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Aprile SF, Rodolico A, Di Francesco A, Varrasi S, Bighelli I, Castellano S, Signorelli MS, Leucht S, Caraci F. Oral versus long-acting injectable antipsychotics in schizophrenia spectrum disorders: A systematic review of patients' subjective experiences. Psychiatry Res 2025; 348:116460. [PMID: 40158367 DOI: 10.1016/j.psychres.2025.116460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 03/20/2025] [Accepted: 03/23/2025] [Indexed: 04/02/2025]
Abstract
Schizophrenia spectrum disorders significantly impact daily functioning, with antipsychotic medications regarded as the gold standard treatment. However, their efficacy is often limited by side effects and adherence rates. Understanding patient perspectives and subjective experiences, particularly regarding oral versus long-acting injectable (LAI) antipsychotics, is crucial for improving medication outcomes and patient-tailored treatments. A systematic review of qualitative studies was conducted following the ENTREQ guidelines. Data were extracted from PubMed, Scopus, and PsycInfo, with thematic synthesis used to identify key themes in patient-reported experiences. Thirty-nine studies (1.477 patients) were included and analyzed, revealing three core themes: (1) perception and experience of medication, (2) social dynamics and influence, and (3) trust and communication with healthcare providers. Side effects and lack of information were often mentioned by patients. While LAI antipsychotics were linked to symptom stability and functional improvements, many patients lacked adequate information about their effects, contributing to adherence difficulties. Stigma and negative beliefs were common across both oral and LAI formulations, thus determining significant barriers to medication adherence. This review emphasizes that patients' experiences with antipsychotic medications are shaped by three key factors: the environment, the therapeutic relationship, and the drug itself. Two critical areas warrant particular attention: psychoeducation and stigma. Bridging psychoeducational gaps and addressing stigma could significantly enhance treatment adherence and outcomes. Additionally, greater emphasis on providing comprehensive and accurate information about antipsychotic treatment options is essential to support patient-centred care and informed decision-making.
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Affiliation(s)
- Sofia Francesca Aprile
- Department of Educational Sciences, Section of Psychology, University of Catania, Via Teatro Greco 84, 95124 Catania, Italy
| | - Alessandro Rodolico
- Technical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Munich, Germany; Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy
| | - Antonio Di Francesco
- Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy
| | - Sofia Varrasi
- Department of Drug and Health Sciences, Viale Andrea Doria 6, 95123 , University of Catania, Catania, Italy
| | - Irene Bighelli
- Technical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Munich, Germany; German Center for Mental Health, Berlin, Germany
| | - Sabrina Castellano
- Department of Educational Sciences, Section of Psychology, University of Catania, Via Teatro Greco 84, 95124 Catania, Italy
| | - Maria Salvina Signorelli
- Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy; Oasi Research Institute - IRCCS, Via Conte Ruggero 73, 94018 Troina, Italy
| | - Stefan Leucht
- Technical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Munich, Germany; German Center for Mental Health, Berlin, Germany
| | - Filippo Caraci
- Department of Drug and Health Sciences, Viale Andrea Doria 6, 95123 , University of Catania, Catania, Italy; Oasi Research Institute - IRCCS, Via Conte Ruggero 73, 94018 Troina, Italy.
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Yadav G, Ashraf S, Saad M, Mian N, Naveed MA, Ali A, Husain K, Mansuri Z, Jain S. Trends and disparities in schizophrenia related mortality in the United States: An analysis of CDC WONDER database, 1999-2020. Asian J Psychiatr 2025; 108:104496. [PMID: 40250200 DOI: 10.1016/j.ajp.2025.104496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 03/28/2025] [Accepted: 04/11/2025] [Indexed: 04/20/2025]
Abstract
BACKGROUND Schizophrenia is a mental health condition that typically begins between ages 18 and 25, significantly impairs daily functioning, ranks among the leading causes of disability worldwide, and is associated with a shortened lifespan. Mortality in schizophrenia is often linked to cardiovascular disease, driven by poor lifestyle choices, limited access to physical healthcare, frequent comorbidities, and non-compliance with antipsychotic medications. This article analyzes mortality trends among U.S. adults aged 35-85 + years with schizophrenia from 1999 to 2020 using CDC Wonder data, contributing valuable insights to the existing literature on this topic. METHOD Data from death certificates between 1999 and 2020 were obtained from the CDC WONDER database using ICD-10 code F20 to identify deaths where schizophrenia was listed as a primary or contributing cause, covering all 50 states and the District of Columbia. Demographic data, including race/ethnicity, age, and gender, and information on the place, year, and setting of death-residences, hospices, nursing homes/long-term care facilities, and medical institutions-were collected. We analyzed schizophrenia-related mortality trends in the U.S. from 1999 to 2020. We used the Joinpoint Regression Program (Version 5.1.0, National Cancer Institute) to calculate the annual percent change (APC) and Average Annual Percentage Change (AAPC) in AAMR, along with their 95 % CIs, to identify significant trends over time. Statistical significance was set at P < 0.05. RESULTS We identified 80,836 schizophrenia-related deaths, with the highest proportion occurring in nursing homes and long-term care facilities. The overall age-adjusted mortality rate (AAMR) rose from 23.9 in 1999-27.2 in 2020. Notably, the AAMR decreased between 1999 and 2015, with a significant increase from 2015 to 2020. CONCLUSIONS This study reveals an increase in the age-adjusted mortality rate (AAMR) for schizophrenia-related deaths among adults from 1999 to 2020, which highlights critical insights for healthcare professionals and policymakers. Further research is needed to identify modifiable factors to reduce morbidity and mortality, potentially easing the burden on healthcare resources and improving the quality of life for those with schizophrenia. Understanding these trends is essential for addressing gaps in the healthcare system and directing resources to areas of greatest need.
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Affiliation(s)
- Garima Yadav
- Department of Psychiatry, Texas Tech University and Health Sciences Center, Permian Basin, United States.
| | - Sahar Ashraf
- Department of Psychiatry, Texas Tech University and Health Sciences Center, Permian Basin, United States
| | - Muhammad Saad
- Department of Psychiatry, Texas Tech University and Health Sciences Center, Permian Basin, United States
| | - Nadeem Mian
- Department of Psychiatry, Texas Tech University and Health Sciences Center, Permian Basin, United States
| | - Muhammad Abdullah Naveed
- Department of Psychiatry, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Ahila Ali
- Department of Psychiatry, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Karrar Husain
- Department of Psychiatry, Texas Tech University and Health Sciences Center, Permian Basin, United States
| | - Zeeshan Mansuri
- Department of Psychiatry, Yale New Haven School of Medicine, CT, United States
| | - Shailesh Jain
- Department of Psychiatry, Texas Tech University and Health Sciences Center, Permian Basin, United States
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3
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Chauhan R, Mohan M, Mannan A, Devi S, Singh TG. Unravelling the role of Interleukin-12 in Neuroinflammatory mechanisms: Pathogenic pathways linking Neuroinflammation to neuropsychiatric disorders. Int Immunopharmacol 2025; 156:114654. [PMID: 40294470 DOI: 10.1016/j.intimp.2025.114654] [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: 12/12/2024] [Revised: 04/08/2025] [Accepted: 04/08/2025] [Indexed: 04/30/2025]
Abstract
Neuropsychiatric disorders are clinically characterized conditions involving both neurology and psychiatry, arising from dysfunctioning of cerebral function, or indirect effects of extra cerebral disease. Neuropsychiatric disorders tend to influence emotions, mood, and brain functioning. Growing evidence indicates that the etiology of these disorders is not confined to neuronal abnormalities but extends to include inflammation. While the underlying mechanism of these disorders is still in its infancy, recent data highlights the significant role of neuroinflammation in their pathophysiology. Neuroinflammation concerns the inflammation within the neural tissue characterized by alteration in astrocytes, cytokines, microglia, and chemokines within the central nervous system. The cytokines include IFN-γ, IL-1β, IL-2, IL4, IL-6, IL-8, IL-10, and IL-12. This review focuses on interleukin-12 (IL-12), a key mediator of neuroinflammation, and its potential involvement in neuropsychiatric disorders. IL-12 promotes neuroinflammation and influences neurotransmitter systems. Additionally, it also affects the HPA axis, impairs neuroplasticity, and activates microglia by interacting with TLR, JAK-STAT, PI3K/Akt, GSK-3, NMDA, MAPK, PKC, VEGFR, ROCK, and Wnt signaling pathways and elicit its role in ND. In this review, we dwell on the current evidence supporting IL-12's pathogenic role and explore the possible mechanisms by which it contributes to the development and progression of these conditions. This review aims to provide insights that may aid in future therapeutic strategies by illuminating the interplay between neuroinflammation and neuropsychiatric disorders.
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Affiliation(s)
- Rupali Chauhan
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India
| | - Maneesh Mohan
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India
| | - Ashi Mannan
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.
| | - Sushma Devi
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India
| | - Thakur Gurjeet Singh
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.
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Zuccarello P, Carnazza G, Petralia A, Barbera N. Post Mortem Paliperidone Blood Concentrations Following Long-Acting Injectable Treatments. Diagnostics (Basel) 2025; 15:1290. [PMID: 40428283 PMCID: PMC12109829 DOI: 10.3390/diagnostics15101290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Revised: 05/04/2025] [Accepted: 05/19/2025] [Indexed: 05/29/2025] Open
Abstract
Background/Objectives: I Paliperidone is an antipsychotic recently added into the market in various formulations. There are few data about safety and on therapeutic, toxic, or lethal blood concentrations. Currently, the published analytical methods are often applied to serum or plasma that are not obtained from cadaveric blood. Alternatively, aliquots of high volume of whole blood are used, but often in forensic investigations using samples at very small quantities. The aims of the present study were (a) to develop an analytical method to detect and quantify paliperidone in whole blood using only a small sample volume (10 µL) and (b) to summarize data on post-mortem blood analysis obtained from authentic autopsy cases. Methods: Method validation was carried out on 10 µL of whole blood, extracted by LLE and analyzed by LC-MS. Paliperidone concentrations obtained from blood analysis of 16 authentic autopsy cases were reported. Results: The method showed a good linearity and sensitivity, a normal distribution, the absence of anomalous values, an interday RSD% always less than 10%, and an 80-120% recovery, as required by AAFS guidelines. Femoral blood concentrations obtained from authentic autopsy cases ranged between 23.4 and 146.9 ng/mL. Conclusions: This method is to be used properly in all cases where it is necessary (a) to monitor the therapeutic adherence of patients, (b) to establish the psycho-physical conditions of the treated subject at the time of the death, and (c) to ascertain if the drug may have played a causal role in the obitus. This study reported the first data obtained from post-mortem investigation of subjects treated with paliperidone LAI. Cadaveric blood concentrations could be higher than ante-mortem reference values due to post-mortem redistribution.
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Affiliation(s)
- Pietro Zuccarello
- Department of Psychology and Health Sciences, Pegaso Telematic University, 80143 Naples, Italy
| | - Giulia Carnazza
- Department of Medical, Surgical and Advanced Technologies Sciences “G.F. Ingrassia”, University of Catania, 95125 Catania, Italy; (G.C.); (N.B.)
| | - Antonino Petralia
- Psychiatry Unit, Department of Clinical and Experimental Medicine, School of Medicine, University of Catania, 95123 Catania, Italy;
| | - Nunziata Barbera
- Department of Medical, Surgical and Advanced Technologies Sciences “G.F. Ingrassia”, University of Catania, 95125 Catania, Italy; (G.C.); (N.B.)
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Laimou-Geraniou M, Quireyns M, Boogaerts T, Heath D, Covaci A, van Nuijs ALN, Heath E. Stability of antipsychotic biomarkers for wastewater-based epidemiology. J Pharm Biomed Anal 2025; 257:116702. [PMID: 39879822 DOI: 10.1016/j.jpba.2025.116702] [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: 09/11/2024] [Revised: 01/23/2025] [Accepted: 01/23/2025] [Indexed: 01/31/2025]
Abstract
Wastewater-based epidemiology (WBE) offers a promising approach by providing objective data on antipsychotic drug consumption within a population that can be used to monitor abuse, misuse, and regional prescription patterns. However, accurate estimations depend on knowing the stability of drug biomarkers. This study provides a comprehensive analysis of the stability of 11 antipsychotic biomarkers (parent drugs and their metabolites) in influent wastewater, using a series of experiments mimicking in-sewer transport (in-sewer setup and deconjugation) and in-sample stability (benchtop, frozen cartridge, long-term sample storage, and freeze-thaw). In-sample stability experiments are exposed to various conditions (i.e., filtration, acidification) commonly used for storage. The results reveal compound-specific stability profiles, with quetiapine showing notable high stability across most experiments. In contrast, N-desmethylolanzapine and dehydroaripiprazole demonstrated rapid degradation. Acidification before storage led to significant degradation of some compounds, decreasing the accuracy of WBE consumption estimates and rendering it unsuitable as a sample storage method. Overall, the study found that compound-specific degradation patterns underscore the necessity for tailored analytical approaches when using WBE to monitor antipsychotic drug use. Future research should focus on bioreactor studies mimicking in-sewer conditions and the application of correction factors to enhance the accuracy of consumption estimates, facilitating more reliable public health surveillance through WBE.
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Affiliation(s)
- Maria Laimou-Geraniou
- Jožef Stefan Institute, Jamova 39, Ljubljana 1000, Slovenia; Jožef Stefan International Postgraduate School, Jamova 39, Ljubljana 1000, Slovenia
| | - Maarten Quireyns
- Toxicological Centre, University of Antwerp, Universiteitsplein 1, Wilrijk 2610, Belgium
| | - Tim Boogaerts
- Toxicological Centre, University of Antwerp, Universiteitsplein 1, Wilrijk 2610, Belgium
| | - David Heath
- Jožef Stefan Institute, Jamova 39, Ljubljana 1000, Slovenia
| | - Adrian Covaci
- Toxicological Centre, University of Antwerp, Universiteitsplein 1, Wilrijk 2610, Belgium
| | | | - Ester Heath
- Jožef Stefan Institute, Jamova 39, Ljubljana 1000, Slovenia; Jožef Stefan International Postgraduate School, Jamova 39, Ljubljana 1000, Slovenia.
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Crutzen S, Gangadin S, Hua KH, Visser E, Jörg F, van der Meer L, Pijnenborg GHM, Veling W, Castelein S. Trends in Antipsychotic Polypharmacy and Potential Overtreatment with Antipsychotics: A Naturalistic Cohort Study of People in Long-term Care. Schizophr Bull 2025:sbaf041. [PMID: 40329432 DOI: 10.1093/schbul/sbaf041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/08/2025]
Abstract
BACKGROUND Due to the side effects of antipsychotics, overtreatment is an important concern. Previous research focused on antipsychotic polypharmacy and excessively high doses. In this study, the aim is to map changes over the years in potential overtreatment, antipsychotic polypharmacy, total antipsychotic dose, and subjective side effect burden. Moreover, the association of the total dose and antipsychotic polypharmacy with the subjective side effect burden will be investigated. STUDY DESIGN Data from a naturalistic longitudinal cohort were used (PHAMOUS, 2013-2021). Potential overtreatment was defined as a antipsychotic dose equivalent to > 5 mg risperidone or antipsychotic polypharmacy, in combination with a high subjective side effect burden. Mixed effect models were used to investigate trends in potential overtreatment, antipsychotic polypharmacy, total antipsychotic dose, and subjective side effect burden and to assess the association of total dose and antipsychotic polypharmacy with subjective side effect burden. STUDY RESULTS Overall, 15,717 observations nested in 5,107 participants were used. One-third of the participants were potentially overtreated, which did not change over time. The prevalence of a dose above the equivalent of 5 mg risperidone decreased, antipsychotic polypharmacy prevalence increased, and the subjective side effect burden decreased. A higher dose and antipsychotic polypharmacy were associated with higher subjective side effect burden. CONCLUSION Potentially overtreated patients should be revaluated to assess whether changes are needed. To assess whether a patient is truly overtreated, their clinical history, number of relapses, patients' preferences, overall functioning, previous attempts to reduce antipsychotic treatment, and previous severity of disease should be taken into account.
