Health economics study of paliperidone palmitate in the treatment of schizophrenia: a 12-month cohort study.

BACKGROUND: To analyze the economic benefits of paliperidone palmitate in the treatment of schizophrenia. METHODS: We collected 546 patients who met the diagnostic criteria for schizophrenia according to the 《International Statistical Classification of Diseases and Related Health Problems,10th》(ICD-10). We gathered general population data such as gender, age, marital status, and education level, then initiated treatment with paliperidone palmitate. Then Follow-up evaluations were conducted at 1, 3, 6, 9, and 12 months after the start of treatment to assess clinical efficacy, adverse reactions, and injection doses. We also collected information on the economic burden before and after 12 months of treatment, as well as the number of outpatient visits and hospitalizations in the past year to analyze economic benefits. RESULTS: The baseline patients totaled 546, with 239 still receiving treatment with paliperidone palmitate 12 months later. After 12 months of treatment, the number of outpatient visits per year increased compared to before (4 (2,10) vs. 12 (4,12), Z=-5.949, P < 0.001), while the number of hospitalizations decreased (1 (1,3) vs. 1 (1,2), Z = 5.625, P < 0.001). The inpatient costs in the direct medical expenses of patients after 12 months of treatment decreased compared to before (5000(2000,12000) vs. 3000 (1000,8050), P < 0.05), while there was no significant change in outpatient expenses and direct non-medical expenses (transportation, accommodation, meal, and family accompanying expenses, etc.) (P > 0.05); the indirect costs of patients after 12 months of treatment (lost productivity costs for patients and families, economic costs due to destructive behavior, costs of seeking non-medical assistance) decreased compared to before (300(150,600) vs. 150(100,200), P < 0.05). CONCLUSION: Palmatine palmitate reduces the number of hospitalizations for patients, as well as their direct and indirect economic burdens, and has good economic benefits.

Hyaluronidase impacts exposures of long-acting injectable paliperidone palmitate in rodent models.

A significant challenge in the development of long-acting injectable drug formulations, especially for anti-infective agents, is delivering an efficacious dose within a tolerable injection volume. Co-administration of the extracellular matrix-degrading enzyme hyaluronidase can increase maximum tolerable injection volumes but is untested for this benefit with long-acting injectable formulations. One concern is that hyaluronidase could potentially alter the tissue response surrounding an injection depot, a response known to be important for drug release kinetics of long-acting injectable formulations. The objective of this pilot study was to evaluate the impact of co-administration of hyaluronidase on the drug release kinetics, pharmacokinetic profiles, and injection site histopathology of the long-acting injectable paliperidone palmitate for up to four weeks following intramuscular injection in mouse and rat models. In both species, co-administration of hyaluronidase increased paliperidone plasma exposures the first week after injection but did not negate the overall long-acting release nature of the formulation. Hyaluronidase-associated modification of the injection site depot was observed in mice but not in rats. These findings suggest that further investigation of hyaluronidase with long-acting injectable agents is warranted.

Evaluating the 6-month formulation of paliperidone palmitate: a twice-yearly injectable treatment for schizophrenia in adults.

INTRODUCTION: Paliperidone Palmitate is the only antipsychotic that has been developed in three different intramuscular long-acting injectable (LAI) dosing regimen: monthly (PP1M), quarterly (PP3M), and from 2020 also twice-yearly (PP6M). The latter was approved for the maintenance treatment of adults with schizophrenia and clinically stabilized with PP1M or PP3M. AREAS COVERED: Data from studies evaluating efficacy in the maintenance treatment of schizophrenia with PP6M are reviewed. Since no post-marketing safety studies are currently available, data from spontaneous reporting system databases, FAERS and Eudravigilance, are analyzed and the reported treatment-emergent adverse events of PP6M are discussed. EXPERT OPINION: The efficacy of PP6M is comparable to that of PP3M in terms of relapses prevention in patients with schizophrenia previously stabilized on PP3M or PP1M. Also, the maintenance of clinical efficacy in the long term has been demonstrated. Data from pharmacovigilance analyses, as well as from phase 3 studies, show that PP6M is generally well tolerated, consistently with PP3M safety data. PP6M allows a longer dosing interval than any other LAI antipsychotics, potentially reducing nonadherence and disease relapses. In future, an increase in the prescription rates of PP6M is expected and real-world efficacy and tolerability studies will be conducted.

