• Cardiometabolic Safety of Atypical Antipsychotic Medications among Publicly Insured U.S. Youth

      Burcu, Mehmet; Zito, Julie Magno; 0000-0003-4572-0987 (2017)
      Background: The use of atypical antipsychotics (AAPs) among publicly insured U.S. youth has substantially increased in the past two decades. Furthermore, more than half of AAP-treated youth have concomitant antidepressant or stimulant use, although the cardiometabolic effects of such combinations are largely unknown. Methods: The main focus of this dissertation was to evaluate the risk of incident type 2 diabetes mellitus (T2DM) and adverse cardiovascular events in AAP-treated youth according to the concomitant use of stimulants or serotonin reuptake inhibitors (SSRI/SNRIs)-the leading antidepressant subclass. The risk of T2DM and adverse cardiovascular events were assessed using discrete time failure models. To adjust for confounding, disease risk score methodology was employed using >125 baseline and time-dependent covariates. Medication use was assessed using four time-varying exposure measures: current/former/non-use, duration of use, cumulative dose, and average daily dose. Results: In a large regionally diverse cohort of Medicaid-insured youth, AAP use was associated with an increased risk of T2DM that increased with duration of AAP use and cumulative AAP dose. Further, in AAP-treated youth, concomitant SSRI/SNRI use was associated with an additional increased risk of T2DM, which intensified with duration of SSRI/SRNI use and SSRI/SNRI dose. In a separate set of analyses that focused on youth who initiated antidepressant treatment (regardless of AAP use), an increased risk of T2DM was also observed for SSRI/SNRIs. Finally, following treatment initiation with AAPs, current AAP use was also associated with an increased risk of incident cardiovascular events that led to hospitalizations or emergency department visits. This increased risk also intensified with increasing AAP dose and when SSRI/SNRIs were used concomitantly with AAPs. By contrast, in AAP-treated youth, concomitant use of stimulants was not associated with an increased risk of T2DM or cardiovascular events. Conclusions: In view of the growing complexity of atypical antipsychotic regimens in Medicaid-insured youth and low rates of baseline metabolic monitoring in youth initiating AAP treatment, these findings suggest that complex AAP regimens should be used judiciously with appropriate cardiometabolic monitoring. Continued efforts are warranted to support Medicaid oversight policies that assure safe and effective use of complex AAP regimens in youth populations.
    • Correlates of psychopharmacologic treatment outcomes for schizophrenia

      Kreyenbuhl, Julie Anne; Zito, Julie Magno (1999)
      Schizophrenia is a severe and persistent mental illness that affects upwards of two million Americans and its treatment is estimated to cost {dollar}32 billion annually. Although pharmacotherapy represents the mainstay of treatment for schizophrenia, recent pharmacoepidemiologic data on practice patterns in large U.S. populations are limited. To address this need, a study was conducted with the following aims: (1) to characterize the patterns of pharmacologic management of schizophrenia and its demographic and clinical correlates in typical clinical practice settings; (2) to develop analytic models to examine the associations between characteristics of drug therapy and outcomes; and (3) to look for evidence of behavioral toxicity of antipsychotic medications. The data from this study were derived from a patient survey supplemented with medical record information of 719 participants recruited from inpatient and outpatient psychiatric facilities in two states for the Schizophrenia Patient Outcomes Research Team (PORT) study. The final study samples consisted of 224 inpatients and 358 outpatients that met eligibility criteria and had valid medical record data. Ethnic disparities in prescribing were identified, such that non-white patients received fewer newer antipsychotic medications, more long-acting injectable (depot) antipsychotic medications, higher average daily antipsychotic doses, and fewer adjunctive medications than their white counterparts, regardless of treatment setting. Geographic variations in prescribing patterns, in which newer antipsychotics and adjunctive medications (inpatients only) were prescribed more frequently in rural areas of State A and in urban areas of State B, and depot antipsychotics were prescribed more often in urban areas of State A and rural areas of State B, were also noted. The hypothesized model of an indirect relationship among pharmacotherapy and outcomes variables (functioning and satisfaction) that is mediated by symptoms and medication side effects was not supported by the data in either treatment setting. Also, evidence of behavioral toxicity of antipsychotics was not identified. Pronounced variations in the pharmacologic management of schizophrenia were revealed. Investigations of the outcomes of pharmacotherapy and the behavioral toxicity of antipsychotic medications should be undertaken, utilizing different measurement scales and a prospective, longitudinal study design.
    • Impact of Food and Drug Administration pediatric antidepressant use warnings on treatment of depression, physician specialty practice patterns, and pharmaceutical stock prices

