Evaluating the impact of COVID-19 on medication adherence and health care utilization among individuals with psychotic disorders who are prescribed long-acting injectables (LAIs) or clozapine: A population-based study in Manitoba, Canada.

BACKGROUND: Ongoing psychiatric follow-up and medication adherence improve outcomes for patients with psychotic disorders. Due to COVID-19, outpatient care may have been disrupted, impacting healthcare utilization. METHODS: A retrospective population-wide study was conducted for adults in Manitoba, Canada. Medication adherence and healthcare utilization were examined from 2019 to 2021. The presence of a diagnosed psychotic disorder was identified in the five years before the index date in each year. The LAI and clozapine cohorts consisted of those who received at least two prescriptions in each year 180 days before the March 20th index date. The change in adherence was measured using the average Medication Possession Ratio. Healthcare utilization rates were compared using Generalized Estimating Equation models. RESULTS: There were no significant differences between LAI and clozapine discontinuation rates before and during the pandemic. In the LAI cohort, general practitioner visits decreased significantly (-3.5 %, p = 0.039) across four quarters of 2021 versus 2019. All-cause hospitalizations decreased by 16.8 % in 2020 versus 2019 (p = 0.0055), while psychiatric hospitalizations decreased by 18.7 % across four quarters in 2020 (p = 0.0052) and 13.7 % in 2021 (p = 0.0425), versus 2019 in the LAI cohort. There was a significant transition to virtual care during the first wave of COVID-19 (71 % in clozapine, 51 % in LAI cohorts). Trends in total outpatient visits and non-psychiatric hospitalizations remained stable. CONCLUSION: COVID-19 had no substantial impact on LAI and clozapine discontinuation rates for patients previously adherent. Outpatient care remained stable, with a significant proportion of visits being done virtually at the outset of the pandemic.

Long-acting antipsychotic treatments: focus on women with schizophrenia.

Effective management of schizophrenia (SZ) requires long-term treatment with antipsychotics (APs) to prevent clinical relapse, attain remission and improve patients' personal and social functioning, and quality of life. Although APs remain the cornerstone treatment for patients with SZ, despite their potential benefits, long-acting injectable APs (LAI-APs) remain underused, most notably in women with SZ. The efficacy and tolerability of APs differ significantly between men and women, and some of these differences are more noticeable depending on the patient's age and the stage of the disorder. Although sex differences may influence treatment outcomes in SZ, their pertinence has been insufficiently addressed, especially regarding the use of LAI-APs. Some biological and social experiences, such as pregnancy, lactation, contraception and menopause, are specific to women, but these remain under-researched issues. Implications of this disorder in parenting are also of special pertinence regarding women; therefore, taking sex differences into account when treating SZ patients is now recommended, and improving personalized approaches has been proposed as a priority in the management of psychosis. In this narrative, critical review, we address some aspects specific to sex and their implications for the clinical management of women with SZ, with a special focus on the potential role of LAI-AP treatments.

• Schizophrenia is a chronic mental illness, and patients often need to take antipsychotic medications in the long-run in order to stay well, avoid re-occurrence of symptoms and improve their everyday functioning and quality of life. • Antipsychotics are available in both pill and injection form. The latter is known as long-acting injectable antipsychotics (LAI-APs) and can be administered from weekly to twice a year. • Despite their effectiveness and practicality due to less frequent administration, LAI-APs remain largely underused, especially in women with schizophrenia. • The efficacy and tolerability of antipsychotics can be very different between men and women, and some of these differences may be more pronounced depending on the patient's age and the phase of the illness. • Notably, physical and social aspects such as pregnancy, lactation, contraception, parenting and menopause and their effects on the treatment with antipsychotics and particularly LAI-APs in women with schizophrenia are under-studied. • Nevertheless, we have now become more aware of the importance of these sex differences, and it is recommended to take them routinely into consideration when treating patients with schizophrenia in clinical practice. • In this article, we discuss how factors specific to sex can influence the treatment of women with schizophrenia and focus on the potential role of LAI-AP medications.

Unlocking treatment success: predicting atypical antipsychotic continuation in youth with mania.

