Faculty Bibliography

BACKGROUND AND OBJECTIVE/OBJECTIVE:) is a nonstimulant medication that has been approved by the United States Food and Drug Administration (FDA) for treatment of attention-deficit/hyperactivity disorder (ADHD) in children (> 6 years old) and adults. This phase 3 open-label extension to a pivotal phase 3, double-blind trial evaluated the long-term safety and continued efficacy of viloxazine ER in adults with ADHD. METHODS:This was a multicenter, flexible-dose, open-label extension to a phase III, double-blind, placebo-controlled trial (NCT04016779). Viloxazine ER was initiated at 200 mg/day and adjusted (between 200 and 600 mg/day) to achieve optimal efficacy and tolerability. Trial enrollment was halted temporarily (24 March 2020 to 23 July 2020) due to the coronavirus disease 2019 (COVID-19) pandemic. Participants completing double-blind treatment during that time were offered delayed enrollment upon trial requalification. Safety outcomes were the primary objectives. Secondary objectives were efficacy outcomes, including the ADHD Investigator Symptom Rating Scale (AISRS), and were assessed relative to double-blind baseline (or trial re-entry baseline for those whose enrollment was delayed by the COVID-19 pandemic). RESULTS:Overall, 159 participants (133 immediate and 26 delayed rollover) received viloxazine ER, with a mean exposure of 265 ± 254.9 days. Adverse events (AEs) included (> 10% incidence) insomnia (13.8%), nausea (13.8%), headache (10.7%), and fatigue (10.1%). AEs led to discontinuation for 17.6% of participants [most commonly insomnia (2.5%), nausea (2.5%), and fatigue (1.9%)]. AISRS total score [baseline mean ± standard deviation (SD): 37.9 ± 6.3] improved by the first follow-up visit (-11.4 ± 9.5; week 2) with continued improvement at subsequent visits (last on-study visit: -18.2 ± 11.54). Similar patterns of improvement were seen for other measures of efficacy, including quality of life and executive function. Following initial dose optimization, most participants (73%) used viloxazine ER doses ≥ 400 mg/day, with 36% using doses of 600 mg/day. CONCLUSIONS:Long-term viloxazine ER use was well tolerated, with no new long-term safety findings. Improvements in ADHD symptoms and associated measures were sustained throughout trial participation. In total, 73% percent of adult participants in this long-term study used viloxazine ER doses of 400 mg or more during maintenance treatment. CLINICAL TRIAL REGISTRATION/BACKGROUND:Clinicaltrials.gov Identifier: NCT04143217.

OBJECTIVE/UNASSIGNED:Several studies have shown that Adult ADHD presents differently in younger and older adults. We sought to assess the difference in care between these two groups using previously identified quality measures (QMs). METHODS/UNASSIGNED:Using electronic health record data, we matched a younger group of ADHD patients to an older group. We then assessed the achievement of the QMs using probit models with and without interaction terms. RESULTS/UNASSIGNED:The majority of QMs shown an increase in achievement for both groups over time. However, significant differences in quality of care between younger and older adult ADHD patients persisted. By the end of the study period, with the exception of three QMs, younger patients achieved the QMs more. CONCLUSION/UNASSIGNED:While, in general, the quality of care for adult ADHD increased from 2010 to 2020, there were still differences in care between younger and older adult ADHD patients.

OBJECTIVE/UNASSIGNED:To examine the effects of triple beaded mixed amphetamine salts (TB MAS) on ADHD and executive dysfunction symptoms throughout the day in adults with DSM-5 ADHD. METHOD/UNASSIGNED:This was a 6 week, single-blind, placebo-lead in trial of TB MAS (12.5-37.5 mg/day); all participants received 2 weeks of single-blind placebo); one individual was a placebo responder and was discontinued. One of these 18 dropped after 1 week on 12.5 mg/day, while all others completed the trial and received 37.5 mg/day TB MAS. RESULTS/UNASSIGNED:There were significant effects of TB MAS on all clinical measures, including investigator overall symptoms (AISRS); self-report overall (ASRS), time-sensitive ADHD (TASS) scores throughout the day, impairment (CGI) and executive function scores (BRIEF-A). TB MAS was generally well tolerated. CONCLUSIONS/UNASSIGNED:This study extends prior findings of TB MAS to adults with DSM-5 ADHD; it further re-validates findings of efficacy of TB MAS throughout the day.

OBJECTIVE/UNASSIGNED:Examine differences in care patterns around adult ADHD between race (White/Non-White) and ethnic (Hispanic/Non-Hispanic) groups utilizing existing quality measures (QMs), concerning diagnosis, treatment, and medication prescribing. METHODS/UNASSIGNED:The AAFP National Research Network in partnership with SUNY Upstate Medical used an EHR dataset to evaluate achievement of 10 ADHD QMs. The dataset was obtained from DARTNet Institute and includes 4 million patients of 873 behavioral and primary care practices with at least 100 patients from 2010 to 2020. Patients 18-years or older with adult ADHD were included in this analysis. RESULTS/UNASSIGNED:White patients and Non-Hispanic/Latinx patients were more likely to achieve these QMs than Non-White patients and Hispanic/Latinx patients, respectively. Differences between groups concerning medication and monitoring demonstrate a disparity for Non-White and Hispanic/Latinx populations. CONCLUSIONS/UNASSIGNED:Using QMs in EHR data can help identify gaps in ADHD research. There is a need to continue investigating disparities of quality adult ADHD care.

