AMPlifying metabolic screening for inpatients on antipsychotic medications with a nurse-driven protocol.

INTRODUCTION: Patients on antipsychotic medications are at higher risk of developing metabolic syndrome; nevertheless, metabolic screening for patients on antipsychotics is suboptimal. METHODS: This project developed and implemented AMP (Antipsychotic Metabolic screening Protocol), a nurse-driven protocol on inpatient psychiatric units that allowed nursing staff to collect all components of a metabolic screening. Nurses working on units with AMP were surveyed pre- and post-implementation on perception of AMP and empowerment. RESULTS: AMP significantly increased overall metabolic screening as well as the most frequently missing component (lipid panel). The screening rates pre-intervention were similar to those found in the literature (on average, only two-thirds of patients were screened). However, AMP improved the rate such that nine out of every ten patients on the units were screened. Nurses had a negative perception and no change in empowerment from AMP implementation. CONCLUSIONS: AMP can be used to increase metabolic screening for patients on antipsychotics. Further research is needed to better understand adoptability of nurse-driven protocols in the psychiatric inpatient setting as well as other applications, such as smoking cessation or safety sitters.

The New Horizon of Antipsychotics beyond the Classic Dopaminergic Hypothesis-The Case of the Xanomeline-Trospium Combination: A Systematic Review.

Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of the positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline-trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer's disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected twenty-one sources referring to fourteen studies focused on KarXT, out of which only four have available results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline-trospium are good, but more data are needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.

Aripiprazole as protector against COVID-19 mortality.

The relation of antipsychotics with severe Coronavirus Disease 19 (COVID-19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial results have been published on this issue. We aimed to prove whether antipsychotics might exert adverse or protective effects against fatal outcomes derived from COVID-19. A population-based retrospective cohort study (January 2020 to November 2020) comprising inpatients (15,968 patients) who were at least 18 years old and had a laboratory-confirmed COVID-19 infection. Two sub-cohorts were delineated, comprising a total of 2536 inpatients: individuals who either had no prescription medication or were prescribed an antipsychotic within the 15 days preceding hospitalization. We conducted survival and odds ratio analyses to assess the association between antipsychotic use and mortality, reporting both unadjusted and covariate-adjusted results. We computed the average treatment effects, using the untreated group as the reference, and the average treatment effect on the treated, focusing solely on the antipsychotic-treated population. Among the eight antipsychotics found to be in use, only aripiprazole showed a significant decrease in the risk of death from COVID-19 [adjusted odds ratio (OR) = 0.86; 95% CI, 0.79-0.93, multiple-testing adjusted p-value < 0.05]. Importantly, these findings were consistent for both covariate-adjusted and unadjusted analyses. Aripiprazole has been shown to have a differentiated beneficial effect in protecting against fatal clinical outcome in COVID-19 infected individuals. We speculate that the differential effect of aripiprazole on controlling immunological pathways and inducible inflammatory enzymes, that are critical in COVID19 illness, may be associated with our findings herein.

Challenges and proposed solutions to conducting Alzheimer's disease psychosis trials.

Alzheimer's disease psychosis (ADP) produces a significant burden for patients and their care partners, but at present there are no approved treatments for ADP. The lack of approved treatments may be due to the challenges of conducting clinical trials for this disease. This perspective article discusses distinct challenges and proposed solutions of conducting ADP trials involving seven key areas: (1) methods to reduce the variable and sometimes high rates of placebo response that occur for treatments of neuropsychiatric symptoms; (2) the use of combined or updated criteria that provide a precise, consensus definition of ADP; (3) the use of eligibility criteria to help recruit individuals representative of the larger ADP population and overcome the difficulty of recruiting patients with moderate-to-severe ADP; (4) consideration of multiple perspectives and implementation of technology to reduce the variability in the administration and scoring of neuropsychiatric symptom assessments; (5) the use of clinically appropriate, a priori-defined severity thresholds and responder cutoffs; (6) the use of statistical approaches that address absolute effect sizes and a three-tier approach to address the fluctuation of neuropsychiatric symptoms; and (7) the implementation of feasible diagnostic and target-engagement biomarkers as they become available. The goal of these proposed solutions is to improve the evaluation of potential ADP therapies, within the context of randomized, placebo-controlled trials with clinically meaningful endpoints and sustained treatment responses.