PURPOSE: This study aimed to create and validate robust machine-learning-based prediction models for antipsychotic drug (risperidone) continuation in children and teenagers suffering from mania over one year and to discover potential variables for clinical treatment. METHOD: The study population was collected from the national claims database in China. A total of 4,532 patients aged 4-18 who began risperidone therapy for mania between September 2013 and October 2019 were identified. The data were randomly divided into two datasets: training (80%) and testing (20%). Five regularly used machine learning methods were employed, in addition to the SuperLearner (SL) algorithm, to develop prediction models for the continuation of atypical antipsychotic therapy. The area under the receiver operating characteristic curve (AUC) with a 95% confidence interval (CI) was utilized. RESULTS: In terms of discrimination and robustness in predicting risperidone treatment continuation, the generalized linear model (GLM) performed the best (AUC: 0.823, 95% CI: 0.792-0.854, intercept near 0, slope close to 1.0). The SL model (AUC: 0.823, 95% CI: 0.791-0.853, intercept near 0, slope close to 1.0) also exhibited significant performance. Furthermore, the present findings emphasize the significance of several unique clinical and socioeconomic variables, such as the frequency of emergency room visits for nonmental health disorders. CONCLUSIONS: The GLM and SL models provided accurate predictions regarding risperidone treatment continuation in children and adolescents with episodes of mania and hypomania. Consequently, applying prediction models in atypical antipsychotic medicine may aid in evidence-based decision-making.

Characteristics of eye disorders induced by atypical antipsychotics: a real-world study from 2016 to 2022 based on Food and Drug Administration Adverse Event Reporting System.

Background: Common atypical antipsychotics include risperidone, paliperidone, olanzapine, lurasidone, quetiapine, clozapine, aripiprazole, ziprasidone, asenapine, brexpiprazole, and cariprazine. Previous studies on ocular adverse reactions of antipsychotics were mainly focused on typical antipsychotics. Systematic research on atypical antipsychotics remains limited. Objective: This study aimed to evaluate the potential risks of different atypical antipsychotics causing ocular side effects by mining the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Extract reports from the FAERS from the first quarter of 2016 to the fourth quarter of 2022 were obtained. Data mining of eye disorders associated with atypical antipsychotics was carried out using The Reporting Odds Ratio (ROR) method and The Medicines and Healthcare Products Regulatory Agency (MHRA) method to determine positive signals. Results: FAERS reports for 9913783 cases were included in these 28 quarters. 64 defined ocular adverse events were classified into 10 categories according to High-Level Group Terms (HLGT). Conclusions: There were differences in the types and severity of ocular-related adverse events associated with atypical antipsychotics. Ocular neuromuscular-related adverse events were found among all 11 atypical antipsychotics. Olanzapine had the highest signal intensity in oculogyric crisis. Aripiprazole had the highest signal strength in blepharospasm. Cariprazine was associated with cataract-related ocular adverse reactions. In terms of the types of adverse events, our study found that aripiprazole was associated with 28 types of ocular adverse events, followed by quetiapine. Clozapine was only associated with two types of ocular adverse events.

Informing the development of antipsychotic-induced weight gain management guidance: patient experiences and preferences - qualitative descriptive study.

BACKGROUND: Antipsychotic-induced weight gain (AIWG) is a substantial contributor to high obesity rates in psychiatry. Limited management guidance exists to inform clinical practice, and individuals with experience of managing AIWG have had no or minimal input into its development. A lack of empirical research outlining patient values and preferences for management also exists. Recommendations addressing weight management in psychiatry may be distinctly susceptible to ideology and sociocultural values regarding intervention appropriateness and expectations of self-management, reinforcing the need for co-produced management guidance. This study is the first to ask: how do individuals conceptualise preferred AIWG management and how can this be realised in practice? AIMS: 1. Explore the management experiences of individuals with unwanted AIWG. 2. Elicit their values and preferences regarding preferred management. METHOD: Qualitative descriptive methodology informed study design. A total of 17 participants took part in semi-structured interviews. Data analysis was undertaken using reflexive thematic analysis. RESULTS: Participants reported that clinicians largely overestimated AIWG manageability using dietary and lifestyle changes. They also reported difficulties accessing alternative management interventions, including a change in antipsychotic and/or pharmacological adjuncts. Participants reported current management guidance is oversimplified, lacks the specificity and scope required, and endorses a 'one-size-fits-all' management approach to an extensively heterogenous side-effect. Participants expressed a preference for collaborative AIWG management and guidance that prioritises early intervention using the range of evidence-based management interventions, tailored according to AIWG risk, participant ability and participant preference. CONCLUSION: Integration of this research into guideline development will help ensure recommendations are relevant and applicable, and that individual preferences are represented.

