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.

A systematic review of the real-world effectiveness and economic and humanistic outcomes of selected oral antipsychotics among patients with schizophrenia in the United States: Updating the evidence and gaps.

BACKGROUND: Schizophrenia is a chronic, relapsing, and burdensome psychiatric disorder affecting approximately 0.25%-0.6% of the US population. Oral antipsychotic treatment (OAT) remains the cornerstone for managing schizophrenia. However, nonadherence and high treatment failure lead to increased disease burden and medical spending. Cost-effective management of schizophrenia requires understanding the value of current therapies to facilitate better planning of management policies while addressing unmet needs. OBJECTIVE: To review existing evidence and gaps regarding real-world effectiveness and economic and humanistic outcomes of OATs, including asenapine, brexpiprazole, cariprazine, iloperidone, lumateperone, lurasidone, olanzapine/samidorphan, paliperidone, and quetiapine. METHODS: We conducted a literature search using PubMed, American Psychological Association PsycINFO (EBSCOhost), and the Cumulative Index of Nursing and Allied Health Literature from January 2010 to March 2022 as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English-language articles describing adults with schizophrenia receiving at least 1 of the selected OATs and reporting real-world effectiveness, direct or indirect costs, humanistic outcomes, behavioral outcomes, adherence/persistence patterns, or product switching were identified. RESULTS: We identified 25 studies from a total of 24,190 articles. Real-world effectiveness, cost, and adherence/persistence outcomes were reported for most OATs that were selected. Humanistic outcomes and product switching were reported only for lurasidone. Behavioral outcomes (eg, interpersonal relations and suicide ideation) were not reported for any OAT. The key economic outcomes across studies were incremental cost-effectiveness ratios, cost per quality-adjusted life-years, and health care costs. In studies that compared long-acting injectables (LAIs) with OATs, LAIs had a higher pharmacy and lower medical costs, while total health care cost was similar between LAIs and OATs. Indirect costs associated with presenteeism, absenteeism, or work productivity were not reported for any of the selected OATs. Overall, patients had poor adherence to OATs, ranging between 20% and 61% across studies. Product switching did not impact the all-cause health care costs before and after treatment. CONCLUSIONS: Our findings showed considerable gaps exist for evidence on behavioral outcomes, humanistic outcomes, medication switching, and adherence/persistence across OATs. Our findings also suggest an unmet need regarding treatment nonadherence and lack of persistence among patients receiving OATs. We identified a need for research addressing OATs' behavioral and humanistic outcomes and evaluating the impact of product switching in adults with schizophrenia in the United States, which could assist clinicians in promoting patient-centered care and help payers understand the total value of new antipsychotic drugs.

Continuity of care among patients newly initiated on second-generation oral or long-acting injectable antipsychotics during a schizophrenia-related inpatient stay.

BACKGROUND: Maintaining continuity of care after schizophrenia-related hospitalization is challenging for patients and healthcare providers and systems. Prior evidence suggests that second-generation long-acting injectable antipsychotics (SGLAIs) may reduce the risk of treatment nonadherence and readmission versus oral atypical antipsychotics (OAAs). Therefore, quality measures were compared between patients initiated on SGLAIs and OAAs in the United States. METHODS: Adults newly initiated on an SGLAI or OAA during a schizophrenia-related inpatient stay were identified in HealthVerity databases (01/2015-12/2020); the index date was the hospital discharge date. Patients had continuous health insurance coverage for pharmacy and medical services for 6 months pre-admission and post-discharge from the inpatient stay and ≥1 pharmacy or medical claim (i.e. treatment as indicated by the observed insurance claims) for an antipsychotic other than the index SGLAI or OAA in the 6 months pre-admission. Antipsychotic use and adherence, and schizophrenia-related readmissions and outpatient visits were compared during the 6-month period post-discharge. Characteristics between cohorts were balanced using inverse probability weights. RESULTS: Post-discharge, only 36.9% and 40.7% of weighted SGLAI (N = 466) and OAA (N = 517) patients had ≥1 pharmacy or medical claim for the antipsychotic initiated during the inpatient stay, among whom SGLAI patients were 4.4 times more likely to be adherent to that antipsychotic compared to OAA patients (p < .001). Additionally, SGLAI patients were 2.3 and 3.0 times more likely to have a pharmacy or medical claim for and be adherent to any antipsychotic relative to OAA patients (including index antipsychotic; all p < .001). Within 7 and 30 days post-discharge, 1.7% and 13.0% of SGLAI patients and 4.1% and 12.6% of OAA patients had a readmission. Further, SGLAI patients were 51% more likely to have an outpatient visit compared to OAA patients (p = .044). CONCLUSIONS: Less than half of patients initiated on antipsychotics during a schizophrenia-related inpatient stay continued the same treatment post-discharge. However, SGLAI patients were more likely to be adherent to the initiated antipsychotic and to have an outpatient visit, which may suggest improved continuity of care post-discharge relative to OAA patients.

Cost-effectiveness analysis of monthly, 3-monthly, and 6-monthly long-acting injectable and oral paliperidone in adults with schizophrenia.

BACKGROUND: Paliperidone is among the most cost-effective antipsychotics in adults with schizophrenia, and it has different formulations, including oral paliperidone extended-release (ER) and long-acting injectable (LAI) paliperidone formulations administered every month (PP1M), 3 months (PP3M), or 6 months (PP6M). However, cost-effectiveness analyses comparing different paliperidone formulations were limited. OBJECTIVE: To compare the cost-effectiveness across different paliperidone formulations. METHODS: A Markov model was developed to simulate 1,000 adults aged 40 years with stable schizophrenia transitioning among stable disease-medication adherent, stable disease-medication nonadherent, relapse with hospitalization, relapse with ambulatory care, and death states every 3 months for 5 years. Drug costs were estimated using the prices listed in the Veterans Affairs Federal Supply Schedule, and costs for treating complications were estimated from published studies. All costs were estimated from the US health care system perspective and standardized to 2022 US dollars using the Consumer Price Index Inflation Calculator. Quality-adjusted life-years (QALYs) were estimated using relapse rates from randomized clinical trials and health-related quality of life scores from observational studies. The estimated future costs and QALYs were discounted at 3%. We reported incremental net monetary benefits between alternative formulations at the $50,000 willingness-to-pay (WTP) threshold with a positive value indicating cost-effectiveness. The impact of parameter uncertainty on study outcomes was assessed using 1-way deterministic and probabilistic sensitivity analyses. RESULTS: In adults with schizophrenia stabilized with paliperidone ER, switching to LAI formulations was associated with increased QALY (PP1M = 0.05, PP3M = 0.14, PP6M = 0.15) and increased cost (PP1M = 49,433, PP3M = 26,698, PP6M = 26,147), leading to a negative incremental net monetary benefit (PP1M = -$46,804, PP3M = -$19,508, PP6M = -$18,886) compared with continuing ER. Among LAI formulations, PP6M was cost-saving with the most QALYs gained (cost = $63,277, QALY = 3.731), followed by PP3M (cost = $63,828, QALY = 3.729) and PP1M (cost = $86,563, QALY = 3.638). At the $50,000 WTP threshold, the probabilities for PP1M, PP3M, and PP6M being cost-effective compared with paliperidone ER were 0.4%, 10.2%, and 9.8%, respectively. The probability of PP6M being cost-effective was 92.6% for the PP6M-PP1M pair and 55.2% for the PP6M-PP3M pair, and 91.1% of PP3M use was cost-effective in the PP3M-PP1M pair. The results were generally robust in the sensitivity analyses, even at the $190,000 WTP threshold. CONCLUSIONS: For patients with schizophrenia stabilized with paliperidone ER, switching to LAI formulations was not cost-effective, suggesting the high drug costs for LAI may not justify the improved quality of life within 5 years. Among LAI formulations, PP6M was cost-effective over PP1M and PP3M.

