Paliperidone Research Articles

Analyzing Demographic Variabilities Associated With Age of Diagnosis of Schizophrenia Among Patients in Controlled Clinical Trials

AbstractBackgroundPrior literature and epidemiological data suggests that the age of diagnosis of schizophrenia (AOD) follows a bimodal and trimodal distribution for males and females, respectively. The studies used to generate these findings were often small and relied on self-reported patient data from a single geographic region in addition to other methodological limitations. We replicated these studies using a modern big data approach by combining raw data from large randomized controlled clinical trials.MethodsPatient-level data from 15 similarly designed, randomized, double-blind, placebo-controlled, crossover studies with patients using paliperidone extended-release tablets, paliperidone palmitate 1-month, and paliperidone palmitate 3-month, were obtained through the Yale Open Data Access Initiative (YODA). Descriptive statistics and histograms were calculated for continuous variables. A multivariable linear regression was performed with AOD as the outcome variable. Race and sex were used as predictor variables.ResultsOur final analysis included 7881 patients consisting of male (n=4962) and female (n=2919) patients among different racial demographics. Race was consolidated into the following groups: Asian (n=949), Black (n=1692), Hispanic (n=3), Southeast Asian (n=17), White (n=4769), and other (n=343) based on patient self-identification on the YODA datasets. A chi-square test revealed that there is a statistically significant association between patient sex and AOD (x2=295.61, df=68, p < 0.0001). By proxy, this likely means that sex affects age of onset (AOS) as well. Our linear regression output with sex as a predictor of AOD revealed that only the male variable was found to have a statistically significant relationship (p<0.0001) with AOD and resulted in a lower AOD. Histograms generated with the frequency of occurrences against AOD for both male and female patients appeared to be unimodally distributed and skewed right. However, the AOD for female and male patients were found to be 28.79 and 25.44 years old, respectively. This demonstrates that while both male and female AOD are distributed unimodally, there are slight differences in their distributions.ConclusionOur analysis differs from previous studies and finds that AOD for male and female patients are seen in a unimodal distribution as compared to previous literature that shows a bimodal and trimodal distribution. Our findings not only call for a re-evaluation of previous epidemiological understandings of AOD but may support future efforts in understanding the origins and typical clinical presentations of patients with newly developed symptomatology of schizophrenia as well as support clinicians’ perspectives as part of clarifying differential diagnoses. Further studies can also continue to evaluate possible correlations among different races.FundingNo Funding

Feasibility study to evaluate capabilities for conducting psychiatric clinical research within the Rwandan mental healthcare system

ObjectiveTo evaluate the feasibility of conducting a large clinical trial within the Rwandan mental healthcare system that would establish the safety, efficacy and benefit of paliperidone palmitate once-monthly (PP1M) and...

Aripiprazole: Examining the Clinical Implications of D2 Affinity

AbstractBackgroundAripiprazole has high binding affinity for the dopamine D2 receptor, which is thought to be responsible for the antipsychotic effect, though aripiprazole is not the most potent of the second-generation antipsychotics. Theoretically, aripiprazole could displace or outcompete more potent antipsychotics, prompting decreased antipsychotic effect. We describe a case of aripiprazole potentially worsening psychiatric symptoms by blocking paliperidone.CaseMs. A is a 43-year-old woman with schizophrenia, multiple inpatient hospitalizations, and a history of court-ordered treatment. She historically has had good response to oral and long-acting formulations of risperidone and paliperidone. Ms. A requested a medication change and was transitioned to aripiprazole lauroxil injection with plan for bimonthly administration. Approximately 1 month after receiving her aripiprazole lauroxil injection, Ms. A presented to our CPEP due to symptoms of psychosis and was admitted to our inpatient unit. She was restarted on oral paliperidone, titrated up to her previously effective dose, and was transitioned to paliperidone palmitate LAI. In contrast to prior admissions, she did not respond well to paliperidone and displayed continued and worsened psychosis.DiscussionPrior studies have examined how adding aripiprazole to another, more potent D2 antagonist can cause a relapse in psychotic symptoms; however, few studies have investigated the inverse relationship or mechanism. Those that have proposed mechanisms typically refer to aripiprazole’s partial agonist activity as the causative factor, rather than an impediment to antipsychotic binding which we have described. Prescribers should be aware of this potential interaction and carefully consider initiating long-acting injectable forms of aripiprazole to avoid this phenomenon.FundingNo Funding

Effectiveness of SGA-LAIs on Clinical, Cognitive, and Social Domains in Schizophrenia: Results from a Prospective Naturalistic Study

