Antipsychotic Research Articles

NeuropsychopharmARCology: Shaping Neuroplasticity through Arc/Arg3.1 Modulation

Activity-regulated cytoskeletal associated protein (aka activity-regulated gene Arg3.1) belongs to the effector gene family of the immediate early genes. This family encodes effector proteins, which act directly on cellular homeostasis and function. Arc/Arg3.1 is localized at dendritic processes, allowing the protein local synthesis on demand, and it is considered a reliable index of activitydependent synaptic changes. Evidence also exists showing the critical role of Arc/Arg3.1 in memory processes. The high sensitivity to changes in neuronal activity, its specific localization as well as its involvement in long-term synaptic plasticity indeed make this effector gene a potential, critical target of the action of psychotropic drugs. In this review, we focus on antipsychotic and antidepressant drugs as well as on psychostimulants, which belong to the category of drugs of abuse but can also be used as drugs for specific disorders of the central nervous system (i.e., Attention Deficit Hyperactivity Disorder). It is demonstrated that psychotropic drugs with different mechanisms of action converge on Arc/Arg3.1, providing a means whereby Arc/Arg3.1 synaptic modulation may contribute to their therapeutic activity. The potential translational implications for different neuropsychiatric conditions are also discussed, recognizing that the treatment of these disorders is indeed complex and involves the simultaneous regulation of several dysfunctional mechanisms.

Antipsychotic prescribing practices and their association with rehospitalization in a forensic psychiatric sample.

While there is extensive literature examining the effectiveness of antipsychotic prescribing to patients with schizophrenia spectrum or other psychotic disorders in general psychiatric services, there is a dearth of studies examining antipsychotic prescribing practices and their effectiveness in forensic psychiatric services. Forensic psychiatric patients have unique challenges often due to their high-profile offences, public scrutiny, and legal requirements. This longitudinal, retrospective study aimed to examine antipsychotic prescribing and rehospitalization rates in a forensic psychiatric sample, along with relevant socio-demographic, clinical, and forensic characteristics. All patients had a psychotic illness and were prescribed antipsychotic medication. The sample included 153 patients, of which the majority were male (85.6%), Caucasian (71.2%), middle aged (30s to 50s), had schizophrenia or schizoaffective disorder (76.5%), had a substance use disorder (62.1%), and had a most serious index offence against the person (80.4%). Atypical antipsychotics accounted for the majority of antipsychotic prescriptions (75.9%) and the sample had an antipsychotic polypharmacy rate of 39.9%. The sample was divided into four primary antipsychotic formulation types, which were oral (34.0%), injection (39.2%), clozapine (19.0%), and subtherapeutic (7.8%). Regarding rehospitalization, 52.9% of the sample was rehospitalized, with the average number of rehospitalizations being 1.2 (SD = 1.7) and proportion of the follow up period rehospitalized being 16.4% (SD = 27.7%). Patients prescribed clozapine had numerically lower rates of rehospitalization than those prescribed oral and injection formulation types, but it was not statistically significant. With a 19.0% prescription rate, clozapine may be underutilized in this sample. Further research is needed to demonstrate the potential benefits of clozapine regarding rehospitalization in forensic psychiatric patients, as has already been done in general psychiatry. Advancing treatment of the high-profile forensic population can reduce stigma toward people with mental illness and criminal justice involvement.

Clinical, Quality of Life, and Health Care Utilization Outcomes of Switching the Administration Route of Antipsychotic Medications Among People With Schizophrenia Spectrum Disorder: A Systematic Review and Meta-Analysis.

Using long-acting injectable (LAI) antipsychotic medications can improve the outcomes of patients with schizophrenia, such as reducing symptom severity and hospitalization risk. However, the outcomes of switching from oral to LAI antipsychotic medications are unclear. The purpose of this review is to provide a summary of the clinical, quality of life, and health care utilization outcomes of switching from oral to LAI antipsychotics among patients with Schizophrenia Spectrum Disorder. We thoroughly searched the PubMed, Scopus, PsycInfo, and CINAHL databases. To conduct the meta-analysis, we used the Comprehensive Meta-Analysis Program. Forty-one articles met our inclusion criteria. After switching to LAIs, symptom severity, the number of rehospitalizations, emergency department visits, and overall health care costs were reduced. Also, social functioning significantly improved. However, no differences were observed in the frequency of outpatient visits. Pharmacy costs were increased between pre- and post-LAI initiation. Our findings support evidence that changing the route of administration of antipsychotic medications from oral to long-acting intramuscular injections can improve the clinical, quality of life, and health care utilization outcomes in people with schizophrenia. Health care practitioners might consider encouraging LAI use earlier during treatment for schizophrenia for better clinical outcomes and to reduce health care utilization associated with treatment.

