Faculty Bibliography

OBJECTIVE: Adults with attention-deficit/hyperactivity disorder (ADHD) have higher rates of alcohol and drug use disorders than adults without ADHD. The study aim was to determine if atomoxetine was superior to placebo in improving ADHD and alcohol use in recently abstinent adults with ADHD and comorbid alcohol use disorder. METHODS: Adults with DSM-IV diagnoses of ADHD and alcohol abuse and/or dependence were abstinent from alcohol at least 4 days (maximum 30 days) before study randomization. Participants received atomoxetine (25-100mg daily) or placebo for 12 weeks. ADHD symptoms were assessed using ADHD Investigator Symptom Rating Scale (AISRS) total score. Time-to-relapse to heavy alcohol use was analyzed using a 2-sided log-rank test based on Kaplan-Meier estimates and cumulative heavy drinking events over time were evaluated post hoc with recurrent-event analysis. RESULTS: Subjects received atomoxetine (n=72) or placebo (n=75) and 80 subjects completed the 12-week double-blind period (n=32 and 48, respectively). ADHD symptoms were significantly improved in the atomoxetine cohort compared to placebo (AISRS total score mean [S.D.], atomoxetine: -13.63 [11.35], P<.001; placebo: -8.31 [11.44], P<.001, difference: P=.007; effect size=0.48). No significant differences between treatment groups occurred in time-to-relapse of heavy drinking (P=.93). However, cumulative heavy drinking days were reduced 26% in atomoxetine-treated subjects versus placebo (event ratio=0.74, P=.023). There were no serious adverse events or specific drug-drug reactions related to current alcohol use. CONCLUSIONS: This 3-month, double-blind, placebo-controlled study of atomoxetine in adults with ADHD and comorbid alcohol use disorder demonstrates clinically significant ADHD improvement, and inconsistent effects on drinking behavior

OBJECTIVE: To review and provide details about the primary and secondary findings from the Multimodal Treatment study of ADHD (MTA) published during the past decade as three sets of articles. METHOD: In the second of a two part article, we provide additional background and detail required by the complexity of the MTA to address confusion and controversy about the findings outlined in part I (the Executive Summary). RESULTS: We present details about the gold standard used to produce scientific evidence, the randomized clinical trial (RCT), which we applied to evaluate the long-term effects of two well-established unimodal treatments, Medication Management (MedMGT) and behavior therapy (Beh), the multimodal combination (Comb), and treatment 'as usual' in the community (CC). For each of the first three assessment points defined by RCT methods and included in intent-to-treat analyses, we discuss our definition of evidence from the MTA, interpretation of the serial presentations of findings at each assessment point with a different definition of long-term varying from weeks to years, and qualification of the interim conclusions about long-term effects of treatments for ADHD based on many exploratory analyses described in additional published articles. CONCLUSIONS: Using a question and answer format, we discuss the possible clinical relevance of the MTA and present some practical suggestions based on current knowledge and uncertainties facing families, clinicians, and investigators regarding the long-term use of stimulant medication and behavioral therapy in the treatment of children with ADHD

OBJECTIVE: To review the primary and secondary findings from the Multimodal Treatment study of ADHD (MTA) published over the past decade as three sets of articles. METHOD: In a two-part article-Part I: Executive Summary (without distracting details) and Part II: Supporting Details (with additional background and detail required by the complexity of the MTA)-we address confusion and controversy about the findings. RESULTS: We discuss the basic features of the gold standard used to produce scientific evidence, the randomized clinical trial, for which was used to contrast four treatment conditions: medication management alone (MedMgt), behavior therapy alone (Beh), the combination of these two (Comb), and a community comparison of treatment 'as usual' (CC). For each of the three assessment points we review three areas that we believe are important for appreciation of the findings: definition of evidence from the MTA, interpretation of the serial presentations of findings at each assessment point with a different definition of long-term, and qualification of the interim conclusions about long-term effects of treatments for ADHD. CONCLUSION: We discuss the possible clinical relevance of the MTA and present some practical suggestions based on current knowledge and uncertainties facing families, clinicians, and investigators regarding the long-term use of stimulant medication and behavioral therapy in the treatment of children with ADHD

