Keith Saylor

Validation of the Adult ADHD Investigator Symptom Rating Scale (AISRS)

Objective: Validation of the Adult ADHD Investigator Symptom Rating Scale (AISRS) that measures aspects of ADHD in adults. Method: Psychometric properties of the AISRS total and AISRS subscales are analyzed and compared to the Conners’ Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) and the Clinical Global Impression-ADHD-Severity Scale using data from a placebo-controlled 6-month clinical trial of once-daily atomoxetine. Results: The AISRS has high internal consistency, good convergent, and discriminant validities; modest divergent validity; and small ceiling and floor effects (≤1%). It correlates highly with the CAARS-Inv:SV. Factor analysis confirms 2 AISRS subscales, hyperactivity-impulsive scale and inattention. The AISRS total and AISRS subscales perform stably. All scales demonstrate responsiveness to change with medication. Conclusion: The AISRS and its subscales are robust, valid efficacy measures of ADHD symptoms in adult patients. Its anchored items and semistructured interview are advancements over existing scales. (J. of Att. Dis. 2010; 14(1) 57-68)

Quality of life assessment in adult patients with attention-deficit/hyperactivity disorder treated with atomoxetine

Background: Attention-deficit/hyperactivity disorder (ADHD) has its onset during childhood and is estimated to affect 3% to 7% of school-aged children. Unfortunately, the disorder frequently persists into adult life. The burden of this disorder is considerable and is often characterized by academic (or occupational) impairment and dysfunction within the family and society. Despite the existence of research demonstrating the effects of ADHD on certain aspects of life, the clinical trials of treatments for this disorder have focused primarily on efficacy and safety. Methods: Atomoxetine was approved in the United States in November 2002 for the treatment of ADHD in children, adolescents, and adults. The present study uses data from a clinical trial of atomoxetine in adult patients with ADHD that incorporated a measure of health-related quality of life (the Medical Outcomes Study 36-item short-form health survey [SF-36]) as part of the overall assessment of the success of this relatively new treatment. The primary outcome measure for ADHD symptoms was the Conners Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS) ADHD total symptom score. Results: In agreement with previous studies, adult patients with ADHD treated with atomoxetine at typical doses showed significant amelioration of ADHD symptoms, as measured on the CAARS. At baseline, the measures of overall mental health (one aspect of quality of life) of adult patients with ADHD were below the average level, as measured on the SF-36. Treatment with atomoxetine significantly improved the measures of mental health and ameliorated the ADHD symptoms. In addition, the 2 measures were correlated. Conclusions: These data suggest that pharmacological intervention with atomoxetine not only ameliorates ADHD symptoms in adult patients but also improves their perceived quality of life.

Effect of Atomoxetine on Executive Function Impairments in Adults with ADHD.

Objective: To assess the effect of atomoxetine on ADHD-related executive functions over a 6-month period using the Brown Attention-Deficit Disorder Scale (BADDS) for Adults, a normed, 40-item, self-report scale in a randomized, double-blind, placebo-controlled clinical trial. Method: In a randomized, double-blind clinical trial, adults with ADHD received either atomoxetine 25 to 100 mg/day or placebo for 6 months. Patients completed the BADDS to report their current daily functioning in 5 clusters of ADHD-related impairments of executive functioning: (1) Organizing and Activating to Work; (2) Focusing for Tasks; (3) Regulating Alertness and Effort; (4) Modulating Emotions; and (5) Utilizing Working Memory. Results: Mean scores were significantly more improved in the atomoxetine group compared to the placebo group: total score, -27.0 versus -19.0 (p < .001); all 5 cluster scores, p < .01. Conclusions: Once-daily atomoxetine can improve executive function impairments in adults with ADHD as assessed by the BADDS. (J. of Att. Dis. 2011; 15(2) 130-138)

Emotional Expression in Children Treated with ADHD Medication: Development of a New Measure.