Medical Professionals and Pharmacological Intervention for the Treatment of Insomnia: A Cross-Sectional Study

Abstract Objective To explore the preferences of medical practitioners concerning various medications and other remedies to manage insomnia, and to ascertain whether these preferences are associated with their respective medical specialties. Materials and Methods Employing the snowball sampling technique, we administered two versions of a questionnaire to an international group of medical professionals, including trainees and specialists from diverse medical backgrounds. Results Zopiclone, zolpidem, and mirtazapine were evaluated as the most effective treatments for insomnia, while physicians would typically avoid using other tricyclic antidepressants, dual orexin receptor antagonists, and tryptophan for insomnia treatment. Noteworthy statistical correlations between physicians' specialty and preferred drug therapy, were observed in three out of five cases: 1) first-line drug treatment for short-term intervention against insomnia; (2) second-line treatment for long-term intervention; and 3) cases involving the elderly. Discussion Psychiatrists demonstrated a greater preference for antipsychotics and antidepressants for the treatment of insomnia compared with other physicians. Conversely, other medical professionals exhibited a preference for benzodiazepines and Z-drugs (zopiclone and zolpidem). Although Z-drugs were evaluated as the most effective in the treatment of insomnia, in the clinical practice, physicians administer or would administer antidepressant or antipsychotic drugs more often (mirtazapine and quetiapine respectively). Regarding Dual Orexin Receptor Antagonists (DORAs), the high prevalence of “Do not know/No opinion” answers implies that our sample was not familiar with this innovative treatment.

Effectiveness of antipsychotic drug therapy for treating psychosis in people with epilepsy: A systematic review.

Individuals with epilepsy are at risk of developing preictal, ictal, postictal and interictal psychoses. Antipsychotic drugs (APDs) are the main class of drugs used to treat psychosis and schizophrenia. The efficacy and safety of APDs as a treatment for epileptic psychosis is not well understood. This systematic review aimed to assess the effectiveness and adverse effects of APDs for treating psychosis in people with epilepsy. We adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched MEDLINE, Embase, PsycInfo, and AMED (Allied and Complementary Medicine) from database inception to June 20, 2023. We contacted experts in the field and performed citation searches to identify additional records. Title, abstract, full-text review, and data analysis were conducted in duplicate, with conflicts resolved by discussion among authors. Given the considerable heterogeneity of study designs, meta-analysis was not deemed appropriate; instead, the results were tabulated in a narrative synthesis. The Joanna Briggs Institute Risk of Bias tool and GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework were used to assess study quality. We identified 13 studies with a total of 1180 participants. In the four case series included, the psychotic symptoms of 25 of 28 patients treated with APDs partially improved or fully resolved. Three of the four cohort studies reported an association between antipsychotic use and longer duration of psychotic episodes, two found similar results in both APD and non-APD groups, and two did not report control psychosis outcomes. When reported, seizure frequency was observed to remain unchanged or decrease following APD treatment. The evidence on the effectiveness of antipsychotics in the treatment of psychosis in epilepsy is inconclusive and may reflect confounding by indication. However, most studies suggest that antipsychotics were not associated with a marked worsening in seizure frequency. It remains unclear whether antipsychotics should be used in epilepsy, and well-controlled cohort studies and randomized controlled trials are necessary to draw definitive conclusions.