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Affiliation(s)
- Stijn Crutzen
- Rob Giel Research Center, University Center Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Lentis Research, Lentis Psychiatric Institute, Groningen, The Netherlands
| | - Shiral Gangadin
- Rob Giel Research Center, University Center Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Ken Ho Hua
- Apotheek Spaarne Gasthuis, Spaarne Gasthuis, Haarlem/Hoofddorp, The Netherlands
| | - Ellen Visser
- Rob Giel Research Center, University Center Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Frederike Jörg
- Rob Giel Research Center, University Center Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Lisette van der Meer
- Department of Clinical & Developmental Neuropsychology, University of Groningen, 9712 TS Groningen, The Netherlands
- Department of Rehabilitation, Lentis Psychiatric Institute, 9470 AC, Zuidlaren, The Netherlands
| | - Gerdina Hendrika Maria Pijnenborg
- Faculty of Behavioural and Social Sciences, University of Groningen, Grote Kruisstraat 2/1, 9712 TS, Groningen, The Netherlands
- Department of Psychotic Disorders, GGZ Drenthe Mental Health Institution, Dennenweg 9, 9404 LA, Assen, The Netherlands
| | - Wim Veling
- Psychosis Department, University Center for Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Stynke Castelein
- Lentis Research, Lentis Psychiatric Institute, Groningen, The Netherlands
- Faculty of Behavioural and Social Sciences, University of Groningen, Grote Kruisstraat 2/1, 9712 TS, Groningen, The Netherlands
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Mohamed AA, Almulhim AS, Alnijadi AA, Abd Aziz FB, Alajmi KK, Al-Mudhaffar AA, Almutairi MS. Evaluation of Prescription Patterns of Antipsychotics in Schizophrenia Patients-A Single-Center Prospective Study. J Clin Med 2025; 14:2941. [PMID: 40363973 PMCID: PMC12072535 DOI: 10.3390/jcm14092941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 04/12/2025] [Accepted: 04/22/2025] [Indexed: 05/15/2025] Open
Abstract
Inappropriate prescription patterns and polypharmacy are critical challenges facing the optimal management of schizophrenia patients, especially in regard to patient safety. Background/Objectives: The purpose of this study was to examine the relationship between patient safety and the existence of incorrect prescription patterns and/or polypharmacy in the medications prescribed to individuals with schizophrenia. This issue is addressed in a broad context, highlighting the purpose of this study. Methods: A cross-sectional study was adopted, involving a prospective analysis of the prescriptions of schizophrenia patients receiving treatment. Prescription patterns deemed inappropriate were evaluated based on evidence-based guidelines. Antipsychotic maximum allowable daily doses were calculated using the British National Formulary Maximum Daily Dose (BNFmax), an online tool. Patient safety outcomes were assessed using the Glasgow Antipsychotic Side-effect Scale (GASS). Results: A total of 198 patients diagnosed with schizophrenia and receiving treatment consented to participate in the GASS survey. A total of 116 (58.6%) males participated. The mean age of patients was 40.1 (±12.7). Thirty-one (66.2%) reported mild side effects, while 67 (33.8%) reported moderate side effects. Polypharmacy was detected in 103 (52%) patients' prescriptions. The correlation between GASS and BNFmax was positive and statistically significant (p < 0.001). The elevation in GASS score was associated with polypharmacy prescriptions (OR 3.21; 95% CI 1.64-6.29), the presence of first-generation antipsychotics (FGAP) (OR 2.79; 95% CI 0.236-5.951), any combination of antipsychotics containing haloperidol (OR 3.22; 95% CI 1.11-9.32), and olanzapine (OR 3.46; 95% CI 1.36-8.79). Conclusions: The safety of patients with schizophrenia has been proven to be impacted by the improper use of psychotropic drugs. Following evidence-based guidelines is a cornerstone to ensuring optimal, effective, and safe patient treatment plans.
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Affiliation(s)
- Ahmed Adel Mohamed
- Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia;
| | - Abdulaziz Saleh Almulhim
- Department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Al Ahsaa 31982, Saudi Arabia;
| | - Abdulrahman Abdullah Alnijadi
- Department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Al Ahsaa 31982, Saudi Arabia;
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Urien L, Lertxundi U, Garcia M, Aguirre C, Jauregizar N, Morera-Herreras T. Oral Adverse Effects of Antipsychotic Medications: A Case/Noncase Analysis of EudraVigilance Data. Oral Dis 2025. [PMID: 40259575 DOI: 10.1111/odi.15337] [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: 12/10/2024] [Revised: 03/27/2025] [Accepted: 04/01/2025] [Indexed: 04/23/2025]
Abstract
OBJECTIVE Neuropsychiatric disorders are associated with poor oral health, with antipsychotics as potential contributors. This study aimed to analyse the oral adverse effects of antipsychotics using the EudraVigilance database. METHODS A case/noncase analysis was conducted to calculate reporting odds ratios (ROR) and assess the disproportionality of oral adverse events. RESULTS A total of 5663 reports of oral adverse effects related to antipsychotics were identified. Atypical antipsychotics had a higher overall incidence (5663 vs. 787 for typical), but typical antipsychotics showed stronger associations with specific oral issues (ROR = 2.2 vs. 1.6 for atypical). The most commonly reported effects were disturbances in salivary flow, including xerostomia and hypersalivation. Olanzapine and quetiapine were linked to dry mouth (ROR = 1.8 and 3.0) and tooth loss (ROR = 1.7 and 1.8). Clozapine had the highest number of reports (1619) and ROR (33.1) for hypersalivation. Disproportionality analysis revealed significant associations with orofacial dyskinesia for all antipsychotics, except clozapine. Aripiprazole had the highest ROR (13.7) for orofacial dyskinesia and was linked to a swollen tongue in patients aged ≤ 17 years (12 cases, ROR = 3.6). No sex-based differences were identified. CONCLUSIONS Antipsychotics significantly affect oral health, highlighting the need for preventive dental care and interventions to reduce these effects and improve patient well-being.
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Affiliation(s)
- Leire Urien
- Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
| | - Unax Lertxundi
- Bioaraba Health Research Institute; Osakidetza Basque Health Service, Araba Mental Health Network, Araba Psychiatric Hospital, Pharmacy Service, Vitoria-Gasteiz, Spain
| | - Montserrat Garcia
- Biobizkaia Health Research Institute, Osakidetza Basque Health Service, Galdakao-Usansolo Hospital, Basque Country Pharmacovigilance Unit, Galdakao, Spain
| | - Carmelo Aguirre
- Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
- Biobizkaia Health Research Institute, Osakidetza Basque Health Service, Galdakao-Usansolo Hospital, Basque Country Pharmacovigilance Unit, Galdakao, Spain
| | - Nerea Jauregizar
- Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
- Grupo Red de Salud Mental, Biobizkaia Health Research Institute, Barakaldo, Bizkaia, Spain
| | - Teresa Morera-Herreras
- Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
- Neurodegenerative Diseases Group, Biobizkaia Health Research Institute, Barakaldo, Bizkaia, Spain
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Harris K, Fosdick C, Zappia KJ, Dominick KC, Lamy M. Safety and Effectiveness of Clozapine in Youth and Young Adults with Neurodevelopmental Disorders and Severe, Treatment-Refractory Irritability and Aggression: A Retrospective Chart Review. J Child Adolesc Psychopharmacol 2025. [PMID: 40127992 DOI: 10.1089/cap.2024.0104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/26/2025]
Abstract
Objective: The purpose of this article was to review the safety, tolerability, and effectiveness of clozapine in youth and young adults with autism spectrum disorder (ASD) and/or intellectual disability. Methods: An IRB-approved retrospective chart review of youth and young adults with autism and/or intellectual disability who were prescribed clozapine between January 2012 and June 2020 was completed. Information was collected from 1 year before through 1 year after clozapine initiation related to medications prescribed, hospitalizations, emergency department (ED) visits, and Clinical Global Impressions-Severity and Clinical Global Impressions-Improvement (CGI-I) ratings. Adverse effects and reasons for stopping clozapine were documented. Results: Fifty-eight patients were included in analysis. Forty patients remained on clozapine through June 2020 and 18 did not. Most patients were prescribed clozapine for treatment of irritability. Reasons for stopping clozapine included side effects, continued behavior concerns, difficulty with blood draws, and improvement in symptoms. For those who remained on clozapine for the duration of the review period, the number of hospitalizations and ED presentations for psychiatric concerns or medical concerns potentially related to clozapine significantly decreased in the year following clozapine initiation compared with the year prior (2.13 vs. 3.48, p = 0.010). There was a significant reduction in CGI-I scores from 3.96 to 2.53 (p < 0.001) from clozapine initiation to 1 year later. There was a nonsignificant trend toward reduction in use of multiple antipsychotics simultaneously from time of clozapine initiation to 1 year later in those who remained on clozapine (38.5% vs. 25%, p = 0.232). Conclusions: Use of clozapine for treatment-refractory irritability in youth and young adults with ASD and/or intellectual disability is generally well-tolerated. Observed benefits included a decrease in number of hospitalizations and ED visits and a decrease in CGI-I score in the year after clozapine initiation.
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Affiliation(s)
- Katherine Harris
- Department of Psychiatry, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA
- Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Cara Fosdick
- Department of Psychiatry, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA
- Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Katherine J Zappia
- Department of Psychiatry, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA
- Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Kelli C Dominick
- Department of Psychiatry, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA
- Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Martine Lamy
- Department of Psychiatry, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA
- Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
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Lakshminarasimhan K, Buck J, Kellendonk C, Horga G. A corticostriatal learning mechanism linking excess striatal dopamine and auditory hallucinations. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.03.18.643990. [PMID: 40166304 PMCID: PMC11956939 DOI: 10.1101/2025.03.18.643990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
Auditory hallucinations are linked to elevated striatal dopamine, but their underlying computational mechanisms have been obscured by regional heterogeneity in striatal dopamine signaling. To address this, we developed a normative circuit model in which corticostriatal plasticity in the ventral striatum is modulated by reward prediction errors to drive reinforcement learning while that in the sensory-dorsal striatum is modulated by sensory prediction errors derived from internal belief to drive self-supervised learning. We then validate the key predictions of this model using dopamine recordings across striatal regions in mice, as well as human behavior in a hybrid learning task. Finally, we find that changes in learning resulting from optogenetic stimulation of the sensory striatum in mice and individual variability in hallucination proneness in humans are best explained by selectively enhancing dopamine levels in the model sensory striatum. These findings identify plasticity mechanisms underlying biased learning of sensory expectations as a biologically plausible link between excess dopamine and hallucinations.
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Affiliation(s)
- Kaushik Lakshminarasimhan
- Zuckerman Mind Brain Behavior Institute, Department of Neuroscience, Columbia University, New York, NY, USA
| | - Justin Buck
- Zuckerman Mind Brain Behavior Institute, Department of Neuroscience, Columbia University, New York, NY, USA
- Department of Psychiatry, Columbia University, New York, NY, USA
| | - Christoph Kellendonk
- Department of Psychiatry, Columbia University, New York, NY, USA
- Department of Molecular Pharmacology and Therapeutics, Columbia University, New York, NY, USA
| | - Guillermo Horga
- Zuckerman Mind Brain Behavior Institute, Department of Neuroscience, Columbia University, New York, NY, USA
- Department of Psychiatry, Columbia University, New York, NY, USA
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11
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Cho H, Jo H, Jeong YD, Jang W, Park J, Yim Y, Lee K, Lee H, Lee S, Fond G, Boyer L, Pizzol D, Jung J, Yon DK. Antipsychotic use during pregnancy and outcomes in pregnant individuals and newborns. J Affect Disord 2025; 373:495-504. [PMID: 39755128 DOI: 10.1016/j.jad.2024.12.102] [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: 09/02/2024] [Revised: 12/03/2024] [Accepted: 12/27/2024] [Indexed: 01/06/2025]
Abstract
BACKGROUND Despite the increasing use of antipsychotics during pregnancy, comprehensive evaluations of their individual safety profiles using global data remain limited. This study aimed to assess the safety of various antipsychotics during pregnancy by comparing them to quetiapine, which has a relatively large body of safety data. METHOD Utilizing the World Health Organization pharmacovigilance database (1968-2023; n = 131,255,418 reports), we identified 11,406 reports of antipsychotic exposure during pregnancy. A disproportionality analysis was performed to calculate reporting odds ratios (RORs) for adverse pregnancy, fetal, or neonatal outcomes associated with haloperidol, ziprasidone, clozapine, olanzapine, risperidone, aripiprazole, and paliperidone, compared to quetiapine. RESULTS Haloperidol had a significantly higher reporting frequency for congenital malformations compared to quetiapine (ROR 3.83; 95 % CI, 2.62-5.59). No statistically significant differences were found for other antipsychotics regarding congenital malformations or neonatal complications compared to quetiapine. All studied antipsychotics had lower reporting frequencies for gestational diabetes mellitus than quetiapine (overall ROR 0.22; 95 % CI, 0.18-0.28). Haloperidol, clozapine, olanzapine, risperidone, and aripiprazole were more frequently reported for abortion or stillbirth. Paliperidone and ziprasidone had similar or lower reporting frequencies for major adverse outcomes compared to quetiapine, though conclusions regarding ziprasidone are limited by the small number of reports and the relatively high proportion mentioning adverse pregnancy outcomes. LIMITATIONS Incomplete data and reporting bias hinder establishing causality. CONCLUSIONS Compared to quetiapine, several antipsychotics with less established safety data, particularly ziprasidone and paliperidone, have the potential to serve as safe alternatives for use during pregnancy. However, further research is needed to verify these findings and ensure the safety of these antipsychotics as treatment options during pregnancy.
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Affiliation(s)
- Hanseul Cho
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea
| | - Hyesu Jo
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Regulatory Science, Kyung Hee University, Seoul, South Korea
| | - Yi Deun Jeong
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea
| | - Wonwoo Jang
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea
| | - Jaeyu Park
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Regulatory Science, Kyung Hee University, Seoul, South Korea
| | - Yesol Yim
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea
| | - Kyeongmin Lee
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Regulatory Science, Kyung Hee University, Seoul, South Korea
| | - Hayeon Lee
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea
| | - Sooji Lee
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea
| | - Guillaume Fond
- Assistance Publique-Hopitaux de Marseille, Research Centre on Health Services and Quality of Life, Aix Marseille University, Marseille, France
| | - Laurent Boyer
- Assistance Publique-Hopitaux de Marseille, Research Centre on Health Services and Quality of Life, Aix Marseille University, Marseille, France
| | - Damiano Pizzol
- Health Unit Eni, Maputo, Mozambique; Health Unit, Eni, San Donato Milanese, Italy
| | - Junyang Jung
- Department of Anatomy and Neurobiology, Kyung Hee University College of Medicine, Seoul, South Korea.
| | - Dong Keon Yon
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Regulatory Science, Kyung Hee University, Seoul, South Korea; Department of Pediatrics, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea.
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12
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Lute N, Lemmers-Jansen I, Krabbendam L, van Buuren M. Functional connectivity of subsystems of the default-mode network in patients with early psychotic symptoms. NEUROIMAGE. REPORTS 2025; 5:100248. [PMID: 40567890 PMCID: PMC12172822 DOI: 10.1016/j.ynirp.2025.100248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 02/17/2025] [Accepted: 03/04/2025] [Indexed: 06/28/2025]
Abstract
Resting-state connectivity of the default-mode network (DMN) is aberrant in patients with chronic psychotic disorders as well in individuals with early stage psychosis. Studies of the DMN in healthy volunteers revealed that the DMN comprises several subnetworks. However, it is not yet clear if connectivity between and within these DMN subnetworks is aberrant in patients with early psychotic symptoms nor whether these connectivity patterns are related to symptomatology. This initial investigation examined functional connectivity between and within the DMN subnetworks in patients with early psychotic symptoms and in healthy volunteers, and probed how these connectivity patterns were related to the severity of clinical symptomatology. Functional connectivity was measured during resting-state in 30 patients with early psychotic symptoms and in 39 controls using functional MRI. We did not observe differences in connectivity within and between the subnetworks of the DMN between the control group and the early psychosis group. However, lower functional connectivity between the medial prefrontal and posterior medial subnetworks and between medial prefrontal and anterior temporal subnetworks of the DMN did predict the severity of the negative symptoms. The findings of this initial investigation provide insight into the associations between functional connectivity of DMN subnetworks and symptomatology in patients with early psychotic symptoms.