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.

Real-world calibration and transportability of the Disease Recovery Evaluation and Modification (DREaM) randomized clinical trial in adult Medicaid beneficiaries with recent-onset schizophrenia.

BACKGROUND: The Disease Recovery Evaluation and Modification study (DREaM; NCT02431702) assessed the benefit of initiating paliperidone palmitate (PP), a long-acting injectable antipsychotic, in patients with recent-onset schizophrenia or schizophreniform disorder. OBJECTIVE: To determine whether reductions in psychiatric hospitalizations with early initiation of PP vs oral antipsychotic (OAP) therapy observed in a DREaM post hoc analysis are transportable to a real-world population of patients with recent-onset schizophrenia. METHODS: Patients enrolled in DREaM were randomized to receive OAP or PP for 9 months, after which OAP recipients were re-randomized to receive OAP or PP for another 9 months. We used this design to form treatment arms: OAP-OAP, OAP-PP, and PP-PP. Inclusion/exclusion criteria were used to identify a Medicaid Managed Care (MMC) OAP-treated cohort of 1,000 patients diagnosed with schizophrenia using IBM Truven databases from 2015 to 2019. The MMC cohort was combined with the subset of patients diagnosed with schizophrenia enrolled in DREaM from US sites (N = 45, 43, and 44 for OAP-OAP, OAP-PP, and PP-PP, respectively). Propensity scores for the MMC cohort were estimated using baseline variables identified via double-lasso regression. Estimated propensity scores were used to weight psychiatric hospitalizations in the DREaM OAP-OAP group and compared with observed MMC OAP cohort psychiatric hospitalizations. After the successful calibration of the DREaM OAP-OAP group, similar approaches were taken for the OAP-PP and PP-PP groups to transport DREaM effects to MMC data. RESULTS: Standardized mean differences in baseline covariates between DREaM treatment arms and MMC groups were substantially reduced after calibration. The 18-month cumulative numbers of psychiatric hospitalizations per patient (SE) were 0.83 (0.14) for the MMC cohort, 0.43 (0.14) for the unweighted OAP-OAP, and 0.80 (0.37) for the calibrated OAP-OAP. The difference between the calibrated OAP-OAP and MMC was not statistically significant (difference, 0.03 [95% CI = -0.67 to 0.81]), indicating successful calibration. The mean difference in 18-month cumulative psychiatric hospitalizations relative to the MMC cohort was -0.77 (95% CI = -1.08 to -0.47) for OAP-PP and -0.83 (95% CI = -1.15 to -0.60) for PP-PP. CONCLUSIONS: Our study demonstrates that results from the DREaM OAP-OAP group reflect psychiatric hospitalizations in a real-world population when calibrated using specific baseline characteristics. Transporting the DREaM effects, we find that using OAP-PP and PP-PP treatment strategies for patients with recent-onset schizophrenia in the MMC population could reduce psychiatric hospitalizations compared with the use of OAP. These findings, along with the potential reduction in associated costs, should be considered when assessing the value of PP formulations. DISCLOSURES: Dr Basu reports consulting fees through Salutis Consulting LLC related to this work. Dr Mavros is a former employee of the Janssen Pharmaceutical Companies of Johnson & Johnson, Inc, and holds stock in the company. Ms Benson, Dr Fu, Ms Patel, and Dr Brown are employees of Janssen Scientific Affairs, LLC, and hold stock in Johnson & Johnson. This research was funded by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design; collection, analysis, and interpretation of data; and development and review of the manuscript. All authors had full access to the study data and take responsibility for data integrity and the accuracy of the analyses. All authors provided direction and comments on the manuscript, reviewed and approved the final version prior to submission, made the final decision about where to publish these data, and approved submission to this journal.

Projecting the economic outcomes of switching patients with schizophrenia from oral atypical antipsychotics to once-monthly, once-every-3-months, and once-every-6-months paliperidone palmitate.

BACKGROUND: Among patients with schizophrenia, nonadherence to oral atypical antipsychotics (OAAs) leads to increased risk of relapses, which entails substantial economic burden. OBJECTIVE: To evaluate the impact on health care costs and relapse rates of switching patients with schizophrenia from OAAs to once-monthly paliperidone palmitate (PP1M), with subsequent transitions to once-every-3-months (PP3M) and once-every-6-months paliperidone palmitate (PP6M). METHODS: A 36-month Markov model was developed from a Medicaid payer's perspective. Two non-mutually exclusive subpopulations of adults with schizophrenia who were nonadherent to OAAs were considered: (1) recently relapsed and (2) young adults (aged 18-35). Patients were assumed nonadherent to OAAs until switching treatments, which was permissible multiple times during the 36-month period. Patients switching to PP1M could subsequently transition to PP3M and PP6M. Relapse rates were assumed consistent across treatments based on patients' adherence. Model inputs were literature based. PP6M transition rates were assumed similar to PP3M. Cost savings were reported at the plan level and per patient switched. RESULTS: In a hypothetical health plan of 1 million Medicaid beneficiaries, an estimated 10,053 adults with schizophrenia were nonadherent to OAAs, among whom 7,454 were recently relapsed and 4,002 were young adults. Switching 5% of recently relapsed adults (N = 373) from OAAs to PP1M prior to subsequent relapse resulted in 541 relapses avoided and plan-level savings of $8.2M after 3 years. Incorporating transitions to PP3M/PP6M increased net savings to $9.1M and 631 relapses were avoided. Among young adults, switching 5% (N = 200) from OAAs to PP1M saved $1.8M at the plan level with 178 relapses avoided after 3 years. Including transitions to PP3M/PP6M, 3-year plan-level savings were $2.0M with 223 relapses avoided. Per recently relapsed patient switched to PP1M, and subsequently to PP3M/PP6M, cumulative 3-year cost savings were $22,100 and $24,300, respectively. Among young adults, corresponding 3-year cost savings per patient were $8,900 and $9,800. CONCLUSIONS: Switching nonadherent patients from OAAs to PP1M results in substantial cost savings and reduces relapse rates. Incorporating transitions to PP3M/PP6M leads to incremental cost savings and additional relapses avoided. DISCLOSURES: Financial support for this research was provided by Janssen Scientific Affairs, LLC. Ms Morrison, Ms Ghelerter, Ms Vermette-Laforme, Mr Lefebvre, and Mr Pilon are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC., which funded the development and conduct of this study and manuscript. Dr Lin and Ms Benson are employees of Janssen Scientific Affairs, LLC., and stockholders of Johnson & Johnson.