Olanzapine-Induced Weight Gain in A 13-Year-Old Patient with Trichotillomania: A Case Report

Objective: To emphasize a case of olanzapine-induced weight gain in a 13-year-old girl with trichotillomania and discuss the management strategies implemented. Case Summary: A 13-year-old female diagnosed with trichotillomania experienced significant weight gain after being prescribed olanzapine. The patient also developed increased appetite. Consequently, olanzapine was discontinued and replaced with other antipsychotic agent, alongside lifestyle modifications including diet modifications and regular physical activity. Conclusion: The case highlights the potential for olanzapine to induce significant weight gain and emphasizes the need for careful monitoring and timely intervention. A shift to safer option and lifestyle changes are essential in managing the patient’s condition. Keywords: Trichotillomania, Olanzapine, Weight Gain, Paediatrics, Atypical Antipsychotics, Metabolic Effects

A Comprehensive Review on the Screening Models for the Pharmacological Assessment of Antipsychotic Drugs

Background: Psychosis is a debilitating mental disorder characterized by a profound disconnection from reality, manifesting in symptoms such as hallucinations, delusions, and disorganized thinking. The pathophysiology of psychosis is multifaceted, involving an interplay of neurobiological, genetic, and environmental factors. Neurobiologically, dysregulation of neurotransmitter systems particularly dopaminergic, serotonergic, and glutamatergic pathways-plays a central role, with excessive dopaminergic activity linked to positive symptoms and glutamatergic dysfunction implicated in cognitive impairments. Genetic predisposition, evidenced by significant heritability and associations with specific genetic variants, intersects with environmental factors such as stress, trauma, and substance use to influence the onset and progression of psychosis. Cognitive disruptions, including deficits in attention, memory, and executive function, exacerbate the disorder’s impact. This phenomenon has led to short-term as well as long-term psychosocial and mental health implications for all. Objective: To determine the antipsychotic activity of pharmaceuticals, numerous antipsychotic screening models are available. Determining the optimal animal model for measuring antipsychotic activity is the primary goal of this study. Methods: A search for literature was carried out using several keywords, including "Antipsychotic," "In-vivo models," "In-vitro models," and "Behavior models," on the databases Science Direct and PubMed. For the purpose of obtaining the most appropriate articles to fulfil the goal of this review article, the search was customized by using the necessary filters. Results: Research and review articles based on neuroleptic screening models are available to determine the antipsychotic activity of novel pharmacological compounds. Conclusion: Following our research, we identified several helpful models for evaluating the antipsychotic activity of pharmaceuticals and proposed that combining invitro and in-vivo techniques with behavioral methodologies might yield the most appropriate results for our field of study.

A case report of adolescent lactation due to the drug blonanserin

BackgroundSecond-generation antipsychotic drugs are increasingly used to treat depressive disorders with psychotic symptoms. In addition to effectively managing psychotic symptoms, second-generation antipsychotics can also result in adverse drug reactions in patients, which should not be underestimated.Case presentationWe report the case of 14 years old unmarried female patient with depression. At first, she started with moping and gradually developed into self-injury and whispering. After antidepressant treatment combined with the second-generation antipsychotic drug blonanserin, the patient’s psychotic and depressive symptoms improved significantly, while the patient developed lactation, which stopped after the medication was changed.ConclusionsAlthough Blonanserin’s clinical trials have reported rare adverse reactions like elevated prolactin levels and even lactation, caution is still needed in clinical application of the drug. This case is expected to improve psychiatrists’ choice of antidepressant therapy in combination with antipsychotic drugs.

Neuronal alterations in AKT isotype expression in schizophrenia.

Schizophrenia is characterized by substantial alterations in brain function, and previous studies suggest insulin signaling pathways, particularly involving AKT, are implicated in the pathophysiology of the disorder. This study demonstrates elevated mRNA expression of AKT1-3 in neurons from schizophrenia subjects, contrary to unchanged or diminished total AKT protein expression reported in previous postmortem studies, suggesting a potential decoupling of transcript and protein levels. Sex-specific differential AKT activity was observed, indicating divergent roles in males and females with schizophrenia. Alongside AKT, upregulation of PDPK1, a critical component of the insulin signaling pathway, and several protein phosphatases known to regulate AKT were detected. Moreover, enhanced expression of the transcription factor FOXO1, a regulator of glucose metabolism, hints at possible compensatory mechanisms related to insulin signaling dysregulation. Findings were largely independent of antipsychotic medication use, suggesting inherent alterations in schizophrenia. These results highlight the significance of AKT and related signaling pathways in schizophrenia, proposing that these changes might represent a compensatory response to a primary defect of canonical insulin signaling pathways. This research underscores the need for a detailed understanding of these signaling pathways for the development of effective therapeutic strategies.

