Real-World Outcomes and Costs Following 6 Months of Treatment with the Long-Acting Injectable (LAI) Aripiprazole Lauroxil for the Treatment of Schizophrenia.

BACKGROUND: Continuous antipsychotic therapy is recommended as part of long-term maintenance treatment of schizophrenia, and gaps in antipsychotic treatment have been associated with increased risks of relapse and rehospitalization. Because the use of long-acting injectable (LAI) antipsychotics may reduce the likelihood of undetected medication gaps, initiating an LAI medication may affect resource utilization and costs. The LAI aripiprazole lauroxil (AL) was approved in the United States (US) in 2015 for the treatment of schizophrenia in adults. OBJECTIVE: The objective of this retrospective observational cohort study was to examine treatment patterns, resource utilization, and costs following initiation of AL for the treatment of schizophrenia in adults. METHODS: A retrospective analysis of Medicaid claims data identified a cohort of patients (N = 485) starting AL shortly after Food and Drug Administration approval in October 2015. Treatment patterns, resource utilization, and costs were compared 6 months before and after treatment initiation. Subgroup analyses were conducted based on the type of antipsychotic (LAI, oral, or none) received before initiation of AL. RESULTS: Over 6 months of follow-up, patients received an average of 4.6 injections out of a maximum of six (77%). After initiating AL, all-cause inpatient admissions decreased by 22.4%; other significant reductions were observed in mental health-related admissions and emergency room (ER) visits. All-cause inpatient costs decreased by an average of US$2836 per patient (p < 0.05) in the 6-month post-AL period, whereas outpatient pharmacy costs increased by US$4121 (p < 0.05), resulting in no significant difference in overall costs between the pre- and post-AL periods. The subgroup of patients who had been prescribed an oral antipsychotic before starting AL had significant reductions in proportion of patients with inpatient and ER visits and costs, but also reported a significant increase in pharmacy costs. CONCLUSIONS: AL was associated with a significant reduction in inpatient costs and an increase in outpatient pharmacy costs, resulting in no changes in total healthcare costs over 6 months. The adherence rate and reductions in inpatient use may indicate the potential for greater clinical stability among patients initiated on AL compared with their previous treatment.

Tratamento com aripiprazol para Esquizofrenia no contexto do Sistema Único de Saúde em Goiás: análise de impacto orçamentário e revisão de estudos de análise de custo-utilidade / Aripiprazol for Schizophrenia treatment in the Goiás Public Health System perspective: budget impact analysis and review of cost-utility analysis studies

Tecnologia: Aripiprazol, medicamento antipsicótico de segunda geração. Indicação: tratamento da esquizofrenia. Objetivos: Apresentar evidências de análise econômicas em saúde, no cenário do SUS e contextos internacionais, do tratamento com Aripiprazol para esquizofrenia, comparado a outros antipsicóticos de uso oral de primeira e segunda geração utilizados no SUS. Realizar uma análise de impacto orçamentário para o contexto do SUS em Goiás e estimar uma projeção de gastos diretos com aquisição de Aripiprazol pela Secretaria de Saúde de Goiás, em cenário de incorporação do Aripiprazol para tratamento de esquizofrenia, no período de 2021 a 2025. Materiais e Métodos: Levantamentos bibliográficos nas bases de dados PUBMED e Biblioteca Virtual em Saúde, no mês de junho de 2020. Realizada avaliação da qualidade metodológica das revisões sistemáticas e dos estudos econômicos com as ferramentas Assessing the Methodological Quality of Systematic Reviews (AMSTAR), e Quality of Health Economic Studies (QHES) checklist, respectivamente. Foi calculado o impacto orçamentário, seguindo diretrizes do Ministério da Saúde, e projeção de gastos para a Secretaria de Saúde de Goiás. Resultados: Foram selecionadas e incluídas 1 revisão sistemática e 1 estudo econômico brasileiro no estudo de revisão rápida de evidências. Conclusão: No contexto brasileiro, o Aripiprazol é custo-efetivo, quando comparado a Clorpromazina, Haloperidol, Quetiapina e Ziprasidona. Porém, é menos custo-efetivo que Risperidona e Olanzapina. Caso seja padronizado pela Secretaria de Saúde de Goiás, promoverá economia anual para o SUS de R$ 250.042,05 a R$ 407.418,41, em sua máxima difusão. A projeção de gastos diretos é estimada em R$1.582.115,24 a R$27.960.108,08

