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Meza N, Franco JV, Sguassero Y, Núñez V, Escobar Liquitay CM, Rees R, Williams K, Rojas V, Rojas F, Pringsheim T, Madrid E. Atypical antipsychotics for autism spectrum disorder: a network meta-analysis. Cochrane Database Syst Rev 2025; 5:CD014965. [PMID: 40396498 PMCID: PMC12093454 DOI: 10.1002/14651858.cd014965.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/22/2025]
Abstract
RATIONALE Individuals with autism spectrum disorder (ASD) exhibit a wide variety of symptoms related to social interaction and behaviour. Atypical antipsychotics have been widely evaluated and prescribed to treat distressing symptoms (e.g. irritability, aggression, obsessions, repetitive behaviours, etc.) in children and adults with ASD. Still, their effects and relative efficacy remain unclear. OBJECTIVES Primary: to assess the comparative benefits of atypical antipsychotics for irritability through network meta-analyses in children and adults with ASD at short-term follow-up. Secondary: to assess the benefits and harms of atypical antipsychotics, compared to placebo or any other atypical antipsychotic, for different symptoms (e.g. aggression, obsessive-compulsive behaviours, inappropriate speech) and side effects (e.g. extrapyramidal symptoms, weight gain, metabolic side effects) in children and adults with ASD at short-, medium- and long-term follow-up. SEARCH METHODS We searched CENTRAL, MEDLINE, 10 other databases, and two trial registers, together with reference checking, citation searching and contact with study authors to identify studies for inclusion. The latest search was 3 January 2024. ELIGIBILITY CRITERIA Randomised controlled trials (RCTs) comparing any atypical antipsychotic drug with placebo or another atypical antipsychotic drug for adults and children with a clinical diagnosis of ASD. OUTCOMES Critical outcomes included irritability, aggression, weight gain, extrapyramidal side effects, obsessive-compulsive behaviours and inappropriate speech. RISK OF BIAS We used the Cochrane RoB 2 tool to assess risk of bias in the included studies. SYNTHESIS METHODS We performed statistical analyses using a frequentist network meta-analysis for combined estimates for the outcome irritability and a random-effects model for pairwise comparisons for other outcomes. We rated the certainty of the evidence using GRADE. INCLUDED STUDIES We included 17 studies with 1027 randomised participants. One study evaluated adults (31 participants); the remaining 16 studies evaluated children (996 participants). The interventions were risperidone, aripiprazole, lurasidone and olanzapine. SYNTHESIS OF RESULTS Comparative efficacy on irritability Based on the network meta-analysis, risperidone and aripiprazole may reduce symptoms of irritability compared to placebo in the short term in children with ASD (risperidone: mean difference (MD) -7.89, 95% confidence interval (CI) -9.37 to -6.42; 13 studies, 906 participants; low-certainty evidence; aripiprazole: MD -6.26, 95% CI -7.62 to -4.91; 13 studies, 906 participants; low-certainty evidence). Lurasidone probably results in little to no difference in irritability compared to placebo in the short term (MD -1.30, 95% CI -5.46 to 2.86; 13 studies, 906 participants; moderate-certainty evidence). Efficacy and safety on other outcomes We are very uncertain about the effects of atypical antipsychotics on aggression compared to placebo at short-term follow-up in children with ASD (risk ratio (RR) 1.06, 95% CI 0.96 to 1.17; 1 study, 66 participants; very low-certainty evidence). The certainty of the evidence was very low due to concerns about risk of bias and serious imprecision. We are very uncertain about the effects of atypical antipsychotics on the occurrence of weight gain (above predefined levels) compared to placebo in the short term in children with ASD (RR 2.40, 95% CI 1.25 to 4.60; 7 studies, 434 participants; very low-certainty evidence). We are also very uncertain about the effects of atypical antipsychotics on weight gain (in kilograms) compared to placebo in the short term in children with ASD (MD 1.22 kg, 95% CI 0.55 to 1.88; 3 studies, 297 participants; very low-certainty evidence). In both, the certainty of the evidence was very low due to concerns about risk of bias and serious imprecision. We are very uncertain about the effects of atypical antipsychotics on the occurrence of extrapyramidal side effects compared to placebo in the short term in children with ASD (RR 2.36, 95% CI 1.22 to 4.59; 6 studies, 511 participants; very low-certainty evidence). The certainty of the evidence was very low due to concerns about risk of bias and serious imprecision. Atypical antipsychotics may improve obsessive-compulsive behaviours compared to placebo in the short term in children with ASD (MD -1.36, 95% CI -2.45 to -0.27; 5 studies, 467 participants; low-certainty evidence). The certainty of the evidence was low due to concerns about risk of bias and heterogeneity. Atypical antipsychotics may reduce inappropriate speech compared to placebo in the short term in children with ASD (MD -1.44, 95% CI -2.11 to -0.77; 8 studies, 676 participants; low-certainty evidence). The certainty of the evidence was low due to concerns about risk of bias and heterogeneity. We were unable to evaluate the effects of other atypical antipsychotics. Furthermore, our findings on adults with autism were scarce due to the lack of available studies. AUTHORS' CONCLUSIONS Risperidone and aripiprazole may reduce symptoms of irritability compared to placebo in children with ASD in the short term, but lurasidone probably has little to no effect on irritability compared to placebo. Other benefits and potential harms observed ranged from moderate- to very low-certainty evidence. The available data did not allow comprehensive subgroup analyses. New randomised controlled trials with larger sample sizes are needed to balance the efficacy and safety of interventions with enough certainty, which are currently scarce (or even absent in the case of the adult population). Authors should report population and intervention characteristics transparently, providing disaggregated or individual patient data when possible. Furthermore, consistent measurement methods for each outcome should be reported to avoid problems during the data synthesis process. FUNDING This Cochrane review had no dedicated funding. REGISTRATION Protocol available via 10.1002/14651858.CD014965.
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Affiliation(s)
- Nicolás Meza
- Interdisciplinary Centre for Health Studies CIESAL, Universidad de Valparaíso, Viña del Mar, Chile
| | - Juan Va Franco
- Institute of General Practice, Medical Faculty of the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | | | - Vicente Núñez
- Interdisciplinary Centre for Health Studies CIESAL, Universidad de Valparaíso, Viña del Mar, Chile
| | | | - Reginald Rees
- Department of Psychiatry, School of Medicine, Universidad de Valparaíso, Valparaíso, Chile
| | - Katrina Williams
- Department of Paediatrics, Monash University, Melbourne, Australia
| | - Valeria Rojas
- Department of Child Neurology, School of Medicine, Universidad de Valparaíso, Viña del Mar, Chile
| | - Francisca Rojas
- Interdisciplinary Centre for Health Studies CIESAL, Universidad de Valparaíso, Viña del Mar, Chile
| | - Tamara Pringsheim
- Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
| | - Eva Madrid
- Interdisciplinary Centre for Health Studies CIESAL, Universidad de Valparaíso, Viña del Mar, Chile
- Iberoamerican Cochrane Centre, Barcelona, Spain
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Perrotta C, Carnovale C, Pozzi M, De Palma C, Cervia D, Nobile M, Clementi E. Antipsychotics and dietary interventions: Pharmacodynamics, pharmacokinetics, and synergisms in therapy. Pharmacol Rev 2025; 77:100061. [PMID: 40412008 DOI: 10.1016/j.pharmr.2025.100061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 04/18/2025] [Accepted: 04/19/2025] [Indexed: 05/27/2025] Open
Abstract
Antipsychotic (AP) medications are the primary treatment for severe mental illnesses, including schizophrenia and severe mood disorders. APs are currently categorized into typical or first-generation APs and atypical or second-generation APs. Although both first-generation and second-generation APs are considered effective in treating psychotic symptoms in severe mental disorders, they differ in their mechanisms, treatment strategies, and side effect profiles. Because of their potential motor and metabolic side effects, which often compromise patient adherence and clinical outcomes, whether and how to use APs remains controversial. The use of dietary interventions in combination with APs is emerging as a viable strategy to reduce AP adverse effects while maintaining their efficacy and enhance patient adherence to treatment. In contrast to drugs that possess a well defined molecular mechanism of action, dietary interventions act in pleiotropic ways by nature. While providing a holistic approach to patient care this pleiotropy needs to be analyzed and systematized to enhance the efficacy and safety of the combination of them with APs. Guidelines for this type of treatment are still needed. In this review, we explore the pharmacological properties, therapeutic applications, and limitations of APs, and discuss the potential benefits and limitations of those dietary interventions that are employed to improve the efficacy and counteract side effects of APs discussing also their mechanisms of action. Finally, we critically discuss the main results of clinical studies combining APs and dietary interventions and provide a view on future directions in terms of research and clinical use of these combinations. SIGNIFICANCE STATEMENT: Antipsychotic drugs are useful in a variety of psychiatric conditions, yet their use is hampered by issues of efficacy and safety. An important step toward therapy optimization is their use in combination with dietary interventions (ie, dietary supplements and nutraceuticals) that have shown promising results in clinical trials.
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Affiliation(s)
- Cristiana Perrotta
- Department of Biomedical and Clinical Sciences (DIBIC), Università degli Studi di Milano, Milano, Italy
| | - Carla Carnovale
- Department of Biomedical and Clinical Sciences (DIBIC), Università degli Studi di Milano, Milano, Italy
| | - Marco Pozzi
- Scientific Institute IRCCS Eugenio Medea, Bosisio Parini, Italy
| | - Clara De Palma
- Department of Medical Biotechnology and Translational Medicine (BioMeTra), Università degli Studi di Milano, Segrate, Italy
| | - Davide Cervia
- Department for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), Università degli Studi della Tuscia, Viterbo, Italy
| | - Maria Nobile
- Scientific Institute IRCCS Eugenio Medea, Bosisio Parini, Italy.
| | - Emilio Clementi
- Scientific Institute IRCCS Eugenio Medea, Bosisio Parini, Italy; Department of Biomedical and Clinical Sciences (DIBIC), ASST Fatebenefratelli-Sacco Hospital, Università degli Studi di Milano, Milano, Italy.
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Samara MT, Kottmaier E, Helfer B, Leucht C, Christodoulou NG, Huhn M, Rothe PH, Schneider-Thoma J, Leucht S. Switching antipsychotics versus continued current treatment in people with non-responsive schizophrenia. Cochrane Database Syst Rev 2025; 4:CD011885. [PMID: 40214650 PMCID: PMC11988422 DOI: 10.1002/14651858.cd011885.pub2] [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] [Indexed: 04/14/2025]
Abstract
BACKGROUND Many people with schizophrenia do not respond to an initially prescribed antipsychotic drug. In such cases, one treatment strategy could be to switch to a different antipsychotic drug. OBJECTIVES To examine the effects of switching antipsychotic drugs in treating people with schizophrenia who have not responded to initial antipsychotic treatment. SEARCH METHODS We searched the Cochrane Schizophrenia Group Trials Register (to December 2022). We inspected the references of all included studies for further relevant trials. SELECTION CRITERIA We included all relevant randomised controlled trials (RCTs) comparing switching to a different antipsychotic drug rather than continuing treatment with the same antipsychotic drug for people with schizophrenia who did not respond to their initial antipsychotic treatment. DATA COLLECTION AND ANALYSIS At least two review authors independently extracted data. The primary outcomes were: clinically relevant response as defined by study authors; tolerability (participants leaving the study early due to adverse effects); and quality of life assessed by the change score in the 36-Item Short Form survey. We analysed dichotomous data using the risk ratio (RR) and its 95% confidence interval (CI). We analysed continuous data using mean differences (MD) and corresponding 95% CI. We assessed the risk of bias of the included studies and used GRADE to evaluate the certainty of evidence for the following outcomes: clinically relevant response, tolerability (leaving the study early due to adverse effects), quality of life score change, acceptability (leaving the study early for any reason), general mental state (average change in general mental state scores), duration of hospitalisation, and number of participants experiencing at least one adverse effect. MAIN RESULTS We included 10 RCTs with 997 participants in the review. Nine studies used a parallel design, and one used a cross-over design. Seven studies were double-blind, two were single-blind and one did not provide any detail regarding blinding. All studies included people who were non-responsive to ongoing antipsychotic treatment. The minimum duration of the ongoing antipsychotic treatment ranged from three days to two years. The length of the comparison phase varied from two weeks to six months. The studies were published between 1993 and 2022. In about half of the studies, the methods of randomisation, allocation and blinding were poorly reported. The evidence is very uncertain regarding the effect of switching antipsychotics on clinically relevant response (RR 1.25, 95% CI 0.77 to 2.03; I² = 43%; 7 studies, 693 participants), quality of life (MD -1.30, 95% CI -3.44 to 0.84; 1 study, 188 participants), Positive and Negative Syndrome Scale (PANSS) score change (MD -0.92, 95% CI -4.69 to 2.86; I² = 47%; 6 studies, 777 participants), duration of hospitalisation (in days) (MD 9.19, 95% CI -8.93 to 27.31; I² = 0%; 2 studies, 34 participants) and the number of people experiencing at least one adverse effect (RR 1.29, 95% CI 0.81 to 2.05; I² = 36%; 3 studies, 412 participants). Compared to continuing current treatment, switching antipsychotics may result in little to no difference in tolerability, defined as the number of participants leaving the study early due to adverse effects (RR 0.73, 95% CI 0.24 to 2.26; I² = 31%; 6 studies, 672 participants; low-certainty evidence) and leaving the study early for any reason (RR 0.91, 95% CI 0.71 to 1.17; I² = 0%; 6 studies, 672 participants; low-certainty evidence). AUTHORS' CONCLUSIONS This review synthesises currently available RCT evidence on switching antipsychotics versus continuing the same antipsychotic in individuals with schizophrenia who did not respond to their initial treatment. Overall, the evidence remains highly uncertain regarding the effects of either strategy on efficacy and safety outcomes, and no definitive recommendations can currently be made. There is an urgent need for larger, well-designed trials to identify the optimal treatment strategy for these cases.
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Affiliation(s)
- Myrto T Samara
- Department of Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich, Munich, Germany
- Department of Psychiatry, University of Thessaly, Larissa, Greece
| | - Elisabeth Kottmaier
- Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Bartosz Helfer
- Institute of Psychology, University of Wroclaw, Wroclaw, Poland
- Meta Research Centre, University of Wroclaw, Wroclaw, Poland
| | | | | | - Maximilian Huhn
- Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen, Erlangen, Germany
- Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, District Hospital Bayreuth/Psychiatric Health Care Facilities of Upper Franconia, Bayreuth, Germany
| | - Philipp H Rothe
- Kbo-Inn-Salzach-Klinikum, Departement for Psychosis disorders and Personality disorders, Wasserburg (Inn), Germany
| | - Johannes Schneider-Thoma
- Department of Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Stefan Leucht
- Department of Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich, Munich, Germany
- German Center for Mental Health, partner site Munich/Augsburg, Germany
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Thela L, Paruk S, Nkambule BB, Ntlantsana V, Abbai NS, Msibi Z, Chhagan U, Tomita A, Naidu T, Nkosi S, Chiliza B. Longitudinal analysis of proinflammatory and anti-inflammatory cytokines in the cerebrospinal fluid and peripheral blood of treatment-naïve first-episode psychosis patients, and their correlation with psychosis severity and cognitive impairment in sub-Saharan Africa. BMJ Open 2025; 15:e098347. [PMID: 40180368 PMCID: PMC11966998 DOI: 10.1136/bmjopen-2024-098347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Accepted: 03/18/2025] [Indexed: 04/05/2025] Open
Abstract
BACKGROUND Inflammation is indicated as one of the factors that play a role in the development of schizophrenia, with several studies having found considerable inconsistencies in their results. Few have investigated the role of inflammation in primary psychosis in blood and cerebrospinal fluids simultaneously, the aim of this study being to investigate the expression of blood and cerebrospinal fluid inflammatory cytokines in treatment-naive first-episode psychotic participants. METHODS AND ANALYSIS This is a combined cross-sectional and prospective observational study, which is currently taking place in Durban, South Africa, will recruit 60 participants (30 cases and 30 matched controls). The primary objective is to describe baseline CSF and longitudinal expression/levels of inflammatory cytokines in the blood in persons diagnosed with first-episode psychosis (FEP) for 12 months. The secondary objective is to describe the associations between inflammatory cytokines and psychosis severity, neurocognitive performance, antipsychotic response and metabolic changes at different time points (baseline, 3, 6 and 12 months). INTERVENTIONS We will collect the sociodemographic details of all participants, and the Positive and Negative Symptoms Scale, Patient Health Questionnaire-9, Childhood Trauma Scale, Repeatable Battery for the Assessment of Neuropsychological Status Update, metabolic markers and inflammatory markers (venous blood and lumbar puncture cerebrospinal fluid) for those with FEP. Data from matched controls will only be collected at one point and no follow-ups (cross-sectional). ETHICS AND DISSEMINATION The study protocol has been approved by the University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC/00004714/2022). The study is nested in an ongoing study titled the burden of HIV and Psychosis in an African setting: a longitudinal study of HIV-infected and non-infected patients with First-Episode Psychosis (BREC 571/18). The results will be actively disseminated through peer-reviewed journal publications and conference presentations.
