A Comprehensive Guide to Long-Acting Injectable Antipsychotics for Primary Care Clinicians.

We propose a paper that provides education on commonly used long-acting injectable antipsychotics (LAIs) to improve primary care based mental health interventions in patients with severe mental illnesses (SMIs) such as schizophrenia, schizoaffective disorder, and bipolar disorders. With the expanding interface of primary care and psychiatry across all healthcare settings, it has become increasingly important for primary care clinicians to have a broader understanding of common psychiatric treatments, including LAIs. Long-acting injectable antipsychotics have been shown to be helpful in significantly improving treatment adherence, preventing disease progression, improving treatment response, decreasing readmission rates, and reducing social impairment. We discuss evidence-based indications and guidelines for use of long-acting injectable antipsychotics. We provide an overview of the treatment of SMI with LAIs, mainly focusing on the most commonly used long-acting injectable antipsychotics, advantages and disadvantages of each, along with outlining important clinical pearls for ease of practical application. Equipped with increased familiarity and understanding of these essential therapies, primary care clinicians can better facilitate early engagement with psychiatric care, promote more widespread use, and thus significantly improve the wellbeing and quality of life of patients with severe mental illness.

Health-Care Utilisation and Costs of Transition from Paliperidone Palmitate 1-Monthly to 3-Monthly Treatment for Schizophrenia: A Real-World, Retrospective, 24-Month Mirror-Image Study.

Introduction: Poor adherence to antipsychotics in patients with schizophrenia is a leading cause of relapse and functional deterioration. Long-acting injectable paliperidone may reduce relapse risks, health-care utilisation, and health-care costs in these patients. Methods: In this 24-month mirror-image study, we compared health-care utilization and costs before and after the initiation of paliperidone palmitate 3-monthly (PP3M) treatment in patients with schizophrenia spectrum disorders. Before the initiation of PP3M, the patients received paliperidone 1-monthly (PP1M) treatment. The primary study outcomes were changes in health-care utilisation and costs over the study period. Results: This study included 34 patients with schizophrenia spectrum disorders. During the 12-months period after the initiation of PP3M treatment, the mean duration of hospitalisation decreased from 57.7 to 28.5 days (p = 0.03). Moreover, significant reductions were noted in emergency room visits (PP1M vs PP3M: 0.3 vs 0.0, respectively; p = 0.05) and health-care costs (PP1M vs PP3M: 107,328.8 vs 57,848.6, respectively; p = 0.03). Conclusion: PP3M may significantly reduce hospitalisation duration, emergency room visits, and health-care costs in patients with schizophrenia.

Impact of Demographics and Insurance Coverage on Schizophrenia Treatment and Healthcare Resource Utilization Within an Integrated Healthcare System.

Purpose: Little is known about the impact of health disparities on antipsychotic treatment and healthcare resource utilization (HRU) among patients with schizophrenia. The objective of this analysis is to examine treatment patterns and HRU by age, race/ethnicity, and insurance coverage among patients with schizophrenia in an integrated delivery network (IDN). Patients and Methods: This cross-sectional study used electronic health record data from MedStar Health, an IDN in the Baltimore-Washington, DC, area. Patients were aged ≥18 years and had ≥2 outpatient encounters or ≥1 hospitalization with a diagnosis of schizophrenia between January 1, 2017 and March 31, 2021. Outcomes assessed included oral antipsychotic prescriptions, long-acting injectable antipsychotic (LAI) utilization, hospitalizations, emergency department (ED) visits, and outpatient visits. Analyses compared subgroups based on age, race/ethnicity (non-Hispanic Black, non-Hispanic White, and other), and type of insurance coverage at index (Medicare, Medicaid, and other) during 12 months of follow-up. Results: A total of 78.1% of patients had ≥1 prescription for an antipsychotic and 69.1% received ≥1 second-generation antipsychotic. Second-generation long-acting injectables (SGA LAI) were utilized by 9.0% of patients, with the elderly and Medicaid beneficiaries having the lowest SGA LAI utilization. Overall, 61.7% of patients had ≥1 hospitalization, 56.4% had ≥1 outpatient visit, and 50.5% had ≥1 ED visit. Hospitalizations and ED visits were most common in those 18 to 24 years of age and in Medicaid beneficiaries, whereas outpatient visits were more common for the elderly and Medicare beneficiaries. Conclusion: At the population level, the results indicate widespread underprescription/underutilization of antipsychotics that have been shown to improve clinical and economic outcomes in patients with schizophrenia, particularly SGA LAI. Within specific subpopulations, disparities in treatment selection and HRU were observed, suggesting the need for increased attention to at-risk groups to ensure consistent quality of care regardless of age, race/ethnicity, or insurance coverage.