We hypothesized that shifting from oral second-generation antipsychotics (SGA) to their long-acting injectable (LAI) counterpart would be beneficial for the psychopathological, cognitive, social, and general health domains in outpatients suffering from schizophrenia. We aimed to evaluate the prospective usefulness of SGA-LAI treatment by carrying out a head-to-head comparison of two different medications (i.e., aripiprazole monohydrate (Ari-LAI) and paliperidone palmitate 1 and 3 month (PP1M, PP3M)) in a real-world setting, assessing the effectiveness and tolerability of Ari-LAI and PP1M/PP3M over a 15 month follow-up. A total of 69 consecutive individuals affected by schizophrenia were screened for eligibility. Finally, 46 outpatients (29 treated with Ari-LAI, 13 with PP1M, and four with PP3M) were evaluated through clinical, functional, and neuropsychological assessment administrated at baseline and after 3-, 12-, and 15-month follow-up periods. Moreover, periodic general medical evaluations were carried out. We estimated an overall improvement over time on the explored outcomes, without differences with respect to the type of LAI investigated, and with a global 16.4% dropout rate. Our findings suggest that switching from oral SGA to SGA-LAIs represents a valid and effective treatment strategy, with significant improvements on psychopathological, cognitive, social, and clinical variables for patients suffering from schizophrenia, regardless of the type of molecule chosen.

Invega Hafyera (Paliperidone Palmitate): Extended-Release Injectable Suspension for Patients With Schizophrenia.

Objective: The objective of this study was to describe the safety, efficacy, and potential role in therapy of once in 6 months paliperidone palmitate formulation (PP6M; Invega Hafyera). PP6M is a long-acting injectable antipsychotic recently approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia. Data Sources: A PubMed literature search was conducted using the following terms: paliperidone palmitate and long-acting antipsychotic injections (January 1, 2017, to November 1, 2022). FDA product labeling was also reviewed for pertinent data. Study Selection and Data Extraction: All relevant English-language articles focused on the efficacy and safety of PP6M were considered for inclusion. Data Synthesis: A multicenter, randomized, active controlled relapse prevention noninferiority study showed that PP6M is comparable to paliperidone palmitate once in 3 months formulation (PP3M) in terms of efficacy and safety in clinically stable schizophrenia patients. Place in Therapy: PP6M is indicated in the treatment of adult patients with schizophrenia, who need treatment over a prolonged period. It improves adherence and decreases the rate of relapse and hospitalizations among patients with schizophrenia. It is useful for patients who may have difficulty accessing health care or would prefer the convenience of less frequent injections. Conclusion: PP6M with its long duration of action and lowered frequency of administration (once every 6 months) expands the therapeutic choices available to patients with schizophrenia. More studies in patients with schizophrenia with PP6M, and perhaps other mental illnesses (eg, schizoaffective disorder), are required to fully elucidate the therapeutic potential of PP6M.

Alternative initiations with 6-monthly paliperidone palmitate. A retrospective study

Introduction6-monthly paliperidone palmitate features an initiation regimen through 1-monthly paliperidone palmitate or 3-monthly paliperidone palmitate. Some patients do not have sufficient adherence to treatment and it is necessary at the clinical level to start directly with 6-monthly paliperidone palmitate. There is little clinical experience with these alternative initiations and through this work those that have been carried out for 12 months at the Hospital Universitario Infanta Elena are exposed.ObjectivesThe main objective of the study is to describe the alternative initiations performed with 6-monthly paliperidone palmitate in routine clinical practice, having opted for a regimen different from the standard for clinical reasons.MethodsA retrospective selection of patients will be made through non-probabilistic consecutive sampling, including all patients who have been administered 6-monthly paliperidone palmitate with a start different from the standard during the last 4 months. To do this, the electronic medical record will be used, first selecting the patients who have started 6-monthly paliperidone palmitate through the anonymized digital records and, later, including in the study only those who have followed an alternative initiation pattern. The variables studied will be the following: age, sex, diagnosis, dose of paliperidone palmitate, initiation regimen, consumption of toxic substances, absenteeism from 6-monthly paliperidone palmitate, and visits to the emergency room and admissions.ResultsThe study included a total of 20 patients (n: 20). 80% of the patients were male and 20% were female. The mean age was 39.7 years. 75% of the patients had an associated substance use disorder. The following alternate starting schedules were performed with biannual paliperidone palmitate: monthly paliperidone palmitate on days 1 and 8, and 6-monthly paliperidone palmitate on day 38 (n: 11); monthly paliperidone palmitate 150 mg together with semi-annual paliperidone palmitate both on day 1 (n: 5); biannual paliperidone palmitate on day 1 supplemented with oral paliperidone for 45 days (n:4). A total of 0 visits to the emergency department and 0 admissions were observed after the 6-monthly paliperidone palmitate regimen.ConclusionsAlternative initiations with 6-monthly paliperidone palmitate may be a useful and safe clinical alternative in patients with very low adherence who, due to clinical needs, require starting 6-monthly paliperidone palmitate earlier in order to guarantee adherence.Disclosure of InterestNone Declared

Use of paliperidone palmitate half-yearly release in patients diagnosed with psychotic disorder: profile and satisfaction of use

