Hospitalization Risk for Adults with Bipolar I Disorder Treated with Oral Atypical Antipsychotics as Adjunctive Therapy with Mood Stabilizers: A Retrospective Analysis of Medicaid Claims Data.

Background: Atypical antipsychotics (AAPs) with mood stabilizers are recommended as a first-line treatment for patients with bipolar disorder. No studies have compared the inpatient health care resource utilization for patients with bipolar disorder treated with lurasidone as adjunctive therapy with mood stabilizers compared with other oral AAPs. Objective: To compare the risk of hospitalization for adult Medicaid beneficiaries with bipolar I disorder when treated with lurasidone compared with other oral AAPs as adjunctive therapy with mood stabilizers. Methods: This retrospective cohort study used the MarketScan Research Databases Multi-State Medicaid Database (IBM, Armonk, NY) claims data to assess patients with bipolar I disorder between January 1, 2014, and June 30, 2019. Adult patients who initiated oral AAP treatment with mood stabilizers (index date) and who were continuously enrolled 12 months before (pre-index) and 24 months after (post-index) the index date were included. Treatment categories assigned by patient-month included lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone with mood stabilizers; no/minimal treatment; AAP monotherapy; and other. Marginal structural models were performed to estimate the all-cause and psychiatric hospitalization rates and hospital length of stay associated with each adjunctive AAP therapy by controlling for both time-invariant and time-varying confounders. Results: Adults with bipolar I disorder (N = 11,426; mean age = 39.4 years; female=73%) treated with an adjunctive oral AAP with mood stabilizers during the index month were categorized into lurasidone (12%), aripiprazole (17%), olanzapine (7%), quetiapine (32%), risperidone (11%), ziprasidone (7%), or other (15%) treatment groups. The adjusted odds of all-cause and psychiatric hospitalization were significantly higher for olanzapine (all causes: adjusted odds ratio [aOR] = 1.59; 95% CI, 1.13-2.25; psychiatric: aOR = 1.61, 95% CI, 1.12-2.32), quetiapine (all-causes: aOR = 1.27, 95% CI, 1.01-1.58; psychiatric: aOR = 1.28, 95% CI, 1.02-1.59), and ziprasidone (all-causes: aOR = 1.68, 95% CI, 1.05-2.66; psychiatric: aOR = 1.55, 95% CI, 1.02-2.35) compared with lurasidone with mood stabilizers. The adjusted odds of all-cause and psychiatric hospitalizations were numerically lower for lurasidone compared with aripiprazole. The all-cause hospital length of stay per 100 patient-months was significantly higher for olanzapine (20.3 days) and quetiapine (16.0 days) compared with lurasidone (12.2 days, both P values < 0.05). Conclusions: In a Medicaid population, adults with bipolar I disorder treated with lurasidone as adjunctive therapy with mood stabilizers had significantly lower all-cause and psychiatric hospitalization rates compared with olanzapine, quetiapine, and ziprasidone. Fewer hospitalizations may reduce the economic burden associated with bipolar disorder. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).

Efficacy of adjunctive aripiprazole in patients with major depressive disorder whose symptoms worsened with antidepressant monotherapy.

