Showing papers by "Stephen V. Faraone published in 2023"

Response of peer relations and social activities to treatment with viloxazine extended‐release capsules (Qelbree®): A post hoc analysis of four randomized clinical trials of children and adolescents with attention‐deficit/hyperactivity disorder

Abstract: Attention‐deficit/hyperactivity disorder (ADHD) is associated with impairments related to peer relations (PR) and social activities (SA). The objective of this post hoc analysis was to assess the degree to which viloxazine extended‐release (viloxazine ER; viloxazine extended‐release capsules; Qelbree®) improves clinical assessments of PR and SA in children and adolescents with ADHD.

Growth Trajectories in Stimulant-Treated Children Ages 6 to 12: An Electronic Medical Record Analysis

Abstract: This article has supplementary material on the web site: www.jdbp.org. ABSTRACT: Objective: The aim of this study was to evaluate growth trajectories in stimulant-exposed and stimulant-unexposed children using electronic medical record data from a large health care organization attending to moderating effects of the magnitude of exposure to stimulants, sex, and race. Methods: Weight, height, body mass index (BMI), prescription, and sociodemographic information were extracted from the electronic medical records of a large health care organization. Included were children who were 6 to 12 years at the time they were receiving stimulants with a concurrent growth assessment (index assessment) plus 1 to 4 years of additional growth assessments thereafter. Non–attention-deficit/hyperactivity disorder (ADHD) children who were unexposed to stimulants were age and sex matched to those exposed. Stimulant exposure was examined as the total number of months with stimulant prescriptions, percentage of follow-up time exposed to stimulants, and cumulative stimulant dose. Results: Our sample consisted of 323 children exposed to stimulants with available growth data and 1615 unexposed children. Small but significant decreases in height trajectories were found over time in exposed children compared with those unexposed. Weight and BMI trajectories decreased in the first year of follow-up with stabilization and increased thereafter. Growth trajectory effects were largest in girls (height, weight, and BMI), White children (weight), and children with more total stimulant exposure (weight). Conclusion: This comprehensive analysis of an ecologically informative sample attending to key covariates of the magnitude of exposure to stimulants, sex, and race extends previous findings, showing that effects on growth trajectories are small and do not appear to pose a significant clinical concern for most children with ADHD treated with stimulants from childhood onto adolescent years.

Joseph Biederman, MD (1947-2023).

