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.

Comparative cost-effectiveness of amisulpride and olanzapine in the treatment of schizophrenia in China.

BACKGROUND: Both amisulpride and olanzapine are leading treatments for schizophrenia in China. This study aimed to investigate the long-term cost-effectiveness of amisulpride and olanzapine in the treatment of schizophrenia in China. METHODS: A decision-analytic Markov model was developed to simulate the lifetime clinical and economic outcomes of schizophrenia treatment from the healthcare payer perspective. The long-term costs and QALYs were estimated. Sensitivity analyses were performed to explore the impact of variance of parameters on the results. RESULTS: Treatment with amisulpride provided an effectiveness gain of 16.59 QALYs at an average cost of USD 25,884 whereas olanzapine resulted in 16.38 QALYs at a cost of USD 34,839 over a lifetime horizon. One-way sensitivity analysis suggested that the most sensitive variable was the unit cost of olanzapine. In a probabilistic sensitivity analysis based on a Monte Carlo simulation with a lifetime horizon, the probability of amisulpride being cost-effective was 99.8% at a willingness-to-pay threshold of USD 9,322, the GDP per capita in China 2018. A scenario analysis with updated olanzapine unit cost suggested an ICER of 7,857 USD/QALY. CONCLUSIONS: Amisulpride is likely to be a cost-effective option with increased effectiveness compared with olanzapine in the treatment of schizophrenia patients 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.

Lights and shadows of schizophrenia therapy research: Lessons from oral risperidone and olanzapine.

BACKGROUND: Recently, patents of several atypical antipsychotics have reached their expiration date. AIMS: The purpose of the study was to highlight whether modifications of economic/scientific factors may be associated with possible changes in ongoing clinical research on antipsychotic drugs. METHODS: A large systematic analysis was used to depict the time-dependent distribution of published research articles addressing the clinical properties of oral risperidone and olanzapine conventional tablets, two largely prescribed atypical antipsychotics for which the patents have already expired in most of the countries. RESULTS: The systematic analysis indicated that the time-dependent distribution of the selected research articles followed a wave-shape pattern. A dramatic decline of primary and secondary analyses investigating the clinical effects of oral risperidone and olanzapine has occurred in the last decade, complemented by an expected strong reduction in the numbers of industrial-supported clinical studies and a smaller, but significant, decline in the amount of independent research articles. CONCLUSIONS: To date, greater involvement of independent research seems to be the only realistic chance to properly continue the investigation on the clinical properties of oral risperidone and olanzapine conventional tablets, as well as those of other off-patent antipsychotic drugs. However, the limits and potentialities of independent research in accomplishing such a demanding and enduring scientific effort should be addressed.

Randomized Phase II Trial to Compare the Efficacy of Haloperidol and Olanzapine in the Control of Chemotherapy-Induced Nausea and Vomiting in Nepal.

PURPOSE: The purpose of the study was to compare efficacy and toxicity of olanzapine (OLN; a higher-cost drug) and haloperidol (HAL; a lower-cost drug) in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who receive highly emetogenic chemotherapy (HEC). PATIENTS AND METHODS: In a randomized, phase II trial, patients were randomly assigned to receive either OLN 10 mg orally on days 1 to 4 or HAL 1 mg orally on day 1 and 0.5 mg twice daily on days 2 to 4. Both groups received ondansetron 16 mg and dexamethasone 12 mg intravenously on day 1. Patients recorded their nausea using the Edmonton Symptom Assessment Scale (ESAS) and recorded daily episodes of vomiting from day 1 to day 5. The primary end point was complete nausea prevention (CNP; ie, ESAS of 0). Secondary end point was complete emesis prevention (CEP). RESULTS: Sixty-five patients were randomly assigned, and 64 received their allocated treatment (n = 32 in each arm). There was no difference in CNP during the overall period (days 1 to 5) between OLN and HAL (68.7% v 71.8%; P = .78). In the acute period (day 1) and the delayed period (days 2 to 5), CNP was similar between OLN and HAL (acute: 84.3% v 81.2%; delayed: 68.7% v 75%). No difference was identified in the rate of CEP during the overall period (81.2% with OLN v 78.1% with HAL; P = .75), during the acute period (93.7% with OLN v 90.6% with HAL), or during the delayed period (84.3% with OLN v 84.3% with HAL). No difference in toxicities was noted between treatment arms. CONCLUSION: In this study, HAL had comparable efficacy to OLN in the management of CINV, which suggests that it is the higher-value option in patients who receive HEC in resource-scarce countries.

Cost-effectiveness analysis of olanzapine-containing antiemetic therapy for managing highly emetogenic chemotherapy in Southeast Asia: a multinational study.

