The Economic Impact of Cognitive Impairment and Negative Symptoms in Schizophrenia: A Targeted Literature Review With a Focus on Outcomes Relevant to Health Care Decision-Makers in the United States.

Abstract.Objective: To conduct a targeted literature review to examine the impact of cognitive impairment and negative symptoms among patients with schizophrenia treated in the United States across a range of outcomes pertinent to the US health care system decision-makers, such as payers and policy-makers.Data Sources: The authors searched EMBASE and PubMed from January 2012 to January 2024. Search terms included schizophrenia, cognitive impairment and negative symptoms, and direct medical and nonmedical, indirect, and societal outcomes.Study Selection: Considered for inclusion were US-based studies reporting on the relationship between cognitive impairment or negative symptoms and direct medical and nonmedical, indirect, and societal outcomes in patients with schizophrenia. A total of 4,212 articles were initially identified for screening.Data Extraction: One reviewer extracted data and another reviewer ensured studies met Population, Intervention, Comparison, Outcomes, Study Design-Time Period (PICOS-T) criteria for inclusion and exclusion.Results: Eight studies (n = 262,683) were included that reported specifically on associations between cognitive impairment or negative symptoms and targeted outcomes. Patients with schizophrenia and moderate/severe cognitive impairment had a 100% increase in relapse-related hospitalizations (0.6 vs 0.3, adjusted incidence rate ratio = 1.85, P < .05) and ER visits (0.4 vs 0.2, adjusted odds ratio = 1.77, P < .05) vs patients with no/mild cognitive impairment. Additionally, there was an almost 50% increase in outpatient visits (8.4 vs 5.5, P < .001) and inpatient admissions (6.8 vs 4.5, P < .001) over the study period (2014 Q1-2017 Q4) for patients with negative symptoms vs without negative symptoms. Direct nonmedical, indirect, and societal outcomes are described.Conclusions: This review highlights the economic burden of cognitive impairment and negative symptoms by focusing on outcomes relevant to health care decision-makers in the United States.

A real-world data analysis of electronic health records to investigate the associations of predominant negative symptoms with healthcare resource utilisation, costs and treatment patterns among patients with schizophrenia.

OBJECTIVES: Negative symptoms in schizophrenia are associated with significant illness burden. We sought to investigate clinical outcomes for patients with schizophrenia who present with predominant negative symptoms (PNS) vs without PNS. DESIGN: Retrospective analysis of electronic health record (EHR) data. SETTING: 25 US providers of mental healthcare. PARTICIPANTS: 4444 adults with schizophrenia receiving care between 1999 and 2020. EXPOSURE: PNS defined as ≥3 negative symptoms and ≤3 positive symptoms recorded in EHR data at the time of the first recorded schizophrenia diagnosis (index date). Symptom data were ascertained using natural language processing applied to semistructured free text records documenting the mental state examination. A matched sample (1:1) of patients without PNS was used to compare outcomes. Follow-up data were obtained up to 12 months following the index date. PRIMARY OUTCOME MEASURE: Mean number of psychiatric hospital admissions. SECONDARY OUTCOME MEASURES: Mean number of outpatient visits, estimated treatment costs, Clinical Global Impression - Severity score and antipsychotic treatments (12 months before and after index date). RESULTS: 360 (8%) patients had PNS and 4084 (92%) did not have PNS. Patients with PNS were younger (36.4 vs 39.7 years, p<0.001) with a greater prevalence of psychiatric comorbidities (schizoaffective disorders: 25.0 vs 18.4%, p=0.003; major depressive disorder: 17.8 vs 9.8%, p<0.001). During follow-up, patients with PNS had fewer days with an antipsychotic prescription (mean=111.8 vs 140.9 days, p<0.001). Compared with matched patients without PNS, patients with PNS were more likely to have a psychiatric inpatient hospitalisation (76.1% vs 59.7%, p<0.001) and had greater estimated inpatient costs ($16 893 vs $13 732, p=0.04). CONCLUSIONS: Patients with PNS were younger and presented with greater illness severity and more psychiatric comorbidities compared with patients without PNS. Our findings highlight an unmet need for novel therapeutic approaches to address negative symptoms to improve clinical outcomes.

