Amy B. Goldstein

Comprehensive Versus Usual Community Care for First-Episode Psychosis: 2-Year Outcomes From the NIMH RAISE Early Treatment Program

OBJECTIVE The primary aim of this study was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first-episode psychosis designed for implementation in the U.S. health care system, with community care on quality of life. METHOD Thirty-four clinics in 21 states were randomly assigned to NAVIGATE or community care. Diagnosis, duration of untreated psychosis, and clinical outcomes were assessed via live, two-way video by remote, centralized raters masked to study design and treatment. Participants (mean age, 23) with schizophrenia and related disorders and ≤6 months of antipsychotic treatment (N=404) were enrolled and followed for ≥2 years. The primary outcome was the total score of the Heinrichs-Carpenter Quality of Life Scale, a measure that includes sense of purpose, motivation, emotional and social interactions, role functioning, and engagement in regular activities. RESULTS The 223 recipients of NAVIGATE remained in treatment longer, experienced greater improvement in quality of life and psychopathology, and experienced greater involvement in work and school compared with 181 participants in community care. The median duration of untreated psychosis was 74 weeks. NAVIGATE participants with duration of untreated psychosis of <74 weeks had greater improvement in quality of life and psychopathology compared with those with longer duration of untreated psychosis and those in community care. Rates of hospitalization were relatively low compared with other first-episode psychosis clinical trials and did not differ between groups. CONCLUSIONS Comprehensive care for first-episode psychosis can be implemented in U.S. community clinics and improves functional and clinical outcomes. Effects are more pronounced for those with shorter duration of untreated psychosis.

Cardiometabolic Risk in Patients With First-Episode Schizophrenia Spectrum Disorders Baseline Results From the RAISE-ETP Study

IMPORTANCE The fact that individuals with schizophrenia have high cardiovascular morbidity and mortality is well established. However, risk status and moderators or mediators in the earliest stages of illness are less clear. OBJECTIVE To assess cardiometabolic risk in first-episode schizophrenia spectrum disorders (FES) and its relationship to illness duration, antipsychotic treatment duration and type, sex, and race/ethnicity. DESIGN, SETTING, AND PARTICIPANTS Baseline results of the Recovery After an Initial Schizophrenia Episode (RAISE) study, collected between July 22, 2010, and July 5, 2012, from 34 community mental health facilities without major research, teaching, or clinical FES programs. Patients were aged 15 to 40 years, had research-confirmed diagnoses of FES, and had less than 6 months of lifetime antipsychotic treatment. EXPOSURE Prebaseline antipsychotic treatment was based on the community clinicians and/or patients decision. MAIN OUTCOMES AND MEASURES Body composition and fasting lipid, glucose, and insulin parameters. RESULTS In 394 of 404 patients with cardiometabolic data (mean [SD] age, 23.6 [5.0] years; mean [SD] lifetime antipsychotic treatment, 47.3 [46.1] days), 48.3% were obese or overweight, 50.8% smoked, 56.5% had dyslipidemia, 39.9% had prehypertension, 10.0% had hypertension, and 13.2% had metabolic syndrome. Prediabetes (glucose based, 4.0%; hemoglobin A1c based, 15.4%) and diabetes (glucose based, 3.0%; hemoglobin A1c based, 2.9%) were less frequent. Total psychiatric illness duration correlated significantly with higher body mass index, fat mass, fat percentage, and waist circumference (all P<.01) but not elevated metabolic parameters (except triglycerides to HDL-C ratio [P=.04]). Conversely, antipsychotic treatment duration correlated significantly with higher non-HDL-C, triglycerides, and triglycerides to HDL-C ratio and lower HDL-C and systolic blood pressure (all P≤.01). In multivariable analyses, olanzapine was significantly associated with higher triglycerides, insulin, and insulin resistance, whereas quetiapine fumarate was associated with significantly higher triglycerides to HDL-C ratio (all P≤.02). CONCLUSIONS AND RELEVANCE In patients with FES, cardiometabolic risk factors and abnormalities are present early in the illness and likely related to the underlying illness, unhealthy lifestyle, and antipsychotic medications, which interact with each other. Prevention of and early interventions for psychiatric illness and treatment with lower-risk agents, routine antipsychotic adverse effect monitoring, and smoking cessation interventions are needed from the earliest illness phases.

