Transforming primary care for older Canadians living with frailty: mixed methods study protocol for a complex primary care intervention.

INTRODUCTION: Older Canadians living with frailty are high users of healthcare services; however, the healthcare system is not well designed to meet the complex needs of many older adults. Older persons look to their primary care practitioners to assess their needs and coordinate their care. They may need care from a variety of providers and services, but often this care is not well coordinated. Older adults and their family caregivers are the experts in their own needs and preferences, but often do not have a chance to participate fully in treatment decisions or care planning. As a result, older adults may have health problems that are not properly assessed, managed or treated, resulting in poorer health outcomes and higher economic and social costs. We will be implementing enhanced primary healthcare approaches for older patients, including risk screening, patient engagement and shared decision making and care coordination. These interventions will be tailored to the needs and circumstances of the primary care study sites. In this article, we describe our study protocol for implementing and testing these approaches. METHODS AND ANALYSIS: Nine primary care sites in three Canadian provinces will participate in a multi-phase mixed methods study. In phase 1, baseline information will be collected through questionnaires and interviews with patients and healthcare providers (HCPs). In phase 2, HCPs and patients will be consulted to tailor the evidence-based interventions to site-specific needs and circumstances. In phase 3, sites will implement the tailored care model. Evaluation of the care model will include measures of patient and provider experience, a quality of life measure, qualitative interviews and economic evaluation. ETHICS AND DISSEMINATION: This study has received ethics clearance from the host academic institutions: University of Calgary (REB17-0617), University of Waterloo (ORE#22446) and Université Laval (#MP-13-2019-1500 and 2017-2018-12-MP). Results will be disseminated through traditional means, including peer-reviewed publications and conferences and through an extensive network of knowledge user partners. TRIAL REGISTRATION NUMBER: NCT03442426;Pre-results.

Learning from health system reform trajectories in seven Canadian provinces.

In publicly funded health systems, reform efforts have proliferated to adapt to increasingly complex demands. In Canada, prior research (Lazar et al., 2013, Paradigm Freeze: Why is it so Hard to Reform Health Care in Canada?, McGill-Queen's Press) found that reforms at the end of the 20th century failed to change the fundamentals of the Canadian system based on physician independence and assured universal coverage only for medical and hospital services. This paper focuses on reforms since the turn of the millennium to explore the transformative capacities developed in seven provinces within this system architecture. Longitudinal case studies, based on scientific and grey literature, and interviews with key informants, trace the patterns of reform in each province and reveal five objectives that, to varying degrees, preoccupied reformers: (1) address chronic disease, (2) align health system actors with provincial objectives, (3) shift from hospital to community-based care, (4) integrate physicians, and (5) develop improvement capacities. The range of strategies adopted to achieve these objectives in different provinces is compared to identify emerging pathways of reform and extract lessons for future reformers. We find significant cross-learning between provinces, but also note an emergent dimension to reforms, where multiple strategies aggregate through time to create unique patterns, presenting their own set of possibilities and limitations for the future.

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.

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.

Use of the Functioning Assessment Short Test (FAST) in defining functional recovery in bipolar I disorder. Post-hoc analyses of long-term studies of aripiprazole once monthly as maintenance treatment.

PURPOSE: There is growing agreement that definitions of "recovery" in bipolar-I disorder (BP-I) should include functional outcomes beyond sustained symptomatic remission. In this post-hoc analysis, we assessed functional recovery rates according to the validated Functioning Assessment Short Test (FAST) in participants with BP-I after 52 weeks of maintenance treatment with aripiprazole once monthly (AOM). PATIENTS AND METHODS: Rates of functional recovery with AOM 400 were investigated in two 52-week studies. NCT01567527 was a placebo-controlled, double-blind, randomized-withdrawal study and NCT01710709 was an open-label study. Functional recovery, assessed at the end of the respective maintenance phases, was defined as a total FAST score of ≤11 for 8 consecutive weeks. RESULTS: Post-hoc analyses included 229 patients from the randomized-withdrawal study (AOM 400 n=116; placebo n=113). The open-label study included 402 patients (including 321 de novo patients and 81 rollover patients who had completed the randomized-withdrawal study). In the randomized-withdrawal study, functional recovery was achieved by 30.2% (n=35) of the AOM 400 group compared with 24.8% (n=28) in the placebo group. The difference was not statistically significant (p=0.39). In the open-label study, 36% (n=116) of de novo patients and 43% (n=35) of rollover patients had functionally recovered after 52 weeks of AOM 400 treatment. CONCLUSION: These data highlight the utility of a sustained FAST total score of ≤11 as a definition of recovery and emphasize the possibility of achieving this ambitious treatment goal with effective long-term treatment.

