Childhood asthma diagnoses declined during the COVID-19 pandemic in the United States.

BACKGROUND: Prior studies have documented declines in pediatric asthma exacerbations and asthma-related health care utilization during the COVID-19 pandemic, but less is known about the incidence of asthma during the pandemic. METHODS: We conducted a retrospective cohort study of children under age 18 without a prior diagnosis of asthma within a large US commercial claims database. Incident asthma was defined using a combination of diagnosis codes, location of services, and medication dispensing. Crude quarterly rates of asthma diagnosis per 1000 children were calculated, and the incidence rate ratio and 95% confidence interval were estimated for newly diagnosed asthma during versus before the pandemic using negative binomial regression, adjusted for age, sex, region, and season. RESULTS: Compared with 3 years prior to the pandemic, crude incident diagnosis rates of asthma decreased by 52% across the first four quarters of the US pandemic. The covariate-adjusted pandemic-associated incidence rate ratio was 0.47 (95% confidence interval 0.43, 0.51). CONCLUSIONS: New diagnoses of childhood asthma in the US declined by half during the first year of the pandemic. These findings raise important questions whether pandemic-related changes in infectious or other triggers truly altered the incidence of childhood asthma beyond the well-described disruptions in healthcare access.

Impact of the COVID-19 Pandemic on the Management of Juvenile Idiopathic Arthritis: Analysis of United States Commercial Insurance Data.

BACKGROUND/OBJECTIVE: Given limited information on health care and treatment utilization for juvenile idiopathic arthritis (JIA) during the pandemic, we studied JIA-related health care and treatment utilization in a commercially insured retrospective US cohort. METHODS: We studied rates of outpatient visits, new disease-modifying antirheumatic drug (DMARD) initiations, intra-articular glucocorticoid injections (iaGC), dispensed oral glucocorticoids and opioids, DMARD adherence, and DMARD discontinuation by quarter in March 2018-February 2021 (Q1 started in March). Incident rate ratios (IRR, pandemic vs prepandemic) with 95% confidence intervals (CIs) were estimated using multivariable Poisson or Quasi-Poisson models stratified by diagnosis recency (incident JIA, <12 months ago; prevalent JIA, ≥12 months ago). RESULTS: Among 1294 children diagnosed with JIA, total and in-person outpatient visits for JIA declined during the pandemic (IRR, 0.88-0.90), most markedly in Q1 2020. Telemedicine visits, while higher during the pandemic, declined from 21% (Q1) to 13% (Q4) in 2020 to 2021. During the pandemic, children with prevalent JIA, but not incident JIA, had lower usage of iaGC (IRR, 0.60; 95% CI, 0.34-1.07), oral glucocorticoids (IRR, 0.47; 95% CI, 0.33-0.67), and opioids (IRR, 0.44; 95% CI, 0.26-0.75). Adherence to and discontinuation of DMARDs was similar before and during the pandemic. CONCLUSIONS: In the first year of the pandemic, visits for JIA dropped by 10% to 12% in commercially insured children in the United States, declines partly mitigated by use of telemedicine. Pandemic-related declines in intra-articular glucocorticoids, oral glucocorticoids, and opioids were observed for children with prevalent, but not incident, JIA. These changes may have important implications for disease control and quality of life.

Lithium treatment and risk for dementia in adults with bipolar disorder: population-based cohort study.

BackgroundLithium inhibits glycogen synthase kinase-3, an enzyme implicated in the pathogenesis of dementia.AimsTo examine the association of lithium and dementia risk in a large claims-based US cohort of publicly insured older adults with bipolar disorder.MethodThe cohort included individuals ≥50 years diagnosed with bipolar disorder who did not receive dementia-related services during the prior year. Each follow-up day was classified by past-year cumulative duration of lithium use (0, 1-60, 61-300 and 301-365 days). Dementia diagnosis was the study outcome. Anticonvulsants commonly used as mood stabilisers served as a negative control.ResultsCompared with non-use, 301-365 days of lithium exposure was associated with significantly reduced dementia risk (hazard ratio (HR) = 0.77, 95% CI 0.60-0.99). No corresponding association was observed for shorter lithium exposures (HR = 1.04, 95% CI 0.83-1.31 for 61-300 days; HR = 1.07, 95% CI 0.67-1.71 for 1-60 days) or for any exposure to anticonvulsants.ConclusionsContinuous lithium treatment may reduce dementia risk in older adults with bipolar disorder.

