomes (heart rate variability [HRV] and blood samples to measure inflammation via high-sensitivity C-reactive protein [hs-CRP]). Results The response rate was 80% (12/15 participants), with a statistically and clinically significant decrease in depression severity according to the 21-question Hamilton depression rating scale (HDRS21) (p < 0.001), the Beck Depression Inventory (BDI) (p < 0.003), and quality of life (QoL) questionnaires (p < 0.002). We found body constitution heterogeneity in the participants with major depressive disorder (MDD), predominantly blood stagnation and Qi stagnation (in 70% of participants). Conclusion An interdisciplinary outpatient treatment method of complementary therapies can be applied successfully with pharmacological treatment in clinical practice to reduce depression symptomatology. Section Physical/Mental practices. Taxonomy Major Depressive Disorder, Collaborative healthcare Treatment, Observational study.
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Affiliation(s)
- Sara Maria Tamayo
- Graduate Institute of Acupuncture Science, China Medical University, Taichung, 40402, Taiwan
| | - Tsu-Hsuan Wei
- Department of Acupuncture, China Medical University Hospital, Taichung, 40402, Taiwan
| | - Liang-yu Chen
- Department of Acupuncture, China Medical University Hsinchu Hospital, Hsinchu, 302, Taiwan
| | - Wen-Chao Ho
- Department of Public Health, China Medical University, Taichung, 40402, Taiwan
| | - Gil Ton
- Graduate Institute of Acupuncture Science, China Medical University, Taichung, 40402, Taiwan
| | - Yu-Chen Lee
- Graduate Institute of Acupuncture Science, China Medical University, Taichung, 40402, Taiwan
- Department of Acupuncture, China Medical University Hospital, Taichung, 40402, Taiwan
- Department of Acupuncture, China Medical University Hsinchu Hospital, Hsinchu, 302, Taiwan
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33
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Fan B, Zhao Y, Chai J, Bing B, Wang W. Effectiveness of acupuncture in postpartum depression: A protocol for an overview of systematic reviews. Medicine (Baltimore) 2022; 101:e28678. [PMID: 35960108 PMCID: PMC9371482 DOI: 10.1097/md.0000000000028678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
INTRODUCTION Since conflicting evidence from systematic reviews and meta-analyses (SRs/MAs) on the effectiveness of acupuncture in the treatment of postpartum depression is observed. To systematically collate, appraise and synthesize the evidence from these SRs/MAs, an overview will be performed, and this study is an overview protocol. METHODS AND ANALYSIS Eight databases will be searched: Medicine, Web of science, Cochrane Library, Embase, China National Knowledge Infrastructure, SinoMed, VIP, and Wanfang Data. SRs/MAs of acupuncture on postpartum depression will be included. Literature screening, data extraction, and evaluation of the review quality will be performed by 2 independent reviewers. The methodological quality, reporting quality, and evidence quality will be assessed using the assessment of multiple systematic reviews-2 tool, the preferred reporting items for systematic reviews and meta-analyses checklists, and the grading of recommendations, assessment, development, and evaluation system, respectively. The results will be presented in the context of the topic and the objects of the overview. This study will help bridge the implementation gap between clinical evidence and its translation in clinical application, identify flaws in research and guide future high-quality study.
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Affiliation(s)
- Bu Fan
- Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China
- Postdoctoral Station of Integrated Medicine, Fudan University, Shanghai, China
- *Correspondence: Bu Fan, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China (e-mail: )
| | - Yonghou Zhao
- Department of Neurology, Heilongjiang Mental Hospital, Harbin, Heilongjiang Province, China
- Postdoctoral Station of Integrated Medicine, Fudan University, Shanghai, China
- *Correspondence: Bu Fan, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China (e-mail: )
| | - Jianbo Chai
- Department of Neurology, Heilongjiang Mental Hospital, Harbin, Heilongjiang Province, China
- Postdoctoral Station of Integrated Medicine, Fudan University, Shanghai, China
| | - Bai Bing
- Department of Neurology, Heilongjiang Mental Hospital, Harbin, Heilongjiang Province, China
- Postdoctoral Station of Integrated Medicine, Fudan University, Shanghai, China
| | - Wanyu Wang
- Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China
- Postdoctoral Station of Integrated Medicine, Fudan University, Shanghai, China
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Scherf-Clavel M, Weber H, Wurst C, Stonawski S, Hommers L, Unterecker S, Wolf C, Domschke K, Rost N, Brückl T, Lucae S, Uhr M, Binder EB, Menke A, Deckert J. Effects of Pharmacokinetic Gene Variation on Therapeutic Drug Levels and Antidepressant Treatment Response. PHARMACOPSYCHIATRY 2022; 55:246-254. [PMID: 35839823 PMCID: PMC9458342 DOI: 10.1055/a-1872-0613] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Introduction
Pharmacogenetic testing is proposed to minimize adverse
effects when considered in combination with pharmacological knowledge of the
drug. As yet, limited studies in clinical settings have investigated the
predictive value of pharmacokinetic (pk) gene variation on therapeutic drug
levels as a probable mechanism of adverse effects, nor considered the combined
effect of pk gene variation and drug level on antidepressant treatment
response.
Methods
Two depression cohorts were investigated for the relationship
between pk gene variation and antidepressant serum concentrations of
amitriptyline, venlafaxine, mirtazapine and quetiapine, as well as treatment
response. For the analysis, 519 patients (49% females; 46.6±14.1
years) were included.