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.

Three-dimensional assessment of the asymptomatic and post-stroke shoulder: intra-rater test-retest reliability and within-subject repeatability of the palpation and digitization approach.

Purpose: Altered three-dimensional (3D) joint kinematics can contribute to shoulder pathology, including post-stroke shoulder pain. Reliable assessment methods enable comparative studies between asymptomatic shoulders of healthy subjects and painful shoulders of post-stroke subjects, and could inform treatment planning for post-stroke shoulder pain. The study purpose was to establish intra-rater test-retest reliability and within-subject repeatability of a palpation/digitization protocol, which assesses 3D clavicular/scapular/humeral rotations, in asymptomatic and painful post-stroke shoulders. Methods: Repeated measurements of 3D clavicular/scapular/humeral joint/segment rotations were obtained using palpation/digitization in 32 asymptomatic and six painful post-stroke shoulders during four reaching postures (rest/flexion/abduction/external rotation). Intra-class correlation coefficients (ICCs), standard error of the measurement and 95% confidence intervals were calculated. Results: All ICC values indicated high to very high test-retest reliability (≥0.70), with lower reliability for scapular anterior/posterior tilt during external rotation in asymptomatic subjects, and scapular medial/lateral rotation, humeral horizontal abduction/adduction and axial rotation during abduction in post-stroke subjects. All standard error of measurement values demonstrated within-subject repeatability error ≤5° for all clavicular/scapular/humeral joint/segment rotations (asymptomatic ≤3.75°; post-stroke ≤5.0°), except for humeral axial rotation (asymptomatic ≤5°; post-stroke ≤15°). Conclusions: This noninvasive, clinically feasible palpation/digitization protocol was reliable and repeatable in asymptomatic shoulders, and in a smaller sample of painful post-stroke shoulders. Implications for Rehabilitation In the clinical setting, a reliable and repeatable noninvasive method for assessment of three-dimensional (3D) clavicular/scapular/humeral joint orientation and range of motion (ROM) is currently required. The established reliability and repeatability of this proposed palpation/digitization protocol will enable comparative 3D ROM studies between asymptomatic and post-stroke shoulders, which will further inform treatment planning. Intra-rater test-retest repeatability, which is measured by the standard error of the measure, indicates the range of error associated with a single test measure. Therefore, clinicians can use the standard error of the measure to determine the "true" differences between pre-treatment and post-treatment test scores.

Multidimensional Assessment of Functional Outcomes in Schizophrenia: Results From QUALIFY, a Head-to-Head Trial of Aripiprazole Once-Monthly and Paliperidone Palmitate.