PURPOSE: Recent studies suggested that olanzapine, together with dexamethasone and serotonin-3 receptor antagonist (5HT3RA), is effective in preventing chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC). This regimen is particularly useful in Southeast Asia (SEA) countries where resources are limited. We aimed to evaluate the cost-effectiveness of incorporating olanzapine into standard antiemetic regimens for the prevention of CINV in patients receiving HEC among SEA countries. METHODS: Using a decision tree model, clinical and economic outcomes associated with olanzapine-containing regimen and standard antiemetic regimen (doublet antiemetic regimen: dexamethasone+first generation 5HT3RA) in most SEA countries except in Singapore (triplet antiemetic regimen: dexamethasone+first generation 5HT3RA + aprepitant) for CINV prevention following HEC were evaluated. This analysis was performed in Thailand, Malaysia, Indonesia, and Singapore, using societal perspective method with 5-day time horizon. Input parameters were derived from literature, network meta-analysis, government documents, and hospital databases. Outcomes were incremental cost-effectiveness ratio (ICER) in USD/quality-adjusted life year (QALY) gained. A series of sensitivity analyses including probabilistic sensitivity analysis were also performed. RESULTS: Compared to doublet antiemetic regimen, addition of olanzapine resulted in incremental QALY of 0.0022-0.0026 with cost saving of USD 2.98, USD 27.71, and USD 52.20 in Thailand, Malaysia, and Indonesia, respectively. Compared to triplet antiemetic regimen, switching aprepitant to olanzapine yields additional 0.0005 QALY with cost saving of USD 60.91 in Singapore. The probability of being cost-effective at a cost-effectiveness threshold of 1 GDP/capita varies from 14.7 to 85.2% across countries. CONCLUSION: The use of olanzapine as part of standard antiemetic regimen is cost-effective for the prevention of CINV in patients receiving HEC in multiple SEA countries.

Effectiveness of Antiemetic Regimens for Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: A Systematic Review and Network Meta-Analysis.

BACKGROUND: It is important to control chemotherapy-induced nausea and vomiting (CINV) to maintain dose intensity and patients' quality of life. The National Comprehensive Cancer Network guidelines suggest combination therapy of antiemetic agents. The growing number of antiemetic regimens, and in particular the growing use of regimens containing antagonists to the Nk-1 receptor (NK1RAs) and the antipsychotic drug olanzapine (OLZ), call for the re-evaluation of the optimal regimen for CINV. This study assessed the efficacy and safety of antiemetic regimens for highly emetogenic chemotherapy, using Bayesian network meta-analysis. METHODS: Randomized trials that compared different antiemetic regimens were included. We strictly followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The main outcomes were the odds ratio (OR) for overall complete response (absence of vomiting). We conducted network meta-analysis within a Bayesian model to combine the direct and indirect evidence. Safety was assessed from the trial description. All statistical tests were two-sided. RESULTS: We systematically reviewed 27 randomized control trials (13,356 participants), which compared 12 different antiemetic regimens: serotonin-3 receptor antagonist (5HT3), 5HT3 + dexamethasone (Dex), palonosetron (PAL), PAL + Dex, PAL at 0.75 mg (PAL0.75), PAL0.75 + Dex, NK1RA + 5HT3 + Dex, NK1RA + PAL + Dex, an oral combination of netupitant and palonosetron (NEPA) + Dex, OLZ + 5HT3 + Dex, OLZ + PAL + Dex, and OLZ + NK1RA + 5HT3 + Dex. An NK1RA + 5HT3 + Dex regimen and an NK1RA + palonosetron + Dex regimen gave a higher complete response (CR) rate than the reference regimen, 5HT3 + Dex (OR, 1.75; 95% credibility interval [95% CrI], 1.56-1.97, and OR, 2.25; 95% CrI, 1.66-3.03, respectively). A regimen containing NEPA was more effective in producing CR than conventional regimens without NEPA or olanzapine. Further analysis, based on the surface under the cumulative ranking probability curve, indicated that olanzapine-containing regimens were the most effective in producing CR. CONCLUSION: Our meta-analysis supports the conclusion that olanzapine-containing regimens are the most effective for CINV of highly emetogenic chemotherapy. We confirmed that NK1RA + PAL + Dex is the most effective of conventional regimens. Substituting olanzapine for an Nk-1 receptor antagonist may offer a less costly and more effective alternative for patients. IMPLICATIONS FOR PRACTICE: Nausea and vomiting during chemotherapy often pose difficulties for patients and doctors, making it hard to continue the proper therapy and to maintain the quality of life. This article gives insights into the optimal choice of medicine to treat nausea during chemotherapy. The findings reported here provide readers with a robust efficacy ranking of antinausea medicine, which can be used as a reference for the best possible treatment. Furthermore, the 70% less costly drug, olanzapine, is suggested to be equally effective to aprepitant in reducing nausea and vomiting. The possibility of offering a cost-effective treatment to a wider range of the population is discussed.