IntroductionThe lack of insight can be present among patients with a diagnosis of schizophrenia, which often results in lack of adherence to pharmacological treatments1 and, subsequently, in treatment discontinuation and relapses2. This vicious pattern leads to further clinical deterioration, impaired functioning, and reduced quality of life 3. There is a plethora of evidence supporting the fact that long-acting injectable and depot antipsychotics can increase adherence to treatment, reduce the risk of discontinuation and hospital admissions4. It is also known that low fluctuations between peaks and lows in plasma drug levels could be related to a better tolerability profiles5. A new paliperidone palmitate prolonged release formulation, which is administered twice annually, has been approved as maintenance treatment for patients with schizophrenia who are already stable on the monthly or quarterly prolonged release paliperidone palmitate6.ObjectivesWe aimed to evaluate the transition of monthly and quarterly paliperidone palmitate to the new six-monthly formulation and patients’ satisfaction with it in a real-world clinical setting.MethodsWe collected a basic epidemiologic questionnaire, responses to a query about local pain after administration, and the Drugs Attitude Inventory (DAI).ResultsA total of 21 patients from an outpatient clinic for severe mental disorders with a long evolution of their disease in Salamanca, Spain, were included. All of them had a DSM5-TR diagnosis of Schizophrenia. Sixteen were male and 5 female. The mean age was 42.6 years. 14 were receiving quartlery paliperidone palmitate (10 with high doses (525 mg) and 4 with moderate doses (350 mg)) and 7 were on monthly injections (6 with high doses (150 mg) and 1 with a moderate dose (100 mg)). Those receiving moderate doses of quarterly or monthly paliperidone palmitate were administered 700 mg of six-monthly paliperidone palmitate; 1000 mg were injected to those with higher doses. The mean score on the DAI scale was 8. Only one patient reported an increase in local pain after the injection, and another reported dissatisfaction with the administration in the gluteus instead of the deltoid muscle. The first administration of the new formulation in our site was on June 26th; to date none of these patients have required hospital admission due to relapse.ConclusionsSix-monthly prolonged release paliperidone palmitate seems to be an effective maintenance treatment for schizophrenia. In addition, this new formulation is well received and tolerated by patients previously on monthly or quarterly formulations of the same drug.Disclosure of InterestNone Declared

Alternative initiations with 6-monthly paliperidone palmitate. A descriptive study

Introduction 6-monthly paliperidone palmitate features an initiation regimen through 1-monthly paliperidone palmitate or 3-monthly paliperidone palmitate. Some patients don´t have sufficient adherence to treatment and it is necessary at the clinical level to start directly with 6-monthly paliperidone palmitte. There is une little clinical experience with these alternative initiations and throuht this work those that have been carried out for 12 months at the Rey Juan Carlos Hospital are exposed. Objectives The main objective of the study is to describe the alternative initations performed with 6-monthly paliperidone palmitate in routine clinical practice, having opted for a regimen different from the standard for clinical reasons. Methods A retrospective selection of patiens will be made throuht non-probabilistic consecutive sampling, including all patients who have benn administered 6-monthly paliperidone palmitate with a stard different form the standard during the last 6 months. To do his, the electronic medical record will be used, first selecting the patients who have started 6-monthly paliperidone palmitate through the anonymized digital records and, later, including in the study only those who have followed and alternative initiation pattern. The variables studied will be the following: age, sex, diagnosis, dose of paliperidone palmitate, initiation regimen, consumption of toxic substances, absenteeism from 6-monthly paliperidone palmitate, visits to the emergency room and admissions. Results The study included a total of 5 patients ( n:5). 80% of the patients were male and 20%were female. The mean age was 39.7 years. 80% of the patients had an associated substance use disorder. The following alternate sarting schedules were with biannual paliperidone palmitate: monthly paliperidone palmitate 150 mg together with semi-annual paliperidone palmitate both on day 1 ( n: 2) or monthly paliperidone palmitate 150 mg on day 1, monthly paliperidone palmitate 100 mg on day 5 and semi-annual paliperidone palmitate on day 12 ( n: 3 ). A total of 0 visits to the emergency department and 0 admissions were observed after the 6-monthly paliperidone palmitate regimen. Conclusions Alternative initations with 6-monthly paliperidone palmitate may be a useful and safe clinical alternative in patients with very low adherence who, due to clinical needs, require startin 6-monthly paliperidone palmitate earlier in order to guarantee adherence . Disclosure of Interest None Declared

Clinical experiences with 6-monthly paliperidone palmitate after 12 months of use. A retrospective study