Results
Serum concentration of amitriptyline was associated with
CYP2D6
(higher concentrations in poor metabolizers compared to normal
metabolizers), of venlafaxine with
CYP2C19
(higher concentrations in
intermediate metabolizers compared to rapid/ultrarapid metabolizers) and
CYP2D6
(lower metabolite-to-parent ratio in poor compared to
intermediate and normal metabolizers, and intermediate compared to normal and
ultrarapid metabolizers). Pk gene variation did not affect treatment
response.
Discussion
The present data support previous recommendations to reduce
starting doses of amitriptyline and to guide dose-adjustments via therapeutic
drug monitoring in CYP2D6 poor metabolizers. In addition, we propose including
CYP2C19
in routine testing in venlafaxine-treated patients to improve
therapy by raising awareness of the risk of low serum concentrations in CYP2C19
rapid/ultrarapid metabolizers. In summary, pk gene variation can predict
serum concentrations, and thus the combination of pharmacogenetic testing and
therapeutic drug monitoring is a useful tool in a personalized therapy approach
for depression.
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Affiliation(s)
- Maike Scherf-Clavel
- Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
| | - Heike Weber
- Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
| | - Catherina Wurst
- Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany.,Interdisciplinary Center for Clinical Research, University Hospital of Würzburg, Würzburg, Germany.,Comprehensive Heart Failure Center (CHFC), University Hospital of Würzburg, Würzburg, Germany
| | - Saskia Stonawski
- Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany.,Interdisciplinary Center for Clinical Research, University Hospital of Würzburg, Würzburg, Germany.,Comprehensive Heart Failure Center (CHFC), University Hospital of Würzburg, Würzburg, Germany
| | - Leif Hommers
- Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany.,Interdisciplinary Center for Clinical Research, University Hospital of Würzburg, Würzburg, Germany.,Comprehensive Heart Failure Center (CHFC), University Hospital of Würzburg, Würzburg, Germany
| | - Stefan Unterecker
- Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
| | - Christiane Wolf
- Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
| | - Katharina Domschke
- Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Nicolas Rost
- Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.,International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Germany
| | - Tanja Brückl
- Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
| | | | - Manfred Uhr
- Max Planck Institute of Psychiatry, Munich, Germany
| | - Elisabeth B Binder
- Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
| | - Andreas Menke
- Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany.,Department of Psychosomatic Medicine and Psychotherapy, Medical Park Chiemseeblick, Bernau, Germany.,Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
| | - Jürgen Deckert
- Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
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35
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Hu X, Fan Q, Ma L, Jin R, Gong R, Zhao X, Qiu F, Zhou L. Reliability of Evidence to Guide Decision-Making in the Use of Acupuncture for Postpartum Depression. Front Public Health 2022; 10:942595. [PMID: 35910879 PMCID: PMC9329701 DOI: 10.3389/fpubh.2022.942595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 06/09/2022] [Indexed: 11/23/2022] Open
Abstract
Background There is conflicting evidence on the effectiveness of acupuncture in the treatment of postpartum depression (PPD). This study aimed to assess previous systematic reviews/meta-analyses (SRs/MAs) on the effectiveness of acupuncture to treat PPD. Method SRs/MAs regarding the use of acupuncture for PPD were identified from the establishment of digital databases to November 2021. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) was applied to evaluate the methodological quality of included SRs/MAs. The Grades of Recommendations, Assessment, Development and Evaluation (GRADE) was utilized to evaluate the evidence quality for outcomes of interest. Results Six studies that conducted quantitative syntheses were included. According to AMSTAR-2, the methodological quality of these SRs/MAs was critically low owing to limitations of items 2, 4, and 7. According to GRADE, no study included high-quality evidence and most studies included low-quality evidence. Conclusions Acupuncture m be beneficial for PPD, however, due to limitations of current evidence and inconsistent findings, further studies are needed to provide stronger evidence to draw definitive conclusions.
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Affiliation(s)
- Xiuwu Hu
- Nanchang Hongdu Hospital of Traditional Chinese Medicine, Nanchang, China
| | - Qian Fan
- Department of Acupuncture, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
| | - Li Ma
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Rui Jin
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Rui Gong
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiaoying Zhao
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Fenfen Qiu
- Nanchang Hongdu Hospital of Traditional Chinese Medicine, Nanchang, China
| | - Liang Zhou
- Nanchang Hongdu Hospital of Traditional Chinese Medicine, Nanchang, China
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36
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Cotter TG, Beresford T. Treatment of Mental Health in Patients With Chronic Liver Disease. Clin Liver Dis (Hoboken) 2022; 20:57-60. [PMID: 36033423 PMCID: PMC9405486 DOI: 10.1002/cld.1200] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/20/2021] [Accepted: 12/15/2021] [Indexed: 02/04/2023] Open
Abstract
Content available: Author Interview and Audio Recording.
