Gregory E. Simon

Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study

Objective To investigate if the widely publicized warnings in 2003 from the US Food and Drug Administration about a possible increased risk of suicidality with antidepressant use in young people were associated with changes in antidepressant use, suicide attempts, and completed suicides among young people. Design Quasi-experimental study assessing changes in outcomes after the warnings, controlling for pre-existing trends. Setting Automated healthcare claims data (2000-10) derived from the virtual data warehouse of 11 health plans in the US Mental Health Research Network. Participants Study cohorts included adolescents (around 1.1 million), young adults (around 1.4 million), and adults (around 5 million). Main outcome measures Rates of antidepressant dispensings, psychotropic drug poisonings (a validated proxy for suicide attempts), and completed suicides. Results Trends in antidepressant use and poisonings changed abruptly after the warnings. In the second year after the warnings, relative changes in antidepressant use were −31.0% (95% confidence interval −33.0% to −29.0%) among adolescents, −24.3% (−25.4% to −23.2%) among young adults, and −14.5% (−16.0% to −12.9%) among adults. These reflected absolute reductions of 696, 1216, and 1621 dispensings per 100 000 people among adolescents, young adults, and adults, respectively. Simultaneously, there were significant, relative increases in psychotropic drug poisonings in adolescents (21.7%, 95% confidence interval 4.9% to 38.5%) and young adults (33.7%, 26.9% to 40.4%) but not among adults (5.2%, −6.5% to 16.9%). These reflected absolute increases of 2 and 4 poisonings per 100 000 people among adolescents and young adults, respectively (approximately 77 additional poisonings in our cohort of 2.5 million young people). Completed suicides did not change for any age group. Conclusions Safety warnings about antidepressants and widespread media coverage decreased antidepressant use, and there were simultaneous increases in suicide attempts among young people. It is essential to monitor and reduce possible unintended consequences of FDA warnings and media reporting.

Breast and Cervical Cancer Screening. Specific Effects of Depression and Obesity

BACKGROUND Obesity and depression may each be associated with lower rates of cervical and breast cancer screening. Studies have examined obesity or depression alone, but not together, despite the established link between them. PURPOSE This article aims to disentangle the effects of depression and obesity on receipt of breast and cervical cancer screening. METHODS A stratified sampling design was used to recruit women aged 40-65 years with information on BMI from an integrated health plan in Washington State in 2003-2005. A telephone survey included the Patient Health Questionnaire-9 for depression, weight, and height. Automated data assessed Paps for 3097 women over a 3-year period and screening mammograms over a 2-year period for 2163 women aged > or =51 years. Logistic regression models (conducted in 2008) examined the association between obesity and depression and receipt of screening tests. RESULTS In univariate logistic regression models, women were less likely to receive a Pap if they were obese (OR=0.53, 95% CI=0.41, 0.69) or depressed (OR=0.60, 95% CI=0.42, 0.87). Further, women were less likely to receive a screening mammogram if they were depressed (OR=0.45, 95% CI=0.30, 0.67). In multivariable models, only obesity remained significantly associated with a lower likelihood of Pap screening (OR=0.67, 95% CI=0.0.49, 0.93), and only depression remained significantly associated with lower rates of screening mammography (OR=0.49, 95% CI=0.31, 0.76). Obesity and depression did not interact significantly in either model. CONCLUSIONS Obesity and depression appear to have specific effects on receipt of different cancer-screening tests.

A guide to research partnerships for pragmatic clinical trials

#### Summary points Pragmatic clinical trials are comparative effectiveness studies conducted in real-world settings to answer questions relevant to patients, clinicians, and healthcare decision makers. In contrast, explanatory clinical trials study how treatments or interventions work in carefully controlled settings and study populations, often to investigate a biological hypothesis or test a drug or device to meet regulatory requirements. The pragmatic approach requires unique methods to achieve the goal of identifying sustainable, generalizable, evidence based ways to improve healthcare.1 2 3 4 5 While previous authors addressed statistical considerations,6 little guidance is available on the methods for establishing partnerships between researchers and the people and processes in usual care settings that are necessary to conduct a pragmatic clinical trial. Based on insights from an initiative to accelerate pragmatic research,7 this article summarizes best practices for researchers and partners in healthcare systems as they establish collaborative relationships, develop research questions, and implement sustainable pragmatic clinical trials. A recent example …

Association between change in depression and change in weight among women enrolled in weight loss treatment.

