Faculty Bibliography

BACKGROUND: Although DSM-IV attention deficit hyperactivity disorder (ADHD) is known to be associated with numerous adverse outcomes, uncertainties exist about how much these associations are mediated temporally by secondary co-morbid disorders. METHOD: The US National Comorbidity Survey Replication Adolescent Supplement (NCS-A), a national survey of adolescents aged 13-17 years (n = 6483 adolescent-parent pairs), assessed DSM-IV disorders with the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). Statistical decomposition was used to compare direct effects of ADHD with indirect effects of ADHD through temporally secondary mental disorders (anxiety, mood, disruptive behavior, substance disorders) in predicting poor educational performance (suspension, repeating a grade, below-average grades), suicidality (ideation, plans, attempts) and parent perceptions of adolescent functioning (physical and mental health, interference with role functioning and distress due to emotional problems). RESULTS: ADHD had significant gross associations with all outcomes. Direct effects of ADHD explained most (51.9-67.6%) of these associations with repeating a grade in school, perceived physical and mental health (only girls), interference with role functioning and distress, and significant components (34.5-44.6%) of the associations with school suspension and perceived mental health (only boys). Indirect effects of ADHD on educational outcomes were predominantly through disruptive behavior disorders (26.9-52.5%) whereas indirect effects on suicidality were predominantly through mood disorders (42.8-59.1%). Indirect effects on most other outcomes were through both mood (19.8-31.2%) and disruptive behavior (20.1-24.5%) disorders, with anxiety and substance disorders less consistently important. Most associations were comparable for girls and boys. CONCLUSIONS: Interventions aimed at reducing the adverse effects of ADHD might profitably target prevention or treatment of temporally secondary co-morbid disorders.

Objective: This study evaluated the efficacy and tolerability of modafinil at a range of doses, versus placebo, in alleviating symptoms of ADHD in adults. Method: Adult patients with ADHD were randomized in 1:1:1:1:1 fashion to double-blind treatment with modafinil 255, 340, 425, or 510 mg daily or placebo for 9 weeks. The primary efficacy outcome was the change from baseline at final visit in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score. Results: A total of 338 patients were enrolled, of whom 330 received at least 1 dose of study medication (modafinil or placebo). No statistically significant difference in the AISRS total score was observed at final visit between any modafinil group and placebo; however, some observations among patients who completed the trial may warrant further investigation. Conclusion: Modafinil was reasonably tolerated but did not demonstrate a benefit on ADHD symptoms in adults. (J. of Att. Dis. 2012; XX(X) 1-XX).

Reports an error in "Atomoxetine treatment of attention-deficit/hyperactivity disorder in young adults with assessment of functional outcomes. A randomized, double-blind, placebo-controlled clinical trial" by Todd M. Durell, Lenard A. Adler, Dave W. Williams, Ahmed Deldar, James J. McGough, Paul E. Glaser, Richard L. Rubin, Teresa A. Pigott, Elias H. Sarkis and Bethanv K. Fox (Journal of Clinical Psychopharmacology, 2013[Feb], Vol 33[1], 45-54). In the original article, there were some errors in Table 2. The corrected Table 2 is present in the erratum. (The following abstract of the original article appeared in record 2013-02386-008). Background: Attention-deficit/hyperactivity disorder (ADHD) is associated with significant impairment in multiple functional domains. This trial evaluated efficacy in ADHD symptoms and functional outcomes in young adults treated with atomoxetine. Methods: Young adults (18-30 years old) with ADHD were randomized to 12 weeks of double-blind treatment with atomoxetine (n = 220) or placebo (n = 225). The primary efficacy measure of ADHD symptom change was Conners' Adult ADHD Rating Scale (CAARS): Investigator-Rated: Screening Version Total ADHD Symptoms score with adult prompts. Secondary outcomes scales included the Adult ADHD Quality of Life-29, Clinical Global Impression-ADHD-Severity, Patient Global Impression-Improvement, CAARS Self-Report, Behavior Rating Inventory of Executive Function-Adult Version Self-Report, and assessments of depression, anxiety, sleepiness, driving behaviors, social adaptation, and substance use. Results: Atomoxetine was superior to placebo on CAARS: Investigator-Rated: Screening Version (atomoxetine [least-squares mean + SE, -13.6 + 0.8] vs placebo [-9.3 + 0.8], 95% confidence interval [-6.35 to -2.37], P < 0.001), Clinical Global Impression-ADHD-Severity (atomoxetine [-1.1 + 0.1] vs placebo [-0.7 + 0.1], 95% confidence interval [-0.63 to -0.24], P < 0.001), and CAARS Self-Report (atomoxetine [-11.9 + 0.8] vs placebo [-7.8 + 0.7], 95% co!