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Affiliation(s)
- Nicky Lute
- Department of Clinical, Neuro and Developmental Psychology, Faculty of Behavioral and Movement Sciences. Vrije Universiteit Amsterdam, Van der Boechorststraat 7, 1081, BT Amsterdam, the Netherlands
| | - Imke Lemmers-Jansen
- Department of Clinical, Neuro and Developmental Psychology, Faculty of Behavioral and Movement Sciences. Vrije Universiteit Amsterdam, Van der Boechorststraat 7, 1081, BT Amsterdam, the Netherlands
- Institute for Brain and Behavior Amsterdam, Vrije Universiteit Amsterdam, Van der Boechorststraat 7, 1081, BT Amsterdam, the Netherlands
| | - Lydia Krabbendam
- Department of Clinical, Neuro and Developmental Psychology, Faculty of Behavioral and Movement Sciences. Vrije Universiteit Amsterdam, Van der Boechorststraat 7, 1081, BT Amsterdam, the Netherlands
- Institute for Brain and Behavior Amsterdam, Vrije Universiteit Amsterdam, Van der Boechorststraat 7, 1081, BT Amsterdam, the Netherlands
| | - Mariët van Buuren
- Department of Clinical, Neuro and Developmental Psychology, Faculty of Behavioral and Movement Sciences. Vrije Universiteit Amsterdam, Van der Boechorststraat 7, 1081, BT Amsterdam, the Netherlands
- Institute for Brain and Behavior Amsterdam, Vrije Universiteit Amsterdam, Van der Boechorststraat 7, 1081, BT Amsterdam, the Netherlands
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13
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Lu YW, Wang JY, Hsu TJ, Chung WS. Risk of rhabdomyolysis in patients with mental disorders. Postgrad Med 2025; 137:201-208. [PMID: 39962880 DOI: 10.1080/00325481.2025.2466411] [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: 07/27/2024] [Accepted: 02/06/2025] [Indexed: 02/20/2025]
Abstract
OBJECTIVES Rhabdomyolysis is caused by rapid muscle breakdown. Although patients with mental disorders are more susceptible to rhabdomyolysis, its incidence in this group is poorly established. Therefore, we conducted a population-based cohort study to investigate its incidence and risk in this group. METHODS We conducted a retrospective cohort study of 120,094 patients with mental disorders and 120,094 control patients from the Taiwan National Health Insurance Research Database. We excluded patients with rhabdomyolysis diagnosed before the index date, which was defined as the date of the first diagnosis of the mental disorder and beginning of antipsychotic medication. We matched the case cohort 1:1 with a control cohort by a propensity score method. RESULTS The overall incidence of rhabdomyolysis were 3.21 per 1000 person-years in the patients with mental disorders and 1.16 per 1000 person-years in the patients without mental disorders. After controlling for potential covariates, the patients with mental disorders showed an adjusted hazard ratio (aHR) of 2.77 (95% Cl: 2.62-2.92) compared with the controls. Men exhibited a risk of rhabdomyolysis 1.29-fold that exhibited by women (95% CI: 1.22-1.35). Alcoholic liver disease (aHR, 2.35) and generalized convulsive epilepsy (aHR, 2.06) were independent risk factors for rhabdomyolysis. Phenothiazines with aliphatic side-chains (aHR, 1.43), or piperidine structures (aHR, 1.54); butyrophenone derivatives (aHR, 1.24); lithium (aHR, 1.18) were independent risk factors for rhabdomyolysis after adjustment for covariates. CONCLUSIONS The risk of rhabdomyolysis is significantly higher for patients with mental disorders than that for patients without mental disorders.
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Affiliation(s)
- Ya-Wen Lu
- Pharmaceutical department, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan
| | - Jong-Yi Wang
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
| | - Tzu-Ju Hsu
- Management Office for Health Data (DryLab), Clinical Trial Research Center (CTC), China Medical University Hospital, Taichung, Taiwan
| | - Wei-Sheng Chung
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
- Department of Internal Medicine, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan
- Department of Healthcare Administration, Central Taiwan University of Science and Technology, Taichung, Taiwan
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14
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Lohman MC, Scott V, Verma M, Jones P, Fields E. Distribution and correlates of long-acting injectable antipsychotic use among community mental health center patients. Psychiatry Res 2025; 345:116378. [PMID: 39879897 DOI: 10.1016/j.psychres.2025.116378] [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: 12/20/2024] [Revised: 01/23/2025] [Accepted: 01/25/2025] [Indexed: 01/31/2025]
Abstract
Although long-acting injectable antipsychotics (LAIs) are an important pharmaceutical option in the management of schizophrenia and related disorders, little is known about patient characteristics related to LAI use in real-world outpatient settings. We analyzed electronic medical records from 41,401 patients who received psychiatric services from one of 16 regional mental health centers operated by the South Carolina Department of Mental Health in 2022. We compared the use of first- and second-generation LAIs and oral antipsychotics by sociodemographic (age, gender, race/ethnicity, zip code, payment source) and clinical characteristics (psychiatric diagnoses, service use). We used logistic regression models to estimate associations between patient characteristics and the likelihood of using LAIs. In total, 7,029 (17.0 %) patients used LAIs in 2022, including 5,901 with schizophrenia or another psychotic disorder. Compared to White patients, Black (Odds Ratio (OR): 2.19, 95 % Confidence Interval (CI): 1.96 - 2.44) and Asian (OR: 3.39, 95 % CI: 1.54 - 7.43) patients were significantly more likely to use LAIs, controlling for other patient demographic and clinical characteristics. LAI users were also more likely to be male (OR: 1.83, 95 % CI: 1.64, 2.03), to live in suburban areas (OR: 1.25, 95 % CI: 1.10, 1.42), and to use Medicaid (OR: 1.55, 95 % CI: 1.34, 1.79). Similar differences were not found for oral antipsychotics. Results suggest that LAI use differs substantially by patient characteristics independent of psychiatric diagnoses. Identifying and understanding reasons for differences in LAI use is important to promote equitable access to and use of LAIs across racial, geographic, and other sociodemographic groups.
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Affiliation(s)
- Matthew C Lohman
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene St, Columbia, SC 29201, United States.
| | - Victoria Scott
- Department of Psychological Science, University of North Carolina at Charlotte, 9201 University City Blvd, Charlotte, NC 28223, United States
| | - Mansi Verma
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene St, Columbia, SC 29201, United States
| | - Paige Jones
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene St, Columbia, SC 29201, United States
| | - Eve Fields
- South Carolina Department of Mental Health, 220 Executive Dr, Greer, SC 29651, United States; Department of Neuropsychiatry and Behavioral Science, University of South Carolina School of Medicine, 15 Medical Park, Suite 301, Columbia, SC 29203, United States
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15
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Kelebie M, Kibralew G, Tadesse G, Rtbey G, Aderaw M, Endeshaw W, Belachew M, Muche M, Getnet D, Fentahun S. Effectiveness of antipsychotic medication in patients with schizophrenia in a real world retrospective observational study in Ethiopia. Sci Rep 2025; 15:4663. [PMID: 39920141 PMCID: PMC11806019 DOI: 10.1038/s41598-025-85832-3] [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: 11/15/2024] [Accepted: 01/06/2025] [Indexed: 02/09/2025] Open
Abstract
Antipsychotic medications have become the cornerstone of treatment for schizophrenia. The antipsychotic drugs are high-affinity antagonists of dopamine D2 receptors that are most effective against psychotic symptoms, but antipsychotic drugs can have side effects that overshadow their advantages, like sedation, extrapyramidal symptoms, and weight gain, which are often experienced as adverse effects. In our country, the relative effectiveness of antipsychotic medication as well as their tolerance in schizophrenia patients is not fully addressed. This study aims to determine the effectiveness of antipsychotic medication and associated factors in schizophrenia patients at the psychiatry clinic. An institutional-based retrospective cohort study was conducted using administrative data of patients with schizophrenia disorder based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) that initiated or changed to a new antipsychotic treatment by clinicians assessments from April 1, 2023, to March 1, 2024 at university of Gondar specialized hospital. The effectiveness of prescribed antipsychotic medication was evaluated using the Clinical Global Impressions-Schizophrenia scale (CGI-SCH), inclusive of subscales for positive, negative, depressive, and cognitive symptoms. A total of 608 patients were receiving antipsychotic medications as follows: 118 patients (19.4%) were prescribed haloperidol, 88 patients (14.5%) were taking chlorpromazine, 48 patients (7.9%) received fluphenazine (decanoate), 126 patients (20.7%) were on risperidone, and 228 patients (37.5%) were treating with olanzapine. In total, 64.8% of patients show improvement in the prescribed medications within one year of treatment (Kaplan-Meier estimate 35.2%) for haloperidol, 31 (26.3%) for chlorpromazine, 30 (34.1%) for Fluphenazine, 19 (39.6%) for risperidone, 51 (40.5%), and 83 (36.4%) for olanzapine. Effectiveness was assessed using the Clinical Global Impressions-Improvement (CGI-I); the overall improvements like negative, positive, depressive, and cognitive symptoms were significantly higher for olanzapine, followed by haloperidol (p < .001). Good adherence (AHR = 0.63; 95% CI 0.5-0.78), history of relapse (AHR = 1.43; 95% CI 1.13-1.82), unemployment (AHR = 1.4; 95% CI 1.06-1.85), and history of suicidal ideation (AHR = 1.79; 95% CI 1.24-2.58) were significant predictors of symptoms improvement. The study found olanzapine is more effective in improving schizophrenia symptoms than other antipsychotic drugs. Medication adherence, symptom relapse, and suicidal thoughts significantly impacted antipsychotic effectiveness in individuals with schizophrenia disorder.
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Affiliation(s)
- Mulualem Kelebie
- Department of Psychiatry, School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia.
| | - Getasew Kibralew
- Department of Psychiatry, School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Gebresilassie Tadesse
- Department of Psychiatry, School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Gidey Rtbey
- Department of Psychiatry, School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Mekidem Aderaw
- Department of Psychiatry, School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Wondale Endeshaw
- Department of Psychiatry, School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Mitiku Belachew
- Department of Psychiatry, School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Mulu Muche
- Department of Environmental Biotechnology, Institute of Biotechnology, University of Gondar, Gondar, Ethiopia
| | - Diemesew Getnet
- Department of Psychiatry, School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Setegn Fentahun
- Department of Psychiatry, School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
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16
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Salatin S, Shafiee-Kandjani AR, Hamidi S, Amirfiroozi A, Kalejahi P. Individualized psychiatric care: integration of therapeutic drug monitoring, pharmacogenomics, and biomarkers. Per Med 2025; 22:29-44. [PMID: 39706800 DOI: 10.1080/17410541.2024.2442897] [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: 08/23/2024] [Accepted: 12/12/2024] [Indexed: 12/23/2024]
Abstract
Personalized treatment optimization considers individual clinical, genetic, and environmental factors influencing drug efficacy and tolerability. As evidence accumulates, these approaches may become increasingly integrated into standard psychiatric care, potentially transforming the treatment landscape for mental health disorders. While personalized treatment optimization shows promise in enhancing therapeutic outcomes and minimizing adverse effects, further research is needed to establish its clinical utility and cost-effectiveness across various psychiatric disorders. This review examines the potential utility of personalized treatment optimization in psychiatry, addressing the challenge of suboptimal effectiveness and variable patient responses to psychiatric medications. It explores how therapeutic drug monitoring, pharmacogenomics, and biomarker testing can be used to individualize and optimize pharmacotherapy for mental disorders such as depression, bipolar disorder, and schizophrenia.
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Affiliation(s)
- Sara Salatin
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Reza Shafiee-Kandjani
- Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Samin Hamidi
- Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Akbar Amirfiroozi
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Genetics, Tabriz, Iran
| | - Parinaz Kalejahi
- Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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17
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Dhieb D, Bastaki K. Pharmaco-Multiomics: A New Frontier in Precision Psychiatry. Int J Mol Sci 2025; 26:1082. [PMID: 39940850 PMCID: PMC11816785 DOI: 10.3390/ijms26031082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/19/2025] [Accepted: 01/21/2025] [Indexed: 02/16/2025] Open
Abstract
The landscape of psychiatric care is poised for transformation through the integration of pharmaco-multiomics, encompassing genomics, proteomics, metabolomics, transcriptomics, epigenomics, and microbiomics. This review discusses how these approaches can revolutionize personalized treatment strategies in psychiatry by providing a nuanced understanding of the molecular bases of psychiatric disorders and individual pharmacotherapy responses. With nearly one billion affected individuals globally, the shortcomings of traditional treatments, characterized by inconsistent efficacy and frequent adverse effects, are increasingly evident. Advanced computational technologies such as artificial intelligence (AI) and machine learning (ML) play crucial roles in processing and integrating complex omics data, enhancing predictive accuracy, and creating tailored therapeutic strategies. To effectively harness the potential of pharmaco-multiomics approaches in psychiatry, it is crucial to address challenges such as high costs, technological demands, and disparate healthcare systems. Additionally, navigating stringent ethical considerations, including data security, potential discrimination, and ensuring equitable access, is essential for the full realization of this approach. This process requires ongoing validation and comprehensive integration efforts. By analyzing recent advances and elucidating how different omic dimensions contribute to therapeutic customization, this review aims to highlight the promising role of pharmaco-multiomics in enhancing patient outcomes and shifting psychiatric treatments from a one-size-fits-all approach towards a more precise and patient-centered model of care.
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Affiliation(s)
| | - Kholoud Bastaki
- Pharmaceutical Sciences Department, College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar;
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18
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Marques D, Vaziri N, Greenway SC, Bousman C. DNA methylation and histone modifications associated with antipsychotic treatment: a systematic review. Mol Psychiatry 2025; 30:296-309. [PMID: 39227433 DOI: 10.1038/s41380-024-02735-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 08/21/2024] [Accepted: 08/28/2024] [Indexed: 09/05/2024]
Abstract
Antipsychotic medications are essential when treating schizophrenia spectrum and other psychotic disorders, but the efficacy and tolerability of these medications vary from person to person. This interindividual variation is likely mediated, at least in part, by epigenomic processes that have yet to be fully elucidated. Herein, we systematically identified and evaluated 65 studies that examine the influence of antipsychotic drugs on epigenomic changes, including global methylation (9 studies), genome-wide methylation (22 studies), candidate gene methylation (16 studies), and histone modification (18 studies). Our evaluation revealed that haloperidol was consistently associated with increased global hypermethylation, which corroborates with genome-wide analyses, mostly performed by methylation arrays. In contrast, clozapine seems to promote hypomethylation across the epigenome. Candidate-gene methylation studies reveal varying effects post-antipsychotic therapy. Some genes like Glra1 and Drd2 are frequently found to undergo hypermethylation, whereas other genes such as SLC6A4, DUSP6, and DTNBP1 are more likely to exhibit hypomethylation in promoter regions. In examining histone modifications, the literature suggests that clozapine changes histone methylation patterns in the prefrontal cortex, particularly elevating H3K4me3 at the Gad1 gene and affecting the transcription of genes like mGlu2 by modifying histone acetylation and interacting with HDAC2 enzymes. Risperidone and quetiapine, however, exhibit distinct impacts on histone marks across different brain regions and cell types, with risperidone reducing H3K27ac in the striatum and quetiapine modifying global H3K9me2 levels in the prefrontal cortex, suggesting antipsychotics demonstrate selective influence on histone modifications, which demonstrates a complex and targeted mode of action. While this review summarizes current knowledge, the intricate dynamics between antipsychotics and epigenetics clearly warrant more exhaustive exploration with the potential to redefine our understanding and treatment of psychiatric conditions. By deciphering the epigenetic changes associated with drug treatment and therapeutic outcomes, we can move closer to personalized medicine in psychiatry.
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Affiliation(s)
- Diogo Marques
- Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Nazanin Vaziri
- Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Steven C Greenway
- Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Chad Bousman
- Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
- Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
- Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
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Gonçalves CC, Waters Z, Quirk SE, Haddad PM, Lin A, Williams LJ, Yung AR. Barriers and facilitators to mental health care access and engagement for LGBTQA+ people with psychosis: A scoping review. Psychiatry Res 2025; 343:116281. [PMID: 39616980 DOI: 10.1016/j.psychres.2024.116281] [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: 07/29/2024] [Revised: 11/11/2024] [Accepted: 11/19/2024] [Indexed: 12/16/2024]
Abstract
LGBTQA+ individuals are at increased risk of experiencing psychosis and face barriers in accessing appropriate and timely mental health support. This scoping review maps the existing literature to identify barriers and facilitators to access and engagement to care for LGBTQA+ people across the psychosis spectrum. Select databases and grey literature were searched up to May 2024. Following screening according to pre-determined eligibility criteria, 37 papers were included in this review. A total of 89 barriers and 63 facilitators to mental health care were identified. Using inductive thematic analysis, five themes were developed to synthesise these items: (1) service-related factors, (2) stigma, (3) social networks, (4) personal factors, and (5) psychosis-related factors. These findings illustrate the complex interplay of factors affecting pathways to care in this population and highlight the significance of intersectionality. Improving LGBTQA+ and psychosis competencies in the public and in services that support these populations may enable earlier detection of psychosis and provision of effective care. Scoping review registration: This protocol is registered in Open Science Framework Registries (https://doi.org/10.17605/OSF.IO/AT6FC).
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Affiliation(s)
- Cláudia C Gonçalves
- Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC, Australia.
| | - Zoe Waters
- Telethon Kids Institute, University of Western Australia, Perth, WA, Australia
| | - Shae E Quirk
- Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC, Australia
| | - Peter M Haddad
- Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC, Australia; University Hospital Geelong, Barwon Health, Geelong, VIC, Australia
| | - Ashleigh Lin
- School of Population and Global Health, University of Western Australia, Perth, WA, Australia
| | - Lana J Williams
- Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC, Australia
| | - Alison R Yung
- Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC, Australia; School of Health Sciences, University of Manchester, Manchester, United Kingdom
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20
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D'Addario C, Di Bartolomeo M. Epigenetic Control in Schizophrenia. Subcell Biochem 2025; 108:191-215. [PMID: 39820863 DOI: 10.1007/978-3-031-75980-2_5] [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: 01/19/2025]
Abstract
Schizophrenia is a severe and complex psychiatric condition ranking among the top 15 leading causes of disability worldwide. Despite the well-established heritability component, a complex interplay between genetic and environmental risk factors plays a key role in the development of schizophrenia and psychotic disorders in general. This chapter covers all the clinical evidence showing how the analysis of the epigenetic modulation in schizophrenia might be relevant to understand the pathogenesis of schizophrenia as well as potentially useful to develop new pharmacotherapies.