Multi-country rapid adverse drug event assessment: the Asian Pharmacoepidemiology Network (AsPEN) antipsychotic and acute hyperglycaemia study.

PURPOSE: To undertake a multi-country study to investigate the risk of acute hyperglycaemia with antipsychotic use. METHODS: Using a distributed network model with a common minimal data set, we performed a prescription sequence symmetry analysis (PSSA) to investigate the risk of acute hyperglycaemia associated with antipsychotic initiation. Incident insulin prescriptions were used as a proxy indicator of acute hyperglycaemia. Participating countries and population datasets included Australia (300,000 persons), Japan I (300,000 persons), Japan II (200,000 persons), Korea (53 million persons) Taiwan (1 million persons), Sweden (9 million persons), USA-Public (87 million persons) and USA-Private (47 million persons). RESULTS: Olanzapine showed a trend towards increased risk in most databases, with a significant association observed in the USA-Public database (Adjusted sequence ratio (ASR) = 1.14; 95% Confidence Interval (CI) 1.10-1.17) and Sweden (ASR = 1.53; 95% CI 1.13-2.06). Null or negative associations were observed for haloperidol, quetiapine and risperidone. CONCLUSION: Acute hyperglycaemia appears to be associated with olanzapine use, however, this effect was only observed in two large databases. Despite different patterns of utilization of both antipsychotics and insulin, PSSA analysis results for individual antipsychotic medicines were qualitatively similar across most countries. PSSA, used in conjunction with existing methods, may provide a simple and timely method further supporting multi-national drug safety monitoring.

"Are You Safe at Home?": Clinician's Assessments for Intimate Partner Violence at the Initial Obstetric Visit.

Few studies have empirically examined patient-clinician conversations to assess how intimate partner violence (IPV) screening is performed. Our study sought to examine audio-recorded first obstetric encounters' IPV screening conversations to describe and categorize communication approaches and explore associations with patient disclosure. We analyzed 247 patient encounters with 47 providers. IPV screening occurred in 95% of visits: 57% used direct questions, 25% used indirect questions, 17% repeated IPV screening later in the visit, 11% framed questions with a reason for asking, and 10% described IPV types. Patients disclosed IPV in 71 (28.7%) visits. There were no associations between disclosure and any categories of IPV screening.

Antidepressant treatment and adherence to antiretroviral medications among privately insured persons with HIV/AIDS.

In order to examine relationships between depression treatments (antidepressant and/or psychotherapy utilization) and adherence to antiretroviral therapy (ART), we conducted a retrospective analysis of medical and pharmacy insurance claims for privately insured persons living with HIV/AIDS (PLWHA) diagnosed with depression (n = 1,150). Participants were enrolled in 80 insurance plans from all 50 states. Adherence was suboptimal. Depression treatment initiators were significantly more likely to be adherent to ART than the untreated. We did not observe an association between psychotherapy utilization and ART adherence, yet given the limitations of the data (e.g., there is no information on types of psychological treatment and its targets), the lack of association should not be interpreted as lack of efficacy.

Suicide Risk in Medicare Patients With Schizophrenia Across the Life Span.