Technology: Aripiprazole, second generation antipsychotic medication. Indication: treatment of schizophrenia. Objectives: To show evidence of health economic analysis in the scenario of Brazilian Public Health System (BPHS) and international contexts, for schizophrenia treatment with Aripiprazole, compared to other oral antipsychotics used in BPHS. To make a budget impact analysis for the Goias Public Health System perspective and estimate direct expenditures for the acquisition of Aripiprazole by State Department of Health of Goias, in a scenario of technology incorporation of Aripiprazole for the treatment of schizophrenia, in the period from 2021 to 2025. Materials and Methods: Bibliographical searches were done in the PUBMED and Virtual Health Library databases, in 2020 June. An evaluation of the methodological quality of systematic reviews and economic studies was done using the tools AMSTAR (Assessing the Methodological Quality of Systematic Reviews), and QHES (Quality of Health Economic Studies) checklist, respectively. Calculation of budget impact, following guidelines of the Brazilian Health Ministry, and projection of expenditures for the State Department of Health of Goias. Results: 1 systematic review and 1 Brazilian economic study were selected and included in the study of rapid evidence review. Conclusion: In the Brazilian context, Aripiprazole is cost-effective when compared to Chlorpromazine, Haloperidol, Quetiapine and Ziprasidone. However, it is less cost-effective than Risperidone and Olanzapine. If it is standardized by State Department of Health of Goias, it will promote anual savings for BPHS from R$ 250,042.05 to R$ 407,418.41, in its maximum dissemination. The direct expenses are estimated at R$ 1,582,115.24 to R $ 27,960,108.08

Cost-effectiveness of aripiprazole orally disintegrating tablets in the treatment of schizophrenia in China.

BACKGROUND: Orally disintegrating tablet (ODT) formulation of antipsychotics is one of the innovative drug delivery systems developed to improve medication adherence. We aimed to evaluate the cost-effectiveness of aripiprazole ODT vs. aripiprazole standard oral tablet (SOT), as well as olanzapine SOT in China. METHODS: We developed a discrete event simulation model from government payers' perspective. On the entry, 100,000 patients in each group were simulated for relapse, adverse events, changing adherence level, medication discontinuation, switching or quitting in response to three different medication adherence levels. The model projected quality adjusted life years (QALYs) and treatment costs over a 1-year time horizon. Parameter uncertainties were assessed through sensitivity analyses. RESULTS: The QALYs per patient over 1-year treatment with aripiprazole ODT, aripiprazole SOT, or olanzapine SOT, were 0.7282, 0.7112, and 0.7218, respectively. The corresponding costs were $1,423, $2,215, and $1,493. In both comparisons, aripiprazole ODT was dominant. Compared with aripiprazole SOT and olanzapine SOT, the likelihood of aripiprazole ODT being cost-effective was 99.2% and 69.2%, respectively, using 3 times per capita GDP per QALY as willingness-to-pay threshold. CONCLUSIONS: The aripiprazole ODT is associated with more QALYs at lower costs compared with both aripiprazole SOT and olanzapine SOT in treating schizophrenia in China.

Health Care Cost in Patients With Schizophrenia Treated With Brexpiprazole Versus Other Oral Atypical Antipsychotic Therapy.

PURPOSE: Brexpiprazole is an oral atypical antipsychotic (OAA) for the treatment of schizophrenia (SCZ). This study compared all-cause and psychiatric inpatient hospitalization and medical costs in adult patients with SCZ newly treated with brexpiprazole versus other US Food and Drug Administration-approved OAAs in a real-world setting. METHODS: This retrospective cohort study analyzed data from: (1) the IBM MarketScan Commercial and Medicare Supplemental databases, and the MarketScan Multi-State Medicaid database; and (2) the de-identified Optum Clinformatics Datamart. Adult patients were identified if they had SCZ and initiated either brexpiprazole or another OAA during the study identification period (July 1, 2015, to September 30, 2016, for MarketScan Commercial and Medicare Supplemental and for Optum; July 1, 2015, to June 30, 2016, for MarketScan Multi-State Medicaid) and had ≥12 months of continuous enrollment before (baseline) and after (follow-up) the first treatment date. Linear regression analyses were performed to test associations between treatment groups (brexpiprazole vs another OAA) and costs (total and medical); negative binomial regression models were used to estimate number of hospitalizations per year, adjusting for baseline characteristics and medication adherence to index treatment during the 12-month follow-up. FINDINGS: The final study sample consisted of 6254 patients with SCZ: 176 initiated brexpiprazole; 391, ziprasidone; 453, paliperidone; 523, lurasidone; 786, aripiprazole; 1234, quetiapine; 1264, olanzapine; and 1427, risperidone. Controlling for baseline characteristics and medication adherence, the adjusted number of hospitalizations (both all-cause and psychiatric), all-cause total costs, and all-cause medical costs did not differ across groups. Brexpiprazole users had the lowest mean psychiatric costs among all OAA users ($12,013; 95% bootstrap CI, 7488-16,538). Compared with brexpiprazole users, paliperidone (incidence rate ratio [95% CI], 1.52 [1.05-2.19]; P = 0.027) and quetiapine (incidence rate ratio [95% CI], 1.47 [1.04-2.07]; P = 0.029) users had more psychiatric hospitalizations per year. Paliperidone had higher psychiatric costs than brexpiprazole (total, $32,066 [95% bootstrap CI, 28,779-35,353] vs $23,851 [18,907-28,795]; medical, $19,343 [16,294-22,392] vs $12,013 [7488-16,538]). Psychiatric medical costs were also $6744 higher in olanzapine users (95% bootstrap CI, 1694-11,795; P = 0.009) than in brexpiprazole users. IMPLICATIONS: Patients with SCZ treated with brexpiprazole had fewer psychiatric hospitalizations and lower psychiatric costs than those treated with paliperidone. Differences in the number of all-cause hospitalizations and medical costs among treatments were not statistically significant. Although treatment decisions are driven by a number of factors (eg, clinical circumstances and drug costs), choice of OAA may affect health care costs.