Abstract: In January of 2023, child psychiatry lost an iconic thought leader with the passing of Joseph Biederman, MD, after his courageous battle with cancer. Simply stated, Dr. Biederman was a legend in our field. His research, carried out over more than 4 decades, propelled forward the field of child and adolescent psychiatry. Dr. Biederman was an active and distinguished member of the child and adolescent mental health community for over 40 years. He participated in hundreds of presentations of original research at AACAP’s annual meetings. According to PubMed, he (co)authored over 950 articles: 242 research and review articles and 76 letters to the editor in JAACAP alone. He worked closely with his colleague and great friend Dr. Jack McDermott, editor of JAACAP from 1988-1997, and took pride in the publishing of a repertoire of empirically-based studies that enhanced the reputation of the Journal, advanced the science and practice of child and adolescent psychiatry, and helped the Journal double publication going from alternating months to monthly. Dr. Biederman is best known by AACAP’s members for his expertise in pediatric psychopharmacology and especially known for his systematic research advancing our knowledge base of attention-deficit/hyperactivity disorder (ADHD). Due to his pioneering efforts and advocacy, he is regarded as the “Father of Pediatric Psychopharmacology.” His contribution to many of the seminal regulatory studies submitted for FDA approval covering a variety of conditions helped establish credible outcome methodology in children and adolescents and moved the field to utilize more empirically validated medications for a variety of childhood psychiatric disorders. In particular, he tested many pharmacological interventions for ADHD across the lifespan, bipolar disorder, obsessive-compulsive disorder, and autism spectrum disorders. He studied the short- and longer- term treatment response, as well as safety and adverse effects of medications. Always searching for new treatments, he conducted seminal studies of nonstimulants for ADHD which culminated in the study and eventual approval of atomoxetine. Having been one of the first to document extensive comorbidity in ADHD and familial transmission of comorbid conditions, he was unique in developing pharmacological strategies to manage comorbid disorders commonly associated with childhood-onset psychopathology. Many of the most highly regarded texts in psychopharmacology over the past 4 decades include chapters written by Dr. Biederman. But his work was not limited to youth. In the 1990s, he was one of the first to systematically study, diagnose, and treat adults with ADHD. Dr. Biederman's work has been internationally recognized, accepted, and integrated into the practice of medicine. Many of his key research findings are now facts taught to medical students, residents, and fellows. He held the distinction of the most cited child and general psychiatrist in all of medicine for almost 2 decades, as well as one of the most productive researchers at Harvard Medical School. His work has been validated and replicated multifold by researchers across the globe. If all he did was research, that would have been sufficient for an extraordinary legacy. But Dr. Biederman was so much more than just a researcher. He maintained a full case load of patients to nearly the end of his life and was a mentor to several generations of faculty, both at the Massachusetts General Hospital (MGH) and at other institutions internationally. He worked closely with junior clinical investigators who now themselves mentor the next generation of researchers. Clinical scientists worldwide conduct research-often rooted either in work initiated and/or in collaboration with Dr. Biederman’s laboratory. The MGH Division of Child and Adolescent Psychiatry is a testament to Dr. Biederman's decades-long inspirational leadership during which, at every turn, he guided the fulfillment of the faculty’s collective work. It wasn’t easy being Dr. Biederman. As the son of parents who escaped the Nazis as Schindler’s Jews, he was reminded frequently of the vulnerability of life. After training in psychiatry in Israel, he moved his young family to Boston to access treatment for his wife, who soon succumbed to cancer leaving him to raise a toddler son alone in a strange city while grieving and completing his child and adolescent fellowship. Dr. Biederman’s bold ideas and quotable, pithy remarks resulted in both admiration and consternation by clinicians and fellow researchers. His efforts to treat serious psychopathology in youngsters made him a target for antipsychiatry zealots who protested at his lectures and maligned him in the press, and yet he was undeterred in his treatment of patients. In 2008, Senator Chuck Grassley leveled serious conflict of interest accusations at Dr. Biederman, as well as other researchers, many in child psychiatry. The Senator called into question Dr. Biederman’s integrity as a clinician and researcher, a personal and public humiliation that was only slightly abated by Harvard Medical School’s subsequent declaration of no wrongdoing after an intensive and time-consuming investigation. Despite this undeserved blow to his reputation, Dr. Biederman stood firm in his attention to children and adolescents with mental illness and their families. He continued to lecture, to research and to publish, undaunted by efforts to thwart his work. In recent years, he thrived, continuing his work on ADHD, and starting the now endowed “Alan and Lorraine Bressler Program for Autism Spectrum Disorder.” His program continues to serve over 5,000 patient visits yearly for patients with ADHD and/or high functioning ASD. In the year prior to his death, he was honored with a Massachusetts General Hospital endowed chair in pediatric psychopharmacology. This chair now bears his name, the Joseph Biederman MD Chair in Pediatric Psychopharmacology, and Dr. Janet Wozniak, one of his well-known mentees, is now the inaugural recipient. Dr. Biederman was a staunch champion of supporting children with psychopathology and their families. He reminded us daily of the need to support families – not blame them – for the psychiatric illness affecting their children. He continually taught us to listen to our patients, to observe, to generate solutions and to innovate – all to better the lives of those sitting across from us. Dr. Biederman’s work was rooted in his clinical practice, inspired by the wish to help his patients. AACAP members with active clinical practices crowded the rooms of his many symposia at the Annual Meetings to learn new clinically relevant information while feeling supported in the art of patient care by a researcher who was to the end an active clinician. Those who knew Dr. Biederman appreciated his love for his family. He was deeply devoted to his wife, Helen Charlupski, who accompanied him on many work-related trips and provided a wonderful balance to Joe’s fast paced and consuming work life. He was immensely proud of his 3 children and their significant others: Itai, Daniela and Seth, Ari and Tracy; and his 4 grandchildren, all of whom brought him joy beyond description. Those of us who worked closely with Joe extend our gratitude to his family for their generosity in sharing him with us and with the world. We thank them for supporting him, and us, during challenging times and for celebrating the many victories along our collective journey. Dr. Biederman's accomplishments, too many to mention here, collectively have left an indelible body of work, impacting clinicians, researchers and countless patients and their families. While we mourn the passing of our witty, passionate, bold, and brilliant friend and colleague, let us all also celebrate Dr. Biederman as a pioneer and maverick in the field of child psychiatry and a fierce advocate for patients and their families.