INTRODUCTION: Efficacy of depression treatments, including adjunctive antipsychotic treatment, has not been explored for patients with worsening symptoms after antidepressant therapy (ADT). METHODS: This post-hoc analysis utilized pooled data from 3 similarly designed, randomized, double-blind, placebo-controlled trials that assessed the efficacy, safety, and tolerability of adjunctive aripiprazole in patients with major depressive disorder with inadequate response to ADT. The studies had 2 phases: an 8-week prospective ADT phase and 6-week adjunctive (aripiprazole or placebo) treatment phase. This analysis focused on patients whose symptoms worsened during the prospective 8-week ADT phase (worsening defined as >0% increase in Montgomery-Åsberg Depressive Rating Scale [MADRS] Total score). During the 6-week, double-blind, adjunctive phase, response was defined as ≥50% reduction in MADRS Total score and remission as ≥50% reduction in MADRS Total score and MADRS score ≤10. RESULTS: Of 1065 patients who failed to achieve a response during the prospective phase, 160 exhibited worsening of symptoms (ADT-Worseners), and 905 exhibited no change/reduction in MADRS scores (ADT-Non-worseners). Response rates for ADT-Worseners at endpoint were 36.6% (adjunctive aripiprazole) and 22.5% (placebo). Similarly, response rates at endpoint for ADT-Non-worseners were 37.5% (adjunctive aripiprazole) and 22.5% (placebo). Remission rates at endpoint for ADT-Worseners were 25.4% (adjunctive aripiprazole) and 12.4% (placebo). For ADT-Non-worseners, remission rates were 29.9% (adjunctive aripiprazole) and 17.4% (placebo). CONCLUSION: These results suggest that adjunctive aripiprazole is an effective intervention for patients whose symptoms worsen during antidepressant monotherapy. The results challenge the view that benefits of adjunctive therapy with aripiprazole are limited to partial responders to ADT.

Real-world predictors of relapse in patients with schizophrenia and schizoaffective disorder in a large health system.

Schizophrenia is often characterized by recurring relapses, which are associated with a substantial clinical and economic burden. Early identification of individuals at the highest risk for relapse in real-world treatment settings could help improve outcomes and reduce healthcare costs. Prior work has identified a few consistent predictors of relapse in schizophrenia, however, studies to date have been limited to insurance claims data or small patient populations. Thus, this study used a large sample of health systems electronic health record (EHR) data to analyze relationships between patient-level factors and relapse and model a set of factors that can be used to identify the increased prevalence of relapse, a severe and preventable reality of schizophrenia. This retrospective, observational cohort study utilized EHR data extracted from the largest Midwestern U.S. non-profit healthcare system to identify predictors of relapse. The study included patients with a diagnosis of schizophrenia (ICD-10 F20) or schizoaffective disorder (ICD-10 F25) who were treated within the system between October 15, 2016, and December 31, 2021, and received care for at least 12 months. A relapse episode was defined as an emergency room or inpatient encounter with a pre-determined behavioral health-related ICD code. Patients' baseline characteristics, comorbidities and healthcare utilization were described. Modified log-Poisson regression (i.e. log Poisson regression with a robust variance estimation) analyses were utilized to estimate the prevalence of relapse across patient characteristics, comorbidities and healthcare utilization and to ultimately identify an adjusted model predicting relapse. Among the 8119 unique patients included in the study, 2478 (30.52%) experienced relapse and 5641 (69.48%) experienced no relapse. Patients were primarily male (54.72%), White Non-Hispanic or Latino (54.23%), with Medicare insurance (51.40%), and had baseline diagnoses of substance use (19.24%), overweight/obesity/weight gain (13.06%), extrapyramidal symptoms (48.00%), lipid metabolism disorder (30.66%), hypertension (26.85%), and diabetes (19.08%). Many differences in patient characteristics, baseline comorbidities, and utilization were revealed between patients who relapsed and patients who did not relapse. Through model building, the final adjusted model with all significant predictors of relapse included the following variables: insurance, age, race/ethnicity, substance use diagnosis, extrapyramidal symptoms, number of emergency room encounters, behavioral health inpatient encounters, prior relapses episodes, and long-acting injectable prescriptions written. Prevention of relapse is a priority in schizophrenia care. Challenges related to historical health record data have limited the knowledge of real-world predictors of relapse. This study offers a set of variables that could conceivably be used to construct algorithms or models to proactively monitor demographic, comorbidity, medication, and healthcare utilization parameters which place patients at risk for relapse and to modify approaches to care to avoid future relapse.

Impact of lurasidone on health-related quality of life in adults with bipolar depression: a post-hoc analysis.