Association of antipsychotic formulations with sudden cardiac death in patients with schizophrenia: A nationwide population-based case-control study.

The aim of this study was to clarify the association between various antipsychotic formulations-oral-daily antipsychotics (OAPs), long-acting injectable antipsychotics (LAIs), and their combination-and the risk of sudden cardiac death (SCD). We conducted a nationwide population-based case-control study using data from 2011 to 2020 from the National Health Insurance Research Database and multiple-cause-of-death data from Taiwan. The study included patients with a new diagnosis of schizophrenia who were followed for SCD occurrence until 2020. Cases and controls were frequency-matched at a 1:4 ratio by age, sex, and year of new schizophrenia diagnosis. Compared with the use of OAP monotherapy, the use of LAI and OAP combination (OR = 1.91) and LAI monotherapy (OR = 1.45) were associated with an increased risk of SCD. Additionally, cardiovascular comorbidities (adjusted OR = 11.15) were identified as a significant risk factor for SCD. This study revealed the following hierarchy of SCD risk associated with antipsychotic formulations (listed from lowest to highest risk): nonuse of antipsychotics, OAP monotherapy, LAI monotherapy, and their combination. These findings underscore the importance of assessing cardiovascular disease history before LAIs are prescribed to patients with schizophrenia and indicate that physicians should avoid prescribing combined antipsychotics when using LAIs.

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.

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.

Long-Acting Injectable Antipsychotic Initiation in Child and Adolescent Patients with Psychiatric Disorders.

Objectives: There are currently no long-acting injectable antipsychotics (LAIAs) that are approved by the Food and Drug Administration for use in child and adolescent patients, however these agents are used off-label for the treatment of various psychiatric disorders. This study aims to describe the initiation and maintenance dosing strategies of LAIAs in child and adolescent psychiatry inpatients. Methods: This was a single-site retrospective chart review of patients less than 18 years of age initiated on an LAIA during an acute psychiatric hospitalization between October 1, 2015, and October 31, 2022. Patient demographics and hospital encounter information were collected and analyzed using descriptive statistics. Results: Of the 6402 unique pediatric patients discharged from the acute psychiatric hospital within the specified timeframe, 45 (0.7%) were newly initiated on an LAIA. The average age was 15.6 years (range 10-17), with a greater proportion of male (n = 26, 57.8%) and Black or African American (n = 27, 60%) patients. The LAIA agents prescribed included paliperidone palmitate (n = 21, 46.7%), aripiprazole monohydrate (n = 15, 33.3%), aripiprazole lauroxil (n = 7, 15.6%), haloperidol decanoate (n = 1, 2.2%), and risperidone microspheres (n = 1, 2.2%). Primary diagnosis via International Classification of Diseases-10 code at discharge included schizophrenia spectrum and other psychotic disorders (n = 19, 42.2%); bipolar disorder (n = 14, 31.1%); disruptive, impulse control, and conduct disorders (n = 6, 13.3%); autistic disorder (n = 5, 11.1%); and attention-deficit/hyperactivity disorder (n = 1, 2.2%). Seventeen patients (37.8%) received a loading dose regimen and/or a maintenance dose regimen that differed from adult package-insert dosing. The mean length of stay was 23.7 days, and 14 patients (31.1%) were readmitted to the psychiatric hospital within 6 months of discharge. The mean number of days to readmission was 71.9 days. Conclusions: This retrospective study is the first to focus on LAIA initiation and maintenance dosing strategies of multiple agents in both a child and adolescent patient population. Further research is required to evaluate the impact of LAIAs on clinical outcomes in this patient population.

Efficacy and safety of long-acting injectable versus oral antipsychotics in the treatment of patients with early-phase schizophrenia-spectrum disorders: a systematic review and meta-analysis.