Valproate, risperidone, and paliperidone: A case of valproate-induced hyperammonemic encephalopathy.

Hyperammonemia is a well-known adverse effect of valproate that can progress to a potentially fatal condition known as valproate-induced hyperammonemic encephalopathy (VHE). VHE is more common when valproate is used in combination therapy with other antiepileptic medications. A growing number of case reports have pointed to a possible interaction with the antipsychotic risperidone leading to an increased risk of VHE. We present a case of VHE in which a 20-year-old male patient with bipolar affective disorder developed VHE when on concomitant valproate, risperidone, and paliperidone palmitate. On the seventh day of treatment with oral risperidone, oral divalproex sodium was added. Intramuscular paliperidone palmitate was initiated on day 13, and oral risperidone was discontinued after the second loading dose on day 16. The following day, the patient displayed worsening psychomotor retardation, swaying gait, drowsiness, and vomiting. The patient was found to have hyperammonemia and transferred to the emergency department for treatment of suspected VHE.

Relapse Rates With Paliperidone Palmitate in Adult Patients With Schizophrenia: Results for the 6-Month Formulation From an Open-label Extension Study Compared to Real-World Data for the 1-Month and 3-Month Formulations.

BACKGROUND: The 3 paliperidone palmitate (PP) long-acting injectable antipsychotic formulations, PP 1-month (PP1M), PP 3-month (PP3M), and PP 6-month (PP6M), have shown to reduce the risk of relapse in schizophrenia. The current phase-4 study constructed external comparator arms (ECAs) using real-world data for PP3M and PP1M and compared relapse prevention rates with PP6M from an open-label extension (OLE) study in adult patients with schizophrenia. METHODS: PP6M data were derived from a single-arm, 24-month, OLE study (NCT04072575), which included patients with schizophrenia who completed a 12-month randomized, double-blind, noninferiority, phase-3 study (NCT03345342) without relapse. Patients in the PP3M and PP1M ECAs were identified from the IBM® MarketScan® Multistate Medicaid Database based on similar eligibility criteria as the PP6M cohort. RESULTS: A total of 178 patients were included in each cohort following propensity score matching. Most patients were men (>70%; mean age: 39-41 years). Time to relapse (primary analysis based on Kaplan-Meier estimates) was significantly delayed in the PP6M cohort (P < .001, log-rank test). The relapse rate was lower in the PP6M cohort (3.9%) vs PP3M (20.2%) and PP1M (29.8%) cohorts. Risk of relapse decreased significantly (P < .001) by 82% for PP6M vs PP3M (HR = 0.18 [95% CI = 0.08 to 0.40]), 89% for PP6M vs PP1M (HR = 0.11 [0.05 to 0.25]), and 35% for PP3M vs PP1M (HR = 0.65 [0.42 to 0.99]; P = .043). Sensitivity analysis confirmed findings from the primary analysis. Although the ECAs were matched to mimic the characteristics of the PP6M cohort, heterogeneity between the groups could exist due to factors including prior study participation, unmeasured confounders, variations in data capture and quality, and completeness of clinical information. CONCLUSIONS: In a clinical trial setting, PP6M significantly delayed time to relapse and demonstrated lower relapse rates compared with PP3M and PP1M treatments in real-world settings among adult patients with schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04072575; EudraCT number: 2018-004532-30.

Characteristics of patients with schizophrenia switching from oral antipsychotics to once-monthly paliperidone palmitate (PP1M): a systematic review.