Economic evaluations on the use of aripiprazole for patients with schizophrenia: A systematic review.

WHAT IS KNOWN AND OBJECTIVES: Schizophrenia is a serious mental disorder and is associated with substantial economic and social burden. Cost-effectiveness analysis is important to assess the costs of different therapeutic options. However, there is a lack of information on the reporting quality of economic evaluations, cost drivers, as well as updated data focused on aripiprazole, an antipsychotic drug commonly prescribed in schizophrenia. This study evaluates and summarizes the evidence of economic evaluations of the use of aripiprazole in schizophrenia. In addition, we aimed to identify cost drivers and critically assess the reporting qualities of these studies. METHODS: A comprehensive literature research was conducted using PubMed, NHS Economic Evaluation Database, CEA Registry and LILACS databases dated until March 2018. Full economic analyses of aripiprazole in schizophrenia that were based on decision analytical models and published in English, Portuguese or Spanish languages were included. Two independent authors identified the studies and performed data extraction and quality assessment using 24 items from the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. RESULTS AND DISCUSSION: A total of 79 potential studies were identified, of which 17 studies performing model-based economic evaluations fully met the eligibility criteria. Of these, 15 were industry-funded studies. A trend favouring olanzapine, lurasidone and paliperidone could be observed, whereas aripiprazole was extensively described as a dominated alternative. However, notably, 93% of the industry-funded studies presented results favouring their sponsors, only two of them being the manufacturer of aripiprazole. Cost drivers were usually related to the relapse rates/probabilities regardless of the funding source. The overall quality of reporting of the economic analyses was poor, with most studies scoring around 12-13 points. The most frequent problems were the lack of description of relevance of the outcome measures, characteristics of the base case population and report of precision measures for all the parameters of the model. WHAT IS NEW AND CONCLUSION: No consistent conclusion on the cost-effectiveness of aripiprazole could be drawn due to the context-specific costs, conflicting parameters of effectiveness and safety, and bias related to industry sponsorship. Cost drivers, though, were usually related to the relapse rates/probabilities. In addition, poor reporting quality of the studies performing full economic analysis requires further improvement to ensure greater transparency of the findings.

Receipt of Promotional Payments at the Individual and Physician Network Level Associated with Higher Branded Antipsychotic Prescribing Rates.

Pharmaceutical promotion can lead to market size expansion, which is beneficial if previously untreated patients access treatment but deleterious if it leads to overuse, an area of concern for second generation antipsychotics (SGA). We contribute to a growing body of work suggesting that networks of social and professional relationships shape prescribing behavior. We examined 88,439 Medicare Part D prescribing physicians, finding that promotion is associated with SGA market size expansion (elasticity: 0.062) and that network-level promotional activity is associated with network members' branded product prescribing. Research on the effects of promotion should account for its effects in prescribers' networks.

Cost-effectiveness of olanzapine in the first-line treatment of schizophrenia in China.