Suicide Prevention in an Emergency Department Population: The ED-SAFE Study

Importance Suicide is a leading cause of deaths in the United States. Although the emergency department (ED) is an opportune setting for initiating suicide prevention efforts, ED-initiated suicide prevention interventions remain underdeveloped. Objective To determine whether an ED-initiated intervention reduces subsequent suicidal behavior. Design, Setting, and Participants This multicenter study of 8 EDs in the United States enrolled adults with a recent suicide attempt or ideation and was composed of 3 sequential phases: (1) a treatment as usual (TAU) phase from August 2010 to December 2011, (2) a universal screening (screening) phase from September 2011 to December 2012, and (3) a universal screening plus intervention (intervention) phase from July 2012 to November 2013. Interventions Screening consisted of universal suicide risk screening. The intervention phase consisted of universal screening plus an intervention, which included secondary suicide risk screening by the ED physician, discharge resources, and post-ED telephone calls focused on reducing suicide risk. Main Outcomes and Measures The primary outcome was suicide attempts (nonfatal and fatal) over the 52-week follow-up period. The proportion and total number of attempts were analyzed. Results A total of 1376 participants were recruited, including 769 females (55.9%) with a median (interquartile range) age of 37 (26-47) years. A total of 288 participants (20.9%) made at least 1 suicide attempt, and there were 548 total suicide attempts among participants. There were no significant differences in risk reduction between the TAU and screening phases (23% vs 22%, respectively). However, compared with the TAU phase, patients in the intervention phase showed a 5% absolute reduction in suicide attempt risk (23% vs 18%), with a relative risk reduction of 20%. Participants in the intervention phase had 30% fewer total suicide attempts than participants in the TAU phase. Negative binomial regression analysis indicated that the participants in the intervention phase had significantly fewer total suicide attempts than participants in the TAU phase (incidence rate ratio, 0.72; 95% CI, 0.52-1.00; P = .05) but no differences between the TAU and screening phases (incidence rate ratio, 1.00; 95% CI, 0.71-1.41; P = .99). Conclusions and Relevance Among at-risk patients in the ED, a combination of brief interventions administered both during and after the ED visit decreased post-ED suicidal behavior.

Prescription Practices in the Treatment of First-Episode Schizophrenia Spectrum Disorders: Data From the National RAISE-ETP Study

OBJECTIVE Treatment guidelines suggest distinctive medication strategies for first-episode and multiepisode patients with schizophrenia. To assess the extent to which community clinicians adjust their usual treatment regimens for first-episode patients, the authors examined prescription patterns and factors associated with prescription choice in a national cohort of early-phase patients. METHOD Prescription data at study entry were obtained from 404 participants in the Recovery After an Initial Schizophrenia Episode Projects Early Treatment Program (RAISE-ETP), a nationwide multisite effectiveness study for patients with first-episode schizophrenia spectrum disorders. Treatment with antipsychotics did not exceed 6 months at study entry. RESULTS The authors identified 159 patients (39.4% of the sample) who might benefit from changes in their psychotropic prescriptions. Of these, 8.8% received prescriptions for recommended antipsychotics at higher than recommended dosages; 32.1% received prescriptions for olanzapine (often at high dosages), 23.3% for more than one antipsychotic, 36.5% for an antipsychotic and also an antidepressant without a clear indication, 10.1% for psychotropic medications without an antipsychotic, and 1.2% for stimulants. Multivariate analysis showed evidence for sex, age, and insurance status effects on prescription practices. Racial and ethnic effects consistent with effects reported in previous studies of multiepisode patients were found in univariate analyses. Despite some regional variations in prescription practices, no region consistently had different practices from the others. Diagnosis had limited and inconsistent effects. CONCLUSIONS Besides prescriber education, policy makers may need to consider not only patient factors but also service delivery factors in efforts to improve prescription practices for first-episode schizophrenia patients.

Duration of Untreated Psychosis in Community Treatment Settings in the United States

OBJECTIVE This study is the first to examine duration of untreated psychosis (DUP) among persons receiving care in community mental health centers in the United States. METHODS Participants were 404 individuals (ages 15-40) who presented for treatment for first-episode psychosis at 34 nonacademic clinics in 21 states. DUP and individual- and site-level variables were measured. RESULTS Median DUP was 74 weeks (mean=193.5±262.2 weeks; 68% of participants had DUP of greater than six months). Correlates of longer DUP included earlier age at first psychotic symptoms, substance use disorder, positive and general symptom severity, poorer functioning, and referral from outpatient treatment settings. CONCLUSIONS This study reported longer DUP than studies conducted in academic settings but found similar correlates of DUP. Reducing DUP in the United States will require examination of factors in treatment delay in local service settings and targeted strategies for closing gaps in pathways to specialty FEP care.