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Affiliation(s)
- Lindokuhle Thela
- Psychiatry, University of KwaZulu-Natal Nelson R Mandela School of Medicine, Durban, KwaZulu-Natal, South Africa
| | - Saeeda Paruk
- University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa
| | - Bongani B Nkambule
- University of KwaZulu-Natal College of Health Sciences, Durban, South Africa
- University of KwaZulu-Natal, South Africa
| | - Vuyokazi Ntlantsana
- University of KwaZulu-Natal, South Africa
- University of KwaZulu-Natal, Congella, KwaZulu-Natal, South Africa
| | - Nathlee S Abbai
- Clinical Medicine Laboratory, University of KwaZulu-Natal Nelson R Mandela School of Medicine, Durban, South Africa
| | - Zama Msibi
- School of Laboratory Medicine, University of KwaZulu-Natal, Durban, South Africa
| | - Usha Chhagan
- University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa
| | - Andrew Tomita
- University of KwaZulu-Natal College of Health Sciences, Durban, South Africa
| | - Thirusha Naidu
- Department of Innovation in Medical Education Canada, Ottawa University, Ottawa, Kansas, USA
| | - Sanele Nkosi
- Psychiatry, University of KwaZulu-Natal Nelson R Mandela School of Medicine, Durban, KwaZulu-Natal, South Africa
| | - Bonginkosi Chiliza
- School of Clinical Medicine, University of KwaZulu-Natal, Durban, South Africa
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Levit A, Procyshyn RM, Keramatian K. Acute dystonia following the two-injection start of aripiprazole once-monthly. BMJ Case Rep 2025; 18:e263842. [PMID: 39947725 DOI: 10.1136/bcr-2024-263842] [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: 05/09/2025] Open
Abstract
We present a case of an acute dystonic reaction (ADR) following the two-injection start of aripiprazole once-monthly (AOM) in a patient who previously tolerated equivalent doses of oral aripiprazole (20 mg daily). The ADR occurred two times within 3 weeks of the two-injection start and was effectively treated with benztropine each time. The patient tolerated maintenance treatments of AOM 400 mg without recurrent ADR. A key risk factor in this patient was a prior ADR to a different antipsychotic. We also speculate on the potential roles of strenuous physical activity and infection in increasing the sensitivity to the two-injection initiation regimen compared with the conventional one-injection start. The two-injection start of AOM has been approved by regulatory bodies on the basis of population pharmacokinetic modelling. Our case may, therefore, identify a new safety concern with this alternative initiation option that was not captured in the modelling.
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Affiliation(s)
- Alexander Levit
- Department of Psychiatry, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
| | - Ric M Procyshyn
- Department of Psychiatry, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
| | - Kamyar Keramatian
- Department of Psychiatry, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada
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Germanova O, Galati G, Germanov A, Shchukin Y, Syunyakov T, Biondi-Zoccai G. Arterial vascular complications predictive score in extrasystolic arrhythmia "EX-prognosis". Minerva Cardiol Angiol 2025; 73:86-94. [PMID: 39377695 DOI: 10.23736/s2724-5683.24.06549-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/09/2024]
Abstract
BACKGROUND The aim of this study was the creation of an optimal model for predicting arterial vascular complications in patients with extrasystolic arrhythmia. METHODS A single-center prospective study was performed with involving 634 patients with supraventricular or ventricular extrasystoles (ES) of 700 or more per 24 hours. The control group consisted of 106 people with ES less than 700 per 24 hours. The main and control groups were initially equivalent in anthropometric criteria and concomitant pathology. The list of examinations included laboratory methods (including lipid profile, coagulograms), as well as instrumental studies (transthoracic and/or transesophageal echocardiography (EchoCG), Doppler ultrasound of the brachiocephalic arteries and arteries of the lower extremities, 24-hours ECG monitoring, according to the indications - computed tomography or magnetic resonance imaging of the brain, coronary angiography, stress echocardiography. Prospective observation of patients performed for 1 year after the initial examination. Combined end points: development of arterial vascular complications - stroke, myocardial infarction, distal arterial embolism of other locations. We studied the data on identified complications. Next, we built models for predicting complications in various ways: Decision Tree; Bootstrap Forest; Boosted Tree; Neural Boosted; Support Vector Machines; Fit Stepwise; Nominal Logistic; Generalized Regression Lasso; Generalized Regression Forward Selection; Generalized Regression Pruned Forward Selection; Generalized Regression Elastic Net; Generalized Regression Ridge. To assess the quality of the models and compare them we used cross-validation with 30 replications. RESULTS The highest profit values with minimal values of false positive results were obtained for the Bootstrap Forest model. Basing on this model, we created arterial vascular complications predictive score in extrasystolic arrhythmia "EX-prognosis" that included the following parameters: atheroma type III in carotid arteries - 3 points; age 69+ years old - 2 points; ES appearing before transmitral blood flow peak in cardiac cycle 700 and more per 24 hours - 1 point; carotid arteries stenosis, non-significant - 1 point. If total number is 3 and more points, the risk of arterial vascular complications within 1 year is high. CONCLUSIONS We recommend to use the scale "EX-prognosis" in the clinical practice. For a quick assessment of the total risk, it is optimal to implement the risk14.exe program - calculator - developed by us for a personal computer, based on this scale.
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Affiliation(s)
- Olga Germanova
- International Center for Education and Research in Cardiovascular Pathology and Cardiovisualization, Samara State Medical University, Samara, Russia -
| | - Giuseppe Galati
- International Center for Education and Research in Cardiovascular Pathology and Cardiovisualization, Samara State Medical University, Samara, Russia
- Unit of Cardiology, IRCCS Ospedale Multimedica - Cardiovascular Scientific Institute, Milan, Italy
| | | | - Yurii Shchukin
- Department of Propedeutical Therapy with Course of Cardiology, Samara State Medical University, Samara, Russia
| | - Timur Syunyakov
- International Center for Education and Research in Cardiovascular Pathology and Cardiovisualization, Samara State Medical University, Samara, Russia
| | - Giuseppe Biondi-Zoccai
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University, Rome, Italy
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Chhagan U, Ntlantsana V, Karim E, Thela L, Tomita A, Chiliza B, Paruk S. Clinical presentation of first episode psychosis in people with and without HIV in KwaZulu-Natal, South Africa. Early Interv Psychiatry 2025; 19:e13561. [PMID: 38803138 PMCID: PMC11729481 DOI: 10.1111/eip.13561] [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: 03/29/2023] [Revised: 12/06/2023] [Accepted: 05/09/2024] [Indexed: 05/29/2024]
Abstract
AIM Mental disorders and HIV are the main contributors to the increase in years lived with disability rates per person in sub-Saharan Africa. A complex inter-relationship exists between HIV and mental illness, especially in a region with a high HIV prevalence. We examined the duration of untreated psychosis (DUP), and the nature of psychotic and cognitive symptoms in people with first episode psychosis (FEP) living with and without HIV. METHODS Adults aged between 18 and 45 years were assessed using a clinical interview, physical examination and several psychiatric tools. These included the Mini International Neuro-psychiatric Interview to confirm psychosis, Positive and Negative Syndrome Scale, International HIV Dementia Scale and other scales to measure symptom variables. HIV ELISA was used for HIV serology testing, with measures being carried out within 6 weeks of the first presentation. RESULTS Of the 172 people presenting with FEP, 36 (21%) had comorbid HIV, those with both being older and more likely to be female (p < .001). Clinically, participants with FEP and HIV scored lower on the positive subscale (p = .008). There were no statistically significant differences for DUP or cognitive screening. Of those living with HIV and FEP (n = 36) comorbidity, nine were newly diagnosed with HIV at the time of the study. CONCLUSION Individuals presenting with FEP and comorbid HIV were older, female and reported more mood symptoms. The identification of nine new HIV infections also reflects the ongoing need to test for HIV in people presenting with severe mental illness.
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Affiliation(s)
- Usha Chhagan
- Department of Psychiatry, College of Health Sciences, Nelson R Mandela School of MedicineUniversity of Kwazulu‐NatalDurbanSouth Africa
| | - Vuyokazi Ntlantsana
- Department of Psychiatry, College of Health Sciences, Nelson R Mandela School of MedicineUniversity of Kwazulu‐NatalDurbanSouth Africa
| | - Enver Karim
- Department of Psychiatry, College of Health Sciences, Nelson R Mandela School of MedicineUniversity of Kwazulu‐NatalDurbanSouth Africa
| | - Lindokuhle Thela
- Department of Psychiatry, College of Health Sciences, Nelson R Mandela School of MedicineUniversity of Kwazulu‐NatalDurbanSouth Africa
| | - Andrew Tomita
- KwaZulu‐Natal Research Innovation and Sequencing Platform (KRISP), College of Health SciencesUniversity of KwaZulu‐NatalDurbanSouth Africa
- Centre for Rural Health, School of Nursing and Public Health, College of Health SciencesUniversity of KwaZulu‐NatalDurbanSouth Africa
| | - Bonginkosi Chiliza
- Department of Psychiatry, College of Health Sciences, Nelson R Mandela School of MedicineUniversity of Kwazulu‐NatalDurbanSouth Africa
| | - Saeeda Paruk
- Department of Psychiatry, College of Health Sciences, Nelson R Mandela School of MedicineUniversity of Kwazulu‐NatalDurbanSouth Africa
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Shamabadi A, Rafiei-Tabatabaei ES, Kazemzadeh K, Farahmand K, Fallahpour B, Khodaei Ardakani MR, Akhondzadeh S. Pentoxifylline adjunct to risperidone for negative symptoms of stable schizophrenia: a randomized, double-blind, placebo-controlled trial. Int J Neuropsychopharmacol 2024; 28:pyae051. [PMID: 39716387 PMCID: PMC11781224 DOI: 10.1093/ijnp/pyae051] [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: 08/03/2024] [Accepted: 11/01/2024] [Indexed: 12/25/2024] Open
Abstract
BACKGROUND Negative symptoms of schizophrenia represent an unmet therapeutic need for many patients in whom pentoxifylline may be effective in terms of its dopaminergic, anti-inflammatory, and cerebral blood flow-increasing properties. This study aimed to evaluate pentoxifylline as a therapeutic agent for improving negative symptoms of schizophrenia. METHODS Chronic schizophrenia outpatients experiencing significant negative symptoms were randomly allocated to receive pentoxifylline 400 mg or matched placebo every 12 hours for 8 weeks. All patients were clinically stable as they had received risperidone for at least 2 months, which was continued. The participants were assessed using the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale, Extrapyramidal Symptom Rating Scale, and side effect checklist. RESULTS The patients' baseline characteristics were comparable between the groups. There was a significant time-treatment interaction effect on PANSS negative subscale scores (ηP2=0.075), with the pentoxifylline group showing significantly greater reductions until weeks 4 (Cohen d = 0.512) and 8 (Cohen d = 0.622). Also, this group showed a significantly better response by week 8. Other PANSS scores, Hamilton Depression Rating Scale scores, Extrapyramidal Symptom Rating Scale scores, and side effect frequencies were comparable between the groups. Pentoxifylline showed a nonsignificant higher remission of 37.1% compared with 14.7% in the placebo group. CONCLUSIONS Pentoxifylline was safely and tolerably beneficial for the primary negative symptoms of chronic schizophrenia.
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Affiliation(s)
- Ahmad Shamabadi
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Kimia Kazemzadeh
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Kimia Farahmand
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Bita Fallahpour
- Department of Psychiatry, Razi Hospital, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | | | - Shahin Akhondzadeh
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran
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9
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Ghanem J, Orri M, Moro L, Lavigne KM, Raucher-Chéné D, Malla A, Joober R, Lepage M. Exploring the Relationship Between Suicidality and Persistent Negative Symptoms Following a First Episode of Psychosis. Schizophr Bull 2024; 51:67-74. [PMID: 37847817 PMCID: PMC11661949 DOI: 10.1093/schbul/sbad146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2023]
Abstract
BACKGROUND AND HYPOTHESIS Suicide is a leading cause of death in first-episode psychosis (FEP), with an elevated risk during the first year following illness onset. The association between negative symptoms and suicidality remains contentious. Some studies suggest that negative symptoms may be associated with lower suicidality, while others fail to find an association between the two. No previous studies have specifically investigated suicidality in Persistent Negative Symptoms (PNS) and its associated subgroups. STUDY DESIGN In a large cohort of FEP patients (n = 515) from an early intervention service, we investigated suicidality in those with PNS, secondary PNS (ie, sPNS; PNS with clinical-level positive, depressive, or extrapyramidal symptoms), and non-PNS (all other patients) over 24 months. Patients were categorized into PNS groups based on symptoms from month 6 to month 12, and suicidality was evaluated using the Brief Psychiatric Rating Scale (BPRS). STUDY RESULTS Covarying for age and sex, we found that sPNS had higher suicidality relative to PNS and non-PNS throughout the 24-month period, but PNS and non-PNS did not differ. These differences were maintained after adjusting for depressive symptoms. CONCLUSION We observed that PNS did not significantly differ from non-PNS. However, we identified sPNS as a group with elevated suicidality above and beyond depression, suggesting that sPNS would benefit from targeted intervention and that PNS categorization identifies a subgroup for whom negative symptoms are not associated with lower suicidality.
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Affiliation(s)
- Joseph Ghanem
- DouglasMental Health University Institute, McGill University, Montreal, Canada
- Department of Psychology, McGill University, Montreal, Canada
| | - Massimiliano Orri
- DouglasMental Health University Institute, McGill University, Montreal, Canada
- Department of Psychiatry, McGill University, Montreal, Canada
| | - Laura Moro
- DouglasMental Health University Institute, McGill University, Montreal, Canada
- Department of Psychology, Université de Montreal, Montreal, Canada
| | - Katie M Lavigne
- DouglasMental Health University Institute, McGill University, Montreal, Canada
- Department of Psychiatry, McGill University, Montreal, Canada
- McGill Centre for Integrative Neuroscience, Montreal Neurological Institute, McGill University, Montreal, Canada
| | - Delphine Raucher-Chéné
- DouglasMental Health University Institute, McGill University, Montreal, Canada
- Department of Psychiatry, McGill University, Montreal, Canada
| | - Ashok Malla
- DouglasMental Health University Institute, McGill University, Montreal, Canada
- Department of Psychiatry, McGill University, Montreal, Canada
- Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, Montreal, Canada
| | - Ridha Joober
- DouglasMental Health University Institute, McGill University, Montreal, Canada
- Department of Psychiatry, McGill University, Montreal, Canada
- Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, Montreal, Canada
| | - Martin Lepage
- DouglasMental Health University Institute, McGill University, Montreal, Canada
- Department of Psychology, McGill University, Montreal, Canada
- Department of Psychiatry, McGill University, Montreal, Canada
- Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, Montreal, Canada
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10
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Mazhar S, Shamabadi A, Kazemzadeh K, Farahvash MA, Heidari Dalfard A, Fallahpour B, Khodaei Ardakani MR, Akhondzadeh S. Crocus sativus (saffron) adjunct to risperidone for negative symptoms of schizophrenia: a randomized, double-blind, placebo-controlled trial. Int Clin Psychopharmacol 2024:00004850-990000000-00154. [PMID: 39661337 DOI: 10.1097/yic.0000000000000575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2024]
Abstract
Current treatments for schizophrenia encounter resistance, limited efficacy, and limiting complications, necessitating novel approaches. The effects of saffron on negative symptoms were investigated as it has shown neuroprotective and antipsychotic properties. Fifty-six clinically stable chronic schizophrenic outpatients were equally assigned to saffron 15 mg q12hr or placebo groups while continuing risperidone. The Positive and Negative Syndrome Scale (PANSS) was used to assess schizophrenia-related symptoms in weeks 4 and 8. Also, the patients were assessed for the Hamilton depression rating scale (HDRS) and adverse effects. The baseline characteristics of the groups were comparable (Ps > 0.05). There were significant time-treatment interaction effects on negative ( = 0.137), general psychopathology ( = 0.193), and total ( = 0.113) PANSS scores. Affirmatively, their reductions were significantly greater in the saffron group until weeks 4 (Cohen's ds = 0.922, 0.898, and 0.759, respectively) and 8 (Cohen's ds = 0.850, 1.047, and 0.705, respectively). Regarding the negative symptoms, a better 25% response rate was obtained in the saffron group until the endpoint (P = 0.003). The HDRS scores, extrapyramidal symptom rating scale scores, and side effect frequencies were comparable between the groups (Ps > 0.05). Saffron was beneficial for primary negative symptoms of chronic schizophrenia in a safe and tolerable manner. It also outperformed placebo in improving general psychopathology and total symptoms.