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Affiliation(s)
- Thomas G. Cotter
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTX
| | - Thomas Beresford
- Laboratory for Clinical and Translational Research in PsychiatryMental Health ServiceRocky Mountain Regional VA Medical CenterAuroraCO,Department of PsychiatryUniversity of Colorado School of MedicineAuroraCO
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Espinola CW, Khoo Y, Parmar R, Demchenko I, Frey BN, Milev RV, Ravindran AV, Parikh SV, Ho K, Rotzinger S, Lou W, Lam RW, Kennedy SH, Bhat V. Males and females differ in reported sexual functioning with escitalopram treatment for major depressive disorder: A CAN-BIND-1 study report. J Psychopharmacol 2022; 36:604-613. [PMID: 35546043 DOI: 10.1177/02698811221095832] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
BACKGROUND Antidepressant use for major depressive disorder (MDD) is frequently associated with sexual dysfunction. AIMS Cross-sectional and longitudinal relationships between antidepressant treatment outcomes and sexual functioning (SF) were evaluated separately for males and females receiving escitalopram. We further assessed the association between pre- and posttreatment SF. METHODS In all, 208 of the 211 CAN-BIND-1 trial participants (77 males and 131 females) with MDD and detectable drug blood levels were eligible for the analyses. All received escitalopram (10-20 mg) for 8 weeks. At baseline and Week 8, participants completed the Montgomery-Åsberg Depression Rating Scale (MADRS) and the SexFx scale, which measures sexual satisfaction and SF frequency. Mixed-model repeated measures assessed baseline to Week 8 SF changes among participants with different response/remission statuses. Multiple linear regression analyses examined SF differences between treatment outcomes at Week 8 as well as associations between pretreatment and eventual SF. RESULTS For both sexes, overall sexual satisfaction improved among responders but not among nonresponders (p < 0.05). For females, overall SF frequency did not change significantly over time regardless of response status. For males, overall SF decreased significantly among nonresponders; orgasm decreased significantly among nonresponders and, to a lesser extent, among responders (p < 0.05). For both sexes, pretreatment SF was significantly associated with SF at Week 8 across all domains (p < 0.05). CONCLUSION For both sexes, sexual satisfaction improves with response to escitalopram. For females, the response does not correspond to improvements in SF frequency. For males, SF frequency, particularly that of orgasm, declines regardless of response/nonresponse.ClinicalTrials.gov identifier: NCT01655706.
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Affiliation(s)
- Caroline W Espinola
- Interventional Psychiatry Program, Centre for Depression & Suicide Studies, St. Michael's Hospital, Toronto, ON, Canada.,Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Yuelee Khoo
- Interventional Psychiatry Program, Centre for Depression & Suicide Studies, St. Michael's Hospital, Toronto, ON, Canada
| | - Roohie Parmar
- Interventional Psychiatry Program, Centre for Depression & Suicide Studies, St. Michael's Hospital, Toronto, ON, Canada
| | - Ilya Demchenko
- Interventional Psychiatry Program, Centre for Depression & Suicide Studies, St. Michael's Hospital, Toronto, ON, Canada
| | - Benicio N Frey
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.,Mood Disorders Program and Women's Health Concerns Clinic, St. Joseph's Healthcare, Hamilton, ON, Canada
| | - Roumen V Milev
- Departments of Psychiatry and Psychology, Queen's University, Providence Care Hospital, Kingston, ON, Canada
| | - Arun V Ravindran
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada.,Institute of Medical Science, University of Toronto, Toronto, ON, Canada
| | - Sagar V Parikh
- Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA
| | - Keith Ho
- Interventional Psychiatry Program, Centre for Depression & Suicide Studies, St. Michael's Hospital, Toronto, ON, Canada
| | - Susan Rotzinger
- Interventional Psychiatry Program, Centre for Depression & Suicide Studies, St. Michael's Hospital, Toronto, ON, Canada
| | - Wendy Lou
- Dalla Lana School of Public Health, University of Toronto, ON, Canada
| | - Raymond W Lam
- Department of Psychiatry, The University of British Columbia, Vancouver, BC, Canada
| | - Sidney H Kennedy
- Interventional Psychiatry Program, Centre for Depression & Suicide Studies, St. Michael's Hospital, Toronto, ON, Canada.,Department of Psychiatry, University of Toronto, Toronto, ON, Canada.,Institute of Medical Science, University of Toronto, Toronto, ON, Canada.,Li Ka Shing Knowledge Institute & Krembil Research Institute, Toronto, ON, Canada
| | - Venkat Bhat
- Interventional Psychiatry Program, Centre for Depression & Suicide Studies, St. Michael's Hospital, Toronto, ON, Canada.,Department of Psychiatry, University of Toronto, Toronto, ON, Canada.,Institute of Medical Science, University of Toronto, Toronto, ON, Canada.,Li Ka Shing Knowledge Institute & Krembil Research Institute, Toronto, ON, Canada
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Anderson HD, Thant TM, Kao DP, Crooks KR, Mendola N, Aquilante CL. Pharmacogenetic testing among patients with depression in a US managed care population. Clin Transl Sci 2022; 15:1644-1653. [PMID: 35385214 PMCID: PMC9283740 DOI: 10.1111/cts.13279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 01/14/2022] [Accepted: 03/10/2022] [Indexed: 12/01/2022] Open
Abstract
Actionable drug–gene pairs relevant to depression treatment include CYP2D6 and CYP2C19 with specific antidepressants. While clinical use of pharmacogenetic testing is growing, little is known about pharmacogenetic testing for depression treatment in managed care. We determined the incidence of single‐gene CYP2D6 and CYP2C19 testing following a new depression episode among US managed care patients, and described characteristics and antidepressant use of patients receiving tests. We used paid medical and pharmacy claims for patients from commercial health plans in the US. For adult patients with a new depression episode from January 1, 2013 to June 30, 2018, we identified covered claims for single‐gene CYP2D6 and CYP2C19 pharmacogenetic tests and antidepressant fills. Fewer than 1% (n = 1795) of the depressed cohort (n = 438,534) received a single‐gene CYP2D6 or CYP2C19 test through their insurance within 365 days of their earliest depression episode. The percentage of patients who received a test nearly tripled from 0.2% in 2013 to 0.5% in 2014 before plateauing at 0.4% from 2014 to 2017. Among the patients who received a single‐gene CYP2D6 or CYP2C19 test and filled an antidepressant within 365 days of their depression diagnosis, up to 30% may have had their initial antidepressant informed by the test result. Our findings describe the use of antidepressants before and after pharmacogenetic testing, which is clinically relevant as pharmacogenomic testing becomes more common in clinical practice. Our study also emphasizes the need for procedure and billing codes that capture multiple‐gene panel tests to be more widely implemented in administrative databases.