Medication burden reduction and early clinical benefit through aripiprazole once monthly in schizophrenia patients with polypharmacy.

Antipsychotic polypharmacy is commonly used in clinical settings, with a growing trend in using long-acting injections to mitigate many side effects of polypharmacy. A previous study demonstrated that long-acting aripiprazole once-monthly (AOM) injection increased treatment adherence, restored functionality, and improved symptoms. However, there is insufficient evidence to demonstrate the therapeutic effects of AOM in polypharmacy practice. This observational study aimed to investigate the real-world clinical benefits and effectiveness of AOM by assessing changes in drug dosage, the number of drugs, clinical functioning, psychotic symptoms, and the duration of drug efficacy. Study participants were recruited from eight study sites, with the baseline visit marking the initiation of drug treatment. Clinical and demographic data were collected from medical records at screening, baseline, and months 1, 3, 6, 9, and 12. Over 12 months, we analyzed changes in drug dosage, the number of drugs, and scores of the Positive and Negative Syndrome Scale-6 (PANSS-6), Global Assessment of Functioning (GAF), and Clinical Global Impression-Severity (CGIS). Data from 139 participants were analyzed. Total 12-month antipsychotic doses calculated in chlorpromazine equivalents (CPE) were reduced by 32.6%. A comparison of total monthly antipsychotic doses in CPE between the first and last months showed a 24.6% reduction in the dose. Additionally, the quantity of benzodiazepine tablets/capsules, total benzodiazepine doses calculated in lorazepam equivalents, and quantity of tablets/capsules of mood stabilizers, anticholinergics, and beta blockers were significantly reduced. GAF scores increased by 14.1% over 12 months, and PANSS-6 total scores reduced by 17.3% over 12 months, with significant differences observed from month 1 and baseline, respectively. The scores steadily improved until month 9 compared to those of the previous months, continuing to improve through month 12. The CGI-S score reduced by 14.3% over 12 months, showing a significant decrease from month 1 and a steady improvement until month 6, maintaining this improvement until month 12. In conclusion, this study demonstrated the early effectiveness of AOM in treating Korean patients with schizophrenia on polypharmacy. AOM improved function and clinical symptoms in patients with schizophrenia from treatment onset and caused a decrease in the quantity and dosage of drugs taken by the patients.

An Updated Safety Review of the Relationship Between Atypical Antipsychotic Drugs, the QTc Interval and Torsades de Pointe As: Implications for Clinical Use.

INTRODUCTION: The rising prevalence of psychiatric disorders has resulted in a significant increase in the use of antipsychotic medications. These agents may prolong the corrected QT interval (QTc), running the risk of precipitating ventricular arrhythmias, notably Torsades de Pointes (TdP). Current recommendations vary regarding the optimal approach to safe prescribing practices and QTc surveillance for antipsychotics. This review summarizes the current literature addressing these clinical concerns. AREAS COVERED: The physiologic basis of the QTc interval, mechanisms underlying its susceptibility to pharmacological influence, specific risks associated with atypical antipsychotic agents, and recommendations for safe prescription practices. We performed a literature review using Pubmed and Embase databases, searching for 'antipsychotics' and 'torsades de pointes.' EXPERT OPINION: Finding a safe and universally accepted protocol for prescribing antipsychotics remains a persistent challenge in medicine. Predictive models that integrate clinical history with demographic and ECG characteristics can help estimate an individual's susceptibility to therapy-associated risks, including QTc prolongation. Agents such as ziprasidone and iloperidone are significantly more likely to prolong the QTc interval compared to others such as brexpiprazole, cariprazine, olanzapine, and clozapine. A personalized approach using low-risk medications when clinically feasible, and at the lowest efficacious dose, offers a promising path toward safer antipsychotic prescribing.

Antipsychotic medications are used to treat conditions such as schizophrenia and bipolar disorder; however, they can also affect cardiac electrical conduction. This effect on cardiac function increases the risk of a dangerous heart rhythm, which can potentially be fatal. Patients and doctors need to be aware of and monitor for these potential heart-related side effects, although antipsychotics can be very helpful for mental health conditions.