New drug treatments for schizophrenia: a review of approaches to target circuit dysfunction.

Schizophrenia is a leading cause of global disease burden. Current drug treatments are associated with significant side-effects and have limited efficacy for many patients; highlighting the need to develop new approaches that target other aspects of the neurobiology of schizophrenia. Preclinical, in vivo imaging, post-mortem, genetic and pharmacological studies have highlighted the key role of cortical GABA-glutamatergic microcircuits and their projections to subcortical dopaminergic circuits in the pathoetiology of negative, cognitive and psychotic symptoms. Antipsychotics primarily act downstream of the dopaminergic component of this circuit. However, multiple drugs are currently in development that could target other elements of this circuit to treat schizophrenia. These include drugs for GABA or glutamatergic targets, including glycine transporters, d-amino acid oxidase, sodium channels or potassium channels. Other drugs in development are likely to primarily act on pathways that regulate the dopaminergic system such as muscarinic or trace amine receptors or serotonin 2A receptors, whilst phosphodiesterase 10 A inhibitors are being developed to modulate the downstream consequences of dopaminergic dysfunction. Our review considers where new drugs may act on this circuit and their latest clinical trial evidence in terms of indication, efficacy and side-effects. Limitations of the circuit model, including whether there are neurobiologically distinct subgroups of patients, and future directions are also considered. Several drugs based on the mechanisms reviewed have promising clinical data, with the muscarinic agonist KarXT most advanced. If they are approved for clinical use, they have the potential to revolutionise understanding of the pathophysiology and treatment of schizophrenia.

A review on the pharmacology of cariprazine and its role in the treatment of negative symptoms of schizophrenia.

Management of negative symptoms is one of the most challenging and important unmet needs of schizophrenia treatment. Negative symptoms together with positive symptoms result in significant psychosocial impairment and poor quality of life. Existing studies on atypical antipsychotics reported limited treatment adherence due to higher prevalence of treatment-emergent adverse events, such as diabetes, weight gain, hyperlipidemia, hyperprolactinemia and hypertension. A compound with greater affinity for dopamine D2/D3 receptors may improve negative symptoms, mood, and cognitive impairment associated with schizophrenia. In 2015, the US FDA has approved cariprazine, a partial D2/D3 agonist for treatment of schizophrenia, mania or mixed episodes. Midlands and Lancashire Commissioning Support Unit, UK (2019) has particularly suggested cariprazine for the treatment of predominant negative symptoms of schizophrenia. India's Central Drugs Standard Control Organization (CDSCO) has approved cariprazine in 2021 for the treatment of schizophrenia, manic or mixed episodes associated with bipolar I disorder. A ten-fold greater affinity for D3 receptors and partial agonism to serotonin receptors, along with longer half-life make cariprazine distinct when compared with other atypical antipsychotics. Cariprazine is also reported to have fewer incidents of metabolic and hormonal adverse events, and has been shown to provide better relapse prevention. Recent evidence indicates promising effect of cariprazine in ameliorating negative symptoms as well as psychotic symptoms in patients with schizophrenia. In addition, improved adherence to treatment (adjunctive/monotherapy) with cariprazine in patients having inadequate response to an ongoing antipsychotic treatment has also been clinically established. This review presents the evidence-based safety and efficacy of cariprazine for treatment of predominant negative symptoms of schizophrenia.

Exploring Risk Factors for Adverse Reactions in Children with an Acute Psychotic Episode Using the Global Trigger Tool: Does Age Matter?