Schizophrenia, Off-Label Antipsychotics, and Dementia Risk in People with HIV.

Comorbidities such as schizophrenia and medication such as antipsychotics may influence the risk of dementia among people living with HIV (PLWH). The objective of this paper is to assess the associations among HIV patients with schizophrenia, off-label antipsychotics, and dementia risk. US Department of Veterans Affairs healthcare facilities from 2000 to September 2023. Retrospective cohort study of PLWH treated by the U.S. Department of Veterans Affairs with prior history of schizophrenia, off-label antipsychotic use and neither schizophrenia nor antipsychotic use. Propensity score matched non-HIV controls were included for the respective HIV groups. The hazard of dementia is estimated using Cox proportional hazards models. PLWH and schizophrenia, were found to have a 2.49 higher hazard of dementia compared to HIV patients with no history of schizophrenia or antipsychotic medication use (HR=2.49, 95%CI=(1.85-3.35)). PLWH and off-label antipsychotic use were found to have a 1.77-fold higher hazard of dementia compared to HIV patients with no history of schizophrenia or antipsychotic medication use (HR=1.77, 95% CI=(1.37-2.28)). Propensity score matched analysis reveals that, among schizophrenia patientis, those with HIV had a 1.65-fold higher hazard of dementia (HR=1.65, 95%CI=(1.12-2.44)). Among patients with no schizophrenia or antipsychotic medication, those with HIV had a 1.47 fold higher hazard of dementia (HR=1.47, 95%CI=(1.33-1.63)). This study demonstrates that among PLWH, history of schizophrenia or off-label antipsychotic medication use are associated with substantial increases in dementia incidence. Furthermore, propensity-matched control analysis reveals that HIV infection itself is independently and significantly associated with elevated dementia risk.

Exposure-Efficacy Analysis and Dopamine D2 Receptor Occupancy in Adults with Schizophrenia after Treatment with the Monthly Intramuscular Injectable Risperidone ISM.

Dopamine D2 receptor occupancy (D2RO) significantly influences the clinical effectiveness and safety of many antipsychotic drugs. Maintaining a D2RO range of 65%-80% provides the best antipsychotic effects while minimizing adverse reactions. Data from a Phase III trial were used to establish an exposure-response relationship for monthly intramuscular Risperidone ISM (75 and 100 mg) or placebo administered to adults with schizophrenia. Pharmacodynamic analysis was based on an Emax model for Positive and Negative Syndrome Scale (PANSS) developed in NONMEM. Plasma concentrations of the active moiety were derived using a previously developed population pharmacokinetic model, which was used for D2RO simulations in conjunction with a published Emax model. The optimal D2RO range (65%-80%) was reached for the median within hours following the first injection of both Risperidone ISM doses. At steady state, median D2RO for both doses remained above 65% throughout the 28-day dosing period and demonstrated lower variability than oral risperidone. PANSS response did not differ significantly between dose groups, most likely because active moiety concentrations had already reached the plateau of the concentration-response relationship. The pharmacokinetic/pharmacodynamic analysis showed a profound placebo effect (-11.7%), and an additional maximal drug effect (-6.6%) resulting in a total PANSS improvement over time of -18.3%. Pharmacokinetic/pharmacodynamic modeling quantified a PANSS improvement over time after Risperidone ISM administration. The response was not significantly different in either dose group, likely because D2RO was already above the proposed efficacy threshold (65%) within 1 h after the first Risperidone ISM injection and remained above this level following repeated administrations.

Antipsychotic drugs and their possible cardiovascular adverse effects – literature review

Antipsychotic drugs and their possible cardiovascular adverse effects – literature review

Effects of Chitosan and N-Succinyl Chitosan on Metabolic Disorders Caused by Oral Administration of Olanzapine in Mice.