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Affiliation(s)
- Heather D Anderson
- Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA
| | - Thida M Thant
- Department of Psychiatry, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - David P Kao
- Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Kristy R Crooks
- Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Nicholas Mendola
- Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA
| | - Christina L Aquilante
- Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA
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Gabriel FC, Stein AT, de Melo DO, Henrique Fontes-Mota GC, Dos Santos IB, de Oliveira AF, Fráguas R, Ribeiro E. Quality of clinical practice guidelines for inadequate response to first-line treatment for depression according to AGREE II checklist and comparison of recommendations: a systematic review. BMJ Open 2022; 12:e051918. [PMID: 35365512 PMCID: PMC8977814 DOI: 10.1136/bmjopen-2021-051918] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
OBJECTIVE To assess similarities and differences in the recommended sequence of strategies among the most relevant clinical practice guidelines (CPGs) for the treatment of depression in adults with inadequate response to first-line treatment. DATA SOURCES We performed a systematic review of the literature spanning January 2011 to August 2020 in Medline, Embase, Cochrane Library and 12 databases recognised as CPGs repositories. CPGs quality was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II). STUDY SELECTION The eligibility criteria were CPGs that described pharmacological recommendations for treating depression for individuals aged 18 years or older in outpatient care setting. We included CPGs considered of high-quality (≥80% in domain 3 of AGREE II) or recognised as clinically relevant. DATA EXTRACTION Two independent researchers extracted recommendations for patients who did not respond to first-line pharmacological treatment from the selected CPGs. RESULTS We included 46 CPGs and selected 8, of which 5 were considered high quality (≥80% in domain 3 of AGREE II) and 3 were recognised as clinically relevant. Three CPGs did not define inadequate response to treatment and 3 did not establish a clear sequence of strategies. The duration of treatment needed to determine that a patient had not responded was not explicit in 3 CPGs and was discordant in 5 CPGs. Most CPGs agree in reassessing the diagnosis, assessing the presence of comorbidities, adherence to treatment, and increase dosage as first steps. All CPGs recommend psychotherapy, switching antidepressants, and considering augmentation/combining antidepressants. CONCLUSION Relevant CPGs present shortcomings in recommendations for non-responders to first-line antidepressant treatment including absence and divergencies in definition of inadequate response and sequence of recommended strategies. Overall, most relevant CPGs recommend reassessing the diagnosis, evaluate comorbidities, adherence to treatment, increase dosage of antidepressants, and psychotherapy as first steps. PROSPERO REGISTRATION NUMBER CRD42016043364.
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Affiliation(s)
- Franciele Cordeiro Gabriel
- Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, São Paulo, Brasil
| | - Airton Tetelbom Stein
- Departamento de Saúde Coletiva, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brasil
- Curso de Pós-graduação em Avaliação de Tecnologia em Saúde, Hospital Conceição, Porto Alegre, Rio Grande do Sul, Brasil
| | - Daniela Oliveira de Melo
- Departamento de Ciências Farmacêuticas, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, São Paulo, Brasil
| | | | - Itamires Benício Dos Santos
- Departamento de Ciências Farmacêuticas, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, São Paulo, Brasil
| | | | - Renério Fráguas
- Laboratório de Neuro-imagem em Psiquiatria - LIM-21, Departamento e Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo; Divisão de Psiquiatria e Psicologia, Hospital Universitário, Universidade de São Paulo, São Paulo, São Paulo, Brasil
| | - Eliane Ribeiro
- Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, São Paulo, Brasil
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Ch S, Sudha S, Reddy CG, T P, KSBS KS, Dasari P, Battula P, T N, A S. A Comparative Study on Safety and Efficacy of Desvenlafaxine Versus Sertraline in Depression. Cureus 2022; 14:e22717. [PMID: 35371643 PMCID: PMC8971119 DOI: 10.7759/cureus.22717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/28/2022] [Indexed: 11/10/2022] Open
Abstract
Background Depression is one of the most predominant mental health issues that are prevalent now. Therefore, many clinical trials were being conducted to find the safest, most effective, and tolerable anti-depressant. This study aims to compare desvenlafaxine and sertraline regarding their safety and efficacy in treating depression. Methodology The patients who were diagnosed with depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria were included in the study and were divided into two groups. The severity of depression in these patients was evaluated using Beck Depression Inventory and Hamilton depression scale (HAM-D) before and after the treatment (four weeks). Results About 64% of the study sample were males, and 36% were females, with 77% of the patients in the desvenlafaxine group taking 100 mg dosage and about 74% patients taking 50 mg dosage in the sertraline group. The patients in both groups showed statistically significant (p < 0.00001) improvement after using these drugs. Conclusion Both desvenlafaxine and sertraline showed their efficacy in treating depression by improving the clinical outcome in patients. Sertraline was marginally better in clinical results. Finally, it is advisable to carry out more randomized trials to improve the patient’s quality of life.
