• Early Symptom Improvement as a Predictor of Antidepressant Response in Children and Adolescents Diagnosed with Depression: Translating Evidence from Randomized Controlled Trials to Community Practice

      Spence, O'Mareen; dosReis, Susan (2020)
      Statement of the Problem: A common problem among children and adolescents diagnosed with depression who receive care in community settings is that antidepressant regimen changes such as psychotropic augmentation may occur soon after starting treatment. This raises the question as to whether such changes are implemented among youth who would otherwise respond to the antidepressant. Thus, the overarching objectives of this dissertation were to 1) distinguish early in treatment children and adolescents who are likely to respond, and 2) empirically evaluate the association between predicted response and psychotropic augmentation or switching in real world settings. Summary of Methods: Using randomized clinical trial (RCT) data, this research applied a Bayesian approach to predict the likelihood of initial (12 week) and sustained (18 week) response to treatment as a function of early changes in depressive symptoms (i.e. mood, somatic, subjective and behavioral) and other demographic and clinical factors. An innovative application of combined sample multiple imputations (CSMI) was used to estimate the 12-week predicted probability of response among commercially insured adolescents who received care in real-world settings. Each adolescent received a probability of treatment response, which was then used to compare the odds of psychotropic augmentation or switch. Results: Early changes in mood and somatic symptoms within the first six weeks of treatment are primary predictors of initial (at 12 weeks) and sustained (at 18 weeks) response to an antidepressant. Baseline depression severity is an important prognostic factor for initial response, and additional, though minimal improvement, in somatic symptoms from weeks 6 to 12 is indicative of sustained response. In a highly selected cohort of adolescents receiving care in community settings, an augmentation or switch occurred similarly among adolescents with a high versus low likelihood of responding to fluoxetine. Conclusion: The results suggest that other factors beyond expected antidepressant response (or lack thereof) might influence current treatment practices. Our findings have clinical and public health implications that support measurement-based care in pediatric depression. Our application of CSMI highlights several key areas of consideration for future pharmacoepidemiologic research aimed at translating RCT evidence to real world data to better understand clinical practices patterns.
    • Epidemiology and outcomes of depression following cardiovascular events in elderly Medicare beneficiaries

      Blanchette, Christopher Michael; Simoni-Wastila, Linda (2007)
      Objective. To assess and compare elderly Medicare beneficiaries' occurrence of depression and associated treatment following a thrombotic cardiovascular event (TCE) for (1) annual prevalence rates, (2) healthcare services utilization outcomes in the first twelve months following a TCE, and (3) the occurrence of recurrent TCEs or death in the first twelve months following a TCE. Methods. Elders enrolled in the 1997 to 2002 Medicare Current Beneficiary Survey with a TCE (International Classification of Diseases, Ninth Revision (ICD-9) codes 410, 411, 413, 414, 415, 433--438, 452, or 453). Depression (ICD-9 codes 296.2, 296.3, 296.5, 296.6, 298.0, 300.4, 308.0, 309.0, 309.1, 309.4, or 311) was assessed by a claim within six months after the TCE. Demographic and descriptive characteristics were assessed. Prevalence rates of depression and associated antidepressant utilization rates by class were calculated. Time to first healthcare service use, recurrent TCE, and death were assessed using Cox-proportional hazard models. Counts of office visits were assessed using negative binomial regression models. Results. The sample included 7,051 elders with a TCE. The prevalence rate of depression was 7.6% across the study period. Close to 70% of elders with a depression claim were using an antidepressant in the year of depression diagnosis and 53% were using SSRI antidepressants. A depression claim was associated with 51% sooner hospitalization (95% CI = 1.31, 1.76), 56% sooner emergency department visit (95% CI = 1.29, 1.90), 19% sooner outpatient hospital visit (95% CI = 1.03, 1.38). Depression was associated with a shorter time to death (p = 0.008) in the unadjusted analysis; however not associated with time to death or recurrent events in adjusted analysis. Antidepressant use was not associated with any outcome. Conclusions. Prevalence rates of post-TCE depression were much lower than rates reported in previous studies. Depression is associated with more acute healthcare services and sooner during the first twelve months following a TCE; however not associated with time to recurrent event or death. Antidepressant use has no effect on outcomes.
    • Impact of Undertreatment of Depression on Suicide and Suicide Attempt among Children and Adolescents: A Simulation Study with Microsimulation and Agent-Based Models