Polypharmacy to Clozapine Monotherapy in Treatment-Resistant Schizophrenia: A Case Report and Review of the Literature.

This case report discusses a 25-year-old Middle Eastern female with a 14-year history of schizophrenia, managed as an inpatient for nearly eight years. Initially referred to a psychiatrist at age 12, with one-year-long concerns about preoccupation with the idea of having a serious illness, depressed mood, decreased appetite, social withdrawal, and aggression, she underwent multiple admissions, various medication combinations, and electroconvulsive therapy but remained resistant to treatment until clozapine monotherapy was initiated in 2023. After starting clozapine, improvements were noted in speech, communication, and eye contact, though negative symptoms and bouts of aggression persisted. This case highlights the efficacy of clozapine monotherapy in managing treatment-resistant schizophrenia after years of ineffective polypharmacy treatment. The importance of clozapine in treating treatment-resistant schizophrenia cannot be understated. Despite its efficacy, clozapine is often underutilised globally due to concerns about adverse effects and the need for blood monitoring, leading to the overuse of antipsychotic polypharmacy. This polypharmacy is associated with higher adverse event rates, increased costs, and uncertain long-term safety. This case report demonstrates the successful management of treatment-resistant schizophrenia with clozapine monotherapy. The patient's significant improvement supports the need to prioritise clozapine, highlighting its benefits over polypharmacy and advocating for its broader use to enhance patient outcomes.

Long-term metabolic side effects of second-generation antipsychotics in Chinese patients with schizophrenia: A within-subject approach with modelling of dosage effects.

BACKGROUND: Second-generation antipsychotics (SGAs) are commonly used to treat schizophrenia (SCZ), but SGAs may differ in the severity of side effects. Long-term studies are lacking, and previous observational studies have limitations, such as failure to account for confounding factors and short follow-up durations. AIMS: To compare the long-term anthropometric and metabolic side effects of seven SGAs in a Chinese population, using a within-subject approach to reduce the risk of confounding. METHOD: We collected longitudinal data of SGA prescriptions, concomitant medications, fasting blood glucose (BG), lipid profiles, and BMI in a cohort of 767 patients with SCZ, with follow-up lasting up to 18.7 years (median ∼6.2 years). A total of 192,152 prescription records were retrieved, with 27,723 metabolic measures analysed. Linear mixed models were used to estimate the effects of SGA on BG, lipid profiles and BMI. Besides studying the effects of SGA medications (as binary predictors), we also investigated the effects of SGA dosage on metabolic profiles. RESULTS: Considering SGA medications as binary predictors, clozapine and olanzapine were associated with the most substantial worsening of lipid profiles and BMI. A significant increase in BG was observed with clozapine only. Amisulpride, paliperidone and quetiapine were associated with worsened lipid profiles and increased BMI. Conversely, aripiprazole was associated with significant improvement in lipid profiles but a small increase in BMI. When SGA dosage was considered, the model showed consistent results overall. At the minimum effective dose, clozapine was associated with the most severe metabolic side effects, followed by olanzapine. Risperidone and aripiprazole showed the least metabolic side effects, with aripiprazole being significantly associated with lower lipids. CONCLUSIONS: This study clarified the long-term and dose-dependent effects of different SGAs on anthropometric and metabolic parameters in Chinese SCZ patients. Our findings may inform clinicians and SCZ patients of SGA choices.

Efficacy and acceptability of long-acting antipsychotics in acutely ill individuals with schizophrenia-spectrum disorders: A systematic review and network meta-analysis.