IntroductionLong-acting injectable antipsychotics (LAIA) have provided a significant improvement in the treatment of schizophrenia. Although there is already significant clinical experience with paliperidone palmitate, it is important to evaluate the clinical response of patients to this new 6-monthly presentation, so descriptive studies based on real clinical evidence can be very useful for this purpose.ObjectivesThe main objective of the study is to describe the use of 6-monthly paliperidone palmitate in routine clinical practice, providing variables that objectify the evolution such as the number of admissions and visits to the emergency room.MethodsRetrospective descriptive study with a sample selected by non-probabilistic consecutive sampling, retrospective type, in a time interval of 12 months (n=40). The patients selected were all those who received 6-monthly paliperidone palmitate treatment, with a diagnosis of schizophrenia, in 12 months of use at Hospital Universitario Infanta Elena. A descriptive analysis was performed. Mean and standard deviation were calculated for quantitative variables and N and percentage for categorical variables.ResultsA total of 40 administrations of 6-monthly paliperidone palmitate were performed in the study. None of the patients presented adverse reactions related to the administration of the drug, not reporting local pain or inflammation of the puncture area, except for the characteristic discomfort of an intramuscular puncture. Regarding the efficacy of 6-monthly paliperidone palmitate, none of the patients presented a psychotic decompensation after its administration, maintaining psychopathological stability after the change. The switch to 6-monthly paliperidone palmitate was made from both 1-monthly paliperidone palmitate and 3-monthly paliperidone palmitate, both showing the same efficacy. Regarding tolerability, all the patients who were administered 6-monthly paliperidone palmitate were previously treated with the monthly and quarterly presentation of the same molecule, having presented good tolerability to it, maintaining said tolerability after treatment. change to 6-monthly paliperidone palmitate, with no adverse reaction being recorded after the change. The adherence presented by the patients was very good, performing 100% of the administrations of 6-monthly paliperidone palmitateConclusions6-monthly paliperidone palmitate may be an effective and well-tolerated treatment for the treatment of schizophrenia. In the present study, the use of said LAIA in a group of 40 patients is objectified, showing excellent efficacy and tolerability. All study patients were already stable with the 1-monthly and 3-monthly paliperidone palmitate formulations, maintaining said psychopathological stability when switching to the 6-monthly paliperidone palmitate formulation, with excellent adherence and adverse effect profile .Disclosure of InterestNone Declared

Paliperidone Palmitate: A Breakthrough Treatment for Schizophrenia? A Review on Patient Adherence Levels, Healthcare Resource Utilization and Costs.

International guidelines suggest long-term antipsychotic therapies for treating schizophrenia; however, medication compliance remains a critical issue in schizophrenia. Paliperidone palmitate (PP) is a second-generation antipsychotic long-acting injectable (SGA-LAI) approved for the treatment of schizophrenia. To date, the majority of studies on PP compliance patterns did not use specific instruments to assess medications' adherence, have been performed in not naturalistic samples and present partially overlapping populations. We conducted a systematic review in which we aimed to review the current knowledge on PP-LAI adherence levels and to describe healthcare resource utilisation and costs related to PP-LAI treatment. The evaluation has been conducted by searching in different databases (PubMed, Ovid, Scopus, and Cochrane Library) from inception to September 2022. Our findings suggest that paliperidone palmitate should be considered a good treatment strategy for patients affected by schizophrenia: PP showed both a good efficacy and tolerability and better adherence patterns and more favourable healthcare resource utilisation and costs, compared to OA.

Mothers and fathers with schizophrenia: Treatment and quality of life

IntroductionSchizophrenia is a chronic disease that deteriorates the functionality of patients, especially when raising a family and caring for children. We are interested in analyzing the characteristics of mothers and fathers diagnosed with schizophrenia and their degree of global activity when switching from oral treatments to injectable treatments.Objectives1 To evaluate the quality of life and functional level of mothers with schizophrenia treated with quarterly paliperidone palmitate. 2. To compare the quality of life and functional level when switching from oral treatment to long-acting injectables.MethodsParticipants were 3 mothers and 3 fathers, 33-40 years old, with a diagnosis of schizophrenia in monotherapy who changed treatment with monthly paliperidone palmitate to quarterly paliperidone palmitate LD IM (525 mg/every 12 weeks). Retrospective data collection. QLS quality of life scale.ResultsSix patients were included, caregivers of 1 child (80%), 2 children (20%) who met the inclusion criteria and completed the questionnaires. After its application and correction by means of non-parametric tests (N<30). During oral treatment, scores are observed in the QLS questionnaire of: intrapsychic functions mean 34.2, interpersonal relationships mean 19, instrumental role mean 8, daily activities mean 8. After 12 months of treatment with intramuscular paliperidone palmitate (injectable every 12 weeks ) scores were obtained: intrapsychic functions mean 36, interpersonal relationships mean 23, instrumental role mean 15, daily activities mean 11. A better functioning of the patients was observed in the instrumental categories and daily activities. As well as the patients referred better adherence to treatment.ConclusionsIn our experience, injectable long-acting Paliperidone Palmitate every 12 weeks is associated with the perception of a better quality of life in parents with schizophrenia and increases administration facilities as well as planning in their daily lives.Disclosure of InterestNone Declared

Budget impact of introducing once-every-6-months paliperidone palmitate in US health care plans.