Treatment patterns and hospitalizations following rejection, reversal, or payment of the initial once-monthly paliperidone palmitate long-acting injectable antipsychotic claim among patients with schizophrenia or schizoaffective disorder.

BACKGROUND: Once-monthly paliperidone palmitate (PP1M) is a long-acting injectable antipsychotic approved for the treatment of schizophrenia and schizoaffective disorder (SCA) in adults. OBJECTIVE: To assess treatment patterns and schizophrenia/SCA-related hospitalization following payer rejection, patient reversal, or payment of an initial PP1M claim. METHODS: This was a retrospective cohort study using the IQVIA Formulary Impact Analyzer database linked to the Medical Claims, Hospital Charge Detail Master, and Experian consumer databases. Patients with schizophrenia/SCA and ≥1 PP1M pharmacy claim from January 1, 2018, to February 28, 2022, were identified and stratified into 3 cohorts based on the transaction status of the initial PP1M claim (index date): rejected (payer not approved), reversed (payer approved, patient abandoned), and paid (payer approved, patient filled). Patient characteristics during the 12 months before the index date, subsequent treatment patterns, and schizophrenia/SCA-related hospitalization for patients with >6 months of follow-up were assessed by cohort. RESULTS: The rejected, reversed, and paid cohorts included 1,260, 1,046, and 1,686 patients, respectively. Across these cohorts, the mean ages ranged between 39.2 and 44.5 years; more than half were male (50.8%-51.6%) and White (50.6%-58.3%); 19.8%-24.6% of patients had a Quan-Charlson Comorbidity Index score of ≥2. Rates of prior atypical oral and long-acting injectable antipsychotic use ranged between 76.4%-80.3% and 7.8%-12.7%, respectively. Among patients with ≥6 months of follow-up, 52.2% in the rejected and 53.1% in the reversed cohorts had a subsequent paid PP1M claim during the study period; the median (quartile 1-quartile 3) time to the first paid PP1M claim was 22 (5-74) days for rejection and 11 (1-41) days for reversal. In the rejected and reversed cohorts, 10.2% (n = 111) and 9.8% (n = 90) of patients, respectively, did not receive any paid claim for an antipsychotic after the initial PP1M rejection/reversal. The prevalence of schizophrenia/SCA-related hospitalization during follow-up was similar between patients with a paid (7.4%) and rejected PP1M claim (7.0%; P = 0.689) but higher among patients with a reversed claim (10.8%; P = 0.004). After adjusting for confounders, patients in the reversed cohort were 39% more likely to have a schizophrenia/SCA-related hospitalization than those in the paid cohort (odds ratio = 1.39; 95% CI = 1.03-1.87). CONCLUSIONS: Payer rejection and patient reversal of initial PP1M claims is a form of primary nonadherence and may influence patient trajectory. Data from this study suggest that patient reversal of PP1M may lead to an increased risk of schizophrenia/SCA-related hospitalizations, potentially caused by missed or delayed treatment. Policy initiatives that remove barriers to primary adherence or fulfillment may help improve patients' clinical outcomes.

Adherence, health care utilization, and costs between long-acting injectable and oral antipsychotic medications in South Carolina Medicaid beneficiaries with schizophrenia.