To assess the effect of Long-acting injectable (LAI) antipsychotics in acutely ill patients, we systematically searched major databases for randomized controlled trials (RCTs) comparing LAIs with other LAIs, oral antipsychotics, or placebo in acutely symptomatic adults with schizophrenia-spectrum disorders. Data were analyzed with a random-effects network meta-analysis. Co-primary outcomes were efficacy (mean change in psychopathology rating scales) and acceptability (all-cause discontinuations) at study endpoint. Of 25 RCTs, 19 studies tested second-generation LAIs (SGA-LAIs) and six first-generation LAIs (FGA-LAIs). Due to a disconnected network, FGA-LAIs were analyzed separately, with poor data quality. The SGA-LAIs network included 8,418 individuals (males=63%, mean age=39.3 years). All SGA-LAIs outperformed placebo in reducing acute symptoms at study endpoint (median follow-up=13 weeks). They were more acceptable than placebo with the only exception of olanzapine, for which no differences with placebo emerged. Additionally, we distinguished between different LAI formulations of the same antipsychotic to explore potential pharmacokinetic differences. Most formulations outperformed placebo in the very short-term (2 weeks or less), regardless of the need for initial oral supplementation. SGA-LAIs are evidence-based treatments in acutely ill individuals with schizophrenia-spectrum disorders. Findings support the use of SGA-LAIs to manage psychopathology and improve adherence right from the acute phases of illness.

[Pharmacotherapy of schizophrenia: clinical and some age-related aspects]. / Farmakoterapiya shizofrenii: klinicheskie i nekotorye vozrastnye aspekty.

The article discusses modern approaches to the rational choice of therapy for schizophrenia in accordance with the principles of personalized medicine. Clinical markers for determining the optimal treatment tactics are considered depending on the syndromic features and stereotype of the course of the disease, and the possibility of justified combination therapy with drugs of different pharmacological classes. The specifics of the treatment of schizophrenia in childhood/adolescence and adult are discussed, including the basic principles of choosing drug classes, daily doses and drug therapy tactics.

Revisiting diabetes risk of olanzapine versus aripiprazole in serious mental illness care.

BACKGROUND: Exposure to second-generation antipsychotics (SGAs) carries a risk of type 2 diabetes, but questions remain about the diabetogenic effects of SGAs. AIMS: To assess the diabetes risk associated with two frequently used SGAs. METHOD: This was a retrospective cohort study of adults with schizophrenia, bipolar I disorder or severe major depressive disorder (MDD) exposed during 2008-2013 to continuous monotherapy with aripiprazole or olanzapine for up to 24 months, with no pre-period exposure to other antipsychotics. Newly diagnosed type 2 diabetes was quantified with targeted minimum loss-based estimation; risk was summarised as the restricted mean survival time (RMST), the average number of diabetes-free months. Sensitivity analyses were used to evaluate potential confounding by indication. RESULTS: Aripiprazole-treated patients had fewer diabetes-free months compared with olanzapine-treated patients. RMSTs were longer in olanzapine-treated patients, by 0.25 months [95% CI: 0.14, 0.36], 0.16 months [0.02, 0.31] and 0.22 months [0.01, 0.44] among patients with schizophrenia, bipolar I disorder and severe MDD, respectively. Although some sensitivity analyses suggest a risk of unobserved confounding, E-values indicate that this risk is not severe. CONCLUSIONS: Using robust methods and accounting for exposure duration effects, we found a slightly higher risk of type 2 diabetes associated with aripiprazole compared with olanzapine monotherapy regardless of diagnosis. If this result was subject to unmeasured selection despite our methods, it would suggest clinician success in identifying olanzapine candidates with low diabetes risk. Confirmatory research is needed, but this insight suggests a potentially larger role for olanzapine in the treatment of well-selected patients, particularly for those with schizophrenia, given the drug's effectiveness advantage among them.

Exploring the Relationships Between Antipsychotic Dosage and Voice Characteristics in Relation to Extrapyramidal Symptoms.

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.

Self-prescription with psychotropic medications by healthcare professionals working at mental health institutions in Saudi Arabia.