BACKGROUND: The utilization of once-monthly paliperidone palmitate (PP1M) in schizophrenia treatment has increased due to its enhanced adherence and convenience. However, there is limited evidence on patient characteristics that may influence treatment outcomes when switching from oral antipsychotics (OAPs) to PP1M therapy. This systematic review aims to identify such patient characteristics and explore potential beneficial factors to aid healthcare professionals in clinical practice. METHODS: A systematic literature search was conducted in the PubMed, Embase, and Cochrane Library databases up to July 19, 2022. Studies related to patients with schizophrenia who had been previously treated with OAPs and switched to PP1M were identified and included. Outcomes included the Positive and Negative Syndrome Scale (PANSS) total score, the clinical Global Impressions - Severity (CGI-S) score, the Personal and Social Performance (PSP) total score, and hospitalisation rate. Data were independently extracted and analysed. The results were presented through a narrative synthesis. RESULTS: Eleven studies with a total of 4150 patients were included, identifying nine potential characteristics. The most commonly reported characteristics was patient's prior treatment with OAPs, followed by the stage of disease, duration of illness (DI), ethnicity, reason for switching to PP1M, history of hospitalisation, time of start injection of PP1M, the PANSS and PSP total score at baseline. Patients in the acute stage, with a shorter DI, a less than 1-week time interval to PP1M injection, and a lower PANSS total score at baseline may have a trend on providing better improvements on PANSS total score. Acute stage and shorter DI also showed potential trends in reducing CGI-S score. Early initiation of PP1M, switching for reasons other than lack of efficacy, and a higher PSP score at baseline exhibited potential trends towards better PSP total score improvements. CONCLUSION: Our findings may suggest that patients in acute stage, with a shorter duration of illness, with early initiation of PP1M injection, and lower PANSS or PSP scores may trend towards better clinical results when transitioning to PP1M from OAPs. Further research is necessary to validate these potential associations and identify any unexplored characteristics. Such investigations are crucial for providing comprehensive clinical recommendations and informing treatment strategies in this context.

A randomized, prospective, active-controlled study comparing intramuscular long-acting paliperidone palmitate versus oral antipsychotics in patients with schizophrenia at risk of violent behavior.

OBJECTIVE: Paliperidone palmitate (PP) is an effective long-acting antipsychotic injection, but its impact on the behavior of schizophrenia patients with dangerous tendencies requires further investigation. This study aims to explore the effects of long-term antipsychotic treatment on this population in the community. METHODS: This 49-week, randomized controlled trial was conducted across 21 communities in Wuhan and enrolled 134 schizophrenia patients at risk for violent behavior. With a fixed block size of 10, participants were randomly assigned to receive either intramuscular PP 1-month formulation (PP1M) or oral antipsychotic medication (OAP) at a 1:1 ratio. Changes in patients' risk for violent/aggressive behavior, family burden, social, and cognitive functioning were measured using VRAPP, MOAS, PANSS, FBS, PSP, and RBANS scales from baseline to endpoint. Longitudinal data from multiple repeated measures were analyzed using linear mixed-effects models. RESULTS: The study protocol was completed by 77.6% of the patients overall. Significant improvements were observed in the risk assessment scores, MOAS total score, PANSS total score, PSP total score, and FBS total score of patients in the PP1M group from baseline to the end of treatment (all P < 0.05). Importantly, compared to patients in the OAP group, the improvements in these measures were also significantly greater in the PP1M group. Commonly observed AEs, such as hyperprolactinemia (70.3% vs. 62.65%) and muscle tension (45.3% vs. 57.8%), were considered to be the PP-related AEs. Nonetheless, the differences between the two groups did not reach statistical significance, and no new safety concerns emerged. CONCLUSIONS: Our study suggests that PP long-acting injection (LAI) is a safe and effective treatment option for community-dwelling schizophrenia patients with impulsive violence and risky behaviors.

Efficacy and safety of paliperidone palmitate versus other long-acting injectable antipsychotic drugs in the treatment of schizophrenia:a meta-analysis / 药物流行病学杂志

