Faculty Bibliography

Objective: Evaluate the efficacy and tolerability of triple-bead mixed amphetamine salts (MAS) in ADHD. Method: Adults with ADHD Rating Scale IV (ADHD-RS-IV) total scores ≥32 were randomized to 6 weeks of triple-bead MAS (25, 50, or 75 mg) or placebo. The primary endpoint was ADHD-RS-IV total score change from baseline at end of study (EOS). Results: Least squares mean (95% confidence interval [CI]) treatment differences for ADHD-RS-IV total score changes from baseline to EOS significantly favored triple-bead MAS (all doses combined: -10.6 [-13.2, -8.0]; p < .0001); there were no significant differences between triple-bead MAS dosages. The most frequently reported TEAEs with triple-bead MAS (all doses combined) included insomnia, decreased appetite, and dry mouth. Mean ± SD pulse and systolic blood pressure increases at EOS were 3.5 ± 10.33 bpm and 0.3 ± 10.48 mmHg with triple-bead MAS (all doses combined). Conclusion: Triple-bead MAS significantly reduced adult ADHD symptoms; the safety profile was consistent with previous triple-bead MAS studies.

Objectives: To identify the relationship between the core Diagnostic and Statistical Manual of Mental Disorders (5th ed.) ADHD symptoms and executive function deficits (EFDs), to evaluate ADHD characteristics of those with executive dysfunction (ED), and to examine the predictive utility of the Adult ADHD Investigator Symptom Rating Scale (AISRS) in identifying those with adult ADHD and ED. Method: Two samples (referred and primary care practice) were pooled together for present analysis. Results: Final analysis included 297 respondents, 171 with adult ADHD. Spearman correlation coefficients and binary logistic regressions demonstrated that ADHD inattentive (IA) and hyperactive-impulsive (H-I) symptoms were moderately to strongly correlated with and highly predictive of EFDs. Receiver operating characteristic curve analysis showed that an AISRS DSM 18-item score of ⩾ 28 was most predictive of clinical ED. Conclusion: ADHD symptoms were strongly correlated with and predictive of EFDs, clinicians should screen adults with ADHD for EFDs and ADHD treatment providers should track EFD improvement in addition to DSM-5 ADHD symptoms.

Reports an error in "The World Health Organization Adult Attention-Deficit/Hyperactivity Disorder Self-Report Screening Scale for DSM-5" by Berk Ustun et al. (JAMA Psychiatry, 2017[May], Vol 74[5], 520-526). In the original article, there were errors in the footnote to Table 1 and in a corresponding section of Results. In Table 1 footnote a, the phrase "the highest scores are 5 for questions 1 and 2" should have read "the highest scores are 6 for question 3, 5 for questions 1 and 2," and the range given as "the range 0 of 24" should have been "in the range of 0 to 25." The corresponding 2 mentions in the Results of "0to 24" should have been "0to 25." This article was also corrected on October 25, 2017, to fix an error in Results. This article was corrected online. (The abstract of the original article appeared in record 2017-32659-009). Importance: Recognition that adult attention-deficit/hyperactivity disorder (ADHD) is common, seriously impairing, and usually undiagnosed has led to the development of adult ADHD screening scales for use in community, workplace, and primary care settings. However, these scales are all calibrated to DSM-IV criteria, which are narrower than the recently developed DSM-5 criteria. Objectives: To update for DSM-5 criteria and improve the operating characteristics of the widely used World Health Organization Adult ADHD Self-Report Scale (ASRS) for screening. Design, setting, and participants: Probability subsamples of participants in 2 general population surveys (2001-2003 household survey [n = 119] and 2004-2005 managed care subscriber survey [n = 218]) who completed the full 29-question self-report ASRS, with both subsamples over-sampling ASRS-screened positives, were blindly administered a semistructured research diagnostic interview for DSM-5 adult ADHD. In 2016, the Risk-Calibrated Supersparse Linear Integer Model, a novel machine-learning algorithm designed to create screening scales with optimal integer weights and limited numbers of screening questions, was applied to the pooled data to create a DSM-5 version of the ASRS screening scale. The accuracy of the new scale was then confirmed in an independent 2011-2012 clinical sample of patients seeking evaluation at the New York University Langone Medical Center Adult ADHD Program (NYU Langone) and 2015-2016 primary care controls (n = 300). Data analysis was conducted from April 4, 2016, to September 22, 2016. Main outcomes and measures: The sensitivity, specificity, area under the curve (AUC), and positive predictive value (PPV) of the revised ASRS. Results: Of the total 637 participants, 44 (37.0%) household survey respondents, 51 (23.4%) managed care respondents, and 173 (57.7%) NYU Langone respondents met DSM-5 criteria for adult ADHD in the semistructured diagnostic interview. Of the respondents who met DSM-5 criteria for adult ADHD, 123 were male (45.9%); mean (SD) age was 33.1 (11.4) years. A 6-question screening scale was found to be optimal in distinguishing cases from noncases in the first 2 samples. Operating characteristics were excellent at the diagnostic threshold in the weighted (to the 8.2% DSM-5/Adult ADHD Clinical Diagnostic Scale population prevalence) data (sensitivity, 91.4%; specificity, 96.0%; AUC, 0.94; PPV, 67.3%). Operating characteristics were similar despite a much higher prevalence (57.7%) when the scale was applied to the NYU Langone clinical sample (sensitivity, 91.9%; specificity, 74.0%; AUC, 0.83; PPV, 82.8%). Conclusions and relevance: The new ADHD screening scale is short, easily scored, detects the vast majority of general population cases at a threshold that also has high specificity and PPV, and could be used as a screening tool in specialty treatment settings.

