Patient preference for early onset of efficacy of preventive migraine treatments.

OBJECTIVE: The objective of this study was to ascertain to what extent adults with migraine value an early onset of efficacy for preventive migraine treatments. BACKGROUND: In placebo-controlled clinical trials, treatment with eptinezumab resulted in a lower proportion of adults with migraine on the first day following infusion (day 1; 14% point-reduction for chronic migraine [CM] in PROMISE-2 and 8% point-reduction for episodic migraine [EM] in PROMISE-1). METHODS: Adults with migraine completed an online preference-elicitation thresholding exercise to ascertain to what extent they value not having a migraine on day 1 postdosing relative to a clinically relevant reduction in number of migraine days during the first month postdosing (≥2 migraine-free days for CM and ≥1 migraine-free days for EM). RESULTS: One hundred and one participants (mean age, 50.6 ± 12.4 years; 81 [80%] women) were included. In participants with CM, 29 of 50 (58%) considered the eptinezumab-generated reduction in the likelihood of migraine on day 1 postdosing to be at least as important as a clinically relevant reduction in number of migraine days the first month postdosing, whereas 37 of 50 (74%) considered a clinically relevant reduction of migraine days the first month postdosing to have a value equivalent to the eptinezumab-generated reduction in the likelihood of migraine on day 1 postdosing. In participants with EM, 18 of 35 (51%) considered the eptinezumab-generated reduction in the likelihood of migraine on day 1 postdosing to be at least as important as a clinically relevant reduction in migraine days the first month postdosing, whereas 24 of 35 (69%) considered a clinically relevant reduction of migraine days the first month postdosing to have a value equivalent to the eptinezumab-generated reduction in the likelihood of migraine on day 1 postdosing. CONCLUSION: Most participants considered the reduction in the likelihood of migraine offered by eptinezumab on day 1 postdosing to be at least as important as a clinically relevant reduction in migraine days the first month postdosing.

Treatment patterns and burden of behavioral disturbances in patients with dementia in the United States: a claims database analysis.

BACKGROUND: Although patients with dementia frequently experience neuropsychological symptoms (NPS) such as agitation, which profoundly impacts patients, caregivers, and the healthcare system, few studies have evaluated the associated burden of agitation or agitation-related symptoms in dementia. METHODS: This retrospective analysis of claims data from the Truven Health MarketScan® database (2012-2015) compared clinical characteristics, treatment patterns, healthcare resource utilization, and costs among patients with dementia with behavioral disturbances (BD) versus patients with dementia without BD. Existing BD diagnosis codes 294.11 or 294.21 were used as a means to identify patients with agitation/agitation-related symptoms. RESULTS: From a starting sample of 6.4 million beneficiaries, 103,402 patients with dementia were identified, of whom 16,440 (16%) had BD during an average of 17 months of follow-up. Patients with BD had significantly more medical and psychiatric comorbidities and greater comedication use (i.e., antidementia drugs, antidepressants, and antipsychotics; all values, P < .0001) compared with patients without BD. A significantly greater number of hospitalizations, hospital days, outpatient hospital/clinic visits, number of skilled nursing visits, and number of patients with hospice visit were reported during follow-up in patients with BD compared with patients without BD (all values, P <  0.0001). Costs were also significantly higher among patients with BD versus those patients without BD ($42,284 vs. $32,640, respectively; P <  0.0001). CONCLUSIONS: Patients with dementia with BD had a higher prevalence of comorbidities, greater use of comedications, and greater healthcare utilization and costs than patients with dementia without BD.

Using electronic health records to estimate the prevalence of agitation in Alzheimer disease/dementia.

BACKGROUND: Agitation is a common neuropsychiatric symptom of Alzheimer disease (AD). Data are scarce regarding agitation prevalence among community-dwelling patients with AD. OBJECTIVE: To estimate agitation prevalence in a sample of US patients with AD/dementia overall and by AD/dementia disease severity, using data from electronic health records (EHR). METHODS: This retrospective database study examined community-dwelling patients with ≥1 EHR record indicating AD/dementia from January 2008 to June 2015 and no evidence of non-Alzheimer dementia during the 12-month preindex and postindex periods. Agitation was identified using diagnosis codes for dementia with behavioral disturbance and EHR abstracted notes records indicating agitation symptoms compiled from the International Psychogeriatric Association provisional consensus definition. RESULTS: Of 320 886 eligible patients (mean age, 76.4 y, 64.7% female), 143 160 (44.6%) had evidence of agitation during the observation period. Less than 5% of patients with agitation had a diagnosis code for behavioral disturbance. The most prevalent symptom categories among patients with agitation, preindex and postindex, were agitation (31.4% and 41.3%), falling (22.6% and 21.7%), and restlessness (18.3% and 23.3%). Among the 78 827 patients (24.6%) with known AD/dementia severity, agitation prevalence was 61.3%. Agitation during the observation period was most prevalent for moderate-to-severe and severe AD/dementia (74.6% and 68.3%, respectively) and lowest for mild AD/dementia (56.4%). CONCLUSIONS: Agitation prevalence was 44.6% overall and 61.3% among patients with staged AD/dementia. Behavioral disturbance appeared to be underdiagnosed. While agitation has previously been shown to be highly prevalent in the long-term care setting, this study indicates that it is also common among community-dwelling patients.