Aim: To establish significant risk factors for the development of adverse drug effects (ADEs) in children and adolescents with an acute psychotic episode taking antipsychotics. Materials and Methods: The research team randomly selected 15 patient records each month for 3 years (2016-2018). Overall, 450 patient records were included (223 boys and 227 girls, mean age was 14.52 ± 2.21 years). Adverse effects were identified using the standard algorithm of the Global Trigger Tool method. A "trigger" is an indication that an adverse reaction is likely to occur, e.g., an antihistamine prescription on a prescribing list. When a trigger was detected, the case history was studied in further detail to confirm the occurrence of ADEs. We divided patients into two groups: the "children" group (under 12 years old) and the "adolescents" group (13 years and older). Data were analyzed using the statistical package IBM SPSS Statistics 23.0. Results: Of the 450 patient records, 402 (89.3%) had at least one trigger detected. In total, 126 case histories contained evidence of ADE (28%). The total number of ADEs per 1000 patient days was 5.39 and the number of ADEs per 100 admissions was 32.0. Among adolescents, two or more triggers per patient were significantly more frequently identified (61.3% vs. 44.6%; p = 0.001). ADEs were rare in "Children" compared with "Adolescents" (13.8% vs. 30.4%; p = 0.006). The logistic regression analysis confirmed high predictive role of "Adolescence" (odds ratio [OR] = 2.58; 95% confidence interval [CI] 1.22-5.4; p = 0.013), "Polypharmacy" (OR = 1.96; 95% CI 1.23-3.1; p = 0.004), and "First-life hospitalization" (OR = 2.17; 95% CI 1.34-3.48; p = 0.001) for ADE fact in patient records. Conclusion: We found that significant risk factors for ADEs to antipsychotics in patients with acute psychotic episode were adolescence (13 years and older), polypharmacy, and first-life hospitalization. The fact that children (i.e., younger than 13 years of age) are less likely to experience ADEs was not associated with high-risk drugs or higher doses in our study.

Incorporating clinician insight and care plans into an audit and feedback initiative for antipsychotic prescribing to Medicaid-enrolled youth in Philadelphia.

BACKGROUND: Audit and feedback (A/F), which include initiatives like report cards, have an inconsistent impact on clinicians' prescribing behavior. This may be attributable to their focus on aggregate prescribing measures, a one-size-fits-all approach, and the fact that A/F initiatives rarely engage with the clinicians they target. METHODS: In this study, we describe the development and delivery of a report card that summarized antipsychotic prescribing to publicly-insured youth in Philadelphia, which was introduced by a Medicaid managed care organization in 2020. In addition to measuring aggregate prescribing behavior, the report card included different elements of care plans, including whether youth were receiving polypharmacy, proper medication management, and the concurrent use of behavioral health outpatient services. The A/F initiative elicited feedback from clinicians, which we refer to as an "audit and feedback loop." We also evaluate the impact of the report card by comparing pre-post differences in prescribing measures for clinicians who received the report card with a group of clinicians who did not receive the report card. RESULTS: Report cards indicated that many youth who were prescribed antipsychotics were not receiving proper medication management or using behavioral health outpatient services alongside the antipsychotic prescription, but that polypharmacy was rare. In their feedback, clinicians who received report cards cited several challenges related to antipsychotic prescribing, such as the logistical difficulties of entering lab orders and family members' hesitancy to change care plans. The impact of the report card was mixed: there was a modest reduction in the share of youth receiving polypharmacy following the receipt of the report card, while other measures did not change. However, we documented a large reduction in the number of youth with one or more antipsychotic prescription fill among clinicians who received a report card. CONCLUSIONS: A/F initiatives are a common approach to improving the quality of care, and often target specific practices such as antipsychotic prescribing. Report cards are a low-cost and feasible intervention but there is room for quality improvement, such as adding measures that track medication management or eliciting feedback from clinicians who receive report cards. To ensure that the benefits of antipsychotic prescribing outweigh its risks, it is important to promote quality and safety of antipsychotic prescribing within a broader care plan.

Genetic predisposition and antipsychotic treatment effect on metabolic syndrome in schizophrenia: a ten-year follow-up study using the Estonian Biobank.

