Search

Daisy Ng-Mak,1 Jiat-Ling Poon,2 Laurie Roberts,2 Leah Kleinman,2 Dennis A Revicki,2 Krithika Rajagopalan1 1Global Health Economics and Outcomes Research, Sunovion Pharmaceuticals Inc., Marlborough, MA, 2Patient-Centered Research, Evidera, Bethesda, MD, USA Purpose: The purpose of this study was to assess patient preferences regarding pharmacological treatment attributes for bipolar depression using a discrete choice experiment (DCE).Methods: Adult members of an Internet survey panel with a self-reported diagnosis of bipolar depression were invited via e-mail to participate in a web-based DCE survey. Participants were asked to choose between hypothetical medication alternatives defined by attributes and levels that were varied systematically. The six treatment attributes included in the DCE were time to improvement, risk of becoming manic, weight gain, risk of sedation, increased blood sugar, and increased cholesterol. Attributes were supported by literature review, expert input, and results of focus groups with patients. Sawtooth CBC System for Choice-Based Conjoint Analysis was used to estimate the part-worth utilities for the DCE analyses.Results: The analytical sample included 185 participants (50.8% females) from a total of 200 participants. The DCE analyses found weight gain to be the most important treatment attribute (relative importance =49.6%), followed by risk of sedation (20.2%), risk of mania (13.0%), increased blood sugar (8.3%), increased cholesterol (5.2%), and time to improvement (3.7%).Conclusion: Results from this DCE suggest that adults with bipolar depression considered risks of weight gain and sedation associated with pharmacotherapy as the most important attributes for the treatment of bipolar depression. Incorporating patient preferences in the treatment decision-making process may potentially have an impact on treatment adherence and satisfaction and, ultimately, patient outcomes. Keywords: bipolar depression, treatment preference, adverse events, weight gain

OBJECTIVE: To explore whether early treatment would shorten the duration of headache from headache onset to its peak and reduce headache severity at peak. BACKGROUND: Prior clinical studies almost exclusively focused on headache relief after dosing. No data are available on whether early intervention affects the duration from headache onset to peak and headache severity at peak. METHODS: Adult migraineurs were enrolled in this observational study from multi-site headache clinics. Patients recorded their migraine experiences via an electronic diary over 1 month. Patients reported the time and pain severity at onset, dosing, and peak. We used a linear mixed model to evaluate the impact of the timing of treatment and to adjust for covariates and correlation of observations within subjects. RESULTS: A total of 182 patients reported 970 migraine episodes, 620 of which were treated before headaches progressed to peak. Mean time from headache onset to peak varied from 1.9 hours to 8.9 hours for patients treated within 15 minutes of onset and those who waited for 4 or more hours, respectively. However, early intervention was not associated with reduced headache severity at peak. In multivariate analysis, early treatment, use of triptans, and mild migraine headache in the past 3 months were significantly associated with shorter time from onset to headache peak. A separate model indicated that the timing of medication was not associated with the duration between dosing and headache peak, but use of triptans shortened the time from dosing to headache peak. CONCLUSIONS: Early treatment and use of triptans may lead to shorter duration from migraine headache onset to its peak but did not alleviate headache severity at peak. This could result in decreased migraine burden by reducing total migraine headache duration. [ABSTRACT FROM AUTHOR]

Abstract Background To estimate utility values for different levels of migraine pain severity from a United Kingdom (UK) sample of migraineurs. Methods One hundred and six migraineurs completed the EQ-5D to evaluate their health status for mild, moderate and severe levels of migraine pain severity for a recent migraine attack, and for current health defined as health status within seven days post-migraine attack. Statistical tests were used to evaluate differences in mean utility scores by migraine severity. Results Utility scores for each health state were significantly different from 1.0 (no problems on any EQ-5D dimension) (p Conclusions Results indicate that all levels of migraine pain are associated with significantly reduced utility values. As severity worsened, utility decreased and severe migraine pain was considered a health state worse than death. Results can be used in cost-utility models examining the relative economic value of therapeutic strategies for migraine in the UK.

Measures of psychopathology among mentally ill chemical abusers (MICAs) were examined as predictors of levels of functioning in two types of community based, residential programs: therapeutic community (TC) and community residence (CR). Non-significant associations were generally observed between scales of psychiatric symptoms (e.g., depression, psychotic ideation, cognitive disorientation, and hostility) and counselors' ratings of the residents' capacity to meet the social and interpersonal expectations of the programs (e.g., personal care, involvement in interpersonal relationships, and development of work skills). The study suggests that individuals with moderately severe psychopathology can be successfully engaged in residential treatment, even in programs with relatively high expectations for interpersonal involvement and functioning, such as the therapeutic community. [ABSTRACT FROM AUTHOR]