OBJECTIVE: The objective of this post-hoc analysis was to assess the impact of lurasidone monotherapy on health-related quality of life (HRQoL) in adults with bipolar depression. METHODS: Data were analyzed from a 6-week randomized, double-blind (DB), placebo-controlled trial of lurasidone monotherapy (NCT00868699) and a 6-month open label extension (OLE; NCT00868959). Patients who received lurasidone monotherapy or placebo during the DB trial were eligible to continue or switch to lurasidone monotherapy during the OLE. The 16-item Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) was collected at DB baseline, DB week 6/OLE baseline, OLE month 3, and OLE month 6. Effect size (ES) and mean changes from baseline were reported for Q-LES-Q-SF total and item scores during the DB trial and OLE, respectively. RESULTS: Of 485 patients in the DB trial (lurasidone monotherapy: n = 323; placebo: n = 162), 316 patients continued or switched to lurasidone monotherapy during the OLE. Significant improvements in Q-LES-Q-SF scores in lurasidone vs. placebo were reported for 13 of 16 items (all p < .05) at DB week 6. The greatest improvements were overall life satisfaction (ES = 0.57), social relationships (0.55), medication satisfaction (0.48), family relationships (0.46), and ability to function in daily life (0.45, all p < .001). Improvements in Q-LES-Q-SF total and item scores were sustained at OLE month 6. CONCLUSIONS: Treatment with lurasidone provided a significant improvement across HRQoL items including overall life satisfaction, social and family relationships, medication satisfaction, and ability to function in daily life. Improvements were sustained during the 6-month OLE.

Hospitalization risk among adults with bipolar I disorder treated with lurasidone versus other oral atypical antipsychotics: a retrospective analysis of Medicaid claims data.

OBJECTIVE: To compare the risk of hospitalization for adult Medicaid beneficiaries with bipolar I disorder treated with lurasidone vs. other oral atypical antipsychotics (AAPs) as monotherapy. METHODS: A retrospective cohort study of the IBM MarketScan Multi-State Medicaid Claims database identified adults with bipolar I disorder who initiated an AAP (index date) between 1 January 2014 and 30 June 2019. Patients were continuously enrolled 12 months pre- and 24 months post-index date. Each month during the post-index period was categorized as monotherapy with lurasidone, aripiprazole, olanzapine, quetiapine or risperidone, no/minimal treatment, or other. Marginal structural models were performed to estimate hospitalization risk and length of stay (LOS) (all-cause and bipolar I disorder-related) compared to lurasidone. RESULTS: The analysis included 8262 adults. Compared to lurasidone, the adjusted odds ratios (aORs) of all-cause hospitalization were significantly higher for olanzapine (aOR = 1.60, 95% CI = 1.09-2.10) and quetiapine (aOR = 1.54, 95% CI = 1.18-1.89). The risk was significantly higher for bipolar I disorder-related hospitalization for quetiapine (aOR = 1.57, 95% CI = 1.10-2.04) and risperidone (aOR = 1.80, 95% CI = 1.04-2.56) compared to lurasidone. The bipolar I disorder-related LOS per 100 patient-months was more than twice as long for quetiapine (8.42 days) compared to lurasidone (3.97 days, p < .01). CONCLUSIONS: Lurasidone-treated adult Medicaid patients with bipolar I disorder had significantly lower risk of all-cause hospitalization than those treated with olanzapine and quetiapine and lower risk of bipolar I disorder-related hospitalization than quetiapine and risperidone. Bipolar I disorder-related hospital LOS was significantly shorter for patients treated with lurasidone compared to quetiapine.

Gender and stress: differential psychophysiological reactivity to stress reexposure in the laboratory.