Background: Schizophrenia (SCZ) patients exhibit 30% higher prevalence of metabolic syndrome (MetS) compared to the general population with its suboptimal management contributing to increased mortality. Large-scale studies providing real-world evidence of the underlying causes remain limited. Methods: To address this gap, we used real-world health data from the Estonian Biobank, spanning a median follow-up of ten years, to investigate the impact of genetic predisposition and antipsychotic treatment on the development of MetS in SCZ patients. Specifically, we set out to characterize antipsychotic treatment patterns, genetic predisposition of MetS traits, MetS prognosis, and body mass index (BMI) trajectories, comparing SCZ cases (n = 677) to age- and sex-matched controls (n = 2708). Findings: SCZ cases exhibited higher genetic predisposition to SCZ (OR = 1.75, 95% CI 1.58-1.94), but lower polygenic burden for increased BMI (OR = 0.88, 95% CI 0.88-0.96) and C-reactive protein (OR = 0.88, 95% CI 0.81-0.97) compared to controls. While SCZ cases showed worse prognosis of MetS (HR 1.95, 95% CI 1.54-2.46), higher antipsychotic adherence within the first treatment year was associated with reduced long-term MetS incidence. Linear mixed modelling, incorporating multiple BMI timepoints, underscored the significant contribution of both, antipsychotic medication, and genetic predisposition to higher BMI, driving the substantially upward trajectory of BMI in SCZ cases. Interpretation: These findings contribute to refining clinical risk prediction and prevention strategies for MetS among SCZ patients and emphasize the significance of incorporating genetic information, long-term patient tracking, and employing diverse perspectives when analyzing real-world health data. Funding: EU Horizon 2020, Swedish Research Council, Estonian Research Council, Estonian Ministry of Education and Research, University of Tartu.

Update of the World Health Organization's Mental Health Gap Action Programme Guideline for Psychoses (Including Schizophrenia).

BACKGROUND AND HYPOTHESIS: The World Health Organization's (WHOs) Mental Health Gap Action Programme (mhGAP) aims to improve healthcare for mental, neurological, and substance use disorders in nonspecialized settings, with a focus on low- and middle-income countries (LMICs). mhGAP includes guidelines for the treatment of psychoses (including schizophrenia), which were recently updated in 2023. The complexity of the WHO guideline update process and the updated recommendations on psychoses are presented. STUDY DESIGN: The WHO guideline development process is outlined as well as the evidence appraisal and the translation of the evidence into recommendations following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The guideline update process includes a review of the literature, a compilation of systematic reviews, and extracting data related to critical and important outcomes. The updated recommendations and the justifying evidence are discussed. STUDY RESULTS: The WHO mhGAP guidelines for psychoses are adapted to LMICs, and consist of 13 recommendations in 2023, whereof 5 were updated, and 1 recommendation was newly developed. Background information on how these recommendations were obtained, and significant changes since the previous guideline update in 2015 are provided. CONCLUSIONS: Unlike other guidelines, the WHO must consider various countries, contextual factors, and the WHO Model Lists of Essential Medicines when developing its guidelines. A transformation of the WHO guideline for psychoses into a living guideline would ensure always up-to-date recommendations and facilitate shared decision-making.

Comparison of long-acting injectable antipsychotics with oral antipsychotics and hospital readmission rates in pediatric patients.