      Valluri, Satish; Zito, Julie Magno; Mullins, C. Daniel (2009)
      Background: To investigate the impact of the FDA pediatric antidepressant warning in March 2004 on: 1) the treatment of new-onset depression diagnosis (NODD); 2) physician specialty practice patterns; and 3) the stock returns of the antidepressant manufacturers. Methods: Youth 2-17 years old with a NODD from 2003-2006 constituted the study population. i3 Innovus database containing administrative claims information of U.S. commercial insurance enrollees was used. National Ambulatory Medical Care Survey data (2001-2006) were used to examine antidepressant use by physician specialty during youth mental health visits. CRSP stock price data (2003-2006) was used to examine the warning impact on stock returns and volatility. Results: The warnings led to a statistically significant decrease in the likelihood of antidepressant use [Odds Ratio (OR) =0.83; CI: 0.75,0.92] and an increase in the likelihood of psychotherapy in NODD but not a significant impact on youth with MDD. The likelihood of an antidepressant prescription was significantly higher for psychiatrist visits compared to primary care (OR=3.78; CI: 2.72,5.25). The warning was associated with a non-significant impact on the magnitude of stock returns but a significant increase in the volatility of stock returns (mean change = 0.30; CI: 0.10,0.49). Conclusions: The FDA warning did not lead to a A) decrease in the likelihood of antidepressant use for youth with a diagnosis of major depression, whereas psychotherapy use increased; B) increase the likelihood of antidepressant prescribing by psychiatrists relative to primary care; C) decrease in stock returns but only a modest increase in volatility of stock returns.
    • Longitudinal Patterns of Early Mental Health Service Utilization in a Medicaid-insured Birth Cohort and the Impact of Continuity of Care on the Quality of Pediatric Mental Health Treatment

      Pennap, Dinci; Zito, Julie Magno (2018)
      Background: The prevalence of pediatric mental health (MH) diagnosis and treatment have expanded in the U.S. We assessed the longitudinal patterns of incident diagnosis and new psychotropic medication use in a Medicaid-insured birth cohort. Additionally, continuity and quality of MH service utilization were assessed in a publicly-insured pediatric population. Quality care was defined by the 2009 Children's Health Insurance Program Reauthorization Act (CHIPRA) mandated children's health care quality measures. Methods: We applied longitudinal designs to Medicaid claims data from a Mid-Atlantic state (2007-2014). Using Kaplan-Meier estimators we assessed the cumulative incidence of MH service use in a cohort of newborns (aim 1). We assessed the association between relational patient-provider continuity of care and: 1) emergency department (ED) visits or hospitalizations in the 12 months following first MH diagnosis among 3-16 year olds (aim 2); and 2) the quality of follow-up care among 6-12 year old new users of ADHD medications (aim 3), using logistic regression models. Quality was defined as having ≥1 follow-up outpatient visit in the 30 days following medication initiation and ≥2 follow-up visits in the 270 days after the first follow-up visit, with a total medication supply of ≥210 days. Results: By age 8, 19.7% and 10.2% of the birth cohort (n=35,244) had received a MH diagnosis or psychotropic medication, respectively. Among medication users, 80.5% received monotherapy, 16.4% received 2 medication classes, and 4.3% received ≥3 medication classes concomitantly for ≥60 days. Compared to children with high CoC, the odds of ED visits was significantly higher among youths with low CoC [Odds Ratio(OR)=1.27; 95% CI=1.13-1.41] and low CoC was associated with greater odds of hospitalization [OR=1.17; 95% CI=1.06-1.29]. Compared to those with low CoC, children with higher continuity of care had greater odds of meeting CHIPRA initiation- [OR=1.41; 95% CI=1.25-1.60] and continuation-phase [OR=1.45; 95% CI=1.29-1.64] visit-based measures. Conclusions: Early exposure to psychotropic medications and prolonged duration of use have implications for long-term safety, highlighting the need for safety and outcomes research in pediatric populations. Our findings suggest a need for more research in the areas of quality assessment and continuity of care among youths with mental health conditions.
    • Patterns of psychopharmacologic treatment for attention deficit hyperactivity disorder

      dosReis, Susan; Zito, Julie Magno (1999)
      Outpatient office visits and stimulant medication treatments for attention deficit hyperactivity disorder (ADHD), the most common childhood psychiatric disorder, show sizeable increases in the US from 1990-1995. Current research findings do not fully explain the increases in diagnostic and treatment prevalence. Descriptive information of ADHD treatments across different youth populations would inform how clinical, demographic, and cultural factors influence treatment practices. This study examines child characteristics, parental perceptions, and health care system factors associated with ADHD medication treatment to understand their role in clinical decision-making. The specific aims of the study are to: compare ADHD treatment patterns for health maintenance organization (HMO) child members with Medicaid child members in the same geographic region; describe ADHD treatment referral patterns among a sample of school-aged children in an HMO; and survey parents' knowledge, attitude, and satisfaction with their child's ADHD treatment. Data were obtained from HMO and Medicaid computerized medical and prescription databases and a self-administered Attitude, Satisfaction, Knowledge and Medication Experiences (ASK-ME) survey for parents of children with ADHD. Findings from the computerized data show that HMO youths receiving care from a non-mental health provider were 4 times more likely to be diagnosed with ADHD than Medicaid youths. The survey study findings revealed that Caucasian parents had significantly greater knowledge of and more positive attitudes towards ADHD medication treatment. A larger proportion of non-Caucasian than Caucasian parents preferred counseling over medication and believed that stimulant medication led to substance abuse. Parents in both groups had false expectations about the medication's ability to improve the child's academic performance and behavior later in life. Parents were less satisfied with the medication's ability to enhance their child's self-esteem and social relations at home and at school. This study identified health care system, clinical, economic, and racial differences in perceptions of and treatments for ADHD among HMO and Medicaid youths. Additional research that includes a broader range of racial, cultural, and economic characteristics is needed to corroborate these findings. This work is important for the advancement of scientific knowledge of pediatric psychopharmacologic practices and for improvement in the clinical management of children with ADHD.