OBJECTIVE/UNASSIGNED:Studies show adult ADHD presents differently in men and women, however few studies contrast ADHD in cisgender and gender diverse adults. We assessed care differences between these groups using previously identified quality measures (QMs). METHODS/UNASSIGNED:Using EHR data, we matched a group of male ADHD patients to a female group. We followed the same procedure with a cisgender group and one identified as gender diverse through a gender dysphoria diagnosis. QM achievement was measured using logistic regression models. RESULTS/UNASSIGNED:Most QMs exhibited increasing achievement over time for all groups. Variations in care quality between males and females persisted, with female patients achieving QMs more often. There were no appreciable differences between the cisgender and gender diverse groups. CONCLUSION/UNASSIGNED:Though quality care for adult ADHD improved from 2010 to 2020, differences between male and female patients lingered. This effect was not observed in cisgender and gender diverse patients.

We conducted a prospective, single arm, multisite, multinational, open label trial assessing the safety and efficacy of a novel amygdala derived neurofeedback treatment, designated Amygdala-Derived-EFP, for chronic PTSD. Participants, including veterans and civilians, underwent screening, training, 15 neurofeedback sessions over 8 weeks and; baseline, termination (8 weeks) and 3 month post treatment assessments with validated measures. The primary endpoint was more than 50 % of the participants demonstrating a Minimally Clinically Important Difference (MCID) defined as a 6-point reduction, on the Clinician Administered PTSD Scale (CAPS-5) total score at 3 months. Secondary measures included the PCL-5, ERQ, PHQ-9, and CGI. Statistical analyses were performed using SAS®V9.4. The primary endpoint was met, with a CAPS-5 MCID response rate of 66.7 %. The average reduction in CAPS-5 total scores at 3 month follow up was 13.5 points, more than twice the MCID. Changes from baseline in CAPS-5, PCL-5, PHQ-9 scores at 8 weeks and the 3 month follow-up demonstrated statistically significant improvements in response and; demonstrated effect sizes ranging from 0.46 to 1.07. Adverse events were mild and resolved after treatment. This study builds on prior research demonstrating similar outcomes using amygdala-derived neurofeedback. Positive attributes of this therapy include monitoring by non-physician personnel, affordability, accessibility, and tolerability.

OBJECTIVE/UNASSIGNED:A pilot study to preliminarily examine the effects of Prism EFP NeuroFeedback (NF) in adult ADHD. METHOD/UNASSIGNED:Prism EFP NF is a form of NF specifically designed to target emotional dysregulation (ED) through down regulation of amygdala activity. Prism EFP NF has been shown to improve other disorders with significant ED. Nine participants with adult ADHD received an open trial of Prism EFP NF consisting of fifteen sessions over 8 weeks; all completed at least 5 weeks of treatment with seven completing all 8 weeks. Outcomes were assessed by change in ADHD symptoms from baseline to End of Treatment. RESULTS/UNASSIGNED:About two-third reduction was seen in total DSM ADHD symptom scores (primary outcome measure) with improvement observed in all other clinical measures. No significant adverse events were seen. CONCLUSION/UNASSIGNED:This preliminary trial found substantial effects of Prism EFP NF on ADHD/ED symptoms and global impairment.

OBJECTIVE/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED:< .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/UNASSIGNED: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.

PURPOSE/BACKGROUND/OBJECTIVE:Centanafadine is an inhibitor of norepinephrine, dopamine, and serotonin reuptake transporters under investigation for the treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS/PROCEDURES/METHODS:Two phase 3 randomized, double-blind, placebo-controlled, parallel-group studies of 200 mg/d or 400 mg/d centanafadine sustained-release tablets versus placebo included adults (18-55 years of age) with a diagnosis of ADHD. The primary and key secondary efficacy endpoints were the change from baseline at day 42 in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score and the Clinical Global Impression-Severity of Illness Scale, respectively. FINDINGS/RESULTS/RESULTS:Subjects randomized in study 1 (centanafadine 200 mg/d, n = 149; centanafadine 400 mg/d, n = 149; placebo, n = 148) and study 2 (centanafadine 200 mg/d, n = 145; centanafadine 400 mg/d, n = 143; placebo, n = 142) had moderate to severe ADHD (mean AISRS total score, 38.7 [SD, 6.8] across both studies). At day 42, statistically significant least-squares mean differences in AISRS total score were observed in favor of centanafadine versus placebo in study 1 (200 mg/d: -3.16, P = 0.019; 400 mg/d: -2.74, P = 0.039) and study 2 (200 mg/d: -4.01, P = 0.002; 400 mg/d: -4.47, P = 0.001). Effect sizes versus placebo were -0.28 for 200 mg/d and -0.24 for 400 mg/d in study 1 and -0.37 for 200 mg/d and -0.40 for 400 mg/d in study 2. The overall rate of treatment-emergent adverse events (TEAEs) was low, but there was a small increase in TEAE occurrence with increasing dose. Incidences of serious TEAEs and abuse potential-related AEs were low. IMPLICATIONS/CONCLUSIONS/CONCLUSIONS:These are the first large-scale studies to demonstrate the efficacy and safety profiles of 200 mg/d and 400 mg/d centanafadine in adults with ADHD.