BACKGROUND: Healthcare professionals who work in mental health institutions are more exposed to psychotropic medications than those in other healthcare institutions and are, therefore, more likely to self-prescribe. Self-prescription is a concerning phenomenon because of the potential for medication misuse, drug interaction, addiction, and other social, physical, and psychological consequences. This study investigated the prevalence of self-prescription of psychotropic medications and the most common self-prescribed psychotropic medications by healthcare professionals in mental health institutions in Saudi Arabia. It also aimed to determine the possible side effects and factors associated with self-prescription of psychotropic medications. MATERIALS AND METHODS: This was a cross-sectional study using an electronic survey consisting of a researcher-designed checklist, targeting healthcare professionals in mental health institutions in Saudi Arabia. The independent variables were sex, nationality, occupation, place of residence, place of work, previous diagnosis of mental illness, marital, and living status. Data were analyzed, using SPSS, and frequency distribution and percentages were calculated. Chi-square test was employed to determine association between self-prescription and various independent variables. RESULTS: The final sample size was 588; 9.5% healthcare professionals working at mental health institutions in Saudi Arabia admitted to self-prescription with psychotropic medications. Almost half of those who admitted to self-prescription (48.2%) and about 1/4 (23.2%) self-prescribed selective serotonin reuptake inhibitors and benzodiazepines, respectively. The most commonly reported side effects of self-prescription were gastrointestinal symptoms and drowsiness. The study also suggested that males were significantly more prone to self-prescribing than females (P < 0.001). CONCLUSION: To our knowledge, this is the first study in Saudi Arabia to assess the self-prescription of psychotropic medications by healthcare professionals at mental health institutions. This study is important for decision-makers in their planning and updating of prescription policies. It is also equally important to spread awareness among healthcare professionals about the consequences of self-prescription.

Impact of federal antipsychotic use policy in nursing homes on new diagnoses for approved indications in dementia residents.

BACKGROUND: Federal policies targeting antipsychotic use among nursing home (NH) residents may have increased reporting of diagnoses for approved uses, including schizophrenia, Tourette's syndrome, and Huntington's Disease (called "exclusionary diagnoses" because they exclude residents from the antipsychotic quality metric). We assessed changes in new exclusionary diagnoses among long-stay NH admissions specifically with dementia following federal policies. METHODS: Retrospective, quarterly, interrupted time-series analysis (2009-2018) of new long-stay NH residents with dementia and no exclusionary diagnoses reported before NH admission. The National Partnership and the addition of facility level antipsychotic use to the Five Star Quality Rating system were key time exposures. Outcome was quarterly facility level predicted percentage of exclusionary diagnoses within 2 years of admission stratified by NH characteristics. RESULTS: For 264,095 long-stay admissions, mean percentage of new exclusionary diagnoses was 2.2% before the Partnership. After the Partnership, there was an unadjusted increase in the percentage over time (slope change, 0.044, p = 0.018), but the percentage never exceeded 2.9%. The Partnership contributed to a one-time decrease in diagnoses in NHs with an intermediate percentage of Black residents (-1.29%, p = 0.004). Before the Partnership, diagnoses were increasing among not-for-profit relative to for-profit NHs (0.044; p = 0.012), but after the Partnership, the pattern reversed. For-profit NHs saw an increase (+0.034, p = 0.002); not-for-profit NHs experienced a decrease (-0.014, p = 0.039). Quality Rating modifications had no significant effect. CONCLUSIONS: Exclusionary diagnosis reporting among long-stay NH residents with dementia, the group most at risk from antipsychotics, did not increase in response to federal policies. Evaluation of reasons for the observed increase in exclusionary diagnoses among non-dementia NH residents is warranted along with continued attention to how to incentivize the appropriate use of medications in residents with dementia that is crucial for high-quality NH care.

Pharmacological Treatment of Cognitive Impairment Associated With Schizophrenia: State of the Art and Future Perspectives.

Cognitive Impairment Associated with Schizophrenia (CIAS) represents one of the core dimensions of Schizophrenia Spectrum Disorders (SSD), with an important negative impact on real-world functional outcomes of people living with SSD. Treatment of CIAS represents a therapeutic goal of considerable importance, and while cognition-oriented evidence-based psychosocial interventions are available, effective pharmacological treatment could represent a game-changer in the lives of people with SSD. The present critical review reports and discusses the evidence regarding the effects of several pharmacological agents that are available in clinical practice or are under study, commenting on both current and future perspectives of CIAS treatment. In particular, the effects on CIAS of antipsychotic medications, anticholinergic medications, benzodiazepines, which are currently commonly used in the treatment of SSD, and of iclepertin, d-serine, luvadaxistat, xanomeline-trospium, ulotaront, anti-inflammatory molecules, and oxytocin, which are undergoing regulatory trials or can be considered as experimental agents, will be reported and discussed. Currently, available pharmacological agents do not appear to provide substantial benefits on CIAS, but accurate management of antipsychotic medications and avoiding treatments that can further exacerbate CIAS represent important strategies. Some molecules that are currently being investigated in Phase 2 and Phase 3 trials have provided very promising preliminary results, but more information is currently required to assess their effectiveness in real-world contexts and to provide clear recommendations regarding their use in clinical practice. The results of ongoing and future studies will reveal whether any of these molecules represents the awaited pharmacological game-changer in the treatment of CIAS.