Adherence, Persistence, Readmissions, and Costs in Medicaid Members with Schizophrenia or Schizoaffective Disorder Initiating Paliperidone Palmitate Versus Switching Oral Antipsychotics: A Real-World Retrospective Investigation.

INTRODUCTION: Long-acting injectable antipsychotic agents have been suggested to improve adherence and patient outcomes in schizophrenia or schizoaffective disorder. The purpose of this study was to assess medication use patterns (i.e., medication adherence, persistence), hospital and emergency department readmissions, and total direct medical costs of Oklahoma Medicaid members with schizophrenia or schizoaffective disorder switching from an oral antipsychotic (OAP) to once-monthly paliperidone palmitate (PP1M) or to another OAP (OAP-switch). METHODS: A historical cohort analysis was conducted from 1 January 2016 to 31 December 2020 among adults aged ≥ 18 and ≤ 64 years with schizophrenia or schizoaffective disorder who were previously treated with an OAP. The first claim for PP1M or a new OAP defined the study index date. Members who transitioned from PP1M to 3-month formulation (PP3M) were included (i.e., PP1M/PP3M). Proportion of days covered (PDC), 45-day treatment gaps, 30-day readmissions to hospitals or emergency department, and total direct medical costs were assessed using multivariable, machine-learning least absolute shrinkage, and selection operator (Lasso) regressions controlling for numerous demographic, clinical, mental health, and provider characteristics. RESULTS: Among 295 Medicaid members meeting full inclusion criteria, 183 involved PP1M/PP3Ms (44 PP1M cases transitioned to PP3M) and 112 involved an OAP-switch. The multivariable-adjusted odds of readmission were significantly associated with a 45-day treatment gap (p < 0.05) and non-adherence (i.e., PDC < 80%) (p < 0.05). Relative to PP1M/PP3Ms, the multivariable analyses also indicated that OAP-switch was associated with an 18.5% lower PDC, 92.3% higher number of 45-day treatment gaps, and an approximately 90% higher odds of all-cause 30-day readmission (p < 0.05). The adjusted pre- to post-index change in cost was approximately 49% lower for OAP-switches versus PP1M/PP3Ms (p < 0.001), although unadjusted post-index costs did not differ between groups (p = 0.440). CONCLUSION: This real-world investigation of adult Medicaid members with schizophrenia or schizoaffective disorder observed improved adherence and persistence with fewer readmissions with PP1M/PP3Ms versus OAP-switches.

Health care resource utilization and costs in patients receiving long-acting injectable vs oral antipsychotics: A comparative analysis from the Disease Recovery Evaluation and Modification (DREaM) study.

BACKGROUND: Given relapse frequency early in the course of schizophrenia, recently diagnosed patients may benefit from longacting injectable antipsychotics, which are associated with reduced risk of relapse and hospitalization compared with oral antipsychotics (OAPs). OBJECTIVE: To compare health care resource utilization (HCRU) and costs in patients with recent-onset schizophrenia treated with continuous paliperidone palmitate (PP) or continuous OAP or who switched from OAP to PP. METHODS: In this analysis, we combined the 2 randomized phases of the prospective, open-label Disease Recovery Evaluation and Modification (DREaM) clinical study using the principal stratification method to generate 3 treatment strategies: continuous PP for 18 months (PP-PP), continuous OAP for 18 months (OAP-OAP), and initial OAP switched to PP after 9 months (OAP-PP). HCRU metrics included psychiatric hospitalizations, psychiatric and nonpsychiatric emergency department visits, and ambulatory visits. Costs were analyzed using generalized linear models with inverse-probability weighting based on time-varying probabilities of exposure. Robust SEs were estimated using individual-level clustered bootstrapping. Subgroup analyses were performed by region and prior antipsychotic use (< 6 vs ≥ 6 months). RESULTS: A total of 181 patients were included in the PP-PP (n = 61), OAP-OAP (n = 61), and OAP-PP (n = 59) groups. The majority of patients (73%) were enrolled at study sites in the United States, and 48% had received an antipsychotic for less than 6 months prior to study entry. Baseline characteristics were well balanced, and no significant differences in discontinuation rates were observed across treatment strategies. Compared with OAP-OAP, significantly lower cumulative HCRU and costs were apparent before 9 months in the PP-PP group and after 9 months in the OAP-PP group. The cumulative 18-month effects of PP-PP and OAP-PP vs OAP-OAP on the number of psychiatric hospitalizations were ‒0.28 (95% CI = ‒0.51 to ‒0.08) and ‒0.27 (95% CI = ‒0.50 to 0.04), respectively, and those on cumulative mean per-patient total health care costs (in 2020 USD) were -$2,867 (95% CI = ‒$5,133 to ‒$750) and ‒$2,789 (95% CI = ‒$5,155 to ‒$701), respectively. Subgroup analyses indicated a greater reduction in psychiatric hospitalizations and costs with PP-PP or OAP-PP relative to OAP-OAP in patients with less than 6 vs 6 or more months of prior antipsychotic therapy. CONCLUSIONS: Continuous early use of PP in adults with recentonset schizophrenia significantly reduced psychiatric hospitalizations and associated estimated costs compared with OAP; these effects were particularly notable for patients with a shorter duration of prior antipsychotic use. As this was a post hoc analysis of a study that was not powered for HCRU assessments, future studies calibrating these effects to larger real-world populations will be useful. DISCLOSURES: Dr Basu reports consulting fees through Salutis Consulting LLC related to this work. Ms Benson, Dr Turkoz, Ms Patel, Dr Baker, and Dr Brown are employees of Janssen Scientific Affairs, LLC, and stockholders of Johnson & Johnson, Inc. This research was funded by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design; collection, analysis, and interpretation of data; development and review of the manuscript; and decision to submit the manuscript for publication.

Assessment of risk factors of treatment discontinuation among patients on paliperidone palmitate and risperidone microspheres in France, Germany and Belgium.