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Pharmacologic Treatment for Perinatal Mental Health Disorders. Obstet Gynecol 2022; 139:297-303. [DOI: 10.1097/aog.0000000000004638] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Accepted: 10/21/2021] [Indexed: 11/25/2022]
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Moraga-Amaro R, Guerrin CGJ, Reali Nazario L, Lima Giacobbo B, J O Dierckx RA, Stehberg J, de Vries EFJ, Doorduin J. A single dose of ketamine cannot prevent protracted stress-induced anhedonia and neuroinflammation in rats. Stress 2022; 25:145-155. [PMID: 35384793 DOI: 10.1080/10253890.2022.2045269] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Worldwide, millions of people suffer from treatment-resistant depression. Ketamine, a glutamatergic receptor antagonist, can have a rapid antidepressant effect even in treatment-resistant patients. A proposed mechanism for the antidepressant effect of ketamine is the reduction of neuroinflammation. To further explore this hypothesis, we investigated whether a single dose of ketamine can modulate protracted neuroinflammation in a repeated social defeat (RSD) stress rat model, which resembles features of depression. To this end, male animals exposed to RSD were injected with ketamine (20 mg/kg) or vehicle. A combination of behavioral analyses and PET scans of the inflammatory marker TSPO in the brain were performed. Rats submitted to RSD showed anhedonia-like behavior in the sucrose preference test, decreased weight gain, and increased TSPO levels in the insular and entorhinal cortices, as observed by [11C]-PK11195 PET. Whole brain TSPO levels correlated with corticosterone levels in several brain regions of RSD exposed animals, but not in controls. Ketamine injection 1 day after RSD disrupted the correlation between TSPO levels and serum corticosterone levels, but had no effect on depressive-like symptoms, weight gain or the protracted RSD-induced increase in TSPO expression in male rats. These results suggest that ketamine does not exert its effect on the hypothalamic-pituitary-adrenal axis by modulation of neuroinflammation.
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Affiliation(s)
- Rodrigo Moraga-Amaro
- Department of Nuclear Medicine and Medical Imaging, University Medical Center Groningen, University of Groningen, Groningen, GZ, The Netherlands
| | - Cyprien G J Guerrin
- Department of Nuclear Medicine and Medical Imaging, University Medical Center Groningen, University of Groningen, Groningen, GZ, The Netherlands
| | - Luiza Reali Nazario
- Department of Nuclear Medicine and Medical Imaging, University Medical Center Groningen, University of Groningen, Groningen, GZ, The Netherlands
| | - Bruno Lima Giacobbo
- Department of Nuclear Medicine and Medical Imaging, University Medical Center Groningen, University of Groningen, Groningen, GZ, The Netherlands
| | - Rudi A J O Dierckx
- Department of Nuclear Medicine and Medical Imaging, University Medical Center Groningen, University of Groningen, Groningen, GZ, The Netherlands
| | - Jimmy Stehberg
- Laboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina y Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, Chile
| | - Erik F J de Vries
- Department of Nuclear Medicine and Medical Imaging, University Medical Center Groningen, University of Groningen, Groningen, GZ, The Netherlands
| | - Janine Doorduin
- Department of Nuclear Medicine and Medical Imaging, University Medical Center Groningen, University of Groningen, Groningen, GZ, The Netherlands
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Benoit JRA, Dursun SM, Greiner R, Cao B, Brown MRG, Lam RW, Greenshaw AJ. Using Machine Learning to Predict Remission in Patients With Major Depressive Disorder Treated With Desvenlafaxine. CANADIAN JOURNAL OF PSYCHIATRY. REVUE CANADIENNE DE PSYCHIATRIE 2022; 67:39-47. [PMID: 34379019 PMCID: PMC8808003 DOI: 10.1177/07067437211037141] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Major depressive disorder (MDD) is a common and burdensome condition that has low rates of treatment success for each individual treatment. This means that many patients require several medication switches to achieve remission; selecting an effective antidepressant is typically a sequential trial-and-error process. Machine learning techniques may be able to learn models that can predict whether a specific patient will respond to a given treatment, before it is administered. This study uses baseline clinical data to create a machine-learned model that accurately predicts remission status for a patient after desvenlafaxine (DVS) treatment. METHODS We applied machine learning algorithms to data from 3,399 MDD patients (90% of the 3,776 subjects in 11 phase-III/IV clinical trials, each described using 92 features), to produce a model that uses 26 of these features to predict symptom remission, defined as an 8-week Hamilton Depression Rating Scale score of 7 or below. We evaluated that learned model on the remaining held-out 10% of the data (n = 377). RESULTS Our resulting classifier, a trained linear support vector machine, had a holdout set accuracy of 69.0%, significantly greater than the probability of classifying a patient correctly by chance. We demonstrate that this learning process is stable by repeatedly sampling part of the training dataset and running the learner on this sample, then evaluating the learned model on the held-out instances of the training set; these runs had an average accuracy of 67.0% ± 1.8%. CONCLUSIONS Our model, based on 26 clinical features, proved sufficient to predict DVS remission significantly better than chance. This may allow more accurate use of DVS without waiting 8 weeks to determine treatment outcome, and may serve as a first step toward changing psychiatric care by incorporating clinical assistive technologies using machine-learned models.