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: Quality measures (QMs; also known as Quality Indicators) quantify health care processes, outcomes, patient perceptions, and organizational structure and/or systems that are relevant to the provision of high-quality health care. We describe the first phase of a project that has as its ultimate goal the creation and validation of QMs for tracking the screening, diagnosis, treatment, and clinical follow-up of adults with ADHD. This will fill an important gap in the field of Adult ADHD because QMs for adult ADHD do not exist. Method: We followed the guidelines of the U.S. Agency for Healthcare Research and Quality (AHRQ) for the development of QMs. These guidelines call for two phases: (1) Identify Candidate QMs and (2) Assess Candidate QMs. This article describes the results of our Phase 1 activities. To generate QMs for adult ADHD, we took the following steps: (a) searched the clinical/research literature for adult ADHD QMs; (b) convened a multidisciplinary panel comprising clinical and research experts and had them brainstorm potential QMs in the areas of screening, diagnosis, treatment, follow-up, care coordination, and patient experience; (c) compared these QMs with existing guidelines for adult ADHD to see if any potential QMs had been missed, this led to a draft list of 46 QMs; (d) had 28 ADHD experts rate the importance, reliability, validity, feasibility, and usability of the QMs. Results: The literature review found several QMs for ADHD in youth but none for ADHD in adults. The brainstorming session generated 52 QMs. The survey showed that all of these QMs were highly rated but that there was sufficient variability in ratings to prioritize some QMs over others. Conclusion: Based on these results, we prioritized QMs to carry forward into the next phase of the project. This work fills an important gap for the clinical care of adult patients with ADHD and helps to set a precedent for mental health, which has lagged behind other areas of medicine in developing QMs.

Objective: The aim of this study is to validate the Adult ADHD Self-Report Scale (ASRS) and Adult ADHD Investigator Symptom Rating Scale (AISRS) expanded versions, including executive function deficits (EFDs) and emotional dyscontrol (EC) items, and to present ASRS and AISRS pilot normative data. Method: Two patient samples (referred and primary care physician [PCP] controls) were pooled together for these analyses. Results: Final analysis included 297 respondents, 171 with adult ADHD. Cronbach's alphas were high for all sections of the scales. Examining histograms of ASRS 31-item and AISRS 18-item total scores for ADHD controls, 95% cutoff scores were 70 and 23, respectively; histograms for pilot normative sample suggest cutoffs of 82 and 26, respectively. Conclusion: (a) ASRS- and AISRS-expanded versions have high validity in assessment of core 18 adult ADHD Diagnostic and Statistical Manual of Mental Disorders (DSM) symptoms and EFD and EC symptoms. (b) ASRS (31-item) scores 70 to 82 and AISRS (18-item) scores from 23 to 26 suggest a high likelihood of adult 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.

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.