OBJECTIVES: This study aimed to analyze (1) the cost-effectiveness of olanzapine orally disintegrating tablet (ODT) compared to olanzapine standard oral tablet (SOT) and (2) the cost-effectiveness of olanzapine-SOT compared to aripiprazole-SOT for patients with schizophrenia in China. METHODS: A microsimulation model was adapted from a healthcare payers' perspective. The model ran over a 1-year time horizon, using quarterly cycles. The costs of adverse events were acquired through a clinical expert panel. The average bidding prices in China of olanzapine-ODT, olanzapine-SOT, aripiprazole-SOT, and other switch alternatives were used. Inpatient and outpatient medical costs were sourced from the Urban Employee Basic Medical Insurance database in Tianjin. Additionally, adherence, efficacy, safety, and utility data were taken from the literature. Uncertainty of parameters were assessed through one-way and probabilistic sensitivity analyses. RESULTS: The total annual costs per patient in aripiprazole-SOT arm, olanzapine-SOT arm, and olanzapine-ODT arm are USD 2,296.05, USD 1,940.05, and USD 2,292.81, respectively. The average number of relapses per patient in 1 year in the aripiprazole-SOT arm, olanzapine-SOT arm, and olanzapine-ODT arm, are 0.734, 0.325, and 0.198, respectively. The quality-adjusted life years (QALYs) gained per patient in 1 year in the aripiprazole-SOT arm, olanzapine-SOT arm, and olanzapine-ODT arm are 0.714, 0.737, and 0.758, respectively. Consequently, (1) the incremental cost-effectiveness ratios (ICERs) of administrating olanzapine-ODT over olanzapine-SOT are USD 2,791.96 per relapse avoided and USD 16,798.39 per QALY gained; and (2) the ICERs of using olanzapine-SOT over aripiprazole-SOT are USD -870.39 per relapse avoided and USD -15,477.93 per QALY gained. All ICERs are under the willingness-to-pay threshold in China of USD 25,772.67. The sensitivity analyses confirmed the robustness of the results. CONCLUSION: As the first-line treatment for schizophrenia in China, olanzapine-ODT is cost-effective compared to olanzapine-SOT and olanzapine-SOT is cost-effective compared to aripiprazole-SOT.

[Cost-effectiveness analysis of aripiprazole once-monthly versus paliperidone palmitate once-monthly in the treatment of schizophrenia in France]. / Analyse coût-efficacité de l'aripiprazole injectable à libération prolongée (AILP) comparé au palmitate de palipéridone (PP) dans le traitement de la schizophrénie en France.

OBJECTIVE: The aim of the study was to estimate the cost-effectiveness ratio of aripiprazole once-monthly compared to once-monthly injectable paliperidone palmitate in the treatment of schizophrenia in France on the basis of results and data from the QUALIFY study. METHODS: Consumed resources data measured with a dedicated questionnaire and results on the quality of life scales from the QUALIFY study were combined with French standard unit costs of each collected consumed resources during QUALIFY to estimate the cost-effectiveness ratios of the two products. Multivariate sensitivity analyses were performed to test the combined impact of the different assumptions. RESULTS: Findings of the study showed greater efficacy on the quality of life (QLS) and psychiatric evaluation scales (CGI-S and CGI-I) observed in QUALIFY of aripiprazole compared with paliperidone palmitate. Findings also suggest a trend (P=0.0733) in the reduction of total costs linked to a statistical decrease (P<0,0001) in drug costs in the aripiprazole group. These findings are reinforced by the probabilistic sensitivity analyses. CONCLUSION: Aripiprazole appeared to be more cost-effective than paliperidone palmitate in the French context. Limits of this study are mainly related with the duration of the clinical trial and to assumptions on the transposability of measured consumed resources in the international clinical trial to the French healthcare system.

Budget impact analysis of long-acting injectable aripiprazole once-monthly 400 mg in bipolar I disorder in the USA.

AIM: To estimate the budget impact (BI) of introducing aripiprazole once-monthly 400 mg/300 mg (AOM 400) in the maintenance monotherapy treatment of bipolar I disorder versus long-acting injectables, oral antipsychotics and best supportive care. METHODS: A BI model was developed from a US-payer perspective using treatment-related, hospitalization and adverse event management cost estimates for a hypothetical 1,000,000-member health plan over a 5-year period. RESULTS: Market share of AOM 400 was predicted to increase from 0.6% in Year 1 (current scenario) to 1.3% in Year 5 (predicted scenario), with predicted increases for paliperidone palmitate, asenapine and cariprazine. Treatment-related costs explained the BI increase, while adverse event and hospitalization costs were reduced. The per member per month incremental cost ranged from US$0.06 to US$0.26 in Years 1-5. The largest increases were predicted for paliperidone palmitate. CONCLUSION: As market shares of atypical antipsychotics are predicted to increase, payers may wish to re-evaluate their use.

Cost-effectiveness of long-acting injectable aripiprazole once-monthly 400 mg in bipolar I disorder in the USA.