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Affiliation(s)
- James R A Benoit
- Faculty of Nursing, 98623University of Alberta, Edmonton, Alberta
| | - Serdar M Dursun
- Department of Psychiatry, 3158University of Alberta, Edmonton, Alberta
| | - Russell Greiner
- Department of Psychiatry, 3158University of Alberta, Edmonton, Alberta.,Department of Computing Science, 3158University of Alberta, Edmonton, Alberta
| | - Bo Cao
- Department of Psychiatry, 3158University of Alberta, Edmonton, Alberta
| | - Matthew R G Brown
- Department of Computing Science, 3158University of Alberta, Edmonton, Alberta
| | - Raymond W Lam
- Department of Psychiatry, University of British Columbia, Vancouver, British Columbia
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Chen CM, Ding H, Mabry KM, Ko MC. Enhanced antidepressant-like effects of a delta opioid receptor agonist, SNC80, in rats under inflammatory pain. Pharmacol Biochem Behav 2022; 214:173341. [DOI: 10.1016/j.pbb.2022.173341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 01/18/2022] [Accepted: 01/25/2022] [Indexed: 10/19/2022]
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Chauhan M, Parry R, Bobo WV. Vilazodone for Major Depression in Adults: Pharmacological Profile and an Updated Review for Clinical Practice. Neuropsychiatr Dis Treat 2022; 18:1175-1193. [PMID: 35726313 PMCID: PMC9206504 DOI: 10.2147/ndt.s279342] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 06/08/2022] [Indexed: 12/16/2022] Open
Abstract
This article provides an updated review of the pharmacological profile and available efficacy and tolerability/safety data for vilazodone, one of the most recent antidepressant drugs to be approved in the USA for the treatment of major depressive disorder (MDD) in adults. The efficacy of vilazodone for MDD in adults is supported by four positive short-term (8-10 weeks), randomized, placebo-controlled trials. Beyond these pivotal trials, we review updated research findings pertaining to the clinical effects of vilazodone for MDD including the results of switch studies, small comparative efficacy trials, key pooled and secondary data analyses focused on important depressive subtypes (anxious depression) and predictors of treatment outcome, and safety studies including direct studies of sexual side-effects. Despite these additional research efforts and use for over a decade, important gaps in the clinical evidence base remain with vilazodone. Hypothesized differences in efficacy and adverse effects between other antidepressants and vilazodone based on its multimodal mechanism of action (combining serotonin reuptake inhibition with serotonin 5-HT1A partial agonist effects) have not been comprehensively demonstrated in clinical studies and its effectiveness as a continuation- or maintenance-phase therapeutic is not yet established. Questions remain regarding its reproductive and lactational safety profiles and its efficacy as a potential next-step therapeutic for patients with MDD who do not respond to first-line antidepressants such as selective serotonin reuptake inhibitors. Suggestions for clinical use of vilazodone and discussion of its place among the broad range of pharmacotherapies for adults with MDD are provided.
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Affiliation(s)
- Mohit Chauhan
- Department of Psychiatry & Psychology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Rebecca Parry
- Department of Psychiatry & Psychology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - William V Bobo
- Department of Psychiatry & Psychology, Mayo Clinic Florida, Jacksonville, FL, USA.,Center for Individualized Medicine, Mayo Clinic Florida, Jacksonville, FL, USA
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Mahran A, GamalEl Din S, Ezzat A, Taha A, Ragab A. Effect of drug naïve versus escitalopram on sexual function of depressed females: A cross-sectional comparative study. SEXOLOGIES 2021. [DOI: 10.1016/j.sexol.2021.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Kim IB, Park SC. Machine Learning-Based Definition of Symptom Clusters and Selection of Antidepressants for Depressive Syndrome. Diagnostics (Basel) 2021; 11:1631. [PMID: 34573974 PMCID: PMC8468112 DOI: 10.3390/diagnostics11091631] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 09/03/2021] [Accepted: 09/03/2021] [Indexed: 12/30/2022] Open
Abstract
The current polythetic and operational criteria for major depression inevitably contribute to the heterogeneity of depressive syndromes. The heterogeneity of depressive syndrome has been criticized using the concept of language game in Wittgensteinian philosophy. Moreover, "a symptom- or endophenotype-based approach, rather than a diagnosis-based approach, has been proposed" as the "next-generation treatment for mental disorders" by Thomas Insel. Understanding the heterogeneity renders promise for personalized medicine to treat cases of depressive syndrome, in terms of both defining symptom clusters and selecting antidepressants. Machine learning algorithms have emerged as a tool for personalized medicine by handling clinical big data that can be used as predictors for subtype classification and treatment outcome prediction. The large clinical cohort data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D), Combining Medications to Enhance Depression Outcome (CO-MED), and the German Research Network on Depression (GRND) have recently began to be acknowledged as useful sources for machine learning-based depression research with regard to cost effectiveness and generalizability. In addition, noninvasive biological tools such as functional and resting state magnetic resonance imaging techniques are widely combined with machine learning methods to detect intrinsic endophenotypes of depression. This review highlights recent studies that have used clinical cohort or brain imaging data and have addressed machine learning-based approaches to defining symptom clusters and selecting antidepressants. Potentially applicable suggestions to realize machine learning-based personalized medicine for depressive syndrome are also provided herein.
