Thomas E. Brown

Assess executive function (EF) improvement with SHP465 mixed amphetamine salts (MAS) extended-release in adults with attention-deficit/hyperactivity disorder (ADHD) using responder analyses of the Brown Attention-Deficit Disorder Scale (BADDS). Post hoc analyses examined data from placebo-controlled SHP465 MAS dose-optimization (12.5–75 mg) and fixed-dose (25–75 mg) studies. Treatment response was assessed using two definitions (BADDS total score at endpoint p < .0001) in the dose-optimization (BADDS <50: 41.9% vs. 19.2%; below 90% CI range: 57.4% vs. 29.6%) and fixed-dose (BADDS <50: 51.9% vs. 16.7%; below 90% CI range: 70.6% vs. 32.3%) studies. Improvement in EF measured by BADDS response rates was approximately 2-fold greater with SHP465 MAS than placebo.

Executive function (EF) deficits are not generally considered synonymous with attention-deficit/hyperactivity disorder (ADHD). Evidence suggests stimulants improve ADHD symptoms and EF deficits in adults with ADHD, but the relationships between improvements in these domains have not been studied. These post hoc analyses used data from a 10-week double-blind, placebo-controlled study of adults with ADHD and EF deficits treated with lisdexamfetamine dimesylate (30-70 mg) or placebo conducted from May 2010 to November 2010. Efficacy endpoints included change from baseline at week 10/early termination (ET) in self-report Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Global Executive Composite (GEC) T-score and ADHD-Rating Scale with Adult Prompts total score (ADHD-RS-AP-TS). Relationships between ADHD symptom and EF changes were examined using recursive path analyses. Mediation proportions were 0.62 (indirect and total treatment effect coefficients [95% CI]: -6.85 [-9.83 to -3.86] and -11.12 [-14.88 to -7.37]) for self-report BRIEF-A GEC T-score change from baseline at week 10/ET on ADHD-RS-AP-TS change from baseline at week 10/ET and 0.93 (indirect and total treatment effect coefficients [95% CI]: -10.34 [-14.11 to -6.57] and -11.18 [-15.80 to -6.55]) for ADHD-RS-AP-TS change from baseline at week 10/ET on self-report BRIEF-A GEC T-score change from baseline at week 10/ET. Although these data suggest ADHD symptom and EF deficit improvement following lisdexamfetamine are interdependent, it is advantageous to use measures like the BRIEF-A to assess stimulant effects on the wide range of EF deficits associated with ADHD that are not captured by the ADHD-RS-AP alone. Data used in this secondary analysis came from ClinicalTrials.gov identifier: NCT01101022.

To characterize impairments in daily life experienced by pharmacologically treated adults with attention-deficit/hyperactivity disorder (ADHD) versus adults without ADHD and to identify unmet needs in ADHD treatment from the perspective of adults with ADHD. Adults with ADHD taking prescription medication for ≥ 6 months and adults without ADHD agreed to participate in a cross-sectional online survey during December 2016. Participants with ADHD were stratified by their current ADHD medication: long-acting (LA) once daily, short-acting (SA) ≤ 2 times/d, and augmenters (AU; LA > 1 time/d, SA > 2 times/d, or LA plus SA). A total of 616 adults with ADHD (SA: n = 166, LA: n = 201, AU: n = 249) and 200 adults without ADHD completed the survey. Even with treatment, adults with ADHD reported substantial impairments in their everyday life, particularly at home, at school/work, and in their social life and relationships. Participants with ADHD experienced impairments throughout the day, especially in the afternoon and evening. Signs or symptoms were reported when the ADHD medication was wearing off, resulting in negative effects (including school work, homework, work responsibilities, household responsibilities, emotional responses, mood, and relationships) on the daily life of adults with ADHD. Adults with ADHD, despite receiving medication, experienced impairments and challenges in many aspects of their daily life. Adults with ADHD described various unmet needs, especially those relating to the duration of treatment effect. When optimizing treatment for adults with ADHD, it is important that the treatment regimen is sufficient to meet the needs of the patient throughout the day.