BACKGROUND: In the United States, most patients with schizophrenia have Medicaid coverage. Antipsychotic treatments are the cornerstone of schizophrenia management; most patients are treated with daily oral antipsychotics but struggle with medication adherence. Evidence suggests that medication adherence is inversely correlated with dosing frequency. Once-monthly paliperidone palmitate (PP) has been demonstrated to improve adherence compared with oral antipsychotics; transitioning to once-every-3-months PP (PP3M) further improved adherence. In 2021, once-every-6-months PP (PP6M) was approved by the US Food and Drug Administration to provide even longer between-dose intervals. Public health stakeholders who aim to improve medication adherence are interested in understanding how introducing PP6M to the formulary will impact the budget. OBJECTIVE: To evaluate the budget impact of introducing PP6M to the formulary from the perspectives of a hypothetical US multistate health care payer and state Medicaid programs using California, Georgia, and Ohio as examples. METHODS: The budget impact model was developed from a payer perspective, comparing the reference scenario (without PP6M in the market) with a new scenario (with PP6M). The study population included patients with schizophrenia who were eligible to receive PP6M. Market shares were assigned to the reference and new market scenarios. Efficacy was measured by the relative risk of relapse while receiving treatment. Adherence effects were included in the model and affected costs of treatment and relapse rates. A deterministic 1-way sensitivity analysis was performed. RESULTS: Base-case results for a multistate payer with 1 million members demonstrate that adding PP6M to the market results in total incremental plan-level costs ranging from $7,747 in year 1 to $11,501 in year 5. Increased drug costs were offset by administration and relapse cost savings ($105 and $881 in year 5, respectively). The average incremental cost per treated patient per year was stable at $180.06 for each year, and the incremental cost per member per month stayed below $0.01 for each year. The results of the model from the state-level Medicaid scenarios are broadly similar to those of the multistate base-case perspective. The 1-way sensitivity analysis demonstrated the model is most sensitive to the per-package costs of PP6M and PP3M, along with the proportion of patients fully adherent with PP3M. CONCLUSIONS: The budget impact of introducing PP6M as a treatment option is minimal. With the expected cost offsets from reduced administration and relapse costs due to adherence benefits, these results suggest that PP6M can be a viable treatment option from a clinical and a budgetary perspective. DISCLOSURES: This study was funded by Janssen Scientific Affairs, LLC. The study sponsor provided funds to Xcenda and ApotheCom for medical writing, editorial support, and submission of the manuscript. Hilary Phelps was an employee of Janssen Global Services, LLC, at the time of the development and finalization of the manuscript. Alex Keenan is an employee of Janssen Global Services, LLC, and holds stock in Johnson & Johnson, Inc. Dee Lin and Carmela Benson are employees of Janssen Scientific Affairs, LLC, and hold stock in Johnson & Johnson, Inc. Aditya Raju was an employee of Xcenda at the time of the development and finalization of the manuscript, and Danmeng Huang is an employee of Xcenda, a health care consulting firm that was contracted by Janssen Scientific Affairs, LLC. Chih-Yuan Cheng is an employee of Janssen NV.

The Effect of Longer Dosing Intervals for Long-Acting Injectable Antipsychotics on Outcomes in Schizophrenia.

Medication nonadherence in schizophrenia can have serious implications including relapses and hospitalization. Long-acting injectable (LAI) antipsychotics require fewer administrations, while ensuring sustained medication coverage. In this review, we summarize the expected real-world benefits of longer dosing intervals in the management of schizophrenia. LAIs are associated with improved clinical outcomes of less frequent relapses and reduced functional impairment, encouraging patients to regain control of their lives. Aripiprazole lauroxil and paliperidone palmitate three-monthly (PP3M) LAIs have longer dosing intervals of 2-3 months and provide improved outcomes in patients with schizophrenia. Paliperidone palmitate six-monthly (PP6M) LAI provides the longest dosing interval, twice-yearly dosing, among existing LAIs. Decreasing the frequency of LAI administrations has the potential to reduce occurrence of serious outcomes associated with poor medication adherence. By eliminating the need for daily oral antipsychotic dosing, LAIs could increase the likelihood of patient acceptance, decrease stigma, and promote self-esteem. Longer intervals of medication coverage may be desirable for patients with higher risk of relapse including adults with recent-onset schizophrenia, those living in circumstances that may deprive them of regular access (eg, homeless), those that are in transitions between care settings or to reduce interpersonal contact during public health emergencies (eg, COVID-19 pandemic).

In vitro Evaluation of Paliperidone Palmitate Loaded Cubosomes Effective for Nasal-to-Brain Delivery.