BACKGROUND: Schizophrenia and schizoaffective disorder require long-term antipsychotic treatment with antipsychotic medications, but poor medication adherence can lead to increased health care utilization and costs. Long-acting injectable antipsychotics (LAIs) offer potential therapeutic advantages in that they require less frequent dosing and improved medication adherence. South Carolina has the highest adoption of LAIs among US states, making it an ideal population for comparing the effectiveness of LAIs vs oral antipsychotics (OAPs) in treating schizophrenia or schizoaffective disorder. OBJECTIVE: To evaluate the effect of LAIs compared with OAPs on medication adherence, health care resource utilization, and costs among South Carolina Medicaid beneficiaries with schizophrenia or schizoaffective disorder. METHODS: South Carolina Medicaid beneficiaries with at least 1 claim for an LAI or OAP between January 1, 2015, and December 31, 2018, aged 18 to 65, with at least 2 claims with diagnoses of schizophrenia or schizoaffective disorder were included. Propensity scores (PSs) were calculated using logistic regression adjusting for confounders and predictors of the outcome. We estimated the "average treatment effect on the treated" by employing PS-weighted t-tests and chi-square tests. RESULTS: A total of 3,531 patients met the inclusion criteria, with 1,537 (44.5%) treated with LAIs and 1,994 (56.5%) treated with OAPs. In PS-weighted analyses, the LAI cohort had a greater proportion of days covered than the OAP cohort with a 365-day fixed denominator (69% vs 64%; P < 0.0001), higher medication possession ratio with a variable denominator while on therapy (85% vs 80%; P < 0.0001), and higher persistence (82% vs 64%; P < 0.0001). The average number of inpatient visits and emergency department visits did not significantly differ between cohorts (0.28 hospitalizations, P = 0.90; 3.68 vs 2.96 emergency department visits, P = 0.19). The number of outpatient visits, including visits for medication administration, were greater in the LAI cohort (23.1 [SD 24.2]) vs OAP (16.9 [SD 21.2]; P < 0.0001); however, including the costs for medication administration visits, outpatient costs (per member) were approximately $2,500 lower in the LAI cohort (P < 0.0001). The number of pharmacy visits was greater in the OAP cohort (LAI 21.0 [SD 17.0] vs OAP 23.0 [SD 15.0]; P = 0.006). All-cause total costs were greater in the LAI cohort ($26,025 [SD $29,909]) vs the OAP cohort ($17,291 [SD $25,261]; P < 0.0001) and were driven by the difference in pharmaceutical costs (LAI $15,273 [SD $16,183] vs OAP $4,696 [SD $10,371]; P < 0.0001). CONCLUSIONS: Among South Carolina Medicaid beneficiaries, treatment with LAIs for schizophrenia or schizoaffective disorder was associated with greater medication adherence rates. Patients using LAIs had higher drug costs and total costs, but lower outpatient and total nondrug costs compared with those using OAPs.

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.

Reasons for switching oral antipsychotic medications and related patterns of care and costs in patients with schizophrenia initiating monotherapy treatment: Claims-linked chart study.

BACKGROUND: Antipsychotic switching is frequent in schizophrenia and is associated with poor clinical outcomes, increased health care resource utilization (HCRU), and increased health care costs. Research describing the reasons for antipsychotic switching in patients with schizophrenia and the associated impacts on HCRU and costs is limited. OBJECTIVE: To explore the reasons for oral antipsychotic medication (OAM) switching and describe HCRU and costs associated with OAM switching, stratified by reasons for switching, in patients with commercial or Medicare Advantage insurance in the United States. METHODS: This retrospective observational study used medical and pharmacy claims from the Optum Research Database linked to patient medical chart data. Adults with a diagnosis of schizophrenia who initiated OAM monotherapy between January 1, 2015, and June 30, 2021, and switched from their initial OAM monotherapy to a second one were included. Reasons for OAM switching were recorded from medical charts abstracted between 4 months preceding and 2 months following the patient's switch date. HCRU and costs incurred up to 3 months before and 3 months after the OAM switch were stratified and compared by reasons for switching among individuals who switched OAM monotherapy. RESULTS: Among 134 patients with valid, abstracted charts, the 2 most common reasons for switching were lack of efficacy (57.5% of switches) and at least 1 tolerability issue (41.8%). Mutually exclusive categories of switching reasons included lack of efficacy and no tolerability issues (56/134; 41.8%), tolerability and no efficacy issues (35/134; 26.1%), lack of efficacy and tolerability issues (21/134; 15.7%), and other or unknown (22/134; 16.4%). All-cause and schizophrenia-related HCRU and costs in any health services category did not appear to differ across the reason-for-switching cohorts, with costs for inpatient stays accounting for greater than half of the total costs, regardless of switching reason. CONCLUSIONS: These findings provide insight on patient experiences that contribute to OAM switching, with nearly half of patients switching because of lack of efficacy, more than one-fourth because of tolerability issues, and an additional one-sixth for reasons of both efficacy and tolerability. Health care providers should address patients' expectations regarding OAM effectiveness, symptom resolution, and side effect tolerability at treatment initiation to minimize switching before the medication has reached peak effectiveness. Prescribing access to a broad selection of antipsychotics with different side effect profiles may help physicians better match treatment to individual patients, fostering greater acceptance of therapy, increased medication adherence, and better long-term outcomes.