Importance: Although adults with schizophrenia have an increased risk of suicide, sample size limitations of previous research have hindered characterizations of suicide risk across the life span. Objective: To describe suicide mortality rates and correlates among adults with schizophrenia across the life span and standardized mortality ratios (SMRs) for suicide compared with the general US population. Design, Setting, and Participants: Five national retrospective longitudinal cohorts of patients with schizophrenia in the Medicare program from January 1, 2007, to December 31, 2016, were identified by age: 18 to 34, 35 to 44, 45 to 54, 55 to 64, and 65 years or older. Death record information was obtained from the National Death Index. The total cohort included 668 836 Medicare patients with schizophrenia, 2 997 308 years of follow-up, and 2218 suicide deaths. Data were analyzed from September 30, 2020, to March 10, 2021. Main Outcomes and Measures: For each age group, suicide mortality rates per 100 000 person-years and adjusted hazard ratios (aHRs) with 95% CIs of suicide were determined. Suicide SMRs were estimated for the total cohort and by sex and age cohorts standardized to the general US population by age, sex, and race/ethnicity. Results: The study population of adults 18 years and older included 668 836 Medicare recipients with schizophrenia (52.5% men, 47.5% women). The total suicide rate per 100 000 person-years was 74.00, which is 4.5 times higher than that for the general US population (SMR, 4.54; 95% CI, 4.35-4.73) and included a rate of 88.96 for men and 56.33 for women, which are 3.4 (SMR, 3.39; 95% CI, 3.22-3.57) and 8.2 (SMR, 8.16; 95% CI, 7.60-8.75) times higher, respectively, than the rates for the general US population. Suicide rates were significantly higher for men (aHR, 1.44; 95% CI, 1.29-1.61) and those with depressive (aHR, 1.32; 95% CI, 1.17-1.50), anxiety (aHR, 1.15; 95% CI, 1.02-1.30), drug use (aHR, 1.55; 95% CI, 1.36-1.76), and sleep disorders (aHR, 1.22; 95% CI, 1.07-1.39), suicidal ideation (aHR, 1.41; 95% CI, 1.22-1.63), and suicide attempts or self-injury (aHR, 2.48; 95% CI, 2.06-2.98). The adjusted hazards of suicide were lower for Hispanic patients (aHR, 0.66; 95% CI, 0.54-0.80) or Black patients (aHR, 0.29; 95% CI, 0.24-0.35) than White patients. The suicide rate declined with age, from 141.95 (SMR, 10.19; 95% CI, 9.29-11.18) for patients aged 18 to 34 years to 24.01 (SMR, 1.53; 95% CI, 1.32-1.77) for patients 65 years or older. The corresponding declines per 100 000 person-years were from 153.80 (18-34 years of age) to 34.17 (65 years or older) for men and from 115.70 (18-34 years of age) to 18.66 (65 years or older) for women. In the group aged 18 to 34 years, the adjusted hazards of suicide risk were significantly increased for patients with suicide attempt or self-injury (aHR, 2.57; 95% CI, 18.20-2.04) and with comorbid drug use disorders (aHR, 1.48; 95% CI, 1.17-1.88), but not with comorbid depressive disorders (aHR, 0.99; 95% CI, 0.38-1.26) during the year before the start of follow-up. Conclusions and Relevance: In this cohort study of adult Medicare patients with schizophrenia, suicide risk was elevated, with the highest absolute and relative risk among young adults. These patterns support suicide prevention efforts with a focus on young adults with schizophrenia, especially those with suicidal symptoms and substance use.

Mortality Risk of Antipsychotic Augmentation for Adult Depression.

(Reprinted with permission from PLOS ONE 2020).

Age-Specific Prevalence and Incidence of Dementia Diagnoses Among Older US Adults With Schizophrenia.