Background: QUALIFY was a 28-week, randomized, open-label, head-to-head trial that assessed improvements across multiple measures in stable patients with schizophrenia with aripiprazole once-monthly 400 mg vs paliperidone palmitate. Methods: Secondary effectiveness assessments included physician-rated readiness for work using the Work Readiness Questionnaire, the Clinical Global Impression-Severity and Clinical Global Impression-Improvement scales, and quality of life with the rater-blinded Heinrichs-Carpenter Quality of Life Scale. Patients assessed their treatment satisfaction and quality of life with Subjective Well-Being under Neuroleptic Treatment-short version and Tolerability and Quality of Life questionnaires. Results: Odds of being ready for work at week 28 were significantly higher with aripiprazole once-monthly 400 mg vs paliperidone palmitate (adjusted odds ratio, 2.67; 95% CI, 1.39-5.14; P=.003). Aripiprazole once-monthly 400 mg produced numerically or significantly greater improvements from baseline vs paliperidone palmitate in all Quality of Life Scale items. With aripiprazole once-monthly 400 mg vs paliperidone palmitate at week 28, there were significantly more Clinical Global Impression-Severity and Clinical Global Impression-Improvement responders (adjusted odds ratio, 2.26; P=.010, and 2.51; P=.0032) and significantly better Clinical Global Impression-Improvement scores (least squares mean treatment difference, -0.326; 95% CI, -0.60 to -0.05; P=.020). Numerically larger improvements with aripiprazole once-monthly 400 mg vs paliperidone palmitate were observed for patient-rated scales Subjective Well-Being under Neuroleptic Treatment-short version and Tolerability and Quality of Life. Partial correlations were strongest among clinician-rated and among patient-rated scales but poorest between clinician and patient-rated scales. Conclusions: Consistently greater improvements were observed with aripiprazole once-monthly 400 mg vs paliperidone palmitate across all measures. Partial correlations between scales demonstrate the multidimensionality of various measures of improvement. More patients on aripiprazole once-monthly 400 mg were deemed ready to work by the study end. Trial registry: National Institutes of Health registry, NCT01795547, https://clinicaltrials.gov/ct2/results?id=NCT01795547).

Pharmacoeconomic comparison of aripiprazole once-monthly and paliperidone palmitate from a head-to-head clinical trial in schizophrenia: a US analysis.

Schizophrenia presents a substantial clinical and economic burden to the health-care system. In QUAlity of LIfe with AbiliFY Maintena (QUALIFY), a randomized head-to-head study of aripiprazole once-monthly 400 mg (AOM 400) compared with paliperidone palmitate (PP; 78-234 mg/mo), AOM 400 demonstrated greater improvement in health-related quality of life and functioning in patients with stable schizophrenia. The present analysis used health economics assessment data collected during the QUALIFY study to determine the direct medical and pharmacy costs and the cost-effectiveness associated with each treatment over 6 months. Compared with those receiving PP, patients receiving AOM 400 incurred significantly lower direct total costs ($8908±186 vs $9675±190, p=0.005) and treatment costs ($7967±113 vs $8706±116, p<0.001). Effectiveness results in the subset of patients included in the cost analyses were similar to the overall population: mean (95% CI) improvement in Heinrichs-Carpenter Quality of Life Scale total score was greater with AOM 400 (5.97 [3.87; 8.08]) compared with PP (2.85 [0.56; 5.08]). Likewise, Clinical Global Impression-Severity improved more in the AOM 400 group (-0.59 [-0.71; -0.47]) compared with PP group (-0.37 [-0.46; -0.27]). Therefore, the analysis of data from stabilized patients with schizophrenia in the QUALIFY study indicated that AOM 400 is associated with lower health-care costs and greater effectiveness compared with PP and thus represents the economically dominant strategy.

Approaching Etuaptmumk--introducing a consensus-based mixed method for health services research.

With the recognized need for health systems' improvements in the circumpolar and indigenous context, there has been a call to expand the research agenda across all sectors influencing wellness and to recognize academic and indigenous knowledge through the research process. Despite being recognized as a distinct body of knowledge in international forums and across indigenous groups, examples of methods and theories based on indigenous knowledge are not well documented in academic texts or peer-reviewed literature on health systems. This paper describes the use of a consensus-based, mixed method with indigenous knowledge by an experienced group of researchers and indigenous knowledge holders who collaborated on a study that explored indigenous values underlying health systems stewardship. The method is built on the principles of Etuaptmumk or two-eyed seeing, which aim to respond to and resolve the inherent conflicts between indigenous ways of knowing and the scientific inquiry that informs the evidence base in health care. Mixed methods' frameworks appear to provide a framing suitable for research questions that require data from indigenous knowledge sources and western knowledge. The nominal consensus method, as a western paradigm, was found to be responsive to embedding of indigenous knowledge and allowed space to express multiple perspectives and reach consensus on the question at hand. Further utilization and critical evaluation of this mixed methodology with indigenous knowledge are required.