Objective: This study tests the hypotheses that (a) adolescents and adults with ADHD score lower on two normed measures of verbal working memory, relative to their overall verbal abilities, than the general population and (b) a specific story memory test is a more sensitive and relevant measure of working memory impairment than a numerically based test. Method: Scores on normed story memory and numerical memory tests of 220 adolescents and adults with ADHD were corrected for the individual’s verbal abilities and compared with each other and national norms. Results: Participants with ADHD scored significantly below their verbal ability measure on both verbal and numerically based memory tests in comparison with national norms. Scores on verbal memory test were lower than scores for numerically based memory tests. Conclusion: This story memory test is a more sensitive measure of working memory impairments in adolescents and adults with ADHD than measures based on recall of numerical data.

This analysis assessed the relationship of various cutoff scores of the ADHD Rating Scale IV (ADHD-RS-IV) to levels of improvement in ADHD-related executive function (EF), measured by the Brown ADD Scale for Adults (BADDS), which may provide a measure of clinically meaningful EF improvement after ADHD treatment. Post hoc analysis of a 4-week, open-label, dose-optimization phase in a double-blind, placebo-controlled study of lisdexamfetamine dimesylate (LDX) in adults with ADHD. The BADDS for Adults, a validated, normed, self-report measure of EF in ADHD, provides a qualitative measure to rate treatment progress. The ADHD-RS-IV assesses current symptom status based on DSM-IV criteria. Postbaseline ADHD-RS-IV scores were categorized according to four cutoff criteria of symptom remission: (1) ADHD-RS-IV total score ≤18; (2) ADHD-RS-IV total score ≤10; (3) no ADHD-RS-IV item scored >1; and (4) ADHD-RS-IV total score ≤18 and ≤2 items per subscale with a score of 2. Sensitivity and specificity of criteria for identifying participants with optimal BADDS scores were assessed using receiver operating characteristics (ROC). Safety evaluation included treatment-emergent adverse events (TEAEs). At endpoint, 85/127 participants had optimal BADDS scores. Linear ANOVA indicated limited overlap between BADDS and ADHD-RS-IV scores (r ² = 0.20; P < 0.0001). Specificity was similar for criteria 1–4 (0.46, 0.39, 0.39, and 0.42), as were ROC (0.699, 0.776, 0.732, and 0.668). Sensitivity was high for criteria 2 and 3 (0.96, 0.92), lower for criteria 1 and 4 (0.72, 0.75). TEAEs were consistent with those of stimulants. Criteria 2 and 3 had satisfactorily high sensitivity, but no criteria had adequate specificity. AUC comparison indicated that criteria 2 and 3 ADHD-RS-IV thresholds may be more accurate assessments of EF normalization as measured by the BADDS. The open-label design, small sample size, and selection criteria limit the applicability of these results to a larger treatment population.

The gastrointestinal motility agents metoclopramide and domperidone are known to increase pituitary prolactin (PRL) secretion and breast milk production. This study compared the effect of single doses of two strengths of metoclopramide and a single dose of domperidone on PRL secretion. Ten nonpregnant women had baseline evaluation of serum PRL concentrations. The PRL concentrations were then determined after random oral administration of metoclopramide 10 mg, metoclopramide 5 mg, and domperidone 10 mg. Blood samples were drawn in the first 7 days of the menstrual cycle, at 13 time points over a 6-hour period (0, 15, 30, 45, 60, 75, 90, 120, 150, 180, 240, 300, and 360 minutes), with the zero time point beginning at 0800 hours. Variables such as weight, height, age, gravidity, parity, and oral contraceptive use were recorded. Baseline PRL concentrations showed the natural circadian rhythm. Metoclopramide and domperidone both caused a significant increase in PRL. However, PRL secretion was most influenced by parity. Nulliparous women had the quickest and highest PRL secretion with metoclopramide 10 mg, compared with the PRL response with metoclopramide 5 mg and domperidone 10 mg. Conversely, multiparous women had PRL secretion patterns that were equivalent between the medications. The PRL response to the medications was most influenced by parity. Therefore, we suggest that the medication therapy of choice for enhancing lactation may not be the same in all women, but may instead be determined by parity.