Agitation in patients with dementia: a systematic review of epidemiology and association with severity and course.

OBJECTIVES: More than 90% of individuals with Alzheimer's disease (AD) experience behavioral and neuropsychiatric symptoms (NPS), such as agitation. However, little is known regarding the specific burden of agitation for Alzheimer's patients. DESIGN: A global systematic literature review was conducted in MEDLINE and Embase for studies of clinical, humanistic, and economic burden of agitation in AD/dementia published from 2006-2016. References of identified papers and related literature reviews were examined. Studies meeting predetermined inclusion criteria for burden of agitation/NPS were summarized. RESULTS: Eighty papers met the inclusion criteria for burden of agitation in dementia. Wide ranges of agitation prevalence were reported, but few papers provided information on incidence. The association of agitation with AD severity was presented in multiple studies; a few suggested positive association of agitation with mortality. CONCLUSIONS: High prevalence of agitation is consistent with earlier reports, but several gaps in understanding of agitation in AD need further exploration.

Assessing the burden of treatment-emergent adverse events associated with atypical antipsychotic medications.

BACKGROUND: Treatment of schizophrenia and major depressive disorder (MDD) with atypical antipsychotics (AAPs) show improved efficacy and reduced side effect burden compared with older antipsychotic medications. However, a risk of treatment-emergent adverse events (TEAEs) remains. TEAEs are hard to quantify and perspectives on the importance of TEAEs differ across patients and between patients and physicians. The current study is a qualitative assessment that investigates TEAEs of AAPs from both patient and physician perspectives to provide better understanding of the occurrence and burden of TEAEs associated with these medications. METHODS: Focus groups comprised of patients with MDD and interviews with patients with schizophrenia were conducted at two qualitative research facilities, along with a physician focus group at one of the facilities. Information collected from patients included an exhaustive list of TEAEs experienced, and the frequency and level of bother of each TEAE; from psychiatrists, information included an exhaustive list of TEAEs based on personal observations and patient report, frequency of TEAEs, clinically important TEAEs, and levels of patient-perceived bother. Standard qualitative analysis methods were used to identify, quantify, characterize, and summarize patterns found in the data collected. RESULTS: A total of 42 patients (25 with MDD and 17 with schizophrenia) and 4 psychiatrists participated in the study. TEAEs reported as bothersome across both patients groups included cognitive issues, weight gain and/or increased appetite, low energy, extrapyramidal symptoms (EPS), and need to sleep/excessive sleep/excessive sleepiness. TEAEs considered more bothersome by patients with schizophrenia were weight gain, low energy, EPS, mental anxiety, and increased positive symptoms; those considered more bothersome by patients with MDD were cognitive issues, somnolence/sedation, and flat/restricted affect. TEAEs considered most clinically important by psychiatrists included metabolic syndrome, weight gain, neutropenia, hyperglycemia, and QT prolongation; those TEAEs considered most bothersome to patients from physicians' perspectives included weight gain, reduced sexual desire or performance, EPS, akathisia, and hormonal issues. CONCLUSIONS: The wide range of TEAEs that are both frequent and bothersome and the variation in perceived burden according to diagnosis highlight the need for a tailored TEAE-awareness approach when choosing an AAP.

Estimating prevalence of early symptomatic Alzheimer's disease in the United States.

INTRODUCTION: Understanding the prevalence of treatment-eligible Alzheimer's disease (AD) is crucial for policy planning. METHODS: We used a comprehensive literature review and population cascade approach to estimate the number of amyloid-positive, clinically diagnosed patients with mild cognitive impairment (MCI) or mild dementia due to AD in the United States. RESULTS: An estimated 666,646 individuals were identified as having MCI due to AD (range: 351,926-1,227,776) and 620,850 individuals as having mild dementia due to AD (range: 445,082-820,339). In a US population of 76 million individuals aged 60 or older in 2021, the estimates of MCI and mild dementia due to AD increased with age. CONCLUSIONS: As earlier diagnosis of AD and new disease-modifying treatments become available, accurate population estimates are required to reduce uncertainty in the number of clinically diagnosed patients eligible for amyloid-targeting therapies.