Objective: Although existing instruments contain items addressing the effect of ADHD medications on emotional expression, a review of measures did not yield any instruments that thoroughly evaluated positive and negative aspects of emotional expression. Method: The Expression and Emotion Scale for Children (EESC), a parent-report measure, was developed from an analysis of qualitative data from parent focus groups and expert opinion. Data from 179 parents and children treated with stimulants or atomoxetine are used to examine the psychometric properties of the EESC. Results: The EESC demonstrates good internal consistency and test-retest reliability. A factor analysis yields three factors (positive, flat, and emotional lability) that were consistent with the predicted structure of the measure. Small to moderate correlations between the EESC and psychological symptom measures are found, with the strength of the relationships varying by symptom measure. Conclusion: The EESC shows appropriate psychometric properties and is appropriate for use in clinical and research settings. (J. of Att. Dis. 2008; 11(5) 568-579)

A long-term open-label safety and effectiveness trial of lisdexamfetamine dimesylate in adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVE Information on psychostimulant treatment in long-term studies for attention-deficit/hyperactivity disorder (ADHD) in adolescents is limited. This study aimed to assess the safety and effectiveness of lisdexamfetamine dimesylate (LDX) over 52 weeks in adolescents with ADHD. METHODS This open-label multicenter study enrolled eligible participants after their participation in a randomized, double-blind, placebo-controlled 4 week trial in adolescents with ADHD. Following a 4 week dose-optimization phase, participants were maintained on treatment for up to ∼48 weeks on an optimal dose. Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, laboratory findings, and electrocardiograms. Effectiveness measures included the ADHD Rating Scale IV (ADHD-RS-IV; primary) and Clinical Global Impressions-Improvement (CGI-I). The Youth Quality of Life-Research Version (YQOL-R) was also included in this study; raw scores are transformed to a 0-100 point scale. RESULTS Of 269 enrolled (from the antecedent study), 265 (98.5%) were in the safety population and effectiveness population. Common TEAEs (≥5%) with LDX included upper respiratory tract infection (21.9%), decreased appetite (21.1%), headache (20.8%), decreased weight (16.2%), irritability (12.5%), insomnia (12.1%), nasopharyngitis (7.2%), influenza (6.8%), dizziness (5.3%), and dry mouth (5.3%). At end point, for all LDX doses in the overall safety population, mean (SD) increase from baseline in systolic blood pressure was 2.3 (10.53) mm Hg, diastolic blood pressure was 2.5 (8.37) mm Hg, and pulse rate was 6.3 (12.74) bpm. No clinically meaningful electrocardiogram or vital sign changes were observed. At end point with LDX treatment, the ADHD-RS-IV mean (SD) total score change from antecedent study baseline was -26.2 (9.75) (p<0.001); 87.2% of participants were improved (CGI-I=1 or 2). Baseline (antecedent study) mean (SD) YQOL-R perceptual total score was 79.8 (11.28) and increased by 3.9 (9.73) at end point (p<0.001). CONCLUSIONS LDX demonstrated a long-term safety profile similar to that of other long-acting psychostimulants and was effective, as indicated by improvements in ADHD symptoms and participant-perceived YQOL, in adolescents with ADHD. CLINICAL TRIAL REGISTRATION NCT00764868, http://www.clinicaltrials.gov/ct2/show/NCT00764868?term=SPD489-306&rank=1.

Self-Reported quality of life in adults with attention-deficit/hyperactivity disorder and executive function impairment treated with lisdexamfetamine dimesylate: a randomized, double-blind, multicenter, placebo-controlled, parallel-group study