Improving Suicide Risk Screening and Detection in the Emergency Department

INTRODUCTION The Emergency Department Safety Assessment and Follow-up Evaluation Screening Outcome Evaluation examined whether universal suicide risk screening is feasible and effective at improving suicide risk detection in the emergency department (ED). METHODS A three-phase interrupted time series design was used: Treatment as Usual (Phase 1), Universal Screening (Phase 2), and Universal Screening + Intervention (Phase 3). Eight EDs from seven states participated from 2009 through 2014. Data collection spanned peak hours and 7 days of the week. Chart reviews established if screening for intentional self-harm ideation/behavior (screening) was documented in the medical record and whether the individual endorsed intentional self-harm ideation/behavior (detection). Patient interviews determined if the documented intentional self-harm was suicidal. In Phase 2, universal suicide risk screening was implemented during routine care. In Phase 3, improvements were made to increase screening rates and fidelity. Chi-square tests and generalized estimating equations were calculated. Data were analyzed in 2014. RESULTS Across the three phases (N=236,791 ED visit records), documented screenings rose from 26% (Phase 1) to 84% (Phase 3) (χ(2) [2, n=236,789]=71,000, p<0.001). Detection rose from 2.9% to 5.7% (χ(2) [2, n=236,789]=902, p<0.001). The majority of detected intentional self-harm was confirmed as recent suicidal ideation or behavior by patient interview. CONCLUSIONS Universal suicide risk screening in the ED was feasible and led to a nearly twofold increase in risk detection. If these findings remain true when scaled, the public health impact could be tremendous, because identification of risk is the first and necessary step for preventing suicide. TRIAL REGISTRATION Emergency Department Safety Assessmentand Follow-up Evaluation (ED-SAFE) ClinicalTrials.gov: (NCT01150994). https://clinicaltrials.gov/ct2/show/NCT01150994?term=ED-SAFE&rank=1.

The Potential to Reduce Mental Health Disparities Through the Comprehensive Community Mental Health Services for Children and Their Families Program

Few service systems are currently in place with the explicit purpose to reduce youth mental health disparities across socioeconomic status and race–ethnicity, despite substantial interest by the federal government and other institutions to redress health disparities. This study examines the potential for the Comprehensive Community Mental Health Services for Children and Their Families Program to address health disparities, even though this program was not explicitly designed for disparity reduction. Specifically, this study examines whether program sites disproportionately provide services within their catchment areas for youth who come from poor families, who are Black, and who are Hispanic. Data for this study come from 45 sites and 19,189 youth who were enrolled in program sites from 1997 to 2005. Meta-analysis was used to generate Forest plots and to obtain single, pooled estimates of risk ratios and their standard errors across all Children’s Mental Health Initiative communities. The results indicate that in comparison to the targeted catchment area (a) the percentage poor youth in the programs was almost three times higher, (b) the percentage Black in the programs was about twice as high, and (c) the percentage Hispanic in the programs was about the same. These results indicate that the program successfully reaches disadvantaged youth and can bring substantial infrastructure to address youth mental health disparities. In fact, to the extent that the program successfully improves mental health among enrollees it may be serving as one of the largest initiatives to redress health disparities, although its role in disparity reduction is not widely recognized.

Factors Associated With Suicide Outcomes 12 Months After Screening Positive for Suicide Risk in the Emergency Department

OBJECTIVE The main objective was to identify which patient characteristics have the strongest association with suicide outcomes in the 12 months after an index emergency department (ED) visit. METHODS Data were analyzed from the first two phases of the Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE). The ED-SAFE study, a quasi-experimental, interrupted time-series design, involved participation from eight general medical EDs across the United States. Participants included adults presenting to the ED with active suicidal ideation or an attempt in the past week. Data collection included baseline interview; six- and 12-month chart reviews; and six-, 12-, 24-, 36-, and 52-week telephone follow-up assessments. Regression analyses were conducted. RESULTS Among 874 participants, the median age was 37 years (interquartile range 27-47), with 56% of the sample being female (N=488), 74% white (N=649), and 13% Hispanic (N=113). At baseline, 577 (66%) participants had suicidal ideation only, whereas 297 (34%) had a suicide attempt in the past week. Data sufficient to determine outcomes were available for 782 (90%). In the 12 months after the index ED visit, 195 (25%) had documentation of at least one suicide attempt or suicide. High school education or less, an ED visit in the preceding six months, prior nonsuicidal self-injury, current alcohol misuse, and suicidal intent or plan were predictive of future suicidal behavior. CONCLUSIONS Continuing to build an understanding of the factors associated with future suicidal behaviors for this population will help guide design and implementation of improved suicide screening and interventions in the ED and better allocation of scarce resources.

