Faculty Bibliography

Objective: This study examined adult attention-deficit/hyperactivity disorder (ADHD) screening and management patterns among healthcare provider (HCP) subgroups. Methods: An online survey of US-based HCPs (neurologists, n=200; nurse practitioners [NPs], n=100; psychiatrists, n=201; primary care physicians [PCPs], n=201) was conducted from May to June 2017. The survey assessed issues relating to adult ADHD screening and management and HCP perceptions of factors influencing patient choice of pharmacotherapy. Participants were required to be experienced in diagnosing and/or treating ADHD in adults (≥5 patients/month for neurologists and NPs; ≥10 patients/month for psychiatrists and PCPs). Results: Significantly greater percentages of psychiatrists than non-psychiatrists were confident in diagnosing ADHD (P<0.001) and screened/evaluated for ADHD in patients with depression/anxiety disorders (P<0.001). Significantly greater percentages of psychiatrists versus non-psychiatrists prescribed once-daily long-acting (LA) stimulants (71.6% vs 62.2%; P=0.023) or short-acting (SA) stimulants more than once daily (40.3% vs 29.7%; P=0.009) as first-line therapy. In contrast, a significantly greater percentage of non-psychiatrists than psychiatrists prescribed once-daily SA stimulants (32.9% vs 17.4%; P<0.001). Psychiatrist and non-psychiatrist HCPs viewed insurance coverage/treatment costs (79.9%), perceived duration of effect (72.2%), and side effects (66.5%) as important factors to patients when choosing treatment. HCPs reported that the greatest mean ± SD percentages of patients changed their treatment regimen in the past 6 months because of perceptions of insufficient duration of effect (35.4%±22.1%) and lack of efficacy (30.3%±21.0%). Conclusion: Compared with psychiatrists, non-psychiatrists exhibited less confidence in diagnosing adult ADHD and experienced greater difficulty determining optimal treatment regimens.

OBJECTIVE:We conducted a two-period (open-label and double-blind) pilot investigation of droxidopa, with and without carbidopa, for ADHD. METHOD/METHODS:Twenty adult ADHD patients received open-label droxidopa titrated from 200 to 600 mg 3 times per day (TID; Weeks 1-3), then open-label droxidopa plus carbidopa titrated from 25 or 50 mg TID (Weeks 4-6). In Weeks 7 to 8, patients were randomized to continued co-treatment or matching placebo substitution. RESULTS:Improvements in mean total Adult ADHD Investigator Symptom Report Scale (AISRS) scores were seen at Week 1 (p < .0001) and Week 3 (p < .0001). Improvements were maintained but not increased with carbidopa. Thirteen of 20 patients completed open-label treatment. In the double-blind period, mean total AISRS scores were similar between the co-treatment (n = 6) and placebo (n = 5) groups. No serious adverse events were reported. CONCLUSION/CONCLUSIONS:These preliminary findings indicate that droxidopa can improve adult ADHD symptoms. Further studies are warranted to examine the efficacy and safety of droxidopa in ADHD.