The issue of human mental health is gaining more and more attention nowadays. However, most mental disorders are treated with antipsychotic drugs that cause weight gain and metabolic disorders, which include olanzapine (OLZ). The search for and development of natural compounds for the prevention of obesity when taking antipsychotic drugs is an urgent task. The biopolymer chitosan (Chi) and its derivatives have lipid-lowering and anti-diabetic properties, which makes them potential therapeutic substances for use in the treatment of metabolic disorders. The purpose of this work was to analyze the effect of the natural biopolymer Chi, its derivative N-succinyl chitosan (SuChi), and Orlistat (ORL) as a control on the effects caused by the intake of OLZ in a mouse model. Mice were fed with pearl barley porridge mixed with OLZ or combinations OLZ + Chi, OLZ + SuChi, or OLZ + ORL for 2 months. The weight, lipid profile, blood chemokines, expression of genes associated with appetite regulation, and behavior of the mice were analyzed in dynamics. For the first time, data were obtained on the effects of Chi and SuChi on metabolic changes during the co-administration of antipsychotics. Oral OLZ increased body weight, food and water intake, and glucose, triglyceride, and cholesterol levels in blood. ORL and SuChi better normalized lipid metabolism than Chi, decreasing triglyceride and cholesterol levels. OLZ decreased the production of all chemokines tested at the 4th week of treatment and increased CXCL1, CXCL13, and CCL22 chemokine levels at the 7th week. All of the supplements corrected the level of CXCL1, CXCL13, and CCL22 chemokines but did not recover suppressed chemokines. SuChi and ORL stimulated the expression of satiety associated proopiomelanocortin (POMC) and suppressed the appetite-stimulating Agouti-related protein (AgRP) genes. All supplements improved the locomotion of mice. Taken collectively, we found that SuChi more than Chi possessed an activity close to that of ORL, preventing metabolic disorders in mice fed with OLZ. As OLZ carries positive charge and SuChi is negatively charged, we hypothesized that SuChi's protective effect can be explained by electrostatic interaction between OLZ byproducts and SuChi in the gastrointestinal tract.

Antipsychotic Drugs and Cognitive Function

Cognitive deficits are a substantial part of the symptoms of schizophrenia spectrum disorders (SSDs) and contribute heavily to the burden of disease. Antipsychotic drugs are not cognitive enhancers, but due to their different receptor-binding profiles, they could differ in their effects on cognition. No previous network meta-analysis compared antipsychotics to placebo, which is important to determine whether use of these drugs is associated with cognitive performance in SSDs at all. To determine the association of treatment with various antipsychotics and cognition in patients with SSDs. Cochrane Schizophrenia Trials Register through June 25, 2023. Randomized clinical trials examining the effects on cognition of antipsychotic drugs or placebo in participants with SSD. A systematic review and random-effects frequentist network meta-analysis was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses-Network Meta-analysis reporting guideline. The primary outcome was change in overall cognition score calculated for each study. Secondary outcomes included cognitive domains, quality of life, and functioning. This study included 68 studies involving 9525 participants (mean [SD] age, 35.1 [8.9] years; 5878 male [70%] and 2890 [30%] female; some studies did not provide this information). There were few clear differences between antipsychotics, but first-generation dopamine antagonists haloperidol (standardized mean difference [SMD], 0.04; 95% CI, -0.25 to 0.33) and fluphenazine (SMD, 0.15; 95% CI, -0.39 to 0.69) as well as clozapine (SMD, 0.12; 95% CI, -0.23 to 0.48) ranked low. No individual antipsychotic was associated with a clearly better outcome than placebo, but antipsychotics as a group were, with small effect sizes (mean SMDs: adrenergic/low dopamine, 0.21; serotonergic/dopaminergic, 0.26; muscarinic, 0.28; dopaminergic, 0.40). Although data are relatively sparse, those reviewed in this study suggest that first-generation dopamine antagonists and clozapine should be avoided when cognitive deficits are a concern. Antipsychotics are not procognitive drugs. The overall small superior outcomes compared to placebo may be explained by less disordered thought patterns associated with fewer positive symptoms rather than cognitive deficits in the proper sense. The findings also suggest that harmonizing measurement of cognitive function in randomized clinical trials would be beneficial.

Olanzapine Versus Quetiapine: Corrected QT Changes in Critically Ill Patients.