BackgroundThis study examined the effects of lisdexamfetamine dimesylate (LDX) on quality of life (QOL) in adults with attention-deficit/hyperactivity disorder (ADHD) and clinically significant executive function deficits (EFD).MethodsThis report highlights QOL findings from a 10-week randomized placebo-controlled trial of LDX (30–70 mg/d) in adults (18–55 years) with ADHD and EFD (Behavior Rating Inventory of EF-Adult, Global Executive Composite [BRIEF-A GEC] ≥65). The primary efficacy measure was the self-reported BRIEF-A; a key secondary measure was self-reported QOL on the Adult ADHD Impact Module (AIM-A). The clinician-completed ADHD Rating Scale version IV (ADHD-RS-IV) with adult prompts and Clinical Global Impressions-Severity (CGI-S) were also employed. The Adult ADHD QoL (AAQoL) was added while the study was in progress. A post hoc analysis examined the subgroup having evaluable results from both AIM-A and AAQoL.ResultsOf 161 randomized (placebo, 81; LDX, 80), 159 were included in the safety population. LDX improved AIM-A multi-item domain scores versus placebo; LS mean difference for Performance and Daily Functioning was 21.6 (ES, 0.93, P<.0001); Impact of Symptoms: Daily Interference was 14.9 (ES, 0.62, P<.0001); Impact of Symptoms: Bother/Concern was 13.5 (ES, 0.57, P=.0003); Relationships/Communication was 7.8 (ES, 0.31, P=.0302); Living With ADHD was 9.1 (ES, 0.79, P<.0001); and General Well-Being was 10.8 (ES, 0.70, P<.0001). AAQoL LS mean difference for total score was 21.0; for subscale: Life Productivity was 21.0; Psychological Health was 12.1; Life Outlook was 12.5; and Relationships was 7.3. In a post hoc analysis of participants with both AIM-A and AAQoL scores, AIM-A multi-item subgroup analysis scores numerically improved with LDX, with smaller difference for Impact of Symptoms: Daily Interference. The safety profile of LDX was consistent with amphetamine use in previous studies.ConclusionsOverall, adults with ADHD/EFD exhibited self-reported improvement on QOL, using the AIM-A and AAQoL scales in line with medium/large ES; these improvements were paralleled by improvements in EF and ADHD symptoms. The safety profile of LDX was similar to previous studies.Trial registrationClinicalTrials.gov, NCT01101022

The Life Participation Scale for Attention-Deficit/Hyperactivity Disorder–Child Version: Psychometric Properties of an Adaptive Change Instrument

INTRODUCTION The Life Participation Scale for Attention-Deficit/Hyperactivity Disorder (ADHD)-Child Version (LPS-C) was developed to capture treatment-related improvements in adaptive functioning, including quality of life, social development, and emotion regulation, that may be missed by scales that assess only the 18 ADHD symptoms in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). The 24-item LPS-C is intended to augment traditional ADHD measures. This analysis assessed the scales psychometric properties. METHODS The LPS-C was completed by the investigators while questioning the parents of 979 children in three placebo-controlled clinical trials that measured the effects of atomoxetine for treating ADHD. In addition to a factor analysis, assessments of responsiveness; internal consistency; item-to-total correlations; and convergent, divergent, and discriminant validity were completed. RESULTS The LPS-C showed evidence of internal consistency and convergent, divergent, and discriminant validity. The factor analysis suggested two subscales (labeled the Self-Control and Agreeable subscales). The LPS-C demonstrated responsiveness in two of the three trials. The effect sizes suggest responsiveness between that for psychosocial measures and core symptom measures. CONCLUSIONS The LPS-C appears to be a valid research and clinical instrument for assessing change in ADHD-related adaptive functioning that may not be captured by traditional measures of core ADHD symptoms.

Atomoxetine once daily for 24 weeks in adults with attention-deficit/ hyperactivity disorder (ADHD): Impact of treatment on family functioning