AIM: To evaluate the cost-effectiveness of aripiprazole once-monthly 400/300 mg (AOM 400) in maintenance monotherapy treatment of bipolar I disorder (BP-I). METHODS: A de novo lifetime Markov model was developed for BP-I using available data for AOM 400 and relevant comparators. Base-case analysis considered costs and outcomes from the US payer perspective. RESULTS: The cost per quality-adjusted life year gained with AOM 400 versus comparators ranged from US$2007 versus oral asenapine to dominance (i.e., lower cost with quality-adjusted life gain) versus long-acting injectable risperidone, paliperidone palmitate, oral cariprazine and best supportive care. Patients treated with AOM 400 were estimated to have fewer mood episodes and hospitalizations per patient (5.37) than comparators (6.33, asenapine or cariprazine; 6.54, risperidone long-acting injectable; 7.64, paliperidone palmitate; and 8.93, best supportive care). Sensitivity analyses showed results were robust to parameter uncertainty. CONCLUSION: AOM 400 may be considered cost effective in the maintenance monotherapy treatment of BP-I in adults.

Comparing Cost-Effectiveness of Aripiprazole Augmentation With Other "Next-Step" Depression Treatment Strategies: A Randomized Clinical Trial.

OBJECTIVE: To compare the cost-effectiveness of 3 common alternate treatments for depression. METHODS: The cost-effectiveness analysis was conducted as part of a randomized clinical trial, the Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) trial, in which patients were randomized from December 2012 to May 2015 and followed for 12 weeks in 35 Veterans Affairs medical centers. Depression diagnosis was based on ICD-9 codes. Patients were randomized to standard antidepressant therapy augmented with aripiprazole, standard antidepressant therapy augmented with bupropion, or switch to bupropion. Remission was measured using the 16-item Quick Inventory of Depressive Symptomatology-Clinican Rated. Outcomes included the incremental cost-effectiveness ratio (ICER) comparing costs per remission and costs per quality-adjusted life-year (QALY) with 12 weeks as the time horizon using the health care sector perspective. RESULTS: The mean age of participants enrolled in the trial (N = 1,522) was 54 years, and participants were predominantly male. The rate of remission at 12 weeks was highest for the aripiprazole augmentation arm (29%), followed by bupropion augmentation (27%), and lowest for switching to bupropion (22%). Switching to bupropion was strongly dominated by bupropion augmentation at an ICER of -$640/remission (95% CI, -$5,770 to $3,008). The ICER for the aripiprazole augmentation versus switching to bupropion was $1,074/remission (95% CI, $47 to $5,022), and the ICER for aripiprazole augmentation versus bupropion augmentation was $5,094/remission (95% CI, -$34,027 to $32,774). There were no significant differences in QALYs, mental health care costs, employment, or other work and social adjustment outcomes between treatment groups. CONCLUSIONS: In treatment of depression with less than optimal response, augmentation with either aripiprazole or bupropion was cost-effective relative to switching to bupropion. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01421342.

Treatment Patterns, Health Care Resource Utilization, and Spending in Medicaid Beneficiaries Initiating Second-generation Long-acting Injectable Agents Versus Oral Atypical Antipsychotics.

PURPOSE: Second-generation long-acting injectable therapies (SGA-LAIs) may reduce health care resource utilization (HRU) and health care costs compared with daily oral atypical antipsychotics (OAAs) in patients with schizophrenia due to reduced dosing frequency, delivery/monitoring by a health care provider, and improved adherence. The aim of the present study was to compare treatment patterns, HRU, and Medicaid spending in patients with schizophrenia initiated on SGA-LAIs (overall and according to agent) versus OAAs. METHODS: Medicaid claims data (2010-2015) from 6 states were used to identify adult schizophrenia patients initiated on SGA-LAIs or OAAs. Treatment patterns (proportion of days covered [PDC] ≥80% and persistence [no gap ≥30, 60, or 90 days] to index treatment), HRU, and costs were evaluated over 12 months and compared by using multivariable logistic, Poisson, and ordinary least squares regression models, respectively. P values for HRU and cost outcomes were obtained from a nonparametric bootstrap procedure. Costs (2015 US dollars) reflect the Medicaid payer's perspective before any rebate. FINDINGS: Overall, 3307 and 21,355 patients initiated SGA-LAIs and OAAs, respectively (paliperidone palmitate LAI [PP-LAI; n = 2182], risperidone LAI [n = 968], aripiprazole LAI [n = 108], and olanzapine LAI [n = 49]). During follow-up and compared with OAA patients, SGA-LAI patients were more likely to reach PDC ≥80% (odds ratio [OR], 1.28; P < 0.001) and be persistent (eg, no gap ≥60 days; OR, 1.45; P < 0.001) to the index treatment. Relative to OAA patients, SGA-LAI patients had fewer long-term care days (incidence rate ratio [IRR], 0.75; P < 0.001) and home care visits (IRR, 0.75; P < 0.001) but more mental health institute (IRR, 1.16; P < 0.001) and 1-day mental health institute (IRR, 1.16; P < 0.001) admissions. Moreover, PP-LAI patients had fewer inpatient days (IRR, 0.78; P = 0.004) versus OAA patients. SGA-LAI patients had lower medical costs (mean monthly cost difference [MMCD], -$168; P < 0.001) than OAA patients, offsetting more than one half of the higher pharmacy costs (MMCD, $271; P < 0.001). Compared with OAAs, only PP-LAI was associated with significant medical cost savings (MMCD, -$225; P < 0.001). IMPLICATIONS: Medicaid beneficiaries with schizophrenia initiated on SGA-LAIs had better adherence and persistence to therapy over 12 months than patients initiated on OAAs. SGA-LAIs, particularly PP-LAI, were associated with lower medical costs that successfully offset more than one half of the higher pharmacy costs relative to OAA.