Reduction in inpatient resource utilization and costs associated with long-acting injectable antipsychotics across different age groups of Medicaid-insured schizophrenia patients.

OBJECTIVE: Evaluate utilization of inpatient healthcare resources and associated costs after 12 months of treatment using long-acting injectable (LAI) antipsychotic medications among a large sample of Medicaid-insured patients categorized by different age groups. METHOD: Adult patients with schizophrenia were identified from the Thomson Reuters MarketScan Research database (1/1/2006-12/31/2010) before initiation of treatment using LAI antipsychotic agents. Utilization of inpatient healthcare resources and associated direct medical costs were compared for 12-month baseline and 12-month follow-up periods. RESULTS: Among 3,094 Medicaid-insured patients with schizophrenia initiating treatment with LAIs, the mean number of all-cause hospitalizations and hospitalization days were reduced by 24% and 31% (p<0.0001) compared with baseline, respectively, with similar significant reductions among all age groups (18-30, 31-40, 41-50, and 51-60 years). During 12-month follow-up with LAIs, mean reductions in all-cause costs were $4,369 (18-30 years, p<0.0001), $3,681 (31-40 years, p<0.0001), $2,051 (41-50 years, p=0.1332), and $4,492 (51-60 years, p=0.0107). Subanalyses separating first-generation and second-generation medication groups resulted in mean reduction in all-cause costs of $3,561 and $3,645, respectively. CONCLUSIONS: Results from this large cohort study provide naturalistic real-world evidence of the utility of LAIs in patients with schizophrenia and suggest that these agents may help to reduce the risk of relapse across all age groups (especially among younger patients). Given that relapse prevention is the ultimate goal of antipsychotic treatment, results from this large Medicaid patient population establish the value of LAIs for the management of schizophrenia.

Hospitalization rates in patients switched from oral anti-psychotics to aripiprazole once-monthly: final efficacy analysis.

OBJECTIVE: To compare hospitalization rates in patients with schizophrenia treated prospectively with aripiprazole once-monthly 400 mg (AOM 400; an extended-release injectable suspension) vs the same patients' retrospective rates with their prior oral anti-psychotic therapy. RESEARCH DESIGN AND METHODS: Multi-center, open-label, mirror-image, naturalistic study in a community setting in North America. Patients who required a change in treatment and/or would benefit from long-acting injectable anti-psychotic therapy were treated prospectively for 6 months with AOM 400. Retrospective data on hospitalization rates were obtained. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT01432444. MAIN OUTCOME MEASURES: The proportion of patients with ≥ 1 psychiatric inpatient hospitalization with oral anti-psychotic therapy examined retrospectively (months -4 to -1 before oral conversion) and after switching to AOM 400 (months 4-6 after initiating AOM 400). RESULTS: Psychiatric hospitalization rates were significantly lower when patients were treated with AOM 400 compared with oral anti-psychotic therapy both in the 3-month primary efficacy sample (2.7% [n = 9/336] vs 27.1% [n = 91/336], respectively; p < 0.0001) and in the total sample (6-month prospective rate: 8.8% [n = 38/433] vs 6-month retrospective rate: 38.1% [n = 165/433]; p < 0.0001). Discontinuations due to adverse events (AEs) during cross-titration were lower in patients cross-titrated on oral aripiprazole for >1 and <4 weeks (2.9% [n = 7/239]) compared with patients cross-titrated for ≤ 1 week (10.4% [n = 5/48]). The most common treatment-emergent AEs during the prospective treatment phase were insomnia (6.7% [n = 29/431]) and akathisia (6.5% [n = 28/431]). Patient-rated injection-site pain decreased from the first injection to the last visit. CONCLUSIONS: In a community setting, patients with schizophrenia demonstrated significantly lower psychiatric hospitalization rates after switching from their prior oral anti-psychotic therapy to AOM 400. Patients served as their own control, and thus an active control group was not included in this study. Confounding factors, such as insurance coverage and availability of hospital beds, were not examined here and deserve further consideration.