Technical Review of Clinical Outcomes Assessments Across the Continuum of Alzheimer's Disease.

INTRODUCTION: Insight into the relationship between concepts that matter to the people affected by Alzheimer's disease (AD) and the clinical outcome assessments (COAs) commonly used in AD clinical studies is limited. Phases 1 and 2 of the What Matters Most (WMM) study series identified and quantitatively confirmed 42 treatment-related outcomes that are important to people affected by AD. METHODS: We compared WMM concepts rated as "very important" or higher to items included in COAs used commonly in AD studies. RESULTS: Twenty COAs designed to assess signs, symptoms, and impacts across the spectrum of AD were selected for review. Among these 20 COAs, only 5 reflected 12 or more WMM concepts [Integrated Alzheimer's Disease Rating Scale (iADRS), Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL), Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory-Mild Cognitive Impairment (ADCS-ADL-MCI), Alzheimer's Disease Composite Scores (ADCOMS), and Clinical Dementia Rating; Clinical Dementia Rating-Sum of Boxes (CDR/CDR-SB)]. Multiple symptoms and impacts of AD identified as important and meaningful in the WMM studies map only indirectly at best to 7 of the 20 most widely used COAs. CONCLUSION: While many frequently used COAs in AD capture some concepts identified as important to AD populations and their care partners, overlap between any single measure and the concepts that matter to people affected by AD is limited. The highest singly matched COA reflects fewer than half (45%) of WMM concepts. Use of multiple COAs expands coverage of meaningful concepts. Future research should explore the content validity of AD COAs planned for AD trials based on further confirmation of the ecological validity of the WMM items. This research should inform development and use of core outcome sets that capture WMM items and selection or development of new companion tools to fully demonstrate clinically meaningful outcomes spanning WMM.

Assessing What Matters to People Affected by Alzheimer's Disease: A Quantitative Analysis.

INTRODUCTION: In this phase of the ongoing What Matters Most study series, designed to evaluate concepts that are meaningful to people affected by Alzheimer's disease (AD), we quantified the importance of symptoms, impacts, and outcomes of AD to people at risk for or with AD and care partners of people with AD. METHODS: We administered a web-based survey to individuals at risk for or with AD (Group 1: unimpaired cognition with evidence of AD pathology; Group 2: AD risk factors and subjective cognitive complaints/mild cognitive impairment; Group 3: mild AD) and to care partners of individuals with moderate AD (Group 4) or severe AD (Group 5). Respondents rated the importance of 42 symptoms, impacts, and outcomes on a scale ranging from 1 ("not at all important") to 5 ("extremely important"). RESULTS: Among the 274 respondents (70.4% female; 63.1% white), over half of patient respondents rated all 42 items as "very important" or "extremely important," while care partners rated fewer items as "very important" or "extremely important." Among the three patient groups, the minimum (maximum) mean importance rating for any item was 3.4 (4.6), indicating that all items were at least moderately to very important. Among care partners of people with moderate or severe AD, the minimum (maximum) mean importance rating was 2.1 (4.4), indicating that most items were rated as at least moderately important. Overall, taking medications correctly, not feeling down or depressed, and staying safe had the highest importance ratings among both patients and care partners, regardless of AD phase. CONCLUSION: Concepts of importance to individuals affected by AD go beyond the common understanding of "cognition" or "function" alone, reflecting a desire to maintain independence, overall physical and mental health, emotional well-being, and safety. Preservation of these attributes may be key to understanding whether interventions deliver clinically meaningful outcomes.

A Comparison of Daily Average Consumption Of Oxycodone Controlled Release (OxyContin CR) And Oxymorphone Extended Release (Opana ER) In Patients With Low Back Pain.

OBJECTIVE: Our goal was to examine the daily average consumption (DACON) of oxycodone controlled-release tablets (OxyContin CR)and oxymorphone extended-release tablets (Opana ER) in patients with low back pain. STUDY DESIGN: An observational, retrospective cohort study enrolled patients with multiple prescriptions for oxycodone CR or oxymorphone ER tablets. These patients also had International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for low back pain. Pharmacy prescription medication claims data were obtained from a large commercially insured health plan in the U.S. Mean daily consumption was calculated for a 90-day period. METHODS: We used descriptive statistics to evaluate patient demographics and health plan characteristics. Univariate analyses were used to examine the data as observed. A generalized linear model with a gamma distribution and log-link function provided a sensitivity measure, adjusting for heterogeneity among patients and the skewed nature of the DACON variable. RESULTS: A total of 4,023 patients received oxycodone CR, and 374 patients received oxymorphone ER. The mean age of patients (standard deviation, SD) was 49.0 (11.6) years for oxycodone CR and 47.3 (10.6) years for oxymorphone ER. DACON of oxycodone CR was 3.2 tablets per day, and DACON of oxymorphone ER was 2.7 tablets per day (P < 0.01). Utilization of maximum-strength tablets of oxycodone CR 80 mg was 3.9 tablets per day, which was significantly higher, by one tablet per day, than the utilization of equipotent oxymorphone ER maximum-strength tablets of 40 mg at 2.9 tablets per day (P < 0.01). CONCLUSION: The use of oxycodone CR, measured as mean daily consumption over a 90-day period, was significantly higher than that for oxymorphone ER in these patients, a finding that could have financial implications for health care systems.