Further Evidence of an Association Between a Positive Child Behavior Checklist-Bipolar Profile and a Diagnosis of Pediatric Bipolar Disorder: A Meta-Analysis

Abstract: Abstract Background Previous research has found that a unique profile of the Child Behavior Checklist comprising of aggregate elevations of the Attention, Anxiety/Depression and Aggression scales (A-A-A profile, CBCL-Bipolar (BP) profile, CBCL-Dysregulation profile (DP); henceforth CBCL-BP/DP profile) is associated with a clinical diagnosis of pediatric bipolar (BP) disorder. Objective The main aim of the study is to evaluate the strength of the association between the CBCL-BP/DP profile and the clinical diagnosis of pediatric BP disorder through a meta-analysis. Methods A literature search was performed to identify studies that examined the association between a positive CBCL-BP/DP profile and a clinical diagnosis of pediatric BP disorder. The meta-analyses first examined studies assessing the rates of a positive CBCL-BP/DP profile in youth with BP disorder versus those with 1) ADHD, anxiety/depression, or disruptive behavior disorders (DBDs), and 2) non-bipolar controls. The second analysis evaluated studies examining the rates of pediatric BP disorder in youth with and without a positive CBCL-BP/DP profile. Results Eighteen articles met our inclusion and exclusion criteria, and fifteen articles had adequate data for meta-analysis. Results showed that BP youth were at significantly increased odds of having a positive CBCL-BP/DP profile compared to those with other psychiatric disorders (i.e., ADHD, anxiety/depression, or DBDs) (pooled OR=4.34, 95% CI=2.82, 8.27; p<0.001) and healthy control groups (pooled OR=34.77, 95% CI=2.87, 420.95; p=0.005). Further, meta-analysis results showed that youth with a positive CBCL-BP/DP profile were at significantly increased odds of having a BP disorder diagnosis compared to those without (pooled OR=4.25, 95% CI=2.12, 8.52; p<0.001). Conclusion Our systematic review and meta-analysis of the extant literature provides strong support for the association between the CBCL-BP/DP profile and pediatric BP disorder.

Progress and Pitfalls in the Provision of Quality Care for Adults With Attention Deficit Hyperactivity Disorder in Primary Care

Abstract: Objective: Quality care for attention deficit hyperactivity disorder (ADHD) in adults has lagged behind other psychiatric disorders. We sought to assess how the achievement of quality measures (QMs) for diagnosing and treating ADHD in adults has changed over time. Method: We assessed 10 QMs in electronic health records (EHRs) from primary care and behavioral health clinics from 2010 to 2020 for 71,310 patients diagnosed with ADHD. Results: The achievement of QMs increased over time (p < .001). Some showed increases to high levels; others remained low throughout the observation period. No patients achieved more than six of 10 QMs in any year. Small but significant effects for sex, race, ethnicity, practice ownership, practice type, and age. Conclusion: Increase in quality care from 2010 to 2020 along with clear evidence that more efforts are needed to improve quality of care for adults with ADHD seen in primary care.

Joint polygenic and environmental risks for childhood attention‐deficit/hyperactivity disorder (ADHD) and ADHD symptom dimensions

Abstract: Background attention-deficit/hyperactivity disorder (ADHD) is associated with both polygenic liability and environmental exposures, both intrinsic to the family, such as family conflict, and extrinsic, such as air pollution. However, much less is known about the interplay between environmental and genetic risks relevant to ADHD—a better understanding of which could inform both mechanistic models and clinical prediction algorithms. Methods Two independent data sets, the population-based Adolescent Brain Cognitive Development Study (ABCD) (N = 11,876) and the case-control Oregon-ADHD-1000 (N = 1449), were used to examine additive (G + E) and interactive (GxE) effects of selected polygenic risk scores (PRS) and environmental factors in a cross-sectional design. Genetic risk was measured using PRS for nine mental health disorders/traits. Exposures included family income, family conflict/negative sentiment, and geocoded measures of area deprivation, lead exposure risk, and air pollution exposure (nitrogen dioxide and fine particulate matter). Results ADHD PRS and family conflict jointly predicted concurrent ADHD symptoms in both cohorts. Additive-effects models, including both genetic and environmental factors, explained significantly more variation in symptoms than any individual factor alone (joint R2 = .091 for total symptoms in ABCD; joint R2 = .173 in Oregon-ADHD-1000; all delta-R2 p-values <2e-7). Significant effect size heterogeneity across ancestry groups was observed for genetic and environmental factors (e.g., Q = 9.01, p = .011 for major depressive disorder PRS; Q = 13.34, p = .001 for area deprivation). GxE interactions observed in the full ABCD cohort suggested stronger environmental effects when genetic risk is low, though they did not replicate. Conclusions Reproducible additive effects of PRS and family environment on ADHD symptoms were found, but GxE interaction effects were not replicated and appeared confounded by ancestry. Results highlight the potential value of combining exposures and PRS in clinical prediction algorithms. The observed differences in risks across ancestry groups warrant further study to avoid health care disparities.