Background: Long-acting injectable antipsychotics (LAIs) have advantages over oral antipsychotics (OAPs) in preventing relapse and hospitalization in chronically ill patients with schizophrenia-spectrum disorders (SSDs), but evidence in patients with first-episode/recent-onset, that is, early-phase-SSDs is less clear. Objectives: To assess the relative medium- and long-term efficacy and safety of LAIs versus OAPs in the maintenance treatment of patients with early-phase SSDs. Method: We searched major electronic databases for head-to-head randomized controlled trials (RCTs) comparing LAIs and OAPs for the maintenance treatment of patients with early-phase-SSDs. Design: Pairwise, random-effects meta-analysis. Relapse/hospitalization and acceptability (all-cause discontinuation) measured at study-endpoint were co-primary outcomes, calculating risk ratios (RRs) with their 95% confidence intervals (CIs). Subgroup analyses sought to identify factors moderating differences in efficacy or acceptability between LAIs and OAPs. Results: Across 11 head-to-head RCTs (n = 2374, median age = 25.2 years, males = 68.4%, median illness duration = 45.8 weeks) lasting 13-104 (median = 78) weeks, no significant differences emerged between LAIs and OAPs for relapse/hospitalization prevention (RR = 0.79, 95%CI = 0.58-1.06, p = 0.13) and acceptability (RR = 0.92, 95%CI = 0.80-1.05, p = 0.20). The included trials were highly heterogeneous regarding methodology and patient populations. LAIs outperformed OAPs in preventing relapse/hospitalization in studies with stable patients (RR = 0.65, 95%CI = 0.45-0.92), pragmatic design (RR = 0.67, 95%CI = 0.54-0.82), and strict intent-to-treat approach (RR = 0.64, 95%CI = 0.52-0.80). Furthermore, LAIs were associated with better acceptability in studies with schizophrenia patients only (RR = 0.87, 95%CI = 0.79-0.95), longer illness duration (RR = 0.88, 95%CI = 0.80-0.97), unstable patients (RR = 0.89, 95%CI = 0.81-0.99) and allowed OAP supplementation of LAIs (RR = 0.90, 95%CI = 0.81-0.99). Conclusion: LAIs and OAPs did not differ significantly regarding relapse prevention/hospitalization and acceptability. However, in nine subgroup analyses, LAIs were superior to OAPs in patients with EP-SSDs with indicators of higher quality and/or pragmatic design regarding relapse/hospitalization prevention (four subgroup analyses) and/or reduced all-cause discontinuation (five subgroup analyses), without any instance of OAP superiority versus LAIs. More high-quality pragmatic trials comparing LAIs with OAPs in EP-SSDs are needed. Trial registration: CRD42023407120 (PROSPERO).

OBJECTIVE: We aimed to uncover whether LAIs or regular antipsychotic pills demonstrate better outcomes over the medium and long term for individuals in the early stages of schizophrenia. METHOD: We scrutinized several studies comparing LAIs to regular pills in treating early-stage schizophrenia. Employing a combined analysis, we assessed factors such as preventing relapses and hospitalizations, as well as patient treatment adherence. DESIGN: We combined different study results in one unique analysis. We delved into whether LAIs surpassed regular pills in preventing relapses and hospitalizations and in patient treatment adherence. RESULTS: In our study of 11 trials involving over 2000 participants, we observed that LAIs and regular antipsychotic pills were generally comparable regarding preventing relapses, hospitalizations, and treatment adherence. However, on closer inspection, LAIs appeared slightly more effective for specific groups in the early stages of schizophrenia. CONCLUSION: While LAIs and regular antipsychotic pills showed similar results for most individuals in the early stages of schizophrenia, our findings hint at the possibility that LAIs might have a slight edge for certain groups. Nevertheless, we emphasize the need for more high-quality studies to gain a clearer understanding. REGISTRATION: This study is registered under CRD42023407120 (PROSPERO).

Comparing long-acting injections and pills for early schizophrenia: a study review and combined analysis Background: We explored whether antipsychotics long-acting injections (LAIs) might outperform regular antipsychotics pills for people dealing with early-stage conditions like schizophrenia. While LAIs have clear benefits for those with long-term challenges, their effectiveness for those just starting to grapple with these issues is less certain.

Barriers to long-acting injectable atypical antipsychotic use in Japan: Insights from a comparative psychiatrist survey.