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Affiliation(s)
- Siamand Mazhar
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences
| | - Ahmad Shamabadi
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences
| | - Kimia Kazemzadeh
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences
| | - Mohammad Aidin Farahvash
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences
| | - Atiye Heidari Dalfard
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences
| | - Bita Fallahpour
- Department of Psychiatry, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | | | - Shahin Akhondzadeh
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences
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11
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Kalniunas A, James K, Pappa S. Prevalence of spontaneous movement disorders (dyskinesia, parkinsonism, akathisia and dystonia) in never-treated patients with chronic and first-episode psychosis: a systematic review and meta-analysis. BMJ MENTAL HEALTH 2024; 27:e301184. [PMID: 39313255 PMCID: PMC11418527 DOI: 10.1136/bmjment-2024-301184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 08/12/2024] [Indexed: 09/25/2024]
Abstract
BACKGROUND The aim of this systematic review and meta-analysis is to evaluate and compare the prevalence rates of spontaneous movement disorders (SMDs), including dyskinesia, parkinsonism, akathisia and dystonia, in antipsychotic-naïve individuals with chronic psychosis and first-episode psychosis (FEP) and gain a more nuanced understanding of factors influencing their presence. METHODS Several literature databases were systematically searched and screened based on predetermined eligibility criteria. Included articles underwent risk of bias assessment. The prevalence rates of SMDs were calculated using a random-effects model. RESULTS Out of 711 articles screened, 27 were included in this meta-analysis. The pooled prevalence of spontaneous dyskinesia was 7% (3% FEP and 17% chronic schizophrenia) across 24 studies (95% CI 3 to 11; I2=94%, p<0.01) and 15% for spontaneous parkinsonism (14% FEP and 19% chronic schizophrenia) in 21 studies (95% CI 12 to 20; I2=81%, p<0.01). A meta-regression analysis found a significant positive correlation between age (p<0.05) and duration of untreated psychosis (DUP) (p<0.05) with dyskinesia but not parkinsonism prevalence. Akathisia and dystonia appear to be both less studied and less frequent in occurrence with a pooled prevalence of 4% (95% CI: 3 to 6; I2=0%, p=0.65) for akathisia in eight studies and a mean prevalence of 6% (range 0%-16%) for dystonia in five studies. CONCLUSION The presence of varying degrees of neurodysfunction in antipsychotic-naïve patients with schizophrenia underscores the need for individualised treatment approaches that consider each patient's unique predisposition and neuromotor profile. Further research is warranted into the role of specific SMDs and risk factors including sex, race and diagnostic variations. PROSPERO REGISTRATION NUMBER CRD42024501951.
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Affiliation(s)
- Arturas Kalniunas
- Research and Development, West London NHS Trust, London, UK
- Greater Manchester Mental Health NHS Foundation Trust, Manchester, UK
| | - Katie James
- Addiction Services, Central and North West London Mental Health NHS Trust, London, Greater London, UK
| | - Sofia Pappa
- Research and Development, West London NHS Trust, London, UK
- Department of Psychiatry, Imperial College London, London, UK
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12
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Bokhari SA, Alhosani M, Jalal L, Al Mansour A, M Elhassan N. A Rare Occurrence of Delayed Olanzapine-Induced Oculogyric Crisis in a Postpartum Patient: A Case Report. Cureus 2024; 16:e70127. [PMID: 39463585 PMCID: PMC11502221 DOI: 10.7759/cureus.70127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/24/2024] [Indexed: 10/29/2024] Open
Abstract
Oculogyric crisis (OGC) is an acute dystonic reaction characterized by involuntary upward deviation of the eyes, often linked to the use of antipsychotic medications. While commonly associated with first-generation antipsychotics (FGAs) due to their higher propensity to cause extrapyramidal symptoms (EPS), OGC remains a rare but documented occurrence with second-generation antipsychotics (SGAs). SGAs, including olanzapine, are generally preferred in clinical practice due to their reduced risk of EPS; however, they are not completely devoid of such adverse effects. The emergence of OGC in the context of SGAs, particularly in unique clinical scenarios, highlights the importance of awareness and careful management of potential adverse effects in clinical practice. This case report presents a rare instance of OGC in a 25-year-old postpartum woman following an independent reduction in her olanzapine dosage, a medication usually associated with a low risk of dystonia. The patient, with no previous psychiatric history, had been treated with olanzapine for postpartum depression with psychotic features and demonstrated stability. The onset of OGC, occurring three months after the initiation of olanzapine and precipitated by stressors such as interpersonal conflicts and high-pressure situations, underscores the critical need for comprehensive patient education on the dangers of unsupervised medication adjustments. It also highlights the importance of vigilant monitoring, particularly in vulnerable populations, such as postpartum patients. This case underscores the necessity for individualized treatment approaches and highlights the rarity and clinical significance of OGC in patients on SGAs, contributing to the understanding of atypical presentations associated with these medications.
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Affiliation(s)
- Syed Ali Bokhari
- Psychiatry, Al Amal Psychiatric Hospital, Emirates Health Services, Dubai, ARE
| | - Mariam Alhosani
- Psychiatry, Al Amal Psychiatric Hospital, Emirates Health Services, Dubai, ARE
| | - Louai Jalal
- Psychiatry, Al Amal Psychiatric Hospital, Emirates Health Services, Dubai, ARE
| | - Alma Al Mansour
- Emergency Medicine, Al Qassimi Hospital, Emirates Health Services, Sharjah, ARE
| | - Nahid M Elhassan
- Psychiatry, Al Amal Psychiatric Hospital, Emirates Health Services, Dubai, ARE
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13
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Kim H, Kim S, Lee S, Lee K, Kim E. Exploring the Relationships Between Antipsychotic Dosage and Voice Characteristics in Relation to Extrapyramidal Symptoms. Psychiatry Investig 2024; 21:822-831. [PMID: 39111750 PMCID: PMC11321868 DOI: 10.30773/pi.2023.0417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 02/19/2024] [Accepted: 04/09/2024] [Indexed: 08/15/2024] Open
Abstract
OBJECTIVE Extrapyramidal symptoms (EPS) are common side effects of antipsychotic drugs. Despite the growing interest in exploring objective biomarkers for EPS prevention and the potential use of voice in detecting clinical disorders, no studies have demonstrated the relationships between vocal changes and EPS. Therefore, we aimed to determine the associations between voice changes and antipsychotic dosage, and further investigated whether speech characteristics could be used as predictors of EPS. METHODS Forty-two patients receiving or expected to receive antipsychotic drugs were recruited. Drug-induced parkinsonism of EPS was evaluated using the Simpson-Angus Scale (SAS). Participants' voice data consisted of 16 neutral sentences and 2 second-long /Ah/utterances. Thirteen voice features were extracted from the obtained voice data. Each voice feature was compared between groups categorized based on SAS total score of below and above "0.6." The associations between antipsychotic dosage and voice characteristics were examined, and vocal trait variations according to the presence of EPS were explored. RESULTS Significant associations were observed between specific vocal characteristics and antipsychotic dosage across both datasets of 1-16 sentences and /Ah/utterances. Notably, Mel-Frequency Cepstral Coefficients (MFCC) exhibited noteworthy variations in response to the presence of EPS. Specifically, among the 13 MFCC coefficients, MFCC1 (t=-4.47, p<0.001), MFCC8 (t=-4.49, p<0.001), and MFCC12 (t=-2.21, p=0.029) showed significant group differences in the overall statistical values. CONCLUSION Our results suggest that MFCC may serve as a predictor of detecting drug-induced parkinsonism of EPS. Further research should address potential confounding factors impacting the relationship between MFCC and antipsychotic dosage, possibly improving EPS detection and reducing antipsychotic medication side effects.
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Affiliation(s)
- Hyeyoon Kim
- Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea
| | - Seoyoung Kim
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Subin Lee
- Music and Audio Research Group, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea
| | - Kyogu Lee
- Music and Audio Research Group, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea
| | - Euitae Kim
- Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Psychiatry, College of Medicine, Seoul National University, Seoul, Republic of Korea
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14
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Koch J, Launio M, Williams AM. Extrapyramidal side effects with nonantipsychotic medications. Ment Health Clin 2024; 14:233-235. [PMID: 39104434 PMCID: PMC11298035 DOI: 10.9740/mhc.2024.08.233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 02/29/2024] [Indexed: 08/07/2024] Open
Affiliation(s)
- Jessa Koch
- (Corresponding author) Associate Professor, Department of Pharmacy Practice, Loma Linda University School of Pharmacy, Loma Linda, California,
| | - Meljorie Launio
- Attending Psychiatrist, Loma Linda University Health, Loma Linda, California
| | - Andrew M. Williams
- Supervising Clinical Pharmacist, Behavioral Health Pharmacy Services, Riverside University Health System, Riverside, California
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15
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Marshall RD, Menniti FS, Tepper MA. A Novel PDE10A Inhibitor for Tourette Syndrome and Other Movement Disorders. Cells 2024; 13:1230. [PMID: 39056811 PMCID: PMC11274801 DOI: 10.3390/cells13141230] [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: 06/06/2024] [Revised: 07/15/2024] [Accepted: 07/16/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND Tourette syndrome is a neurodevelopmental movement disorder involving basal ganglia dysfunction. PDE10A inhibitors modulate signaling in the striatal basal ganglia nuclei and are thus of interest as potential therapeutics in treating Tourette syndrome and other movement disorders. METHODS The preclinical pharmacology and toxicology, human safety and tolerability, and human PET striatal enzyme occupancy data for the PDE10A inhibitor EM-221 are presented. RESULTS EM-221 inhibited PDE10A with an in vitro IC50 of 9 pM and was >100,000 selective vs. other PDEs and other CNS receptors and enzymes. In rats, at doses of 0.05-0.50 mg/kg, EM-221 reduced hyperlocomotion and the disruption of prepulse inhibition induced by MK-801, attenuated conditioned avoidance, and facilitated novel object recognition, consistent with PDE10A's inhibition. EM-221 displayed no genotoxicity and was well tolerated up to 300 mg/kg in rats and 100 mg/kg in dogs. In single- and multiple-day ascending dose studies in healthy human volunteers, EM-221 was well tolerated up to 10 mg, with a maximum tolerated dose of 15 mg. PET imaging indicated that a PDE10A enzyme occupancy of up to 92.8% was achieved with a ~24 h half-life. CONCLUSIONS The preclinical and clinical data presented here support the study of EM-221 in phase 2 trials of Tourette syndrome and other movement disorders.
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Affiliation(s)
| | - Frank S. Menniti
- MindImmune Therapeutics, Inc., Kingston, RI 02881, USA;
- The George & Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA
| | - Mark A. Tepper
- EuMentis Therapeutics Inc., 275 Grove Street, 2-400, Newton, MA 02466, USA;
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16
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Nasiri M, Parmoon Z, Farahmand Y, Moradi A, Farahmand K, Moradi K, Basti FA, Mohammadi MR, Akhondzadeh S. l -carnitine adjunct to risperidone for treatment of autism spectrum disorder-associated behaviors: a randomized, double-blind clinical trial. Int Clin Psychopharmacol 2024; 39:232-239. [PMID: 37551601 DOI: 10.1097/yic.0000000000000496] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/09/2023]
Abstract
The present study was designed to evaluate the efficacy and safety of l-carnitine as an adjuvant agent to risperidone in the treatment of autism spectrum disorder (ASD)-associated behaviors. In this study, 68 children with confirmed ASD were randomly allocated to receive either l-carnitine (150 mg/day) or matched placebo in addition to risperidone. We utilized the Aberrant Behavior Checklist-Community Edition scale (ABC-C) and a checklist of potential adverse effects to assess changes in behavioral status and safety profile at weeks 0, 5 and 10 of the trial. The primary outcome was defined as a change in the irritability subscale score. Sixty patients with similar baseline characteristics completed the trial period. Although scores of ABC-C subscales significantly decreased in both groups over the trial period, the combination of l-carnitine and risperidone resulted in more reduction on the irritability and hyperactivity subscales compared to the combination of risperidone and placebo ( P = 0.033 and P < 0.001, respectively). However, changes in lethargy, stereotypic behavior and inappropriate speech subscales were similar between groups. In conclusion, l-carnitine adjuvant to risperidone could improve irritability and hyperactivity features in children with ASD. Results of this study should be considered preliminary and further clinical trials with larger sample sizes and longer follow-up periods are warranted.
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Affiliation(s)
- Mehry Nasiri
- Psychiatric Research Center, Roozbeh Psychiatric Hospital
| | - Zohal Parmoon
- Psychiatric Research Center, Roozbeh Psychiatric Hospital
| | | | - Ali Moradi
- Psychiatric Research Center, Roozbeh Psychiatric Hospital
| | | | - Kamyar Moradi
- Psychiatric Research Center, Roozbeh Psychiatric Hospital
| | - Fatemeh A Basti
- Islamic Azad University, Tehran Medical Branch, Tehran, Iran
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17
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Sharif AF, Sobh ZK, Abdo SAEF, Alahmadi OM, Alharbi HA, Awaji MS, Alabdullatif FA, Baghlaf AM, Alanazi AF, Fayed MM. Evaluation of Global Dystonia Rating Scale as a predictor of unfavorable outcomes among acute antipsychotics poisoned patients. Drug Chem Toxicol 2024; 47:386-403. [PMID: 38348658 DOI: 10.1080/01480545.2024.2313561] [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: 11/17/2023] [Accepted: 01/25/2024] [Indexed: 07/02/2024]
Abstract
Worldwide, acute antipsychotic poisoning results in high morbidities and mortalities. Though extrapyramidal syndromes are commonly associated, the extent of extrapyramidal syndromes in relation to the severity of antipsychotic poisoning has not been addressed yet. Thus, this study aimed to assess the Global Dystonia Rating Scale (GDRS) as an unfavorable outcomes predictive tool in acute antipsychotic poisoning. A cross-sectional study included 506 antipsychotic-poisoned patients admitted to Tanta University Poison Control Center, Egypt, over three years was conducted. The mean GDRS was 9.1 ± 16.7 in typical antipsychotic poisoning, which was significantly higher than that of atypical antipsychotics (4.2 ± 11.5) (p = 0.003). Patients with GDRS> 20 showed significantly higher liability for all adverse outcomes (p < 0.05). However, poisoning with typical antipsychotics was associated with significantly more cardiotoxicity (p = 0.042), particularly prolonged QRS (p = 0.005), and intensive care unit (ICU) admission (p = 0.000). In contrary to the PSS, which failed to predict the studied adverse outcomes, GDRS significantly predicted all adverse outcomes (p < 0.000) for all antipsychotic generations. In atypical antipsychotics, GDRS above three accurately predicted cardiotoxicities, prolonged QTc interval, and respiratory failure with Area under curves (AUC) of 0.937, 0.963, and 0.941, respectively. In typical antipsychotic poisoning, at higher cutoffs (7.5, 27.5, 18, and 7.5), cardiotoxicities, prolonged QTc interval, and respiratory failure were accurately predicted (AUC were 0.974, 0.961, and 0.960, respectively). GDRS is an objective, substantially useful tool that quantifies dystonia and can be used as an early reliable predictor of potential toxicity in acute antipsychotic poisoning.