Importance: People with schizophrenia are at high risk of receiving a diagnosis of dementia. Understanding the magnitude and timing of this increased risk has important implications for practice and policy. Objective: To estimate the age-specific incidence and prevalence of dementia diagnoses among older US adults with schizophrenia and in a comparison group without serious mental illness (SMI). Design, Setting, and Participants: This retrospective cohort study used a 50% random national sample of Medicare beneficiaries 66 years or older with fee-for-service plans and Part D prescription drug coverage from January 1, 2007, to December 31, 2017. The cohort with schizophrenia included adults with at least 12 months of continuous enrollment in fee-for-service Medicare and Part D and at least 2 outpatient claims or at least 1 inpatient claim for schizophrenia during the qualifying years. The comparison group included adults with at least 12 months of continuous enrollment in fee-for-service Medicare and Part D and without a diagnosis of schizophrenia, bipolar disorder, or recurrent major depressive disorder during the qualifying year. Data were analyzed from January 1 to July 31, 2020. Main Outcomes and Measures: Dementia was defined using the Centers for Medicare & Medicaid Services Chronic Conditions Warehouse diagnosis codes for Alzheimer disease and related disorders or senile dementia. Incident diagnoses were defined by at least 12 consecutive eligible months without a qualifying code before meeting dementia criteria. Results: The study population of 8 011 773 adults 66 years or older (63.4% women; mean [SD] age, 74.0 [8.2] years) included 74 170 individuals with a diagnosis of schizophrenia (56.6% women) and 7 937 603 without an SMI diagnosis (63.5% women) who contributed 336 814 and 55 499 543 person-years of follow-up, respectively. At 66 years of age, the prevalence of diagnosed dementia was 27.9% (17 640 of 63 287) among individuals with schizophrenia compared with 1.3% (31 295 of 2 389 512) in the group without SMI. By 80 years of age, the prevalence of dementia diagnoses was 70.2% (2011 of 2866) in the group with schizophrenia and 11.3% (242 094 of 2 134 602) in the group without SMI. The annual incidence of dementia diagnoses per 1000 person-years at 66 years of age was 52.5 (95% CI, 50.1-54.9) among individuals with schizophrenia and 4.5 (95% CI, 4.4-4.6) among individuals without SMI and increased to 216.2 (95% CI, 179.9-252.6) and 32.3 (95% CI, 32.0-32.6), respectively, by 80 years of age. Conclusions and Relevance: In this cohort study, compared with older adults without SMI, those with schizophrenia had increased risk of receiving a diagnosis of dementia across a wide age range, possibly because of cognitive and functional deterioration related to schizophrenia or factors contributing to other types of dementia. High rates of dementia among adults with schizophrenia have implications for the course of illness, treatment, and service use.

Hepatic Sensing Loop Regulates PCSK9 Secretion in Response to Inhibitory Antibodies.

BACKGROUND: Monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9i) lower LDL-C by up to 60% and increase plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels by 10-fold. OBJECTIVES: The authors studied the reasons behind the robust increase in plasma PCSK9 levels by testing the hypothesis that mechanisms beyond clearance via the low-density lipoprotein receptor (LDLR) contribute to the regulation of cholesterol homeostasis. METHODS: In clinical cohorts, animal models, and cell-based studies, we measured kinetic changes in PCSK9 production and clearance in response to PCSK9i. RESULTS: In a patient cohort receiving PCSK9i therapy, plasma PCSK9 levels rose 11-fold during the first 3 months and then plateaued for 15 months. In a cohort of healthy volunteers, a single injection of PCSK9i increased plasma PCSK9 levels within 12 hours; the rise continued for 9 days until it plateaued at 10-fold above baseline. We recapitulated the rapid rise in PCSK9 levels in a mouse model, but only in the presence of LDLR. In vivo turnover and in vitro pulse-chase studies identified 2 mechanisms contributing to the rapid increase in plasma PCSK9 levels in response to PCSK9i: 1) the expected delayed clearance of the antibody-bound PCSK9; and 2) the unexpected post-translational increase in PCSK9 secretion. CONCLUSIONS: PCSK9 re-entry to the liver via LDLR triggers a sensing loop regulating PCSK9 secretion. PCSK9i therapy enhances the secretion of PCSK9, an effect that contributes to the increased plasma PCSK9 levels in treated subjects.