AIMS: To investigate the negative attitudes of Japanese psychiatrists toward atypical long-acting injectable (LAI) antipsychotics, which are the current mainstream LAIs in Japan. METHODS: We surveyed 69 Japanese psychiatrists using a 5-point Likert scale to assess their attitudes toward atypical LAI antipsychotics. Our assessment referenced concerns identified in a study conducted in Japan a decade ago, which found significant differences when compared with a survey of German psychiatrists. We also identified the factors influencing these negative attitudes. Additionally, the results were compared with those of previous Japanese and German studies. RESULTS: More than 50% of Japanese psychiatrists expressed negative attitudes toward atypical LAI antipsychotics in various areas. These concerns included apprehensions about cost, reluctance to recommend them initially, pain from injections, complexity of switching to LAI, usage in first-episode cases, and sufficient medication adherence with oral drugs. In all three studies, cost and adequate adherence to oral medication were concerns that exceeded the average of the three negative comments. Age and experience in psychiatry influenced the psychiatrists' attitudes toward using these drugs in first-episode cases. CONCLUSIONS: These findings shed light on the reasons for the underutilization of atypical LAI antipsychotics and suggest opportunities to enhance their appropriate use in clinical settings.

Long-acting second-generation injectable antipsychotics for the maintenance treatment of bipolar disorder: a narrative review.

INTRODUCTION: Non-adherence to medication significantly affects bipolar disorder outcomes. Long-Acting Injectable antipsychotics show promise by ensuring adherence and averting relapses. AREAS COVERED: This narrative review sought to evaluate the efficacy of second-generation injectable antipsychotics in bipolar disorder through searches in Embase, MEDLINE, and PsycInfo for randomized controlled trials and mirror-image studies.Risperidone and aripiprazole Long-Acting Injectables demonstrated effectiveness in preventing mood recurrences compared to placebos in adults with bipolar disorder. They showed superiority in preventing mania/hypomania relapses over placebos but did not appear to significantly outperform active oral controls. Notably, active controls seem to be more effective in preventing depression relapses than Long-Acting Injectables. Mirror-Image studies point toward the reduction of hospitalization rates following LAI initiation. EXPERT OPINION: The available evidence points thus toward the efficacy of LAIs, especially in managing manic episodes and reducing hospitalizations, The current evidence does not however immediately support prioritizing LAIs over oral medications in bipolar disorder treatment. More high-quality studies, especially comparing LAIs directly with active controls, are crucial to gain a comprehensive understanding of their efficacy. These findings highlight the need for further research to guide clinicians in optimizing treatment strategies for bipolar disorder.

Therapeutic Outcomes of Treatment With Long-Acting Injectable Antipsychotics in Forensic Populations With Schizophrenia-Spectrum Diagnoses.

The advantages of long-acting injectable antipsychotics (LAIs) in schizophrenia are well studied. However, forensic involvement is common in schizophrenia, and incarcerated individuals are often excluded from clinical trials. Nonadherence and oral medication diversion in forensic populations with schizophrenia, and the relationship between antipsychotic nonadherence and crime support LAI utilization in this subset of patients. Yet, federal regulations limit data generation in forensic populations. This review characterizes data on therapeutic outcomes of LAIs in correctional populations with schizophrenia-spectrum diagnoses. A search for primary literature was conducted in PubMed. Favorable effects of LAIs were observed on adherence, psychiatric symptomatology, patient satisfaction, health care costs, and frequency of criminal charges. Data were primarily retrospective and included small samples and individuals with historical versus current forensic involvement. Although limited, available literature and insights into the correctional system suggest advantages to LAI use in forensic populations. Barriers to conducting research in correctional settings must be addressed to facilitate further data generation.

Efficacy, acceptability and side-effects of oral versus long-acting- injectables antipsychotics: Systematic review and network meta-analysis.

Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment of schizophrenia. We conducted a systematic review and frequentist network meta-analysis of randomized-controlled trials (RCTs), focusing on adult patients in the acute phase of schizophrenia. Interventions were risperidone, paliperidone, aripiprazole, olanzapine, and placebo, administered either orally or as LAI. We synthesized data on overall symptoms, complemented by 17 other efficacy and tolerability outcomes. Confidence in the evidence was assessed with the Confidence-in-Network-Meta-Analysis-framework (CINeMA). We included 115 RCTs with 25,550 participants. All drugs were significantly more efficacious than placebo with the following standardized mean differences and their 95 % confidence intervals: olanzapine LAI -0.66 [-1.00; -0.33], risperidone LAI -0.59[-0.73;-0.46], olanzapine oral -0.55[-0.62;-0.48], aripiprazole LAI -0.54[-0.71; -0.37], risperidone oral -0.48[-0.55;-0.41], paliperidone oral -0.47[-0.58;-0.37], paliperidone LAI -0.45[-0.57;-0.33], aripiprazole oral -0.40[-0.50; -0.31]. There were no significant efficacy differences between LAIs and oral formulations. Sensitivity analyses of the primary outcome overall symptoms largely confirmed these findings. Moreover, some side effects were less frequent under LAIs than under their oral counterparts. Confidence in the evidence was moderate for most comparisons. LAIs are efficacious for acute schizophrenia and may have some benefits compared to oral formulations in terms of side effects. These findings assist clinicians with insights to weigh the risks and benefits between oral and injectable agents when treating patients in the acute phase.

Long-acting injectable antipsychotics as maintenance therapy for schizophrenia during the COVID-19 pandemic: A micro-narrative review.

The coronavirus disease pandemic has presented healthcare systems with unprecedented challenges globally and substantially impacted the management of chronic diseases such as schizophrenia. This narrative review highlights the usefulness of long-acting injectable antipsychotics (LAIs) as maintenance therapy for patients with schizophrenia during the pandemic. The analysis of relevant literature and psychiatric survey data revealed diverse trends in LAIs prescription and patient adherence with oral antipsychotics. Although some studies have reported a decrease in LAIs prescriptions owing to pandemic-related disruptions, others have suggested stable patient adherence with oral antipsychotics. Approximately 70% of Japanese psychiatrists reported an increase in schizophrenia relapse rates in a survey, underscoring the critical role of LAIs in maintaining therapeutic stability. The potential benefits of LAIs with extended dosing intervals have been highlighted, including improving oral medication adherence and reducing the frequency of hospital visits. In conclusion, this review emphasizes the continued need for uninterrupted LAIs therapy in conjunction with community and home-based care despite the disruptions caused by the coronavirus disease pandemic. Further development of LAIs maintenance therapy strategies considering the ongoing pandemic and potential future public health emergencies are required.

Preliminary data from a 4-year mirror-image and multicentre study of patients initiating paliperidone palmitate 6-monthly long-acting injectable antipsychotic: the Paliperidone 2 per Year study.

Background: Paliperidone palmitate 6-monthly (PP6M) is the first long-acting antipsychotic injectable (LAI) to allow for only two medication administrations per year, though there is presently limited insight into its effectiveness and potential added value in real clinical practice conditions. Objectives: To present our ongoing study and draw its preliminary data on patient characteristics initiating PP6M and adherence during the first year of treatment. Methods: The paliperidone 2 per year (P2Y) study is a 4-year, multicentre, prospective mirror-image pragmatic study taking place at over 20 different sites in Europe. The mirror period covers 2 years either side of the PP6M LAI initiation. Retrospective data for the previous 2 years are collected for each patient from the electronic health records. Prospective data are recorded at baseline, 6, 12, 18 and 24 months of drug administration and also cover information on concomitant psychiatric medication, relapses, hospital admissions, side effects, discontinuation and its reasons. Meanwhile, here we present preliminary data from the P2Y study at basal and 6-month period (first and second PP6M administration). Results: At the point of PP6M initiation, the most frequent diagnosis was schizophrenia (69%), the clinical global impression scale mean score was 3.5 (moderately markedly ill) and the rate of previous hospital admissions per patient and year was 0.21. PP6M was initiated after a median of 3-4 years on previous treatment: 146 (73%) from paliperidone palmitate 3-monthly, 37 (19%) from paliperidone palmitate 1-monthly and 17 (9%) from other antipsychotics. The mean dose of the first PP6M was 1098.9 mg. The retention rate at 6 months and 1 year of treatment on PP6M in our cohort was 94%. Conclusion: Patient and clinician preference for LAIs with longer dosing intervals was the main reason for PP6M initiation/switching resulting in high treatment persistence. Future data are needed to evaluate the full impact of PP6M in clinical practice.