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Affiliation(s)
- Asmaa Fady Sharif
- Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
- Clinical Medical Sciences Department, College of Medicine, Dar Al-Uloom University, Riyadh, Saudi Arabia
| | - Zahraa Khalifa Sobh
- Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Sanaa Abd El-Fatah Abdo
- Public Health and Community Medicine Department, Faculty of Medicine, Tanta University, Egypt
| | - Osama M Alahmadi
- College of Medicine, Dar Al-Uloom University, Riyadh, Saudi Arabia
| | - Hatem A Alharbi
- College of Medicine, Dar Al-Uloom University, Riyadh, Saudi Arabia
- Respiratory Care Practitioner, Pediatric Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Mohannad Saif Awaji
- College of Medicine, Dar Al-Uloom University, Riyadh, Saudi Arabia
- Emergency Medicine Department, EMS section, King Abdullah Bin Abdulaziz University Hospital, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Faris A Alabdullatif
- College of Medicine, Dar Al-Uloom University, Riyadh, Saudi Arabia
- Emergency Operation Center, General Directorate of Health Affairs in Riyadh Region, Ministry of Health, Riyadh, Saudi Arabia
| | | | - Ahmad F Alanazi
- College of Medicine, Dar Al-Uloom University, Riyadh, Saudi Arabia
| | - Manar Maher Fayed
- Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
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18
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Cernvall M, Bengtsson J, Bodén R. The Swedish version of the Motivation and Pleasure Scale self-report (MAP-SR): psychometric properties in patients with schizophrenia or depression. Nord J Psychiatry 2024; 78:339-346. [PMID: 38436927 DOI: 10.1080/08039488.2024.2324060] [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: 12/22/2021] [Accepted: 02/23/2024] [Indexed: 03/05/2024]
Abstract
PURPOSE Negative symptoms are commonly regarded as a symptom dimension belonging to schizophrenia spectrum disorders but are also present in depression. The recently developed Clinical Assessment Interview for Negative Symptoms (CAINS) has shown to be reliable and valid. A corresponding self-report questionnaire has also been developed, named the Motivation and Pleasure Scale - Self Report (MAP-SR). The purpose was to evaluate the psychometric properties of the Swedish version of the MAP-SR in patients with either schizophrenia or depression. MATERIALS AND METHODS The MAP-SR was translated to Swedish. Participants were 33 patients with schizophrenia spectrum disorders and 52 patients with a depressive disorder and they completed the MAP-SR, the CAINS and other measures assessing adjacent psychopathology, functioning and cognition. RESULTS The internal consistency for the MAP-SR was adequate in both groups (schizophrenia spectrum α = .93, depressive disorder α = .82). Furthermore, the MAP-SR had a large correlation to the motivation and pleasure subscale of the CAINS in patients with schizophrenia disorders (r = -0.75, p < .001), however among patients with depression this correlation was medium-to-large (r = -0.48, p < 0.001). CONCLUSIONS Findings suggest that the Swedish version of the MAP-SR shows promise as a useful measure of motivation and pleasure, especially in patients with schizophrenia spectrum disorders. Furthermore, results also suggest that the MAP-SR does not assess negative symptoms specifically, but that there is an overlap between depressive and negative symptoms.
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Affiliation(s)
- Martin Cernvall
- Department of Medical Sciences, Psychiatry, Uppsala University, Uppsala, Sweden
| | - Johan Bengtsson
- Department of Medical Sciences, Psychiatry, Uppsala University, Uppsala, Sweden
| | - Robert Bodén
- Department of Medical Sciences, Psychiatry, Uppsala University, Uppsala, Sweden
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19
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Kim DD, Procyshyn RM, Jones AA, Gicas KM, Jones PW, Petersson AM, Lee LHN, McLellan-Carich R, Cho LL, Panenka WJ, Leonova O, Lang DJ, Thornton AE, Honer WG, Barr AM. Relationship between drug-induced movement disorders and psychosis in adults living in precarious housing or homelessness. J Psychiatr Res 2024; 170:290-296. [PMID: 38185074 DOI: 10.1016/j.jpsychires.2024.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 12/07/2023] [Accepted: 01/02/2024] [Indexed: 01/09/2024]
Abstract
BACKGROUND Studies have reported positive associations between drug-induced movement disorders (DIMDs) and symptoms of psychosis in patients with schizophrenia. However, it is not clear which subtypes of symptoms are related to each other, and whether one symptom precedes another. The current report assessed both concurrent and temporal associations between DIMDs and symptoms of psychosis in a community-based sample of homeless individuals. METHODS Participants were recruited in Vancouver, Canada. Severity of DIMDs and psychosis was rated annually, allowing for the analysis of concurrent associations between DIMDs and Positive and Negative Syndrome Scale (PANSS) five factors. A brief version of the PANSS was rated monthly using five psychotic symptoms, allowing for the analysis of their temporal associations with DIMDs. Mixed-effects linear and logistic regression models were used to assess the associations. RESULTS 401 participants were included, mean age of 40.7 years (SD = 11.2) and 77.4% male. DIMDs and symptoms of psychosis were differentially associated with each other, in which the presence of parkinsonism was associated with greater negative symptoms, dyskinesia with disorganized symptoms, and akathisia with excited symptoms. The presence of DIMDs of any type was not associated with depressive symptoms. Regarding temporal associations, preceding delusions and unusual thought content were associated with parkinsonism, whereas dyskinesia was associated with subsequent conceptual disorganization. CONCLUSIONS The current study found significant associations between DIMDs and symptoms of psychosis in individuals living in precarious housing or homelessness. Moreover, there were temporal associations between parkinsonism and psychotic symptoms (delusions or unusual thought content), and the presence of dyskinesia was temporally associated with higher odds of clinically relevant conceptual disorganization.
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Affiliation(s)
- David D Kim
- Department of Anesthesiology, Pharmacology & Therapeutics, 2176 Health Sciences Mall, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada; British Columbia Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada
| | - Ric M Procyshyn
- British Columbia Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Andrea A Jones
- British Columbia Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, BC, Canada
| | - Kristina M Gicas
- Department of Psychology, University of the Fraser Valley, Abbotsford, BC, Canada
| | - Paul W Jones
- Department of Psychology, Simon Fraser University, Burnaby, BC, Canada
| | - Anna M Petersson
- Department of Psychology, Simon Fraser University, Burnaby, BC, Canada
| | - Lik Hang N Lee
- Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada
| | - Rachel McLellan-Carich
- Department of Anesthesiology, Pharmacology & Therapeutics, 2176 Health Sciences Mall, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada; British Columbia Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada
| | - Lianne L Cho
- British Columbia Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - William J Panenka
- British Columbia Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Olga Leonova
- British Columbia Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Donna J Lang
- British Columbia Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Radiology, University of British Columbia, Vancouver, BC, Canada
| | - Allen E Thornton
- Department of Psychology, Simon Fraser University, Burnaby, BC, Canada
| | - William G Honer
- British Columbia Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Alasdair M Barr
- Department of Anesthesiology, Pharmacology & Therapeutics, 2176 Health Sciences Mall, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada; British Columbia Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada.
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20
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Weintraub D, Espay AJ, Sharma VD, Tariot PN, Abler V, Pathak S, Stankovic S. Pimavanserin for psychosis in Parkinson's disease dementia: Subgroup analysis of the HARMONY Trial. Parkinsonism Relat Disord 2024; 119:105951. [PMID: 38113700 DOI: 10.1016/j.parkreldis.2023.105951] [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: 07/14/2023] [Revised: 11/15/2023] [Accepted: 12/03/2023] [Indexed: 12/21/2023]
Abstract
INTRODUCTION Pimavanserin is FDA-approved to treat Parkinson's disease (PD) psychosis. We analyzed the effect of pimavanserin on psychosis in the PD dementia (PDD) subgroup from the phase 3 HARMONY trial. METHODS This subgroup analysis included PDD patients enrolled in an international, multicenter, randomized discontinuation study of pimavanserin for dementia-related psychosis. PDD patients with moderate-to-severe psychosis, age 50-90 years, received pimavanserin 34 mg/day for 12 weeks (open-label period). Those with a sustained psychosis response to pimavanserin at weeks 8 and 12 were randomized during the double-blind period to continue pimavanserin or receive placebo. Primary efficacy endpoint was time to psychosis relapse as measured by the SAPS-H + D and CGI-I. Safety was assessed, as were effects on motor symptoms and cognitive abilities using the ESRS-A and MMSE. RESULTS 392 patients were enrolled in HARMONY (mean age: 72.6 years; 38.8 % female): 59 had PDD; 49/59 remained on pimavanserin during the open-label period (safety analysis set), and 36/49 were randomized to pimavanserin (n = 16) or placebo (n = 20) in the double-blind phase (intent-to-treat analysis set). Risk of psychosis relapse was lower with pimavanserin 34 mg compared with placebo in the double-blind phase (HR = 0.052; 95 % CI 0.016-0.166; 1-sided nominal p < 0.001). During the open-label period, 46.9 % experienced a treatment-emergent adverse event; event incidence was similar across arms in the double-blind period. Pimavanserin did not adversely affect motor or cognitive function in either treatment phase. CONCLUSIONS Pimavanserin significantly reduced risk of psychosis relapse in patients with PDD, was well tolerated, and did not worsen motor or cognitive function.
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Affiliation(s)
- Daniel Weintraub
- Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, 3615 Chestnut Street, #330, Philadelphia, PA, 19104, USA.
| | - Alberto J Espay
- Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, 3113 Bellevue Ave, Cincinnati, OH, 45219, USA.
| | - Vibhash D Sharma
- Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA.
| | - Pierre N Tariot
- Banner Alzheimer's Institute and University of Arizona College of Medicine, 901 E Willetta St, Phoenix, AZ, 85006, USA.
| | - Victor Abler
- Acadia Pharmaceuticals Inc., 12830 El Camino Real #400, San Diego, CA, 92130, USA.
| | - Sanjeev Pathak
- Acadia Pharmaceuticals Inc., 12830 El Camino Real #400, San Diego, CA, 92130, USA.
| | - Srdjan Stankovic
- Acadia Pharmaceuticals Inc., 12830 El Camino Real #400, San Diego, CA, 92130, USA.
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21
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Dragonetti JD, Posada JG, Key RG, Kugler JL. Catatonia-related adverse outcomes after long-acting injectable antipsychotics: Case series. SAGE Open Med Case Rep 2024; 12:2050313X241229008. [PMID: 38304856 PMCID: PMC10832410 DOI: 10.1177/2050313x241229008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 01/11/2024] [Indexed: 02/03/2024] Open
Abstract
Due to a lack of controlled, prospective trials examining the pathophysiology and treatment of catatonia, current guidelines vary regarding how and when to best use antipsychotics in the presence of catatonia and what factors to consider in a thorough risk-benefit analysis. The literature is especially limited in describing the risks and benefits of using long-acting injectable antipsychotics in the presence of catatonia. We describe four cases where patients with preexisting catatonia received long-acting injectable first generation antipsychotics and experienced severe adverse effects (three experienced worsening of catatonia and one experienced neuroleptic malignant syndrome). The evidence base for managing comorbid catatonia and psychosis remains underdeveloped and inconsistent, but there are numerous known risk factors for adverse antipsychotic reactions, which we describe in relation to these cases. Finally, we present best practices to consider when managing comorbid psychosis and catatonia, especially when considering the use of long-acting injectable antipsychotics.
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Affiliation(s)
- Joseph D Dragonetti
- Department of Psychiatry & Behavioral Sciences, The University of Texas at Austin Dell Medical School, Austin, TX, USA
| | - Jacqueline G Posada
- Department of Psychiatry & Behavioral Sciences, The University of Texas at Austin Dell Medical School, Austin, TX, USA
| | - Richard Garrett Key
- Department of Psychiatry & Behavioral Sciences, The University of Texas at Austin Dell Medical School, Austin, TX, USA
| | - Joseph L Kugler
- Department of Psychiatry & Behavioral Sciences, The University of Texas at Austin Dell Medical School, Austin, TX, USA
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22
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Shamabadi A, Fattollahzadeh-Noor S, Fallahpour B, A Basti F, Khodaei Ardakani MR, Akhondzadeh S. L-Theanine adjunct to risperidone in the treatment of chronic schizophrenia inpatients: a randomized, double-blind, placebo-controlled clinical trial. Psychopharmacology (Berl) 2023; 240:2631-2640. [PMID: 37697164 DOI: 10.1007/s00213-023-06458-9] [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: 04/17/2023] [Accepted: 08/24/2023] [Indexed: 09/13/2023]
Abstract
RATIONALE Inadequate responses to current schizophrenia treatments have accelerated research into novel therapeutic approaches. OBJECTIVES This study investigated the efficacy and tolerability of adjunctive L-theanine, an ingredient with neuroimmunomodulatory and neuroprotective properties, for chronic schizophrenia. METHODS Eighty chronic schizophrenia inpatients were equally assigned to receive risperidone (6 mg/day) plus either L-theanine (400 mg/day) or matched placebo in this 8-week, randomized, parallel-group, double-blind, placebo-controlled trial. The participants were assessed using the Positive and Negative Syndrome Scale (PANSS) by recording the results of subscales at baseline and weeks 4 and 8 to measure treatment efficacy. Additionally, the participants were assessed for the Hamilton Depression Rating Scale (HDRS) and adverse events, including the Extrapyramidal Symptom Rating Scale (ESRS). RESULTS Sixty patients, 30 in each group, were included in the analyses. All baseline demographic and clinical characteristics were comparable between the groups (p-values > 0.05). The reduction rates from baseline to endpoint in negative, general psychopathology, and total scores of PANSS were greater in the L-theanine group (p-values = 0.03, 0.01, and 0.04, respectively). Regarding general psychopathology scores, the reduction in the L-theanine group was also greater until week 4 (p-value < 0.01). The time × treatment interaction effect was significant on negative (p-value = 0.03), general psychopathology (p-value < 0.01), and total (p-value = 0.04) scores of PANSS, indicating additional improvements in the L-theanine group. The HDRS and side effects were comparable between the groups (p-values > 0.05). CONCLUSIONS L-Theanine adjunct to risperidone safely and tolerably outperformed adjunctive placebo for schizophrenia, and promising evidence indicated its effects on primary negative symptoms, which need to be scrutinized in further studies. TRIAL REGISTRATION The study protocol was registered and published prospectively in the Iranian Registry of Clinical Trials ( http://www.irct.ir ; registration number: IRCT20090117001556N133) on 2020-12-12.
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Affiliation(s)
- Ahmad Shamabadi
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Setareh Fattollahzadeh-Noor
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Bita Fallahpour
- Department of Psychiatry, Razi Hospital, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Fatemeh A Basti
- Tehran Medical Branch, Islamic Azad University, Tehran, Iran
| | | | - Shahin Akhondzadeh
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran.
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23
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Lai YJ, Lin YC, Hsu CH, Tseng HH, Lee CN, Huang PC, Hsu HY, Kuo LC. Are the sensorimotor control capabilities of the hands the factors influencing hand function in people with schizophrenia? BMC Psychiatry 2023; 23:807. [PMID: 37936136 PMCID: PMC10631069 DOI: 10.1186/s12888-023-05259-w] [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: 06/16/2023] [Accepted: 10/07/2023] [Indexed: 11/09/2023] Open
Abstract
BACKGROUND Previous works reported people with schizophrenia experienced inferior hand functions which influence their daily participation and work efficiency. Sensorimotor capability is one of indispensable elements acting in a well-executed feed-forward and feedback control loop to contribute to hand performances. However, rare studies investigated contribution of sensorimotor ability to hand functions for people with schizophrenia. This study aimed to explore hand function in people with schizophrenia based on the perspective of the sensorimotor control capabilities of the hands. METHODS Twenty-seven people at the chronic stage of schizophrenia were enrolled. The following assessment tools were used: the Purdue Pegboard Test (PPT) and the VALPAR Component Work Sample-8 (VCWS 8) system for hand function; the Self-Reported Graphic version of the Personal and Social Performance (SRG-PSP) scale for functionality; and the Semmes-Weinstein Monofilaments (SWM), the pinch-holding-up-activity (PHUA) test and the Manual Tactile Test (MTT) for the sensory and sensorimotor parameters. The Clinical Global Impression-Severity (CGI-S) scale and the Extrapyramidal Symptom Rating Scale (ESRS) were used to grade the severity of the illness and the side-effects of the drugs. Spearman's rank correlation coefficient was used to analyze associations among hand function, functionality, and sensorimotor capabilities. A multiple linear regression analysis was used to identify the determinants of hand function. RESULTS The results indicated that both hand function and sensorimotor capability were worse in people with schizophrenia than in healthy people, with the exception of the sensory threshold measured with the SWM. Moreover, the sensorimotor abilities of the hands were associated with hand function. The results of the regression analysis showed that the MTT measure of stereognosis was a determinant of the PPT measure of the dominant hand function and of the performance on the VCWS 8, and that the ESRS and the MTT measure of barognosis were determinants of the performance on the assembly task of the PPT. CONCLUSIONS The findings suggested that sensorimotor capabilities, especially stereognosis and barognosis, are crucial determinants of hand function in people with schizophrenia. The results also revealed that the side effects of drugs and the duration of the illness directly affect hand function. CLINICAL TRAIL REGISTRATION ClinicalTrials.gov , identifier NCT04941677, 28/06/2021.