Research has shown that women are more prone to the development of depression and anxiety disorders throughout their lifetimes. Stress reactivity and adaptation to repeated stressors have been linked to depression and anxiety, but studies examining gender differences in psychophysiological responses to repeated stressors are very limited. This study examined gender differences in response to initial and repeated exposure to a laboratory stressor as well as potential mechanisms for these differences. Participants viewed a Holocaust video on two occasions with a 2-day interval between sessions. Self reported negative affect and cardiovascular reactivity were recorded at both sessions. Although gender differences were not found following initial exposure, women exhibited significantly greater heart rate (HR) and negative affect (NA) reactivity to the second exposure as compared to men. Women also reported significantly greater intrusive thoughts and avoidance after the first exposure than men, but these were not found to be significant mediators. The findings indicate that women may be more vulnerable to repeated stress exposures compared to men suggesting sensitization. The implications of our findings and suggestions for future research are discussed.

Social barriers to emotional expression and their relations to distress in male and female cancer patients.

OBJECTIVE: Emotional expression is an important means of coping with stressful experiences such as cancer. Social barriers to expression may have adverse effects. Research has suggested that men are less likely to express their emotions and have different patterns of social support compared to women. We examined whether male cancer patients have a lower tendency to express emotions, are less likely to perceive social barriers to expression, and are differentially affected by social barriers from different support sources as compared to women. DESIGN: Questionnaires were administered to 41 women and 41 men using a cross-sectional study design. METHOD: Patients diagnosed with gynaecological or prostate cancer within the past 5 years completed questionnaires on moods, intrusive thoughts, social constraints and emotional expressivity. RESULTS: There was a trend towards greater emotional expressivity in women as compared to men, but no significant gender differences in perceptions of social constraints from spouse/partner or others. Multiple regression analyses revealed that men experienced significantly greater distress in association with social constraints from their spouse/partner than did women. CONCLUSION: Men may be more vulnerable to social barriers to expression than previously assumed. Gender differences in emotional expressivity may be less important than the social context in which expression takes place.

Formulary restrictions on atypical antipsychotics: impact on costs for patients with schizophrenia and bipolar disorder in Medicaid.

OBJECTIVES: To measure the impact of state Medicaid formulary policies on costs for patients with schizophrenia and bipolar disorder. STUDY DESIGN: Retrospective analysis of medical and pharmacy claims for patients diagnosed with schizophrenia or bipolar disorder in 24 state Medicaid programs. METHODS: We combined information on formulary restrictions in Medicaid with the medical and pharmacy claims of 117,908 patients with schizophrenia and 170,596 patients with bipolar disorder in Medicaid who were single-eligible, and newly prescribed a second-generation antipsychotic from 2001 to 2008. We tested the impact of formulary restrictions on the medical costs and utilization of patients in the 12 months after the index prescription. To capture social costs in addition to medical expenditures in Medicaid, we estimated the incremental costs of incarcerating patients with schizophrenia and bipolar disorder associated with formulary restrictions. RESULTS: Patients with schizophrenia subject to formulary restrictions were more likely to be hospitalized (odds ratio 1.13, P <.001), had 23% higher inpatient costs (P <.001), and 16% higher total costs (P <.001). Similar effects were observed for patients with bipolar disorder. Our estimates suggest restrictive formulary policies in Medicaid increased the number of prisoners by 9920 and incarceration costs by $362 million nationwide in 2008. CONCLUSIONS: Applying formulary restrictions to atypical antipsychotics is associated with higher total medical expenditures for patients with schizophrenia and bipolar disorder in Medicaid. Combined with the other social costs such as an increase in incarceration rates, these formulary restrictions could increase state costs by $1 billion annually, enough to offset any savings in pharmacy costs.

Diagnoses associated with use of atypical antipsychotics in a commercial health plan: a claims database analysis.