Real-World Treatment Patterns and Characteristics Among Patients with Agitation and Dementia in the United States: Findings from a Large, Observational, Retrospective Chart Review.

BACKGROUND: Few studies have examined patient characteristics and treatment patterns among patients with dementia and agitation in the United States (US). OBJECTIVE: To examine real-world treatment patterns and characteristics of patients with agitation related to dementia who were treated with antipsychotics in US residential care and community-based settings. METHODS: This retrospective chart review collected US physician-level data from patients 55 to 90 years old initiated on an antipsychotic medication for the treatment of agitation related to dementia from January 2018 to May 2018. Clinical characteristics and treatment patterns were assessed overall and stratified by residential care and community-based settings. RESULTS: A total of 313 participating physicians, 59.5% of whom were primary care physicians, abstracted 801 patient charts (residential care: n = 312; community-based: n = 489). Of patients with agitation who were initiated on an antipsychotic, most patients (74.5%) were initiated within 3 months of the onset of their studied agitation episode, and 62.8% experienced multiple agitation episodes before initiation. While non-pharmacological therapies are recommended first-line approach for agitation in dementia, use of non-pharmacological therapy before initiation of antipsychotics was reported for only 37.8% of patients in residential care and 21.3% in community-based settings. CONCLUSION: Most patients were initiated on an antipsychotic treatment after multiple episodes of agitation and largely without initial non-pharmacological therapy, suggesting that current treatment guideline recommendations for first-line non-pharmacological intervention may not be adequately followed in clinical practice. Understanding the clinical burden and treatment patterns among dementia patients with agitation is imperative for effective disease management.

Association of the US Food and Drug Administration Antipsychotic Drug Boxed Warning With Medication Use and Health Outcomes in Elderly Patients With Dementia.

Importance: Atypical antipsychotics (AAPs) are often used off-label to manage dementia-associated neuropsychiatric symptoms. In 2005, the US Food and Drug Administration (FDA) issued a boxed warning for the use of AAPs in elderly patients. The long-term association of this warning with health outcomes is unknown to date. Objective: To assess the long-term association of the 2005 FDA boxed warning on AAPs with psychiatric medication and opioid use, health events, and quality of life among elderly individuals with dementia. Design, Setting, and Participants: For this cross-sectional study, data were analyzed from the household component of the Medical Expenditure Panel Survey (MEPS), the National Ambulatory Medical Care Survey (NAMCS), and the National Hospital Ambulatory Medical Care Survey (NHAMCS) fielded between January 1, 1996, and December 31, 2014. This interrupted time-series analysis applied to 3-year moving means derived from the 1996-2014 MEPS, NAMCS, and NHAMCS. All survey respondents included in this analysis were 65 years or older and had dementia. Data analysis was performed from December 1, 2017, to March 15, 2018. Exposures: The 2005 FDA boxed warning on AAPs. Main Outcomes and Measures: Use of psychiatric medications and opioids, prevalence of cerebrovascular and cardiovascular events, prevalence of falls and/or fractures, 2-year mortality, and health-related quality of life assessed by the Medical Outcomes Study 12-Item Short-Form Health Survey scores. Results: A total of 2430 (MEPS) and 5490 (NAMCS and NHAMCS) respondents were identified, corresponding to weighted populations of 22 996 526 (MEPS) and 65 502 344 (NAMCS and NHAMCS) noninstitutionalized elderly individuals with dementia (mean [SD] age, 81.06 [1.13] years; 63.1% female). In the MEPS sample, compared with before 2005, AAP use (from an annual slope of 0.99 to -0.18 percentage points), cerebrovascular events (0.75 to -0.50 percentage points), and falls and/or fractures (-1.72 to -0.40 percentage points) decreased and opioid use (0.04 to 1.29 percentage points), antiepileptic use (-0.42 to 1.21 percentage points), cardiovascular events (-0.13 to 1.30 percentage points), and 2-year mortality risk (-0.68 to 0.18 percentage points) increased. Health-related quality of life remained relatively unchanged. The NAMCS and NHAMCS sample yielded similar findings. Conclusions and Relevance: These data suggest that the 2005 FDA boxed warning was associated with some unintended negative patient outcomes.