BACKGROUND: Long-acting antipsychotics (e.g. 1-monthly (PP1M) / 3-monthly (PP3M) injection forms of paliperidone palmitate) have been developed to improve treatment continuation in schizophrenia patients. We aim to assess risk factors of treatment discontinuation of patients on paliperidone palmitate and risperidone microsphere. Additionally, treatment discontinuation between patients with PP1M and PP3M was compared. METHODS: The IQVIA Longitudinal Prescription databases were used. Risk factors of treatment discontinuation were identified by a multilevel survival regression using Cox proportional hazards model. Kaplan Meier analyses were performed by identified significant risk factors. RESULTS: Twenty-five thousand three hundred sixty-one patients (France: 9,720; Germany: 14,461; Belgium: 1,180) were included. Over a one-year follow-up period, a significant lower treatment discontinuation was observed for patients newly initiated on paliperidone palmitate (53.8%) than those on risperidone microspheres (85.4%). Additionally, a significantly lower treatment discontinuation was found for 'stable' PP3M patients (19.2%) than 'stable' PP1M patients (37.1%). Patients were more likely to discontinue when drugs were prescribed by GP only (HR = 1.68, p < 0.001 vs. psychiatrist only) or if they were female (HR = 1.07, p < 0.001), whereas discontinuation decreased with age (31-50 years: HR = 0.95, p = 0.006 and > 50 years: HR = 0.91, p < 0.001 vs. 18-30 years). CONCLUSIONS: This study demonstrates that patients stay significantly longer on treatment when initiated on paliperidone palmitate as compared to risperidone microspheres. It also indicated a higher treatment continuation of PP3M over PP1M. Treatment continuation is likely to be improved by empowering GPs with mental health knowledge and managing patients by a collaborative primary care-mental health model. Further research is needed to understand why females and younger patients have more treatment discontinuation.

Letter to the Editor: Rethinking The Cost Of Antipsychotic Treatment: The Average Cost Of The Drugs Used In Turkey In 2020. / Editöre Mektup: Çildirigideren Ilaç Tedavisinde Maliyeti Yeniden Düsünmek: Türkiye'de Kullanilan Ilaçlarin 2020 Yili Ortalama Tedavi Maliyeti.