Real-world adherence assessment of lurasidone and other oral atypical antipsychotics among patients with schizophrenia: an administrative claims analysis.

OBJECTIVE: To compare adherence with lurasidone to other oral atypical antipsychotics among Medicaid and commercially insured patients with schizophrenia. RESEARCH DESIGN AND METHODS: Administrative claims of patients with schizophrenia treated with atypical antipsychotics (lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone) from October 2010 to September 2011 were identified from MarketScan Commercial and Medicaid Databases, and were classified by the first (index) antipsychotic. Patients were 18-64 years, had insurance coverage 12 months pre- and 6 months post-index, and no pre-index use of the index drug. MAIN OUTCOME MEASURES: Medication possession ratio (MPR), discontinuation rate, and mean time to discontinuation were assessed post-index. Pairwise comparisons (lurasidone versus each drug) were conducted using chi-square tests and Student's t-tests. RESULTS: There were 146 Medicaid (mean age 43.5 years, 47.9% female) and 63 commercial (mean age 40.0 years, 42.9% female) patients treated with lurasidone. In the Medicaid population, the MPR for patients treated with lurasidone was 0.60, versus 0.41-0.48 for patients treated with other antipsychotics (all p < .05). Patients treated with lurasidone exhibited a lower discontinuation rate compared to patients treated with all other antipsychotics (49.3% versus 62.3%-68.3%, all p < .05). The mean time to discontinuation with lurasidone was significantly longer than with ziprasidone (p < .05). In the commercial population, the MPR for patients treated with lurasidone (0.61) was higher compared to patients treated with quetiapine (0.44) and ziprasidone (0.43) (both p < .05). The discontinuation rate (44.4%) was lower for patients treated with lurasidone compared to patients treated with all other antipsychotics except risperidone (p < .05). The mean time to discontinuation was longer for lurasidone than with other antipsychotics. CONCLUSIONS: In Medicaid and commercial populations, patients treated with lurasidone demonstrated greater adherence compared to patients treated with other atypical antipsychotics. Limitations of using administrative claims data include potential errors or inconsistencies in coding, and lack of complete clinical information.

Cost-Utility Analysis of Lurasidone Versus Aripiprazole in Adults with Schizophrenia.

BACKGROUND: In 2014, lurasidone, an atypical antipsychotic, was approved for the treatment of schizophrenia in adults. It is an alternative treatment option to aripiprazole, and when compared with aripiprazole, lurasidone was associated with improved symptom reduction and reduced risk of weight gain and relapse. We conducted a cost-utility analysis of lurasidone versus aripiprazole from the perspective of healthcare services, using Scotland and Wales as specific case studies. METHODS: A 10-year Markov model, incorporating a 6-week acute phase and a maintenance phase across three health states (discontinuation, relapse, death) was constructed. Six-week probabilities of discontinuation and adverse events were based on a published independent mixed-treatment comparison; long-term risks of relapse and discontinuation were from an indirect comparison. Costs included drug therapy, relapse, and outpatient, primary and residential care. Costs and benefits were discounted at 3.5 %. Utility estimates were taken from published literature, and cost effectiveness was expressed as total 10-year incremental costs and quality-adjusted life-years (QALYs). RESULTS: Lurasidone yielded a cost saving of £3383 and an improvement of 0.005 QALYs versus aripiprazole, in Scotland. Deterministic sensitivity analysis demonstrated that results were sensitive to relapse rates, while probabilistic sensitivity analysis suggested that lurasidone had the highest expected net benefit at willingness-to-pay thresholds of £20,000-30,000 per QALY. The probability that lurasidone was a cost-effective treatment strategy was approximately 75 % at all willingness-to-pay thresholds, with similar results being obtained for the Welsh analysis. CONCLUSIONS: Our analysis suggests that lurasidone would provide an effective, cost-saving alternative for the healthcare service in the treatment of adult patients with schizophrenia.