Introduction: Studies indicate that long-acting injectable antipsychotics (LAIAs) reduce the risk of relapse and hospitalization compared with oral antipsychotics (APs) in adults. Oral formulations of APs are well-studied in the pediatric population, but little is known regarding the off-label use of LAIAs in this population. Methods: This retrospective chart review evaluated readmission rates for pediatric patients admitted to a psychiatric ward in a large academic hospital between January 1, 2015, and December 1, 2022, requiring AP therapy. The experimental group included patients initiated on LAIA therapy, and the control group included patients initiated on a new oral AP. Patients were matched by several clinical factors. Results: Each group consisted of 38 patients. For the primary outcome, hospital readmission rates at 3 months, the LAIA group had a 13.2% readmission rate compared with 26.3% in the comparator group (p = .153). In months 4 through 6, there was a 5.3% versus 15.8% readmission rate, respectively (p = .139). In months 7 through 12, it was 7.9% versus 18.4% (p = .179). There were significantly fewer cumulative readmissions at the 1-year mark in the LAIA group (N = 9, 23.7%) compared with the oral AP group (N = 18, 47.4%) (p = .031). No statistically significant differences were seen in hospital length of stay although results numerically favored LAIA. Discussion: In a pediatric population, the administration of an LAIA when compared with the oral equivalent resulted in numerically fewer hospital readmissions, decreased length of stay, and fewer adverse effects, but these effects were not statistically significant except for cumulative readmissions at 1 year.

Antipsychotic Prescribing in Older Adults after In-Hospital Initiation.

Background: In older adults, the use of antipsychotics to treat delirium or the behavioural and psychological symptoms of dementia is potentially inappropriate and may be associated with adverse effects. Antipsychotics newly initiated in hospital may be inadvertently continued after discharge. In the Saskatchewan Health Authority (SHA) - Regina area, the frequency and duration of antipsychotic continuation for older adults after initiation during a hospital stay is unknown. Objectives: To describe potentially inappropriate antipsychotic use in older adults after discharge from hospital, specifically rates of postdischarge antipsychotic therapy after initiation in hospital and continuation up to 180 days after discharge; prescribing regimens used; risk factors associated with continuation; pharmacist involvement; and plans for antipsychotic discontinuation, tapering, and/or follow-up. Methods: This retrospective chart review included inpatients 65 years of age or older who were discharged from medicine units at SHA - Regina area hospitals between September 30, 2021, and June 28, 2022. Outpatient dispensing histories were also gathered. Results: Of the 189 patients included in the analysis, 60 (31.7%) had continuation of antipsychotic therapy at discharge. Of these, 48 (80.0%), 33 (55.0%), and 24 (40.0%) had continuation of antipsychotic therapy at 30, 90, and 180 days after discharge, respectively. Of the patients with continuing antipsychotic therapy, 53 (88.3%) were 75 years of age or older, and 9 (15.0%) had documentation of an outpatient antipsychotic follow-up plan. Conclusions: Postdischarge continuation of antipsychotics was similar to that reported in the literature. Patients continued on antipsychotics after discharge were at a greater than 50% risk of continuation at 90 days and were unlikely to have a follow-up plan. Future quality improvement efforts should include standardized prioritization of medication reviews, documentation of indications, and regular reassessment of therapy.

Contexte: Chez les personnes âgées, l'utilisation d'antipsychotiques pour traiter le délire ou les symptômes comportementaux et psychologiques de la démence est potentiellement inappropriée et associée à des effets indésirables. Le traitement antipsychotique initié à l'hôpital pourrait se poursuivre par inadvertance après le congé. Dans la région de Regina de la Saskatchewan Health Authority (SHA), la fréquence et la durée du maintien d'antipsychotiques chez les personnes âgées après l'initiation au cours d'un séjour à l'hôpital sont inconnues. Objectifs: Décrire l'utilisation potentiellement inappropriée d'antipsychotiques chez les personnes âgées après le congé de l'hôpital, en particulier les taux de traitement antipsychotique initié à l'hôpital qui continue après le congé et son maintien jusqu'à 180 jours après le congé; les schémas de prescription utilisés; les facteurs de risque associés au maintien; l'implication du pharmacien; et les plans visant à arrêter, réduire progressivement et/ou à faire le suivi de la prise d'antipsychotiques. Méthodologie: Cet examen rétrospectif des dossiers comprenait des patients hospitalisés âgés d'au moins 65 ans qui étaient sortis des unités de médecine d'hôpitaux de la région de Regina de la SHA entre le 30 septembre 2021 et le 28 juin 2022. Les historiques de délivrance en ambulatoire ont également été recueillis. Résultats: Sur les 189 patients inclus dans l'analyse, 60 (31,7 %) ont continué leur traitement antipsychotique au moment du congé. Parmi eux, 48 (80,0 %), 33 (55,0 %) et 24 (40,0 %) continuaient leur traitement antipsychotique à 30, 90 et 180 jours après leur congé, respectivement. Parmi les patients recevant un traitement antipsychotique continu, 53 (88,3 %) étaient âgés d'au moins 75 ans et 9 (15,0 %) avaient un plan de suivi antipsychotique ambulatoire. Conclusions: Le maintien des antipsychotiques après le congé était similaire à celui rapporté dans la littérature. Les patients qui continuaient à prendre des antipsychotiques après leur congé couraient un risque supérieur à 50 % de continuer à 90 jours et étaient peu susceptibles de disposer d'un plan de suivi. Les futurs efforts d'amélioration de la qualité devraient comprendre une priorisation standardisée des examens des médicaments, la documentation des indications et une réévaluation régulière du traitement.