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Affiliation(s)
- Yu-Jen Lai
- Department of Occupational Therapy, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan City, 701, Taiwan
- Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yu-Chen Lin
- Department of Occupational Therapy, Da-Yeh University, Changhua, Taiwan
| | - Chieh-Hsiang Hsu
- Department of Occupational Therapy, Da-Yeh University, Changhua, Taiwan
- Department of Biomedical Engineering, College of Engineering, National Cheng Kung University, Tainan, Taiwan
| | - Huai-Hsuan Tseng
- Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chia-Ning Lee
- Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Pai-Chuan Huang
- Department of Occupational Therapy, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan City, 701, Taiwan.
- Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
| | - Hsiu-Yun Hsu
- Department of Occupational Therapy, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan City, 701, Taiwan.
- Department of Physical Medicine and Rehabilitation, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan City, 701, Taiwan.
| | - Li-Chieh Kuo
- Department of Occupational Therapy, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan City, 701, Taiwan.
- Department of Physical Medicine and Rehabilitation, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan City, 701, Taiwan.
- Department of Biomedical Engineering, College of Engineering, National Cheng Kung University, Tainan, Taiwan.
- Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan.
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24
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McKee KA, Crocker CE, Dikaios K, Otter N, Bardell A, Roy MA, Abdel-Baki A, Palaniyappan L, Malla A, Tibbo PG. Short communication: Prevalence of long-acting injectable antipsychotic use in Canadian early intervention services for psychosis. J Psychiatr Res 2023; 165:77-82. [PMID: 37480668 DOI: 10.1016/j.jpsychires.2023.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 05/24/2023] [Accepted: 07/06/2023] [Indexed: 07/24/2023]
Abstract
The use of long-acting injectable (LAI) antipsychotic drugs for psychotic disorders in Canada has been historically low compared to other jurisdictions despite advantages of LAIs in improving medication adherence and preventing relapse. In response, treatment recommendations were developed in 2013 by the Canadian Consortium for Early Intervention in Psychosis and other Canadian provincial expert groups. The impact of these guidelines needed to be assessed. To document practices in LAI use in early intervention services (EIS) for psychosis, Canadian EIS were surveyed in 2016 (n = 18) and 2020 (n = 12). Trends and descriptive information were examined using repeated cross-sectional survey data. Eight EIS responded to surveys at both time points allowing for longitudinal comparisons. Outcomes of interest included i) LAI use frequency, ii) timing of LAI starts, and iii) factors influencing LAI use. Cross-sectional analysis identified a significant increase in overall LAI usage (24.7% in 2016; 35.1% in 2020). Longitudinal analysis indicated that patients in the second program year saw the greatest increase in LAI use between 2016 and 2020 (25.6% vs. 36.1%), especially among patients under community treatment orders (65.5% vs. 81.5%). Results support increases in LAI use over time, accessibility, awareness, and increasing comfortability among Canadian clinicians.
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Affiliation(s)
- Kyle A McKee
- Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Candice E Crocker
- Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Diagnostic Radiology, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Katerina Dikaios
- Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Nicola Otter
- Canadian Consortium for Early Intervention in Psychosis, Hamilton, Ontario, Canada
| | - Andrea Bardell
- Canadian Consortium for Early Intervention in Psychosis, Hamilton, Ontario, Canada; Department of Psychiatry, University of British Columbia, Victoria, British Columbia, Canada; The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Marc-André Roy
- Canadian Consortium for Early Intervention in Psychosis, Hamilton, Ontario, Canada; Département de Psychiatrie et Neurosciences, Faculté de Médecine de L'Université Laval, Québec, Canada; Clinique Notre-Dame des Victoires, Centre Intégré Universitaire de La Capitale Nationale, Québec, Canada
| | - Amal Abdel-Baki
- Canadian Consortium for Early Intervention in Psychosis, Hamilton, Ontario, Canada; Department of Psychiatry, University of Montreal, Québec, Canada; Department of Psychiatry, Centre Hospitalier de L'Université de Montréal, Québec, Canada; Centre de Recherche Du Centre Hospitalier de L'Université de Montréal, Canada
| | - Lena Palaniyappan
- Canadian Consortium for Early Intervention in Psychosis, Hamilton, Ontario, Canada; Department of Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada; Robarts Research Institute, University of Western Ontario, London, Ontario, Canada; Prevention and Early Intervention Program for Psychosis (PEPP-Montreal), Douglas Mental Health University Institute, Montreal, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada
| | - Ashok Malla
- Canadian Consortium for Early Intervention in Psychosis, Hamilton, Ontario, Canada; Prevention and Early Intervention Program for Psychosis (PEPP-Montreal), Douglas Mental Health University Institute, Montreal, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada
| | - Philip G Tibbo
- Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada; Canadian Consortium for Early Intervention in Psychosis, Hamilton, Ontario, Canada.
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25
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Kim DD, Procyshyn RM, Jones AA, Lee LHN, Panenka WJ, Stubbs JL, Cho LL, Leonova O, Gicas KM, Thornton AE, Lang DJ, MacEwan GW, Honer WG, Barr AM. Movement disorders associated with substance use in adults living in precarious housing or homelessness. Prog Neuropsychopharmacol Biol Psychiatry 2023; 126:110795. [PMID: 37196752 DOI: 10.1016/j.pnpbp.2023.110795] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 05/12/2023] [Accepted: 05/13/2023] [Indexed: 05/19/2023]
Abstract
OBJECTIVE Many individuals living in precarious housing or homelessness have multimorbid illnesses, including substance use, psychiatric, and neurological disorders. Movement disorders (MDs) associated substance use are amongst the poorly studied subtopics of drug-induced MDs. The aim of the present study was, therefore, to determine the proportion affected and severity of different signs of MDs, as well as their associations with substance use in a community-based sample of precariously housed and homeless individuals. METHODS Participants were recruited from an impoverished urban neighborhood and were assessed for substance dependence and self-reported substance use (alcohol, cannabis, cocaine, methamphetamine, nicotine, and opioids), as well as for the severity of signs of MDs (akathisia, dyskinesia, dystonia, and parkinsonism). Adjusted regression models were used to estimate the associations of the severity of signs with the frequency of substance use over the past 4 weeks and with the baseline diagnosis of substance dependence. RESULTS The proportion of the sample with clinically relevant signs of MDs in any of the four categories was 18.6% (n = 401), and these participants demonstrated lower levels of functioning than those without signs. Of the different types of substance use, only methamphetamine (its frequency of use and dependence) was significantly associated with greater severity of overall signs of MDs. Frequency of methamphetamine use significantly interacted with age and sex, whereby older female participants exhibited the greatest overall severity with increased methamphetamine use. Of the different signs of MDs, methamphetamine use frequency was positively associated with the severity of trunk/limb dyskinesia and hypokinetic parkinsonism. Relative to no use, concurrent use of antipsychotics demonstrated lower severity of trunk/limb dyskinesia and greater severity of hypokinetic parkinsonism with methamphetamine use, and greater severity of dystonia with cocaine use. CONCLUSIONS Our study found a high proportion of MDs in a relatively young sample, and their severity was consistently associated with methamphetamine use, moderated by participant demographics and antipsychotic use. These disabling sequelae represent an important and understudied neurological condition that may affect quality of life and will require further study.
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Affiliation(s)
- David D Kim
- Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, BC, Canada; BC Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada
| | - Ric M Procyshyn
- BC Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Andrea A Jones
- BC Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, BC, Canada
| | - Lik Hang N Lee
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - William J Panenka
- BC Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Jacob L Stubbs
- BC Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Lianne L Cho
- BC Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Olga Leonova
- BC Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Kristina M Gicas
- Department of Psychology, York University, Toronto, Ontario, Canada
| | - Allen E Thornton
- Department of Psychology, Simon Fraser University, Burnaby, BC, Canada
| | - Donna J Lang
- BC Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Radiology, University of British Columbia, Vancouver, BC, Canada
| | - G William MacEwan
- BC Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - William G Honer
- BC Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada
| | - Alasdair M Barr
- Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, BC, Canada; BC Mental Health and Substance Use Services Research Institute, Vancouver, BC, Canada.
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26
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Cho LL, Jones AA, Gao C, Leonova O, Vila-Rodriguez F, Buchanan T, Lang DJ, MacEwan GW, Procyshyn RM, Panenka WJ, Barr AM, Thornton AE, Gicas KM, Honer WG, Barbic SP. Rasch analysis of the beck depression inventory in a homeless and precariously housed sample. Psychiatry Res 2023; 326:115331. [PMID: 37437487 DOI: 10.1016/j.psychres.2023.115331] [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: 01/26/2023] [Revised: 07/01/2023] [Accepted: 07/02/2023] [Indexed: 07/14/2023]
Abstract
The approach to analysis of and interpretation of findings from the Beck Depression Inventory (BDI), a self-report questionnaire, depends on sample characteristics. To extend work using conventional BDI scoring, the BDI's suitability in assessing symptom severity in a homeless and precariously housed sample was examined using Rasch analysis. Participants (n=478) recruited from an impoverished neighbourhood in Vancouver, Canada, completed the BDI. Rasch analysis using the partial credit model was done, and the structural validity, unidimensionality, and reliability of the BDI were studied. A receiver operating characteristic curve determined a Rasch cut-off score consistent with clinical depression, and Rasch scores were correlated with raw scores. Good fit to the Rasch model was observed after rescoring all items and removing Item 19 (Weight Loss), and unidimensionality and reliability were satisfactory. Item 9 (Suicidal Wishes) represented the most severe symptom. Rasch-based scores detected clinical depression with moderate sensitivity and specificity, and were positively correlated with conventional scores. The BDI in a community-based sample of homeless and precariously housed adults satisfied Rasch model expectations in a 20-item format, and is suitable for assessing symptom severity. Future research on depression in similar samples may reveal more information on using specific symptoms to determine clinical significance.
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Affiliation(s)
- Lianne L Cho
- Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; BC Mental Health and Substance Use Services Research Institute, Vancouver, British Columbia, Canada
| | - Andrea A Jones
- Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Chloe Gao
- Department of Occupational Science and Occupational Therapy, University of British Columbia, T325 - 2211 Wesbrook Mall, Vancouver, British Columbia, Canada
| | - Olga Leonova
- Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada
| | - Fidel Vila-Rodriguez
- Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada
| | - Tari Buchanan
- Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada
| | - Donna J Lang
- BC Mental Health and Substance Use Services Research Institute, Vancouver, British Columbia, Canada; Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada
| | - G William MacEwan
- Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada
| | - Ric M Procyshyn
- Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; BC Mental Health and Substance Use Services Research Institute, Vancouver, British Columbia, Canada
| | - William J Panenka
- BC Mental Health and Substance Use Services Research Institute, Vancouver, British Columbia, Canada; Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Alasdair M Barr
- BC Mental Health and Substance Use Services Research Institute, Vancouver, British Columbia, Canada; Department of Anesthesia, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
| | - Allen E Thornton
- Department of Psychology, Simon Fraser University, Burnaby, British Columbia, Canada
| | - Kristina M Gicas
- Department of Psychology, York University, Toronto, Ontario, Canada
| | - William G Honer
- Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; BC Mental Health and Substance Use Services Research Institute, Vancouver, British Columbia, Canada
| | - Skye P Barbic
- Department of Occupational Science and Occupational Therapy, University of British Columbia, T325 - 2211 Wesbrook Mall, Vancouver, British Columbia, Canada.
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27
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du Plessis S, Chand GB, Erus G, Phahladira L, Luckhoff HK, Smit R, Asmal L, Wolf DH, Davatzikos C, Emsley R. Two Neuroanatomical Signatures in Schizophrenia: Expression Strengths Over the First 2 Years of Treatment and Their Relationships to Neurodevelopmental Compromise and Antipsychotic Treatment. Schizophr Bull 2023; 49:1067-1077. [PMID: 37043772 PMCID: PMC10318886 DOI: 10.1093/schbul/sbad040] [Citation(s) in RCA: 4] [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] [Indexed: 04/14/2023]
Abstract
BACKGROUND AND HYPOTHESIS Two machine learning derived neuroanatomical signatures were recently described. Signature 1 is associated with widespread grey matter volume reductions and signature 2 with larger basal ganglia and internal capsule volumes. We hypothesized that they represent the neurodevelopmental and treatment-responsive components of schizophrenia respectively. STUDY DESIGN We assessed the expression strength trajectories of these signatures and evaluated their relationships with indicators of neurodevelopmental compromise and with antipsychotic treatment effects in 83 previously minimally treated individuals with a first episode of a schizophrenia spectrum disorder who received standardized treatment and underwent comprehensive clinical, cognitive and neuroimaging assessments over 24 months. Ninety-six matched healthy case-controls were included. STUDY RESULTS Linear mixed effect repeated measures models indicated that the patients had stronger expression of signature 1 than controls that remained stable over time and was not related to treatment. Stronger signature 1 expression showed trend associations with lower educational attainment, poorer sensory integration, and worse cognitive performance for working memory, verbal learning and reasoning and problem solving. The most striking finding was that signature 2 expression was similar for patients and controls at baseline but increased significantly with treatment in the patients. Greater increase in signature 2 expression was associated with larger reductions in PANSS total score and increases in BMI and not associated with neurodevelopmental indices. CONCLUSIONS These findings provide supporting evidence for two distinct neuroanatomical signatures representing the neurodevelopmental and treatment-responsive components of schizophrenia.
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Affiliation(s)
- Stefan du Plessis
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Campus, Cape Town, South Africa
| | - Ganesh B Chand
- Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
- Department of Radiology and Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis
| | - Guray Erus
- Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Lebogang Phahladira
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Campus, Cape Town, South Africa
| | - Hilmar K Luckhoff
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Campus, Cape Town, South Africa
| | - Retha Smit
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Campus, Cape Town, South Africa
| | - Laila Asmal
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Campus, Cape Town, South Africa
| | - Daniel H Wolf
- Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Christos Davatzikos
- Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
| | - Robin Emsley
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Campus, Cape Town, South Africa
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Emsley R, du Plessis S, Phahladira L, Luckhoff HK, Scheffler F, Kilian S, Smit R, Buckle C, Chiliza B, Asmal L. Antipsychotic treatment effects and structural MRI brain changes in schizophrenia. Psychol Med 2023; 53:2050-2059. [PMID: 35441587 PMCID: PMC10106303 DOI: 10.1017/s0033291721003809] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 07/21/2021] [Accepted: 09/01/2021] [Indexed: 11/06/2022]
Abstract
BACKGROUND Progressive brain structural MRI changes are described in schizophrenia and have been ascribed to both illness progression and antipsychotic treatment. We investigated treatment effects, in terms of total cumulative antipsychotic dose, efficacy and tolerability, on brain structural changes over the first 24 months of treatment in schizophrenia. METHODS A prospective, 24-month, single-site cohort study in 99 minimally treated patients with first-episode schizophrenia, schizophreniform and schizoaffective disorder, and 98 matched healthy controls. We treated the patients according to a fixed protocol with flupenthixol decanoate, a long-acting injectable antipsychotic. We assessed psychopathology, cognition, extrapyramidal symptoms and BMI, and acquired MRI scans at months 0, 12 and 24. We selected global cortical thickness, white matter volume and basal ganglia volume as the regions of interest. RESULTS The only significant group × time interaction was for basal ganglia volumes. However, patients, but not controls, displayed cortical thickness reductions and increases in white matter and basal ganglia volumes. Cortical thickness reductions were unrelated to treatment. White matter volume increases were associated with lower cumulative antipsychotic dose, greater improvements in psychopathology and cognition, and more extrapyramidal symptoms. Basal ganglia volume increases were associated with greater improvements in psychopathology, greater increases in BMI and more extrapyramidal symptoms. CONCLUSIONS We provide evidence for plasticity in white matter and basal ganglia associated with antipsychotic treatment in schizophrenia, most likely linked to the dopamine blocking actions of these agents. Cortical changes may be more closely related to the neurodevelopmental, non-dopaminergic aspects of the illness.