Pharmacoeconomics of long-acting atypical antipsychotics for acutely relapsed chronic schizophrenia in Finland.

BACKGROUND: Atypical long-acting injectable (LAI) antipsychotics are increasingly available for treating chronic schizophrenia in patients chronically non-adherent to prescribed regimens. Few economic studies have compared these products. PURPOSE: To determine the cost-effectiveness of aripiprazole (ARI-LAI), paliperidone (PP-LAI), olanzapine (OLZ-LAI), and risperidone (RIS-LAI) in patients with chronic schizophrenia in Finland. METHODS: A 1-year decision tree model was adapted with guidance from an expert panel. Patients started hospitalized in relapse; those who responded continued treatment, others were switched to secondary drugs, then clozapine in the event of 2nd line failure. Rates of adherence, stable disease, relapse, and hospitalization were taken from pivotal trials, and utilities from published research. Included were direct costs paid by the Finnish Ministry of Health, in 2015 euros. Outcomes included quality-adjusted life-years (QALYs), hospitalization rates, and rates of relapse not requiring hospitalization. Model robustness was assessed using a series of 1-way and multivariate sensitivity analyses. RESULTS: Expected costs were lowest for PP-LAI at 41,148€, followed by 41,543€ for ARI-LAI, 42,067€ for RIS-LAI and 45,406€ for OLZ-LAI. Respective QALYs were 0.683, 0.671, 0.666, and 0.672. Re-hospitalization rates and non-admitted relapses were 23.6% and 3.9% for PP-LAI, 28.5% and 4.1% for ARI-LAI, 28.8% and 5.0% for RIS-LAI, 28.3% and 5.2% for OLZ-LAI. PP-LAI treatment was associated with the most days with stable disease (132.0), followed by OLZ-LAI (125.5), ARI-LAI (122.6), and RIS-LAI (114.4). Sensitive inputs between PP-LAI and ARI-LAI included rates of adherence, dropouts, and relapses plus drug prices; dropout and relapse rates for RIS-LAI; OLZ-LAI results were insensitive. In probability sensitivity analyses, PP-LAI dominated ARI-LAI in 75.8% of the 10,000 iterations, RIS-LAI in 83.1% and OLZ-LAI in 95.7%. CONCLUSIONS: PP-LAI dominated the other atypicals. It appears to be the preferred option for treating chronic relapsing schizophrenia.

Health Care Utilization and Treatment Persistence Associated with Oral Paliperidone and Lurasidone in Schizophrenia Treatment.

BACKGROUND: Oral paliperidone and lurasidone are new second-generation antipsychotics (SGAs). Empirical evidence on the comparative costs and persistence of these 2 agents are absent in the literature. OBJECTIVE: To assess health care use and persistence associated with the 2 new agents oral paliperidone and lurasidone and other SGAs. METHODS: Schizophrenia patients who initiated SGA therapy were identified in the January 2007-June 2013 claims databases of a large managed care organization. Multivariate regressions using aripiprazole as the comparator were conducted. Ordinary least squares regressions were used to estimate the total medical and pharmacy costs associated with each drug. Poisson regressions were conducted to evaluate the frequency of hospitalizations and emergency department (ED) visits associated with each drug. A censored regression model was used to evaluate the comparative persistence. Sensitivity analyses using generalized linear models, two-part models, hurdle models, and instrumental variable regressions were also performed.   RESULTS: Compared with aripiprazole, paliperidone was not associated with significantly different total costs, yet lurasidone was associated with lower total costs (-$7,052; 95% CI = -$9,221, -$4,882). Lurasidone was also associated with significantly lower medical services costs (-$5,025; 95% CI = -$7,096, -$2,955), drug costs (-$2,026; 95% CI = -$2,695, -$1,357), hospital costs (-$3,026; 95% CI = -$4,731, -$1,321), outpatient costs (-$1,999; 95% CI = -$2,536, -$1,463), and ED costs (-$2,284; 95% CI = -$3,069, -$1,499), whereas paliperidone did not have significant effects on any types of costs. Paliperidone users had fewer ED visits (-0.25; 95% CI = -0.42, -0.08), while lurasidone users had fewer hospitalizations (-5.98; 95% CI = -6.61, -5.35) and fewer ED visits (-2.51; 95% CI = -2.92, -2.10). Both paliperidone and lurasidone were associated with lower levels of treatment persistence. CONCLUSIONS: Paliperidone does not associate with lower total costs compared with commonly used SGAs, whereas lurasidone is associated with lower total health costs. Thus, high access fees of lurasidone are not necessarily a major concern in prescription.

Cost-effectiveness Analysis of Aripiprazole Once-Monthly for the Treatment of Schizophrenia in the UK.