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Affiliation(s)
- Claudio D'Addario
- Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy.
| | - Martina Di Bartolomeo
- Department of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy
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21
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Martínez-Cano A, de la Sacristana RFBG, Martín-Conty JL, Mordillo-Mateos L, Bernal-Jimenéz JJ, Polonio-López B, Martínez-Lorca M. Fundamental Frequency of the Voice in Schizophrenia and Its Value as a Biomarker of the Disease. J Voice 2024:S0892-1997(24)00394-1. [PMID: 39690086 DOI: 10.1016/j.jvoice.2024.11.005] [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: 09/30/2024] [Revised: 11/02/2024] [Accepted: 11/05/2024] [Indexed: 12/19/2024]
Abstract
Recent research on schizophrenia seeks to identify objective biomarkers of the disease. The voice, and in particular the fundamental frequency (F0), could be one of them. METHODOLOGY We conducted a cross-sectional and descriptive study with a sample of 154 people. Of these, 46 were diagnosed with schizophrenia, 41 were at substance abuse, and 67 formed the control group, matched in variables of sex, age, and educational level, but without substance use compared with the high-risk group. RESULTS The biomechanical analyses of the voice indicated significant differences between the groups, differentiated by gender: in men (F = 5.316; P = 0.006) and in women (F = 4.13; P = 0.004). The greatest differences between groups were observed in the group of vulnerable individuals, with some stability of the F0 in people with schizophrenia. Furthermore, we found correlations between positive symptoms and decreased F0 (r = -0.353; P = 0.016). CONCLUSIONS Our study shows that schizophrenia is associated with decreased F0 in both men and women, and that medication could stabilize this decrease. These findings have important implications for the objective monitoring and diagnosis of schizophrenia.
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Affiliation(s)
- Alfonso Martínez-Cano
- Faculty of Health Sciences, University of Castilla-La Mancha, Talavera de la Reina, 45600, Spain; Department of Medical Sciences, University of Castilla-La Mancha, Albacete 02071, Spain
| | - Roberto Fernández-Baillo Gallego de la Sacristana
- University of Alcalá de Henares, Madrid 28801, Spain; Department of Surgery, Medical and Social Sciences, Human Anatomy and Embryology, University Campus-C/19, Ctra. Madrid-Barcelona, Km 33.600, Alcalá de Henares 28805 Madrid, Spain
| | - Jose Luis Martín-Conty
- Faculty of Health Sciences, University of Castilla-La Mancha, Talavera de la Reina, 45600, Spain; Department of Nursing, Physiotherapy and Occupational Therapy, Faculty of Health Sciences, Universidad de Castilla-La Mancha, Talavera de la Reina, 45600, Spain; Technological Innovation Applied to Health Research Group (ITAS Group), Faculty of Health Sciences, University of de Castilla-La Mancha, Talavera de la Reina, 45600, Spain
| | - Laura Mordillo-Mateos
- Faculty of Health Sciences, University of Castilla-La Mancha, Talavera de la Reina, 45600, Spain; Department of Nursing, Physiotherapy and Occupational Therapy, Faculty of Health Sciences, Universidad de Castilla-La Mancha, Talavera de la Reina, 45600, Spain; Technological Innovation Applied to Health Research Group (ITAS Group), Faculty of Health Sciences, University of de Castilla-La Mancha, Talavera de la Reina, 45600, Spain
| | - Juan José Bernal-Jimenéz
- Faculty of Health Sciences, University of Castilla-La Mancha, Talavera de la Reina, 45600, Spain; Department of Nursing, Physiotherapy and Occupational Therapy, Faculty of Health Sciences, Universidad de Castilla-La Mancha, Talavera de la Reina, 45600, Spain; Technological Innovation Applied to Health Research Group (ITAS Group), Faculty of Health Sciences, University of de Castilla-La Mancha, Talavera de la Reina, 45600, Spain
| | - Begoña Polonio-López
- Faculty of Health Sciences, University of Castilla-La Mancha, Talavera de la Reina, 45600, Spain; Technological Innovation Applied to Health Research Group (ITAS Group), Faculty of Health Sciences, University of de Castilla-La Mancha, Talavera de la Reina, 45600, Spain.
| | - Manuela Martínez-Lorca
- Faculty of Health Sciences, University of Castilla-La Mancha, Talavera de la Reina, 45600, Spain; Department of Psychology, University of Castilla-La Mancha, Albacete 02071, Spain
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22
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Shakir M, van Harten PN, Hoogendoorn AW, Willems AE, Tenback DE. Switching a combination of first- and second-generation antipsychotic polypharmacy to antipsychotic monotherapy in long-term inpatients with schizophrenia and related disorders. The SwAP trial II: Results on side effects. Schizophr Res 2024; 274:105-112. [PMID: 39288473 DOI: 10.1016/j.schres.2024.09.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 08/23/2024] [Accepted: 09/03/2024] [Indexed: 09/19/2024]
Abstract
OBJECTIVE This study examined the effects of switching antipsychotic polypharmacy (APP) to antipsychotic monotherapy (APM) on various side effects in inpatients with schizophrenia. Side effects of interest included psychic, autonomic, and sexual symptoms, as well as metabolic side effects and movement disorders. METHOD A 9-month parallel randomized open-label clinical trial was conducted involving 136 chronic inpatients from two psychiatric hospitals in the Netherlands. Participants were randomly assigned to either a STAY or a SWITCH group. The SWITCH group underwent a 3-month tapering-off period in which either first-generation or second-generation antipsychotic medication was discontinued, followed by APM. Patients were assessed at baseline and at follow-up assessments at 3, 6, and 9 months. Psychic, neurological, autonomic, and sexual side effects were evaluated using the UKU Rating Scale, while movement disorders were measured with the St. Hans Rating Scale. Various metabolic parameters were also recorded. RESULTS In the STAY group, side effects remained generally stable over time, except for a slight reduction in sexual desire. In contrast, the SWITCH group experienced significant reductions in psychic and autonomic symptoms, as well as improvements in akathisia, parkinsonism, and dyskinesia. There were no changes in dystonia, paresthesia, epilepsy, or sexual symptoms for this group. Notably, the SWITCH group also showed significant reductions in BMI and body weight. CONCLUSION Switching APP to APM in long-term inpatients reduces the severity of various side effects, including movement disorders and metabolic side effects.
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Affiliation(s)
- Mushde Shakir
- Veldzicht Center for Transcultural Psychiatry, Custodial Institutions Agency (DJI), Ministry of Justice and Security, Balkbrug, the Netherlands; Parnassia Group Mental Health Service, Den Haag, the Netherlands; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Faculty Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands.
| | - Peter N van Harten
- Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Faculty Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands; GGZ Centraal Mental Health Service, Amersfoort, the Netherlands
| | - Adriaan W Hoogendoorn
- Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
| | | | - Diederik E Tenback
- Veldzicht Center for Transcultural Psychiatry, Custodial Institutions Agency (DJI), Ministry of Justice and Security, Balkbrug, the Netherlands; FPC de Oostvaarderskliniek, Custodial Institutions Agency (DJI), Ministry of Justice and Security, Almere, the Netherlands
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23
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Chang BC, Kuo MH, Lee CH, Chu YL, Chen KP, Tung CL, Yang YH, Hung CS, Tsai JH, Chuang HY. Health-Care Utilisation and Costs of Transition from Paliperidone Palmitate 1-Monthly to 3-Monthly Treatment for Schizophrenia: A Real-World, Retrospective, 24-Month Mirror-Image Study. Neuropsychiatr Dis Treat 2024; 20:1985-1993. [PMID: 39450244 PMCID: PMC11499615 DOI: 10.2147/ndt.s484717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Accepted: 10/11/2024] [Indexed: 10/26/2024] Open
Abstract
Introduction Poor adherence to antipsychotics in patients with schizophrenia is a leading cause of relapse and functional deterioration. Long-acting injectable paliperidone may reduce relapse risks, health-care utilisation, and health-care costs in these patients. Methods In this 24-month mirror-image study, we compared health-care utilization and costs before and after the initiation of paliperidone palmitate 3-monthly (PP3M) treatment in patients with schizophrenia spectrum disorders. Before the initiation of PP3M, the patients received paliperidone 1-monthly (PP1M) treatment. The primary study outcomes were changes in health-care utilisation and costs over the study period. Results This study included 34 patients with schizophrenia spectrum disorders. During the 12-months period after the initiation of PP3M treatment, the mean duration of hospitalisation decreased from 57.7 to 28.5 days (p = 0.03). Moreover, significant reductions were noted in emergency room visits (PP1M vs PP3M: 0.3 vs 0.0, respectively; p = 0.05) and health-care costs (PP1M vs PP3M: 107,328.8 vs 57,848.6, respectively; p = 0.03). Conclusion PP3M may significantly reduce hospitalisation duration, emergency room visits, and health-care costs in patients with schizophrenia.
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Affiliation(s)
- Bo-Chieh Chang
- Department of Pharmacy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Meng-Hsuan Kuo
- Department of Pharmacy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Chi-Hui Lee
- Department of Pharmacy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Ya-Lan Chu
- Department of Pharmacy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Kuang-Peng Chen
- Department of Psychiatry, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Chun-Liong Tung
- Department of Psychiatry, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Ya-Hui Yang
- Department of Long-Term Care and Health Management, Cheng Shiu University, Kaohsiung, Taiwan
| | - Chuan-Sheng Hung
- Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Jui-Hsiu Tsai
- Department of Psychiatry, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Hung-Yi Chuang
- Department of Environmental and Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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24
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Sikiric P, Sever M, Krezic I, Vranes H, Kalogjera L, Smoday IM, Vukovic V, Oroz K, Coric L, Skoro M, Kavelj I, Zubcic S, Sikiric S, Beketic Oreskovic L, Oreskovic I, Blagaic V, Brcic K, Strbe S, Staresinic M, Boban Blagaic A, Skrtic A, Seiwerth S. New studies with stable gastric pentadecapeptide protecting gastrointestinal tract. significance of counteraction of vascular and multiorgan failure of occlusion/occlusion-like syndrome in cytoprotection/organoprotection. Inflammopharmacology 2024; 32:3119-3161. [PMID: 38980576 DOI: 10.1007/s10787-024-01499-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Accepted: 05/28/2024] [Indexed: 07/10/2024]
Abstract
Since the early 1990s, when Robert's and Szabo's cytoprotection concept had already been more than one decade old, but still not implemented in therapy, we suggest the stable gastric pentadecapeptide BPC 157 as the most relevant mediator of the cytoprotection concept. Consequently, it can translate stomach and gastrointestinal mucosal maintenance, epithelium, and endothelium cell protection to the therapy of other tissue healing (organoprotection), easily applicable, as native and stable in human gastric juice for more than 24 h. These overwhelm current clinical evidence (i.e., ulcerative colitis, phase II, no side effects, and no lethal dose (LD1) in toxicology studies), as BPC 157 therapy effectively combined various tissue healing and lesions counteraction. BPC 157 cytoprotection relevance and vascular recovery, activation of collateral pathways, membrane stabilizer, eye therapy, wound healing capability, brain-gut and gut-brain functioning, tumor cachexia counteraction, muscle, tendon, ligament, and bone disturbances counteraction, and the heart disturbances, myocardial infarction, heart failure, pulmonary hypertension, arrhythmias, and thrombosis counteraction appeared in the recent reviews. Here, as concept resolution, we review the counteraction of advanced Virchow triad circumstances by activation of the collateral rescuing pathways, depending on injury, activated azygos vein direct blood flow delivery, to counteract occlusion/occlusion-like syndromes starting with the context of alcohol-stomach lesions. Counteraction of major vessel failure (congested inferior caval vein and superior mesenteric vein, collapsed azygos vein, collapsed abdominal aorta) includes counteraction of the brain (intracerebral and intraventricular hemorrhage), heart (congestion, severe arrhythmias), lung (hemorrhage), and congestion and lesions in the liver, kidney, and gastrointestinal tract, intracranial (superior sagittal sinus), portal and caval hypertension, aortal hypotension, and thrombosis, peripherally and centrally.
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Affiliation(s)
- Predrag Sikiric
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia.
| | - Marko Sever
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Surgery, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Ivan Krezic
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Hrvoje Vranes
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Luka Kalogjera
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Ivan Maria Smoday
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Vlasta Vukovic
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Katarina Oroz
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Luka Coric
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Marija Skoro
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Diagnostic and Interventional Radiology, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
| | - Ivana Kavelj
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Diagnostic and Interventional Radiology, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
| | - Slavica Zubcic
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Suncana Sikiric
- Department of Pathology, School of Medicine, University of Zagreb, 10000, Zagreb, Croatia
| | | | - Ivana Oreskovic
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Vladimir Blagaic
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Klara Brcic
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Sanja Strbe
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Mario Staresinic
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Surgery, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Alenka Boban Blagaic
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Anita Skrtic
- Department of Pathology, School of Medicine, University of Zagreb, 10000, Zagreb, Croatia
| | - Sven Seiwerth
- Department of Pathology, School of Medicine, University of Zagreb, 10000, Zagreb, Croatia
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25
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Wang KC, Chan HY, Yang WS, Huang YM, Ho YF, Hwang TJ. Cardiometabolic biomarkers and comorbid metabolic syndrome in schizophrenia: A cross-sectional study of long-term clozapine/olanzapine users. Asian J Psychiatr 2024; 102:104244. [PMID: 39298914 DOI: 10.1016/j.ajp.2024.104244] [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: 06/16/2024] [Revised: 07/31/2024] [Accepted: 09/12/2024] [Indexed: 09/22/2024]
Abstract
OBJECTIVES Second-generation antipsychotics (SGAs) are often prescribed for patients with schizophrenia; however, SGAs are associated with the risk of metabolic syndrome (MetS). This study aimed to investigate the clinical and biochemical determinants of SGA-related MetS. METHODS Patients with schizophrenia, aged between 20 and 65 years, and under clozapine or olanzapine treatment for at least 9 months, were recruited from a mental hospital. Demographic, comorbidity, clinical status, laboratory, and drug regimen data were collected through chart review. Circulating levels of adiponectin, thyroid hormone responsive protein, and fatty acid binding protein 4 (FABP4) were assayed. Multiple logistic regression was used to identify risk predictors of MetS. RESULTS A total of 176 participants were enrolled, including 138 (78.4 %) clozapine users and 38 (21.6 %) olanzapine users. Forty-five (25.6 %) patients were classified as having MetS. The duration of clozapine or olanzapine usage was significantly shorter in those with MetS (p=0.026) than those without MetS. Patients with MetS had a significantly higher serum FABP4 concentration than their counterparts (22.5 ± 8.8 ng/mL vs. 15.7 ± 6.7 ng/mL, p<0.001), and also a significantly lower adiponectin level (6.9 ±4.0 mg/mL vs. 11.6 ± 6.6 mg/mL, p<0.001). A FABP4 level ≥ 16.98 ng/mL (OR: 24.16, 95 % CI: 7.47-78.09, p<0.001) was positively correlated with MetS, whereas serum adiponectin level was inversely correlated with MetS (OR: 0.7980, 95 % CI: 0.70-0.90, p<0.001). CONCLUSIONS Adiponectin, FABP4, and certain clinical covariates and comedications were highly correlated with SGA-related MetS. Further studies are required to investigate the underlying mechanisms.
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Affiliation(s)
- Kuo-Chan Wang
- Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pharmacy, NTU Cancer Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Yu Chan
- Department of Psychiatry, Taoyuan Psychiatric Center, Taoyuan, Taiwan
| | - Wei-Shiung Yang
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University and Department of Internal Medicine (Division of Endocrinology & Metabolism), National Taiwan University, Taipei, Taiwan
| | - Yen-Ming Huang
- Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yunn-Fang Ho
- Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
| | - Tzung-Jeng Hwang
- Department of Psychiatry, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan.
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Hsieh KP, Liao WL, Ho PS, Lin JW, Tung CL, Yang YH, Hung CS, Tsai JH. Association of antipsychotic formulations with sudden cardiac death in patients with schizophrenia: A nationwide population-based case-control study. Psychiatry Res 2024; 342:116171. [PMID: 39244895 DOI: 10.1016/j.psychres.2024.116171] [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: 03/29/2024] [Revised: 08/16/2024] [Accepted: 08/31/2024] [Indexed: 09/10/2024]
Abstract
The aim of this study was to clarify the association between various antipsychotic formulations-oral-daily antipsychotics (OAPs), long-acting injectable antipsychotics (LAIs), and their combination-and the risk of sudden cardiac death (SCD). We conducted a nationwide population-based case-control study using data from 2011 to 2020 from the National Health Insurance Research Database and multiple-cause-of-death data from Taiwan. The study included patients with a new diagnosis of schizophrenia who were followed for SCD occurrence until 2020. Cases and controls were frequency-matched at a 1:4 ratio by age, sex, and year of new schizophrenia diagnosis. Compared with the use of OAP monotherapy, the use of LAI and OAP combination (OR = 1.91) and LAI monotherapy (OR = 1.45) were associated with an increased risk of SCD. Additionally, cardiovascular comorbidities (adjusted OR = 11.15) were identified as a significant risk factor for SCD. This study revealed the following hierarchy of SCD risk associated with antipsychotic formulations (listed from lowest to highest risk): nonuse of antipsychotics, OAP monotherapy, LAI monotherapy, and their combination. These findings underscore the importance of assessing cardiovascular disease history before LAIs are prescribed to patients with schizophrenia and indicate that physicians should avoid prescribing combined antipsychotics when using LAIs.