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Affiliation(s)
- Robin Emsley
- Department of Psychiatry, Stellenbosch University, Tygerberg Campus, Cape Town, South Africa
| | - Stefan du Plessis
- Department of Psychiatry, Stellenbosch University, Tygerberg Campus, Cape Town, South Africa
| | - Lebogang Phahladira
- Department of Psychiatry, Stellenbosch University, Tygerberg Campus, Cape Town, South Africa
| | - Hilmar K. Luckhoff
- Department of Psychiatry, Stellenbosch University, Tygerberg Campus, Cape Town, South Africa
| | - Frederika Scheffler
- Department of Psychiatry, Stellenbosch University, Tygerberg Campus, Cape Town, South Africa
| | - Sanja Kilian
- Department of Psychiatry, Stellenbosch University, Tygerberg Campus, Cape Town, South Africa
| | - Retha Smit
- Department of Psychiatry, Stellenbosch University, Tygerberg Campus, Cape Town, South Africa
| | - Chanelle Buckle
- Department of Psychiatry, Stellenbosch University, Tygerberg Campus, Cape Town, South Africa
| | - Bonginkosi Chiliza
- Department of Psychiatry, Nelson R Mandela School of Medicine, University of Kwazulu-Natal, Durban, South Africa
| | - Laila Asmal
- Department of Psychiatry, Stellenbosch University, Tygerberg Campus, Cape Town, South Africa
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Inci Izmir SB, Ercan ES. Treatment of preschool children with obsessive compulsive disorder. Clin Child Psychol Psychiatry 2023; 28:734-747. [PMID: 35801811 DOI: 10.1177/13591045221111848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The aim was to examine the clinical features of Obsessive-Compulsive Disorder (OCD) in preschool and the effectiveness of aripiprazole with a standardized Cognitive-Behavioral Family Therapy (CBFT) in the treatment of preschoolers with OCD. Twelve preschool children, 36-72 months of age were diagnosed with OCD according to the Diagnostic and Statistical Manual of Mental Disorders, the Fifth Edition criteria by a fellowship-trained child and adolescent psychiatrist. They were evaluated with Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children Present and Lifetime version and Childhood Yale-Brown Obsessive Compulsive Scale (CY-BOCS) at baseline, at the end of the 12th and 24th weeks of treatment. The baseline mean of total CY-BOCS score decreased from 33.67 to 13.83 at the 12th week and 5.58 at the end of the 24th week of treatment. Also, 66.7% of them had at least one psychiatric comorbidity. Overall, this study revealed the effect of aripiprazole with CBFT in preschool-aged children with OCD. Also, the presence of comorbidity that is seen frequently in preschoolers with OCD may complicate the treatment. Therefore, there is a need to increase awareness of OCD and its comorbidities in preschoolers to supply treatment at an early age.
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Affiliation(s)
| | - Eyüp Sabri Ercan
- 37509Ege University, Child and Adolescent Psychiatry Department, Medical Faculty, Izmir, Turkey
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Karbalaee M, Jameie M, Amanollahi M, TaghaviZanjani F, Parsaei M, Basti FA, Mokhtari S, Moradi K, Ardakani MRK, Akhondzadeh S. Efficacy and safety of adjunctive therapy with fingolimod in patients with schizophrenia: A randomized, double-blind, placebo-controlled clinical trial. Schizophr Res 2023; 254:92-98. [PMID: 36805834 DOI: 10.1016/j.schres.2023.02.020] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 02/05/2023] [Accepted: 02/13/2023] [Indexed: 02/21/2023]
Abstract
OBJECTIVES Studies have suggested that fingolimod, a sphingosine-1-phosphate receptor modulator, exerts neuroprotective and anti-inflammatory effects. Although fingolimod is approved for the treatment of relapsing-remitting multiple sclerosis, limited studies have investigated its effects in patients with schizophrenia. This study investigated the efficacy and safety of fingolimod adjuvant to risperidone in schizophrenia treatment. METHODS This eight-week, randomized, double-blinded, placebo-controlled trial included 80 (clinical trials registry code: IRCT20090117001556N137) patients with chronic schizophrenia. Participants were assigned to two equal arms and received risperidone plus either fingolimod (0.5 mg/day) or a matched placebo. The positive and negative symptom scale (PANSS) was used to measure and compare the effectiveness of treatment strategies at baseline and weeks 2, 4, 6, and 8. Treatment side effects were also compared. RESULTS Seventy participants completed the trial (35 in each arm). The baseline characteristics of the groups were comparable (P-value > 0.05). There were significant time-treatment interaction effects on negative symptoms (P-value = 0.003), general symptoms (P-value = 0.037), and the PANSS total score (P-value = 0.035), suggesting greater improvement in symptoms following the fingolimod adjuvant therapy. In contrast, the longitudinal changes in positive and depressive symptoms were similar between the groups (P-values > 0.05). Regarding the safety of treatments, there were no differences in extrapyramidal symptoms [assessed by the extrapyramidal symptom rating scale (ESRS)] or frequency of other complications between the fingolimod and the placebo groups (P-values > 0.05). CONCLUSIONS This study indicated that fingolimod is a safe and effective adjuvant agent for schizophrenia treatment. However, further clinical trials are required to suggest extensive clinical application.
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Affiliation(s)
- Monire Karbalaee
- Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Melika Jameie
- Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mobina Amanollahi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Fateme TaghaviZanjani
- Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Fatemeh A Basti
- Islamic Azad University, Tehran Medical Branch, Tehran, Iran
| | - Saba Mokhtari
- Department of Psychiatry, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Kamyar Moradi
- Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Shahin Akhondzadeh
- Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.
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Lin MC, Chang YY, Lee Y, Wang LJ. Tardive sensory syndrome related to lurasidone: A case report. World J Psychiatry 2023; 13:126-130. [PMID: 37033893 PMCID: PMC10075022 DOI: 10.5498/wjp.v13.i3.126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/17/2022] [Accepted: 02/15/2023] [Indexed: 03/17/2023] Open
Abstract
BACKGROUND Tardive sensory syndrome (TSS) is a subtype of tardive syndrome (TS), and its etiology is still uncertain. Lurasidone is an atypical antipsychotic that has high affinity for dopamine D2- and serotonergic 5HT2A- and 5-HT7-receptors.
CASE SUMMARY A 52-year-old woman, previously diagnosed with schizophrenia, and with no history of movement disorders and no sensory paresthesia, had taken lurasidone, initiate dose 40 mg daily then up titration to 120 mg daily, since March 2021, and developed mandibular sensory (pain) paresthesia after 3 mo of administration. After switching from lurasidone to quetiapine, she reported obvious impr-ovement in her mandibular pain.
CONCLUSION It is noteworthy that TSS is a rare subtype of TS, and lurasidone, an atypical antipsychotic, usually has a lower risk of causing TS. In light of the temporal relationship, it is therefore concluded that use of lurasidone might have caused TSS in this patient. We reported this rare case as a reminder that clinicians should adopt a cautious approach when prescribing atypical antipsychotics, so as to prevent TS.
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Affiliation(s)
- Mei-Chun Lin
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Kaohsiung 83301, Taiwan
| | - Yung-Yee Chang
- Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Kaohsiung 83301, Taiwan
| | - Yu Lee
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Kaohsiung 83301, Taiwan
| | - Liang-Jen Wang
- Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
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Zhang K, Miao S, Yao Y, Yang Y, Shi S, Luo B, Li M, Zhang L, Liu H. Efficacy and safety of prophylactic use of benzhexol after risperidone treatment. Heliyon 2023; 9:e14199. [PMID: 36925546 PMCID: PMC10010996 DOI: 10.1016/j.heliyon.2023.e14199] [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: 08/04/2022] [Revised: 02/12/2023] [Accepted: 02/24/2023] [Indexed: 03/12/2023] Open
Abstract
To test the effect of prophylactic use of benzhexol in schizophrenia patients after risperidone treatment. Sixty-nine drug naïve schizophrenia patients were recruited. All patients were administered risperidone. Patients in the benzhexol group were given a benzhexol tablet of 2 mg bid daily. The controls received a placebo tablet of 2 mg bid daily. The primary outcome measured using the Extrapyramidal Symptoms Rating Scale (ESRS). The Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS) measured secondary outcome. There were significant time and group effects on the ESRS scores of the two groups. The post hoc analysis yielded significant differences at 1, 2, 4, and 8 weeks between the two groups. There was a significant time effect on the PANSS scores of the two groups. No significant group and interaction effects on the PANSS scores of the two groups. There was a significant time effect on the BPRS scores of the two groups. No serious adverse events were found in this study. Prophylactic use of benzhexol reduced extrapyramidal symptom in schizophrenia patients after risperidone treatment and did not affect the antipsychotic action of risperidone.
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Affiliation(s)
- Kai Zhang
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, China
- Anhui Psychiatric Center, Anhui Medical University, Hefei, 238000, China
| | - Shipan Miao
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, China
- Anhui Psychiatric Center, Anhui Medical University, Hefei, 238000, China
| | - Yitan Yao
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, China
- Anhui Psychiatric Center, Anhui Medical University, Hefei, 238000, China
| | - Yating Yang
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, China
- Anhui Psychiatric Center, Anhui Medical University, Hefei, 238000, China
| | - Shengya Shi
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, China
- Anhui Psychiatric Center, Anhui Medical University, Hefei, 238000, China
| | - Bei Luo
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, China
- Anhui Psychiatric Center, Anhui Medical University, Hefei, 238000, China
| | - Mengdie Li
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, China
- Anhui Psychiatric Center, Anhui Medical University, Hefei, 238000, China
| | - Ling Zhang
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, China
- Anhui Psychiatric Center, Anhui Medical University, Hefei, 238000, China
| | - Huanzhong Liu
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 238000, China
- Anhui Psychiatric Center, Anhui Medical University, Hefei, 238000, China
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Abdallah MS, Mosalam EM, Hassan A, Ramadan AN, Omara‐Reda H, Zidan AA, Samman WA, El‐berri EI. Pentoxifylline as an adjunctive in treatment of negative symptoms in chronic schizophrenia: A double-blind, randomized, placebo-controlled trial. CNS Neurosci Ther 2023; 29:354-364. [PMID: 36341700 PMCID: PMC9804082 DOI: 10.1111/cns.14010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 10/03/2022] [Accepted: 10/18/2022] [Indexed: 11/09/2022] Open
Abstract
AIM The aim of this study was to explore the effectiveness and safety of pentoxifylline as an adjuvant to risperidone in mitigating the negative symptoms in patients with chronic schizophrenia. METHODS In this randomized, placebo-controlled study, eighty outpatients with chronic schizophrenia were given risperidone for 8 weeks along with either pentoxifylline or a placebo. The positive and negative syndrome scale (PANSS) was used to assess patients at the start of the trial, as well as at 2, 4, 6, and 8 weeks. Pre- and posttreatment serum levels of cAMP, TNF-α-, and IL-6 were measured. RESULTS The pentoxifylline group revealed a significant effect for time-treatment interaction on PANSS-negative subscale scores (p < 0.001), PANSS general psychopathology subscale scores (p < 0.001), and PANSS total scores (p < 0.001), but not on PANSS-positive subscale scores (p = 0.169). Additionally, when compared to the placebo group, the pentoxifylline group demonstrated a statistically significant increase in cAMP serum level and a statistically significant decrease in TNF-α and IL-6 serum levels. CONCLUSION Pentoxifylline adjunctive therapy with risperidone for 8 weeks was found to be promising in mitigating the negative symptoms in patients with chronic schizophrenia. TRIAL REGISTRATION NUMBER NCT04094207.
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Affiliation(s)
- Mahmoud S. Abdallah
- Department of Clinical Pharmacy, Faculty of PharmacyUniversity of Sadat CitySadat CityEgypt
| | - Esraa M. Mosalam
- Department of Biochemistry, Faculty of PharmacyMenoufia UniversityShebeen El‐KomEgypt
| | - Ahmed Hassan
- Department of Clinical Pharmacy, Faculty of PharmacyUniversity of Sadat CitySadat CityEgypt
| | - Ahmed N. Ramadan
- Department of Neuropsychiatry, Faculty of MedicineMenoufia UniversityShebeen El‐KomEgypt
| | - Hend Omara‐Reda
- Department of Neuropsychiatry, Faculty of MedicineMenoufia UniversityShebeen El‐KomEgypt
| | | | - Waad A. Samman
- Department of Pharmacology and Toxicology, College of PharmacyTaibah UniversityMedinaSaudi Arabia
| | - Eman I. El‐berri
- Clinical Pharmacy Department, Faculty of PharmacyTanta UniversityTantaEgypt
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Kwong AJ, Zahr NM. Serum biomarkers of liver fibrosis identify globus pallidus vulnerability. Neuroimage Clin 2023; 37:103333. [PMID: 36868044 PMCID: PMC9996367 DOI: 10.1016/j.nicl.2023.103333] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 01/12/2023] [Accepted: 01/19/2023] [Indexed: 01/28/2023]
Abstract
The CNS manifestation of chronic liver disease can include magnetic resonance (MR) signal hyperintensities in basal ganglia structures. Here, relations between liver (serum-derived fibrosis scores) and brain (regional T1-weighted signal intensities and volumes) integrity were evaluated in a sample of 457 individuals including those with alcohol use disorders (AUD), people living with human immunodeficiency virus (HIV), those comorbid for AUD and HIV, and healthy controls. Liver fibrosis was identified from cutoff scores as follows: aspartate aminotransferase to platelet ratio index (APRI) > 0.7 in 9.4% (n = 43) of the cohort; fibrosis score (FIB4) > 1.5 in 28.0% (n = 128) of the cohort; and non-alcoholic fatty liver disease fibrosis score (NFS) > -1.4 in 30.2% (n = 138) of the cohort. Presence of serum-derived liver fibrosis was associated with high signal intensities selective to basal ganglia (i.e., caudate, putamen, and pallidum) structures. High signal intensities in the pallidum, however, explained a significant portion of the variance in APRI (25.0%) and FIB4 (23.6%) cutoff scores. Further, among the regions evaluated, only the globus pallidus showed a correlation between greater signal intensity and smaller volume (r = -0.44, p <.0001). Finally, higher pallidal signal intensity correlated worse ataxia (eyes open ρ = -0.23, p =.0002; eyes closed ρ = -0.21, p =.0005). This study suggests that clinically relevant serum biomarkers of liver fibrosis such as the APRI may identify individuals vulnerable to globus pallidus pathology and contribute to problems with postural balance.
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Affiliation(s)
- Allison J Kwong
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, School of Medicine, Redwood City, CA 94063, USA
| | - Natalie M Zahr
- Department of Psychiatry & Behavioral Sciences, Stanford University, School of Medicine, 401 Quarry Rd. Stanford, CA 94305, USA; Neuroscience Program, SRI International, Menlo Park, CA 94025, USA.
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SLC6A3, HTR2C and HTR6 Gene Polymorphisms and the Risk of Haloperidol-Induced Parkinsonism. Biomedicines 2022; 10:biomedicines10123237. [PMID: 36551993 PMCID: PMC9776373 DOI: 10.3390/biomedicines10123237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 12/07/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022] Open
Abstract
Antipsychotic-induced parkinsonism (AIP) is the most common type of extrapyramidal side effect (EPS), caused by the blockage of dopamine receptors. Since dopamine availability might influence the AIP risk, the dopamine transporter (DAT) and serotonin receptors (5-HTRs), which modulate the dopamine release, may be also involved in the AIP development. As some of the individual differences in the susceptibility to AIP might be due to the genetic background, this study aimed to examine the associations of SLC6A3, HTR2C and HTR6 gene polymorphisms with AIP in haloperidol-treated schizophrenia patients. The Extrapyramidal Symptom Rating Scale (ESRS) was used to evaluate AIP as a separate entity. Genotyping was performed using a PCR, following the extraction of blood DNA. The results revealed significant associations between HTR6 rs1805054 polymorphism and haloperidol-induced tremor and rigidity. Additionally, the findings indicated a combined effect of HTR6 T and SLC6A3 9R alleles on AIP, with their combination associated with significantly lower scores of ESRS subscale II for parkinsonism, ESRS-based tremor or hyperkinesia and ESRS subscales VI and VIII. These genetic predictors of AIP could be helpful in better understanding its pathophysiology, recognizing the individuals at risk of developing AIP and offering personalized therapeutic strategies for the patients suffering from this EPS.