This work aimed to develop chitosan-coated cubosomal nanoparticles intended for nose-to-brain delivery of paliperidone palmitate. They were compared with standard and cationic cubosomal nanoparticles. This comparison relies on numerous classical in vitro tests and powder deposition within a 3D-printed nasal cast. Cubosomal nanoparticles were prepared by a Bottom-up method followed by a spray drying process. We evaluated their particle size, polydispersity index, zeta-potential, encapsulation efficiency, drug loading, mucoaffinity properties and morphology. The RPMI 2650 cell line was used to assess the cytotoxicity and cellular permeation. An in vitro deposition test within a nasal cast completed these measurements. The selected chitosan-coated cubosomal nanoparticles loaded with paliperidone palmitate had a size of 305.7 ± 22.54 nm, their polydispersity index was 0.166 ± 0.022 and their zeta potential was +42.4 ± 0.2 mV. This formulation had a drug loading of 70% and an encapsulation efficiency of 99.7 ± 0.1%. Its affinity with mucins was characterized by a ΔZP of 20.93 ± 0.31. Its apparent permeability coefficient thought the RPMI 2650 cell line was 3.00E-05 ± 0.24E-05 cm/s. After instillation in a 3D-printed nasal cast, the fraction of the injected powder deposited in the olfactory region reached 51.47 ± 9.30% in the right nostril and 41.20 ± 4.59% in the left nostril, respectively. The chitosan coated cubosomal formulation seems to be the most promising formulation for nose-to-brain delivery. Indeed, it has a high mucoaffinity and a significantly higher apparent permeability coefficient than the two other formulations. Finally, it reaches well the olfactory region.

Efficacy of paliperidone palmitate 3-month formulation in preventing hospital admissions and emergency room visits. 66 months of follow-up

IntroductionPaliperidone Palmitate 3-month formulation (PP3M) has shown a significantly longer time to relapse compared to placebo, with similar efficacy and safety to Paliperidone Palmitate 1-month (PP1M) (Carpiniello et al. Drug Des. Devel. Ther. 2016; 10 1731–1742).ObjectivesThe main objective of this study was to determine the effectiveness of PP3M in preventing hospital admissions and emergency room visits, in people with non-acute schizophrenia in a naturalistic psychiatric outpatient settingMethodsSample: 30 people with diagnosis of schizophrenia (DSM 5 criteria), who had started treatment with PP3M, after being stabilized with PP1M (the dose was not modified in the four months prior to inclusion in the study)Quarterly basis, the following evaluations were performed during a follow-up period of 66 months:The Clinical Global Impression-Schizophrenia scale (CGI-SCH)Treatment adherence, concomitant medication and the number of hospitalizations and emergency visitsEfficacy values: Percentage of patients who remained free of admissions at the end of 66 months of follow-up.Other evaluation criteria: Percentage of patients who never visited the emergency department at the end of 66 months of follow-up. Average change from baseline visit to the final evaluation as assessed by score obtained on the following scale: GSI-SCH, percentage of patients on antipsychotic monotherapy and treatment adherence rate.ResultsThe mean dose of PP3M was 401. 55 mgThe percentage of patients who remained free of admissions at the end of the 66 months was 83.25% and the percentage of patients who never visited the emergency department at the end of 66 months was 79.92%Mean variations from baseline scores at 66 months were: (-0.36 ±0-37) on the GCI-SCH.The percentage of patients on antipsychotic monotherapy at the end of the 66 months was 76.56%The rate of adherence was 86.58%.ConclusionsIn our study, we found that paliperidone palmitate 3-month formulation was effective in reducing the number of admissions and visits to the emergency department, under conditions of daily clinical practice.Disclosure of InterestNone Declared

Challenges in Treating Schizophrenia with LAIs – Analysis of Own Results

IntroductionSchizophrenia is a multifactorial and multifarious disorder with an unidentified etiology and pathogenesis, various clinical symptoms, unpredictable course and definite social significance. It’s social significance manifests in the long inability to work, the decrement of qualification and the burdening of family and social services. Patients find following therapy difficult; they often stop it altogether, which leads to new exacerbations and maintaining a vicious cycle.ObjectivesTo present an analysis of the results of the treatment of patients with LAIs – Trevicta and Xeplion in General Psychiatry Ward of UMBAL "Dr. Georgi Stranski” - Pleven for the period October 2016 – October 2022.MethodsOur retrospective research includes 17 patients treated in General Psychiatry Ward of UMBAL “Dr. Georgi Stranski”- Pleven. A treatment with LAI’s – Trevicta and Xeplion (Paliperidone palmitate) had been initiated in these patients. In consideration of the correct applications of the medication, they are always made by qualified personnel who received training for that purpose in the Ward. For assessment of the patients’ condition are used: Positive and Negative Syndrome Scale (PANSS) and Personal Social Performance (PSP). Standard statistic methods are used for processing results.ResultsOur research includes 17 female patients as the Ward’s profile is such, with the average age of 38.65 years at the initiation of the treatment with Xeplion. Some were later introduced to Trevicta. Of all who participated in the research, 12 patients continue their treatment with regular applications, 2 have changed their address and by unreliable data still continue their treatment and for the other 3 we have no information of their status of treatment. The average count of admissions in the Ward before the initiation of treatment with LAI’s is 3.88 against 0.88 after the initiation. Regarding the PANSS scale – all score in the interval 75-100 points before initiation as opposed to the scores marked after the initiation of the medication that vary in the interval 34-48 points with definite distinctions in P and G items. Regarding the PSP scale – all participants score between 50 and 70 points before the initiation of the treatment as opposed to the scores of 89-95 points after the initiation. During the regular check-ups the patients report of subjective improvement, coupled with reports of objective and positive improvement by family.ConclusionsTreatment with LAIs – Xeplion and Trevicta has an unquestionable positive and lasting effect in the treatment of schizophrenia. Proof of that is the definite improvement of the symptoms, the increased social engagement and interpersonal communication. Everything mentioned is a valid reason to direct the treatment of schizophrenia in the direction of preservation of the personality of the patients.Disclosure of InterestNone Declared