OBJECTIVE:Dasotraline is a potent inhibitor of presynaptic dopamine and norepinephrine reuptake with a pharmacokinetic profile characterized by slow absorption and a long elimination half-life. The aim of this study was to evaluate the efficacy and safety of dasotraline in children with attention-deficit/hyperactivity disorder (ADHD). METHODS:Children aged 6-12 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of ADHD were randomized to 6 weeks of double-blind once-daily treatment with dasotraline (2 or 4 mg) or placebo. The primary efficacy endpoint was change from baseline in the ADHD Rating Scale Version IV-Home Version (ADHD RS-IV HV) total score at week 6. RESULTS:A total of 342 patients were randomized to dasotraline or placebo (mean age 9.1 years, 66.7% male). Treatment with dasotraline was associated with significant improvement at study endpoint in the ADHD RS-IV HV total score for the 4 mg/day dose versus placebo (-17.5 vs. -11.4; p < 0.001; effect size [ES], 0.48), but not for the 2 mg/day dose (-11.8 vs. -11.4; ns; ES, 0.03). A regression analysis confirmed a significant linear dose-response relationship for dasotraline. Significant improvement for dasotraline 4 mg/day dose versus placebo was also observed across the majority of secondary efficacy endpoints, including the Clinical Global Impression (CGI)-Severity score, the Conners Parent Rating Scale-Revised scale (CPRS-R) ADHD index score, and subscale measures of hyperactivity and inattentiveness. Discontinuation rates due to adverse events (AEs) were higher in the dasotraline 4 mg/day group (12.2%) compared with the 2 mg/day group (6.3%) and placebo (1.7%). The most frequent AEs associated with dasotraline were insomnia, decreased appetite, decreased weight, and irritability. Psychosis-related symptoms were reported as AEs by 7/219 patients treated with dasotraline in this study. There were no serious AEs or clinically meaningful changes in blood pressure or heart rate on dasotraline. CONCLUSION/CONCLUSIONS:In this placebo-controlled study, treatment with dasotraline 4 mg/day significantly improved ADHD symptoms and behaviors, including attention and hyperactivity, in children aged 6-12 years. The most frequently reported AEs observed on dasotraline included insomnia, decreased appetite, decreased weight, and irritability.

AIMS/OBJECTIVE:To estimate Adult ADHD Self-Report Scale (ASRS-v1.1) Symptom Checklist normative total scores among the US adult general population and to evaluate overall attention-deficit hyperactivity disorder (ADHD) symptom burden among US adults with ADHD. METHODS:Prior 2012 and 2013 US National Health and Wellness Survey respondents were re-contacted. Demographics, comorbidities, and ASRS-v1.1 data were collected. ASRS-v1.1 scores were compared by sex, age, ADHD diagnosis, and ADHD medication use. Group differences were evaluated using chi-square tests and independent samples t-tests for categorical and continuous variables, respectively. RESULTS:Of 22 397 respondents, 465 self-reported being diagnosed with ADHD by a physician; of these, 174 self-reported using ADHD medication. The mean ASRS-v1.1 total score was 2.0 (SD = 3.2); scores differed by age and sex (all, P < 0.001). ADHD (vs no ADHD) was associated with depression (58.1% vs 18.0%), anxiety (53.1% vs 16.0%), and sleep difficulties (37.0% vs 14.0%) (all, P < 0.001). ADHD medication use (vs no use) was associated with depression (68.4% vs 51.9%), anxiety (67.2% vs 44.7%), panic disorder (25.9% vs 17.2%), and insomnia (27.6% vs 19.6%) (all, P < 0.05). ADHD (vs no ADHD) respondents scored higher on all 18 ASRS-v1.1 items (all, P < 0.05). Medication users (vs non-users) scored higher on six items (all, P < 0.05). DISCUSSION/CONCLUSIONS:Adult ADHD may be undertreated or sub-optimally treated, despite a high symptom burden. Normative data will allow comparisons with individuals' scores to support the assessment of ADHD symptom burden among adults. CONCLUSION/CONCLUSIONS:Findings highlight the importance of assessing ADHD symptom burden, especially among adults presenting with comorbidities.