Patterns of care and costs of switching oral antipsychotic medications in patients with schizophrenia initiating monotherapy treatment: A US claims analysis.

BACKGROUND: Antipsychotic medications are the mainstay of schizophrenia therapy but may need to be changed over the course of a patient's illness to achieve the desired therapeutic goals or minimize medication side effects. Investigations of real-world treatment patterns and economic consequences associated with antipsychotic changes, including switching, are limited. OBJECTIVE: To describe treatment patterns among patients with schizophrenia who initiated oral antipsychotic medication (OAM) monotherapy and assess switching-related health care resource utilization (HCRU) and costs in US Medicare Advantage and commercially insured patients. METHODS: Adults with at least 2 claims with a schizophrenia diagnosis who initiated (or reinitiated after ≥6 months) OAM monotherapy between January 1, 2015, and June 30, 2021, were identified in the Optum Research Database. A claims-based algorithm using timing of therapies and treatment gaps identified medication changes, specifically OAM monotherapy switches, among OAM initiators over a period of up to 7 years. Patients who switched from their initial OAM monotherapy to a second OAM monotherapy (initial OAM switchers) were matched based on clinical and demographic characteristics to OAM initiators who had not switched OAMs; switch-related HCRU and costs (incurred up to 3 months before and 3 months after the initial OAM switch) were compared between matched initial OAM switchers and nonswitchers. RESULTS: Among 6,425 OAM monotherapy initiators, 1,505 (23.4%) had at least 1 OAM monotherapy switch at any time during follow-up, with a mean (SD) time to first switch of 209 (333) days (median, 67 days), a rate of 0.65 switches per person-year of follow-up, and 56% of first switches occurring within 3 months of OAM initiation. Of all OAM initiators, 947 (14.7%) were initial OAM switchers. Compared with 865 matched nonswitchers, 865 initial OAM switchers had greater mean counts of all-cause medical visits and greater mean counts of schizophrenia-related emergency and inpatient visits and longer inpatient stays per patient per month. Mean (SD) total schizophrenia-related costs per patient per month were $1,252 ($2,602) for switchers compared with $402 ($2,027) for nonswitchers (P < 0.001). CONCLUSIONS: Changes to antipsychotic therapy in our sample of patients with schizophrenia were common, with nearly one-fourth switching OAMs, the majority within the first 3 months of therapy. Initial OAM switchers experienced greater HCRU and costs than nonswitchers. These findings highlight the importance of initiating OAM monotherapy that effectively maintains symptom control and minimizes tolerability issues, which would limit the need to switch OAMs and therefore prevent excess HCRU and treatment costs.

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.

Acknowledging Patient Heterogeneity in Economic Evaluations in Schizophrenia: A Systematic Review.

OBJECTIVES: Schizophrenia is a severe mental illness with heterogeneous etiology, range of symptoms, and course of illness. Cost-effectiveness analysis often applies averages from populations, which disregards patient heterogeneity even though there are a range of methods available to acknowledge patient heterogeneity. This review evaluates existing economic evaluations of interventions in schizophrenia to understand how patient heterogeneity is currently reflected in economic evaluation. METHODS: Electronic searches of MEDLINE, Embase, and PsycINFO via Ovid and the Health Technology Assessment database were run to identify full economic evaluations of interventions aiming to reduce the symptoms associated with schizophrenia. Two levels of screening were used, and explicit inclusion criteria were applied. Prespecified data extraction and critical appraisal were performed. RESULTS: Seventy-six relevant studies were identified. More than half (41 of 76) of the articles acknowledged patient heterogeneity in some way through discussion or methods. There was a range of patient characteristics considered, including demographics and socioeconomic factors (eg, age, educational level, ethnicity), clinical characteristics (eg, symptom severity, comorbidities), and preferences (eg, preferences related to outcomes or symptoms). Subgroup analyses were rarely reported (8 of 76). CONCLUSIONS: Patient heterogeneity was frequently mentioned in studies but was rarely thoroughly investigated in the identified economic evaluations. When investigated, included patient characteristics and methods were found to be heterogeneous. Understanding and acknowledging patient heterogeneity may alter the conclusions of cost-effectiveness evaluations; subsequently, we would encourage further research in this area.