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Early onset tardive syndromes associated with Lurasidone in patients with mood disorders: A case series and literature review. JOURNAL OF AFFECTIVE DISORDERS REPORTS 2022. [DOI: 10.1016/j.jadr.2022.100423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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Dirks B, Fava M, Atkinson SD, Joyce M, Thase ME, Howell B, Lin T, Stankovic S. Adjunctive Pimavanserin in Patients with Major Depressive Disorder: Combined Results from Two Randomized, Double-Blind, Placebo-Controlled Phase 3 Studies. PSYCHOPHARMACOLOGY BULLETIN 2022; 52:8-30. [PMID: 36339271 PMCID: PMC9611795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Objective In a phase 2 study, pimavanserin demonstrated efficacy as adjunctive treatment for major depressive disorder (MDD). Subsequently, two phase 3 studies (NCT03968159 in the US; NCT03999918 in Europe) were initiated to examine the efficacy and safety of adjunctive pimavanserin in subjects with MDD and inadequate response to antidepressant treatment. Studies were combined with a prespecified statistical analysis plan owing to recruitment challenges related to the COVID-19 pandemic. Experimental design The randomized, double-blind studies enrolled 298 patients with MDD and inadequate response to current antidepressants. Patients were randomly assigned 1:1 to pimavanserin or placebo added to current antidepressant for 6 weeks. Primary endpoint was change from baseline to week 5 in the Hamilton Rating Scale for Depression, 17-item version (HAM-D-17). Principal observations There was no effect of pimavanserin in change from baseline to week 5 in the HAM-D-17 (pimavanserin [n = 138]: least-squares mean [LSM] [standard error {SE}], -9.0 [0.58]; placebo [n = 135]: -8.1 [0.58]; mixed-effects model for repeated measures LSM [SE] difference, -0.9 [0.82], P = 0.2956). Nominal improvement with pimavanserin was observed on 2 secondary endpoints: Clinical Global Impressions-Severity scale, Karolinska Sleepiness Scale. Treatment-emergent adverse events occurred in 58.1% of pimavanserin-treated and 54.7% of placebo-treated patients. Conclusions Adjunctive pimavanserin did not significantly improve depressive symptoms, although pimavanserin was well tolerated.
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Affiliation(s)
- Bryan Dirks
- Bryan Dirks, Acadia Pharmaceuticals Inc, San Diego, CA, USA
| | - Maurizio Fava
- Maurizio Fava, Department of Psychiatry, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA
| | | | - Mark Joyce
- Mark Joyce, CNS Healthcare, Jacksonville, FL, USA
| | - Michael E Thase
- Michael E. Thase, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania and the Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA
| | - Becky Howell
- Becky Howell, Acadia Pharmaceuticals Inc, Princeton, NJ, USA
| | - Tim Lin
- Tim Lin, Acadia Pharmaceuticals Inc, San Diego, CA, USA
| | - Serge Stankovic
- Serge Stankovic, Acadia Pharmaceuticals Inc, San Diego, CA, USA
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Yeh TC, Huang CCY, Chung YA, Im JJ, Lin YY, Ma CC, Tzeng NS, Chang CC, Chang HA. High-Frequency Transcranial Random Noise Stimulation over the Left Prefrontal Cortex Increases Resting-State EEG Frontal Alpha Asymmetry in Patients with Schizophrenia. J Pers Med 2022; 12:1667. [PMID: 36294806 PMCID: PMC9604798 DOI: 10.3390/jpm12101667] [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: 08/26/2022] [Revised: 10/01/2022] [Accepted: 10/04/2022] [Indexed: 12/05/2022] Open
Abstract
Reduced left-lateralized electroencephalographic (EEG) frontal alpha asymmetry (FAA), a biomarker for the imbalance of interhemispheric frontal activity and motivational disturbances, represents a neuropathological attribute of negative symptoms of schizophrenia. Unidirectional high-frequency transcranial random noise stimulation (hf-tRNS) can increase the excitability of the cortex beneath the stimulating electrode. Yet, it is unclear if hf-tRNS can modulate electroencephalographic FAA in patients with schizophrenia. We performed a randomized, double-blind, sham-controlled clinical trial to contrast hf-tRNS and sham stimulation for treating negative symptoms in 35 schizophrenia patients. We used electroencephalography to investigate if 10 sessions of hf-tRNS delivered twice-a-day for five consecutive weekdays would modulate electroencephalographic FAA in schizophrenia. EEG data were collected and FAA was expressed as the differences between common-log-transformed absolute power values of frontal right and left hemisphere electrodes in the alpha frequency range (8-12.5 Hz). We found that hf-tRNS significantly increased FAA during the first session of stimulation (p = 0.009) and at the 1-week follow-up (p = 0.004) relative to sham stimulation. However, FAA failed to predict and surrogate the improvement in the severity of negative symptoms with hf-tRNS intervention. Together, our findings suggest that modulating electroencephalographic frontal alpha asymmetry by using unidirectional hf-tRNS may play a key role in reducing negative symptoms in patients with schizophrenia.
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Affiliation(s)
- Ta-Chuan Yeh
- Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei 114201, Taiwan
| | - Cathy Chia-Yu Huang
- Department of Life Sciences, National Central University, Taoyuan 320317, Taiwan
| | - Yong-An Chung
- Department of Nuclear Medicine, College of Medicine, The Catholic University of Korea, Seoul 21431, Korea
| | - Jooyeon Jamie Im
- Department of Nuclear Medicine, College of Medicine, The Catholic University of Korea, Seoul 21431, Korea
| | - Yen-Yue Lin
- Department of Life Sciences, National Central University, Taoyuan 320317, Taiwan
- Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114202, Taiwan
- Department of Emergency Medicine, Taoyuan Armed Forces General Hospital, Taoyuan 325208, Taiwan
| | - Chin-Chao Ma
- Department of Psychiatry, Tri-Service General Hospital Beitou Branch, National Defense Medical Center, Taipei 112003, Taiwan
| | - Nian-Sheng Tzeng
- Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei 114201, Taiwan
| | - Chuan-Chia Chang
- Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei 114201, Taiwan
| | - Hsin-An Chang
- Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei 114201, Taiwan
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Abler V, Brain C, Ballard C, Berrio A, Coate B, Espay AJ. Motor- and cognition-related safety of pimavanserin in patients with Parkinson's disease psychosis. Front Neurol 2022; 13:919778. [PMID: 36277907 PMCID: PMC9580496 DOI: 10.3389/fneur.2022.919778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 09/07/2022] [Indexed: 12/01/2022] Open
Abstract
Background Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, is the only treatment approved by the US Food and Drug Administration for hallucinations and delusions associated with Parkinson's disease (PD) psychosis. Aim We aimed to evaluate motor- and cognition-related safety in pimavanserin-treated patients with PD psychosis. Methods This analysis included patients with PD psychosis treated with pimavanserin 34 mg from a pooled analysis of 3 randomized, double-blind, placebo-controlled, 6-week studies [NCT00477672 (study ACP-103-012), NCT00658567 (study ACP-103-014), and NCT01174004 (study ACP-103-020)] and a subgroup of patients with PD dementia with psychosis from HARMONY (NCT03325556), a randomized discontinuation study that included a 12-week open-label period followed by a randomized double-blind period of up to 26 weeks. Motor- and cognition-related safety were examined. Results The pooled analysis included 433 randomized patients (pimavanserin, 202; placebo, 231). Least squares mean (standard error [SE]) change from baseline to week 6 Unified Parkinson's Disease Rating Scale (UPDRS) II + III score was similar for pimavanserin [−2.4 (0.69)] and placebo [−2.3 (0.60)] (95% Confidence Interval [CI]:−1.9, 1.6). The change from baseline to week 6 for UPDRS II and UPDRS III scores was similar between groups. In the HARMONY open-label period, 49 patients with PD dementia with psychosis were treated with pimavanserin 34 mg, 36 of whom were randomized in the double-blind period (pimavanserin, 16; placebo, 20). In the open-label period, the mean (SE) change from baseline to week 12 (n = 39) Extra-Pyramidal Symptom Rating Scale (ESRS-A) score was −1.7 (0.74); in the double-blind period, the results were generally comparable between the pimavanserin and placebo arms. The change from baseline in Mini-Mental State Examination (MMSE) score was also comparable between pimavanserin- and placebo-treated patients in HARMONY [open-label (n = 37): mean (SE) change from baseline to week 12, 0.3 (0.66)]. Rates of motor- and cognition-related adverse events were similar between pimavanserin and placebo in both analyses. Conclusions Pimavanserin 34 mg was well tolerated and did not yield a negative impact on motor- or cognition-related function in patients with PD psychosis.
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Affiliation(s)
- Victor Abler
- Acadia Pharmaceuticals Inc, San Diego, CA, United States
| | - Cecilia Brain
- Acadia Pharmaceuticals Inc, San Diego, CA, United States
| | - Clive Ballard
- University of Exeter Medical School, Exeter, United Kingdom
| | - Ana Berrio
- Acadia Pharmaceuticals Inc, San Diego, CA, United States
| | - Bruce Coate
- Acadia Pharmaceuticals Inc, San Diego, CA, United States
| | - Alberto J. Espay
- Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, United States
- *Correspondence: Alberto J. Espay
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Salehi A, Namaei P, TaghaviZanjani F, Bagheri S, Moradi K, Khodaei Ardakani MR, Akhondzadeh S. Adjuvant palmitoylethanolamide therapy with risperidone improves negative symptoms in patients with schizophrenia: A randomized, double-blinded, placebo-controlled trial. Psychiatry Res 2022; 316:114737. [PMID: 35917650 DOI: 10.1016/j.psychres.2022.114737] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 06/22/2022] [Accepted: 07/21/2022] [Indexed: 01/10/2023]
Abstract
BACKGROUND Primary negative symptoms of schizophrenia are usually resistant to monotherapy with antipsychotics. The present study sought to assess the efficacy and tolerability of Palmitoylethanolamide (PEA) adjunctive therapy in treatment of negative symptoms in patients with stable schizophrenia. METHODS This 8-week (trial timepoints: baseline, week 4, week 8), double-blind, placebo-controlled clinical trial randomized patients with schizophrenia in a 1:1 ratio to compare the efficacy and safety of 600 mg twice a day of PEA and matched placebo alongside a stable dose of risperidone. Outcome measures were the positive and the negative syndrome scale (PANSS), the extrapyramidal symptom rating scale (ESRS), and the Hamilton depression rating scale (HDRS). The primary outcome was change in the negative subscale score during the trial period between the groups. Safety of interventions were controlled and addressed during the trial. RESULTS A total of 50 participants completed the trial (25 in each group). Baseline characteristics of the groups were comparable (p>0.05). There was significant effect from time-treatment interaction on negative symptoms (p = 0.012) suggesting greater symptom improvement in the PEA group. In contrast, the longitudinal changes in positive symptoms and depressive symptoms were similar between groups (p values>0.05). Safety assessments showed no significant difference regarding extrapyramidal symptoms, measured by ESRS, and also frequency of other complications between PEA and placebo groups (p values>0.05). CONCLUSIONS Adjunctive therapy with PEA and risperidone alleviates schizophrenia-related primary negative symptoms in a safe manner.
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Affiliation(s)
- Anahita Salehi
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical, Sciences, Tehran, Iran
| | - Parsa Namaei
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical, Sciences, Tehran, Iran
| | - Fateme TaghaviZanjani
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical, Sciences, Tehran, Iran
| | - Sayna Bagheri
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical, Sciences, Tehran, Iran
| | - Kamyar Moradi
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical, Sciences, Tehran, Iran
| | | | - Shahin Akhondzadeh
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical, Sciences, Tehran, Iran.
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Audiovisual temporal processing in adult patients with first-episode schizophrenia and high-functioning autism. SCHIZOPHRENIA 2022; 8:75. [PMID: 36138029 PMCID: PMC9500036 DOI: 10.1038/s41537-022-00284-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 09/03/2022] [Indexed: 11/30/2022]
Abstract
Schizophrenia and autism spectrum disorder (ASD) are both neurodevelopmental disorders with altered sensory processing. Widened temporal binding window (TBW) signifies reduced sensitivity to detect stimulus asynchrony, and may be a shared feature in schizophrenia and ASD. Few studies directly compared audiovisual temporal processing ability in the two disorders. We recruited 43 adult patients with first-episode schizophrenia (FES), 35 average intelligent and verbally-fluent adult patients with high-functioning ASD and 48 controls. We employed two unisensory Temporal Order Judgement (TOJ) tasks within visual or auditory modalities, and two audiovisual Simultaneity Judgement (SJ) tasks with flash-beeps and videos of syllable utterance as stimuli. Participants with FES exhibited widened TBW affecting both speech and non-speech processing, which were not attributable to altered unisensory sensory acuity because they had normal visual and auditory TOJ thresholds. However, adults with ASD exhibited intact unisensory and audiovisual temporal processing. Lower non-verbal IQ was correlated with larger TBW width across the three groups. Taking our findings with earlier evidence in chronic samples, widened TBW is associated with schizophrenia regardless illness stage. The altered audiovisual temporal processing in ASD may ameliorate after reaching adulthood.
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Comparison of Extrapyramidal Symptoms Among Outpatients With Schizophrenia on Long-Acting Injectable Antipsychotics. J Clin Psychopharmacol 2022; 42:475-479. [PMID: 35977035 DOI: 10.1097/jcp.0000000000001580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Extrapyramidal symptoms (EPSs) are adverse effects of antipsychotics. Different risks of EPSs have been attributed to the 3 classes of antipsychotics. This study aimed to assess EPS in a clinical sample of schizophrenia patients who are on LAI and compare the severity of EPSs among the following 3 antipsychotic groups: (1) partial agonist, (2) second-generation antipsychotics, and (3) first-generation antipsychotics. METHODS Ninety-two patients were recruited from the Schizophrenia Program Injection Clinic. Using the Extrapyramidal Symptom Rating Scale (ESRS), severity of EPS was assessed and information regarding factors associated with risk of EPS, including coprescriptions, comorbidities, and demographics, was obtained from medical charts. Group differences in ESRS scores and subscores were analyzed using 1-way analyses of variances. RESULTS Among the 3 groups, there was no significant difference in total ESRS scores and subscores. Risperidone was associated with higher ESRS scores when compared with paliperidone, aripiprazole, and flupenthixol. Doses above maximum were commonly used in the paliperidone group, and there was no significant difference in total ESRS scores between the low, average, or above-maximum doses of paliperidone. CONCLUSIONS Our results demonstrated a comparative risk of EPS across all 3 antipsychotic classes. Risperidone was associated with more EPS compared with other medications. A higher threshold for the "maximum dose" of paliperidone could be considered and higher doses used with the same cautions as low-average doses.
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Ince Guliyev E, Guloksuz S, Ucok A. Impaired Effort Allocation in Patients with Recent-Onset Schizophrenia and Its Relevance to Negative Symptoms Assessments and Persistent Negative Symptoms. J Clin Med 2022; 11:jcm11175060. [PMID: 36078990 PMCID: PMC9457458 DOI: 10.3390/jcm11175060] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 08/24/2022] [Accepted: 08/27/2022] [Indexed: 11/16/2022] Open
Abstract
(1) Background: Our aims in this study were (i) to compare effort allocation capacity measured between patients with recent-onset schizophrenia (SCZ) and healthy controls (HCs), (ii) within the SCZ, to investigate the association of effort allocation capacity with negative symptoms (NS), and (iii) to compare this association with the type of NS scale used. (2) Methods: Thirty-one patients with SCZ and 30 HCs participated in the study. The NS was examined using an older-generation (Scale for the Assessment of Negative Symptoms, SANS), a newer-generation (Brief Negative Symptoms Scale, BNSS), and a self-rated (Self-evaluation of Negative Symptoms Scale, SNS) negative symptom scale, as well as longitudinally by using persistent NS (PNS) distinction. (3) Results: The SCZ group was less willing to expend effort in high/moderate-probability and -magnitude conditions but more in low-probability and -magnitude conditions. A general reduction in effort allocation capacity was also present. Patients with PNS were less likely to choose hard tasks than non-PNS patients. Clinician-rated scales correlated with 50% probability and moderate-reward-magnitude conditions. Correlations with the SNS were minimal. (4) Conclusions: Our findings suggest that patients with SCZ may show a general reduction in effort allocation capacity and make inefficient choices, although they are not totally reward-insensitive. The effects of NS on effort expenditure can be more pronounced when the rewarding stimulus is vague.