Identifying clinically relevant agranulocytosis in people registered on the UK clozapine Central Non-Rechallenge Database: retrospective cohort study.

BACKGROUND: Clozapine is the most effective antipsychotic for treatment-resistant psychosis. However, clozapine is underutilised in part because of potential agranulocytosis. Accumulating evidence indicates that below-threshold haematological readings in isolation are not diagnostic of life-threatening clozapine-induced agranulocytosis (CIA). AIMS: To examine the prevalence and timing of CIA using different diagnostic criteria and to explore demographic differences of CIA in patients registered on the UK Central Non-Rechallenge Database (CNRD). METHOD: We analysed data of all patients registered on the UK Clozaril® Patient Monitoring Service Central Non-Rechallenge Database (at least one absolute neutrophil count (ANC) < 1.5 × 109/L and/or white blood cell count < 3.0 × 109/L) between May 2000 and February 2021. We calculated prevalence rates of agranulocytosis using threshold-based and pattern-based criteria, stratified by demographic factors (gender, age and ethnicity). Differences in epidemiology based on rechallenge status and clozapine indication were explored. The proportion of patients who recorded agranulocytosis from a normal ANC was explored. RESULTS: Of the 3029 patients registered on the CNRD with 283 726 blood measurements, 593 (19.6%) were determined to have threshold-based agranulocytosis and 348 (11.4%) pattern-based agranulocytosis. In the total sample (75 533), the prevalence of threshold-based agranulocytosis and pattern-based agranulocytosis was 0.8% and 0.5%, respectively. The median time to threshold-based agranulocytosis was 32 weeks (IQR 184) and 15 (IQR 170) weeks for pattern-based agranulocytosis. Among age groups, the prevalence of pattern-based agranulocytosis and threshold-based agranulocytosis was highest in the >48 age group. Prevalence rates were greatest for White (18%) and male individuals (13%), and lowest for Black individuals (0.1%). The proportion of people who were determined to have pattern-based agranulocytosis without passing through neutropenia was 70%. CONCLUSIONS: Threshold-based definition of agranulocytosis may over-diagnose CIA. Monitoring schemes should take into consideration neutrophil patterns to correctly identify clinically relevant CIA. In marked contrast to previous studies, CIA occurred least in Black individuals and most in White individuals.

Multiple Adverse Reactions Associated With the Use of Second-Generation Antipsychotics in People With Alzheimer's Disease: A Pharmacovigilance Analysis Based on the FDA Adverse Event Reporting System.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative condition leading to memory loss, cognitive impairment, and neuropsychiatric symptoms. Second-generation antipsychotics (SGAs) are commonly used to manage these neuropsychiatric symptoms, but their safety profile in patients with AD requires further investigation. OBJECTIVE: The objective was to evaluate the safety of SGAs in patients with AD by analyzing adverse drug reactions (ADRs) using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: This study conducted a comprehensive analysis of FAERS data from 2014 to 2023, focusing on ADRs in patients with AD treated with SGAs such as risperidone, quetiapine, olanzapine, clozapine, and aripiprazole. Descriptive, disproportionality, time, and dose analysis were performed using the Bayesian confidence propagation neural network, Weibull, and physiologically based pharmacokinetic model. RESULTS: Out of 1289 patients with AD treated with SGAs, the most common ADRs involved the nervous system, gastrointestinal system, and cardiac disorders. Disproportionality analysis identified significant positive signals in cardiac, renal, and vascular systems. Quetiapine, risperidone, and olanzapine showed more positive signals compared with clozapine and aripiprazole. Time analysis indicated that cardiovascular ADRs occurred randomly, whereas renal ADRs increased with prolonged use. Dose analysis suggested that small doses of SGAs did not elevate the risk of multiple cardiac, renal, or vascular ADRs. CONCLUSION AND RELEVANCE: The study underscores the importance of monitoring for ADRs, particularly in the cardiac and renal systems, when using SGAs in patients with AD. Future research incorporating more comprehensive clinical data is warranted to support safe and rational drug utilization.