Dear Editor, The costs of antipsychotic drugs (APDs) used in the treatment of mental disorders with psychosis are mentioned in treatment guidelines (APA 2021, NICE 2014). While the American Psychiatric Association guideline states that every specialist should make decisions according to the rules and conditions of their country and their region, the National Institute of Health and Clinical Excellence guideline emphasizes that drug costs must be taken into consideration in the treatment process. Classical or first-generation antipsychotic drugs (FAPDs) are relatively cheaper in terms of sales prices compared to atypical or second-generation antipsychotic drugs (SAPDs) with a slightly different effect mechanism. The price difference between the two drug groups can be so large that sometimes it may be necessary to consider whether the cost of a second-generation drug is worth its benefit. While deciding on the use of first-generation or second-generation drugs, a multifaceted assessment should be made, such as the patient's level of compliance with the treatment, the possibility of occurrence of side effects, the possible effects of these side effects on body health and treatment compliance, and whether or not the costs are covered. The most important criterion that determines the choice of medication for psychiatrists is of course the multi-dimensional benefit/harm ratio that the drug used will reveal in the long term. We think that in our country, which, in terms of economic indicators is not in a strong position as an importer of pharmaceutical raw materials from abroad, APDs' cost calculation should be considered because drug costs constitute an important part of the direct treatment costs of psychotic disorders in developing countries such as Turkey (Yildiz and Cerit 2006). We calculated the unit (mg) price based on the box prices of the APDs in use in 2020, thinking that it might work when calculating the cost of the illness using APDs as the main component of the treatment and calculated the annual average drug costs with the daily average dosage. Although the daily treatment dose varies with the stage of the illness and the individual characteristics of the patient, the average doses recommended for maintenance treatment were used here (Öztürk and Ulusahin 2018). The daily and annual cost calculations based on the assumption that the average maintenance treatment dose was used with the unit price obtained from (Drug Prices 2020) the drugs in the Turkish pharmaceutical market in September 2020 are shown in Table 1. A similar study was done in 2005 (Yildiz 2005). The purpose of this article is to redetermine the average costs of APDs in the Turkish pharmaceutical market every 15 years and to bring them to the attention of experts in terms of cost-effectiveness studies. When the costs in 2005 are examined, it is seen that the annual costs of the FAPDs were around 450 TRY, and the annual cost of oral preparations of SAPDs was 2,500 TRY (5 times the first generation). In 2005, there was only one depot of SAPD (risperidon consta) that allowed intramuscular (IM) administration, and its average annual cost was 5,400 TRY, 3 times more than the tablet form (1,700 TRY). In 2005, when the price of risperidone consta, which was the first second-generation depot APD, were compared with the prices of the first-generation depot drugs (fluphenazine = 380 TRY, flupentixol = 876 TRY, zuclopentixol = 730 TRY), the cost difference was 6-14 times. This almost-10-fold difference between the cost of the first and second generation APDs was remarkable. It is seen that this difference (risperidone consta = 10,807 TRY, fluphenazine = 916 TRY, flupentixol = 1,007 TRY, zuclopenthixol = 2,372 TRY, and haloperidol deconate 237 TRY) did not change in 2020. In 2020, the average RETHINKING THE COST OF ANTIPSYCHOTIC TREATMENT: THE AVERAGE COST OF THE DRUGS USED IN TURKEY IN 2020 2 Türk Psikiyatri Dergisi 2 Turkish Journal of Psychiatry Letter to the Editor 146 147 annual cost of oral use preparations of FAPDs is 925 TRY, while the average annual cost of oral forms of SAPDs is 2,580 TRY. The 5-fold difference observed in 2005 between the first and second-generation ones of the oral APDs decreased to 2.5 times in 2020. It is clear that while the difference between the cost of oral use of first- and second-generation drugs was halved in 2020, the difference between the costs of depot preparations applied with IM did not change. In 2005, the average dollar rate was 1.34 TRY, and in 2020 it was 7.02 TRY (Republic of Turkey Central Bank Exchange Rates, 2021). It is understood that the 5-fold increase in dollar exchange rate is not reflected in all drug prices in the same way. For example, there was a 3 to 4-fold increase in the prices of haloperidol, chlorpromazine, fluphenazine, trifluperazine and zuclopenthixol, while a less than two-fold increase in pimozide, flupenthixol, sulpiride, amisulpride and quetiapine and a decrease in the prices of clozapine, olanzapine, ziprasidone and risperidone in the tablet form. There is also a two-fold increase in the price of risperidone consta. The fluctuations in drug prices in 2005 and 2020 are shown in Table 2 in 500, 1,000, 2,000, 3,000 and 5,000 TRY brackets. It is noteworthy that while some drugs have moved into an upper price bracket in terms of annual costs, some have fallen into a lower price bracket. The prices of the second generation long-acting (depot) antipsycotic drugs (LA-APDs), which were not available in the Turkish pharmaceutical market in 2005, are quite high compared to others. In 2020, the annual cost of all of them, including risperidone consta, is over 10 thousand TRY. It is understood that the underlying reason for such price increase is the fact that the drug is wanted/sought after/new/marketed rather than the dollar exchange rate. For example, while there was a certain increase in the price of FAPDs, the increase in the price of some of the SAPDs (sulpiride, amisulpride, quetiapine tablet) was low, while the price of some others (clozapine, olanzapine, ziprasidone, risperidone tablet) decreased. It should also be taken into account that the effect of generic drugs entering the market during this period may have had an impact on price changes. It is noteworthy that while the annual cost of risperidone consta was approximately 3 times higher than the tablet form (5,400 TRY versus 1,700 TRY) in 2005, this difference reached 14 folds (10,807 TRY versus 742 TRY) in 2020. In 2005, the difference between the lowest daily cost (0.07 TRY) and the highest daily cost (14.80 TRY) was 211 times (Yildiz 2005), this difference had receded to 111 times (0.35 TRY versus 38.72 TRY) in 2020. Still a huge difference, isn't it? Table 1. Current Forms, Box Prices, Daily and Annual Costs in For Maintenance Treatment of Antipsychotic Drugs Available in the Pharmaceutical Market in September 2020 in Turkey No Generic name Trade name Dosage forms (mg) BV Price# TRY/Mg ADD Cost/d Cost/y 2005** 1 Haloperidol Norodol 5, 10, 20 tb 5/50 17.57 0.070 5 0.35 127 26 5, 10 amp 5/5 5.35 0.214 5 1.07 390 - 50, 150 LAI 50/1 9.80 0.196 1/15* 0.65 237 - 2 Chlorpromazine Largactil 25,100 tb 100/30 17.92 0.006 300 1.79 653 197 3 Fluphenazine Prolixin 25 LAI 25/1 17.57 0.703 1/7* 2.51 916 380 4 Trifluoperazine Stilizan 1, 2, 5 drj; 1 amp 5/30 14.52 0.096 10 0.97 354 91 5 Pimozide Nörofren 2 tb 2/30 19.33 0.322 4 1.29 470 365 6 Flupenthixol Fluanxol 3 drj 3/50 65.75 0.438 6 2.63 960 526 20 LAI 20/1 19.33 0.966 1/7* 2.76 1,007 876 7 Zuklopenthixol Clopixol 2, 10, 25 tb 2/50 38.65 0.386 20 7.72 2,817 701 200 LAI, 50 acu 200/1 45.55 0.227 1/7* 6.50 2,372 730 8 Sulpirid Dogmatil 200 tb 200/24 23.15 0.005 600 3.00 1,095 876 9 Amisulpirid Solian 200 tb 200/60 146.92 0.012 600 7.20 2,628 2,387 10 Quetiapine Seroquel 25, 50, 100, 200, 300, 400 tb 300/30 137.17 0.015 600 9.00 3,285 2,628 11 Clozapine Leponex 25, 100 tb 100/50 32.56 0.006 400 2.40 876 1,898 12 Olanzapine Zyprexa 5, 10, 20 tb 10/28 152.96 0.546 10 5.46 1,992 2,606 13 Ziprasidone Zeldox 20, 40, 60, 80 tb 60/56 189.89 0.056 120 6.72 2,452 3,541 14 Sertindole Serdolect 4, 12, 16, 20 tb 16/28 453.53 1.012 16 16.19 5,909 - 15 Risperidone Risperdal 1, 2, 3, 4 tb; 1 sol 2/20 20.34 0.508 4 2.03 741 1,719 Ris. Consta 25, 37.5, 50 LAI 37.5/1 444.17 11.840 1/15* 29.61 10,807 5,402 16 Paliperidone Invega 3, 6, 9 tb 6/28 213.15 1.268 6 7.61 2,777 - Xeplion 50, 75, 100, 150 LAI 100/1 1161.56 11.615 1/30* 38.72 14,132 - Trevicta 175, 263, 350, 525 LAI 350/1 3426.95 9.788 1/90* 38.08 13,899 - 17 Aripiprazole Abilify 5, 10, 15, 20 tb; 1 sol 20/28 113.25 0.404 20 8.08 2,949 - Abilify Main. 400 LAI 400/1 971.17 2.420 1/30* 32.37 11,815 - BV: Baseline value (in mg of the form and the number in the box), Price#: Box price of the base value in TRY, TRY/mg: Value per milligram in Turkish Lira, ADD: Average daily dose, Cost/d: Daily cost in TRY, Cost/y: Annual cost in TRY, mg: Milligram, tb: Tablet, drj: Dragee, amp: Ampoule, LAI: Long-acting injectable, acu: Acuphase, d: Day, TRY: Turkish Lira, *LAI per 7,15,30 or 90 days, **Annual cost in TRY in 2005. 148 Received: 14.01.2021, Accepted: 31.03.2021, Available Online Date: 07.01.2022 1Prof., 2Res. Assis., Kocaeli University School of Medicine, Department of Psychiatry, Kocaeli, Turkey. e-mail: myildiz60@yahoo.com https://doi.org/10.5080/u26315 The difference in 2005 between oral FAPDs prices and SAPDs prices seems to have halved in 2020. In 2020, the average daily treatment cost of oral drugs, whether for the first generation or the second generation, is 3 TRY (approximately the same for FAPDs applied with IM), while the daily cost of LA-SAPDs is around 33 TRY. It is seen that the difference between costs is approximately 11 times. This difference increases to 50 times for haloperidol deconate. From here, the following judgment can be made: in order for LA-SAPDs to be preferred, they must be at a value that willconstitute at least 11 times higher cost. This cost can and should be taken, especially for patients who are non-adherend with treatment and who do not adapt to LA-FAPDs. Because for clinicians, preventing the multi-dimensional destructiveness of psychosis in the individual, families and the society should be the priority. In this case, calculating the cost should not be a primary consideration. However, it is also known that patients who are non-adherend with treatment gain the ability to understand their illness and make consistent evaluations with its' results. If a psychosocial therapy has been carried out for a patient using IM medication for six months or a year, it is likely that this period provides insight and increases the level of treatment compliance. After one year of IM application, whether or not the patient will comply with oral treatment should be re-evaluated and the transition to oral treatment should be considered. If there is no problem in the patient's oral treatment compliance, it should be taken into account that the benefit of this transition will be at least 11-folds a year with this transition. Naturally, it will be necessary to apply IM for some patients for years. Moreover, there will be patients who need to switch from monthly administration of LA-SAPDs to quarterly usage patterns. However, we can say that most patients using LA-APDs will not need such use after a while, based on our clinical practice, although there is no study done in this field. With this study, we wanted to emphasize that while prescribing drugs used in the treatment of illnesses with psychotic symptoms, they should take into account the side effects of the drugs, as well as the daily, monthly, annual, and lifetime costs of the drugs. The principle of 'using an effective drug recommended for a specific disorder at the required dose, in sufficient time, at the lowest cost' adopted in the rational drug use guidelines should not be forgotten. It is expected that the modification of drug treatments, considering their costs as well as their efficiency, will contribute significantly to the country's economy in the long run. Mustafa Yildiz1, Emre Osman2 REFERENCES American Psychiatric Association (2021) The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. Third edition. Washington, DC: American Psychiatric Association. Drug Prices. https://www.ilacrehberi.com/ilac-fihrist/ Accession date: 25th September 2020. National Institute for Health and Clinical Excellence (NICE) (2014) Psychosis and schizophrenia in adults: prevention and management. NICE Guideline CG178; https://www.nice.org.uk/guidance/cg178. Accession date: 4th April 2018. Öztürk MO, Ulusahin NA (2018) Mental Health and Disorders. 18th Edit. Ankara: Nobel Tip Kitapevleri. (In Turkish) Republic of Turkey Central Bank Exchange Rates. https://www.tcmb.gov.tr/kurlar/kurlar_tr.html Accession date: 10th January 2021. Yildiz M (2005) The cost of treatment of psychotic disorders. Turk Psikiyatri Derg 16:146-7. (In Turkish) Yildiz M, Cerit C (2006) Annual cost of treatment for schizophrenia: Estimation from a university hospital data in Turkey. Bulletin of Clinical Psychopharmacology 16:239-44. Table 2. Comparison of the Annual Costs of Antipsychotic Drugs Calculated By The Daily Standard Average Dose Use, at Certain Price Ranges, for the Years 2005 and 2020 Price bracket (TRY) 2005 2020 500 ↓ Haloperidol tb, amp, Trifluoperazine drj, Chlorpromazine tb, Pimozid tb, Fluphenazine LAI Haloperidol tb, amp, depo, Trifluoperazine drj, Pimozid tb 500-1,000 Flupenthixol drj, LAI, Zuklopenthixol tb, acu, LAI, Sulpirid tb Chlorpromazine tb, Fluphenazine LAI, Flupenthixol drj, LAI, Clozapine tb, Risperidone tb 1,000-2,000 Clozapine tb, Risperidone tb Olanzapine tb, Sulpirid tb 2,000-3,000 Amisulpirid tb, Olanzapine tb, Quetiapine tb Zuklopenthixol tb, acu, LAI, Amisulpirid tb, Ziprasidone tb, Paliperidone tb, Aripiprazole tb 3,000-5,000 Ziprasidone tb Quetiapine tb 5,000-10,000 Risperidone consta Sertindole tb 10,000 ↑ Risperidone consta, Paliperidone monthly, Paliperidone 3 monthly, Aripiprazole maintana tb: Tablet, drj: Dragee, amp: Ampoule, LAI: Long-acting injectable, acu: Acuphase.