Association of ADHD symptoms with type 2 diabetes and cardiovascular comorbidities in adults receiving outpatient diabetes care

Abstract: The relationship between attention-deficit/hyperactivity disorder (ADHD) symptoms and type 2 diabetes mellitus (T2D) and its cardiovascular outcomes have not been sufficiently studied.2,986 adults with T2D from the Joslin Diabetes Center at Upstate Medical University were assessed for ADHD-like symptoms, executive dysfunction, and emotional control using the Adult Self-Report Scale V1.1 (ASRS) expanded version. Surveys were sent electronically, and clinical data were obtained from the electronic medical record. Pearson chi-square test was used for categorical variables association. When ASRS scores were the dependent variable, negative binomial regression correcting for demographic variables that were associated with the ASRS scores was used.155 (49.2%) of respondents met DSM-5 criteria for ADHD using the ASRS scores; Only ten (3.6%) of respondents had an ICD10 diagnosis of ADHD in their medical record; Forty-three (13.7%) had either a diagnosis of ADHD in the medical history or were taking medications used by people with ADHD. Higher levels of ADHD-like symptoms were found in patients with T2D compared with population norms. There was a modest association of the ASRS executive dysfunction subscale with overall cardiovascular comorbidities (p = 0.03). However, the p-value did not survive the multiple testing correction. Both ADHD-like symptoms and symptoms associated with emotional control, however, were not associated with specific cardiovascular diseases, hypertension, or with HbA1c, LDL-cholesterol, triglycerides, ALT, creatinine, or eGFR.Our results suggest that adults with T2D attending a tertiary care diabetes clinic are at risk for having ADHD-like symptoms, highlighting the importance of screening for ADHD symptoms in this specialty setting and referring undiagnosed adult patients for further assessment and treatment of ADHD. Larger studies are needed to clarify the relationship between ADHD-like symptoms, executive dysfunction, and emotional control with diabetic control and comorbidities.

Efficacy of Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder: Effect Size Across the Day

Abstract: Objective: To evaluate the treatment effect size throughout the day of amphetamine extended-release oral suspension (AMPH EROS; Tris Pharma, Inc., Monmouth Junction, NJ, USA) in a laboratory classroom study conducted in children aged 6–12 years with attention-deficit/hyperactivity disorder (ADHD). Methods: A post hoc analysis was performed to assess the overall effect size as well as the effect size at each time point from early morning through evening (1, 2, 4, 6, 8, 10, 12, and 13 hours postdose) for each efficacy measure evaluated in a 5-week, randomized, dose-optimized, double-blind, placebo-controlled, laboratory classroom assessment, efficacy, and safety study of AMPH EROS (N = 99). Change from baseline of the primary (Swanson, Kotkin, Agler, M-Flynn, Pelham [SKAMP]-C) and key secondary (secondary efficacy assessments included the SKAMP attention [SKAMP-A], SKAMP-deportment subscale [SKAMP-D], Permanent Product Measure of Performance-number of problems attempted [PERMP-A], PERMP-number of problems correct [PERMP-C]) efficacy measures were analyzed using a linear mixed model repeated-measures analysis model. Comparisons among treatments were adjusted for multiple comparisons using the Bonferroni method. The effect size was estimated using Cohen's d, to determine “small,” (0.2), “medium,” (0.5), or “large” (0.8) magnitudes of treatment effects. Results: Large overall effect sizes were observed for all primary and key secondary efficacy assessments. Moreover, the SKAMP-C, PERMP-number of problems attempted, and PERMP-C scores showed large effect sizes at each time point evaluated across the day, from 1 to 13 hours postdose. The SKAMP-A and SKAMP-D scores showed a medium to large effect size at each time point. Conclusions: AMPH EROS demonstrated a large and consistent effect size across the day, including early in the morning, in the treatment of symptoms of ADHD in children aged 6–12 years. Trial Registration: clinicaltrials.gov identifier: NCT02083783

Sudden Increases in U.S. Stimulant Prescribing: Alarming or Not?