OBJECTIVE To examine the association between improvement in depression and loss of weight among women with depressive symptoms entering a behavioral weight loss program. METHODS Women aged 40 to 65 with body mass index (BMI) of 30 or more and co-occurring symptoms of depression were identified by a population-based survey. A total of 203 of these women were enrolled in one of two behavioral treatment programs: one focused on weight loss and another on both weight loss and depression. Both programs included up to 26 group sessions over 12 months. Assessments at baseline, 6 months, 12 months and 24 months included measurement of weight, depressive symptoms, self-reported physical activity and estimated caloric intake (via food frequency questionnaire). RESULTS Over the first 6 months, women with a decrease in depression score were more likely to lose 5 kg or more than women without a significant decrease in depression (38% vs. 22%, odds ratio=2.20, 95% CI=1.09 to 4.44). Over the same period, improvement in depression was associated with increase in physical activity but not with change in caloric intake. Change in depression and change in weight were not significantly associated over later intervals (between 6 and 12 months or between 12 and 24 months). CONCLUSIONS Among women with co-occurring obesity and depression, short-term improvement in depression is associated with weight loss.

Association Between Chronic Physical Conditions and the Effectiveness of Collaborative Care for Depression: An Individual Participant Data Meta-analysis

IMPORTANCE Collaborative care is an intensive care model involving several health care professionals working together, typically a physician, a case manager, and a mental health professional. Meta-analyses of aggregate data have shown that collaborative care is particularly effective in people with depression and comorbid chronic physical conditions. However, only participant-level analyses can rigorously test whether the treatment effect is influenced by participant characteristics, such as chronic physical conditions. OBJECTIVE To assess whether the effectiveness of collaborative care for depression is moderated by the presence, type, and number of chronic physical conditions. DATA SOURCES Data were obtained from MEDLINE, EMBASE, PubMed, PsycINFO, CINAHL Complete, and Cochrane Central Register of Controlled Trials, and references from relevant systematic reviews. The search and collection of eligible studies was ongoing until May 22, 2015. STUDY SELECTION This was an update to a previous meta-analysis. Two independent reviewers were involved in the study selection process. Randomized clinical trials that compared the effectiveness of collaborative care with usual care in adults with depression and reported measured changes in depression severity symptoms at 4 to 6 months after randomization were included in the analysis. Key search terms included depression, dysthymia, anxiety, panic, phobia, obsession, compulsion, posttraumatic, care management, case management, collaborative care, enhanced care, and managed care. DATA EXTRACTION AND SYNTHESIS Individual participant data on baseline demographics and chronic physical conditions as well as baseline and follow-up depression severity symptoms were requested from authors of the eligible studies. One-step meta-analysis of individual participant data using appropriate mixed-effects models was performed. MAIN OUTCOMES AND MEASURES Continuous outcomes of depression severity symptoms measured using self-reported or observer-rated measures. RESULTS Data sets from 31 randomized clinical trials including 36 independent comparisons (N = 10 962 participants) were analyzed. Individual participant data analyses found no significant interaction effects, indicating that the presence (interaction coefficient, 0.02 [95% CI, -0.10 to 0.13]), numbers (interaction coefficient, 0.01 [95% CI, -0.01 to 0.02]), and types of chronic physical conditions do not influence the treatment effect. CONCLUSIONS AND RELEVANCE There is evidence that collaborative care is effective for people with depression alone and also for people with depression and chronic physical conditions. Existing guidance that recommends limiting collaborative care to people with depression and physical comorbidities is not supported by this individual participant data meta-analysis.

Obesity, depression, and health services costs among middle-aged women

BackgroundBoth obesity and depression have been associated with significant increases in health care costs. Previous research has not examined whether cost increases associated with obesity could be explained by confounding effects of depression.ObjectiveExamine whether the association between obesity and health care costs is explained by co-occurring depression.DesignCross-sectional study including telephone survey and linkage to health plan records.Participants4462 women aged 40 to 65 enrolled in prepaid health plan in the Pacific Northwest.Main MeasuresThe telephone survey included self-report of height and weight and measurement of depression by the Patient Health Questionnaire (PHQ9). Survey data were linked to health plan cost accounting records.Key ResultsCompared to women with BMI less than 25, proportional increases in health care costs were 65% (95% CI 41% to 93%) for women with BMI 30 to 35 and 157% (95% CI 91% to 246%) for women with BMI of 35 or more. Adjustment for co-occurring symptoms of depression reduced these proportional differences to 40% (95% CI 18% to 66%) and 87% (95% CI 42% to 147%), respectively. Cost increases associated with obesity were spread across all major categories of health services (primary care visits, outpatient prescriptions, inpatient medical services, and specialty mental health care).ConclusionsAmong middle-aged women, both obesity and depression are independently associated with substantially higher health care costs. These cost increases are spread across the full range of outpatient and inpatient health services. Given the high prevalence of obesity, cost increases of this magnitude have major policy and public health importance

How Does Change in Depressive Symptomatology Influence Weight Change in Patients With Diabetes? Observational Results From the Pathways Longitudinal Cohort