Racial and ethnic differences in patterns of use and discontinuation of long-acting injectable antipsychotics using Medicaid claims data.

Introduction: In general, racial and ethnic differences exist in antipsychotic prescription practices. However, little is known about such differences between individual long-acting injectable (LAI) antipsychotic formulations, specifically. This study's primary objective was to determine racial and ethnic differences among LAI antipsychotic use. Secondary objectives were to identify if discontinuation rates differed between agents and by race or ethnicity. Methods: International Classification of Diseases, 10th edition (ICD-10) codes were used to identify patients with schizophrenia and related disorders (18-64 years) who received an LAI antipsychotic between 2016 and 2020 using Merative Multi-State Medicaid databases. Using National Drug Code numbers for LAI antipsychotics, pharmacy claims were identified and data analyzed. Cochran-Mantel-Haenszel tests and odds ratio estimators were used to investigate conditional association between race or ethnicity and medication, while controlling for age, sex, health plan, and prescription year. Kaplan-Meier survival curves were examined, and stratified log-rank tests were conducted to compare the time until discontinuation distributions by race or ethnicity. Results: The analysis included 37 712 patients. Blacks received an LAI first-generation antipsychotic more often than Whites (OR: 1.64, 95% CI: [1.56, 1.73], Hispanics (OR: 1.46, 95% CI: [1.21, 1.75]) and others (OR: 1.44, 95% CI: [1.20, 1.73]). Aside from fluphenazine decanoate showing earlier discontinuation rates for Whites over Blacks (P = .02), no significant differences in discontinuation across race or ethnicity were identified. Discussion: Despite no significant differences in second-generation antipsychotic LAI discontinuation rates between Blacks and other racial or ethnic groups, Blacks received second-generation antipsychotic LAIs significantly less often than other groups. Further studies are needed to determine why differences may be occurring.

Long-Acting Injectable Antipsychotic Treatment for Schizophrenia in Asian Population: A Scoping Review.

Evidence of comparative benefits of long-acting injectable (LAI) antipsychotics in Asian patients with schizophrenia has been inconsistent. This scoping review aimed to synthesize the current evidence in the past ten years and provide an overview of efficacy, safety, treatment adherence, patient attitudes, and healthcare resource utilization of LAI in this population. A systematic search was conducted with a pre-defined search strategy in six electronic databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang, PubMed, Embase, CINAHL, and PsycArticles. A total of 46 studies were included, including 15 cohort studies, 13 single-arm trials, 10 randomized controlled trials, four mirror-image studies, three cross-sectional studies, and one controlled clinical trial. Paliperidone palmitate once-monthly injection (27/46) and risperidone LAI (14/46) were the most frequently investigated LAIs. Compared with oral antipsychotic medications (OAMs), LAIs demonstrated a lower rate of relapse/hospitalization and comparable improvement in efficacy. Adverse events (AEs) were similar between LAIs and OAMs, although types and incidence varied. Significant reduction in the length of hospitalization and number of outpatient visits/inpatient admission was observed after initiation of LAIs. These findings suggest that LAI demonstrated comparable efficacy and safety among Asian populations with schizophrenia in comparison to OAMs. Better adherence and lower relapse were observed in patients receiving LAIs from published evidence. Future research is warranted to better understand the comprehensive performance of LAI in specific population or context.

Cumulative Clinical Experience of the Use of Paliperidone Palmitate 3-Monthly Long-Acting Injection in the Treatment of Schizophrenia: A Critical Appraisal.