BACKGROUND: Atypical antipsychotics are indicated for specific psychiatric conditions; however, they are frequently used for US Food and Drug Administration-nonapproved indications. OBJECTIVE: This study assessed the types of medical diagnoses associated with atypical antipsychotic prescriptions in commercial health care plans. METHODS: This retrospective cohort study used the OptumInsight commercial data set from January 2008 to June 2011. The index date was defined as the earliest date of prescription for the atypical antipsychotics aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone, from January 1, 2009, through June 30, 2010. Medical claims during a 2-year period (12 months before and 12 months after the index date) were used to identify relevant diagnostic codes from the International Classification of Diseases, Ninth Edition, Clinical Modification associated with the antipsychotic prescription. A logistic regression analysis was conducted to examine the predictors of use of atypical antipsychotics without a relevant diagnosis, that is, schizophrenia, bipolar, or major depressive disorder (MDD). RESULTS: Of 18,352 patients included in the analysis, 3593 (19.5%) who filled a prescription for atypical antipsychotics did not have an approved diagnosis. Off-label utilization varied, with approximately a quarter of patients with prescriptions for quetiapine (24.1%), risperidone (23.1%), or olanzapine (21.8%) being without a relevant diagnostic code, whereas proportions were lower for patients prescribed aripiprazole (14.0%) or ziprasidone (13.1%). Of those with a psychiatric disorder other than schizophrenia, bipolar disorder, or MDD, approximately a third of prescriptions were for anxiety disorders, with similar proportions across all atypical antipsychotics. Patients were often prescribed quetiapine for substance abuse (22.7%), whereas patients with "other psychiatric conditions" were prescribed risperidone (26.3%) or ziprasidone (25.0%). The logistic regression analysis indicated that patients prescribed olanzapine, quetiapine, or risperidone were significantly more likely to have no diagnostic code for schizophrenia, bipolar disorder, or MDD compared with patients prescribed aripiprazole. CONCLUSION: Nearly a fifth of commercially insured patients were prescribed atypical antipsychotics, in particular, olanzapine, quetiapine, or risperidone, for diagnoses that were not aligned with US Food and Drug Administration-approved indications.

Beneficial effects of adjunctive aripiprazole in major depressive disorder are not dependent on antidepressant therapy history: a post hoc analysis of 3 randomized, double-blind, placebo-controlled trials.

OBJECTIVE: To determine whether switching within or between antidepressant therapy (ADT) classes prior to the use of adjunctive antipsychotic treatment is associated with different outcomes in major depressive disorder (MDD). METHOD: This was a post hoc analysis of pooled data from 3 similar, multicenter, randomized, double-blind, placebo-controlled registrational studies of aripiprazole adjunctive to ADT conducted between September 2004 and April 2008. The trials comprised the following 3 phases: a 7- to 28-day screening phase, an 8-week single-blind prospective treatment phase, and a 6-week double-blind, randomized phase. Patients were aged 18-65 years and met DSM-IV-TR criteria for MDD. Patients with an inadequate response to ADT during the screening phase entered the prospective treatment phase, during which they were switched to another ADT medication of either the same or a different class. Those patients with an inadequate response were then randomized to double-blind adjunctive aripiprazole or adjunctive placebo and followed for 6 weeks. RESULTS: Mean improvement in Montgomery-Asberg Depression Rating Scale total score was significantly greater with adjunctive aripiprazole versus adjunctive placebo for both between-class (-9.2 vs -6.2, P < .001) and within-class (-9.8 vs -6.6, P < .001) switch groups. Relative risks for response were 1.6 (95% CI = 1.3-2.1) for those who switched between classes and 1.7 (95% CI = 1.2-2.2) for those who switched within class. CONCLUSIONS: Augmentation with aripiprazole, after either a between-class or within-class switch following initial ADT failure, is an effective option for patients with nonresponsive MDD. In contrast to current strategies employed in clinical practice, these results suggest that adjunctive aripiprazole is a logical strategy in patients unresponsive to ADT. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00105196, NCT00095758, NCT00095823.

Efficacy of adjunctive aripiprazole in major depressive disorder: a pooled response quartile analysis and the predictive value of week 2 early response.