Pre-existing cardiovascular conditions and pharmacological treatment of adult ADHD.

BACKGROUND: Stimulants and atomoxetine should generally not be used or used only with caution in adults with pre-existing cardiovascular conditions. The extent to which pre-existing cardiovascular conditions influence initiation of these ADHD medications in adults is not known. METHODS: We performed a retrospective cohort study of privately insured adults with new ADHD treatment episodes. Pre-existing cardiovascular conditions were assessed by the presence of ICD-9-CM codes for congenital abnormalities, atherosclerosis, cardiac disease, and cerebrovascular disease in the 12 months before the index ADHD diagnosis. The primary outcome was new initiation of a stimulant or atomoxetine in the 3 months after the index date. Multivariate logistic regression was used to predict the likelihood of treatment initiation with stimulants or atomoxetine based on pre-existing cardiovascular conditions, patient demographic characteristics, clinical mental disorder comorbidities, other psychotropic drug use, and provider type. RESULTS: Of 8752 patients with a new ADHD treatment episode, 917 (10.5%) had evidence of >or=1 pre-existing cardiovascular condition. Stimulants were started by 40.8% of patients with and 53.0% of patients without pre-existing cardiovascular conditions (Adjusted Odds Ratio, AOR 0.71; 95%CI 0.61-0.82). Pre-existing cardiovascular conditions reduced the likelihood of initiating stimulant treatment in younger but not in older patients (p-value for age x cardiovascular condition interaction = 0.0002). Initiation of atomoxetine treatment was not affected by pre-existing cardiovascular conditions (AOR 1.19, 95%CI 0.94-1.50). CONCLUSIONS: Pre-existing cardiovascular conditions reduce the likelihood of stimulant therapy but not atomoxetine treatment in adult ADHD patients. However, many adult ADHD patients with pre-existing cardiovascular conditions initiate stimulant therapy.

Mortality risk of antipsychotic augmentation for adult depression.

IMPORTANCE: Randomized controlled trials have demonstrated increased all-cause mortality in elderly patients with dementia treated with newer antipsychotics. It is unknown whether this risk generalizes to non-elderly adults using newer antipsychotics as augmentation treatment for depression. OBJECTIVE: This study examined all-cause mortality risk of newer antipsychotic augmentation for adult depression. DESIGN: Population-based new-user/active comparator cohort study. SETTING: National healthcare claims data from the US Medicaid program from 2001-2010 linked to the National Death Index. PARTICIPANTS: Non-elderly adults (25-64 years) diagnosed with depression who after ≥3 months of antidepressant monotherapy initiated either augmentation with a newer antipsychotic or with a second antidepressant. Patients with alternative indications for antipsychotic medications, such as schizophrenia, psychotic depression, or bipolar disorder, were excluded. EXPOSURE: Augmentation treatment for depression with a newer antipsychotic or with a second antidepressant. MAIN OUTCOME: All-cause mortality during study follow-up ascertained from the National Death Index. RESULTS: The analytic cohort included 39,582 patients (female = 78.5%, mean age = 44.5 years) who initiated augmentation with a newer antipsychotic (n = 22,410; 40% = quetiapine, 21% = risperidone, 17% = aripiprazole, 16% = olanzapine) or with a second antidepressant (n = 17,172). The median chlorpromazine equivalent starting dose for all newer antipsychotics was 68mg/d, increasing to 100 mg/d during follow-up. Altogether, 153 patients died during 13,328 person-years of follow-up (newer antipsychotic augmentation: n = 105, follow-up = 7,601 person-years, mortality rate = 138.1/10,000 person-years; antidepressant augmentation: n = 48, follow-up = 5,727 person-years, mortality rate = 83.8/10,000 person-years). An adjusted hazard ratio of 1.45 (95% confidence interval, 1.02 to 2.06) indicated increased all-cause mortality risk for newer antipsychotic augmentation compared to antidepressant augmentation (risk difference = 37.7 (95%CI, 1.7 to 88.8) per 10,000 person-years). Results were robust across several sensitivity analyses. CONCLUSION: Augmentation with newer antipsychotics in non-elderly patients with depression was associated with increased mortality risk compared with adding a second antidepressant. Though these findings require replication and cannot prove causality, physicians managing adults with depression should be aware of this potential for increased mortality associated with newer antipsychotic augmentation.