Long-term efficacy and safety of paliperidone 6-month formulation: An open-label extension of a double-blind study in adult patients with schizophrenia

IntroductionPaliperidone palmitate 6-month (PP6M), administered twice-yearly, demonstrated non-inferiority to paliperidone palmitate 3-month (PP3M) in preventing relapse in patients with schizophrenia in a phase-3 randomized, double-blind (DB) global study.1 We report results of a 2-year single-arm, open-label extension (OLE) of this study (NCT04072575).ObjectivesTo assess long-term efficacy and safety of PP6M in patients with schizophrenia.MethodsPatients who completed DB study without relapse were enrolled and followed up every 3 months for up to 2 years. Patients received 4 PP6M injections (700/1000 mg eq.) at baseline, 6-month, 12-month, and 18-month visits. Efficacy endpoints included relapse rate, Positive and Negative Syndrome Scale (PANSS) total score, Personal and Social Performance (PSP) score, and Clinical Global Impression-Severity (CGI-S) scale change from baseline. Safety was assessed by treatment-emergent adverse events (TEAEs), physical examinations and laboratory tests.ResultsOf 178 patients, 154 (86.5%) completed the study; mean age: 40.4 years; 70.8% were men. Mean duration of PP6M exposure was 682.1 days. Overall, 7/178 (3.9%) patients relapsed between 20 to 703 days after enrolment. Mean (SD) change from baseline to endpoint: PANSS total score, 0.7 (8.22); CGI-S, 0.0 (0.51); PSP Scale, 0.5 (7.47). Overall, 111/178 patients (62.4%) reported ≥1 TEAE; most common (>10%) TEAEs were headache (13.5%) and blood prolactin increased (10.7%). Total, 7/24 patients withdrew due to TEAEs, and 8/178 (4.5%) patients experienced serious TEAEs; no deaths were reported.ConclusionsRelapse rate with PP6M was very low (<4%). Clinical improvements in PANSS, CGI-S, and PSP scales demonstrated in DB study were maintained during this 2-year OLE study and no new safety concerns were identified.Reference1. D. Najarian et al. Int J Neuropsychopharmacol. 2022 Mar 17;25(3):238-251.Disclosure of InterestD. Najarian Shareolder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, I. Turkoz Shareolder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, S. Galderisi Consultant of: Janssen, Gedeon Richter-Recordati, Angelini, Speakers bureau of: Angelini, Gedeon Richter-Recordati, Janssen, Lundbeck, Sunovion, Recordati, H. Lamaison Grant / Research support from: Novartis, Eli Lilly, Lundbeck, Servier, AstraZeneca, Wyeth, Pfizer, Otsuka, Takeda, Sunovion, Roche, Janssen Pharmaceutical, Speakers bureau of: Servier, Abbot, Raymonds, Raffo, Temis Lostalo and Janssen Pharmaceutical, P. Zalitacz: None Declared, S. Aravind Shareolder of: Johnson & Johnson, Employee of: Advarra, Inc. USA, U. Richarz Shareolder of: Johnson & Johnson, Employee of: Janssen Research & Development-Cilag, Switzerland.

Use and experience with six-monthly paliperidone in the Campo de Gibraltar area. Descriptive study.