ObjectiveTo assess the efficacy of atomoxetine (ATX) and impact of treatment on family functioning in adults with ADHD. MethodsAdults with attention-deficit/hyperactivity disorder (ADHD) having both a spouse/partner and child were randomized to placebo (n = 234) or ATX (n = 268) for 24 weeks. Attention-deficit/hyperactivity disorder measures included the Conners Adult ADHD Rating Scale total ADHD Symptoms score and Clinical Global Impression-ADHD—Severity. Marital measures included the Dyadic Adjustment Scale and the Family Assessment Measure Dyadic Relationship Scale (FAM III). Parenting measures included the Parenting Stress Index, Alabama Parenting Questionnaire, and Parenting Sense of Competence Scale (PSCS). ResultsImprovement was greater with ATX over placebo at 24 weeks on the Conners Adult ADHD Rating Scale (−16.43 vs −8.65; P < 0.001, repeated measures) and Clinical Global Impression (P < 0.001, last observation carried forward). Baseline-to-end point changes in marital and parenting measures were significant but not between treatment groups. Post hoc analyses showed significant interaction of treatment and impairment for the FAM III Task Accomplishment (patient) and Role Performance (patient and spouse) items and PSCS efficacy. Further stratification by sex or presence of a child with ADHD yielded significant interaction and treatment differences for the FAM III Task Accomplishment and the FAM III and Dyadic Adjustment Scale affective expression items, PSCS total score, Alabama Parenting Questionnaire Corporal Punishment, and Parenting Stress Index attachment items. ConclusionsAtomoxetine demonstrated significant ADHD symptom reduction over 24 weeks. Although both groups demonstrated baseline-to-end point changes on many marital and parenting measure items, there were no treatment differences. Maladaptive behaviors of long-standing ADHD may benefit from both medication and behavioral-psychosocial intervention.

Impulsive Aggression as a Comorbidity of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents

Abstract Objective: This article examines the characteristics of impulsive aggression (IA) as a comorbidity in children and adolescents with attention-deficit/hyperactivity disorder (ADHD), focusing on its incidence, impact on ADHD outcomes, need for timely intervention, and limitations of current treatment practices. Methods: Relevant literature was retrieved with electronic searches in PubMed and PsycINFO using the search strategy of “ADHD OR attention deficit hyperactivity disorder” AND “impulsive aggression OR reactive aggression OR hostile aggression OR overt aggression” AND “pediatric OR childhood OR children OR pre-adolescent OR adolescent” with separate searches using review OR clinical trial as search limits. Key articles published before the 2007 Expert Consensus Report on IA were identified using citation analysis. Results: More than 50% of preadolescents with ADHD combined subtype reportedly display clinically significant aggression, with impulsive aggression being the predominant subtype. Impulsive aggression is strongly predictive of a highly unfavorable developmental trajectory characterized by the potential for persistent ADHD, increasing psychosocial burden, accumulating comorbidities, serious lifelong functional deficits across a broad range of domains, delinquency/criminality, and adult antisocial behavior. Impulsive aggression, which triggers peer rejection and a vicious cycle of escalating dysfunction, may be a key factor in unfavorable psychosocial outcomes attributed to ADHD. Because severe aggressive behavior does not remit in many children when treated with primary ADHD therapy (i.e., stimulants and behavioral therapy), a common practice is to add medication of a different class to specifically target aggressive behavior. Conclusions: Impulsive aggression in children and adolescents with ADHD is a serious clinical and public health problem. Although adjunctive therapy with an aggression-targeted agent is widely recommended when aggressive behaviors do not remit with primary ADHD therapy, empirical evidence does not currently support the use of any specific agent. Randomized controlled trials are needed to identify aggression-targeted agents with favorable benefit–risk profiles.

Post Hoc Analysis: Early Changes in ADHD-RS Items Predict Longer Term Response to Atomoxetine in Pediatric Patients

Data from 5 atomoxetine trials in pediatric outpatients with attention-deficit/hyperactivity disorder (ADHD) were divided into training and validation data sets to develop models predicting atomoxetine treatment response, using changes in individual ADHD Rating Scale (ADHD-RS) items early in treatment. Treatment response was predicted after 1 week by a ≥1-point score decrease in ADHD-RS item 15 (“easily distracted;” positive predictive values [PPVs]: 84.9%, 74.3%, and 73.3%; negative predictive values [NPVs]: 52.6%, 50.5%, and 46.3%; training and 2 validation data sets, respectively); after 2 to 3 weeks, by a ≥1-point score decrease in ADHD-RS item 1 (“fails to give close attention or makes careless mistakes;” PPV = 77.7% and 77.9%) and by the absence of a ≥1-point score decrease on ADHD-RS items 1 and 10 (“on the go;” NPV = 72.2% and 77.5%), or by the combination of items 1 and 10 (PPVs: 75.1% and 75.4%; NPVs: 72.2% and 77.5%; training and validation data sets, respectively).