Cost-effectiveness of aripiprazole once-monthly compared with paliperidone palmitate once-monthly injectable for the treatment of schizophrenia in the United States.

OBJECTIVE: To develop a decision-analytic model to estimate the cost-effectiveness of initiating maintenance treatment with aripiprazole once-monthly (AOM) vs paliperidone long-acting injectable (PLAI) once-monthly among patients with schizophrenia in the US. METHODS: A decision-analytic model was developed to evaluate a hypothetical cohort of patients initiating maintenance treatment with AOM or PLAI. Rates of relapse, adverse events (AEs), and direct medical costs were estimated for 1 year. Patients either remained on initial treatment or discontinued treatment due to lack of efficacy, AEs, or other reasons, including non-adherence. Data from placebo-controlled pivotal trials and product prescribing information (PI) were used to estimate treatment efficacy and AEs. Analyses were performed assuming dosing of clinical trials, real-world practice, PIs, and highest therapeutic dose available, because of variation in practice settings. The main outcome of interest was incremental cost per schizophrenia hospitalization averted with AOM vs PLAI. RESULTS: Based on placebo-controlled pivotal trials' dosing, AOM improved clinical outcomes by reducing schizophrenia relapses vs PLAI (0.181 vs 0.277 per person per year [pppy]) at an additional cost of US$1276 pppy, resulting in an incremental cost-effectiveness ratio (ICER) of US$13,280/relapse averted. When PI dosing was assumed, this ICER increased to US$19,968/relapse averted. When real-world dosing and highest available dosing were assumed, AOM was associated with fewer relapses and lower overall treatment costs vs PLAI. CONCLUSIONS: AOM consistently provided favorable clinical benefits. Under various dosing scenarios, AOM results indicated fewer relapses at lower overall costs or a reasonable cost-effectiveness threshold (i.e., less than the cost of a hospitalization relapse) vs PLAI. Given the heterogeneous nature of schizophrenia and variability in treatment response, health plans may consider open access for treatments like AOM. Since model inputs were based on data from separate placebo-controlled trials, generalization of results to the real-world setting is limited.

The costs of developing, implementing, and operating a safety learning system in community practice.

BACKGROUND: The cost of implementing safety systems in primary care has not been examined. One type of safety system is a safety learning system (SLS). An SLS has 2 components: a reporting that monitors patient safety incidents and a learning component that facilitated the development and implementation of improvement strategies. It is important to understand the costs of an SLS to determine if the improvement program is financially sustainable. OBJECTIVE: To determine the costs of the development, implementation, and operation of the community-based SLS. METHODS: Nineteen participating family physician clinics in Calgary, Alberta, were included (15 urban and 4 rural) consisting of 47 physicians, 53 office staff, 18 nurses, and 6 clinic managers. Costs of the SLS were determined by the ingredient method using micro-costing. The costs were divided into 3 stages: development, implementation, and operational. Development costs were processes required to create and initiate the SLS. Implementation costs were accrued as a result of establishing, running, and refining the SLS. Finally, operational costs were those related to maintaining the SLS. Costs were further broken down into fixed, marginal, and in kind; this approach will allow policy and decision makers to apply the appropriate costs to their own settings. RESULTS: The total development, implementation, and operational costs for the SLS in Canadian dollars were $77,011, $19,941, and $166,727, respectively, with a total cost of $263,679 over approximately a 4-year period. During this time, 270 incident reports were submitted, and 54 improvement cycles were implemented. CONCLUSIONS: The results provide quantitative data, which could be useful to legislators, policy makers, and other private and public sector payers of patient safety programs in determining the overall sustainability of an SLS.

Impact of oral antipsychotic medication adherence on healthcare resource utilization among schizophrenia patients with Medicare coverage.