Objective To assess the safety of paliperidone palmitate(PP)injection versus other antipsychotic drugs long-acting injections(LAIs)in the treatment of schizophrenia.Methods PubMed,Web of Science,Embase,Cochrane Library,PsycINFO,CNKI,SinoMed,VIP and WanFang Data databases were searched to collect randomized controlled trials(RCTs)on PP injection versus other antipsychotic drugs LAIs in the treatment of schizophrenia from the inception to April 30,2023.Two reviewers independently screened literature,extracted data and assessed the risk of bias of included studies.Meta-analysis was then performed using RevMan 5.2 software.Results A total of 12 RCTs involving 4 368 patients were included.The results of Meta-analysis showed that there was no significant difference in clinical efficacy between PP injection treated group and risperidone LAIs treated group(P＞0.05),no significant difference was found for positive and negative syndrome scale(PANSS)overall score changes between PP injection treated group and other antipsychotic drugs LAIs treated group(P＞0.05).Compared with other antipsychotic LAIs treated groups,PP injection treated group had a significantly higher rate of total withdrawls(RR=1.14,95％CI 1.06 to 1.24,P＜0.01)and the incidence of adverse reactions of abnormal injection site(RR=2.08,95％CI 1.03 to 4.22,P=0.04).Conclusion Current evidence indicates that PP injection didn't show significant difference in efficacy outcomes,while may increase the incidence of some adverse reactions when compared with other antipsychotic drugs LAIs for schizophrenic.However,due to the limitations of the quantity and quality of the included studies,the above conclusions still need to be validated by more high-quality studies.

Impact of traditional versus nontraditional initiation dosing schedule of paliperidone palmitate on 30-day readmission and safety.

Introduction: Paliperidone palmitate (PP), a second-generation long-acting injectable antipsychotic, requires 2 injections upon initiation. Due to the fast-paced nature of the inpatient setting, the second dose may be administered earlier than recommended by labeled use despite the lack of evidence that evaluates this practice. Methods: This was a retrospective chart review that investigated the outcomes associated with the timing of the second PP initiation dose with the aim of comparing patients who received the second PP dose fewer than 3 days after the first injection with those who received it between 3 and 11 days after the first injection. The primary outcomes included 30-day psychiatric readmission, index hospitalization length of stay, and time until the next psychiatric hospitalization. Secondary outcomes included 6-month readmission and the percentage of patients who experienced an adverse event after the second injection. Results: No statistically significant differences were observed between groups for 30-day readmission. There was a statistically significant shortened index length of hospitalization (median, 2 vs 4 days; P < 0.001) and a non-statistically significant trend for time until the next psychiatric hospitalization (median, 25 vs 47 days) when comparing those who received the nontraditional loading regimen to those who received the traditional labeled loading regimen. No differences were observed in the secondary outcomes or safety/tolerability. Discussion: The results of the study indicate that there are no significant differences in readmission rates and adverse drug reactions in those who received the second PP dose earlier than recommended per labeled use. Larger, controlled studies are needed to further investigate clinical and safety outcomes.

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.

Second Generation Long-Acting Injectable Antipsychotics in Schizophrenia: The Patient's Subjective Quality of Life, Well-Being, and Satisfaction.

Schizophrenia (SZ) is among the twenty most disabling diseases worldwide. Subjective quality of life, well-being, and satisfaction are core elements to achieving personal recovery from the disorder. Long-acting injectable second-generation antipsychotics (SGA-LAIs) represent a valid therapeutic option for the treatment of SZ as they guarantee good efficacy and adherence to treatment. The aim of this rapid review is to summarize the evidence on the efficacy of SGA-LAIs in improving subjective quality of life, well-being, and satisfaction. The PubMed database was searched for original studies using SGA, LAI, risperidone, paliperidone, aripiprazole, olanzapine, SZ, and psychosis as keywords. Twenty-one studies were included: 13 clinical trials, 7 observational studies, and 1 post hoc analysis. It has been shown that SGA-LAIs bring an improvement to specific domains of subjective and self-rated quality of life, well-being, or satisfaction in prospective observational studies without a control arm and in randomized controlled trials versus placebo. The superiority of SGA-LAIs as compared with oral equivalents and haloperidol-LAI has been reported by some randomized controlled and observational studies. Although promising, the evidence is still limited because of the lack of studies and several methodological issues concerning the choice of the sample, the evaluation of the outcome variables, and the study design. New methodologically sound studies are needed.

Comparative effectiveness study of paliperidone palmitate 6-month with a real-world external comparator arm of paliperidone palmitate 1-month or 3-month in patients with schizophrenia.