This network meta-analysis assessed the efficacy and tolerability of lurasidone versus other oral atypical antipsychotic monotherapies in adolescent schizophrenia. A systematic literature review identified 13 randomized controlled trials of antipsychotics in adolescents with schizophrenia-spectrum disorders. A Bayesian network meta-analysis compared lurasidone to aripiprazole, asenapine, clozapine, olanzapine, paliperidone extended-release (ER), quetiapine, risperidone, and ziprasidone. Outcomes included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), weight gain, all-cause discontinuation, extrapyramidal symptoms (EPS), and akathisia. Results were reported as median differences for continuous outcomes and odds ratios (ORs) for binary outcomes, along with 95% credible intervals (95% CrI). Lurasidone was significantly more efficacious than placebo on the PANSS (- 7.95, 95% CrI - 11.76 to - 4.16) and CGI-S (- 0.44, 95% CrI - 0.67 to - 0.22) scores. Lurasidone was associated with similar weight gain to placebo and statistically significantly less weight gain versus olanzapine (- 3.62 kg, 95% CrI - 4.84 kg to - 2.41 kg), quetiapine (- 2.13 kg, 95% CrI - 3.20 kg to - 1.08 kg), risperidone (- 1.16 kg, 95% CrI - 2.14 kg to - 0.17 kg), asenapine (- 0.98 kg, 95% CrI - 1.71 kg to - 0.24 kg), and paliperidone ER (- 0.85 kg, 95% CrI - 1.57 kg to - 0.14 kg). The odds of all-cause discontinuation were significantly lower for lurasidone than aripiprazole (OR = 0.28, 95% CrI 0.10-0.76) and paliperidone ER (OR = 0.25, 95% CrI 0.08-0.81) and comparable to other antipsychotics. Rates of EPS and akathisia were similar for lurasidone and other atypical antipsychotics. In this network meta-analysis of atypical antipsychotics in adolescent schizophrenia, lurasidone was associated with similar efficacy, less weight gain, and lower risk of all-cause discontinuation compared to other oral atypical antipsychotics.

Improvements in patient outcomes from the meaningful use of electronic health records (EHRs) have not been extensively studied among patients with schizophrenia. This study assessed the association between EHR use, provision of quality care, and patient outcomes. Providers who were at least 50% compliant with current requirements for the CMS Electronic Health Records Incentive Program were classified as EHR providers. Quality of mental health care was assessed using 4 Healthcare Effectiveness Data and Information Set indicators. Patient outcomes included inpatient admissions and emergency department visits. A total of 18,305 providers (EHR: 16.6%; non-EHR: 83.3%) treated 27,153 patients with schizophrenia. EHR use was associated with improved rates of diabetes screening (77.9% vs 72.4%; P <.001), diabetes monitoring (72.1% vs 61.4%; P <.001), and better antipsychotic adherence (54.7% vs 36.6%; P <.001). EHR use was also associated with fewer inpatient admissions (15.9% vs 25.2%; P <.001) and emergency department visits (32.2% vs 49.3%; P <.001). These data suggest that EHR use may have a positive influence on the process and outcomes of psychiatric care when treating patients with schizophrenia. More research is needed to identify the drivers of the influence of EHRs and to develop programs that ensure all EHR users enjoy the same potential benefits as demonstrated here.

This study compared the risk of hospitalization among adults with schizophrenia being treated with equivalent dose ranges of lurasidone versus aripiprazole, olanzapine, quetiapine, or risperidone. Administrative claims data for this analysis came from the IBM MarketScan Commercial, Medicare Supplemental, and Multi-State Medicaid databases between January 2011 and June 2017. The study included adults with schizophrenia who initiated treatment with an antipsychotic and were continuously enrolled for 360 days prior to and following the date of the initial antipsychotic prescription. Risk of all-cause and schizophrenia-related hospitalization among patients who received lurasidone monotherapy versus aripiprazole, olanzapine, quetiapine, or risperidone in equivalent dose ranges were assessed. Marginal structural models that accounted for preindex characteristics, changes in antipsychotic treatment, and time-varying covariates assessed differences between lurasidone and other second-generation antipsychotics on all-cause and schizophrenia-related hospitalizations. A sensitivity analysis was conducted without the dose-equivalence requirement. A total of 20,212 patients met the study inclusion criteria. Compared with those treated with lurasidone monotherapy, the adjusted risk of all-cause hospitalization was significantly higher among patients treated with olanzapine (adjusted rate ratio [aRR], 1.49; P = .04), quetiapine (aRR, 1.64; P = .01), or risperidone (aRR, 1.47; P = .04), but not aripiprazole (aRR, 1.24; P = .28). A similar, non-statistically significant pattern of adjusted risks of schizophrenia-related hospitalizations was observed. A sensitivity analysis without the dose-equivalence requirement produced consistent results. As hospitalization is a major cost driver of direct healthcare cost, lurasidone may be a cost-saving treatment option for patients with schizophrenia.

Electronic shared-decision making programs may provide an assistive technology to support physician-patient communication. This mixed methods study examined use of a web-based shared decision-making program (MyCHOIS-CommonGround) by individuals receiving specialty mental health services, and identified qualitative factors influencing adoption during the first 18 months of implementation in two Medicaid mental health clinics. T-tests and χ 2 analyses were conducted to assess differences in patient use between sites. Approximately 80% of patients in both clinics created a MyCHOIS-CommonGround user profile, but marked differences emerged between clinics in patients completing shared decision-making reports (79% vs. 28%, χ 2 (1)  = 109.92, p < .01) and average number of reports (7.20 vs. 3.60, t = - 3.64, p < .01). Results suggest high penetration of computer-based programs in specialty mental health services is possible, but clinic implementation factors can influence patient use including leadership commitment, peer staff funding to support the program, and implementation strategy, most notably integration of the program within routine clinical workflow.