Olanzapine and quetiapine are frequently administered atypical antipsychotic medications and their effects on the corrected QT (QTc) in the critically ill population remain understudied. The objective of this study was to compare the impact of olanzapine and quetiapine on QTc changes in critically ill patients. This was a single-center, retrospective analysis. Adult patients admitted to the intensive care unit (ICU) from January 2023 through July 2023 were included if they received ≥2 doses of either olanzapine or quetiapine within a 48-hour period and had one QTc evaluated within 48 hours of antipsychotic initiation. The major endpoint was a composite of the incidence of QTc prolongation (defined as QTc > 500 ms or QTc > 60 ms above baseline) following antipsychotic initiation. Univariable and multivariable analyses were performed to identify risk factors for QTc prolongation. There was no statistical difference in the major composite endpoint between patients in the olanzapine and quetiapine groups (8/83 [9.6%] vs 19/129 [14.7%]; P = .28). The incidence of QTc > 500 ms (7/244 [2.9%] vs 20/427 [4.7%]; P = .25) and change from baseline >60 ms (5/244 [2.0%] vs 17/427 [4.0%]; P = .26) were not statistically different between the olanzapine and quetiapine groups, respectively. There were no occurrences of Torsades de Pointes or extrapyramidal symptoms in either group. The results of this study suggest olanzapine and quetiapine may have similar impact on QTc prolongation in critically ill patients. These findings could contribute to safer prescribing practices in the ICU.

N-Methyl-d-Aspartate Receptor Antibody and Sensory Gating Deficits in Non-smoking, Minimal Antipsychotic Medication Exposure, and First-Episode Patients With Schizophrenia.

Sensory gating deficit is considered a pathophysiological feature of schizophrenia, which has been linked to N-methyl-d-aspartate receptor (NMDAR) hypofunction as one of the potential underlying mechanisms. Here, we hypothesize that higher levels of NMDAR antibody (Ab) may contribute to the sensory gating deficits in schizophrenia. We enrolled 72 non-smoking inpatients with first-episode schizophrenia (FES), most of them with only a relatively short duration of exposure to antipsychotic medications, and 51 non-smoking healthy controls (HC). Sensory gating was measured by P50 evoked potentials ratio and the difference between the two stimuli in an auditory paired-stimuli paradigm and serum NMDAR Ab levels were quantified by enzyme-linked immunosorbent assay. The FES group showed higher serum NMDAR Ab levels [(9.23 ± 4.15) ng/mL vs. (7.08 ± 2.83) ng/mL; P = .002], higher P50 ratio (P = .002), and less P50 difference (P = .001) than HC. In partial correlation analysis, serum NMDAR Ab levels were positively correlated with the P50 ratio (r = 0.36, P = .003) and negatively with the P50 difference (r = -0.39, P = .001) in the FES group. The NMDAR Ab levels mediated the diagnosis of schizophrenia and P50 sensory gating deficits (P50 ratio and P50 difference). Autoimmunity targeting NMDAR is a crucial intermediate mechanism in impaired sensory gating in patients with schizophrenia. The findings support early intervention targeting NMDAR for patients with schizophrenia.

Capgras Syndrome in Dementia: A Systematic Review of Case Studies.

In an ageing population, dementia has become an imminent healthcare emergency. Capgras syndrome, the most common delusion of misidentification (DMS), is frequently found alongside dementia. Previous research showed that Capgras syndrome has significant negative effects on people living with dementia and their carers due to its complex presentation and impact on their lives. This qualitative systematic review explores the evidence base of the effective management and treatment of Capgras syndrome in dementia. As per our knowledge, this is the first systematic review exploring the symptomatology of Capgras syndrome across different types of dementia. Additionally, it aims to identify the treatments used and their efficacy. Four databases (EMBASE, MEDLINE, PsycINFO, and CINHAL) were screened in March, 2023. Twenty-six studies met the inclusion criteria and were included in the review. Thematic analysis was performed to explore and synthesise the qualitative findings of the studies. Three conceptual themes were identified: diagnostic tools, Capgras syndrome symptomatology, and Capgras syndrome treatment. Results showed that Capgras syndrome in dementia is not diagnosed and treated in a standardised manner. Following the pharmacological intervention, 28% of cases showed resolution of symptoms, and another 28% experienced improvement. However, 7% of cases reported worsening symptoms, and 10.7% experienced no change. While some patients had positive outcomes with specific medications, others either did not respond or experienced a deterioration of their condition. The results highlight that there is no single treatment approach for Capgras syndrome in people living with dementia. This underscores the need for person-centred care, where treatment is tailored to individual needs. The review also reveals a heavy reliance on antipsychotic medications and a noticeable lack of psychosocial interventions. Given the limited benefits and significant risks associated with antipsychotics, future research should prioritise developing and testing psychosocial approaches. Additionally, establishing standardised diagnostic criteria and consistent outcome measures for Capgras syndrome in dementia is crucial for evaluating treatment effectiveness and improving care.