[Cost-effectiveness study of olanzapine pamoate: Mirror-image analysis after one year]. / Étude coût-efficacité du pamoate d'olanzapine : analyse en miroir sur un an.

INTRODUCTION: Olanzapine pamoate has a higher cost of treatment than the oral form and requires administration in a hospital setting (unlike other long-acting antipsychotics), and the cost-effectiveness of this treatment may be questioned. Many scientific societies and national health systems are increasingly interested in the pharmacoeconomic impact of health products. The search for efficacy of a treatment can be done in two ways: medico-economic modeling studies or observational studies i.e. randomized controlled trials or mirror studies. The models are based on theoretical models from published clinical data simulating the course and evolution of patient health conditions, which benefit from a particular therapeutic strategy. Even if the design of observational mirror studies makes it possible to get closer to the clinical reality by observing the patient before and after the initiation of the treatment, the majority of the pharmacoeconomic studies published on olanzapine pamoate are modeling works that do not reflect actual conditions of care. The Guillaume Régnier Hospital Center in Rennes has a large cohort of patients treated with olanzapine pamoate: 121 instauration treatments are recorded from April 1, 2010 to Mars 1, 2015. The objective of this study is to evaluate the cost-effectiveness of olanzapine pamoate in actual clinical practice. METHODS: This is a one-year cost-effectiveness retrospective observational mirror-image study of a cohort of 52 patients with schizophrenia who were treated for at least three months with olanzapine pamoate. The primary efficacy endpoint is the differential in the number of full-time hospitalizations before and after the introduction of olanzapine pamoate versus the hospital cost differential. The secondary criteria are the difference of the number of the days spent in hospital and the number of outpatient consultations between the year preceding the injection and the year following it. The results were calculated on the general cohort and within 2 subgroups: patients treated for more than one year and those receiving less than one year of treatment with olanzapine pamoate. RESULTS: Fifty-two patients were included (median age=35 years, sex ratio H/F=2.7) and only 38.5% discontinued treatment. For patients who maintained long-acting treatment, they received a dosage of 25mg oral olanzapine (min=7.5mg, max=60mg), 5mg more medially than the group having stopped the olanzapine pamoate (20mg; min=10mg, max=40mg). The majority of these patients were receiving off-label authorized marketing doses of oral olanzapine, whereas 22% of them had off-label dosages of olanzapine pamoate. The main causes of discontinuation were symptom persistence, loss of vision and the occurrence of adverse effects (including weight gain and sedation). Olanzapine pamoate significantly reduced the number of hospitalizations compared to the previous management strategy (1 less hospitalization, P<0.001 in patients treated more than one year and in the general cohort). As a logical consequence the number of hospitalization days in day care increased after the establishment of this long-acting antipsychotic with hospital reserve status (18 in median; min=0, max=159). We observed a non-statistically significant tendency of decrease in the number of days of full-time hospitalization and an increase in the number of ambulatory procedures, particularly in patients who have maintained the treatment for one year. This efficiency had a non-significant additional cost of €3361 per year. There was an average multiplication by 8,5 of the drug cost a year later in the general cohort (5.5 in the group of patients treated less than one year and 10.4 in the group of patients who maintained it a year). There was a 23,2% average increase in the cost of hospitalization in the general cohort (3.75 % in patients who maintained treatment compared to 48.9% in patients who discontinued treatment). CONCLUSION: By its mirror design, the study was placed in real conditions of care of the patient with schizophrenia. A total of 61.5% of patients maintained treatment with olanzapine pamoate for a minimum of one year. This APAP is more effective without significantly increasing the cost compared to the previous therapeutic strategy (including oral olanzapine). The additional cost is partly due to the administration restriction in a hospital setting in relation to risk of Post-Injection Delirium/Sedation Syndrom (PDSS). There is currently no acceptable efficiency limit. The results of this cost-effectiveness analysis cannot be extrapolated to the other long-acting antipsychotics since it is the only one with hospital reserve status. The current limitations of medico-economics in psychiatry derive from the heterogeneity of clinical forms and the management of mental pathologies.

One-year mirror-image study of the impact of olanzapine long-acting injection on healthcare resource utilization and costs in severe schizophrenia.