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.

Social impacts and costs of schizophrenia: a national cohort study using New Zealand linked administrative data.

AIM: To identify a national population of individuals living with schizophrenia in New Zealand, and to examine health, social support, justice, economic outcomes and estimated government costs compared to a matched comparison group. METHODS: Data were sourced from the Integrated Data Infrastructure. Individuals with a schizophrenia diagnosis in public hospital discharge or specialist secondary mental health service data, aged 18 to 64 and living in New Zealand were included in the schizophrenia population. Propensity score matching was used to select a comparison group of individuals without schizophrenia from the New Zealand resident population and compare outcomes and costs. RESULTS: In 2015 there were 18,096 people living with schizophrenia in New Zealand, a prevalence of 6.7 per 1,000 people. Compared to the matched comparison population, individuals with schizophrenia had higher hospitalisation rates for mental (OR=52.80) and physical (OR=1.18) health conditions. They were more likely to receive social welfare benefits (OR=17.64), less likely to be employed (OR=0.11) and had lower income ($26,226 lower). Per-person government costs were higher for the schizophrenia group across all domains, particularly health ($14,847 higher) and social support ($11,823 higher). CONCLUSION: Schizophrenia is associated with a range of adverse health, social and economic outcomes and considerably higher government costs compared to the general population.

Economic burden in Medicaid beneficiaries with recently relapsed schizophrenia or with uncontrolled symptoms of schizophrenia not adherent to antipsychotics.

BACKGROUND: Patients with schizophrenia struggle with disease relapses and uncontrolled symptoms, which can either result in or be a result of non-adherence to antipsychotics (APs). The economic burden of such patients is hypothesized to be substantial. OBJECTIVE: To evaluate the economic burden of recently relapsed schizophrenia or of uncontrolled symptoms of schizophrenia with non-adherence to APs in Medicaid beneficiaries. METHODS: Adults with ≥ 2 schizophrenia diagnoses and controls without schizophrenia were identified in Medicaid data (1997Q1-2018Q1) from Iowa, Kansas, Mississippi, Missouri, New Jersey, and Wisconsin. The index date was the last observed schizophrenia diagnosis (cohort with schizophrenia) or the last service claim (control cohort) with ≥ 12 months of continuous Medicaid enrollment before and after it. Cohorts were matched 1:1 using propensity scores. After matching, two subgroups were identified among adults with schizophrenia: (1) patients with schizophrenia and a recent relapse (≥ 1 schizophrenia-related inpatient or emergency department claim ≤ 60 days before or on the index date) and (2) patients with uncontrolled symptoms of schizophrenia (≥ 2 schizophrenia-related hospitalizations) and non-adherence to APs (proportion of days covered < 80%) in the 12-month pre-index period. Previously matched controls were then subset to patients in each subgroup and their matched pairs without schizophrenia, thus maintaining the 1:1 matching ratio. Healthcare resource utilization (HRU) and costs ($2018 USD) in the 12-month post-index (observation) period were compared between matched pairs using adjusted regression models. RESULTS: Among 158,763 patients with schizophrenia, 18,771 (11.8%) had a recent relapse (mean age 50.5 years; 48.6% female, 51.4% male) and 13,697 (8.6%) were not adherent to APs and had uncontrolled symptoms of schizophrenia (mean age 47.1 years; 48.0% female, 52.0% male). During the observation period, patients with recently relapsed schizophrenia and those non-adherent to APs with uncontrolled symptoms of schizophrenia had significantly higher HRU relative to their controls without schizophrenia. Patients with recently relapsed schizophrenia had mean total healthcare costs $21,862 higher relative to their controls ($37,424 vs $15,563), driven by $8,486 higher mean long-term care costs (all P < 0.001). Patients non-adherent to APs with uncontrolled symptoms of schizophrenia had adjusted mean total healthcare costs $20,787 higher relative to their controls ($38,337 vs $15,241), driven by $8,019 higher adjusted mean inpatient costs (all P < 0.001). Additional total healthcare costs incurred by patients with recently relapsed schizophrenia and those of patients non-adherent to APs with uncontrolled symptoms of schizophrenia exceeded by 55.2% and 47.6%, respectively, incremental total healthcare costs incurred by all patients with schizophrenia ($14,087). CONCLUSIONS: Patients with recently relapsed schizophrenia and those non-adherent to AP therapy with uncontrolled symptoms of schizophrenia incurred higher HRU and costs relative to patients without schizophrenia. Additional healthcare costs of these subgroups of patients with schizophrenia appeared higher than in the overall population with schizophrenia. DISCLOSURES: This study was supported by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design, data collection, data analysis, manuscript preparation, and publication decisions. Pilon, Lafeuille, Zhdanava, Côté-Sergent, Rossi, and Lefebvre 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. Patel, Joshi, and Lin are employees of Janssen Scientific Affairs, LLC and stockholders of Johnson & Johnson. Part of the material in this manuscript has been presented at the US Psych Congress, October 3-6, 2019, San Diego, CA, and at the Virtual ISPOR Meeting, May 18-20, 2020.