Assessing what matters most to patients with or at risk for Alzheimer's and care partners: a qualitative study evaluating symptoms, impacts, and outcomes.

BACKGROUND: The What Matters Most (WMM) study was initiated to evaluate symptoms, AD-related impacts, treatment-related needs, preferences, and priorities among individuals with or at risk for Alzheimer's disease (AD) and their care partners. The objective of this qualitative study phase was to identify a comprehensive set of concepts of interest that are meaningful to individuals across the AD continuum. METHODS: Interviews were conducted with 60 clinically referred individuals and care partners across 5 AD stages (n = 12 each): group 1 (non-clinically impaired individuals with AD pathology), group 2 (individuals with mild cognitive impairment and AD pathology), group 3 (individuals with mild AD), group 4 (individuals with moderate AD and their care partners), and group 5 (care partners of individuals with severe AD). Interviews were conducted by experienced interviewers, audio-recorded, and transcribed. Dominant trends were identified in each interview and compared across subsequent interviews to generate themes or patterns in descriptions of AD symptoms, impacts, and desired treatment outcomes. RESULTS: All participants endorsed current issues related to memory; nearly all participants (n = 55; 92%) across the five groups endorsed symptoms related to communication and language. Groups 1-3 reported an impact on mood/emotions (n = 23; 64%) and a decrease in social activities or outgoingness (n = 17; 47%). Current and future concerns reported by the overall sample included memory (n = 48; 80%), dependence (n = 40; 67%), and "other" concerns (n = 33; 55.0%) (e.g., uncertainty about the future, burdening others). The most desired AD treatment outcomes were improvement or restoration of memory (n = 40; 67%) and stopping AD progression (n = 35; 58.3%). Group-level differences were observed in the symptoms, impacts, and desired treatment outcomes among patients and care partners across the AD continuum. CONCLUSIONS: Cognitive functioning issues-particularly in memory and communication-are present even in preclinical and early-stage AD, including among those without a formal AD diagnosis. While the impacts of AD vary across the disease-severity spectrum, improved memory and disease modification were treatment outcomes considered most important to participants across all 5 AD stages. Neuropsychological assessments traditionally used in AD clinical trials may not evaluate the often-subtle concepts that are important to patients and care partners. Results from this study will inform the second phase of the WMM project-a quantitative study to elicit the relative importance of these concepts of interest to people at risk for and living with AD and their care partners.

Real-World Economic Outcomes of Brexpiprazole and Extended-Release Quetiapine Adjunctive Use in Major Depressive Disorder.

PURPOSE: Major depressive disorder (MDD) is a chronic mental disorder with a substantial clinical and economic burden. Despite the efficacy of adjunctive atypical antipsychotics (AAP) for augmentation in patients with major depressive disorder (MDD) who failed first-line antidepressant therapy (ADT), little is known of the impact of AAP choices on healthcare resource use and costs in real-world practice. Therefore, this study compared real-world healthcare utilization and costs in patients with MDD treated with brexpiprazole or extended-release (XR) quetiapine as adjunctive treatment to ADT. PATIENTS AND METHODS: Adults with MDD starting adjunctive treatment with brexpiprazole (n=844) or extended-release (XR) quetiapine (n=688) were identified in the adjudicated health plan claims data (07/2014 - 09/2016). Resource use and healthcare costs in the 6 months following treatment initiation were compared between non-matched populations, and between propensity score-matched groups, and by multivariable regression analyses. RESULTS: During follow-up, unadjusted all-cause hospitalization (6.6% vs 12.5%) and ED visits (17.0% vs 27.5%) were lower with brexpiprazole compared to quetiapine XR (both p<0.001). Brexpiprazole-treated patients had significantly lower mean medical costs (US$6,421 vs US$8,545, p=0.0123) but higher mean pharmacy costs (US$7,401 vs US$4,691, p<0.0001) than quetiapine XR-treated patients did. Total healthcare costs were not significantly different between the two cohorts. Propensity score-matched comparisons of 397 patients in each cohort showed no statistically significant difference in all-cause hospitalization, ED visits, and total healthcare costs; and significantly lower medical costs (US$5,719 vs US$8,602, p=0.0092) but higher pharmacy costs (US$7,091 vs US$5,091, p=0.0007) in brexpiprazole compared to quetiapine XR. In multivariable regressions, brexpiprazole was associated with 16.1% lower medical costs (p=0.0186) and 9.4% higher total healthcare costs (p=0.0463) as compared to quetiapine XR. CONCLUSION: Significantly lower medical costs were observed in patients with MDD treated with brexpiprazole vs quetiapine XR.