Objective: This observational study compared the risk of hospitalization for patients with bipolar disorder when treated with lurasidone versus other oral atypical antipsychotics., Methods: This US commercial claims analysis (4 April 2010 through 24 September 2014) used the Optum Research Database to identify adult patients with bipolar disorder treated with oral atypical antipsychotics (N = 11,132). The first claim for an atypical antipsychotic defined the index date, with pre-index and post-index periods of 180 and 360 days, respectively. Every month of the post-index period was categorized as monotherapy treatment with lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, no/minimal treatment or other. Starting with the initial month of treatment, the risk of psychiatric or all-cause hospitalization in the subsequent month was examined based on treatment in the current month and pre-index covariates (age, gender, hospitalizations, emergency room visits, diagnoses for anxiety, alcohol abuse, substance abuse, hypertension, type 2 diabetes and obesity) and time-varying versions of the pre-index covariates using a marginal structural model., Results: After controlling for covariates, relative to lurasidone, the odds of psychiatric and all-cause hospitalization, respectively, were 2-3 times higher for olanzapine (odds ratio [OR] = 2.78, CI 1.09, 7.08, p = .032; OR = 3.20, CI 1.24, 8.26, p = .016), quetiapine (OR = 2.80, CI 1.13, 6.95, p = .026; OR = 3.23, CI 1.29, 8.11, p = .013), risperidone (OR = 2.50, CI 1.01, 6.21, p = .048; OR = 2.79, CI 1.11, 7.02, p = .029), aripiprazole (OR = 2.13, CI 0.87, 5.20, p = .097; OR = 2.57, CI 1.04, 6.37, p = .041) and ziprasidone (OR =2.31, CI 0.91, 5.85, p = .079; OR = 2.49, CI 0.97, 6.40, p = .058)., Conclusions: In this claims database analysis, lurasidone-treated patients with bipolar disorder had a significantly lower risk of psychiatric hospitalization compared to quetiapine, olanzapine and risperidone, but not aripiprazole or ziprasidone. Lurasidone-treated patients had a significantly lower risk of all-cause hospitalization compared to quetiapine, olanzapine, risperidone and aripiprazole, but not ziprasidone.

Objective: This descriptive study examined the quality of care received by individuals with serious mental illness observed in clinical care using established Healthcare Effectiveness Data and Information Set (HEDIS) measures for individuals with serious mental illness. Methods: Administrative claims (Medicaid, Medicare, and commercial) from a national health and well-being company were used to identify adults with schizophrenia or bipolar disorder. Performance rates for five HEDIS mental health quality measures were computed. Sub-group analyses examined each HEDIS measure by those who were medication adherent vs non-adherent, and by typical vs atypical antipsychotics. Results: Eighty-nine percent of the Medicaid population received a diabetes screening (vs 79% for national benchmark Medicaid rates), 81% (vs 69%) received monitoring for diabetes, 88% (vs 79%) received monitoring for cardiovascular disease, 63% (vs 60%) were adherent with antipsychotic medication, and 34% (vs 61%) had a follow-up visit with a mental health practitioner within 30 days of a discharge. The rates for individuals with Medicare coverage were similar or marginally higher than those reported for those with Medicaid coverage, while rates for the commercially insured population were lower than the other groups. Conclusions: Most (>65%) individuals with serious mental illness received the recommended screening and monitoring for diabetes and cardiovascular disease. Barriers to and reasons for lack of follow-up should be investigated to guide future interventions to improve follow-up after hospitalization for individuals with serious mental illness.

Objectives: To assess the efficacy and tolerability of lurasidone versus other atypical antipsychotic monotherapy agents in patients with bipolar depression, using a Bayesian network meta-analysis., Methods: Fourteen randomised clinical trials (6221 patients) of lurasidone, quetiapine (extended release and immediate release), aripiprazole, olanzapine, and ziprasidone for bipolar depression were included. Efficacy assessments included change in the Montgomery-Åsberg Depression Rating Scale (MADRS), rates of response (≥50% improvement in MADRS) and remission (MADRS ≤12 at study endpoint), and change in the Clinical Global Impressions-Bipolar Disorder-Severity (CGI-BP-S) scale. Tolerability outcomes included weight, somnolence, extrapyramidal symptoms (EPS), and all-cause discontinuation. Changes from baseline or odds ratios (OR) with 95% credible intervals (CrI) were evaluated., Results: Improvement in the MADRS associated with lurasidone treatment was significantly greater than placebo (-4.70, 95%CrI: -7.20, -2.21), aripiprazole (-3.62, 95%CrI: -7.04, -0.20), and ziprasidone (-3.38, 95%CrI: -6.68, -0.11), but not olanzapine (-0.15, 95%CrI: -3.12, 2.74) or quetiapine (0.10, 95%CrI: -2.68, 2.84). Results for improvement in the CGI-BP-S, and for response and remission were similar. Lurasidone was associated with less weight gain than olanzapine (-2.54 kg, 95%CrI: -3.42, -1.67) and quetiapine (-0.83kg, 95%CrI: -1.59, -0.08); and with lower rates of somnolence than quetiapine (OR: 0.33, 95%CrI: 0.11, 0.82) and ziprasidone (OR: 0.34, 95%CrI: 0.09, 0.93). No significant differences among atypical antipsychotic agents were observed in rates of discontinuation or in rates of EPS., Conclusions: In this network meta-analysis, lurasidone was found to be more efficacious than aripiprazole and ziprasidone, and was associated with less weight gain than quetiapine and olanzapine and less somnolence than quetiapine and ziprasidone.

Aim: To assess the relative efficacy and metabolic effects of lurasidone and brexpiprazole in the acute treatment of schizophrenia. Methods: Five lurasidone and three brexpiprazole trials were identified. In the absence of head-to-head trials, a Bayesian network meta-analysis comparing lurasidone and brexpiprazole was performed. Results: Nonstatistically significant differences in efficacy measures were observed between lurasidone and brexpiprazole. Significant differences favoring lurasidone for weight change (-0.69 kg; 95% CrI: -1.22 to -0.15), total cholesterol (-7.60 mg/dl; 95% CrI: -13.94 to -1.22), and low-density lipoprotein (-6.58 mg/dl; 95% CrI: -12.11 to -1.04) were observed, with a trend indicating half the risk of experiencing ≥7% weight gain. Conclusion: This network meta-analysis suggested that lurasidone had similar efficacy and fewer metabolic effects than brexpiprazole in patients with acute schizophrenia.