Paliperidone palmitate 3-monthly (PP3M), an approved maintenance treatment for patients with schizophrenia, was the first long-acting antipsychotic injectable (LAI) to require only four administrations per year. Here, we aimed to review the available evidence about its use in the management of schizophrenia to date and highlight key study findings in order to provide a balanced overview of current experience in clinical practice. For that purpose, an extensive search of available literature from PubMed, Embase, and Web of Science was conducted in March 2023. Emerging data from real-world studies appear to signal that the benefits of the use of PP3M may well extent beyond the obvious convenience for patients and resource efficiency for services and may be actually associated with improved effectiveness and patient satisfaction. Large naturalistic studies from Australia, Europe and the US comparing treatment continuation between newer LAIs and/or oral antipsychotics showed that patients treated with PP3M had higher compliance rates and a longer period of continuous use. The risk of relapse, re-hospitalization and number of bed days was also lower with PP3M compared to PP1M and other LAIs as demonstrated by several cohort studies. Furthermore, patients treated with PP3M were using lower doses of benzodiazepines and concomitant oral antipsychotics compared with other LAIs. What is more, PP3M appears to positively impact patients' satisfaction and quality of life, facilitating long-term goals. In fact, recent studies recorded better quality-adjusted life years and decreased stigma, with improved social acceptability and promotion of rehabilitation for patients transitioning to PP3M. The rates of general satisfaction rates with PP3M were also higher among psychiatrists and caregivers who reported overall less concerns. In conclusion, clinical exposure and a growing body of evidence thus far, reinforce the use of PP3M in an effort to enhance patient outcomes alongside individual experience and treatment persistence.

Schizophrenia Patients Discharged on Clozapine Plus Long-Acting Injectable Antipsychotics From a Public Psychiatric Hospital in Taiwan, 2006-2021.

BACKGROUND: Some schizophrenia patients treated with clozapine experience an inadequate response and adherence problems. The purpose of this study was to compare time to rehospitalization within 6 months in schizophrenia patients discharged on 3 clozapine regimens. Additionally, the temporal trend of prescription rate in each group was also explored. METHODS: Schizophrenia patients discharged from the study hospital from January 1, 2006, to December 31, 2021, (n = 3271) were included in the analysis. The type of clozapine prescribed at discharge was divided into 3 groups: clozapine plus long-acting injectable antipsychotics (clozapine + LAIs), clozapine plus other oral antipsychotics (clozapine + OAPs), and clozapine monotherapy. Survival analysis was used to compare time to rehospitalization within 6 months after discharge among the 3 groups. The temporal trend in the prescription rate of each group was analyzed using the Cochran-Armitage Trend test. RESULTS: Patients discharged on clozapine + LAIs had a significantly longer time to rehospitalization than those on clozapine + OAPs or clozapine monotherapy. The prescription rates of clozapine + LAIs and clozapine + OAPs significantly increased over time, whereas the prescription rates of clozapine monotherapy significantly decreased. CONCLUSIONS: Compared with the clozapine + OAPs group, the clozapine + LAIs group had a lower risk of rehospitalization and a lower dose of clozapine prescribed. Therefore, if a second antipsychotic is required for patients who are taking clozapine alone, LAIs should be considered earlier.

Clinical benefit of second-generation long-acting injectable antipsychotics in preventing re-hospitalization in patients with schizophrenia: A real-world study in Japan.

BACKGROUND: Real-world evidence on the benefits of long-acting injectable (LAI) antipsychotics (AP) in patients with schizophrenia is limited, especially in the employed population in Japan. This study evaluates the effectiveness of LAI AP in preventing re-hospitalization in patients with schizophrenia, including the employed population. METHODS: This retrospective, observational, population-based study used the Japan Medical Data Center (JMDC) health insurance claims database to identify patients having schizophrenia before or on the day of the first LAI AP prescription (index date), and receiving LAI AP between April 1, 2012 and December 31, 2019. The number of all-cause, psychiatric-, and schizophrenia-related hospitalizations at baseline (365 days before index date) and during the 1-year follow-up period were evaluated. RESULTS: Of the 1692 patients who received LAI AP during the study period, 146 were included (employed: 55 [37.7 %]; dependent: 91 [62.3 %]). The mean age was 37 years; 50.7 % (n = 74) were females. During baseline period, 61 (41.8 %) patients were not hospitalized. During the follow-up period, 67 (45.9 %) patients underwent hospitalization ≤ 7 days; all-cause: 100 (68.7 %); psychiatry-related: 104 (76.2 %); schizophrenia-related: 114 (78.1 %). A higher proportion of patients were hospitalization-free during the follow-up in the employed vs. dependent population: all cause: 69.1 % vs. 61.5 %; psychiatric-related 76.4 % vs. 67.0 %, schizophrenia-related: 87.3 % vs. 71.4 %. CONCLUSION: This study demonstrated the effectiveness of LAI AP in preventing hospitalization in Japan. During the follow-up period, patients with schizophrenia receiving LAI AP, including the employed population, had a significant decrease in hospitalization length and re-hospitalization rate compared to baseline.