BACKGROUND Little is known about how change in depressive symptoms over time is associated with change in weight. METHODS Longitudinal associations between change in depression (Patient Health Questionnaire-9 [PHQ-9]) and weight (self-reported and chart abstracted) were examined in 2,600 patients with type 2 diabetes (mean age 62, SD = 11.6) who were surveyed by telephone in 2001-2002 and 5 years later as part of the Pathways study. Mixed effects regression analyses compared a) patients with persistently low depression symptoms with those whose depression worsened (increased at least 5 points on PHQ-9) over 5 years and b) patients with persistently high depression symptoms with those who improved (decreased at least 5 points on PHQ-9) over 5 years. RESULTS Those who worsened in comparison to those with persistently low depression symptoms did not differ in their pattern of weight change (z = 1.54, p = .12). Both groups weighed approximately 92 kg at baseline and lost approximately 2 kg. A significantly different pattern of change over time was observed for those with persistently high depression symptoms in comparison to those whose depression improved (z = 1.98, p = .04). Although the groups had almost identical weight at baseline (approximately 100 kg), at the 5-year assessment, those with persistently high depression symptoms had about half the weight loss (M = -1.71, SD = 9.08) in comparison to those whose depression improved (M = -3.62, SD = 19.93). CONCLUSION In persons with diabetes who have clinically significant levels of depressive symptoms, improvement in depression is accompanied by significantly greater, clinically significant weight loss.

Pragmatic clinical trials embedded in healthcare systems: generalizable lessons from the NIH Collaboratory

BackgroundThe clinical research enterprise is not producing the evidence decision makers arguably need in a timely and cost effective manner; research currently involves the use of labor-intensive parallel systems that are separate from clinical care. The emergence of pragmatic clinical trials (PCTs) poses a possible solution: these large-scale trials are embedded within routine clinical care and often involve cluster randomization of hospitals, clinics, primary care providers, etc. Interventions can be implemented by health system personnel through usual communication channels and quality improvement infrastructure, and data collected as part of routine clinical care. However, experience with these trials is nascent and best practices regarding design operational, analytic, and reporting methodologies are undeveloped.MethodsTo strengthen the national capacity to implement cost-effective, large-scale PCTs, the Common Fund of the National Institutes of Health created the Health Care Systems Research Collaboratory (Collaboratory) to support the design, execution, and dissemination of a series of demonstration projects using a pragmatic research design.ResultsIn this article, we will describe the Collaboratory, highlight some of the challenges encountered and solutions developed thus far, and discuss remaining barriers and opportunities for large-scale evidence generation using PCTs.ConclusionA planning phase is critical, and even with careful planning, new challenges arise during execution; comparisons between arms can be complicated by unanticipated changes. Early and ongoing engagement with both health care system leaders and front-line clinicians is critical for success. There is also marked uncertainty when applying existing ethical and regulatory frameworks to PCTS, and using existing electronic health records for data capture adds complexity.

Early Dropout from Psychotherapy for Depression with Group- and Network-model Therapists

Administrative data were used to examine early dropout among 16,451 health plan members calling to request psychotherapy for depression. Compared to members referred to group-model therapists, those referred to network-model therapists were more likely to drop out before the initial visit (OR 2.33, 95% CI 2.17–2.50) but less likely to drop out after the first visit (OR 0.45, 95% CI 0.43–0.48). These differences were unaffected by adjustment for neighborhood income and educational attainment, antidepressant use, or generosity of insurance coverage. Efforts to increase the effectiveness of psychotherapy may required different strategies in group- and network-model practice.

A pragmatic randomized clinical trial of behavioral activation for depressed pregnant women.

Objective: Depression among pregnant women is a prevalent public health problem associated with poor maternal and offspring development. Behavioral activation (BA) is a scalable intervention aligned with pregnant women’s preference for nonpharmacological depression care. This is the first test of the effectiveness of BA for depression among pregnant women, which aimed to evaluate the effectiveness of BA as compared with treatment as usual (TAU). Method: Pregnant women (mean age = 28.75 years; SD = 5.67) with depression symptoms were randomly assigned to BA (n = 86) or TAU (n = 77). Exclusion criteria included known bipolar or psychotic disorder or immediate self-harm risk. Follow-up assessment occurred 5 and 10 weeks postrandomization and 3 months postpartum using self-report measures of primary and secondary outcomes and putative targets. Results: Compared with TAU, BA was associated with significantly lower depressive symptoms (d = 0.34, p = .04) and higher remission (56.3% vs. 30.3%, p = .003). BA also demonstrated significant advantage on anxiety and perceived stress. Participants attended most BA sessions and reported high satisfaction. Participants in BA reported significantly higher levels of activation (d = 0.69, p < .0002) and environmental reward (d = 0.54, p < .003) than those who received TAU, and early change in both of these putative targets significantly mediated subsequent depression outcomes. Conclusions: BA is effective for pregnant women, offering significant depression, anxiety, and stress benefits, with mediation analyses supporting the importance of putative targets of activation and environmental reward.