Capgras syndrome in children and adolescents: A systematic review.

OBJECTIVES: To improve understanding of Capgras syndrome (CS) in the pediatric population, this study investigates its clinical features and discerns similarities and differences compared to CS in adults. METHODS: We conducted a descriptive systematic review of case reports following PRISMA guidelines, including cases of pediatric patients with CS. Patient demographics, medical and psychiatric history, imposter identity, underlying diagnosis, clinical manifestation, treatments, and outcomes were extracted and analyzed. RESULTS: We included 37 articles comprising 38 cases. The median age of patients was 15, with 23 (60.5%) being male. The most prevalent underlying diagnoses were schizophrenia spectrum and other psychotic disorders (47.3%). Imposter identity involved parents in 32 cases (84.2%). Associated symptoms included persecutory delusions (63.1%), auditory hallucinations (42.1%), aggression (31.5%), and depression (21.0%). CONCLUSION: There is a significant gap in our understanding of CS, particularly in pediatric patients. This is the first systematic review of CS in pediatric patients, encompassing all cases found in English literature since 1923.

Ziprasidone triggers inflammasome signaling via PI3K-Akt-mTOR pathway to promote atrial fibrillation.

BACKGROUND: Second-generation antipsychotics increase the risk of atrial fibrillation. This study explores whether the atypical antipsychotic ziprasidone triggers inflammasome signaling, leading to atrial arrhythmia. METHODS: Electromechanical and pharmacological assessments were conducted on the rabbit left atria (LA). The patch-clamp technique was used to measure ionic channel currents in single cardiomyocytes. Detection of cytosolic reactive oxygen species production was performed in atrial cardiomyocytes. RESULTS: The duration of action potentials at 50 % and 90 % repolarization was dose-dependently shortened in ziprasidone-treated LA. Diastolic tension in LA increased after ziprasidone treatment. Ziprasidone-treated LA showed rapid atrial pacing (RAP) triggered activity. PI3K inhibitor, Akt inhibitor and mTOR inhibitor abolished the triggered activity elicited by ziprasidone in LA. The NLRP3 inhibitor MCC950 suppressed the ziprasidone-induced post-RAP-triggered activity. MCC950 treatment reduced the reverse-mode Na+/Ca2+ exchanger current in ziprasidone-treated myocytes. Cytosolic reactive oxygen species production decreased in ziprasidone-treated atrial myocytes after MCC950 treatment. Protein levels of inflammasomes and proinflammatory cytokines, including NLRP3, caspase-1, IL-1ß, IL-18, and IL-6 were observed to be upregulated in myocytes treated with ziprasidone. CONCLUSIONS: Our findings suggest ziprasidone induces atrial arrhythmia, potentially through upregulation of the NLRP3 inflammasome and enhancement of reactive oxygen species production via the PI3K/Akt/mTOR pathway.

Real-world effectiveness of antidepressants, antipsychotics and their combinations in the maintenance treatment of psychotic depression. Evidence from within-subject analyses of two nationwide cohorts.

Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative effectiveness of medications used in its maintenance treatment. The objective of this study was to investigate the comparative effectiveness of specific antipsychotics and antidepressants, and their combinations, on the risk of psychiatric hospitalization among persons with PD in routine care. Persons aged 16-65 years with a first-time diagnosis of PD were identified from Finnish (years 2000-2018) and Swedish (years 2006-2021) nationwide registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. The main exposures were specific antipsychotics and antidepressants, and the main outcome measure was psychiatric hospitalization as a marker of severe relapse. The risk of hospitalization associated with periods of use vs. non-use of medications (expressed as adjusted hazard ratio, aHR) was assessed by a within-individual design, using each individual as his/her own control, and analyzed with stratified Cox models. The two national cohorts were first analyzed separately, and then combined using a fixed-effect meta-analysis. The Finnish cohort included 19,330 persons (mean age: 39.8±14.7 years; 57.9% women) and the Swedish cohort 13,684 persons (mean age: 41.3±14.0 years; 53.5% women). Individual antidepressants associated with a decreased risk of relapse vs. non-use of antidepressants were bupropion (aHR=0.73, 95% CI: 0.63-0.85), vortioxetine (aHR=0.78, 95% CI: 0.63-0.96) and venlafaxine (aHR=0.92, 95% CI: 0.86-0.98). Any long-acting injectable antipsychotic (LAI) (aHR=0.60, 95% CI: 0.45-0.80) and clozapine (aHR=0.72, 95% CI: 0.57-0.91) were associated with a decreased risk of relapse vs. non-use of antipsychotics. Among monotherapies, only vortioxetine (aHR=0.67, 95% CI: 0.47-0.95) and bupropion (aHR=0.71, 95% CI: 0.56-0.89) were associated with a significantly decreased risk of relapse vs. non-use of both antidepressants and antipsychotics. In an exploratory analysis of antidepressant-antipsychotic combinations, a decreased relapse risk was found for amitriptyline-olanzapine (aHR=0.45, 95% CI: 0.28-0.71), sertraline-quetiapine (aHR=0.79, 95% CI: 0.67-0.93) and venlafaxine-quetiapine (aHR=0.82, 95% CI: 0.73-0.91) vs. non-use of antidepressants and antipsychotics. Benzodiazepines and related drugs (aHR=1.29, 95% CI: 1.24-1.34) and mirtazapine (aHR=1.17, 95% CI: 1.07-1.29) were associated with an increased risk of relapse. These data indicate that, in the maintenance treatment of PD, bupropion, vortioxetine, venlafaxine, any LAI, clozapine, and only few specific antidepressant-antipsychotic combinations are associated with a decreased risk of relapse. These findings challenge the current recommendation by treatment guidelines to combine an antipsychotic with an antidepressant (without further specification) as standard treatment in PD.

Treatment of tardive dyskinesia with clonazepam: A case report.

Clonazepam has some evidence in the treatment of tardive dyskinesia. It can be used as an alternative treatment option in situations where vesicular monoamine transporter 2 inhibitors are not available or when it is not feasible to use them.

Evaluation of the Safer Use of Antipsychotics in Youth Study on Population Level Antipsychotic Initiation: An Interrupted Time Series Analysis.

Background: Antipsychotics carry a higher-risk profile than other psychotropic medications and may be prescribed for youth with conditions in which other first-line treatments are more appropriate. This study aimed to evaluate the population-level effect of the Safer Use of Antipsychotics in Youth (SUAY) trial, which aimed to reduce person-days of antipsychotic use among participants. Methods: We conducted an interrupted time series analysis using segmented regression to measure changes in prescribing trends of antipsychotic initiation rates pre-SUAY and post-SUAY trial at four U.S. health systems between 2013 and 2020. Results: In our overall model, adjusted for age and insurance type, antipsychotic initiation rates decreased by 0.73 (95% confidence interval [CI]: 0.30, 1.16, p = 0.002) prescriptions per 10,000 person-months before the SUAY trial. In the first quarter following the start of the trial, there was an immediate decrease in the rate of antipsychotic initiations of 6.57 (95% CI: 0.99, 12.15) prescriptions per 10,000 person-months. When comparing the posttrial period to the pretrial period, there was an increase of 1.09 (95% CI: 0.32, 1.85) prescriptions per 10,000 person-months, but the increasing rate in the posttrial period alone was not statistically significant (0.36 prescriptions per 10,000 person-months, 95% CI: -0.27, 0.99). Conclusion: The declining trend of antipsychotic initiation seen between 2013 and 2018 (pre-SUAY trial) may have naturally reached a level at which prescribing was clinically warranted and appropriate, resulting in a floor effect. The COVID-19 pandemic, which began in the final three quarters of the posttrial period, may also be related to increased antipsychotic medication initiation.