A 10-year mirror-image study of effectiveness and cost of long-acting paliperidone palmitate injectable in patients with schizophrenia or schizoaffective disorder.

Acute episodes of Schizophrenia and Schizoaffective Disorder often require hospitalizations and/or psychiatry emergency room (PER) visits, with significant economic burden. Long-acting injectables (LAI), such as the once-monthly Palmitate Paliperidone LAI (1MPP) are effective in suppressing symptoms and raise treatment adherence. This study is the first aimed at evaluating long-term efficacy of initiation of 1MPP. This was a mirror-image study with a total 10 year observational length. Sample was divided into five different groups according to time span of observation: 2,4,6,8, and 10 years. Number of participants per group was 162, 129, 95, 77 and 35, respectively. Main outcomes were number and length of hospitalizations and number of PER visit. Significant reductions in these outcomes after initiation of 1MPP were found in all groups. Subgroups consisting only of patients with full adherence were evaluated, and these had better outcomes. A cost evaluation was also performed, which demonstrated decreases every year, for all main outcomes. Sensitivity analysis in the 2-year group showed results in this time-frame are independent of gender, diagnosis, previous LAI or 1MPP initiation setting. Initiation of 1MPP reduces number and length of hospitalizations up to 5 years, decreasing associated costs. This study increases evidence supporting use of 1MPP in patients with Schizophrenia or Schizoaffective disorder.

A health economics study of long-acting injectable once-monthly paliperidone palmitate in schizophrenia: a one-year mirror-image study in China.

Schizophrenia is ranked among the top 25 leading causes of disability worldwide in 2013 which resulting in social and economic burden. By observing patients with schizophrenia one year before and after switching from oral antipsychotics (OAPs) to once-monthly paliperidone palmitate (PP1M), we can better understand the change of total costs in schizophrenic patients, including direct costs and indirect costs, after switching treatment patterns.A total of 100 schizophrenic (ICD-10) patients from Shandong Mental Health Center were collected from December 2016 to June 2019. Treatment modalities, health care resource utilization and costs were compared before and after switching directly from oral antipsychotics to PP1M.Of the 82 patients included in the main analyses, treatment with PP1M resulted in an increase in direct costs of 31.92% (P < 0.01), an increase in medicine costs of approximately 142% (P < 0.01), and a reduction in hospital costs of 68.15% (P > 0.05). There was no significant increase in total costs (P = 0.25), while 31.92% increase in direct costs (P < 0.01), and 35.62% decrease in indirect costs (P < 0.01) after conversion to PP1M. Compared with before administration of PP1M, patients with ≥ 1 inpatient stay in 1 year Pre-PP1M treatment with OAPs (n = 32) had a 20.16% decrease in direct costs (P < 0.01), a 144% increase in medicine costs (P < 0.01), and a significant 72.02% decrease in hospital costs (P < 0.01). The observed reduction in the number of hospitalizations (t = 2.56, P ≤ 0.01) and inpatient stays (t = 1.73, P < 0.05) and after transition to PP1M resulted in a reduction in hospitalization costs (P < 0.01).Switching from OAPs to PP1M decreased the household workforce burden without increasing clinical healthcare costs. Direct costs were significantly reduced in patients with ≥ 1 inpatient stay in 1 year pre-PP1M treatment with OAPs after the switch, which decreased by improving adherence to therapy and reducing the number and length of hospital stays, suggesting that those patients may benefit after switching to PP1M.

Antipsychotic Adherence, Resource Use, and Costs Before and After the Initiation of Once-monthly Paliperidone Palmitate Therapy Among Medicaid Beneficiaries With Prior Schizophrenia Relapse.