Socioeconomic disparities were assessed in predicting metabolic risk among veterans with serious mental illness. Veterans with schizophrenia, schizoaffective, or bipolar disorders were identified in VISN 4 facilities from 10/1/2010 to 9/30/2012. Differences between patients with and without metabolic syndrome were compared using t-tests, Chi square tests and multivariate logistic regressions. Among 10,132 veterans with mental illness, 48.8% had metabolic syndrome. Multivariate logistic regression analysis confirmed that patients with metabolic syndrome were significantly more likely to be older, male, African-American, married, and receiving disability pensions but less likely to be homeless. They were more likely to receive antipsychotics, antidepressants, or anticonvulsants. Bivariate cross-sectional analysis revealed that patients with metabolic syndrome had higher rates of coronary artery disease, cerebrovascular disease, and mortality, and that metabolic syndrome was more often associated with emergency visits and psychiatric or medical hospitalizations. Demographics, socioeconomic status and medications are independent predictors of metabolic syndrome and should be considered in broader screening of risk factors in order to provide preventive interventions for metabolic syndrome.

Background: This study compared hospital admission rates among adult patients with schizophrenia who switched to antipsychotic monotherapy with lurasidone or quetiapine., Methods: This retrospective cohort study used U.S.-based Truven Health MarketScan® Medicaid Multi-State Database (April 2010 through December 2012) and MarketScan® Commercial Claims and Encounters Database (April 2010 through October 2013). Continuous enrollment for 6-months before and after medication initiation was required. Treatment episodes ended after 6-months post lurasidone or quetiapine initiation, a 60-day treatment gap, or initiation of another antipsychotic. Length of treatment episodes (i.e., treatment duration) was compared using a t-test. All-cause, mental-health, and schizophrenia-related hospitalization rates, as well as costs, were compared between lurasidone- and quetiapine-treated patients using multivariable generalized linear models that adjusted for background characteristics., Results: Quetiapine (n = 435) compared to lurasidone (n = 238) treatment was associated with increased all-cause (21% vs 13%, p < 0.05) and mental health-related hospitalizations (20% vs 12%, p < 0.05), but similar rates of schizophrenia-related hospitalizations (14% vs. 10%, p = 0.14). After adjusting for baseline covariates, quetiapine had 64% higher likelihood of all-cause hospitalizations (OR [odds ratio] = 1.64, 95% confidence interval [CI] 1.05-2.57, p = 0.03), 74% higher likelihood of mental health-related hospitalizations (OR = 1.74, 95% CI 1.11-2.75, p = 0.02), and a similar likelihood of schizophrenia-related hospitalization (OR = 1.35, 95% CI 0.82-2.22, p = 0.24). For those with hospital admissions, adjusted all-cause admission costs were higher for quetiapine when compared with lurasidone in both the Medicaid ($22,036 vs. $15,424, p = 0.17) and commercial populations ($23,490 vs. $20,049, p = 0.61). These differences were not significant. The length of treatment episodes was significantly shorter for quetiapine than lurasidone (115.4 vs 123.1 days, p < 0.05)., Conclusions: In this retrospective claims database study, patients with schizophrenia who were switched to lurasidone had significantly fewer all-cause and mental health-related hospitalizations and similar rates of schizophrenia-related hospitalization compared with those switched to quetiapine. Patients switching to lurasidone had a significantly longer treatment duration rate than those switching to quetiapine. These results may reflect differences in efficacy or tolerability between lurasidone and quetiapine.

Objective: To compare patient characteristics, medical comorbidities, health care utilization, and health care costs among patients with bipolar disorder who initiated lurasidone versus other atypical antipsychotics in usual clinical practice., Methods: A retrospective analysis of administrative claims data was conducted using the US Optum Research Database (December 30, 2012, through February 27, 2014). Adult, commercially insured patients with bipolar disorder with an atypical antipsychotic prescription between June 28, 2013, and November 30, 2013, were included. The lurasidone cohort first included any patients with a lurasidone prescription; remaining patients were assigned to their first atypical antipsychotic (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone). Preindex patient characteristics comparisons to lurasidone were conducted with t tests (continuous variables) and χ² or Fisher exact tests (categorical variables)., Results: A total of 3,329 patients were included in this database analysis. A higher percentage of the lurasidone cohort (31.1%) had bipolar depression compared with the other cohorts (23.5%-28.0%). The lurasidone cohort had a statistically significantly higher percentage of patients with prior diabetes mellitus (13.3%) and lipid metabolism disorders (23.2%) than did the quetiapine cohort (8.4% and 16.3%, P < .01). In addition, the lurasidone cohort had significantly more prior antipsychotic polypharmacy (23.0% vs 6.7%-12.9%, P < .01) and atypical antipsychotic use (55.6% vs 11.8%-26.3%, P < .01) than other cohorts. The lurasidone cohort had a statistically significantly higher mean number of prior all-cause and mental health office visits (P < .001) and higher mean prior pharmacy costs than most cohorts (P < .01)., Conclusions: Lurasidone-treated patients with bipolar disorder tended to have a more complex clinical profile, comorbidities, and prior treatment history compared to patients initiated with other atypical antipsychotics in this claims database study. This pattern of treatment may have reflected the overall clinical profile of lurasidone, the role perceived for lurasidone in the therapeutic armamentarium by practitioners, and the recent introduction of lurasidone into clinical practice during the study period., (© Copyright 2017 Physicians Postgraduate Press, Inc.)