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) symptom presentation across age and sex has not been fully elucidated. The present post hoc analyses qualitatively explored the baseline levels of ADHD symptomatology across subgroups in two clinical trials of children and adults with ADHD to elucidate differences in participant presentation. The response to treatment was examined to determine patterns of response among items of the ADHD Rating Scale IV. METHODS: Exploratory post hoc analyses of ADHD Rating Scale IV item scores were conducted on data from two 4-week placebo-controlled trials in children (6-12 years) and in adults (18-55 years) with ADHD. Baseline and endpoint mean item scores were determined for subgroups defined by age (6-9, 10-12, 18-39, and 40-55 years) and sex. RESULTS: The baseline mean item scores were generally numerically similar for all age-by-sex subgroups. The inattention (IA) items were numerically higher than hyperactivity/impulsivity (H/I) items among older children and adults. The endpoint mean item scores were numerically lower after lisdexamfetamine dimesylate treatment for IA and H/I items in all subgroups. CONCLUSION: These results suggest that regardless of age or sex, baseline IA and H/I symptom profiles were comparable; however, IA vs H/I symptoms were more severe in older participants. In all age-by-sex subgroups, IA and H/I symptoms appeared to decrease after active treatment.

BACKGROUND: This 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). METHODS: This 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. RESULTS: Of 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. CONCLUSIONS: Overall, 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 REGISTRATION: ClinicalTrials.gov, NCT01101022.

OBJECTIVES: To compare the effects of metadoxine extended release (ER) with those of placebo on inattentive (IA) versus hyperactive-impulsive (H-I) symptoms and predominantly inattentive (PI) versus combined type (CT) subtype in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: This was a 1:1 randomized, double-blind, parallel-design study of metadoxine ER 1400 mg/day for 6 weeks in 120 adults with ADHD. Efficacy measures were baseline to end-of-treatment changes in Conners' Adult ADHD Rating Scale-Investigator Rated (CAARS-INV) Total ADHD Symptoms scores with adult ADHD prompts, the Test of Variables of Attention ADHD scores, and response rates (>/= 25% or >/= 40% improvement in CAARS-INV Total ADHD Symptoms score). Results: There was a significant decrease in CAARS-INV Total ADHD Symptoms scores in patients with ADHD-PI taking metadoxine ER (40%) compared with those taking placebo (21%) (P < 0.05), while the decrease for patients with ADHD-CT was not significant (27% vs 26%). Similarly, there was a significant decrease in IA scores in patients with ADHD-PI (metadoxine ER, 50% vs placebo, 23%; P < 0.005), while the change in patients with ADHD-CT was not significant. There was no significant difference in percent decreases seen in H-I scores for patients with PI or ADHD-CT. Significantly higher response rates at both cutoffs (ie, 25% and 45% improvement) were seen in the metadoxine ER group compared with the placebo group in CAARS-INV Total ADHD Symptoms scores in patients with ADHD-PI, but not those with ADHD-CT. Test of Variables of Attention ADHD scores were significantly decreased in the metadoxine ER group compared with the placebo group for patients with ADHD-PI, but not those with ADHD-CT. CONCLUSION: These data suggest that metadoxine ER is selectively efficacious for treating IA symptoms in adults with ADHD-PI. Trial registration: www.ClinicalTrials.gov identifier NCT01243242.