PURPOSE: Patients with schizophrenia often struggle with medication adherence and may benefit from the use of a long-acting injectable antipsychotic, including once-monthly paliperidone palmitate (PP1M), which was previously demonstrated to improve outcomes compared with oral antipsychotics. This study assessed the impact of initiating PP1M therapy on medication adherence, health care resource use (HRU), and costs among Medicaid beneficiaries with schizophrenia and a prior schizophrenia relapse. METHODS: A 6-state Medicaid database (from quarter 1 of 2009 to quarter 1 of 2018) was used to identify adults with ≥2 schizophrenia diagnoses who started PP1M therapy on or after January 1, 2010. The index date was the first PP1M claim. Patients had ≥12 months of continuous Medicaid enrollment before and after the index date, ≥1 oral antipsychotic claim in the 12 months before the index date, and ≥1 relapse (proxied as a schizophrenia-related inpatient admission or emergency department [ED] visit) during the 12 months before the index date. Generalized estimating equations were used to compare adherence to antipsychotics (proportion of days covered ≥80%), HRU, and costs (reported in 2018 US dollars) in the 12 months after versus before the index date. Sensitivity analyses were conducted (1) accounting for the minimum and cumulative price inflation Medicaid rebates for pharmacy costs of branded psychiatric medications, (2) among patients with ≥2, ≥3, and ≥4 prior schizophrenia-related inpatient admissions or ED visits, (3) among patients not adherent to antipsychotic treatment before the index date, and (4) among patients switching to PP1M directly from oral risperidone or paliperidone. FINDINGS: A total of 1725 patients met the study inclusion criteria (mean age, 39.5 years; 43% female). After versus before the index date, patients were 93% more likely to be adherent to antipsychotic treatment (P < 0.01). The likelihood of inpatient admissions and ED visits decreased by 89% and 49% (all P < 0.01) after initiating PP1M therapy. The number of inpatient days decreased by 31% (P < 0.01) and the number of ED visits by 16% (P = 0.03). Pharmacy costs increased by $514 per-patient-per-month (PPPM), whereas medical costs, driven by inpatient costs, decreased by $391 PPPM (all P < 0.01). Sensitivity analyses yielded similar trends. Notably, total health care cost savings of $231 PPPM were observed after accounting for the cumulative Medicaid rebate for costs of branded psychiatric medications (P < 0.01). IMPLICATIONS: In Medicaid beneficiaries with relapsed schizophrenia, transitioning from oral antipsychotics to PP1M was associated with improved adherence to antipsychotics and decreased use of inpatient and ED services. Increased pharmacy costs after the initiation of PP1M were offset by decreased medical costs. After applying the cumulative Medicaid rebate, including the price inflation rebate for costs of branded psychiatric medications, initiation of PP1M therapy resulted in statistically significant health care cost savings.

Risk of subsequent relapses and corresponding healthcare costs among recently-relapsed Medicaid patients with schizophrenia: a real-world retrospective cohort study.

AIMS: To compare adherence, rates of subsequent schizophrenia-related relapses, healthcare resource utilization, and healthcare costs among Medicaid beneficiaries with schizophrenia who initiated once-monthly paliperidone palmitate (PP1M) versus a new oral atypical antipsychotic (OAA) following a recent schizophrenia-related relapse. METHODS: Six-state Medicaid data (01/2009-03/2018) were used to identify adults with schizophrenia initiated on PP1M or OAA (index date) within 30 days following a schizophrenia-related relapse (defined as a schizophrenia-related inpatient or emergency room visit). Patients were required to have 12 months of continuous eligibility before (baseline) and after (observation) the index date. Differences in baseline characteristics between PP1M and OAA patients were accounted for using 1:3 matching. RESULTS: After matching, characteristics were well-balanced between PP1M (N=208, mean age=39 years, 35.6% female) and OAA patients (N=624, mean age=40 years, 34.6% female). During the 12-month observation period, the mean proportion of days covered for the index medication was 41.2% in the PP1M cohort and 34.7% in the OAA cohort (p=.008). Relative to the OAA cohort, PP1M patients were 33% (p=.013) less likely to have a subsequent relapse and had 29% (p=.004) fewer all-cause inpatient admissions per-patient-per-year (PPPY). Consequently, a significant mean reduction of $6273 in medical costs PPPY (p=.028) was observed, which fully offset the $4770 (p<.001) increase in pharmacy costs PPPY and resulted in a numerical but not statistically significant, decrease in total healthcare costs of $1503 PPPY (p=.621) relative to OAA patients. CONCLUSIONS: Among patients with a recent schizophrenia-related relapse, PP1M was associated with a lower risk of subsequent relapse while remaining a cost neutral therapeutic option compared to OAAs.

Medication adherence, healthcare resource utilization, and costs among Medicaid beneficiaries with schizophrenia treated with once-monthly paliperidone palmitate or once-every-three-months paliperidone palmitate.

OBJECTIVE: Antipsychotics with reduced dosing frequency may improve adherence and clinical outcomes for patients with schizophrenia. This study compared treatment patterns, healthcare resource utilization (HRU), and costs between Medicaid beneficiaries with schizophrenia treated with once-monthly paliperidone palmitate (PP1M) and those who transitioned to once-every-three-months paliperidone palmitate (PP3M). METHODS: Adults with schizophrenia were identified in a four-state Medicaid database (18 May 2014 to 31 March 2019). The index date was the first PP3M claim (PP3M cohort), or a random PP1M claim (PP1M cohort), following ≥4 months of continuous PP1M treatment among patients with ≥12 months of continuous Medicaid enrollment pre- and post-index. Adherence (proportion of days covered by the index treatment ≥80%), persistence (no gap >90/30 days in the PP3M/PP1M supply), HRU, and costs were compared during the 12-month post-index period between cohorts matched 1:1. RESULTS: Among 2374 patients identified, 374 remained in each cohort after matching (mean age 42 years; 30.5% female). Compared to the PP1M cohort, the PP3M cohort was 2.39 times more likely to be adherent (p < .001), 4.63 times more likely to be persistent (p < .001), 33% less likely to have ≥1 hospitalization (p = .011), and 32% less likely to have ≥1 day with home care services (p = .012). Mean annual medical costs were similar between cohorts ($24,970 in the PP3M cohort and $25,736 in the PP1M cohort; p = .854). CONCLUSIONS: Medicaid beneficiaries who transitioned to PP3M had higher adherence and persistence, and a reduced likelihood of hospitalization relative to those who continued treatment with PP1M. The results suggest potential clinical value to transitioning eligible patients to PP3M.

[Some current trends in the use of prolonged injectable antipsychotics in the conditions of modernization of the psychiatric service]. / Nekotorye sovremennye tendentsii primeneniya prolongirovannykh in"ektsionnykh antipsikhotikov v usloviyakh modernizatsii psikhiatricheskoi sluzhby.