Cost-Sharing Increase, Medication Adherence, and Hospitalizations in Schizophrenia Patients: A Natural Experiment.

Increases in medication cost-sharing rates remain a controversial system-wide cost-containment measure for chronic mental health patients. The objective was to investigate the effects of cost-sharing increases on adherence to prescribed antipsychotic medication and psychiatric hospitalizations among patients with schizophrenia. In July 2012, a Spanish National Law raised the cost-sharing rate from 0 to 10% for pensioner outpatient medication while cost-sharing remained at 0% for other socioeconomic groups. To estimate the effects of the reform, we analyzed the prevalent adult schizophrenic population of Valencia, Spain, followed up 1 year before and after the Law took effect. We used a quasi-experimental design with a patient fixed-effects difference-in-differences regression to evaluate the reform effects on antipsychotic medication adherence, prescription, and hospitalization rates. A total of 5,672 included patients were exposed to the reform, whereas 5,545 were not. There were no differences in adherence, prescription, or hospitalization rates between exposed and nonexposed patients prior to its implementation. The odds ratio of exposed patients remaining adherent to issued prescriptions after the reform took effect were 0.70 99% confidence interval (CI 0.66-0.75), in relation to the nonexposed group. Additionally, the reform was associated with a reduction in exposure to antipsychotic medication (odds ratio (OR) 0.85, 99%CI 0.83-0.88) and an increase in hospitalization risk (OR 1.13, 99% CI 1.05-1.23) during the first year after implementation. Policies raising the cost-sharing rate of medication for patients with schizophrenia are simultaneously associated with unintended effects. We report decreases in antipsychotic exposure and increases in hospitalization rates that lasted for 1 year after follow-up.

Real-World Evidence of the Clinical and Economic Impact of Long-Acting Injectable Versus Oral Antipsychotics Among Patients with Schizophrenia in the United States: A Systematic Review and Meta-Analysis.