Impact of body mass index elevation, Vitamin D receptor polymorphisms and antipsychotics on the risk of Vitamin D deficiency in schizophrenia patients.

Antipsychotics with weight gain as side effect and vitamin D receptor dysfunction associated with single nucleotide polymorphisms (VDR SNPs) may have different effects on vitamin D status. Hence, present study aimed to investigate the relationship between vitamin D with body mass index (BMI), antipsychotics and VDR SNPs (rs2228570, rs1544410, rs7975232 and rs731236) in Malaysian patients with schizophrenia. Serum vitamin D level was measured using competitive enzyme-linked immunosorbent assay kit. VDR SNPs were analyzed using polymerase chain reaction-restriction fragment length polymorphism. We found significantly lower serum vitamin D level in patients with schizophrenia (p < 0.01), especially those taking atypical antipsychotics (p = 0.02) and combined antipsychotics (p = 0.02) and obese (BMI ≥27.5 kg/m2) patients (p = 0.04) after adjustment for covariates. For VDR SNPs, the CT genotype of rs1544410, CA genotype of rs7975232, and AA and AG genotypes of rs731236 may contribute to the significant decreased serum vitamin D level in patients (p < 0.05). Nevertheless, these relationships may differ by populations or medical conditions. The hypotheses of volumetric dilution and sequestration of vitamin D may explain the lower vitamin D level in obese patients. In addition, lifestyle factors such as poor diet and lack of physical activity with less sunlight exposure may cause reduced vitamin D level among patients. As patients in present study were prescribed with various antipsychotics, the effect of each antipsychotic on vitamin D level could not be determined. Thus, future studies should investigate the effect of different types of antipsychotics and obesity on vitamin D level in schizophrenia.

Nursing Home Characteristics Associated with Antipsychotic Prescribing After Implementation of the National Antipsychotic Reduction Initiative (ARI).

OBJECTIVES: To describe nursing home (NH) characteristics associated with antipsychotic use and test whether associations changed after implementation of the National Partnership to Improve Dementia Care's antipsychotic reduction initiative (ARI). METHODS: Longitudinal quasi-experimental design using data from multiple sources and piecewise linear mixed models were used for statistical analyses. RESULTS: There was a significant decrease in monthly antipsychotic use across the study period (pre-ARI b = -0.0003, p <.001; post-ARI b = -0.0012, p <.001), which held after adjusting for NH characteristics. Registered nurse hours (b = -0.0026, p <.001), licensed practical nurse hours (b = -0.0019, p <.001), facility chain membership (b = -0.0013, p <.01), and health inspection ratings (b = -0.0003, p >.01) were associated with decreased antipsychotic use. Post-ARI changes in associations between NH characteristics and antipsychotic use were small and not statistically significant. CONCLUSIONS: Decreases in antipsychotic use were associated with most NH characteristics, and associations persisted post-ARI. Further research is warranted to examine the interactions between ARI policy and NH characteristics on antipsychotic prescribing, as well as other NH factors, such as facility prescribing cultures and clinical specialty of staff. CLINICAL IMPLICATIONS: Decreases in monthly antipsychotic use were observed following the ARI. The decreases in monthly antipsychotic use were associated with most NH characteristics, and these associations persisted during the post-ARI period.