IntroductionLong-acting injectable antipsychotics have demonstrated advantages over therapeutic adherence and can reduce the rates of relapses and due to treatment discontinuation. The novel presentation of paliperidone palmitate six-month (PP6M) can simplify the treatment to two injections per year.ObjectivesThe purpose of the present research is to describe the profile of patients receiving this novel treatment in our area. For this, a descriptive study has been carried out.MethodsWe have collected and analyzed data from a total of 8 patients from the global long-acting injectable nursing registry in our area. The data collection was from May 2022 to October 2022.ResultsID PatientAge GenderMedical comorbidities Social supportAdherence to previous LAIEP001AGC52MNo-YesEP002EGA53MNoLowNoEP003ESL45FYesHIV, HCV, dyslipidemia,EnoughYesEP004ACG60MYesHypertension, dyslipidemiaGoodYesEP005DCP52MYesCOPDEnoughYesEP006ATT47MNoEnough / LowYesEP007AH40FYesTension headacheEnoughYesEP008IAR66FYesType 2 diabetes mellitus, hypertension, hyperuricemiaEnoughYes ID Patient Diagnosis Refractory positive symptoms Last H. Polypharmacy Previous injection Injection date / DoseH. / Side EffectsEP001AGCParanoid schizophrenia-08/03/2014NoPP3M525mg17/05/221.000 mgNoEP002EGASchizoaffective disorderYes19/08/2022YesValproic acid 1.000mgPP1M150mg(once)13/09/221.000mgNoEP003ESLParanoid schizophreniaNo17/04/2019YesOlanzapine 10mgBZDPP3M525mg10/08/221.000mgSedation (low)EP004ACGParanoid schizophreniaNo-YesQuetiapine 50mgPP3M525mg16/09/221.000mgNoEP005DCPParanoid schizophreniaNo16/01/2004YesOlanzapine 20mgBZDPP3M525mg11/10/221.000mgNoEP006ATTPersistent delusional disorderYes-NoPP3M525mg19/09/221.000mgNoEP007AHParanoid schizophreniaNo2017NoPP3M525mg03/08/221.000mgNoEP008IARPersistent delusional disorderYes-YesBZDPaliperidone oral 9mg and laterPP3M350mg(twice)18/10/221.000mgNoFig. 1: Sociodemographic characteristics and Fig. 2: Clinical characteristics.ConclusionsNone of the patients required hospitalization at the time of the study, although this work team considers that it is early to make conclusions in this regard. No serious or minor adverse effects were reported in any of the cases during the time of the investigation, apart from one case of mild sedation.The clinical characteristics of most patients were psychopathological stability and good adherence to previous treatment. Although this study shows that the drug was also used in patients who did not meet these characteristics, specially one case of poor social support. The data collected show that the profile of the patient in whom the drug has been prescribed can be varied and broad.Disclosure of InterestNone Declared

Effects of Long-acting Injectable 3-Monthly Paliperidone Palmitate on the Clinical and Social Performance of Patients with Schizophrenia

To investigate the effects of long-acting injectable 3-monthly paliperidone palmitate on the clinical and social functioning of patients with schizophrenia. This study enrolled patients with schizophrenia receiving long-acting injectable 1-monthly paliperidone palmitate for at least 4 months and who subsequently received 3-monthly paliperidone palmitate. Accordingly, 418 patients were followed up for 24 weeks. Their clinical symptoms and social functioning were measured using the Clinical Global Impression-Severity of Illness and Personal and Social Performance scales. The Personal and Social Performance total score was significantly higher after 3-monthly paliperidone palmitate treatment than at baseline (baseline vs. week 24: 54.3 ± 18.0 vs. 61.0 ± 14.5 [mean ± standard deviation]; p < 0.001; Wilcoxon signed-rank test); the proportion of patients in the mildly ill group (scores 71-100) also increased significantly (baseline vs. week 24: 16.5% vs. 20.6%; p < 0.001; McNemar-Bowker test). The mean Clinical Global Impression-Severity of Illness score decreased significantly (baseline vs. week 24: 3.7 ± 1.0 vs. 3.4 ± 0.9; p < 0.001; Wilcoxon signed-rank test), as did the proportion of patients in the severely ill group (baseline vs. week 24: 4.1% vs. 2.1%; p < 0.001; McNemar-Bowker test). Continuous 3-monthly paliperidone palmitate treatment significantly enhances the personal and social performance of patients with schizophrenia and reduces the proportion of those with severe illness. These findings suggest that long-acting injectable antipsychotic administration at intervals longer than 1 month might improve the social functioning of and promote return to activities of daily living in patients with schizophrenia.

Effectiveness of Switching to Long-acting Injectable Aripiprazole in Patients with Recent-onset and Chronic Schizophrenia.

This study investigated the effectiveness of switching to once-monthly long-acting injectable (LAI) aripiprazole from other second-generation antipsychotics including LAI paliperidone palmitate in both recent-onset and chronic schizophrenia patients. This was a 24-week prospective, open-label, flexible dose-switching study in patients with schizophrenia. Scores on the Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP) scale, Clinical Global Impression (CGI), Subjective Well-being Under Neuroleptics-Short Form (SWN-K), and a computerized emotional recognition test (ERT) were evaluated. Subjects were divided into two groups (recent onset and chronic) based on 5 years' duration of the illness. Among the 82 patients participating, 67 (81.7%) completed the 24-week study. The discontinuation rate after switching to LAI aripiprazole did not differ according to clinical characteristics including type of previous antipsychotics. Scores on the PANSS, PSP, SWN-K, CGI, and ERT were significantly improved after a switch to LAI aripiprazole without exacerbation of metabolic parameters and bodyweight. The improvements in the PANSS, PSP, and CGI scores were significantly greater in patients with recent-onset than in those with chronic schizophrenia; the improvement in metabolic parameters was significantly greater in the latter group. High rates of successful switching to LAI aripiprazole from other antipsychotics suggest its good tolerability and effectiveness. Improvements in psychopathology and social functioning were more evident in patients with recent- onset schizophrenia, and improvements in metabolic abnormalities were more prominent in patients with chronic schizophrenia.