BACKGROUND: Long-acting injectable (LAI) antipsychotics, compared with oral antipsychotics (OA), have been found to significantly improve patient outcomes, including reduced hospitalizations and emergency room (ER) admissions and increased medication adherence among adult patients with schizophrenia. In turn, the clinical benefits achieved may translate into lower economic burden. Real-world evidence of the comparative effectiveness of LAI is needed to understand the potential benefits of LAI outside of the context of clinical trials. This study aimed to provide a comprehensive synthesis of recent published real-world studies comparing healthcare utilization, costs, and adherence between patients with schizophrenia treated with LAI versus OA in the United States. METHODS: In this systematic literature review, MEDLINE® was searched for peer-reviewed, real-world studies (i.e., retrospective or pragmatic designs) published in English between January 1, 2010 and February 10, 2020. Comparative studies reporting hospitalizations, ER admissions, healthcare costs, or medication adherence (measured by proportion of days covered [PDC]) in adults with schizophrenia treated with LAI versus OA (or pre- vs post-LAI initiation) in the United States were retained. Random effects meta-analyses were conducted among eligible studies to evaluate the association of LAI versus OA use on hospitalizations, ER admissions, healthcare costs, and treatment adherence. A sensitivity analysis among the subset of studies that compared OA with paliperidone palmitate once monthly (PP1M), specifically, was conducted. RESULTS: A total of 1083 articles were identified by the electronic literature search, and two publications were manually added subsequently. Among the 57 publications meeting the inclusion criteria, 25 provided sufficient information for inclusion in the meta-analyses. Compared with patients treated with OA, patients initiated on LAI had lower odds of hospitalization (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.54-0.71, n = 7), fewer hospitalizations (incidence rate ratio [IRR] [95% CI] 0.75 [0.65-0.88], n = 9), and fewer ER admissions (IRR [95% CI] 0.86 [0.77-0.97], n = 6). The initiation of LAI was associated with higher per-patient-per-year (PPPY) pharmacy costs (mean difference [MD] [95% CI] $5603 [3799-7407], n = 6), which was offset by lower PPPY medical costs (MD [95% CI] - $5404 [- 7745 to - 3064], n = 6), resulting in no significant net difference in PPPY total all-cause healthcare costs between patients treated with LAI and those treated with OA (MD [95% CI] $327 [- 1565 to 2219], n = 7). Patients initiated on LAI also had higher odds of being adherent to their medication (PDC ≥ 80%; OR [95% CI] 1.89 [1.52-2.35], n = 9). A sensitivity analysis on a subset of publications evaluating PP1M found results similar to those of the main analysis conducted at the LAI class level. CONCLUSIONS: Based on multiple studies with varying sub-types of patient populations with schizophrenia in the United States published in the last decade, this meta-analysis demonstrated that LAI antipsychotics were associated with improved medication adherence and significant clinical benefit such as reduced hospitalizations and ER admissions compared with OA. The lower medical costs offset the higher pharmacy costs, resulting in a non-significant difference in total healthcare costs. Taken together, these findings provide strong evidence on the clinical and economic benefits of LAI compared with OA for the treatment of schizophrenia in the real world.

Economic Impact of Schizophrenia from a Hospital and Social Security System Perspective in Italy.

BACKGROUND: Schizophrenia is one of the mental disorders with the highest economic and social costs, with an important burden on patients, caregivers, and society. OBJECTIVE: The objective of this study was to estimate the direct and social security costs of schizophrenia in Italy. As far as direct costs are concerned, those related to hospitalizations and pharmaceutical expenditure have been analyzed, while disability benefits (DBs) and incapacity pensions (IPs) have been considered for the social security costs. METHODS: In order to provide annual economic burden of schizophrenia using the real-world data, we analyzed the main regional and national databases related to hospitalizations and pharmaceuticals. Hospitalizations have been analyzed considering the Hospital Information System, which collects all the information regarding hospital discharges from all public and private hospitals (psychiatric wards or residential facilities have not been considered). Hospitalizations with a discharge date between 2009 and 2016, and with a primary or secondary diagnosis of schizophrenia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 295.xx) were selected. Hospital costs have been estimated considering the national tariffs associated with each selected hospitalization. In addition, using the same inclusion criteria, the average DBs (for workers with reduced working capacity) and IPs (for workers without working capacity) provided each year have been analyzed from the social security benefit applications database. The estimate of pharmaceutical expenditure was prepared based on the OsMed 2018 Report (Italian Medicines Agency, latest issue 18 July 2019). A one-way deterministic sensitivity analysis was conducted to examine the robustness of the results. RESULTS: In Italy from 2009 to 2016, schizophrenia had an important economic impact from a social perspective. On average, 13,800 patients were hospitalized, with an average of 2.98 hospitalizations per patient. From a National Health Service (NHS) perspective and with specific reference to hospitalizations, the annual economic burden was €101.4 million, with an average cost per patient of €7338. On the other hand, pharmaceutical expenditure amounts to over €147 million each year, while residential, semi-residential, and specialist facilities amount to approximately €1 billion. Again, schizophrenia led to approximately 15,000 recipients of social security benefits (DBs and IPs) yearly from 2009 to 2015, with an average annual expenditure of €160.1 million (average cost per patient = €10,675). CONCLUSIONS: Our study estimates an economic burden of schizophrenia of €1250 million per year in direct costs, of which 20% is related to hospitalizations and pharmaceutical expenditure. With regard to social security benefits, an average annual expenditure of €160.1 million was calculated (average cost per patient = €10,675).