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Affiliation(s)
- Kun-Pin Hsieh
- School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Ling Liao
- School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Pharmacy, Changhua Christian Hospital, Changhua, Taiwan
| | - Pei-Shan Ho
- Division of Medical Statistics and Bioinformatics, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Oral Hygiene, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jiunn-Wen Lin
- Department of Cardiology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Chun-Liong Tung
- Department of Psychiatry, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Ya-Hui Yang
- Department of Long-term Care and Health Management, Cheng Shiu University, Kaohsiung, Taiwan
| | - Chuan-Sheng Hung
- Department of Computer Science and Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Jui-Hsiu Tsai
- Department of Psychiatry, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
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27
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Sun X, He R, Xiao Y, Xiu M, Sun M, Wu F, Zhang XY. Interaction between baseline BMI and baseline disease severity predicts greater improvement in negative symptoms in first-episode schizophrenia. Eur Arch Psychiatry Clin Neurosci 2024; 274:1327-1332. [PMID: 38536473 DOI: 10.1007/s00406-024-01763-6] [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: 03/23/2023] [Accepted: 01/13/2024] [Indexed: 08/30/2024]
Abstract
Several studies have reported that baseline symptom severity in patients with schizophrenia (SCZ) is associated with the efficacy of antipsychotic medication. Overweight/obesity is common in SCZ and has also been reported to be correlated with therapeutic response to antipsychotics. This study aimed to evaluate whether baseline body mass index (BMI) and disease severity were associated with improvements in negative symptoms in patients with first-episode and medication-naïve (FEMN) SCZ. A total of 241 FEMN patients were recruited in this study and treated with oral risperidone over 3 months. Clinical symptoms were measured by the Positive and Negative Syndrome Scale (PANSS) and BMI was assessed at baseline and 3-month follow-up. We found that baseline BMI was correlated with the baseline severity of symptoms. Baseline BMI or baseline disease severity was associated with improvement in negative symptoms after 3 months of treatment. Linear regression analysis indicated that the interaction of BMI and disease severity at baseline was associated with improvement in negative symptoms in the early stage of SCZ after controlling for sex, age, and dose of risperidone. Our study suggests that the interaction of baseline BMI and disease severity may play a role in predicting negative symptom improvement after 3 months of risperidone treatment.
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Affiliation(s)
- Xiaobing Sun
- Jiahui International Hospital (Shanghai), Shanghai, China
| | - Ruiqing He
- Jiahui International Hospital (Shanghai), Shanghai, China
| | - Yuan Xiao
- Qingdao Mental Health Center, Qingdao, China
| | - Meihong Xiu
- Beijing HuiLongGuan Hospital, Peking University HuiLongGuan Clinical Medical School, Beijing, China
| | - Maodi Sun
- North University of China, Taiyuan, China
| | - Fengchun Wu
- Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
- Department of Biomedical Engineering, Guangzhou Medical University, Guangzhou, China
- Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China
| | - Xiang Yang Zhang
- Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
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Rodolico A, Aprile SF, Cutrufelli P, Privitera G, Castellano S, Concerto C, Furnari R, Guerrera CS, Mineo L, Platania GA, Petralia A, Caraci F, Signorelli MS. Disability and Adverse Effects of Oral Versus Long-Acting Injectable Antipsychotics in Schizophrenia-Spectrum and Bipolar Disorder: A Comparison Based on Data-Driven Taxonomy. Clin Drug Investig 2024; 44:715-727. [PMID: 39302586 PMCID: PMC11455686 DOI: 10.1007/s40261-024-01391-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/29/2024] [Indexed: 09/22/2024]
Abstract
BACKGROUND Patients undergoing antipsychotic treatment for psychiatric disorders may experience challenges in functioning, either stemming from the severity of the illness or from the tolerability issues of prescribed medications. OBJECTIVES The aims of this cross-sectional study are to investigate the impact of adverse effects of antipsychotic drugs on patients' daily life functioning, comparing oral and long-acting injectable (LAI) antipsychotics, and further dividing antipsychotics by receptor-binding profiles based on recently defined data-driven taxonomy. METHODS This study involved patients with schizophrenia and bipolar spectrum disorders taking oral or LAI antipsychotics. Disability and functioning levels were assessed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS), and the adverse effects of medications were evaluated using the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and its subscales. RESULTS The total sample consisted of 126 participants with a diagnosis of schizophrenia-spectrum or bipolar disorder, and included 54 males and 72 females ranging from 18 to 78 years of age (mean 45.1, standard deviation 14); 78 patients were taking oral antipsychotics and 48 were taking LAI antipsychotics, with subcategories of muscarinic (31), adrenergic/low dopamine (25), serotonergic/dopaminergic (23), dopaminergic (1), LAI muscarinic (15), LAI adrenergic (6), and LAI serotonergic/dopaminergic (25). The UKU total score for adverse effects showed significant correlations with WHODAS total score (ρ = 0.475; p < 0.001). Compared with oral antipsychotics, LAIs showed significantly lower scores in psychological (p = 0.014), autonomic (p = 0.008), other (p = 0.004), and sexual adverse effects (p = 0.008), as well as the UKU total score (p = 0.002). The Kruskal-Wallis test showed a significant difference in adverse effects between LAI and oral muscarinic subgroups, with LAIs having lower scores compared with antipsychotics binding to muscarinic receptors (p = 0.043). CONCLUSION These findings indicate clinically relevant differences in adverse effects among formulations, warranting further investigation for future observational studies.
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Affiliation(s)
- Alessandro Rodolico
- Department of Psychiatry and Psychotherapy, TUM School of Medicine and Health, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany
| | - Sofia Francesca Aprile
- Section of Psychology, Department of Educational Sciences, University of Catania, Via Teatro Greco 84, 95124, Catania, Italy
| | - Pierfelice Cutrufelli
- Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy.
| | - Gabriele Privitera
- Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Sabrina Castellano
- Section of Psychology, Department of Educational Sciences, University of Catania, Via Teatro Greco 84, 95124, Catania, Italy
| | - Carmen Concerto
- Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Rosaria Furnari
- Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Claudia Savia Guerrera
- Section of Psychology, Department of Educational Sciences, University of Catania, Via Teatro Greco 84, 95124, Catania, Italy
| | - Ludovico Mineo
- Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Giuseppe Alessio Platania
- Section of Psychology, Department of Educational Sciences, University of Catania, Via Teatro Greco 84, 95124, Catania, Italy
| | - Antonino Petralia
- Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Filippo Caraci
- Oasi Research Institute, IRCCS, Via Conte Ruggero 73, 94018, Troina, Italy
- Department of Drug and Health Sciences, University of Catania, Via Valdisavoia, 5, 95123, Catania, Italy
| | - Maria Salvina Signorelli
- Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
- Oasi Research Institute, IRCCS, Via Conte Ruggero 73, 94018, Troina, Italy
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Cocean AM, Vodnar DC. Exploring the gut-brain Axis: Potential therapeutic impact of Psychobiotics on mental health. Prog Neuropsychopharmacol Biol Psychiatry 2024; 134:111073. [PMID: 38914414 DOI: 10.1016/j.pnpbp.2024.111073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 04/18/2024] [Accepted: 06/17/2024] [Indexed: 06/26/2024]
Abstract
One of the most challenging and controversial issues in microbiome research is related to gut microbial metabolism and neuropsychological disorders. Psychobiotics affect human behavior and central nervous system processes via the gut-brain axis, involving neuronal, immune, and metabolic pathways. They have therapeutic potential in the treatment of several neurodegenerative and neurodevelopmental disorders such as depression, anxiety, autism, attention deficit hyperactivity disorder, Alzheimer's disease, Parkinson's disease, schizophrenia, Huntington's disease, anorexia nervosa, and multiple sclerosis. However, the mechanisms underlying the interaction between psychobiotics and the abovementioned diseases need further exploration. This review focuses on the relationship between gut microbiota and its impact on neurological and neurodegenerative disorders, examining the potential of psychobiotics as a preventive and therapeutic approach, summarising recent research on the gut-brain axis and the potential beneficial effects of psychobiotics, highlighting the need for further research and investigation in this area.
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Affiliation(s)
- Ana-Maria Cocean
- Department of Food Science and Technology, Life Science Institute, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăștur 3-5, Cluj-Napoca, Romania.
| | - Dan Cristian Vodnar
- Department of Food Science and Technology, Life Science Institute, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăștur 3-5, Cluj-Napoca, Romania.
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Qiu Y, Guo J, Chen J, Zhang W, Wang W. Metabolic profiling of lumateperone in vitro and in vivo by UPLC-Q Exactive Orbitrap HRMS, and its pharmacokinetic study in rat plasma by LC-MS/MS. J Pharm Biomed Anal 2024; 246:116221. [PMID: 38759324 DOI: 10.1016/j.jpba.2024.116221] [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: 02/05/2024] [Revised: 04/26/2024] [Accepted: 05/12/2024] [Indexed: 05/19/2024]
Abstract
Lumateperone is a novel agent approved by FDA for treatment of schizophrenia in adults. To elucidate the species differences in the of biotransformation of lumateperone and its pharmacokinetic (PK) characteristics in rats, the metabolite identification of lumateperone was carried out in rat, dog and human liver microsomes, and rat plasma after oral administration using UPLC-Q Exactive Orbitrap high-resolution mass spectrometry HRMS. Furtherly, the PK characteristics of lumateperone and its N-demethylated metabolite (M3) in rat plasma were investigated using a validated LC-MS/MS method following intravenous and oral administration. Fourteen phase I metabolites were found in liver microsomes and ten of them were observed in rat plasma. N-demethylation, carbonylation, dehydrogenation, and piperazine ring cleavage were main metabolic pathway of lumateperone. No unique metabolites were formed in human liver microsomes. After rapid absorption in rats, lumateperone was quickly metabolized and eliminated with bioavailability of less than 5%. The exposure level of M3 was about 1.5-fold higher than that of lumateperone in rat plasma. Lumatperone underwent extensive metabolism and was absorbed rapidly in rats. Metabolite M3 had equivalent or slightly higher exposure levels than lumateperone. This study provides essential PK information to facilitate further pharmacodynamic researches of lumateperone.
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Affiliation(s)
- Yifan Qiu
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China
| | - Jing Guo
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China
| | - Jindong Chen
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China
| | - Wenjing Zhang
- State Key Laboratory of Advanced Drug Delivery and Release Systems, Shandong Luye Pharmaceutical Co., Ltd., Yantai, Shandong 264003, China
| | - Wenyan Wang
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China; State Key Laboratory of Advanced Drug Delivery and Release Systems, Shandong Luye Pharmaceutical Co., Ltd., Yantai, Shandong 264003, China.
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Zacker C, Puckett JT, Kamal-Bahl S. Real-World Adherence and Discontinuation of Oral Antipsychotics and Associated Factors in a National Sample of US Medicare Beneficiaries with Schizophrenia. CLINICOECONOMICS AND OUTCOMES RESEARCH 2024; 16:567-579. [PMID: 39161925 PMCID: PMC11330860 DOI: 10.2147/ceor.s469001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 08/03/2024] [Indexed: 08/21/2024] Open
Abstract
Purpose Little is known about adherence to and discontinuation of newly initiated oral antipsychotics (OAPs) as well as associated factors among Medicare beneficiaries with schizophrenia. This study aimed to examine rates of OAP adherence and discontinuation and associated factors in a national sample of fee-for-service Medicare beneficiaries with schizophrenia. Patients and Methods This retrospective study used 100% fee-for-service Medicare claims data to identify adult beneficiaries with schizophrenia, initiating a new OAP between 01/01/2017 and 12/31/2019 (index date = date of new OAP prescription). Outcomes included adherence and discontinuation. Factors associated with adherence were assessed using logistic and linear regressions; Cox regressions were used to assess factors associated with discontinuation. Results In our final sample of 46,452 Medicare beneficiaries with schizophrenia, 35.4% were adherent to their newly initiated OAP (mean [SD] PDC: 0.52 [0.37]) over 12 months after initiation. Most patients (79.4%) discontinued their new OAP (median [IQR] time to discontinuation: 3.6 (1.0, 9.9) months). Factors associated with lower odds of adherence included younger age (OR: 0.43; 95% CI: 0.40-0.47, p <0.001 for patients aged 18-35 relative to patients aged ≥65 years); non-White race (OR: 0.72; 95% CI: 0.69-0.75, p <0.001 relative to White patients); and evidence of prior schizophrenia-related hospitalization (OR: 0.80; 95% CI: 0.77-0.83, p <0.001 relative to patients without evidence of prior schizophrenia-related hospitalization). Similar associations were observed for discontinuation outcomes. Twice-daily dosing frequency was also associated with lower odds of adherence (odds ratio [OR]: 0.93; 95% CI: 0.89-0.97, p = 0.0014) and higher hazard of discontinuation (hazard ratio [HR]: 1.03; 95% CI: 1.00-1.05, p = 0.0244) relative to once-daily dosing frequency. Conclusion We found high rates of non-adherence and discontinuation among Medicare beneficiaries initiated on currently available OAPs. We also identified risk factors that contribute to increased odds of medication non-adherence. By identifying at-risk patient populations, targeted interventions can be initiated to facilitate treatment continuity.
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Puolakka H, Solismaa A, Lyytikäinen LP, Viikki M, Seppälä N, Mononen N, Lehtimäki T, Kampman O. Polymorphisms in ERBB4 and TACR1 associated with dry mouth in clozapine-treated patients. Acta Neuropsychiatr 2024; 36:218-223. [PMID: 38634369 DOI: 10.1017/neu.2024.9] [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: 04/19/2024]
Abstract
BACKGROUND Sialorrhea is a common and uncomfortable adverse effect of clozapine, and its severity varies between patients. The aim of the study was to select broadly genes related to the regulation of salivation and study associations between sialorrhea and dry mouth and polymorphisms in the selected genes. METHODS The study population consists of 237 clozapine-treated patients, of which 172 were genotyped. Associations between sialorrhea and dry mouth with age, sex, BMI, smoking, clozapine dose, clozapine and norclozapine serum levels, and other comedication were studied. Genetic associations were analyzed with linear and logistic regression models explaining sialorrhea and dry mouth with each SNP added separately to the model as coefficients. RESULTS Clozapine dose, clozapine or norclozapine concentration and their ratio were not associated with sialorrhea or dryness of mouth. Valproate use (p = 0.013) and use of other antipsychotics (p = 0.015) combined with clozapine were associated with excessive salivation. No associations were found between studied polymorphisms and sialorrhea. In analyses explaining dry mouth with logistic regression with age and sex as coefficients, two proxy-SNPs were associated with dry mouth: epidermal growth factor receptor 4 (ERBB4) rs3942465 (adjusted p = 0.025) and tachykinin receptor 1 (TACR1) rs58933792 (adjusted p = 0.029). CONCLUSION Use of valproate or antipsychotic polypharmacy may increase the risk of sialorrhea. Genetic variations in ERBB4 and TACR1 might contribute to experienced dryness of mouth among patients treated with clozapine.