Early initiation of long-acting injectable antipsychotic treatment is associated with lower hospitalization rates and healthcare costs in patients with schizophrenia: real-world evidence from US claims data.

Objective: Early initiation of antipsychotic treatment in schizophrenia is associated with improved outcomes. This study aimed to determine if initiation of long-acting injectable (LAI) antipsychotic treatment early in a new schizophrenia episode is associated with lower hospitalization rates and healthcare costs in a real-world setting. Methods: This retrospective (January 1, 2007-June 30, 2016) cohort analysis used claims from Truven Health Analytics MarketScan Commercial, Medicaid, and Medicare Supplemental databases. In adults ≥18 years with a new episode of schizophrenia, two mutually exclusive cohorts were identified based on time from first recorded schizophrenia diagnosis date to first date of LAI initiation (index date): ≤1 year (early initiators) and >1 year (late initiators). Logistic and general linear regression models were performed to estimate adjusted hospitalization rate and healthcare costs in a 1-year follow-up, controlling patient demographic and clinical characteristics, insurance type, baseline all-cause hospitalizations and ED visits, and baseline psychiatric medication use. Results: Of the subjects, 32% (n = 1388) initiated treatment early and 68% (n = 2978) initiated treatment later. In risk-adjusted models, all-cause hospitalization rates were 22.2% (95% CI = 19.9-24.6%) in early initiators and 26.9% (95% CI = 25.2-28.7%) in late initiators (p = .002). Of early initiators, 14.1% (95% CI = 12.3-16.1%) had a psychiatric hospitalization vs 19.2% (95% CI = 17.7-20.8%) of late initiators (p < .001). Adjusted psychiatric healthcare costs were significantly lower in early initiators compared with late initiators [mean (95% CI) = $21,545 (20,355-22,734) vs $24,132 (23,330-24,933)] (p < .001). Conclusions: LAI initiation within 1 year of a new schizophrenia episode led to lower hospitalization rates and healthcare costs compared with LAI initiation more than 1 year after a new episode.

Medication Adherence, Health Care Utilization, and Costs in Patients With Major Depressive Disorder Initiating Adjunctive Atypical Antipsychotic Treatment.

PURPOSE: The purpose of this study was to compare medication adherence, health care utilization, and cost among patients receiving adjunctive treatment for major depressive disorder (MDD) with brexpiprazole, quetiapine, or lurasidone. METHODS: Using Truven Health MarketScan® Commercial, Medicaid, and Medicare Supplemental Databases, we identified adults with MDD initiating adjunctive treatment with brexpiprazole, quetiapine, or lurasidone (index atypical antipsychotic [AAP]). We compared medication adherence and persistence measured by proportion of days covered (PDC) and treatment duration of index AAP, all-cause and psychiatric hospital care (hospitalization or emergency department visit), and medical costs during 6-month follow-up. Models performed included logistic regression for hospital care, linear regression for PDC and cost, and Cox proportional hazards regression for time to discontinuation, adjusting for demographic, clinical, and utilization differences during the 6 months before index AAP. FINDINGS: The total sample included 778 brexpiprazole, 626 lurasidone, and 3458 quetiapine therapy initiators. Adjusting for baseline differences, the risk of discontinuation of index AAP was statistically significantly higher for quetiapine than for brexpiprazole (hazard ratio [HR] = 1.13; 95% CI, 1.02-1.25; P = 0.023) and did not differ between lurasidone and brexipiprazole (HR = 1.14; 95% CI, 1.00-1.29; P = 0.054). The adjusted rate of all-cause hospitalization or emergency department visit in the postindex period was lowest for brexpiprazole at 27.4% (95% CI, 24.0%-31.0%), compared with 31.1% (95% CI, 27.3%-35.2%) for lurasidone and 35.3% (95% CI, 33.5%-37.1%) for quetiapine (P< 0.001 for all comparisons). Quetiapine users had increased all-cause costs compared with brexpiprazole users (estimate = $2309; 95% CI, $31-$4587; P = 0.047); all-cause medical costs did not differ between lurasidone and brexpiprazole (estimate = $913; 95% CI, $-2033 -$3859; P = 0.543). Adjusted psychiatric hospital care, psychiatric costs, and PDC did not differ significantly among the groups. IMPLICATIONS: In patients with MDD and a variety of insurance types, brexpiprazole use was associated with statistically significantly lower risks of discontinuation, risk of hospital care (hospitalization and ED visits), and all-cause medical costs compared with adjunctive quetiapine. Differences between brexpiprazole and lurasidone were not statistically significant. These findings suggest that drug choice is associated with subsequent health care utilization and costs.