BACKGROUND: Schizophrenia is a severe and debilitating psychiatric disorder. Pharmacological interventions aim to ameliorate symptoms and reduce the risk of relapse and costly hospitalisation. Despite the established efficacy of antipsychotic medication, compliance to treatment is poor, particularly with oral formulation. The emergence of long acting injectable (LAI) antipsychotic formulations in recent years has aimed to counteract the poor compliance rates observed and optimise long term patient outcomes. AIMS OF THE STUDY: To estimate the cost-effectiveness of aripiprazole once-monthly 400mg (AOM 400) vs. risperidone long acting injectable (RLAI), paliperidone long acting injectable (PLAI) and olanzapine long acting injectable (OLAI) in the maintenance treatment of chronic, stable schizophrenia patients in the United Kingdom. METHODS: A Markov model was developed to emulate the treatment pathway of a hypothetical cohort of patients initiating maintenance treatment with LAI antipsychotics. The economic analysis was conducted from a National Health Service (NHS) and Personal Social Services (PSS) perspective over a 10 year time horizon. Efficacy and safety probabilities were derived from mixed treatment comparisons (MTCs) where possible. Analyses were conducted assuming pooled dosing from randomised clinical trials included in the MTCs. RESULTS: The model estimates that AOM 400 improves clinical outcomes by reducing relapses per patient comparative to other LAIs over the model time horizon (2.38, 2.53, 2.70, and 2.67 for AOM 400, RLAI, PLAI and OLAI respectively). In the deterministic analysis, AOM 400 dominated PLAI and OLAI; an incremental cost-effectiveness ratio (ICER) of GBP 3,686 per QALY gained was observed against RLAI. Results from the univariate sensitivity analyses highlighted the probability and cost of relapse as main drivers for cost-effectiveness. In the probabilistic sensitivity analysis, AOM 400 demonstrated a marginally higher probability of being cost-effective (51%) than RLAI, PLAI and OLAI (48%, 1% and 0%, respectively) at a willingness to pay threshold of GBP 20,000. DISCUSSION: The model was built to accommodate results of an adjusted MTC analysis. Furthermore the model effectively captures repercussions of deteriorating compliance to treatment by incorporating three levels of compliance with elevated risks of relapse for partial compliance and non-compliance. Limitations of the analysis include the limited number of studies incorporated in the MTC, the extrapolation of short term clinical data and the exclusion of the wider societal burden. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Comparative to other atypical antipsychotics, AOM 400 represents value for money in the maintenance treatment of chronic, stable schizophrenia; however, in light of the PSA findings and comparable cost-effectiveness (i.e. against RLAI), the product profile and wider benefits of the respective treatments must be taken into account when prescribing antipsychotics. IMPLICATIONS FOR FURTHER RESEARCH: Future research should assess the use of LAI antipsychotics earlier in the disease course of schizophrenia to see whether improved compliance and outcomes shortly following the onset of psychosis has the potential to alter the disease trajectory. Moreover it should be assessed whether changes in the disease trajectory can alleviate cost and resource pressures placed on national health services.

Cost analysis of the adverse reactions of bipolar disorder treatment with aripiprazole and olanzapine in Spain.

OBJECTIVE: This study investigates the healthcare costs of adverse events (AE) associated with treatment of bipolar disorder with two atypical oral antipsychotics (AOA): aripiprazole (ARI) and olanzapine (OLA). METHODS: A cost analysis using a Markov model considering the following health states was performed: no existence of adverse events (NAE); extrapyramidal symptoms (EPS); weight gain (WG); and sexual dysfunction (SD). Transition probabilities amongst health states were estimated from meta-analyses of clinical trials and from a retrospective Spanish study. The healthcare costs associated to each health state were obtained from a published Spanish study. The minimum acquisition cost per mg of the mean daily dose for each AOA was used. This is considered to be a relevant efficiency criterion in Hospital Pharmacy Departments. The time horizon applied in the analysis was 12 months. A probabilistic sensitivity analysis was performed for all the variables involved in the analysis with Monte Carlo simulations. All costs were updated to 2013 costs using the Spanish Health System price index. RESULTS: In comparison with OLA, treatment with ARI generates annual average cost savings per patient of ¤289 (CI95% ¤271; ¤308). In the hypothetical scenario in which we assume that ARI may have a similar rate of sexual dysfunction as that of quetiapine (i.e. the lowest rate amongst AOAs), the additional cost per patient would be ¤323 (CI95% ¤330; ¤317). CONCLUSION: The results of this analysis show that patients treated with aripiprazole demonstrate lower adverse events costs in comparison to olanzapine. This difference may generate significant cost savings in the Spanish health system in the treatment of patients affected by bipolar disorders. The robustness of the results was tested via a probabilistic analysis.