Objective: The aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating patients with major depressive disorder (MDD) with mixed features who present with mild and moderate-to-severe levels of anxiety., Methods: The data in this analysis were derived from a study of patients meeting the DSM-IV-TR criteria for unipolar MDD, with a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, who were randomized to 6 weeks of double-blind treatment with either lurasidone 20-60 mg/day (n=109) or placebo (n=100). Anxiety severity was evaluated using the Hamilton Anxiety Rating Scale (HAM-A). To evaluate the effect of baseline anxiety on response to lurasidone, the following two anxiety groups were defined: mild anxiety (HAM-A≤14) and moderate-to-severe anxiety (HAM-A≥15). Change from baseline in MADRS total score was analyzed for each group using a mixed model for repeated measures., Results: Treatment with lurasidone was associated with a significant week 6 change versus placebo in MADRS total score for patients with both mild anxiety (-18.4 vs. -12.8, p<0.01, effect size [ES]=0.59) and moderate-to-severe anxiety (-22.0 vs. -13.0, p<0.001, ES=0.95). Treatment with lurasidone was associated with a significant week 6 change versus placebo in HAM-A total score for patients with both mild anxiety (-7.6 vs. -4.0, p<0.01, ES=0.62), and moderate-to-severe anxiety (-11.4 vs. -6.1, p<0.0001, ES=0.91)., Conclusions: In this post-hoc analysis of an MDD with mixed features and anxiety population, treatment with lurasidone was associated with significant improvement in both depressive and anxiety symptoms in subgroups with mild and moderate-to-severe levels of anxiety at baseline.

Background: To compare outcomes for individuals with major depressive disorder (MDD) with or without subthreshold hypomania (mixed features) in naturalistic settings., Methods: Using the Optum Research Database (1/1/2009─10/31/2014), a retrospective analysis of individuals newly diagnosed with MDD was conducted. Continuous enrollment for 12-months before and after the initial MDD diagnosis was required. MDD with subthreshold hypomania (mixed features) (MDD-MF) was defined based on ≥1 hypomania diagnosis within 30 days after an MDD diagnosis during the one-year follow-up period, in the absence of bipolar I diagnoses. Psychiatric medication use, healthcare utilization, and costs during the one-year follow-up period were compared using multivariate logistic and gamma regressions, controlling for baseline differences., Results: Of 130,626 MDD individuals, 652 (0.5%) met the operational definition of MDD-MF. Compared to the MDD-only group, the MDD-MF group had more suicidality (2.0% vs. 0.5%), anxiety disorders (46.8% vs. 34.0%), and substance use disorders (15.5% vs. 6.1%, all P<0.001). More individuals with MDD-MF were treated with antidepressants (83.6% vs. 71.6%), mood stabilizers (50.5% vs. 2.7%), atypical antipsychotics (39.0% vs. 5.5%), and polypharmacy with multiple drug classes (72.1% vs. 22.7%, all P<0.001). Individuals with MDD-MF had higher hospitalizations rates (24.2% vs. 10.5%) and total healthcare costs (mean: $15,660 vs. $10,744, all P<0.001)., Limitations: The commercial claims data used were not collected for research purposes and may over- or under-represent certain populations. No specific claims-based diagnostic code for MDD with mixed features exists., Conclusions: Greater use of mood stabilizers, atypical antipsychotics, polypharmacy, and healthcare resources provides evidence of the complexity and severity of MDD-MF. Identifying optimal treatment regimens for this population represents a major unmet medical need., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The aim of this study was to describe dosing patterns and medication adherence among bipolar patients who initiated lurasidone in a real-world setting., Methods: Adult bipolar patients who initiated lurasidone between 1 November 2010 and 31 December 2012 (index period) with 6-month pre- and post-index continuous enrollment were identified from the IMS RWD Adjudicated Claims US database. Patients were grouped by starting lurasidone daily dose: 20 mg (7.1%), 40 mg (62.2%), 60-80 mg (28.7%), and 120-160 mg (2.1%). Patient characteristics were compared across doses using Cochran-Armitage trend tests. Multivariable ordinal logistic regression assessed the association between initial lurasidone dose and patient characteristics. Medication adherence was measured using medication possession ratio (MPR)., Results: Of 1114 adult bipolar patients (mean age 40.6 years, 70.6% female), 90% initiated lurasidone at 40 mg or 80 mg/day (mean 51.9 mg/day). Of these, 16.2% initiated lurasidone as monotherapy. Mean lurasidone maintenance dose was 55.2 mg/day and mean MPR was 0.53 [standard deviation (SD) = 0.34] over the 6-month follow up. Substance use, hyperglycemia, obesity, and prior antipsychotic use were associated with higher initial lurasidone doses ( p < 0.05). Odds of a 20 mg/day increase in initial lurasidone dose was 1.6-times higher for patients with substance use [95% confidence interval (CI): 1.16-2.24], 2.6-times higher with hyperglycemia problems (95% CI: 1.15-5.83), 1.7-times higher with obesity (95% CI: 1.05-2.60), and 1.3 (95% CI: 1.01-1.78) and 1.8-times higher (95% CI: 1.17-2.86) with prior use of second- and first-generation antipsychotics, respectively., Conclusions: This real-world analysis of bipolar patients indicated that 40 mg or 80 mg/day were the most common starting doses of lurasidone. A majority of patients used concomitant psychiatric medications (polypharmacy). Higher doses of lurasidone were prescribed to patients with comorbidities or prior antipsychotic use. Adherence to lurasidone was comparable to or better than antipsychotic adherence reported in bipolar disorder literature., Competing Interests: This study was funded by Sunovion Pharmaceuticals Inc. Martha Sajatovic is an employee of Case Western Reserve University (Cleveland, OH, USA) and of University Hospitals Cleveland Medical Center (Cleveland, OH, USA). Daisy Ng-Mak, Krithika Rajagopalan, and Antony Loebel are employees of Sunovion Pharmaceuticals Inc (Marlborough, MA, USA). Caitlyn Solem and Fang-Ju Lin are employees of Pharmerit International (Bethesda, MD, USA) and were paid consultants to Sunovion (Marlborough, MA, USA) in the development and execution of this study.