OBJECTIVE: To assess varying levels of response to aripiprazole adjunctive to standard antidepressant therapy (ADT) and the predictive value of an early response for a sustained response. METHOD: This post hoc analysis of 3 similarly designed randomized, double-blind, placebo-controlled phase 3 studies investigated the efficacy and safety of adjunctive aripiprazole to standard ADT in patients with major depressive disorder (DSM-IV-TR criteria) who had a prior inadequate response to 1-3 ADTs (CN138-139 [September 2004-December 2006], CN138-163 [June 2004-April 2006], and CN138-165 [March 2005-April 2008]). Response levels were defined as percent decreases from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score after 6 weeks of treatment, with a ≤ 25% decrease for minimal, > 25 to < 50% decrease for partial, ≥ 50% to < 75% decrease for moderate, and ≥ 75% decrease for a robust response to treatment. RESULTS: More patients receiving adjunctive aripiprazole exhibited a partial (23.9% vs 17.9%, P = .017), moderate (23.1% vs 15.0%, P < .001), and robust response (14.3% vs 7.4%, P < .001) compared with adjunctive placebo. Adjunctive aripiprazole treatment compared with adjunctive placebo treatment was associated with a significantly greater proportion of patients achieving an early response (week 2, ≥ 50% reduction in MADRS total score, n = 110/539 vs n = 47/525, P < .001, number needed to treat = 9) and an endpoint response (relative risk = 1.7, 95% CI = 1.4-2.0, P < .001, number needed to treat = 7). A univariate logistic regression analysis revealed that an early response was a significant predictor of endpoint remission (P < .001). CONCLUSIONS: Aripiprazole augmentation was associated with a significantly greater proportion of patients achieving a partial, moderate, or robust response to treatment compared with ADT alone. Patients showing an early response (week 2) to augmentation maintained their response through endpoint, suggesting that clinicians may make clinically meaningful decisions early during treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00095823, NCT00095758, and NCT00105196.

Psychological adjustment following diagnosis and treatment of cancer: an examination of the moderating role of positive and negative emotional expressivity.

In support of cognitive processing models, emotional expression appears to reduce associations between intrusions and psychological distress. Past research has focused primarily on the role of the expression of negative emotion, or emotion in general, in cognitive processing and adjustment. In the present study, we examined the role of both positive and negative emotional expressivity on relations between intrusions and both distress and avoidance among 93 individuals diagnosed with and treated for cancer. We hypothesized stronger negative associations between intrusive thoughts and both distress and avoidance for those individuals lower in positive or negative expressivity. Results generally supported hypotheses with regard to relations of intrusions and distress in association with positive expressivity. Negative expressivity, however, moderated relations between intrusions and distress, but not intrusions and avoidance. These findings underscore the importance of examining the impact of individual differences in negative, as well as positive, emotional expression on cognitive processing and psychological adjustment.

The role of spirituality in the psychological adjustment to cancer: a test of the transactional model of stress and coping.

Recent studies in the oncology literature have shown that spirituality, defined as the combination of existential and religious well-being (RWB), is related to both emotional well-being and quality of life. Indeed, spirituality may be particularly important in coping with the potential life threat of the disease. Based on Frankl's (1963) existential theory, in this study, we examined whether the relations between spirituality and emotional well-being are moderated by degree of perceived life threat (PLT). In addition, in this study, we examined the relative importance of religious versus existential well-being in relation to psychological adjustment. Patients diagnosed with various types of cancer (N = 95) completed questionnaires assessing spirituality, PLT, quality of life, and distress. Contrary to theoretical predictions, spirituality was associated with less distress and better quality of life regardless of PLT. Interestingly, existential but not RWB accounted for a major portion of the variance in these outcomes. Taken together, these findings suggest that spirituality, particularly the existential component, may be associated with reduced symptoms of distress in cancer patients regardless of life threat.