Olanzapine long-acting injections (OLAIs) are often prescribed to patients with severe schizophrenia who are typically excluded from randomized clinical trials. To date, no mirror-image study has examined the impact of OLAIs on healthcare resource utilizations in these patients. We conducted a retrospective, one-year mirror-image study of OLAIs on 40 patients with severe schizophrenic disorder. Illness severity was defined by failure to respond to two sequential antipsychotics. Outcomes included: (i) healthcare resource utilizations via hospitalization admissions, bed days, outpatient visits, and inpatient service costs computations (ii) clinical efficacy through changes in the Brief Psychiatric Rating Scale (BPRS) and in the Clinical Global Impression-Schizophrenia Scale (CGI-SCH), and (iii) adverse effects. After one year, OLAIs were associated with significant decreases of 65.7%, 86.2% and 86.2% in hospitalization admissions, bed days, and inpatient service costs respectively. A significant mean change of -0.47 and -0.63 was determined the BPRS and the CGI-SCH scores, respectively. There were no significant differences in the number of outpatient visits and adverse effects, except for post-injection sedation/delirium syndrome whose incidence was 0.30% per injection. This mirror-image study provides the first evidence that prescribing OLAIs reduces in a cost-effective manner average bed days and hospital admissions in patients with severe schizophrenia.

Comparative efficacy and safety between amisulpride and olanzapine in schizophrenia treatment and a cost analysis in China: a systematic review, meta-analysis, and cost-minimization analysis.

BACKGROUND: Amisulpride was introduced into China in 2010 as a second-generation atypical antipsychotic, while olanzapine has been on the market since 1999 as one of the leading treatments for schizophrenia in China. Since more Chinese patients are gaining access to amisulpride, the study aims to compare the efficacy, safety, and costs between amisulpride and olanzapine for schizophrenia treatment in China. METHODS: PubMed, Embase, the Cochrane library, China National Knowledge Infrastructure (CNKI) and WanFang database were systematically searched for randomized controlled trials (RCTs) up to July 2018. The Cochrane Risk of Bias tool was utilized to assess the quality of included studies. A meta-analysis was performed to compare the efficacy and safety of amisulpride and olanzapine, followed by a cost-minimization analysis using local drug and medical costs reported in China. RESULTS: Twenty RCTs with 2000 patients were included in the systematic review. There were no significant differences between amisulpride and olanzapine on efficacy measures based on scores from the Positive and Negative Syndrome Scale, the Scale for the Assessment of Negative Symptoms, the Brief Psychiatric Rating Scale and the Clinical Global Impressions-Severity or Improvement. For safety outcomes, amisulpride was associated with lower fasting blood glucose and less abnormal liver functions as well as significantly lower risks of weight gain, constipation, and somnolence; olanzapine was associated with significantly lower risks of insomnia and lactation/amenorrhea/sexual hormone disorder. No significant differences were found in risks of extrapyramidal symptoms (EPS), tremor, akathisia, abnormal corrected QT interval. Cost-minimization analysis showed that amisulpride was likely to be a cost-saving alternative in China, with potential savings of 1358 Chinese Yuan (CNY) per patient for a three-month schizophrenia treatment compared with olanzapine. CONCLUSION: As the first meta-analysis and cost-minimization analysis comparing the efficacy, safety and cost of amisulpride and olanzapine within a Chinese setting, the study suggests that amisulpride may be an effective, well-tolerated, and cost-saving antipsychotic drug alternative in China.

Costs in the Treatment of Schizophrenia in Adults Receiving Atypical Antipsychotics: An 11-Year Cohort in Brazil.

BACKGROUND: Schizophrenia is associated with significant economic burden. In Brazil, antipsychotic drugs and outpatient and hospital services are provided by the Brazilian National Health System (SUS) for patients with schizophrenia. However, few studies capture the cost of managing these patients within the Brazilian NHS. This is important to appraise different management approaches within universal healthcare systems. OBJECTIVE: Our objective was to use real-world data to describe the costs associated with the treatment of schizophrenia in adults receiving atypical antipsychotics in Brazil from 2000 to 2010. METHODS: We integrated three national databases for adult patients with schizophrenia receiving one or more atypical antipsychotics. We assessed only direct medical costs and the study was conducted from a public-payer perspective. A multivariate log-linear regression model was performed to evaluate associations between costs and clinical and demographic variables. RESULTS: We identified 174,310 patients with schizophrenia, with mean ± standard deviation (SD) annual costs of $US1811.92 ± 284.39 per patient. Atypical antipsychotics accounted for 79.7% of total costs, with a mean annual cost per patient of $US1578.74 ± 240.40. Mean annual costs per patient were $US2482.90 ± 302.92 for psychiatric hospitalization and $US862.96 ± 160.18 for outpatient psychiatric care. Olanzapine was used by 47.7% of patients and represented 62.8% of the total costs of atypical antipsychotics. Patients who used clozapine had the highest mean annual cost per patient for outpatient psychiatric care and psychiatric hospitalization. CONCLUSIONS: Atypical antipsychotics were responsible for the majority of the schizophrenia treatment costs, and psychiatric hospitalization costs were the highest mean annual cost per patient. Authorities should ensure efficient use of atypical antipsychotics and encourage outpatient psychiatric care over psychiatric hospitalization where possible.