Background: The paliperidone palmitate 6-month (PP6M) long-acting injectable formulation is currently the longest dosing interval available for schizophrenia treatment. Objective: To compare treatment outcomes between a real-world external comparator arm (ECA; NeuroBlu database) and the PP6M open-label extension (OLE) clinical trial arm. Methods: The ECA comprised patients receiving PP 1-month (PP1M) or PP 3-month (PP3M) for ⩾12 months without a relapse. The PP6M OLE arm included patients with PP1M treatment prior to randomization who completed the 12-month double-blind PP6M study on either PP3M or PP6M relapse-free. Inverse probability treatment weighting (IPTW) was used to study time-to-relapse (primary outcome) and change in Clinical Global Impressions-Severity (CGI-S) score (secondary outcome). Results: At 24 months, 3.9% (7/178) of patients in the PP6M cohort experienced a relapse versus 15.6% (26/167) in the ECA. Time-to-relapse was longer in the PP6M cohort versus the ECA at 12-, 18-, and 24-months across the different weighting methods; median time-to-relapse was not reached in both cohorts. Hazard ratio (HR) for relapse was significantly lower for the PP6M cohort versus the ECA throughout the duration of the study [HR at 24 months: 0.18 (95% CI: 0.08-0.42), p < 0.001]. At 24 months, change in CGI-S score for the PP6M cohort was 0.76 points lower than the ECA (p < 0.001). Results were similar in a sensitivity analysis using propensity score matching (PSM); IPTW resulted in larger sample sizes in balanced dataset than PSM. Conclusion: Consistent findings across weighting and matching methods suggest PP6M efficacy in reducing and delaying relapses and long-term symptom control compared to PP1M/PP3M in usual-care settings. Additional confounds, such as greater illness severity and more frequent comorbidities and comedications in the ECA, were not fully controlled by the applied statistical methods. Future real-world studies directly comparing PP6M with PP3M/PP1M and adjusting for these confounders are warranted.

Paliperidone long-acting injection in the treatment of an adolescent with schizophrenia with fluctuating mental symptoms during menstrual period: a case report.

Background: The treatment of schizophrenia, a chronic disabling psychiatric disorder, mainly relies on antipsychotics to control the disease and improve clinical symptoms. Various medication options are available, and differences in treatment effects, even for the same medication, have been noted. Treatment efficacy is correlated with the patient's sex, age, and physical condition. When a drug fails to achieve the desired effect or the symptoms are unstable, the drug dose is often increased or a change in medication is advised according to the patient's situation. Case presentation: We report the case of a 16 years-old girl with schizophrenia and apparent psychotic symptoms. According to the genetic testing results, the symptoms were effectively controlled, and she was discharged from the hospital with the prescription of paliperidone sustained-release tablets. During the follow-up, her symptoms fluctuated during menstrual period, causing her great distress. Furthermore, her compliance gradually declined during the following 2 years of treatment, and the medication was often discontinued. We changed the drug from an oral tablet to an injection preparation while maintaining the active ingredients of the drug. The patient's symptoms were significantly controlled, and no fluctuation of symptoms occurred during the menstrual cycle. Conclusion: Long-acting antipsychotic injections can be administered to female adolescents with schizophrenia who experience fluctuating psychotic symptoms during menstruation. This technique can ensure both consistency of medication and improvement in clinical symptoms.

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.

Barriers to the use of three-month Paliperidone Palmitate formulation: a study from an Italian real-world setting.

BACKGROUND: Long-acting injectable paliperidone can improve adherence in psychotic patients and reduce relapses and healthcare resource utilization (HRU). This study compares the effectiveness of the three-monthly paliperidone palmitate (PP3M) with the one-monthly formulation (PP1M) and investigates reasons that hinder the use of PP3M in real-world settings. METHODS: The authors conducted a three-phase observational study. For subjects recruited from six psychiatric services in Milan, HRU outcomes of PP3M prescription were evaluated through a 12-month mirror-image design (phase 1) and a comparison of HRU of PP1M-only subjects and PP3M subjects during the year prior to PP3M initiation (phase 2). Lastly, they conducted a survey among physicians concerning reasons for not switching to PP3M (phase 3). RESULTS: A total of 119 subjects (61 on PP3M and 58 on PP1M) were included. One year after PP3M initiation, outpatients' visits decreased significantly. Comparing PP3M with PP1M subjects, no significant difference was found in HRU. Perception of patient's unstable clinical condition was the main reason for maintaining PP1M (32.8%), followed by the need for monthly monitoring (19.7%). CONCLUSION: PP3M initiation was associated with an overall HRU reduction. Subjects switched to PP3M had similar HRU when compared to those who did not, suggesting similar clinical conditions in both groups.