Background: Long-term improvement of health-related quality of life (HRQoL) in schizophrenia may improve adherence and reduce relapse and rehospitalization. This analysis examines long-term changes in HRQoL among patients with schizophrenia switched to lurasidone from other antipsychotics., Methods: Patients who completed an open-label 6-week switch study continued on lurasidone for an additional 24-weeks. HRQoL was measured using the self-reported Personal Evaluation of Transitions in Treatment (PETiT) scale and Short-Form 12 (SF-12) questionnaire. The PETiT assessed HRQoL via total and domain scores (adherence-related attitude and psychosocial functioning). The SF-12 assessed patients' mental and physical component summary scores (MCS and PCS). Mean changes from the initial baseline were calculated at extension baseline and extension endpoint using analysis of covariance models. Analyses were further stratified by prior antipsychotic medication and responder status; responders were defined as having a ≥20 % improvement in Positive and Negative Syndrome Scale during the first 6-weeks of treatment., Results: The analysis included 144 patients with PETIT or SF-12 data who received ≥1 dose of lurasidone. Mean (standard deviation) PETiT total score improved significantly from 34.9 (9.3) at baseline to 39.5 (8.9) at extension baseline and 39.1 (9.0) at extension endpoint, representing improvements of 4.5 (7.9) and 5.1 (7.2) points, respectively (both p < 0.001). Significant improvements in adherence-related attitude and psychosocial functioning were observed at extension baseline and extension endpoint (all p < 0.001). Improvement in SF-12 MCS score was observed at extension baseline and endpoint, and PCS score at extension endpoint (all p < 0.01). Patients who switched from quetiapine and aripiprazole showed significant improvement of PETiT total score and adherence-related attitude at extension baseline and extension endpoint. In addition, patients who switched from quetiapine, risperidone, aripiprazole, or ziprasidone showed significant improvement in MCS scores from baseline to extension endpoint. Responders to lurasidone demonstrated greater improvement in PETiT total, psychosocial functioning, and MCS scores at extension baseline than nonresponders., Conclusions: After switching to lurasidone, patients with schizophrenia experienced HRQoL improvements that were sustained for an additional 24 weeks of treatment. Further study is warranted to understand the implications of these improvements in terms of employment, adherence, relapse, and rehospitalization., Trial Registration: Clinical trials.gov identifier NCT01143090 (June 10th, 2010).

Background: Depressive symptoms associated with bipolar disorder negatively impact health-related quality of life (HRQoL). The efficacy of lurasidone in reducing depressive symptoms has been previously demonstrated. The objective of this study was to examine the direct and indirect effect (mediated through improvement in depression symptoms) of lurasidone in improving patient HRQoL., Methods: A secondary analysis of data was conducted of two 6-week, double-blind, placebo-controlled trials assessing the effect of lurasidone (lurasidone monotherapy [20-60 mg/day or 80-120 mg/day]; lurasidone adjunctive to lithium or valproate [20-120 mg/day]) in patients with bipolar depression. Patient HRQoL was measured using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q SF). Depression symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS). Analysis of covariance (ANCOVA) was used to estimate the effect of lurasidone on improvement in the Q-LES-Q SF percentage maximum score from baseline to 6 weeks. Path analysis was used to evaluate the total effect (β1), as well as the indirect (β2*β3) and direct (β4) effect of lurasidone on Q-LES-Q SF change through improvements in MADRS., Results: A total of 340 and 485 patients from the monotherapy and adjunctive therapy, respectively, were included in the analysis. At 6-weeks, ANCOVA analyses demonstrated that lurasidone provided significant improvement in adjusted mean Q-LES-Q SF scores in comparison to placebo for monotherapy (22.9 and 22.7 vs. 15.2, both p < 0.01) and adjunctive therapy (23.1 vs. 17.9, p = 0.01). Path analyses indicated that lurasidone treatment predicted MADRS improvement (monotherapy: β2 = -0.44, p < 0.001; adjunctive therapy: β2 = -0.34, p = 0.003), which subsequently predicted improvement in Q-LES-Q SF (monotherapy: β3 = -0.73, p < 0.001; adjunctive therapy: β3 = -0.75, p < 0.001); however, the effect of lurasidone on improvement in Q-LES-Q SF was largely mediated by change in MADRS (monotherapy: β4 = 0.11, p = 0.13; adjunctive therapy: β4 = 0.02, p = 0.77)., Conclusions: Lurasidone as a monotherapy and adjunctive to lithium or valproate is an effective treatment for improving HRQoL in patients with bipolar depression. However, improvement in HRQoL was not independent of improvement in depression, indicating that the effect of lurasidone on improving patient HRQoL may act through a reduction in depressive symptoms associated with bipolar disorder., Trial Registration: Clinicaltrials.gov identifiers: NCT00868699 and NCT00868452 (both registered March 23, 2009).

Estimate the proportion of lurasidone-treated patients with bipolar depression who achieved a clinically meaningful improvement in health-related quality of life (HRQoL) as measured by the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q SF). A post-hoc analysis of data from two 6-week, randomized, placebo-controlled clinical trials of lurasidone as monotherapy (20-60 or 80-120 mg/day) or adjunctive therapy (20-120 mg/day) was carried out. The proportion of patients with clinically meaningful HRQoL improvement at 6 weeks was assessed using the following methods: an anchor-based method using a one-point improvement on the Clinical Global Impression-Severity, Bipolar Version (CGI-BP-S) scale; a distribution-based method using Q-LES-Q SF's SEM; and cumulative distribution functions. Data from 364 and 275 patients were available from the monotherapy and adjunctive therapy trials, respectively. Using anchor-based thresholds, a significantly higher proportion of lurasidone-treated patients reported a clinically meaningful improvement in HRQoL versus placebo in monotherapy (65.0% and 62.5 vs. 41.1%, both P<0.01) and adjunctive therapy (65.2 vs. 50.7%, P<0.05). Similar findings were observed using distribution-based thresholds for monotherapy (82.5% and 78.3 vs. 58.1%, both P<0.01) and adjunctive therapy (74.5 vs. 62.7%, P<0.05), and through the visual display of cumulative distribution functions. Short-term lurasidone monotherapy and adjunctive therapy is associated with a clinically meaningful improvement in HRQoL in patients with bipolar depression.