Comparative Effectiveness of Adjunctive Psychotropic Medications in Patients With Schizophrenia.

Importance: People with schizophrenia are commonly treated with psychotropic medications in addition to antipsychotics, but there is little evidence about the comparative effectiveness of these adjunctive treatment strategies. Objective: To study the comparative real-world effectiveness of adjunctive psychotropic treatments for patients with schizophrenia. Design, Setting, and Participants: This comparative effectiveness study used US national Medicaid data from January 1, 2001, to December 31, 2010, to examine the outcomes of initiating treatment with an antidepressant, a benzodiazepine, a mood stabilizer, or another antipsychotic among adult outpatients (aged 18-64 years) diagnosed with schizophrenia who were stably treated with a single antipsychotic. Data analysis was performed from January 1, 2017, to June 30, 2018. Multinomial logistic regression models were used to estimate propensity scores to balance covariates across the 4 medication groups. Weighted Cox proportional hazards regression models were used to compare treatment outcomes during 365 days on an intention-to-treat basis. Main Outcomes and Measures: Risk of hospitalization for a mental disorder (primary), emergency department (ED) visits for a mental disorder, and all-cause mortality. Results: The study cohort included 81 921 adult outpatients diagnosed with schizophrenia (mean [SD] age, 40.7 [12.4] years; 37 515 women [45.8%]) who were stably treated with a single antipsychotic and then initiated use of an antidepressant (n = 31 117), a benzodiazepine (n = 11 941), a mood stabilizer (n = 12 849), or another antipsychotic (n = 26 014) (reference treatment). Compared with initiating use of another antipsychotic, initiating use of an antidepressant was associated with a lower risk (hazard ratio [HR], 0.84; 95% CI, 0.80-0.88) of psychiatric hospitalization, whereas initiating use of a benzodiazepine was associated with a higher risk (HR, 1.08; 95% CI, 1.02-1.15); the risk associated with initiating use of a mood stabilizer (HR, 0.98; 95% CI, 0.94-1.03) was not significantly different from initiating use of another antipsychotic. A similar pattern of associations was observed in psychiatric ED visits for initiating use of an antidepressant (HR, 0.92; 95% CI, 0.88-0.96), a benzodiazepine (HR, 1.12; 95% CI, 1.07-1.19), and a mood stabilizer (HR, 0.99; 95% CI, 0.94-1.04). Initiating use of a mood stabilizer was associated with an increased risk of mortality (HR, 1.31; 95% CI, 1.04-1.66). Conclusions and Relevance: In the treatment of schizophrenia, initiating adjunctive treatment with an antidepressant was associated with reduced risk of psychiatric hospitalization and ED visits compared with initiating use of alternative psychotropic medications. Associations of benzodiazepines and mood stabilizers with poorer outcomes warrant clinical caution and further investigation.

Antipsychotic Medication Treatment Patterns in Adult Depression.