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Affiliation(s)
- Hanna Puolakka
- Department of Psychiatry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Anssi Solismaa
- Department of Psychiatry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Psychiatry, The Pirkanmaa Wellbeing Services County, Tampere, Finland
| | - Leo-Pekka Lyytikäinen
- Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Merja Viikki
- Department of Psychiatry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Psychiatry, The Wellbeing Services County of Ostrobothnia, Seinäjoki, Finland
| | - Niko Seppälä
- Department of Psychiatry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Psychiatry, Satasairaala Hospital, The Satakunta Wellbeing Services County, Pori, Finland
| | - Nina Mononen
- Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Terho Lehtimäki
- Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Olli Kampman
- Department of Psychiatry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Psychiatry, The Pirkanmaa Wellbeing Services County, Tampere, Finland
- Department of Psychiatry, Department of Clinical Sciences (Psychiatry), Faculty of Medicine, University Hospital of Umeå, Umeå University, Umeå, Sweden
- Department of Clinical Medicine (Psychiatry), Faculty of Medicine, University of Turku, Turku, Finland
- Department of Psychiatry, The Wellbeing Services County of Ostrobothnia, Vaasa, Finland
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Garner S, Barkus E, Kraeuter AK. Positive and negative schizotypy personality traits are lower in individuals on ketogenic diet in a non-clinical sample. Schizophr Res 2024; 270:423-432. [PMID: 38991418 DOI: 10.1016/j.schres.2024.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 05/07/2024] [Accepted: 07/03/2024] [Indexed: 07/13/2024]
Abstract
Schizotypal personality comprises traits such as odd beliefs, perceptual abnormalities, and social difficulties; these traits are distributed throughout the general population. While not meeting the clinical threshold for schizophrenia or schizotypal personality disorder, schizotypal personality traits still provide insights for understanding early clinical risk factors. Ketogenic diet reportedly reduces psychotic symptoms in preclinical and clinical studies. Therefore, we investigated whether ketogenic diet is associated with lower schizotypal traits in the general population. Participants following a ketogenic or other diet were recruited using opportunity sampling. Individuals completed a survey investigating general demographic, socioeconomic, health, diet and lifestyle questions, followed by the Schizotypal Personality Questionnaire - Brief Revised version (SPQ-BR). We found that individuals following a ketogenic diet (n = 118) had lower ideas of reference, magical thinking, suspiciousness, unusual perceptions, constricted affect, social anxiety scores, cognitive (positive) perceptual scores, interpersonal (negative) scores and total SPQ-BR compared to individuals on the other diets (n = 139). Magical thinking, constricted affect, social anxiety, cognitive perceptual, interpersonal scores and total SPQ-BR scores remained significant when we controlled for body mass index (BMI) and age. Disorganised features were not influenced by ketogenic diet. The longer individuals adhered to a ketogenic diet the lower their positive and negative schizotypy traits. These findings highlight that ketogenic diet is associated with lower non-clinical schizotypal personality traits. Our results suggest that ketogenic diet might have potential prophylactic properties for individuals at-risk for psychosis.
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Affiliation(s)
- Sarah Garner
- Faculty of Health and Life Sciences, Psychology, Northumbria University, Newcastle upon Tyne, UK
| | - Emma Barkus
- Faculty of Health and Life Sciences, Psychology, Northumbria University, Newcastle upon Tyne, UK
| | - Ann-Katrin Kraeuter
- Faculty of Health and Life Sciences, Psychology, Northumbria University, Newcastle upon Tyne, UK; Brain, Performance and Nutrition Research Centre, Northumbria University, Newcastle upon Tyne, UK; NUTRAN, Northumbria University, Newcastle upon Tyne, UK.
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Yang S, Kim JW. Electrophysiological Markers Predicting Antipsychotic Treatment Response in Patients with Schizophrenia: A Retrospective Study. Neuropsychiatr Dis Treat 2024; 20:1387-1394. [PMID: 39007072 PMCID: PMC11246663 DOI: 10.2147/ndt.s467180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 06/29/2024] [Indexed: 07/16/2024] Open
Abstract
Purpose This study aimed to provide an objective means of predicting treatment responses in patients with schizophrenia using quantitative electroencephalography (qEEG) as an electrophysiological indicator. We obtained qEEG recordings from patients with schizophrenia and explored them for patterns indicative of treatment responsiveness. Patients and Methods The study included 68 patients had been diagnosed with schizophrenia spectrum disorder. After retrospectively gathering demographic information, clinical data such as qEEG, Positive and Negative Syndrome Scale (PANSS), a multiple regression analysis was performed. This analysis employed baseline qEEG findings as independent variables and PANSS score changes as dependent variables to discern causal relationships. Results The mean age of the participants was 38.4 years(SD =13.73). The mean PANSS score on admission was 92.97, decreasing to 67.41 at discharge. Multiple regression analysis revealed that delta waves in T4 (β=0.346, t=3.165, p=0.002), and high-beta waves in Fp2 (β=0.231, t=2.361, p=0.021) were associated with PANSS changes in absolute power. In addition, the delta waves of O2 (β=0.250, t=3.288, p=0.002); beta waves of T3 (β=-1.463, t=-5.423, p<0.001) and O2 (β=0.551, t=3.366, p=0.001); high beta waves of Fp1 (β=0.307, t=4.026, p<0.001), T3 (β=0.855, t=4.414, p<0.001) and T6 (β=-0.838, t=-4.559, p<0.001) of absolute power using the Z-score were also related to PANSS changes. Pearson's correlation analysis showed that only delta waves at Cz (r= 0.246, p=0.043) in absolute power correlated with changes in the PANSS. Conclusion We found that certain qEEG wave patterns in patients with schizophrenia prior to antipsychotic treatment were linked to PANSS changes before and after treatment. Delta waves and beta waves, primarily in the frontal and temporal regions, were found to be significantly associated with changes in PANSS scores. In the future, the qEEG indicators identified in this study could serve as electrophysiological markers for predicting antipsychotic treatment responses in patients with schizophrenia.
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Affiliation(s)
- Seungheon Yang
- Department of Psychiatry, Daegu Catholic University Medical Center, Daegu, Republic of Korea
| | - Jun Won Kim
- Department of Psychiatry, Daegu Catholic University Medical Center, Daegu, Republic of Korea
- Department of Psychiatry, Daegu Catholic University School of Medicine, Daegu, Republic of Korea
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Azargoonjahromi A. Current Findings and Potential Mechanisms of KarXT (Xanomeline-Trospium) in Schizophrenia Treatment. Clin Drug Investig 2024; 44:471-493. [PMID: 38904739 DOI: 10.1007/s40261-024-01377-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/10/2024] [Indexed: 06/22/2024]
Abstract
Standard schizophrenia treatment involves antipsychotic medications that target D2 dopamine receptors. However, these drugs have limitations in addressing all symptoms and can lead to adverse effects such as motor impairments, metabolic effects, sedation, sexual dysfunction, cognitive impairment, and tardive dyskinesia. Recently, KarXT has emerged as a novel drug for schizophrenia. KarXT combines xanomeline, a muscarinic receptor M1 and M4 agonist, with trospium, a nonselective antimuscarinic agent. Of note, xanomeline can readily cross blood-brain barrier (BBB) and, thus, enter into the brain, thereby stimulating muscarinic receptors (M1 and M4). By doing so, xanomeline has been shown to target negative symptoms and potentially improve positive symptoms. Trospium, on the other hand, is not able to cross BBB, thereby not affecting M1 and M4 receptors; instead, it acts as an antimuscarinic agent and, hence, diminishes peripheral activity of muscarinic receptors to minimize side effects probably stemming from xanomeline in other organs. Accordingly, ongoing clinical trials investigating KarXT's efficacy in schizophrenia have demonstrated positive outcomes, including significant improvements in the Positive and Negative Syndrome Scale (PANSS) total score and cognitive function compared with placebo. These findings emphasize the potential of KarXT as a promising treatment for schizophrenia, providing symptom relief while minimizing side effects associated with xanomeline monotherapy. Despite such promising evidence, further research is needed to confirm the efficacy, safety, and tolerability of KarXT in managing schizophrenia. This review article explores the current findings and potential mechanisms of KarXT in the treatment of schizophrenia.
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Affiliation(s)
- Ali Azargoonjahromi
- Shiraz University of Medical Sciences, Janbazan Blv, 14th Alley, Jahrom, Shiraz, 7417773539, Fars, Iran.
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Ren L, Xuan L, Li A, Yang Y, Zhang W, Zhang J, Zhang Y, An Z. Gamma-aminobutyric acid supplementation improves olanzapine-induced insulin resistance by inhibiting macrophage infiltration in mice subcutaneous adipose tissue. Diabetes Obes Metab 2024; 26:2695-2705. [PMID: 38660748 DOI: 10.1111/dom.15585] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 03/08/2024] [Accepted: 03/19/2024] [Indexed: 04/26/2024]
Abstract
AIMS To investigate whether gamma-aminobutyric acid (GABA) supplementation improves insulin resistance during olanzapine treatment in mice and to explore the underlying mechanisms. MATERIALS AND METHODS Insulin resistance and body weight gain were induced in mice by 10 weeks of olanzapine treatment. Simultaneously, the mice were administered GABA after 4 weeks of olanzapine administration. RESULTS We found that mice treated with olanzapine had lower GABA levels in serum and subcutaneous white adipose tissue (sWAT). GABA supplementation restored GABA levels and improved olanzapine-induced lipid metabolism disorders and insulin resistance. Chronic inflammation in adipose tissue is one of the main contributors to insulin resistance. We found that GABA supplementation inhibited olanzapine-induced adipose tissue macrophage infiltration and M1-like polarization, especially in sWAT. In vitro studies showed that stromal vascular cells, rather than adipocytes, were sensitive to GABA. Furthermore, the results suggested that GABA improves olanzapine-induced insulin resistance at least in part through a GABAB receptor-dependent pathway. CONCLUSIONS These findings suggest that targeting GABA may be a potential therapeutic approach for olanzapine-induced metabolic disorders.
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Affiliation(s)
- Lulu Ren
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Lingling Xuan
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Anning Li
- Beijing Anding Hospital, Capital Medical University, Beijing, China
- National Medical Center for Mental Disorders, Beijing, China
| | - Yaqi Yang
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Wen Zhang
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Jie Zhang
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Yi Zhang
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Zhuoling An
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
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de Moraes FCA, Sudo RYU, Souza MEC, Fernandes MR, Dos Santos NPC. The incidence risk of gynecological cancer by antipsychotic use: a meta-analysis of 50,402 patients. BMC Cancer 2024; 24:712. [PMID: 38858638 PMCID: PMC11163728 DOI: 10.1186/s12885-024-12481-6] [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: 12/23/2023] [Accepted: 06/05/2024] [Indexed: 06/12/2024] Open
Abstract
BACKGROUND Female gynecological cancers represent a serious public health problem, with 1,398,601 new diagnoses and 671,875 deaths per year worldwide. Antipsychotics are often used in psychiatric disorders, including schizophrenia, bipolar disorder, and major depression. It is estimated that the prescription of these drugs is linked to 1,800 deaths a year in the United States, but their association with cancer remains controversial. METHODS We searched PubMed, Scopus, and Web of Science databases for studies reporting the correlation in the incidence risk of gynecological cancer by antipsychotic use. We used DerSimonian and Laird random-effect models to compute logit transformed odds ratio (OR) for the primary binary endpoint with 95% confidence interval (CI). Heterogeneity was assessed through effect size width along with I-squared and Tau-squared statistics. Review Manager 5.4.1. was used for statistical analyses. A p-value of < 0.05 denoted statistically significant. RESULTS 50,402 patients were included, of whom 778 (1,54%) took antipsychotic medication for at least 1 year. 1,086 (2,15%) with ovarian cancer and 49,316 (97,85%) with endometrial cancer. Antipsychotic use (OR 1.50; 1.06 to 2.13 95% CI; p-value 0.02), hypertension (OR 1.50; 95% CI 1.06 to 2.13; p-value < 0.01), nulliparity (OR 1.98; 95% CI 1.53 to 2.57; p-value < 0.01) and multiparity (OR 0.53; 95% CI 0.41 to 0.69; p-value < 0.01) showed significantly different distributions between groups of cancer and cancer-free patients. The primary endpoint of incidence risk of gynecological cancer by antipsychotic therapy showed a statistically significant difference (OR 1.67; 95% CI 1.02 to 2.73; p-value < 0.05) against the use of antipsychotic drugs. CONCLUSIONS Our meta-analysis showed that the use of antipsychotic drugs increases the risk of gynecological cancers, particularly endometrial cancer. This result should be weighed against the potential effects of treatment for a balanced prescribing decision.
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Affiliation(s)
- Francisco Cezar Aquino de Moraes
- Oncology Research Center, University Hospital João de Barros de Barreto, Federal University of Pará, Rua dos Mundurucus, n?4487, Belém, PA, 66073-000, Brazil.
| | | | | | - Marianne Rodrigues Fernandes
- Oncology Research Center, University Hospital João de Barros de Barreto, Federal University of Pará, Rua dos Mundurucus, n?4487, Belém, PA, 66073-000, Brazil
| | - Ney Pereira Carneiro Dos Santos
- Oncology Research Center, University Hospital João de Barros de Barreto, Federal University of Pará, Rua dos Mundurucus, n?4487, Belém, PA, 66073-000, Brazil
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Augustin E, Beaudoin M, Giguère S, Ziady H, Phraxayavong K, Dumais A. The Relationship between Sense of Presence, Emotional Response, and Clinical Outcomes in Virtual Reality-Based Therapy for Treatment-Resistant Schizophrenia: An Exploratory Correlational Study. J Pers Med 2024; 14:614. [PMID: 38929835 PMCID: PMC11204393 DOI: 10.3390/jpm14060614] [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: 04/29/2024] [Revised: 06/03/2024] [Accepted: 06/05/2024] [Indexed: 06/28/2024] Open
Abstract
Avatar therapy (AT) is a novel virtual reality-based psychotherapy that has been developed to treat auditory verbal hallucinations (AVH) in treatment-resistant schizophrenia. Various psychotherapeutic components, such as emotions and sense of presence, could contribute to clinical outcomes. However, the interplay between sense of presence, emotions, and clinical response has seldom been investigated. This study aimed to explore the relations between sense of presence, emotions, and clinical outcomes in AT. To conduct this investigation, data from previous and ongoing AT trials were used. Sense of presence and emotions were assessed using standardized questionnaires. AVH were evaluated using the Psychotic Symptom Rating Scales. While sense of presence was positively associated with positive emotions such as control and serenity, no significant associations were found for negative emotions. Moreover, a higher level of sense of presence was associated with a bigger decrease in AVH. Overall, positive emotions seem to be associated with sense of presence in AT. Sense of presence also seems to be involved in the therapeutic outcome, thereby suggesting that this could be an important component related to clinical response. More studies are needed to confirm these trends, which could be generalized to other virtual reality-based psychotherapies.
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Affiliation(s)
- Elischa Augustin
- Research Center of the University Institute in Mental Health of Montreal, Montreal, QC H1N 3V2, Canada; (E.A.); (M.B.); (S.G.); (H.Z.)
- Department of Psychiatry and Addictology, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada
| | - Mélissa Beaudoin
- Research Center of the University Institute in Mental Health of Montreal, Montreal, QC H1N 3V2, Canada; (E.A.); (M.B.); (S.G.); (H.Z.)
- Department of Psychiatry and Addictology, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada
| | - Sabrina Giguère
- Research Center of the University Institute in Mental Health of Montreal, Montreal, QC H1N 3V2, Canada; (E.A.); (M.B.); (S.G.); (H.Z.)
- Department of Psychiatry and Addictology, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada
- School of Social Work, Faculty of Arts and Sciences, University of Montreal, Montreal, QC H3T 1J4, Canada
| | - Hind Ziady
- Research Center of the University Institute in Mental Health of Montreal, Montreal, QC H1N 3V2, Canada; (E.A.); (M.B.); (S.G.); (H.Z.)
- Department of Psychiatry and Addictology, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada
| | | | - Alexandre Dumais
- Research Center of the University Institute in Mental Health of Montreal, Montreal, QC H1N 3V2, Canada; (E.A.); (M.B.); (S.G.); (H.Z.)
- Department of Psychiatry and Addictology, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada
- Services et Recherches Psychiatriques AD, Montreal, QC H1N 3V2, Canada;
- Institut National de Psychiatrie Légale Philippe-Pinel, Montreal, QC H1C 1H1, Canada
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Jiang Y, Cai Y, Lu Y, Wu G, Zhang XY. Relationship between anemia and its correlates and cognitive function in Chinese patients with chronic schizophrenia: A large cross-sectional study. Schizophr Res Cogn 2024; 36:100300. [PMID: 38288371 PMCID: PMC10823126 DOI: 10.1016/j.scog.2024.100300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 01/12/2024] [Accepted: 01/12/2024] [Indexed: 01/31/2024]
Abstract
Background Although both anemia and schizophrenia (SCZ) can cause cognitive decline, it is unclear whether anemia worsens cognitive decline in patients with SCZ. The primary objective of this study was to investigate the prevalence of anemia and the relationship between anemia, SCZ symptom severity, and cognitive function in patients with SCZ. Methods We obtained demographic and clinical data from 1690 inpatients with SCZ. All psychiatric symptoms and cognitive functioning were assessed by the Positive and Negative Syndrome Scale (PANSS), the Mini-Mental State Examination (MMSE), and the Repeated Battery for the Assessment of Neuropsychological Status (RBANS). Hemoglobin (HGB) values as well as red blood cell (RBC) counts were collected by routine blood tests. Results The proportion of anemia in patients with SCZ was 26.36 % (383/1453). Compared to SCZ patients without anemia, SCZ patients with anemia were older, had a lower bodyweight, a smaller waist circumference and lower apolipoprotein B levels, but longer QT intervals. Further logistic regression analysis revealed that anemia was associated with age, gender, and weight. In addition, there was no difference in cognitive function between SCZ patients with and without anemia. Conclusion Our findings suggest a high proportion of anemia in patients with chronic SCZ in the Han Chinese population. Several demographic and clinical variables are associated with anemia in SCZ patients.