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Affiliation(s)
- Il Bin Kim
- Department of Psychiatry, Hanyang University Guri Hospital, Guri 11923, Korea;
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea
| | - Seon-Cheol Park
- Department of Psychiatry, Hanyang University Guri Hospital, Guri 11923, Korea;
- Department of Psychiatry, Hanyang University College of Medicine, Seoul 04763, Korea
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Wolff J, Reißner P, Hefner G, Normann C, Kaier K, Binder H, Hiemke C, Toto S, Domschke K, Marschollek M, Klimke A. Pharmacotherapy, drug-drug interactions and potentially inappropriate medication in depressive disorders. PLoS One 2021; 16:e0255192. [PMID: 34293068 PMCID: PMC8297778 DOI: 10.1371/journal.pone.0255192] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 07/11/2021] [Indexed: 12/24/2022] Open
Abstract
Introduction The aim of this study was to describe the number and type of drugs used to treat depressive disorders in inpatient psychiatry and to analyse the determinants of potential drug-drug interactions (pDDI) and potentially inappropriate medication (PIM). Methods Our study was part of a larger pharmacovigilance project funded by the German Innovation Funds. It included all inpatients with a main diagnosis in the group of depressive episodes (F32, ICD-10) or recurrent depressive disorders (F33) discharged from eight psychiatric hospitals in Germany between 1 October 2017 and 30 September 2018 or between 1 January and 31 December 2019. Results The study included 14,418 inpatient cases. The mean number of drugs per day was 3.7 (psychotropic drugs = 1.7; others = 2.0). Thirty-one percent of cases received at least five drugs simultaneously (polypharmacy). Almost one half of all cases received a combination of multiple antidepressant drugs (24.8%, 95% CI 24.1%–25.5%) or a treatment with antidepressant drugs augmented by antipsychotic drugs (21.9%, 95% CI 21.3%–22.6%). The most frequently used antidepressants were selective serotonin reuptake inhibitors, followed by serotonin and norepinephrine reuptake inhibitors and tetracyclic antidepressants. In multivariate analyses, cases with recurrent depressive disorders and cases with severe depression were more likely to receive a combination of multiple antidepressant drugs (Odds ratio recurrent depressive disorder: 1.56, 95% CI 1.41–1.70, severe depression 1.33, 95% CI 1.18–1.48). The risk of any pDDI and PIM in elderly patients increased substantially with each additional drug (Odds Ratio: pDDI 1.32, 95% CI: 1.27–1.38, PIM 1.18, 95% CI: 1.14–1.22) and severity of disease (Odds Ratio per point on CGI-Scale: pDDI 1.29, 95% CI: 1.11–1.46, PIM 1.27, 95% CI: 1.11–1.44), respectively. Conclusion This study identified potential sources and determinants of safety risks in pharmacotherapy of depressive disorders and provided additional data which were previously unavailable. Most inpatients with depressive disorders receive multiple psychotropic and non-psychotropic drugs and pDDI and PIM are relatively frequent. Patients with a high number of different drugs must be intensively monitored in the management of their individual drug-related risk-benefit profiles.
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Affiliation(s)
- Jan Wolff
- Peter L. Reichertz Institute for Medical Informatics of TU Braunschweig and Hannover Medical School, Hannover, Germany
- Faculty of Medicine, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany
- Evangelical Foundation Neuerkerode, Braunschweig, Germany
- * E-mail: ,
| | | | - Gudrun Hefner
- Vitos Clinic for Forensic Psychiatry, Eltville, Germany
| | - Claus Normann
- Faculty of Medicine, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany
| | - Klaus Kaier
- Faculty of Medicine, Institute of Medical Biometry and Statistics, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany
| | - Harald Binder
- Faculty of Medicine, Institute of Medical Biometry and Statistics, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany
| | - Christoph Hiemke
- Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany
| | - Sermin Toto
- Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany
| | - Katharina Domschke
- Faculty of Medicine, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany
| | - Michael Marschollek
- Peter L. Reichertz Institute for Medical Informatics of TU Braunschweig and Hannover Medical School, Hannover, Germany
| | - Ansgar Klimke
- Vitos Hochtaunus, Friedrichsdorf, Germany
- Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
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Viswanathan M, Middleton JC, Stuebe AM, Berkman ND, Goulding AN, McLaurin‐Jiang S, Dotson AB, Coker‐Schwimmer M, Baker C, Voisin CE, Bann C, Gaynes BN. Maternal, Fetal, and Child Outcomes of Mental Health Treatments in Women: A Meta-Analysis of Pharmacotherapy. PSYCHIATRIC RESEARCH AND CLINICAL PRACTICE 2021; 3:123-140. [PMID: 36101835 PMCID: PMC9175843 DOI: 10.1176/appi.prcp.20210001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 02/19/2021] [Accepted: 03/24/2021] [Indexed: 11/30/2022] Open
Abstract
Objective The authors systematically reviewed evidence on pharmacotherapy for perinatal mental health disorders. Methods The authors searched for studies of pregnant, postpartum, or reproductive-age women with mental health disorders treated with pharmacotherapy in MEDLINE, EMBASE, PsycINFO, the Cochrane Library, and trial registries from database inception through June 5, 2020 and surveilled literature through March 2, 2021. Outcomes included symptoms; functional capacity; quality of life; suicidal events; death; and maternal, fetal, infant, or child adverse events. Results 164 studies were included. Regarding benefits, brexanolone for third-trimester or postpartum depression onset may be associated with improved depressive symptoms at 30 days when compared with placebo. Sertraline for postpartum depression may be associated with improved response, remission, and depressive symptoms when compared with placebo. Discontinuing mood stabilizers during pregnancy may be associated with increased recurrence of mood episodes for bipolar disorder. Regarding adverse events, most studies were observational and unable to fully account for confounding. Evidence on congenital and cardiac anomalies for treatment compared with no treatment was inconclusive. Brexanolone for depression onset in the third trimester or the postpartum period may be associated with risk of sedation or somnolence, leading to dose interruption or reduction when compared with placebo. Conclusions Evidence from few studies supports the use of pharmacotherapy for perinatal mental health disorders. Although many studies report on adverse events, they could not rule out underlying disease severity as the cause of the association between exposures and adverse events. Patients and clinicians need to make informed, collaborative decisions on treatment choices.