Projecting the Potential Budget Impact Analysis of Paliperidone Palmitate in Egyptian Adult Patients with Schizophrenia.

Background: Schizophrenia is a serious mental disorder that has greater negative consequences on role functioning than many other severe chronic diseases. Objective: We evaluated the economic impact of long-acting injections of paliperidone palmitate (PP) vs daily oral antipsychotics to treat chronic schizophrenia from a societal perspective over a 2-year period. Methods: A static budget impact model was developed to compare PP with daily oral antipsychotics (risperidone, olanzapine, and aripiprazole) in the treatment of patients with chronic schizophrenia. Our study included treatments used during relapse and hospitalization, validated by an expert panel. The clinical parameters were extracted from the PRIDE trial. Direct medical costs and indirect costs were measured. The unit cost of drug acquisition for all medications was extracted from the public sector. One-way sensitivity analyses were conducted. Results: The target population in our model was estimated to be 142 incident patients. In the first year, the total drug costs in Egyptian pounds (EGP) for PP and oral antipsychotics were £2.7 million and £724 004, respectively, while the total medical costs for PP and oral antipsychotics were £3 million and £5.6 million, respectively. In the second year, the total drug costs for PP and oral antipsychotics were £2.7 million and £724 004, respectively, while the total medical costs for PP and oral antipsychotics were £3 million and £5 million, respectively. The total costs for PP (£11.6 million) over 2 years were less than those of oral antipsychotics without PP (£12.7 million). PP produced an estimated budget savings of £1 046 561 (budget savings per patient per year, £3667). In addition, PP resulted in the avoidance of 18 hospitalizations per year compared with the without-PP arm. Sensitivity analyses showed that the percent of hospitalizations for both oral antipsychotics and PP had the greatest impact on the results. Conclusion: The lower hospitalization rates associated with PP offset the increase in drug costs. PP may potentially be cost-saving compared with the standard of care in chronic schizophrenia in Egyptian representative healthcare settings. Policy makers may consider this approach to improve patient outcomes and budget sustainability.

Cost-utility analysis of using paliperidone palmitate in schizophrenia in China.

Objective: Long-acting injections (LAIs) of paliperidone palmitate have been shown to improve medication adherence and relieve psychotic symptoms. However, the specific cost-utility analysis of these LAIs in schizophrenia in China remains unclear. Methods: A multi-state Markov model was constructed to simulate the economic outcomes of patients with schizophrenia in China who received paliperidone palmitate 1-month formulation (PP1M), paliperidone palmitate 3-month formulation (PP3M), and paliperidone extended-release (ER). A cost-utility analysis was conducted, mostly derived from published literature and clinical databases. All costs and utilities were discounted at a rate of 5% per annum. The primary outcome measure was the incremental cost-effectiveness ratios (ICERs). A series of sensitivity analyses were also applied. Results: After 20 years, compared to ER, using PP1M resulted in an increased discounted cost from $36,252.59 to $43,207.28. This increased cost was associated with a gain in quality-adjusted life years (QALYs) from 8.60 to 9.45. As a result, the ICER for PP1M was estimated to be $8,247.46/QALY, which was lower than the willingness-to-pay (WTP) threshold of $12,756.55/QALY. When using PP3M instead of ER, the incremental cost was $768.81 and the incremental utility was 0.88 QALYs, projecting an ICER of $873.13/QALY, which was also lower than the WTP threshold of $12,756.55/QALY. The univariate sensitivity analysis showed that the costs of PP1M, PP3M, and ER had the greatest impact on ICERs. The probability sensitivity analysis (PSA) revealed that when the WTP thresholds were $12,756.55/QALY, the probability of PP1M and PP3M being cost-effective was 59.2% and 66.0%, respectively. Conclusion: From the Chinese healthcare system perspective, PP3M and PP1M are both more cost-effective compared to ER, and PP3M has notable cost-utility advantages over PP1M.