Emergency medicine public health research funded by federal agencies: progress and priorities.

The emergency department (ED) visit provides an opportunity to impact the health of the public throughout the entire spectrum of care, from prevention to treatment. As the federal government has a vested interest in funding research and providing programmatic opportunities that promote the health of the public, emergency medicine (EM) is prime to develop a research agenda to advance the field. EM researchers need to be aware of federal funding opportunities, which entails an understanding of the organizational structure of the federal agencies that fund medical research, and the rules and regulations governing applications for grants. Additionally, there are numerous funding streams outside of the National Institutes of Health (NIH; the primary federal health research agency). EM researchers should seek funding from agencies according to each agencys mission and aims. Finally, while funds from the Department of Health and Human Services (HHS) are an important source of support for EM research, we need to look beyond traditional sources and appeal to other agencies with a vested interest in promoting public health in EDs. EM requires a broad skill set from a multitude of medical disciplines, and conducting research in the field will require looking for funding opportunities in a variety of traditional and not so traditional places within and without the federal government. The following is the discussion of a moderated session at the 2009 Academic Emergency Medicine consensus conference that included panel discussants from the National Institutes of Mental Health, Drug Abuse, and Alcoholism and Alcohol Abuse and the Centers for Disease Control and Prevention (CDC). Further information is also provided to discuss those agencies and centers not represented.

Strength in Numbers

The National Institute of Mental Health (NIMH) maintains a comprehensive portfolio of research on depression risk, etiology, pathophysiology, intervention, and services research. This broad portfolio exists because, as with many of our illnesses, there is still much work to be done to identify potent intervention targets for treatment and prevention, develop novel interventions, optimize the effectiveness of the interventions we know to be efficacious, and develop the science to implement and sustain programs that work. With the goal of expediting scientific advances, NIMH encourages investigators in a given field to communicate, collaborate, and share knowledge, data, and resources. The papers presented in this special issue highlight a concerted, grassroots collaborative effort among the investigators in the field of depression prevention that resulted in a proactive, thoughtful sharing of ideas and sharing of individual-level data across studies. For the field, this collaboration presents an opportunity to Bsee the forest through the trees^ and develop an understanding of the state of the science for depression prevention that goes beyond what we can learn from the report of an individual study. The papers included in this special issue were authored by prevention scientists who are developing and testing interventions—some specifically targeting depression, others targeting associated high-risk behaviors. Reading the papers as a set enables one to identify common findings and themes and allows us to see if an individual study’s effects change when participantlevel data is combined and re-examined across a range of studies. This collaboration offers innovations not just in the data analysis and methodology, as described in the papers by Siddique et al. (2017) and Brincks et al. (2016), but also in our understanding of how wemight enhance or alter existing interventions so we may more effectively prevent the incidence or recurrence of depression among vulnerable youth. The papers go beyond reporting only if an intervention works, but also for whom. A focus on moderators as well as possible mechanisms of action will further our ability to refine intervention strategies and, ultimately, prevent incidence of illness. In the interest of space, wewill not review all of the individual study findings but will, instead, highlight a few key outcomes across the papers. In doing so, we see that early intervention matters. Stronger effects tend to be found for groups who received interventions in earlier grades or earlier in the course of illness (i.e., before symptoms emerged). The set of papers also shows the ways in which family can be a key component to effective depression prevention. Across studies, aspects of the family moderate intervention effects—e.g., parent illness, parent marital status, and overall family functioning. In one study, family characteristics were more important than dose with respect to impact on internalizing behaviors (Mauricio et al. 2016). This special issue also includes an article by Brown and colleagues which combines and re-analyzes participant-level data from 19 studies to identify moderators of intervention response. The rationale for the integrated approach is clear— oftentimes, individual studies are not sufficiently powered to examine effects of specific moderators of interest, and individual studies may take different approaches to conducting a moderator analysis, making the comparison of findings across studies challenging. The data included in the analyses by This manuscript was prepared while Dr. Amy Goldstein was employed at the National Institute of Mental Health. The opinions expressed in this article are the authors own and do not reflect the views ofMedStar Health Research Institute and NIMH.