Objectives: Once-daily dosing with dasotraline, a novel dopamine and norepinephrine reuptakeinhibitor, achieves stable plasma concentrationsover 24 hours with once-daily dosing. This studyevaluated dasotraline in children aged 6-12 years(NCT02428088).
METHOD(S): Patients were randomized 1:1:1 to 6 weeks ofonce-daily, fixed-dose dasotraline 2 or 4 mg/day, or placebo.The primary efficacy endpoint was change from baseline(CFB) at Week 6 in ADHD Rating Scale Version IV-HomeVersion (ADHD RS-IV HV) total score, using a mixed modelfor repeated measures (MMRM) in the intent-to-treat (ITT)population. Secondary endpoints included Clinical GlobalImpression-Severity (CGI-S) score and safety endpoints.
RESULT(S): The mean age of 342 randomized patients was9.1 [SD: 1.9] years; 66.7% were male. Overall, 79% ofpatients completed the study. In the ITT population(N = 336), ADHD RS-IV HV total score improvedsignificantly with dasotraline 4 mg/day vs placebo(leastsquares [LS] mean [SE] CFB at Week 6:-17.53 [+/- 1.31]vs-11.36 [+/- 1.29], respectively, p < 0.001; effect size[ES]: 0.48). Inattentiveness and hyperactivity/impulsivity subscale scores significantly improved with 4 mg/dayvs placebo at Week 6 (p = 0.001, p = 0.003, respectively).Improvement in CGI-S score was statistically significantwith dasotraline 4 mg/day vs placebo(LS mean [SE] CFBat Week 6:-1.39 [+/- 0.12] vs-1.04 [+/- 0.12], respectively,p = 0.040; ES: 0.29). No significant improvement wasobserved on the ADHD RS-IV HV total score and theCGI-S score for dasotraline 2 mg/day vs placebo. Themost frequent treatment-emergent AEs (=5% and higherthan placebo) were (2 mg/day; 4 mg/day; placebo):insomnia (15.3%; 21.7%; 4.3%, all terms combined),decreased appetite (12.6%; 21.7%; 5.2%), weight loss(5.4%; 8.7%; 0%), irritability (3.6%; 7.0%; 6.0%),nasopharyngitis (0.9%; 5.2%; 0.9%), and nausea (0%;5.2%; 2.6%).
CONCLUSION(S): Compared with placebo, dasotraline4 mg/day significantly improved ADHD symptoms inchildren, as assessed by ADHD RS-IV HV total score andinattentiveness and hyperactivity/impulsivity subscalescores. Dasotraline was generally well tolerated; mostcommon AEs were insomnia, decreased appetite, weightloss and irritability

OBJECTIVES/OBJECTIVE:There is a need for brief and publicly-available assessments of attention deficit hyperactivity disorder (ADHD) easily administered in large-scale survey efforts monitoring symptoms among adolescents. The ADHD Self-Report Scale v1.1 (ASRS; Kessler et al., 2005) Screener, a six-item measure of ADHD symptoms, is a valid and reliable screening instrument for ADHD among adults. The current study provides initial evidence for the reliability and validity of the ASRS Screener among a community sample of U.S. adolescents. METHODS:Middle and high school students in grades 6 through 12 (N = 2,472) completed the ASRS Screener, along with the Strengths and Difficulties Questionnaire (SDQ; Goodman, 2001) and several questions about school functioning. RESULTS:The ASRS Screener demonstrated good internal consistency, with items captured by a single underlying latent variable, which was invariant across subsamples differing by gender. The ASRS Screener scores were associated with the SDQ subscale measuring hyperactivity/inattention (r = 0.58) and significantly less strongly associated with other SDQ subscale scores (r = -0.15-0.41). The ASRS Screener scores were also significantly associated with student-reported school functioning. CONCLUSION/CONCLUSIONS:Findings suggest directions for future research and provide preliminary support for use of the ASRS Screener as a brief tool for identifying symptoms of ADHD among adolescents.

In many studies of attention-deficit hyperactivity disorder (ADHD), stimulus encoding and processing (perceptual function) and response selection (executive function) have been intertwined. To dissociate deficits in these functions, we introduced a task that parametrically varied low-level stimulus features (orientation and color) for fine-grained analysis of perceptual function. It also required participants to switch their attention between feature dimensions on a trial-by-trial basis, thus taxing executive processes. Furthermore, we used a response paradigm that captured task-irrelevant motor output (TIMO), reflecting failures to use the correct stimulus-response rule. ADHD participants had substantially higher perceptual variability than controls, especially for orientation, as well as higher TIMO. In both ADHD and controls, TIMO was strongly affected by the switch manipulation. Across participants, the perceptual variability parameter was correlated with TIMO, suggesting that perceptual deficits are associated with executive function deficits. Based on perceptual variability alone, we were able to classify participants into ADHD and controls with a mean accuracy of about 77%. Participants' self-reported General Executive Composite score correlated not only with TIMO but also with the perceptual variability parameter. Our results highlight the role of perceptual deficits in ADHD and the usefulness of computational modeling of behavior in dissociating perceptual from executive processes.