OBJECTIVE: To characterize the role of antipsychotic medications in the community treatment of adult depression. METHODS: We identified adults (aged 18-64 years) with new episodes of depression treatment (ICD-9-CM 296.2, 296.3, 300.4, or 311) in US national Medicaid data (2001-2010). Patients with alternative ICD-9-CM antipsychotic indications, such as schizophrenia or bipolar disorder, were excluded. Each patient was followed for at least 1 year to characterize antipsychotic and antidepressant treatment and emerging alternative antipsychotic indications. For patients without alternative indications through day 45 following start of antipsychotic treatment, antipsychotics were considered to be intended for treatment of depression. Among this group, we determined whether antipsychotic initiation was preceded by minimally adequate treatment with antidepressants, defined as active antidepressant treatment for ≥ 31 days prior to and including the day of antipsychotic initiation. RESULTS: Within 1 year following onset, 14.0% of patients started an antipsychotic medication. A total of 41.3% of antipsychotic initiators developed an antipsychotic indication other than depression through day 45 following antipsychotic initiation, most often bipolar disorder or depression with psychotic features. The remaining 58.7% of antipsychotic initiators presumably started antipsychotics for nonpsychotic depression. Of these, 71.3% did not have minimally adequate antidepressant treatment prior to starting the antipsychotic medication. CONCLUSION: Antipsychotic medications are used in approximately 1 in 7 patients with a new episode of depression. For 1 in 12 patients, the antipsychotic was considered to be intended for nonpsychotic depression. Almost three-quarters of these patients did not receive minimally adequate treatment with antidepressants prior to antipsychotic initiation. This pattern suggests potentially inappropriate and premature initiation of a drug class with substantial adverse effects and medical risks.

Psychotropic Medication Use Among Adults With Schizophrenia and Schizoaffective Disorder in the United States.

OBJECTIVE: The authors examined the use of different classes of psychotropic medication in outpatient treatment of schizophrenia and schizoaffective disorder. METHODS: Data from the United States Medicaid program were used to examine psychotropic medication use in a cohort of patients who had a diagnosis of schizophrenia or schizoaffective disorder in the calendar year 2010. RESULTS: The cohort of Medicaid recipients who filled one or more prescriptions for a psychotropic medication in 2010 included 116,249 patients classified as having schizophrenia and 84,537 classified as having schizoaffective disorder. During 2010, 86.1% of patients with schizoaffective disorder and 70.1% with schizophrenia were treated with two or more different classes of psychotropic. CONCLUSIONS: Psychotropic medications other than antipsychotics were commonly prescribed for individuals with a diagnosis of schizophrenia or schizoaffective disorder. Their widespread use and uncertainty about their net benefits signal a need for research on their efficacy, safety, and appropriate use in these conditions.

Comparative Effectiveness of Clozapine and Standard Antipsychotic Treatment in Adults With Schizophrenia.

OBJECTIVE: The authors compared the effectiveness of initiating treatment with either clozapine or a standard antipsychotic among adults with evidence of treatment-resistant schizophrenia in routine clinical practice. METHOD: U.S. national Medicaid data from 2001 to 2009 were used to examine treatment outcomes in a cohort of patients with schizophrenia and evidence of treatment resistance that initiated clozapine (N=3,123) and in a propensity score-matched cohort that initiated a standard antipsychotic (N=3,123). Interventions were new initiation of clozapine or a standard antipsychotic medication, defined as no exposure to the new medication in the prior 365 days. The primary outcome was hospital admission for a mental disorder. Secondary outcomes included discontinuation of the index antipsychotic, use of an additional antipsychotic, incidence of serious medical conditions, and mortality. RESULTS: Initiation of clozapine was associated with a significantly decreased rate of psychiatric hospital admission (hazard ratio=0.78, 95% CI=0.69-0.88), index antipsychotic discontinuation (hazard ratio=0.60, 95% CI=0.55-0.65), and use of an additional antipsychotic (hazard ratio=0.76, 95% CI=0.70-0.82). Clozapine was associated with significantly increased incidence of diabetes mellitus (2.8% for clozapine vs. 1.4% for standard antipsychotic; hazard ratio=1.63, 95% CI=0.98-2.70), hyperlipidemia (12.9% for clozapine vs. 8.5% for standard antipsychotic; hazard ratio=1.40, 95%CI=1.09-1.78), and intestinal obstruction (0.9% for clozapine vs. 0.3% for standard antipsychotic; hazard ratio=2.50, 95% CI=0.97-6.44). CONCLUSIONS: In adults with schizophrenia and evidence of treatment resistance, initiating clozapine compared with initiating a standard antipsychotic was associated with greater effectiveness on several important outcomes. Increasing the judicious use of clozapine is warranted together with vigilance to prevent and detect serious medical adverse effects.