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Affiliation(s)
- Ezgi Ince Guliyev
- Department of Psychiatry, Erenkoy Training and Research Hospital for Mental and Neurological Diseases, University of Health Sciences, Istanbul 34736, Turkey
- Correspondence:
| | - Sinan Guloksuz
- Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, 6202 Maastricht, The Netherlands
- Department of Psychiatry, Yale School of Medicine, New Haven, CT 06510, USA
| | - Alp Ucok
- Department of Psychiatry, Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey
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Lavigne KM, Raucher-Chéné D, Bodnar MD, Makowski C, Joober R, Malla A, Evans AC, Lepage M. Medial temporal lobe and basal ganglia volume trajectories in persistent negative symptoms following a first episode of psychosis. Prog Neuropsychopharmacol Biol Psychiatry 2022; 117:110551. [PMID: 35304154 DOI: 10.1016/j.pnpbp.2022.110551] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 03/04/2022] [Accepted: 03/11/2022] [Indexed: 01/14/2023]
Abstract
BACKGROUND Persistent negative symptoms (PNS, e.g., avolition, anhedonia, alogia) are present in up to 30% of individuals diagnosed with a first episode of psychosis and greatly impact functional outcomes. PNS and secondary PNS (sPNS: concomitant with positive, depressive, or extrapyramidal symptoms) may index distinct pathophysiologies reflected by structural brain changes, particularly in the medial temporal lobe (MTL) and basal ganglia. AIMS We sought to characterize dynamic brain changes related to PNS over the course of 2 years following a first episode of psychosis. METHOD Longitudinal volumetric trajectories within the MTL (hippocampus, parahippocampal gyrus, entorhinal cortex, perirhinal cortex) and basal ganglia (caudate, putamen, pallidum) were investigated in 98 patients with first-episode psychosis and 86 healthy controls using generalized estimating equations. RESULTS In left hippocampus, PNS (n = 25 at baseline) showed decreased volumes over time, sPNS (n = 26) volumes remained stable, and non-PNS (n = 47) volumes increased over time to control levels. PNS-specific changes were observed in left hippocampus and left perirhinal cortex, with the greatest decline from 12 to 24 months to levels significantly below those of non-PNS and controls. Affective/non-affective diagnosis, antipsychotic medication dosage and adherence at baseline did not significantly impact these findings. Basal ganglia volume trajectories did not distinguish between PNS and sPNS. CONCLUSIONS The current study highlights distinct structural brain trajectories in PNS that are prominent in the left MTL. Basal ganglia alterations may contribute to PNS irrespective of their etiology. Left MTL volume reductions were most evident after 1 year of treatment, highlighting the importance of targeted early interventions.
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Affiliation(s)
- Katie M Lavigne
- Douglas Mental Health University Institute, McGill University, Montreal, Canada; Department of Psychiatry, McGill University, Montreal, Canada; McGill Centre for Integrative Neuroscience, Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada
| | - Delphine Raucher-Chéné
- Douglas Mental Health University Institute, McGill University, Montreal, Canada; Department of Psychiatry, McGill University, Montreal, Canada; Cognition, Health, and Society Laboratory (EA 6291), University of Reims Champagne-Ardenne, Reims, France; Academic Department of Psychiatry, University Hospital of Reims, EPSM Marne, Reims, France
| | | | - Carolina Makowski
- Department of Radiology, University of California San Diego, La Jolla, CA, United States of America
| | - Ridha Joober
- Douglas Mental Health University Institute, McGill University, Montreal, Canada; Department of Psychiatry, McGill University, Montreal, Canada
| | - Ashok Malla
- Douglas Mental Health University Institute, McGill University, Montreal, Canada; Department of Psychiatry, McGill University, Montreal, Canada
| | - Alan C Evans
- Department of Psychiatry, McGill University, Montreal, Canada; McGill Centre for Integrative Neuroscience, Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Department of Biological and Biomedical Engineering, McGill University, Montreal, Quebec, Canada
| | - Martin Lepage
- Douglas Mental Health University Institute, McGill University, Montreal, Canada; Department of Psychiatry, McGill University, Montreal, Canada.
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Motamed M, Karimi H, Sanjari Moghaddam H, Taherzadeh Boroujeni S, Sanatian Z, Hasanzadeh A, Khodaei Ardakani MR, Akhondzadeh S. Risperidone combination therapy with adalimumab for treatment of chronic schizophrenia: a randomized, double-blind, placebo-controlled clinical trial. Int Clin Psychopharmacol 2022; 37:92-101. [PMID: 35258035 DOI: 10.1097/yic.0000000000000399] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
This study aimed to investigate the efficacy and safety of antitumor necrosis factor-alpha (TNF-α) therapy using adalimumab in patients with chronic schizophrenia. This is a randomized, double-blind, placebo-controlled clinical trial carried out at Roozbeh Hospital (Tehran, Iran) from June 2020 to October 2021. The patients were randomly divided into two parallel adalimumab + risperidone and placebo + risperidone groups. Participants in the intervention group received adalimumab subcutaneous injection (40 mg) by pen-injector at weeks 0 and 4. Using the Positive and Negative Symptoms Scale (PANSS), patients' positive and negative symptoms were assessed at weeks 0, 4, and 8. Forty patients (20 in each group) were included. PANSS total (t = 4.43, df = 38, P < 0.001), negative (t = 2.88, df = 38, P = 0.006), and general psychopathology (t = 4.06, df = 38, P < 0.001) scores demonstrated a significantly greater decline in adalimumab compared with the placebo group from baseline study endpoint. However, improvement of PANSS positive subscale scores showed no significant difference from the baseline study endpoint. There was no significant between-group difference regarding levels of C-reactive protein, interleukin (IL)-1β, TNF-α, IL-6, and IL-8 at baseline and also at the week 8 visit (P > 0.05 for all). The current study found adalimumab adjunctive therapy effective in treating schizophrenia, particularly its negative and general psychopathology symptoms, with no side effects.
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Affiliation(s)
- Mahsa Motamed
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences
| | - Hanieh Karimi
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences
| | | | | | - Zahra Sanatian
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences
| | - Alireza Hasanzadeh
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences
| | | | - Shahin Akhondzadeh
- Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences
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Cross-disorder and disorder-specific deficits in social functioning among schizophrenia and alzheimer's disease patients. PLoS One 2022; 17:e0263769. [PMID: 35421108 PMCID: PMC9009658 DOI: 10.1371/journal.pone.0263769] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Accepted: 01/26/2022] [Indexed: 12/18/2022] Open
Abstract
Background Social functioning is often impaired in schizophrenia (SZ) and Alzheimer’s disease (AD). However, commonalities and differences in social dysfunction among these patient groups remain elusive. Materials and methods Using data from the PRISM study, behavioral (all subscales and total score of the Social Functioning Scale) and affective (perceived social disability and loneliness) indicators of social functioning were measured in patients with SZ (N = 56), probable AD (N = 50) and age-matched healthy controls groups (HC, N = 29 and N = 28). We examined to what extent social functioning differed between disease and age-matched HC groups, as well as between patient groups. Furthermore, we examined how severity of disease and mood were correlated with social functioning, irrespective of diagnosis. Results As compared to HC, both behavioral and affective social functioning seemed impaired in SZ patients (Cohen’s d’s 0.81–1.69), whereas AD patients mainly showed impaired behavioral social function (Cohen’s d’s 0.65–1.14). While behavioral indices of social functioning were similar across patient groups, SZ patients reported more perceived social disability than AD patients (Cohen’s d’s 0.65). Across patient groups, positive mood, lower depression and anxiety levels were strong determinants of better social functioning (p’s <0.001), even more so than severity of disease. Conclusions AD and SZ patients both exhibit poor social functioning in comparison to age- and sex matched HC participants. Social dysfunction in SZ patients may be more severe than in AD patients, though this may be due to underreporting by AD patients. Across patients, social functioning appeared as more influenced by mood states than by severity of disease.
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Kameg B, Champion C. Atypical antipsychotics: Managing adverse effects. Perspect Psychiatr Care 2022; 58:691-695. [PMID: 33955013 DOI: 10.1111/ppc.12837] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 02/28/2021] [Accepted: 03/10/2021] [Indexed: 12/19/2022] Open
Abstract
PURPOSE The purpose of this article is to provide an overview of common adverse effects and management strategies related to atypical antipsychotic use. CONCLUSIONS Atypical antipsychotics are commonly prescribed. While effective, atypical antipsychotics are associated with metabolic syndrome, extrapyramidal symptoms, and tardive dyskinesia, among others adverse effects. Management strategies can mitigate adverse effects and promote optimum quality of life. PRACTICE IMPLICATIONS To be able to identify and manage adverse effects associated with the use of atypical antipsychotics, it is important to build a supportive therapeutic environment at each interaction with patients and their caregivers.
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Affiliation(s)
- Brayden Kameg
- Department of Health and Community Systems, University of Pittsburgh, School of Nursing, Pittsburgh, Pennsylvania, USA
| | - Claire Champion
- Department of Health and Community Systems, University of Pittsburgh, School of Nursing, Pittsburgh, Pennsylvania, USA
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Wang SM, Ouyang WC, Hsu HM, Hsu LT. An Instrumental Measure of Hand and Facial Movement Abnormalities in Patients With Schizophrenia. Front Psychiatry 2022; 13:803661. [PMID: 35308887 PMCID: PMC8931260 DOI: 10.3389/fpsyt.2022.803661] [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: 10/28/2021] [Accepted: 01/18/2022] [Indexed: 11/13/2022] Open
Abstract
INTRODUCTION Movement disorders have been suggested to be a cardinal component of schizophrenia. With increased research interests in this area, instrumental measures are needed. This study was to examine if the motion capture system was reliable in measuring hand and facial bradykinesia and dyskinesia and more sensitive to detecting movement differences between schizophrenia patients and healthy people than traditional rating scales. METHODS Sixteen schizophrenia patients and 20 control subjects were recruited. Hand and facial bradykinesia and dyskinesia were measured using the motion capture system and rated using the Extrapyramidal Symptom Rating Scale and the Abnormal Involuntary Movement Scale. RESULTS The system showed strong test-retest reliability and generated larger effect sizes of group differences than did the rating scales. CONCLUSIONS The results may support researchers and clinical practitioners to apply the system to sensitively measuring the hand and facial movement symptoms in schizophrenia patients, which contributes to gaining a deep understanding of movement issues in schizophrenia.
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Affiliation(s)
- Shu-Mei Wang
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
| | - Wen-Chen Ouyang
- Department of Geriatric Psychiatry, Jianan Psychiatric Center, Ministry of Health and Welfare, Tainan, Taiwan.,Department of Nursing, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan.,Department of Psychiatry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsiao-Man Hsu
- Institute of Biomedical Engineering, College of Engineering, National Cheng Kung University, Tainan, Taiwan
| | - Li-Ta Hsu
- Department of Aeronautical and Aviation Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
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Nielsen MØ, Kristensen TD, Borup Bojesen K, Glenthøj BY, Lemvigh CK, Ebdrup BH. Differential Effects of Aripiprazole and Amisulpride on Negative and Cognitive Symptoms in Patients With First-Episode Psychoses. Front Psychiatry 2022; 13:834333. [PMID: 35370857 PMCID: PMC8969108 DOI: 10.3389/fpsyt.2022.834333] [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: 12/13/2021] [Accepted: 02/01/2022] [Indexed: 11/13/2022] Open
Abstract
INTRODUCTION Aripiprazole is hypothesized to have an effect on negative and cognitive symptoms in schizophrenia. Likewise, amisulpride is one of the only second-generation antipsychotics with which an effect on negative symptoms is reported. In the present study, we compare the effect of aripiprazole and amisulpride in initially antipsychotic-naïve patients with first-episode psychoses. METHODS Psychopathology and cognitive measures from two consecutive cohorts of antipsychotic-naïve first episode psychotic patients were obtained before and after 6 weeks of antipsychotic monotherapy with either aripiprazole or amisulpride. Matched healthy controls were included to account for retest effects on the cognitive measures. Analyses of variance (repeated-measures ANOVA) were performed to detect effect of time and possible cohort*time interactions. RESULTS Longitudinal data was obtained from 47 and 48 patients treated for 6 weeks with amisulpride or aripiprazole, respectively. For the Wallwork negative symptom dimension, there was a cohort*time interaction [F (1, 93) = 4.29, p = 0.041] and a significant effect of time [F (1, 93) = 6.03, p = 0.016], which was driven by an improvement in patients treated with aripiprazole [t (47) = 4.1, p < 0.001] and not observed in patients treated with amisulpride (p > 0.5). For the eight cognitive measures, no cohort*time interaction was found and neither was cognitive improvement in any of the cohorts when accounting for retest effect. CONCLUSION Patients treated with aripiprazole improved on negative symptoms, which was not the case for patients treated with amisulpride. This may point to a general effect of a partial D2 receptor agonist on negative symptoms in patients with first-episode psychoses. There was, however, no improvement in cognitive functions.
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Affiliation(s)
- Mette Ødegaard Nielsen
- Center for Neuropsychiatric Schizophrenia Research (CNSR), Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark.,Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark.,Mental Health Center, Glostrup, Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark
| | - Tina Dam Kristensen
- Center for Neuropsychiatric Schizophrenia Research (CNSR), Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark.,Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark.,Mental Health Center, Glostrup, Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark
| | - Kirsten Borup Bojesen
- Center for Neuropsychiatric Schizophrenia Research (CNSR), Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark.,Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark.,Mental Health Center, Glostrup, Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark
| | - Birte Y Glenthøj
- Center for Neuropsychiatric Schizophrenia Research (CNSR), Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark.,Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark.,Mental Health Center, Glostrup, Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark
| | - Cecilie K Lemvigh
- Center for Neuropsychiatric Schizophrenia Research (CNSR), Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark.,Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark.,Mental Health Center, Glostrup, Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark
| | - Bjørn H Ebdrup
- Center for Neuropsychiatric Schizophrenia Research (CNSR), Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark.,Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark.,Mental Health Center, Glostrup, Copenhagen University Hospital - Mental Health Services Copenhagen, Copenhagen, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark
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Bengtsson J, Bodén R, Neider D, Cernvall M. A blinded validation of the Swedish version of the Clinical Assessment Interview for Negative Symptoms (CAINS). Nord J Psychiatry 2022; 76:44-51. [PMID: 34126848 DOI: 10.1080/08039488.2021.1933174] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
PURPOSE The Clinical Assessment Interview for Negative Symptoms (CAINS) was developed in order to advance the assessment of negative symptoms. The aim of this study was to validate the Swedish version of the CAINS. MATERIALS AND METHODS Thirty-four out-patients with a schizophrenia spectrum disorder were recruited. All patients were videotaped while interviewed with the CAINS and the Brief Psychiatric Rating Scale (BPRS). Another rater watched the video recordings in the reverse order, enabling a blinded design. The patients also filled in self-reported measures of depression, quality of life, and social and vocational functioning. We calculated inter-rater agreement and internal consistency for the CAINS. We also calculated validity measures by correlating the subscales Motivation and Pleasure (CAINS-MAP) and Expression (CAINS-EXP) to subscales of the BPRS. RESULTS The blinded inter-rater agreement for the CAINS total score was high (ICC = 0.92) but slightly lower for the expression subscale (ICC = 0.76). Cronbach's alpha was 0.84 for the total score. Convergent validity with the negative symptoms subscale of BPRS was different for the blinded and the unblinded data, with a CAINS-MAP correlation of 0.10 (p = 0.580) and a CAINS-EXP correlation of 0.48 (p = 0.004) in the blinded data. The unblinded data had a CAINS-MAP correlation of 0.38 (p = 0.026) and a CAINS-EXP correlation of 0.87 (p < 0.001). Self-rated measures of anhedonia correlated to CAINS-MAP with a coefficient of 0.68 (p < 0.001), while the CAINS-EXP only had a correlation of 0.16 (p = 0.366) to these measures. CONCLUSION The Swedish version of the CAINS displays adequate psychometric properties in line with earlier validation studies.
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Affiliation(s)
- Johan Bengtsson
- Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden
| | - Robert Bodén
- Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden
| | | | - Martin Cernvall
- Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden
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