Treatment Retention Rates of 3-monthly Paliperidone Palmitate and Risk Factors Associated with Discontinuation: A Population-based Cohort Study.

Objective: Limited evidence exists regarding real-world 3-monthly paliperidone palmitate (PP3M) treatment retention and associated factors. Methods: We conducted a retrospective, nationwide cohort study using the Taiwan National Health Insurance Research Database between October 2017 and December 2019. Adult patients with schizophrenia initiated on PP3M were enrolled. The primary outcomes were time to PP3M discontinuation, time to psychiatric hospitalization, and the proportions of patients receiving the next PP3M dose within 120 days among first-, second-, and third-dose completers. Key covariates included prior PP1M duration and adequate PP3M initiation. Results: The PP3M treatment retention rates were 79.7%, 66.3%, and 52.5% after 6, 12, and 24 months, respectively, with 86.4%, 90.6%, and 90.0% of respective first-, second-, and third-dose completers receiving the next PP3M dose. Adequate PP3M initiation and prior PP1M treatment duration > 180 days were associated with favorable PP3M treatment retention. In multivariate analyses, PP1M durations of 180-360 days (adjusted relative risk [aRR], 1.76) or < 180 days (aRR, 2.79) were associated with PP3M discontinuation at the second dose. Inadequate PP3M initiation was associated with discontinuation at the third dose (aRR, 2.18). Patients fully adherent to PP3M treatment in the first year had a higher probability of being free from psychiatric hospitalization (86.7% at 2 years), compared with those partially adherent or non-adherent to PP3M in the first year. Conclusion: Prior PP1M duration and adequate PP3M initiation are major factors affecting PP3M treatment retention. Higher PP3M treatment retention is associated with a lower risk of psychiatric hospitalization.

Long-Term Efficacy and Safety of Paliperidone 6-Month Formulation: An Open-Label 2-Year Extension of a 1-Year Double-Blind Study in Adult Participants With Schizophrenia.

BACKGROUND: Paliperidone palmitate 6-month (PP6M) demonstrated noninferiority to paliperidone palmitate 3-month in preventing relapse in patients with schizophrenia in a phase 3 double-blind (DB) study (NCT03345342). Here, we report long-term efficacy and safety results from a 2-year single-arm, open-label extension (OLE; NCT04072575) of this DB study. METHODS: Participants who completed the DB study without relapse were enrolled and followed-up every 3 months up to 2 years. Participants received 4 PP6M gluteal injections (700/1000 mg eq.) at baseline, 6-month, 12-month, and 18-month visits. Efficacy endpoints included assessment of relapse, Positive and Negative Syndrome Scale total score, Personal and Social Performance score, and Clinical Global Impression-Severity scale change from baseline. Safety was assessed by treatment-emergent adverse events (TEAEs), physical examinations, and laboratory tests. RESULTS: Of 178 participants enrolled, 154 (86.5%) completed the OLE (mean age: 40.4 years, men: 70.8%; mean duration of PP6M exposure during OLE: 682.1 days). Overall, 7/178 (3.9%) participants relapsed between 20 and 703 days after enrolment. Mean (SD) changes from baseline to endpoint were as follows: Positive and Negative Syndrome Scale total score, 0.7 (8.22); Clinical Global Impression-Severity, 0.0 (0.51); and Personal and Social Performance Scale, 0.5 (7.47). Overall, 111/178 participants (62.4%) reported ≥1 TEAE; most common (>5%) TEAEs were headache (13.5%) and increased blood prolactin/hyperprolactinemia (18.0%); 8/178 (4.5%) participants experienced serious TEAEs, and 6/178 (3.4%) participants withdrew due to TEAEs. No deaths were reported. CONCLUSIONS: The relapse rate observed with PP6M during the 2-year OLE was low (3.9%). Clinical and functional improvements demonstrated in the DB study were maintained during OLE, and no new safety concerns were identified. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04072575; EudraCT number: 2018-004532-30.