Unlabelled: Abstract Objective: To assess the association between incontinence severity, treatment-seeking behavior, and healthcare resource utilization (HRU) among participants with overactive bladder (OAB) in eight countries., Research Design and Methods: A cross-sectional online survey of subjects ≥18 years old in Australia, Europe, and North America, who had a past OAB diagnosis and/or experienced ≥1 urinary incontinence (UI) episode in the preceding 12 months, were eligible to participate. Subjects contacted for the survey were primarily from a voluntary medication monitoring registry, MediGuard. Predominantly stress incontinence subjects were excluded. Incontinence severity was assessed by the number of UI episodes over 3 days and grouped as 0 ('dry'), 1-2, 3-4, and ≥5 UI episodes/day. Subject demographics, employment status, comorbidities, treatment-seeking behavior (past OAB diagnosis; spoken to healthcare provider [HCP]), and HRU (diagnostic tests; HCP visits in 6 months before screening) were analyzed by incontinence severity., Results: Overall, 1341 subjects with OAB (mean age 54.5 years; 70.7% female) were surveyed; 20.2%, 47.7%, 18.8%, and 13.3% of subjects reported 0, 1-2, 3-4, and ≥5 UI episodes/day, respectively. Employment status and comorbidities were significantly (p < 0.05) associated with incontinence severity. The two measures of treatment-seeking behavior were significantly (p < 0.05) associated with incontinence severity groups; the proportion of subjects with a past diagnosis of OAB were 35.8%, 44.8%, 52.4%, and 64.0% in the 0, 1-2, 3-4, and ≥5 UI episodes/day groups, respectively; and 59.0%, 63.6%, 65.9%, and 78.1% of subjects in the respective UI severity groups talked to a HCP about their OAB symptoms. Multivariate linear regression analyses showed a positive and consistent association between incontinence severity and HRU; subjects reported a mean of 2.7, 4.1, 4.4, and 7.7 diagnostic tests overall (p < 0.001), and a mean of 1.4, 2.2, 2.7, and 4.0 HCP visits in the 0, 1-2, 3-4, and ≥5 UI episodes/day groups, respectively (p < 0.001). A potential limitation of the study is the cross-sectional survey methodology which limits the ability to draw causal inferences from the results. Additionally, since this is a web-based survey it is possible respondents who have access to/are familiar with technology were more likely to be enrolled., Conclusions: Incontinence severity was positively associated with both treatment-seeking behavior and HRU among subjects with OAB.

Purpose: To estimate the employer costs associated with employee obesity., Design: The study used cross-sectional analysis of employee health-risk assessment, disability, workers' compensation, and medical claims data from 2006 to 2008., Setting: The study took place in the United States from 2006 to 2008., Subjects: A panel database with 29,699 employees drawn from a panel of employers and observed for 3 years each (N = 89,097) was used., Measures: Workdays lost owing to illness and disability; the cost of medical, short-term disability, and workers' compensation claims; and employees' adjusted body mass indices (BMI) were measured., Analysis: We model the number and probability of workdays lost from illness, short-term disability, and workers' compensation events; short-term disability and workers' compensation payments; and health care spending as a function of BMI. We estimate spline regression models and fit results using a third-degree fractional polynomial., Results: Probability of disability, workers' compensation claims, and number of days missed owing to any cause increase with BMI above 25, as do total employer costs. The probability of a short-term disability claim increases faster for employees with hypertension, hyperlipidemia, or diabetes. Normal weight employees cost on average $3830 per year in covered medical, sick day, short-term disability, and workers' compensation claims combined; morbidly obese employees cost more than twice that amount, or $8067, in 2011 dollars., Conclusion: Obesity is associated with large employer costs from direct health care and insurance claims and indirect costs from lost productivity owing to workdays lost because of illness and disability.

Purpose: To develop a risk-scoring tool to identify in a base year patients likely to have high medical spending in the subsequent year and to understand the role obesity and obesity reduction may play in mitigating this risk., Design: Cross-sectional analysis, using commercial claims and health risk assessment data., Setting: United States, 2004-2009., Subjects: Panel of 192,750 person-year observations from 116,868 unique working-age employees of large companies., Measures: Probability of high medical expenses (80th percentile or above) in the following year; adjusted body mass index (BMI)., Analysis: Generate risk scores by modeling the likelihood of high next-year expenses as a function of base-year age, sex, medical utilization, comorbidities, and BMI. Estimate the effect of simulated bariatric intervention on patient risk scores., Results: Individuals with higher BMI were more likely to be categorized in the very high risk group, in which the average annual medical expense was $8621. A weight-loss intervention transitioning a patient to the next lower obesity class was predicted to reduce this risk by 1.5% to 27.4%-comparable to hypothetically curing a patient of depression or type 2 diabetes., Conclusion: A logistic model was used to capture the effect of BMI on the risk of high future medical spending. Weight-loss interventions for obese patients may generate significant savings by reducing this risk.