OBJECTIVE: A pharmacoeconomical analysis of the use of prolonged injectable antipsychotics in the treatment of patients with schizophrenia in Moscow over 2015-2019 in the context of the reform of the psychiatric service. MATERIAL AND METHODS: The authors studied the economic costs of treatment of psychiatric patients with prolonged injectable antipsychotics on the pharmaceutical market in Moscow for five years on the example of patients diagnosed with paranoid schizophrenia (ICD-10 F20.0) based on the dynamics of the registered contingent of patients with schizophrenic spectrum disorders over the past fifteen years including the period of active modernization of the psychiatric service. RESULTS AND CONCLUSION: A constant increase in public spending on treatment, including therapy with prolonged injectable neuroleptics (both first-generation drugs and atypical antipsychotics), was shown. At the same time, the increase in the use of atypical antipsychotics is ahead of schedule. The number of patients receiving treatment with prolonged injectable haloperidol and zupentixol increased approximately twice during this period, the number of patients receiving treatment with injectable risperidone and paliperidone palmitate increased by more than 3 and 13 times, respectively. There is a significant increase in public spending on the purchase and use of these drugs for the treatment of privileged categories of patients, most of this applies to injectable forms of paliperidone, the cost of using these drugs has increased more than 20 times over a five-year period. These trends indicate a shift in emphasis towards outpatient psychiatric care and improvement of approaches to treatment of patients with schizophrenia, which indicate a new stage in the development of out-of-hospital treatment and rehabilitation systems based on the latest achievements of psychopharmacology and the development of social support systems for patients with schizophrenia spectrum disorders.

[The pharmacoeconomic efficacy of lurasidone in the treatment of schizophrenia]. / Farmakoekonomicheskaya effektivnost' primeneniya preparata Lurazidon pri lechenii shizofrenii.

OBJECTIVE: To conduct a comprehensive pharmacoeconomic evaluation of lurasidone for the treatment of patients with schizophrenia under Russian healthcare system conditions and inclusion in EDL (Essential Drugs List) and Medication List for the Certain Categories of Citizens. MATERIAL AND METHODS: A retrospective study of lurasidone in the treatment of patients with schizophrenia was performed. Methods of pharmacoeconomic analysis were: cost analysis, budget impact analysis and cost-effectiveness analysis. RESULTS: Use of lurasidone for the treatment of patients with schizophrenia requires 50.04% less costs than the use of paliperidone and 46.69% less costs than the use of sertindole allowing to provide additional therapies to 100.1 and 87.6% of patients, respectively. The cost minimization analysis results are stable when prices fluctuate in the range of ±30%. Considering the current volume of antipsychotic drug supply, replacing 100% of paliperidone with lurasidone from the first year will reduce the cost of antipsychotics for patients who received paliperidone by 39.79 or by 360.81 million rubles over 3 years. Replacing 100% of sertindole with lurasidone from the first year will reduce the cost of antipsychotics for patients who received sertindole by 37.21 or 173.87 million rubles over 3 years. The results of the budget impact analysis are resistant to changes in prices for compared drugs in a wide range. CONCLUSION: Lurasidone is a more effective drug for treatment of schizophrenia from a pharmacoeconomic point of view in comparison with paliperidone and sertindole. With comparative efficacy with paliperidone and sertindole the use of lurasidone can significantly reduce the burden on budget of state programs of compensation for certain categories of citizens.

Projecting the Long-Term Economic Impact of Once-Monthly Paliperidone Palmitate Versus Oral Atypical Antipsychotics in Medicaid Patients with Schizophrenia.

BACKGROUND: Recent evidence has demonstrated that, over 12 months, pharmacy costs associated with switching nonadherent recently relapsed patients from oral atypical antipsychotics (OAAs) to once-monthly paliperidone palmitate (PP1M) were offset by reduced relapse rates and schizophrenia-related health care costs. In addition, earlier use of PP1M may generate greater cost savings. OBJECTIVE: To project the long-term economic impact when a proportion of nonadherent patients with a recent relapse switch from OAAs to PP1M. METHODS: A 36-month decision-tree model with twelve 3-month cycles was developed from a Medicaid payer's perspective. The target population was nonadherent, recently relapsed OAA patients. At equal adherence, probability of relapse was equal between PP1M and OAAs, and OAA patients were nonadherent until treatment switch. Event rates (adherence, relapse, and switch) and cost inputs (pharmacy and relapse) were based on the literature, and rates remained constant. Outcomes included number of relapses, pharmacy costs, and relapse costs (2017 U.S. dollars) at years 1, 2, and 3. One-way sensitivity (OSA) and probabilistic sensitivity analyses (PSA) evaluated the effect of varying model inputs on health plan and per-patient level costs. RESULTS: Based on a hypothetical health plan of 1 million members, 3,037 OAA patients were recently relapsed and nonadherent. Compared with continuing OAAs, switching 5% of patients (n = 152) to PP1M resulted in net cost savings of $674,975, $723,298, and $562,310 at the plan level; $4,445, $4,764, and $3,703 per patient switched per year; and $0.0562, $0.0603, and $0.0469 per member per month in years 1, 2, and 3, respectively, resulting in total plan-level savings of > $1.9 million over 3 years. A total of 221 relapses were avoided (year 1: 92; year 2: 72; and year 3: 57). In years 1, 2, and 3, respectively, total annual plan-level schizophrenia-related costs were $114.1 million, $107.2 million, and $105.8 million when all patients switched to PP1M before any subsequent relapse (n = 3,037); $123.4 million, $109.6 million, and $106.7 million when patients switched to PP1M after a first subsequent relapse (n = 2,631); and $127.6 million, $121.6 million, and $117.0 million when all patients remained on OAAs. The cost per patient switched to PP1M was lower when all patients received PP1M before a subsequent relapse versus after their first subsequent relapse at all years (year 1: $37,559 vs. $45,089; year 2: $35,288 vs. $36,321; and year 3: $34,826 vs. $35,155). OSA demonstrated consistent net cost savings per patient switched, ranging from $640 to $10,484 (year 1); $1,774 to $9,245 (year 2); and $1,354 to $7,026 (year 3). PSA demonstrated 96.3%, 99.7%, and 99.7% of iterations were cost saving in years 1, 2 and 3, respectively. CONCLUSIONS: Pharmacy costs associated with switching nonadherent OAA patients with a recent relapse to PP1M were offset by reduced relapse rates and health care costs at years 1, 2, and 3, with earlier use of PP1M resulting in increased cost savings at all years. DISCLOSURES: This research was funded by Janssen Scientific Affairs. Pilon, Morrison, Lefebvre, and Shak are employees of Analysis Group, a consulting company that received research grants from Janssen Scientific Affairs to conduct this study. El Khoury and Kim are employees of Janssen Scientific Affairs. At the time this study was conducted, Llaneza was an employee of HireGenics, which provided services to Janssen Scientific Affairs for the study. Part of the material in this manuscript was presented at the Academy of Managed Care Pharmacy 2019 Annual Meeting; March 25-29, 2019; San Diego, CA.