      Zhang, Chengchen; dosReis, Susan; 0000-0003-3349-8725 (2022)
      Background: Depression is a strong risk factor for suicide, but undertreatment of depression is common among children and adolescents. The impact of undertreatment of depression on suicidal behaviors in this population is largely unknown due to the limitations of conventional data sources and methods. This dissertation research aims to overcome these challenges by using simulation models to answer two questions: 1) Is undertreatment of depression associated with increased risk of suicidal behaviors? 2) Do interventions that reduce undertreatment of depression lower the risk of suicidal behaviors? Methods: A microsimulation model simulated the 1-year suicide rate and suicide attempt risk with 12-, 36-, 52-week antidepressant treatment and no treatment in children and adolescents with depression. Modified Poisson regression estimated the suicide rate ratios and suicide attempt risk ratios for 12-, 36- and 52-week treatment compared with no treatment. An agent-based model simulated the potential impact of the following interventions in preventing suicide and suicide attempt in a synthetic population of children and adolescents: 1) depression screening (i.e. reducing untreated depression); 2) reducing attrition during depression treatment (i.e., increasing the proportion who complete the first 12 weeks of treatment); 3) suicide intervention (i.e., screen and treat individuals who need suicide care) among depressed individuals; 4) universal suicide intervention in medical settings. Results: Compared with no treatment, 12-, 36- and 52-week antidepressant treatment was significantly associated with decreased suicide rate and risk of suicide attempt. Depression screening could reduce the risk of suicide attempt (-0.64% (95% Credible Interval (CI): -1.13%, -0.11%)) only when 80% untreated depression was reduced. Universal suicide intervention showed a significant decrease in the risk of suicide attempt, which increased with the screened proportion (20%: -0.68% (95% CI: -0.87%, -0.55%), 50%: -1.47% (95% CI: -1.61%, -1.77%), 80%: -2.89% (95% CI: -4.57%, -2.31%). The other interventions did not show a significant effect in reducing the risk of suicide attempt in the population. Conclusion: Antidepressant treatment for at least 12 weeks may reduce risk of suicidal behaviors. Universal suicide intervention in medical care settings may be more effective in reducing suicidal behaviors compared with interventions that reduce undertreatment of depression.
    • Influence of Comorbid Depression on Mortality among SSDI-eligible Medicare Beneficiaries with Chronic Obstructive Pulmonary Disease

      Qian, Jingjing; Simoni-Wastila, Linda (2012)
      Background: Chronic obstructive pulmonary disease (COPD) is a condition with high mortality and morbidity. Comorbid depression can place COPD patients at increased risk of adverse outcomes. Although both COPD and depression are associated with significant morbidity, to date few studies addressing COPD-related outcomes have included individuals who receive Social Security Disability Insurance (SSDI). Objectives: To examine the influence of comorbid depression on mortality among a nationally-representative sample of Medicare beneficiaries suffering from COPD by SSDI-eligibility status. Methods: This retrospective cohort study used a 5% random sample of the 2006-2008 Chronic Condition Warehouse administrative data. The study cohort included 93,019 Medicare beneficiaries diagnosed with COPD who lived through 2006 and were continuously enrolled in Medicare Parts A, B, and D. Two-year (2007-2008) all-cause mortality was the study outcome. Comorbid depression was measured in 2006-2008. SSDI-eligibility was defined using the original reason for Medicare entitlement. Multivariable generalized estimating equations models estimated the association between SSDI-eligibility and depression, as well as the modification effect of SSDI-eligibility on their relationship. Survival analyses using extended Cox proportional hazards models further estimated risk of death from depression and antidepressant treatment among beneficiaries aged 65 and older (n=75,699) by SSDI-eligibility. Results: About two-fifths (39.4%) of beneficiaries with COPD had a depression diagnosis in 2006-2008; of those, 79.5% received antidepressant treatment. SSDI-eligibility was not only associated with a 12% (95%CI=10%,15%) higher likelihood of depression but also modified factors in regard to depression diagnosis and receipt of antidepressant treatment. COPD beneficiaries with a baseline depression diagnosis had a higher risk of death (HR=1.13; 95%CI=1.09, 1.18) in non-SSDI-eligible beneficiaries. Those who received antidepressant treatment had reduced risk of death, with greater benefits on mortality in SSDI-eligible than non-SSDI-eligible beneficiaries. Conclusions: This study provides the first evidence suggesting that SSDI-eligibility is not only associated with higher likelihood of having a depression diagnosis, but also is a significant effect modifier of the relationship between antidepressant treatment and mortality in Medicare beneficiaries with COPD. Findings demonstrate the benefits of antidepressant treatment on mortality in both SSDI-eligible and non-SSDI-eligible beneficiaries. In practice, clinicians should consider timely antidepressant treatment to improve outcomes for this population.