Nonadherence to antipsychotic medications is widespread and compromises the outcome of patients with schizophrenia. Using the MarketScan Medicare claims database, this study examined the impact of medication adherence on healthcare utilization among Medicare insured schizophrenia patients. The study population was separated into two cohorts defined by medication adherence, one with a medication possession ratio (MPR) ≥0.7 (high adherence) and the other with a MPR <0.7(low adherence). Of the 354 patients identified, 126 (36 %) had high adherence (mean ± SD MPR 0.94 ± 0.09) and 228 (64 %) had low adherence (MPR 0.24 ± 0.19). All cause hospitalizations (0.68 vs. 0.44; p = 0.015) and length of stay (LOS) (7.0 vs. 2.6 days; p = 0.005), and relapse hospitalizations (0.22 vs. 0.11; p = 0.028) and LOS (3.2 vs. 0.7 days; p = 0.027) were greater among patients with low adherence. Low adherent Medicare insured patients with schizophrenia require significantly more inpatient care and represent a patient population in which effective interventions are needed to improve disease management.

Medical costs and hospitalizations among patients with depression treated with adjunctive atypical antipsychotic therapy: an analysis of health insurance claims data.

BACKGROUND: Depression is frequently debilitating. The American Psychiatric Association recommends adjunctive atypical antipsychotics as a treatment option when response to antidepressants is inadequate. OBJECTIVE: To compare medical costs and hospitalizations among patients with depression treated with adjunctive aripiprazole, olanzapine, or quetiapine. METHODS: This retrospective analysis used medical and pharmacy claims data and enrollment information from a large US health plan. Patients were adult members of a commercial health plan who were diagnosed with depression (ie, ICD-9-CM 296.2x, 296.3x, or 311) and who received an antidepressant with adjunctive atypical antipsychotic therapy (aripiprazole, olanzapine, or quetiapine) between January 1, 2004, and January 31, 2010. Patients were continuously enrolled for 6-month pre- and 12-month postaugmentation periods. Those with schizophrenia or bipolar disorder were excluded. Postaugmentation outcomes were total and mental health-related medical costs and hospitalizations. Costs and hospitalizations were modeled with generalized linear models (ie, gamma distribution, log link) and logistic regression, respectively. Regressions controlled for dose, demographics, and general and medical health-related health status. RESULTS: A total of 10,292 patients were identified across atypical antipsychotic cohorts: 3849 used aripiprazole, 1033 used olanzapine, and 5410 used quetiapine. Mean (SD) age was 44.1 (11.6) years and 70.3% were female. Compared with patients in the aripiprazole cohort, those in the olanzapine cohort had higher total medical costs (cost ratio [CR] 1.22, 95% CI 1.07-1.39) and higher mental health-related medical costs (CR 1.33, 95% CI 1.11-1.59), as well as higher odds of any (total) hospitalization (OR 1.58, 95% CI 1.30-1.92) and any mental health-related hospitalization (OR 1.81, 95% CI 1.38-2.38). Similarly, the quetiapine cohort had higher total medical costs (CR 1.27, 95% CI 1.16-1.39) and higher mental health-related medical costs (CR 1.23, 95% CI 1.09-1.39), as well as higher odds of any (total) hospitalization (OR 1.65, 95% CI 1.44-1.90) and any mental health-related hospitalizations (OR 1.78, 95% CI 1.45-2.18), compared with the aripiprazole cohort. CONCLUSIONS: Compared with adjunctive olanzapine or quetiapine, adjunctive aripiprazole was associated with lower mean total and mental health-related medical costs and with lower odds of total and mental health-related hospitalizations in patients with depression.

Impact on healthcare resource usage and costs among Medicaid-insured schizophrenia patients after initiation of treatment with long-acting injectable antipsychotics.