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Affiliation(s)
- Meera Viswanathan
- RTI International–University of North Carolina at Chapel Hill Evidence‐based Practice CenterChapel HillUSA
- RTI InternationalResearch Triangle ParkChapel HillNorth CarolinaUSA
| | - Jennifer Cook Middleton
- RTI International–University of North Carolina at Chapel Hill Evidence‐based Practice CenterChapel HillUSA
- Cecil G. Sheps Center for Health Services ResearchUniversity of North Carolina at Chapel HillChapel HillUSA
| | - Alison M. Stuebe
- Department of Obstetrics and GynecologyUniversity of North Carolina School of MedicineChapel HillUSA
- Department of Maternal and Child HealthGillings School of Global Public HealthUniversity of North Carolina at Chapel HillChapel HillUSA
| | - Nancy D. Berkman
- RTI International–University of North Carolina at Chapel Hill Evidence‐based Practice CenterChapel HillUSA
- RTI InternationalResearch Triangle ParkChapel HillNorth CarolinaUSA
| | - Alison N. Goulding
- Department of Obstetrics and GynecologyUniversity of North Carolina School of MedicineChapel HillUSA
| | - Skyler McLaurin‐Jiang
- Cecil G. Sheps Center for Health Services ResearchUniversity of North Carolina at Chapel HillChapel HillUSA
| | - Andrea B. Dotson
- Cecil G. Sheps Center for Health Services ResearchUniversity of North Carolina at Chapel HillChapel HillUSA
| | - Manny Coker‐Schwimmer
- RTI International–University of North Carolina at Chapel Hill Evidence‐based Practice CenterChapel HillUSA
- Cecil G. Sheps Center for Health Services ResearchUniversity of North Carolina at Chapel HillChapel HillUSA
| | - Claire Baker
- RTI International–University of North Carolina at Chapel Hill Evidence‐based Practice CenterChapel HillUSA
- Cecil G. Sheps Center for Health Services ResearchUniversity of North Carolina at Chapel HillChapel HillUSA
| | - Christiane E. Voisin
- RTI International–University of North Carolina at Chapel Hill Evidence‐based Practice CenterChapel HillUSA
- Cecil G. Sheps Center for Health Services ResearchUniversity of North Carolina at Chapel HillChapel HillUSA
| | - Carla Bann
- RTI International–University of North Carolina at Chapel Hill Evidence‐based Practice CenterChapel HillUSA
- RTI InternationalResearch Triangle ParkChapel HillNorth CarolinaUSA
| | - Bradley N. Gaynes
- RTI International–University of North Carolina at Chapel Hill Evidence‐based Practice CenterChapel HillUSA
- Department of PsychiatryUniversity of North Carolina School of MedicineChapel HillUSA
- Department of Epidemiology|Gillings Global School of Public HealthUniversity of North Carolina at Chapel HillChapel HillUSA
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Use of Complementary Alternative Medicine and the Associated Factors among Patients with Depression. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:6626394. [PMID: 33854557 PMCID: PMC8019377 DOI: 10.1155/2021/6626394] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 03/10/2021] [Accepted: 03/18/2021] [Indexed: 02/03/2023]
Abstract
Complementary Alternative Medicine (CAM) has been widely used in the world, but limited data are available on the use of CAM in depression. This study aimed to evaluate the use of CAM and its associated factors in depression. This cross-sectional study was conducted on 300 depressed patients referred to the Yasuj Neurology and Psychiatric Clinic, southern Iran, between 2019 and 2020. A valid semistructured international questionnaire was used; amongst the participants, 230 (77%) were female. The mean age of the patients was 41.47 ± 12.2 years and the mean duration of the disease was 4.49 ± 4.88 years. The prevalence of CAM use was 37.6% among the patients. The results showed a significant difference between the CAM users and nonusers regarding the disease duration (p=0.045) and body mass index (p=0.007). Moreover, the results of logistic regression analysis revealed a significant relationship between CAM use and female gender, disease duration, overweight, obesity, and self-employment (p=0.039, p=0.028, p=0.029, p=0.048, and p=0.044, resp.). The most frequently used type of CAM was herbal medicine (97.35%) followed by pray therapy (23.89%). Additionally, the most widely used herbs were borage (77%), chamomile (46.9%), and lavender (21.2%). Furthermore, 62.8% of the patients reported that their main reason for using CAM was its effectiveness. The majority of the patients (77%) had not consulted their physicians prior to utilization of CAM therapies. Herbal medicine was the most common form of CAM in depression, with a high satisfaction level. Thus, it is necessary to increase physicians' awareness in different fields of CAM.
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