Atypical antipsychotic adherence is associated with lower inpatient utilization and cost in bipolar I disorder.

AIMS: This study explored the association between medication adherence to oral atypical antipsychotics (AAP) and both psychiatric hospitalization and associated costs in bipolar I disorder (BD-I) in a real-world setting. MATERIALS AND METHODS: This retrospective study used the Truven Health MarketScan Medicaid, Commercial, and Medicare Supplemental Claims Databases. Adults were identified if they had BD-I and initiated an AAP treatment during the study identification period (July 1, 2015-June 30, 2016 for Medicaid, July 1, 2015-March 31, 2016 for Commercial and Medicare Supplemental) and had ≥6-month continuous enrollment before (baseline) and after (follow-up) the first day of treatment. Medication adherence was measured by the proportion of days covered (PDC) and grouped as: fully-adherent (PDC ≥80%), partially-adherent (40% ≤ PDC <80%), and non-adherent (PDC <40%). Logistic and linear regression models were conducted to estimate the risk of psychiatric hospitalization and costs during the 6-month follow-up period. RESULTS: The final sample consisted of 5,892 (32.0%) fully-adherent, 4,246 (23.1%) partially-adherent, and 8,250 (44.9%) non-adherent patients. The adjusted rate of psychiatric hospitalization during the follow-up period was lower in the fully-adherent (6.0%) vs partially- (8.3%) or non-adherent (8.8%) groups (p < 0.001). Using the fully-adherent cohort as the reference group, the odds of psychiatric hospitalization were significantly higher for the partially-adherent (OR = 1.42; 95% CI = 1.23-1.64) and non-adherent (1.51; 1.33-1.71) cohorts. The mean adjusted psychiatric hospitalization cost over 6 months among hospitalized patients was lower for the fully-adherent cohort ($11,748), than the partially-adherent ($15,051 p = 0.002) or non-adherent cohorts ($13,170, not statistically significant). LIMITATIONS: The medication adherence measures relied on prescription claims data, not actual use. CONCLUSIONS: In the treatment of BD-I, better medication adherence to AAP was associated with fewer psychiatric hospitalizations. Among hospitalized patients, fully-adherent patients had statistically significantly lower psychiatric costs than partially-adherent ones. These findings suggest that improving adherence to AAP in BD-I may be a valuable goal from both clinical and economic perspectives.

Hospitalization risk factors in antipsychotic-treated schizophrenia, bipolar I disorder or major depressive disorder.

AIM: To examine hospitalization risk factors in antipsychotic-treated patients with schizophrenia, bipolar I disorder (BD-I) or major depressive disorder (MDD). PATIENTS & METHODS: Using Truven Health MarketScan® Commercial, Medicaid and Medicare Supplemental data (01/01/2012-06/30/2016), logistic regression models were performed to identify risk factors for both psychiatric and all-cause hospitalization in three separate analyses. RESULTS: Significant risk factors included prior hospitalization (schizophrenia: odds ratio [95% CI]: 2.83 [2.50-3.21; psychiatric]; 2.58 [2.31-2.87; all-cause]; BD-I: 2.42 [2.23-2.63]; 2.09 [1.96-2.23]; MDD: 2.81 [2.49-3.16]; 2.21 [2.03-2.40]), previous antipsychotic treatment (schizophrenia: 1.71 [1.52-1.93]; 1.31 [1.18-1.46]; BD-I: 1.33 [1.23-1.44]; 1.22 [1.14-1.30]; MDD: 1.31 (1.11-1.54); 1.17 (1.04-1.32) and substance abuse (schizophrenia: 1.42 [1.27-1.60]; 1.37 [1.23-1.53]; BD-I: 1.72 [1.58-1.86]; 1.61 [1.50-1.72]; MDD: 1.90 [1.68-2.15] and 1.55 [1.41-1.71]). CONCLUSION: Prior hospitalization, previous antipsychotic treatment and substance abuse were associated with increased hospitalization risk in schizophrenia, BD-I or MDD.

Institutionalization risk and costs associated with agitation in Alzheimer's disease.