OBJECTIVE: This study compared healthcare resource usage and costs before and after initiating LAI antipsychotics among Medicaid-insured schizophrenia patients. METHODS: Schizophrenia patients ≥13 years of age initiating LAI antipsychotics were identified from the Thomson Reuters MarketScan® Research Medicaid database between 7/1/2005 and 6/30/2010. Patients were required to have 6 months of continuous medical/prescription drug coverage prior to LAI initiation (baseline period) and during a variable follow-up period. Annualized healthcare resource usage and costs for the baseline and follow-up periods were determined and compared. RESULTS: Among 5694 eligible patients, 55% were male and 45% were female, and the majority of the population was between the ages of 18-55 (86%). The study population had low general comorbidity, as assessed by the Charlson Comorbidity Index (CCI). Diabetes (17%) and chronic pulmonary disease (14%) were the most prevalent comorbidities. In comparison to the baseline period, during the follow-up period (mean duration = 25.7 months) the mean number of hospitalizations, all cause (1.52 ± 2.41 vs 0.70 ± 1.61, p < 0.001) and schizophrenia-related (1.21 ± 2.04 vs 0.57 ± 1.41, p < 0.001) declined as well as hospital lengths of stay (all cause: 14.77 ± 28.61 vs 5.75 ± 16.26 days, p < 0.001; schizophrenia-related: 12.39 ± 25.86 vs 4.67 ± 13.54 days, p < 0.001). As a result, annualized hospital payments were much lower (all cause: $16,249 ± $36,404 vs $7380 ± $21,087, p < 0.001; schizophrenia-related: $13,388 ± $31,614 vs $5645 ± $15,767, p < 0.001). LIMITATIONS: This study attempted to minimize the impact of differences in patient characteristics by having patients serve as their own controls in the before vs after comparison, however one still may not be able to account for all confounders in this non-randomized study population. CONCLUSION: For patients with schizophrenia who initiate LAI antipsychotic therapy, there is an improvement in disease management based on fewer hospitalizations for relapses, which is also associated with a marked reduction in healthcare costs.

Cost-effectiveness of adjunctive therapy with atypical antipsychotics for acute treatment of major depressive disorder.

BACKGROUND: While the clinical utility of atypical antipsychotics has been established in patients with major depressive disorder (MDD) who are refractory to antidepressant therapy, their cost-effectiveness is unknown. OBJECTIVE: To examine the cost-effectiveness of aripiprazole, quetiapine, and olanzapine/fluoxetine in adults with MDD who are refractory to antidepressant therapy. METHODS: Using techniques of decision analysis, we estimated expected outcomes and costs over 6 weeks in adults with MDD receiving (1) aripiprazole 2-20 mg/day and antidepressant therapy; (2) quetiapine 150 mg/day or 300 mg/day and antidepressant therapy; (3) the fixed-dose combination of olanzapine 6, 12, or 18 mg/day with fluoxetine 50 mg/day; or (4) antidepressant therapy alone. Cost-effectiveness was assessed in terms of the cost per additional responder at 6 weeks, defined as the ratio of the difference in the cost of MDD-related care over 6 weeks versus antidepressant therapy alone to the difference in the number of patients achieving clinical response by 6 weeks. We estimated the model using data from Phase 3 clinical trials of atypical antipsychotics along with other secondary data sources. RESULTS: With antidepressant therapy alone, the estimated clinical response rate at 6 weeks was 30%. Aripiprazole, quetiapine 150 mg/day, quetiapine 300 mg/day, and olanzapine/fluoxetine were estimated to increase clinical response at 6 weeks to 49%, 34%, 38%, and 45%, respectively. Costs of MDD-related care over 6 weeks were estimated to be $192 for antidepressant therapy, $847 for aripiprazole, $541 for quetiapine 150 mg/day, $672 for quetiapine 300 mg/day plus antidepressant therapy, and $791 for olanzapine/fluoxetine. Costs per additional responder (vs antidepressant therapy) over a 6-week period were estimated to be $3447 for aripiprazole, $8725 for quetiapine 150 mg/day, $6000 for quetiapine 300 mg/day, and $3993 for olanzapine/fluoxetine. CONCLUSIONS: Atypical antipsychotics substantially increase clinical response at 6 weeks. Cost per additional responder is lower for aripiprazole than for quetiapine or olanzapine/fluoxetine.