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Affiliation(s)
- Yang Jiang
- Guangxi Brain Disease Prevention & Treatment Research Center, Brain Hospital of Guangxi Zhuang Autonomous Region, Liuzhou, Guangxi, China
| | - Yi Cai
- Shenzhen Mental Health Center/Shenzhen KangNing Hospital, Department of Psychosomatic Disorders, Shenzhen, Guangdong, China
| | - Yaoyao Lu
- Guangxi Brain Disease Prevention & Treatment Research Center, Brain Hospital of Guangxi Zhuang Autonomous Region, Liuzhou, Guangxi, China
| | - Guanghui Wu
- Guangxi Brain Disease Prevention & Treatment Research Center, Brain Hospital of Guangxi Zhuang Autonomous Region, Liuzhou, Guangxi, China
| | - Xiang-Yang Zhang
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
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Chen Y, Yu H, Xue F, Bai J, Guo L, Peng Z. 16S rRNA gene sequencing reveals altered gut microbiota in young adults with schizophrenia and prominent negative symptoms. Brain Behav 2024; 14:e3579. [PMID: 38841824 PMCID: PMC11154826 DOI: 10.1002/brb3.3579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 05/06/2024] [Accepted: 05/07/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND Gut dysbiosis has been established as a characteristic of schizophrenia (SCH). However, the signatures regarding SCH patients with prominent negative symptoms (SCH-N) in young adults have been poorly elucidated. METHODS Stool samples were obtained from 30 young adults with SCH-N, 32 SCH patients with prominent positive symptoms (SCH-P) along with 36 healthy controls (HCs). Microbial diversity and composition were analyzed by 16S rRNA gene sequencing. Meanwhile, psychiatric symptoms were assessed by the positive and negative syndrome scale (PANSS). RESULTS There is a significant difference in β-diversity but not α-diversity indexes among the three groups. Moreover, we found a higher abundance of Fusobacteria and Proteobacteria phyla and a lower abundance of Firmicutes phyla in SCH-N when compared with HC. Besides, we identified a diagnostic potential panel comprising six genera (Coprococcus, Monoglobus, Prevotellaceae_NK3B31_group, Escherichia-Shigella, Dorea, and Butyricicoccus) that can distinguish SCH-N from HC (area under the curve = 0.939). However, the difference in microbial composition between the SCH-N and SCH-P is much less than that between SCH-N and the HC, and SCH-N and SCH-P cannot be effectively distinguished by gut microbiota. CONCLUSION The composition of gut microbiota was changed in the patients with SCH-N, which may help in further understanding of pathogenesis in young adults with SCH-N.
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Affiliation(s)
- Yi‐Huan Chen
- Department of PsychiatryXijing HospitalAir Force Medical UniversityXi'anChina
| | - Huan Yu
- Department of PsychiatryXijing HospitalAir Force Medical UniversityXi'anChina
| | - Fen Xue
- Department of PsychiatryXijing HospitalAir Force Medical UniversityXi'anChina
| | - Jie Bai
- Department of PsychiatryXijing HospitalAir Force Medical UniversityXi'anChina
- Department of PsychiatryGaoxin HospitalXi'anChina
| | - Li Guo
- Department of PsychiatryXijing HospitalAir Force Medical UniversityXi'anChina
| | - Zheng‐Wu Peng
- Department of PsychiatryXijing HospitalAir Force Medical UniversityXi'anChina
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Strube W, Wagner E, Luykx JJ, Hasan A. A review on side effect management of second-generation antipsychotics to treat schizophrenia: a drug safety perspective. Expert Opin Drug Saf 2024; 23:715-729. [PMID: 38676922 DOI: 10.1080/14740338.2024.2348561] [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: 11/09/2023] [Accepted: 04/24/2024] [Indexed: 04/29/2024]
Abstract
INTRODUCTION Effective side effects management present a challenge in antipsychotic treatment with second-generation antipsychotics (SGAs). In recent years, most of the commonly used SGAs, except for clozapine, have been shown to differ only slightly in their effectiveness, but considerably regarding perceived side effects, safety profiles, and compatibility to preexisting medical conditions. AREAS COVERED The current state of available evidence on side-effect management in SGA treatment of patients with schizophrenia spectrum disorders (SSD) is reviewed. In addition, current guideline recommendations are summarized, highlighting evidence gaps. EXPERT OPINION SGA safety and side effects needs to be considered in treatment planning. Shared decision-making assistants (SDMA) can support patients, practitioners and relatives to orient their decisions toward avoiding side effects relevant to patients' adherence. Alongside general measures like psychosocial and psychotherapeutic care, switching to better tolerated SGAs can be considered a relatively safe strategy. By contrast, novel meta-analytical evidence emphasizes that dose reduction of SGAs can statistically increase the risk of relapse and other unfavorable outcomes. Further, depending on the type and severity of SGA-related side effects, specific treatments can be used to alleviate induced side effects (e.g. add-on metformin to reduce weight-gain). Finally, discontinuation should be reserved for acute emergencies.
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Affiliation(s)
- Wolfgang Strube
- Department of Psychiatry, Psychosomatics and Psychotherapy, University of Augsburg, Augsburg, Germany
| | - Elias Wagner
- Department of Psychiatry, Psychosomatics and Psychotherapy, University of Augsburg, Augsburg, Germany
- Evidence-based psychiatry and psychotherapy, Faculty of Medicine, University of Augsburg, Augsburg, Germany
| | - Jurjen J Luykx
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands
- Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands
- Outpatient second opinion clinic, GGNet Mental Health, Warnsveld, The Netherlands
| | - Alkomiet Hasan
- Department of Psychiatry, Psychosomatics and Psychotherapy, University of Augsburg, Augsburg, Germany
- DZPG (German Center for Mental Health), partner site München/Augsburg, Augsburg, Germany
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Gonçalves CC, Waters Z, Quirk SE, Haddad PM, Lin A, Williams LJ, Yung AR. Barriers and facilitators to mental health treatment access and engagement for LGBTQA+ people with psychosis: a scoping review protocol. Syst Rev 2024; 13:143. [PMID: 38816775 PMCID: PMC11137929 DOI: 10.1186/s13643-024-02566-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 05/17/2024] [Indexed: 06/01/2024] Open
Abstract
BACKGROUND The prevalence of psychosis has been shown to be disproportionately high amongst sexual and gender minority individuals. However, there is currently little consideration of the unique needs of this population in mental health treatment, with LGBTQA+ individuals facing barriers in accessing timely and non-stigmatising support for psychotic experiences. This issue deserves attention as delays to help-seeking and poor engagement with treatment predict worsened clinical and functional outcomes for people with psychosis. The present protocol describes the methodology for a scoping review which will aim to identify barriers and facilitators faced by LGBTQA+ individuals across the psychosis spectrum in help-seeking and accessing mental health support. METHODS A comprehensive search strategy will be used to search Medline, PsycINFO, Embase, Scopus, LGBTQ+ Source, and grey literature. Original studies of any design, setting, and publication date will be included if they discuss barriers and facilitators to mental health treatment access and engagement for LGBTQA+ people with experiences of psychosis. Two reviewers will independently screen titles/abstracts and full-text articles for inclusion in the review. Both reviewers will then extract the relevant data according to pre-determined criteria, and study quality will be assessed using the Joanna Briggs Institute (JBI) critical appraisal checklists. Key data from included studies will be synthesised in narrative form according to the Guidance on the Conduct of Narrative Synthesis in Systematic Reviews. DISCUSSION The results of this review will provide a comprehensive account of the current and historical barriers and facilitators to mental healthcare faced by LGBTQA+ people with psychotic symptoms and experiences. It is anticipated that the findings from this review will be relevant to clinical and community services and inform future research. Findings will be disseminated through publication in a peer-reviewed journal and presented at conferences. SCOPING REVIEW REGISTRATION This protocol is registered in Open Science Framework Registries ( https://doi.org/10.17605/OSF.IO/AT6FC ).
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Affiliation(s)
- Cláudia C Gonçalves
- Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC, 3220, Australia.
| | - Zoe Waters
- Telethon Kids Institute, University of Western Australia, Perth, WA, 6009, Australia
| | - Shae E Quirk
- Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC, 3220, Australia
| | - Peter M Haddad
- Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC, 3220, Australia
- University Hospital Geelong, Barwon Health, Geelong, VIC, 3220, Australia
| | - Ashleigh Lin
- School of Population and Global Health, University of Western Australia, Perth, WA, 6009, Australia
| | - Lana J Williams
- Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC, 3220, Australia
| | - Alison R Yung
- Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC, 3220, Australia
- School of Health Sciences, University of Manchester, Manchester, M13 9PL, UK
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Xie Y, Li C, Guan M, Zhang T, Ma C, Wang Z, Ma Z, Wang H, Fang P. The efficacy of low frequency repetitive transcial magnetic stimulation for treating auditory verbal hallucinations in schizophrenia: Insights from functional gradient analyses. Heliyon 2024; 10:e30194. [PMID: 38707410 PMCID: PMC11066630 DOI: 10.1016/j.heliyon.2024.e30194] [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: 01/22/2024] [Revised: 04/20/2024] [Accepted: 04/22/2024] [Indexed: 05/07/2024] Open
Abstract
Background Auditory Verbal Hallucinations (AVH) constitute a prominent feature of schizophrenia. Although low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated therapeutic benefits in ameliorating AVH, the underlying mechanisms of its efficacy necessitate further elucidation. Objective This study investigated the cortical gradient characteristics and their associations with clinical responses in schizophrenia patients with AVH, mediated through 1 Hz rTMS targeting the left temporoparietal junction. Method Functional gradient metrics were employed to examine the hierarchy patterns of cortical organization, capturing whole-brain functional connectivity profiles in patients and controls. Results The 1 Hz rTMS treatment effectively ameliorated the positive symptoms in patients, specifically targeting AVH. Initial evaluations revealed expanded global gradient distribution patterns and specific principal gradient variations in certain brain regions in patients at baseline compared to a control cohort. Following treatment, these divergent global and local patterns showed signs of normalizing. Furthermore, there was observed a closer alignment in between-network dispersion among various networks after treatment, including the somatomotor, attention, and limbic networks, indicating a potential harmonization of brain functionality. Conclusion Low-frequency rTMS induces alternations in principal functional gradient patterns, may serve as imaging markers to elucidate the mechanisms underpinning the therapeutic efficacy of rTMS on AVH in schizophrenia.
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Affiliation(s)
- Yuanjun Xie
- Military Medical Psychology School, Fourth Military Medical University, Xi'an, China
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Chenxi Li
- Military Medical Psychology School, Fourth Military Medical University, Xi'an, China
| | - Muzhen Guan
- Department of Mental Health, Xi'an Medical College, Xi'an, China
| | - Tian Zhang
- Military Medical Psychology School, Fourth Military Medical University, Xi'an, China
| | - Chaozong Ma
- Military Medical Psychology School, Fourth Military Medical University, Xi'an, China
| | - Zhongheng Wang
- Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Zhujing Ma
- Military Medical Psychology School, Fourth Military Medical University, Xi'an, China
| | - Huaning Wang
- Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Peng Fang
- Military Medical Psychology School, Fourth Military Medical University, Xi'an, China
- Shaanxi Provincial Key Laboratory of Bioelectromagnetic Detection and Intelligent Perception, Xi'an, China
- Military Medical Innovation Center, Fourth Military Medical University, Xi'an, China
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Alemany-Navarro M, Sánchez-Barbero B, Reguera-Pozuelo P, Altea-Manzano L, Gómez-Garrido A, Rocha-González I, Garrido-Torres N, Ruiz-Veguilla M, García-Cerro S, Rosso-Fernández CM, Villagrán-Moreno JM, Sarramea F, Cervilla-Ballesteros J, Martínez-Leal R, Mayoral-Cleries F, Crespo-Facorro B. Efficacy of clozapine versus standard treatment in adult individuals with intellectual disability and treatment-resistant psychosis (CLOZAID): study protocol of a multicenter randomized clinical trial. Front Psychiatry 2024; 15:1400621. [PMID: 38807685 PMCID: PMC11130499 DOI: 10.3389/fpsyt.2024.1400621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 04/23/2024] [Indexed: 05/30/2024] Open
Abstract
Background Intellectual disability (ID) affects approximately 1% of the worldwide population and individuals with ID have a higher comorbidity with mental illness, and specifically psychotic disorders. Unfortunately, among individuals with ID, limited research has been conducted since ID individuals are usually excluded from mental illness epidemiological studies and clinical trials. Here we perform a clinical trial to investigate the effectiveness of clozapine in the treatment of resistant psychosis in individuals with ID. The article highlights the complexity of diagnosing and treating psychopathological alterations associated with ID and advocates for more rigorous research in this field. Methods A Phase IIB, open-label, randomized, multicenter clinical trial (NCT04529226) is currently ongoing to assess the efficacy of oral clozapine in individuals diagnosed with ID and suffering from treatment-resistant psychosis. We aim to recruit one-hundred and fourteen individuals (N=114) with ID and resistant psychosis, who will be randomized to TAU (treatment as usual) and treatment-with-clozapine conditions. As secondary outcomes, changes in other clinical scales (PANSS and SANS) and the improvement in functionality, assessed through changes in the Euro-QoL-5D-5L were assessed. The main outcome variables will be analyzed using generalized linear mixed models (GLMM), assessing the effects of status variable (TAU vs. Clozapine), time, and the interaction between them. Discussion The treatment of resistant psychosis among ID individuals must be directed by empirically supported research. CLOZAID clinical trial may provide relevant information about clinical guidelines to optimally treat adults with ID and treatment-resistant psychosis and the benefits and risks of an early use of clozapine in this underrepresented population in clinical trials. Trial registration Clinicaltrials.gov: NCT04529226. EudraCT: 2020-000091-37.
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Affiliation(s)
- María Alemany-Navarro
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Foundation for Health Research Management in Sevilla, Sevilla, Spain
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
| | - Bianca Sánchez-Barbero
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
| | - Pablo Reguera-Pozuelo
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Foundation for Health Research Management in Sevilla, Sevilla, Spain
| | - Laura Altea-Manzano
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
| | - Ana Gómez-Garrido
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
| | - Idalino Rocha-González
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
| | - Nathalia Garrido-Torres
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Mental Health Unit, Virgen del Rocio University Hospital, Seville, Spain
| | - Miguel Ruiz-Veguilla
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Mental Health Unit, Virgen del Rocio University Hospital, Seville, Spain
- Department of Psychiatry, Faculty of Medicine, University of Seville, Seville, Spain
| | - Susana García-Cerro
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Foundation for Health Research Management in Sevilla, Sevilla, Spain
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
| | | | - José María Villagrán-Moreno
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Mental Health Unit, Área de Gestión Sanitaria Jerez, Costa Noroeste y Sierra de Cádiz, Cádiz, Spain
- Neurosciences Department, University of Cádiz, Cádiz, Spain
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Cádiz, Spain
| | | | - Jorge Cervilla-Ballesteros
- Hospital Universitario San Cecilio, Granada, Spain
- Psychiatry Department, University of Granada, Granada, Spain
| | - Rafael Martínez-Leal
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Fundació Villablanca, Unidad de Investigación en Discapacidad Intelectual y Trastornos del Desarrollo (UNIVIDD), Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain
- Psychology Department, Universitat Rovira i Virgili, Tarragona, Spain
| | | | - Benedicto Crespo-Facorro
- Translational Psychiatry Group, Seville Biomedical Research Institute (IBiS)-CSIC, Seville, Spain
- Spanish Network for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Mental Health Unit, Virgen del Rocio University Hospital, Seville, Spain
- Department of Psychiatry, Faculty of Medicine, University of Seville, Seville, Spain
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Richardson B, Clarke C, Blundell J, Bambico FR. Therapeutic-like activity of cannabidiolic acid methyl ester in the MK-801 mouse model of schizophrenia: Role for cannabinoid CB1 and serotonin-1A receptors. Eur J Neurosci 2024; 59:2403-2415. [PMID: 38385841 DOI: 10.1111/ejn.16278] [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: 08/10/2023] [Revised: 01/15/2024] [Accepted: 01/27/2024] [Indexed: 02/23/2024]
Abstract
Schizophrenia is a psychotic disorder with an increasing prevalence and incidence over the last two decades. The condition presents with a diverse array of positive, negative, and cognitive impairments. Conventional treatments often yield unsatisfactory outcomes, especially with negative symptoms. We investigated the role of prefrontocortical (PFC) N-methyl-D-aspartate receptors (NMDARs) in the pathophysiology and development of schizophrenia. We explored the potential therapeutic effects of cannabidiolic acid (CBDA) methyl ester (HU-580), an analogue of CBDA known to act as an agonist of the serotonin-1A receptor (5-HT1AR) and an antagonist of cannabinoid type 1 receptor (CB1R). C57BL/6 mice were intraperitoneally administered the NMDAR antagonist, dizocilpine (MK-801, .3 mg/kg) once daily for 17 days. After 7 days, they were concurrently given HU-580 (.01 or .05 μg/kg) for 10 days. Behavioural deficits were assessed at two time points. We conducted enzyme-linked immunosorbent assays to measure the concentration of PFC 5-HT1AR and CB1R. We found that MK-801 effectively induced schizophrenia-related behaviours including hyperactivity, social withdrawal, increased forced swim immobility, and cognitive deficits. We discovered that low-dose HU-580 (.01 μg/kg), but not the high dose (.05 μg/kg), attenuated hyperactivity, forced swim immobility and cognitive deficits, particularly in female mice. Our results revealed that MK-801 downregulated both CB1R and 5-HT1AR, an effect that was blocked by both low- and high-dose HU-580. This study sheds light on the potential antipsychotic properties of HU-580, particularly in the context of NMDAR-induced dysfunction. Our findings could contribute significantly to our understanding of schizophrenia pathophysiology and offer a promising avenue for exploring the therapeutic potential of HU-580 and related compounds in alleviating symptoms.