Abstract: ADHD is a neurodevelopmental disorder with a prevalence of approximately 6% in children and 3% in adults (Song et al., 2021; Willcutt, 2012). ADHD impacts public health substantially as a potentially causal precursor to many psychiatric (e.g., depression, anxiety, addiction) and somatic conditions (e.g., obesity) (Faraone et al., 2021). It is costly due to educational, vocational, and financial impairments, loss of productivity, and increased healthcare utilization (Song et al., 2021). ADHD reduces life expectancy, mostly due to suicide, accidents, and health problems, and elevates rates of incarceration and public assistance (Faraone et al., 2021). ADHD is better recognized in children than adults with long-standing disparities in care as individuals age. Effective treatments include stimulant/non-stimulant medications and behavioral approaches. A new report from the Centers for Disease Control and Prevention (CDC) documents 5 years of rising U.S. adult stimulant prescriptions, with a substantial spike from 2020 to 2021, particularly for women (Danielson et al., 2023). These trends may stem from gradual efforts (i.e., patient and provider education on adult ADHD, expanding access to ADHD care, reduction of disparity in access to health care) and relatively sudden phenomena (i.e., cognitively/ emotionally overwhelmed patients seeking treatment in the pandemic, a recent online neurodiversity movement producing viral, relatable content on ADHD, digital startups prescribing stimulants online, symptoms of long-COVID). Although seemingly rapid increases in ADHD treatmentseeking may alarm, this increase may be medically appropriate. Women and older/middle-aged adults with ADHD are historically under-identified; stimulant prescription rates became less ageand sex-dependent during the surveillance period (see Figure 1). There also may be improved care access for individuals in rural regions or who traditionally cannot afford treatment. Despite 2016 to 2021 prescribing increases in some subgroups, prescription rates came closer to ADHD’s expected prevalence in adults during this period (Song et al., 2021; Willcutt, 2012). However, we cannot be certain that all patients pescribed stimulants have ADHD or that all prescriptions represent appropriate or effective treatment. As a next step, research could evaluate the expereinces of populations with recent prescribing: who newly sought stimulant treatment? What drove them to seek care? Some evidence suggest ADHD symptoms can wax and wane— did the pandemic exacerbate ADHD in some? Why did women seek treatment at higher rates than men? Did some individuals self-identify and self-advocate for ADHD treatment due to information or advertisements seen online? If so, was ADHD the right diagnosis? Adults driving upticks in stimulant treatment may be late-identified cases, who were missed in childhood. But with rampant ADHD misinformation online (Yeung et al., 2022), and many providers untrained in proper ADHD diagnosis, they also may be misdiagnosed. It is also critical to understand whether the subpopulation with accelerated stimulant prescribing rates received optimal treatment or if alternative strategies would have better addressed their needs. It would help to know trends in behavioral treatment utilization and non-stimulant prescriptions (four are FDA-approved for ADHD in either children, adults, or both–atomoxetine, extended release viloxazine, extended release guanfacine ER, clonidine). In addition, how many stimulant prescriptions were written but not filled? Prescription fills include refills. Did more adherent subgroups (e.g., women, middle-aged adults) create an illusion of higher prescribing in these groups? Many ambiguities must be clarified to guide appropriate public health responses. Unfortunately, knowledge about and support for research on adult ADHD lags well behind childhood ADHD and other common mental disorders. As of January 2023, our reading of the National Institutes of Health (NIH) Reporter (reporter.nih.gov) lists just under $5.5 million in active funding for adult ADHD research; it reports over $42 million in funding on pediatric ADHD. Astoundingly, the NIH Reporter lists at least 10-fold greater support for depression research than ADHD research, despite only slightly higher 1164155 JADXXX10.1177/10870547231164155Journal of Attention DisordersSibley et al. editorial2023