Objectives: To refine a previously published standardized quality and utilization measurement set for migraine care and to establish performance benchmarks., Study Design: Retrospective application of the migraine measurement set to health plan data in order to assess patterns of health service utilization., Methods: Measurement specifications were applied to data from 10 health plans for measurement year 2009., Results: Of the 2.9 million continuously enrolled members of the health plans, 138,004 (4.7%) met inclusion criteria for the migraine population. Of these, 26% did not have a migraine diagnosis, but were utilizing migraine drugs; 12% had a computed tomography scan within the year (range 8%-25% across plans); and 8% had magnetic resonance imaging (range 6%-11%). Nearly 18% of the migraineurs had 1 or more visits to an emergency department/urgent care center for migraine; few (6%) were followed up with primary care visits. Approximately one-fourth of the migraineurs were not being routinely monitored by a physician. Medication utilization also was examined for members of the migraine population with pharmacy benefits. A significant proportion (42%) were given a migraine preventive, 38% had at least 1 prescription for a triptan, and 2% of those on triptans were potentially overutilizing the medication. Among patients aged 18 to 49 years who were given triptans, 3% had a cardiac contraindication; this percentage rose to 7% for patients aged 50 to 64 years., Conclusions: This study demonstrates the value of standardized measures in identifying potential quality issues for migraine care, including underdiagnosis, overutilization of imaging, and underutilization of preventive drugs.

This study proposes a model explaining the association between physical abuse of children and children's social and affective status as one in which children's social expectations and behavior, developed within the context of abusive parenting, mediate current functioning in these two outcome domains. Subjects included one hundred 9 to 12-year-old physically abused children recruited from consecutive entries onto the New York State Register for Child Abuse for New York City and 100 case-matched classmate nonabused comparison children. Sociometric assessments were carried out in classrooms, interviews were conducted with the children and their parents, and teachers, parents, and classmates rated the children's behavior. Path analysis was utilized to test the conceptually derived models. Children's social expectations regarding peers, and two social behaviors--aggressive behavior and prosocial behavior--were found to mediate between abuse and positive and negative social status, as well as between abuse and positive and negative reciprocity. Social expectations and withdrawn behavior mediated between abuse and positive social status, but only where withdrawn behavior was a function of social expectations. Social expectations were generally found to mediate between abuse and internalizing problems. Negative social status (peer rejection) added to social expectations in producing internalizing problems. Identification of these mediating pathways can serve to guide secondary preventive intervention efforts so that they best address the problems abused children face in the absence of adequate parental and peer support as the children enter adolescence.

Objectives: The feasibility and effectiveness of treating homeless mentally ill chemical abusers in community residences compared with a therapeutic community were evaluated., Methods: A total of 694 homeless mentally ill chemical abusers were randomly referred to two community residences or a therapeutic community. All programs were enhanced to treat persons with dual diagnoses. Subjects' attrition, substance use, and psychopathology were measured at two, six, and 12 months., Results: Forty-two percent of the 694 referred subjects were admitted to their assigned program and showed up for treatment, and 13 percent completed 12 months or more. Clients retained at both types of program showed reductions in substance use and psychopathology, but reductions were greater at the therapeutic community. Compared with subjects in the community residences, those in the therapeutic community were more likely to be drug free, as measured by urine analysis and self-reports, and showed greater improvement in psychiatric symptoms, as measured by the Center for Epidemiological Studies--Depression Scale and the Brief Psychiatric Rating Scale. Their functioning also improved, as measured by the Global Assessment of Functioning scale., Conclusions: Homeless mentally ill chemical abusers who are retained in community-based residential programs, especially in therapeutic communities, can be successfully treated.

Aims: To assess the magnitude and psychopathologic predictors of attrition among homeless, mentally ill chemical abusers (MICAs) referred to residential treatment programs in New York City., Design: Homeless, MICAs were randomly referred to a therapeutic community (TC) or community residence (CR) and monitored with regard to pre- and post-admission attrition., Settings: Community based treatment facilities modified to treat both substance abuse and major mental illness., Participants: Homeless individuals with a major mental illness (DSM-III-R) and a history of abusing alcohol or other drugs., Measurements: Attrition rates and selected scales of psychopathology., Findings: From an initial pool of 694 treatment candidates, 147 (22%) were rejected for admission at their assigned facility; 247 (36%) failed to show up for treatment; and 212 (31%) dropped out of treatment at some point during the first 12 months. Contrary to expectation, those with severe levels of psychotic ideation, depressive symptoms and hostility were admitted to treatment more frequently and stayed in treatment longer at the TC, a high demand approach, than the CR, a low demand approach., Conclusion: Clinicians should consider the TC as a viable treatment option for MICAs.

Comparing two types of treatment modalities in treating homeless, mentally ill, chemical-abusing (HMICAs) men and studying their characteristics, 723 HMICAs were interviewed on their childhood and family background and their psychiatric and substance abuse disorders, and then randomly assigned into either therapeutic community (TC) or community residence (CR) programs. The TC and CRs were found to differ from one another in their intake and admission procedures, their preadmission and postadmission dropout rates, and the effects of treatment on psychological status. The TC admitted their clients into treatment faster, tended to take more impaired clients, and had a lower preadmission dropout rate than the CRs did. The CRs had a lower postadmission dropout rate and were able to retain clients longer than the TC did. Comparing clients who stayed in treatment one year or longer, the TC appears to be more effective than the CRs in reducing depressive, psychotic, and functional symptoms. HMICAs' childhood and family background reveal severe parental deprivations and high prevalence of alcohol and other drug abuse, mental illness, and criminal behavior among the clients' parents. HMICAs' characteristics suggest that these men are completely outside mainstream society. They are severely impaired psychiatrically, chronically addicted, and often involved with the criminal system, thus occupying multiple deviant roles.