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MESH Headings
- Animals
- Schizophrenia/drug therapy
- Schizophrenia/chemically induced
- Schizophrenia/metabolism
- Dizocilpine Maleate/pharmacology
- Receptor, Serotonin, 5-HT1A/metabolism
- Receptor, Serotonin, 5-HT1A/drug effects
- Male
- Mice
- Female
- Receptor, Cannabinoid, CB1/metabolism
- Receptor, Cannabinoid, CB1/agonists
- Mice, Inbred C57BL
- Disease Models, Animal
- Cannabinoids/pharmacology
- Receptors, N-Methyl-D-Aspartate/metabolism
- Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
- Antipsychotic Agents/pharmacology
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Affiliation(s)
- Brandon Richardson
- Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada
| | - Courtney Clarke
- Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada
| | - Jacqueline Blundell
- Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada
| | - Francis R Bambico
- Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada
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Utas-Akhan L, Avci D, Basak I. Art Therapy as a Nursing Intervention for Individuals With Schizophrenia. J Psychosoc Nurs Ment Health Serv 2024; 62:29-38. [PMID: 37956349 DOI: 10.3928/02793695-20231025-02] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2023]
Abstract
The aim of the current study was to determine the effects of group art therapy on clinical symptoms, alexithymia, and quality of life among people with schizophrenia. This single-blinded, randomized controlled trial was performed with 66 individuals with schizophrenia from a community mental health center in western Turkey between September 2021 and February 2022. Following art therapy, the intervention group had lower severity of positive, negative, and general psycho-pathology symptoms; lower levels of alexithymia; and higher levels of psychological health, social relationships, and total quality of life than the control group; and the difference between groups was statistically significant (p < 0.05). Results reveal that art therapy combined with pharmacological therapy contributes to good clinical outcomes among individuals with schizophrenia. This evidence can guide psychiatric nurses to use art therapy to reduce psychopathology severity and increase functionality and quality of life among individuals with schizophrenia. [Journal of Psychosocial Nursing and Mental Health Services, 62(5), 29-38.].
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Dodd K, Legget KT, Cornier MA, Novick AM, McHugo M, Berman BD, Lawful BP, Tregellas JR. Relationship between functional connectivity and weight-gain risk of antipsychotics in schizophrenia. Schizophr Res 2024; 267:173-181. [PMID: 38552340 PMCID: PMC11332974 DOI: 10.1016/j.schres.2024.03.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 01/19/2024] [Accepted: 03/18/2024] [Indexed: 05/21/2024]
Abstract
BACKGROUND The mechanisms by which antipsychotic medications (APs) contribute to obesity in schizophrenia are not well understood. Because AP effects on functional brain connectivity may contribute to weight effects, the current study investigated how AP-associated weight-gain risk relates to functional connectivity in schizophrenia. METHODS Fifty-five individuals with schizophrenia (final N = 54) were divided into groups based on previously reported AP weight-gain risk (no APs/low risk [N = 19]; moderate risk [N = 17]; high risk [N = 18]). Resting-state functional magnetic resonance imaging (fMRI) was completed after an overnight fast ("fasted") and post-meal ("fed"). Correlations between AP weight-gain risk and functional connectivity were assessed at the whole-brain level and in reward- and eating-related brain regions (anterior insula, caudate, nucleus accumbens). RESULTS When fasted, greater AP weight-gain risk was associated with increased connectivity between thalamus and sensorimotor cortex (pFDR = 0.021). When fed, greater AP weight-gain risk was associated with increased connectivity between left caudate and left precentral/postcentral gyri (pFDR = 0.048) and between right caudate and multiple regions, including the left precentral/postcentral gyri (pFDR = 0.001), intracalcarine/precuneal/cuneal cortices (pFDR < 0.001), and fusiform gyrus (pFDR = 0.008). When fed, greater AP weight-gain risk was also associated with decreased connectivity between right anterior insula and ventromedial prefrontal cortex (pFDR = 0.002). CONCLUSIONS APs with higher weight-gain risk were associated with greater connectivity between reward-related regions and sensorimotor regions when fasted, perhaps relating to motor anticipation for consumption. Higher weight-gain risk APs were also associated with increased connectivity between reward, salience, and visual regions when fed, potentially reflecting greater desire for consumption following satiety.
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Affiliation(s)
- Keith Dodd
- Department of Psychiatry, University of Colorado School of Medicine, Anschutz Medical Campus, Anschutz Health Sciences Building, 1890 N Revere Ct, Aurora, CO 80045, USA; Department of Bioengineering, University of Colorado Denver, 12705 E Montview Blvd Suite 100, Aurora, CO 80045, USA
| | - Kristina T Legget
- Department of Psychiatry, University of Colorado School of Medicine, Anschutz Medical Campus, Anschutz Health Sciences Building, 1890 N Revere Ct, Aurora, CO 80045, USA; Research Service, Rocky Mountain Regional VA Medical Center, 1700 N Wheeling St, Aurora, CO 80045, USA
| | - Marc-Andre Cornier
- Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Medical University of South Carolina, Clinical Sciences Building, CSB 96 Jonathan Lucas Street, Charleston, SC 29425, USA
| | - Andrew M Novick
- Department of Psychiatry, University of Colorado School of Medicine, Anschutz Medical Campus, Anschutz Health Sciences Building, 1890 N Revere Ct, Aurora, CO 80045, USA
| | - Maureen McHugo
- Department of Psychiatry, University of Colorado School of Medicine, Anschutz Medical Campus, Anschutz Health Sciences Building, 1890 N Revere Ct, Aurora, CO 80045, USA
| | - Brian D Berman
- Department of Neurology, Virginia Commonwealth University, 1101 E Marshall Street, Richmond, VA 23298, USA
| | - Benjamin P Lawful
- Department of Psychiatry, University of Colorado School of Medicine, Anschutz Medical Campus, Anschutz Health Sciences Building, 1890 N Revere Ct, Aurora, CO 80045, USA
| | - Jason R Tregellas
- Department of Psychiatry, University of Colorado School of Medicine, Anschutz Medical Campus, Anschutz Health Sciences Building, 1890 N Revere Ct, Aurora, CO 80045, USA; Research Service, Rocky Mountain Regional VA Medical Center, 1700 N Wheeling St, Aurora, CO 80045, USA.
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Yoon JH, Lee D, Lee C, Cho E, Lee S, Cazenave-Gassiot A, Kim K, Chae S, Dennis EA, Suh PG. Paradigm shift required for translational research on the brain. Exp Mol Med 2024; 56:1043-1054. [PMID: 38689090 PMCID: PMC11148129 DOI: 10.1038/s12276-024-01218-x] [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] [Revised: 02/07/2024] [Accepted: 02/20/2024] [Indexed: 05/02/2024] Open
Abstract
Biomedical research on the brain has led to many discoveries and developments, such as understanding human consciousness and the mind and overcoming brain diseases. However, historical biomedical research on the brain has unique characteristics that differ from those of conventional biomedical research. For example, there are different scientific interpretations due to the high complexity of the brain and insufficient intercommunication between researchers of different disciplines owing to the limited conceptual and technical overlap of distinct backgrounds. Therefore, the development of biomedical research on the brain has been slower than that in other areas. Brain biomedical research has recently undergone a paradigm shift, and conducting patient-centered, large-scale brain biomedical research has become possible using emerging high-throughput analysis tools. Neuroimaging, multiomics, and artificial intelligence technology are the main drivers of this new approach, foreshadowing dramatic advances in translational research. In addition, emerging interdisciplinary cooperative studies provide insights into how unresolved questions in biomedicine can be addressed. This review presents the in-depth aspects of conventional biomedical research and discusses the future of biomedical research on the brain.
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Affiliation(s)
- Jong Hyuk Yoon
- Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea.
| | - Dongha Lee
- Cognitive Science Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea
| | - Chany Lee
- Cognitive Science Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea
| | - Eunji Cho
- Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea
| | - Seulah Lee
- Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea
| | - Amaury Cazenave-Gassiot
- Department of Biochemistry and Precision Medicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119077, Singapore
- Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore
| | - Kipom Kim
- Research Strategy Office, Korea Brain Research Institute, Daegu, 41062, Republic of Korea
| | - Sehyun Chae
- Neurovascular Unit Research Group, Korean Brain Research Institute, Daegu, 41062, Republic of Korea
| | - Edward A Dennis
- Department of Pharmacology and Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093-0601, USA
| | - Pann-Ghill Suh
- Korea Brain Research Institute, Daegu, 41062, Republic of Korea
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Saadullah Khani N, Hudson G, Mills G, Ramesh S, Varney L, Cotic M, Abidoph R, Richards-Belle A, Carrascal-Laso L, Franco-Martin M, Kaas-Hansen BS, Jürgens G, Barrett B, Jin H, Bramon E. A systematic review of pharmacogenetic testing to guide antipsychotic treatment. NATURE. MENTAL HEALTH 2024; 2:616-626. [PMID: 38746691 PMCID: PMC11088993 DOI: 10.1038/s44220-024-00240-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 03/20/2024] [Indexed: 12/12/2024]
Abstract
Pharmacogenomics could optimize antipsychotic treatment by preventing adverse drug reactions, improving treatment efficacy or relieving the cost burden on the healthcare system. Here we conducted a systematic review to investigate whether pharmacogenetic testing in individuals undergoing antipsychotic treatment influences clinical or economic outcomes. On 12 January 2024, we searched MEDLINE, EMBASE, PsycINFO and Cochrane Centrale Register of Controlled Trials. The results were summarized using a narrative approach and summary tables. In total, 13 studies were eligible for inclusion in the systematic review. The current evidence base is either in favor of pharmacogenetics-guided prescribing or showed no difference between pharmacogenetics and treatment as usual for clinical and economic outcomes. In the future, we require randomized controlled trials with sufficient sample sizes that provide recommendations for patients who take antipsychotics based on a broad, multigene panel, with consistent and comparable clinical outcomes.
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Affiliation(s)
- Noushin Saadullah Khani
- Mental Health Neuroscience Research Department, Division of Psychiatry, University College London, London, UK
| | - Georgie Hudson
- Mental Health Neuroscience Research Department, Division of Psychiatry, University College London, London, UK
| | - Georgina Mills
- Mental Health Neuroscience Research Department, Division of Psychiatry, University College London, London, UK
| | - Soumita Ramesh
- Mental Health Neuroscience Research Department, Division of Psychiatry, University College London, London, UK
| | - Lauren Varney
- Mental Health Neuroscience Research Department, Division of Psychiatry, University College London, London, UK
| | - Marius Cotic
- Mental Health Neuroscience Research Department, Division of Psychiatry, University College London, London, UK
- Department of Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, University College London, London, UK
| | - Rosemary Abidoph
- Mental Health Neuroscience Research Department, Division of Psychiatry, University College London, London, UK
- Camden and Islington NHS Foundation Trust, London, UK
| | - Alvin Richards-Belle
- Mental Health Neuroscience Research Department, Division of Psychiatry, University College London, London, UK
- Epidemiology and Applied Clinical Research Department, Division of Psychiatry, University College London, London, UK
| | - Lorena Carrascal-Laso
- Servicio de Psiquiatría, Hospital Provincial de Zamora, Instituto de Investigación Biomédica de Salamanca, Zamora, Spain
| | - Manuel Franco-Martin
- Servicio de Psiquiatría, Hospital Provincial de Zamora, Instituto de Investigación Biomédica de Salamanca, Zamora, Spain
| | - Benjamin Skov Kaas-Hansen
- Department of Intensive Care (4131), Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
| | - Gesche Jürgens
- Clinical Pharmacological Unit, Zealand University Hospital, Roskilde, Denmark
- Institute of Clinical Medicine, Copenhagen University, Copenhagen, Denmark
- Research Unit for Clinical Psychopharmacology, Psychiatry West, Slagelse, Denmark
| | - Barbara Barrett
- Department of Health Services and Population Research, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
| | - Huajie Jin
- King’s Health Economics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
| | - Elvira Bramon
- Mental Health Neuroscience Research Department, Division of Psychiatry, University College London, London, UK
- Camden and Islington NHS Foundation Trust, London, UK
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Gao C, Zhou T, Liu S, Miao C, Feng J, Ding Y, Lv Y. Revealing receptor-ligand interactions of atypical antipsychotic drugs and screening anti-schizophrenia ingredients in Magnolia officinalis based on 5-HTR2A-SNAP-Tag/CMC and DRD2-SNAP-Tag/CMC models. J Chromatogr A 2024; 1720:464784. [PMID: 38442497 DOI: 10.1016/j.chroma.2024.464784] [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: 10/04/2023] [Revised: 02/20/2024] [Accepted: 03/02/2024] [Indexed: 03/07/2024]
Abstract
Schizophrenia is a serious mental illness with unknown etiology, and shows increasing incidence and high lifetime prevalence rate. The main receptors related to the disease are DRD2 and 5-HTR2A. Thus, a comprehensive understanding of the interaction mode between antipsychotic drugs with relevant receptors is very important for developing more effective drugs. 5-HTR2A-SNAP-Tag/CMC and DRD2-SNAP-Tag/CMC models constructed in this work provided a new method for studying the interaction between atypical antipsychotics and the two receptors. The results of comparative experiments showed that the new models not only met the high selectivity and specificity of the screening requirements but were also more stable and long-lasting than the traditional CMC model. Binding assays showed that the effects of three atypical antipsychotics (including clozapine, olanzapine, and quetiapine) on 5-HTR2A were stronger than their effects on DRD2. Additionally, two potentially active components, magnolol and honokiol, were screened in Magnolia officinalis methanol extract using the 5-HTR2A-SNAP-Tag/CMCHPLC-MS system. Nonlinear chromatographic analysis and molecular docking were conducted to study the interactions between screened compounds and the two receptors. The binding constants (KA) of magnolol and honokiol with 5-HTR2A were 17,854 ± 1,117 M-1 and 38,858 ± 4,964 M-1, respectively, and KA values with DRD2 were 4,872 ± 1,618 M-1 and 20,692 ± 10,267 M-1, respectively. We concluded that the established models are reliable for studying receptor-ligand interactions and screening antagonists of schizophrenia.
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Affiliation(s)
- Chunlei Gao
- School of Pharmacy, Xi'an Jiaotong University, 76# Yanta West Road, Xi'an, 710061, China; Institute of Pharmaceutical Science and Technology, Western China Science &Technology Innovation Harbour, Xi'an, 710115, China; Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Tongpei Zhou
- School of Pharmacy, Xi'an Jiaotong University, 76# Yanta West Road, Xi'an, 710061, China; Institute of Pharmaceutical Science and Technology, Western China Science &Technology Innovation Harbour, Xi'an, 710115, China
| | - Sihan Liu
- School of Pharmacy, Xi'an Jiaotong University, 76# Yanta West Road, Xi'an, 710061, China; Institute of Pharmaceutical Science and Technology, Western China Science &Technology Innovation Harbour, Xi'an, 710115, China
| | - Chenyang Miao
- School of Pharmacy, Xi'an Jiaotong University, 76# Yanta West Road, Xi'an, 710061, China; Institute of Pharmaceutical Science and Technology, Western China Science &Technology Innovation Harbour, Xi'an, 710115, China
| | - Jingting Feng
- School of Pharmacy, Xi'an Jiaotong University, 76# Yanta West Road, Xi'an, 710061, China; Institute of Pharmaceutical Science and Technology, Western China Science &Technology Innovation Harbour, Xi'an, 710115, China
| | - Yifan Ding
- School of Pharmacy, Xi'an Jiaotong University, 76# Yanta West Road, Xi'an, 710061, China; Institute of Pharmaceutical Science and Technology, Western China Science &Technology Innovation Harbour, Xi'an, 710115, China
| | - Yanni Lv
- School of Pharmacy, Xi'an Jiaotong University, 76# Yanta West Road, Xi'an, 710061, China; Institute of Pharmaceutical Science and Technology, Western China Science &Technology Innovation Harbour, Xi'an, 710115, China.
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