INTRODUCTION: Agitation in individuals with Alzheimer's disease (AD) may predict institutionalization. This study assessed the incremental risk and costs associated with agitation in individuals with AD. METHODS: A retrospective analysis of the National Alzheimer's Coordinating Center Uniform Data Set (June 2005-February 2018) was conducted. Incremental risk of institutionalization associated with agitation was estimated and used with the number of institutionalized individuals with AD and agitation and costs of living by residential setting in the United States (literature-based), to estimate incremental institutionalization costs. RESULTS: The analysis included 11,348 individuals with AD: 6603 (58.2%) with and 4745 (41.8%) without agitation. Compared with individuals without agitation, those with agitation were 20% more likely to be institutionalized (odds ratio = 1.20; 95% CI = 1.08-1.33). Total incremental cost of institutionalization associated with agitation was $4.3 billion ($50,588/individual). DISCUSSION: Agitation is associated with a higher risk of institutionalization among patients with AD, which translates into a substantial economic burden.

Changes in healthcare resource use and costs associated with early versus delayed initiation of atypical antipsychotic adjunctive treatment in major depressive disorder.

AIMS: The study compared all-cause and major depressive disorder (MDD)-related healthcare resource use (HRU) and costs in patients with MDD treated with atypical antipsychotic (AAP) adjunctive therapy early or later in treatment. MATERIALS AND METHODS: Adults with MDD and antidepressant treatment (ADT) who newly initiated adjunctive aripiprazole, brexpiprazole, lurasidone, or quetiapine between October 1, 2014 and September 30, 2015 were identified in the IQVIA Real-World Data Adjudicated Claims database; the index date was the date of the first AAP claim. Patients were stratified into three cohorts: AAP initiated in the first year (Y1); in the second year (Y2); and more than 2 years (Y3) of first ADT use. Within each cohort, HRU and costs were compared between the 12 months before and after the index date. Pre-post changes in HRU and costs were then compared between cohorts. RESULTS: Five hundred and six (36.7%) patients were categorized as Y1; 252 (18.3%) as Y2; and 622 (45.1%) as Y3. AAP use was associated with significantly decreased rates of all-cause and MDD-related hospitalization and emergency department visits, and increased rates of pharmacy fills and physician office visits; and the magnitude of changes was largest in cohort Y1. Cohort Y1 had the largest reductions in mean (±SD) all-cause medical costs per patient (-$10,496 ± $85,022, p = .015) compared to Y2 (-$2,474 ± $85,022, p = .572) and Y3 (-$472 ± $31,334, p = .823), mainly due to the reduction in hospitalization. After adjusting for differences in baseline characteristics, the largest reductions in hospitalization and medical costs were observed in cohort Y1. Similar increases in all-cause pharmacy costs were seen in all cohorts. A similar trend in costs was observed in MDD-related healthcare services. LIMITATIONS AND CONCLUSIONS: AAP treatment was associated with reductions in all-cause and MDD-related medical costs, primarily in decreased hospitalization. The reductions were largest among patients who initiated treatment in the first year.

Medication adherence and discontinuation of long-acting injectable versus oral antipsychotics in patients with schizophrenia or bipolar disorder.

AIMS: To examine medication adherence and discontinuation in two separate groups of patients with schizophrenia or bipolar disorder (BD), who began receiving a long-acting injectable antipsychotic (LAI) versus those who changed to a different oral antipsychotic monotherapy. MATERIALS AND METHODS: The Truven Health Analytics MarketScan Multi-State Medicaid claims database was used to identify patients with schizophrenia; Truven Health Analytics MarketScan Commercial and Medicaid claims databases were used to identify patients with BD. The analyses included adult patients (≥18 years) who either began receiving an LAI (no prior LAI therapy) or changed to a different oral antipsychotic (monotherapy). The first day of initiating an LAI or changing to a new oral antipsychotic was the index date. Linear and Cox regression models were conducted to estimate medication adherence (proportion of days covered [PDC]) and time to medication discontinuation (continuous medication gap ≥60 days), respectively. Models adjusted for patient demographic and clinical characteristics, baseline medication use, and baseline ED or hospitalizations. RESULTS: Patients with schizophrenia (N = 5638) who began receiving LAIs had better medication adherence (5% higher adjusted mean adherence) during the 1 year post-index period and were 20% less likely to discontinue their medication during the entire follow-up period than patients who changed to a different oral antipsychotic monotherapy, adjusting for differences between LAI users and oral users. Similarly, patients with BD (N = 11,344) who began receiving LAIs also had 5% better medication adherence and were 19% less likely to discontinue their medication than those using oral antipsychotics. LIMITATIONS: Clinical differences unmeasurable in this database may have been responsible for the choice of LAI versus oral antipsychotics, and these differences may be responsible for some of the adherence advantages observed. CONCLUSIONS: This real-world study suggests that patients with schizophrenia or BD who began receiving LAIs had better medication adherence and lower discontinuation risk than those who changed to a different oral antipsychotic monotherapy.