Cost of the Illness of Treatment-Resistant Schizophrenia: A Mirror Image Study Comparing Clozapine With Other Antipsychotics.

PURPOSE/BACKGROUND: This study aimed to evaluate and compare the cost of illness in patients with treatment-resistant schizophrenia (TRS) during 3 months before starting clozapine and for the initial 3 months of treatment with clozapine. METHODS/PROCEDURES: Fifty-two patients with TRS were evaluated for the cost of illness (direct, indirect, and provider cost) by using a structured questionnaire for the period of 3 months before starting clozapine and then at the end of the 3 months of clozapine therapy. FINDINGS/RESULTS: Total treatment cost for the period of 3 months before starting clozapine was Indian rupees (INR) 40,372 (560.72 US dollars), and the total treatment cost for the first 3 months of clozapine therapy was INR 40,553 (563.23 US dollars). At both the assessments, indirect cost formed the main bulk of the total cost, with no significant difference in the indirect cost. The total direct treatment cost reduced from INR 13,931.6 (193.49 US dollars) to INR 8756 (121.61 US dollars), and the difference between the 2 assessments was statistically significant, with an advantage for clozapine. Overall, after starting clozapine, the total direct cost reduced from 34.5% to 21.6%, and the total indirect cost reduced from 54.3% to 40.2%. After starting clozapine, total provider cost increased from 11.2% to 38.2% of the totalcost. IMPLICATIONS/CONCLUSIONS: Treatment with clozapine is not associated with a significant increase in the overall treatment cost, in the short term. However, there is a significant reduction in direct treatment costs.

Using the NIH Research, Condition and Disease Categorization Database for research advocacy: Schizophrenia research at NIMH as an example.

In 2008 the National Institutes of Health established the Research, Condition and Disease Categorization Database (RCDC) that reports the amount spent by NIH institutes for each disease. Its goal is to allow the public "to know how the NIH spends their tax dollars," but it has been little used. The RCDC for 2018 was used to assess 428 schizophrenia-related research projects funded by the National Institute of Mental Health. Three senior psychiatrists independently rated each on its likelihood ("likely", "possible", "very unlikely") of improving the symptoms and/or quality of life for individuals with schizophrenia within 20 years. At least one reviewer rated 386 (90%), and all three reviewers rated 302 (71%), of the research projects as very unlikely to provide clinical improvement within 20 years. Reviewer agreement for the "very unlikely" category was good; for the "possible" category was intermediate; and for the "likely" category was poor. At least one reviewer rated 30 (7%) of the research projects as likely to provide clinical improvement within 20 years. The cost of the 30 projects was 5.5% of the total NIMH schizophrenia-related portfolio or 0.6% of the total NIMH budget. Study results confirm previous 2016 criticisms that the NIMH schizophrenia-related research portfolio disproportionately underfunds clinical research that might help people currently affected. Although the results are preliminary, since the RCDC database has not previously been used in this manner and because of the subjective nature of the assessment, the database would appear to be a useful tool for disease advocates who wish to ascertain how NIH spends its public funds.