Deprescribing antipsychotics in patients with schizophrenia: findings from a specialized clinic.

While antipsychotic medication reduces the risk of relapse for patients with schizophrenia, high prevalence of adverse effects results in low adherence. Lower doses of antipsychotics have been associated with increased level of function but also with increased risk of relapse. This study presents findings from a specialized deprescribing clinic. In addition, we aim to identify clinical predictors for relapse. Patients diagnosed with schizophrenia were referred to the clinic, which offers a six-month guided tapering program. Antipsychotic dose was reduced by 10% every four weeks. Patients were monitored closely for symptom progression or decrease in level of function, with defined cut-offs prompting a pause in or cessation of dose reduction. After 12 months, the antipsychotic dose was reduced from 404 (±320 mg) to 255 (±236 mg) chlorpromazine equivalent. Of the 88 patients included, 22 (27%) experienced relapse during the six-month tapering period, while 29 (37%) experienced relapse at the 12-month follow-up visit and nine patients were antipsychotic free. Patients who remained stable experienced a slightly increased level of functioning and markedly fewer side effects (p < 0.001). Following relapse, patients were clinically stabilized and showed an improved attitude toward antipsychotic medication. The predictive models were weak. We show that most patients undergoing guided antipsychotic tapering remained stable after one year and improved in level of function, while most patients who relapsed were quickly stabilized. Our inability to create strong predictive models could be due to limitations in the study design, warranting future studies exploring tapering of antipsychotics in patients with schizophrenia.

Multi-level barriers and facilitators to implementing evidence-based antipsychotics in the treatment of early-phase schizophrenia.

Long-acting injectable (LAI) antipsychotic medications and clozapine are effective yet underutilized medical therapies in early intervention services. The purpose of this study was to conduct a pre-implementation evaluation of contextual determinants of early intervention programs to implement innovations optimizing LAI antipsychotic and clozapine use within a shared decision-making model. Semi-structured interviews explored barriers and facilitators to implementing LAI antipsychotics and clozapine in early intervention services. Participants were: prescribers (n = 2), non-prescribing clinicians (n = 5), administrators (n = 3), clients (n = 3), and caregivers (n = 3). Interviews were structured and analyzed using the Consolidated Framework for Implementation Research (CFIR 2.0). Participants were supportive of using LAI antipsychotics, despite barriers (e.g., transportation, insurance coverage), while most were unfamiliar with clozapine (Innovation). Critical incidents (e.g., COVID-19) did not interfere with implementation, while barriers included lack of performance measures; stigma affecting willingness to take medication; and clozapine considered to be a "last resort" (Outer Setting). Treatment culture was described as client-centered and collaborative, and most participants indicated LAI antipsychotic use was compatible with clinic workflows, but some were in need of resources (e.g., individuals trained to administer LAI antipsychotics; Inner Setting). Participants on the healthcare team expressed confidence in their roles. Family education and collaborative decision-making were recommended to improve client/family engagement (Individuals). Participants related the importance of tracking medication compliance, addressing client concerns, and providing prescribers with updated guidelines on evidence-based treatment (Implementation Process). Results may guide implementation strategy selection for future programs seeking to optimize the use of LAI antipsychotics and clozapine for early-phase schizophrenia, when appropriate.

In brief: Erzofri - another once-monthly paliperidone formulation.

The FDA has approved Erzofri (Luye), an extended-release injectable formulation of the second-generation antipsychotic drug paliperidone palmitate, for treatment of schizophrenia and schizoaffective disorder in adults. It is the second once-monthly formulation of paliperidone palmitate to be approved in the US for these indications; Invega Sustenna was the first. Longer-acting injectable formulations of paliperidone palmitate are also available.