A real-world data analysis of dose effect of second-generation antipsychotic therapy on hemoglobin A1C level.

Previous studies have demonstrated an association between certain second-generation antipsychotics (SGAs) and diabetes mellitus. The study assessed the impact of SGA dose on hemoglobin A1C (HbA(1c) >6.0) levels in a real-world setting. Patients aged ≥ 18 years during 2002-2006 in Ingenix LabRx claims database were included. The database collects medical and prescription claims and a subset of laboratory results for an employed, commercially insured population distributed throughout the United States. Patients with previously diagnosed diabetes, identified by the ICD-9-CM code of 250.x or use of antidiabetic agents, were excluded. The main exposure measure was the cumulative dose over a 30 day period before the HbA(1c) test, calculated as [sum of (number of pills per day×strength)]/100. A logistic regression was used to examine the relation with HbA(1c) >6.0 by tertile of the cumulative dose and average daily dose, adjusted for the covariates. The study included 391 patients on olanzapine, 467 on quetiapine, and 262 on risperidone. Patients treated with aripiprazole or ziprasidone (n=212) were included as a secondary reference because of their minimal metabolic risk. Compared to lower (Tertiles 1 and 2) cumulative doses of risperidone, patients with a high cumulative dose of risperidone (Tertile 3) had a significantly higher odds ratio (OR) for HbA(1c) >6.0 (adjusted OR=2.45; 95% confidence interval=1.13-5.32; P=0.023). A similar increase in OR was seen in patients with high cumulative dose of olanzapine (2.41; 1.19-4.89; P=0.015). Analyses of average daily dose revealed that quetiapine ≥ 400 mg/day and risperidone ≥ 2 mg/day had an OR of 2.29 (1.04-5.06; P=0.041) and 2.28 (1.08-4.83; P=0.032), respectively, compared to aripiprazole/ziprasidone. Both olanzapine groups (≥ 10 and <10mg/day) were associated with a significantly increased OR. All results remained similar after further adjustment for the predicated probability of having an HbA(1c) test and additional medication covariates. In this claims data study, use of olanzapine was associated with elevated HbA(1c) and risperidone and quetiapine appeared to have dose-related association with elevated HbA(1c). One of the limitations of a claims data analysis is the lack of information on potential confounders such as ethnicity and weight.

Adjunctive aripiprazole for depression: predictive value of early assessment.

OBJECTIVES: To determine whether early symptom improvement with adjunctive aripiprazole in major depressive disorder (MDD) predicts overall symptom remission. STUDY DESIGN: Post hoc pooled analysis of 3 randomized, double-blind studies evaluating efficacy, safety, and tolerability of adjunctive aripiprazole or placebo with standard antidepressant therapy (ADT) in inadequate responders to a prospective 8-week ADT and at least 1 historical ADT. METHODS: A multivariate logistic regression model was developed to determine factors predicting remission most strongly at the end point. Remission was defined as a Montgomery-Asberg Depression Rating Scale (MADRS) total score of 10 or less at end point. RESULTS: Early improvement in depression symptoms was the most significant predictor of remission. In adjunctive aripiprazole and placebo groups, improvement of 20% or more in MADRS total score (week 2) was a significant predictor of remission. At week 2, high sensitivity and high negative predictive values (NPVs) were reported for remission in both treatment arms. In the adjunctive aripiprazole arm, early improvement predicted later MADRS remission with high sensitivity (88.0%) and a high NPV (91.5%). Positive predictive value was moderate in both the adjunctive aripiprazole (45.4%) and placebo (37.5%) arms; specificity was 55.0% with adjunctive aripiprazole and 71.5% with placebo. CONCLUSIONS: Week 2 was a clinically meaningful time point to identify early improvers, and lack of improvement early in treatment was a highly significant predictor of lack of later remission. Early assessment of changes in symptoms could prove useful in clinical practice and more appropriately target healthcare costs.