The Quality of Medication Treatment for Mental Disorders in the Department of Veterans Affairs and in Private-Sector Plans.

OBJECTIVE: The quality of mental health care provided by the U.S. Department of Veterans Affairs (VA) was compared with care provided to a comparable population treated in the private sector. METHODS: Two cohorts of individuals with mental disorders (schizophrenia, bipolar disorder, posttraumatic stress disorder, major depression, and substance use disorders) were created with VA administrative data (N=836,519) and MarketScan data (N=545,484). The authors computed VA and MarketScan national means for seven process-based quality measures related to medication evaluation and management and estimated national-level performance by age and gender. RESULTS: In every case, VA performance was superior to that of the private sector by more than 30%. Compared with individuals in private plans, veterans with schizophrenia or major depression were more than twice as likely to receive appropriate initial medication treatment, and veterans with depression were more than twice as likely to receive appropriate long-term treatment. CONCLUSIONS: Findings demonstrate the significant advantages that accrue from an organized, nationwide system of care. The much higher performance of the VA has important clinical and policy implications.

Premature Mortality Among Adults With Schizophrenia in the United States.

IMPORTANCE: Although adults with schizophrenia have a significantly increased risk of premature mortality, sample size limitations of previous research have hindered the identification of the underlying causes. OBJECTIVE: To describe overall and cause-specific mortality rates and standardized mortality ratios (SMRs) for adults with schizophrenia compared with the US general population. DESIGN, SETTING, AND PARTICIPANTS: We identified a national retrospective longitudinal cohort of patients with schizophrenia 20 to 64 years old in the Medicaid program (January 1, 2001, to December 31, 2007). The cohort included 1,138,853 individuals, 4,807,121 years of follow-up, and 74,003 deaths, of which 65,553 had a known cause. MAIN OUTCOMES AND MEASURES: Mortality ratios for the schizophrenia cohort standardized to the general population with respect to age, sex, race/ethnicity, and geographic region were estimated for all-cause and cause-specific mortality. Mortality rates per 100,000 person-years and the mean years of potential life lost per death were also determined. Death record information was obtained from the National Death Index. RESULTS: Adults with schizophrenia were more than 3.5 times (all-cause SMR, 3.7; 95% CI, 3.7-3.7) as likely to die in the follow-up period as were adults in the general population. Cardiovascular disease had the highest mortality rate (403.2 per 100,000 person-years) and an SMR of 3.6 (95% CI, 3.5-3.6). Among 6 selected cancers, lung cancer had the highest mortality rate (74.8 per 100,000 person-years) and an SMR of 2.4 (95% CI, 2.4-2.5). Particularly elevated SMRs were observed for chronic obstructive pulmonary disease (9.9; 95% CI, 9.6-10.2) and influenza and pneumonia (7.0; 95% CI, 6.7-7.4). Accidental deaths (119.7 per 100,000 person-years) accounted for more than twice as many deaths as suicide (52.0 per 100,000 person-years). Nonsuicidal substance-induced death, mostly from alcohol or other drugs, was also a leading cause of death (95.2 per 100,000 person-years). CONCLUSIONS AND RELEVANCE: In a US national cohort of adults with schizophrenia, excess deaths from cardiovascular and respiratory diseases implicate modifiable cardiovascular risk factors, including especially tobacco use. Excess deaths directly attributable to alcohol or other drugs highlight threats posed by substance abuse. More aggressive identification and management of cardiovascular risk factors, as well as reducing tobacco use and substance abuse, should be leading priorities in the medical care of adults with schizophrenia.