The convergent validity and clinical utility of two parent-report child behavior rating scales, the Behavior Assessment System for Children-Parent Rating Scales (BASC-PRS) and Child Behavior Checklist/Ages 6-18 (CBCL), in children with epilepsy were examined. Analogous broadband and narrowband behavior rating scales were evaluated in 60 subjects aged 6-17 years (mean=11.0, SD=3.4) with Full Scale IQ >70. Correlations for each similarly labeled scale were statistically significant (P<0.002) and greater with broadband (r=0.71-0.79) than with narrowband (r=0.41-0.78) scales. The BASC captured significantly less composite internalizing symptoms (P<0.002), but more unusual thought processes (P<0.0002) and attention problems versus a CBCL DSM-oriented attention-deficit/hyperactivity disorder scale (P<0.002). Variation in the correlations between measures may stem from underlying differences between rationally-and empirically-derived approaches to test construction. Both the CBCL and BASC have diagnostic and clinical utility in assessing behavior problems in pediatric epilepsy

This study evaluates school personnel perceptions, knowledge, and behaviors before and after a 36-hr training program designed to prepare early childhood school personnel for implementation of an after-school family preventive intervention for conduct problems. Participants were 40 female school personnel (22 professionals and 18 paraprofessionals). Research Findings: Participation and satisfaction with the training program were high. Before training, school personnel responded correctly to 53% to 66% of knowledge questions and indicated that they would be 'somewhat comfortable to comfortable' in facilitating the after-school groups with families. Before training, professionals had greater knowledge than paraprofessionals; there was no difference in initial comfort level by professional status. Trainees made substantial gains in knowledge related to cognitive-behavioral strategies for preschoolers, program philosophy, and group facilitation skills, responding correctly to 69% to 77% of questions. These large effects on knowledge were not moderated by professional status. There were no significant changes in comfort level. Gains in knowledge in cognitive-behavioral strategies generalized over time (5 months) but not across contexts (into the classroom). Practice or Policy: This study provides preliminary evidence for the feasibility and potential efficacy of a training program to prepare early childhood school personnel to implement an after-school family preventive intervention for conduct problems

OBJECTIVE: To assess combined antidepressant and cognitive enhancer treatment in elderly patients presenting with depression plus cognitive impairment. METHODS: Twenty-three elderly (>50 years old) depressed, cognitively impaired (DEP-CI) patients participated in a pilot study. We evaluated whether, after 8 weeks of open antidepressant treatment, donepezil HCl (Aricept) would afford added cognitive benefit compared to placebo in a randomized 12-week trial. A subsample continued in an 8-month extension phase of open treatment with donepezil. Neuropsychological testing (NPT) was performed and antidepressant response monitored at baseline and the 8, 20, and 52-week time points. RESULTS: At 8-weeks, the antidepressant response rate was 61% (14/23). Improvement in SRT immediate recall (SRT-IR; e.g. episodic verbal memory) was observed in responders compared to non-responders. During the 12-week, placebo-controlled, donepezil add-on trial, patients on donepezil showed further improvement in SRT-IR versus patients on placebo. In the open extension phase, patients who continued open donepezil treatment (n = 6) maintained improvement in memory and tended to show an advantage over patients who never received donepezil and were evaluated at the 52-week time point (n = 6). There were no observed significant donepezil effects on non-memory cognitive domains. CONCLUSION: These preliminary findings suggest that addition of a cholinesterase inhibitor (AChEI) following antidepressant medication treatment in elderly Dep-CI patients may improve cognition, and support the need for a confirmatory, larger randomized placebo-controlled trial.

Increased availability of research-supported, school-based prevention programs, coupled with the growing national policy emphasis on use of evidence-based practices, has contributed to a shift in research priorities from efficacy to implementation and dissemination. A critical issue in moving research to practice is ensuring high-quality implementation of both the intervention model and the support system for sustaining it. The paper describes a three-level framework for considering the implementation quality of school-based interventions. Future directions for research on implementation are discussed.

Habituation is one of the simplest forms of memory, yet its neurobiological mechanisms remain largely unknown in mammalian systems. This review summarizes recent multidisciplinary analyses of the neurobiology of mammalian odor habituation including in vitro and in vivo synaptic physiology, sensory physiology, behavioral pharmacology, and computational modeling approaches. The findings show that a metabotropic glutamate receptor-mediated depression of afferent synapses to the olfactory cortex is necessary and perhaps sufficient to account for cortical sensory adaptation and short-term behavioral habituation. Furthermore, long-term habituation is an N-methyl-d-aspartate (NMDA) receptor-dependent process within the olfactory bulb. Thus there is both a pharmacological and anatomical distinction between short-term and long-term memory for habituation. The differential locus of change underlying short- and long-term memory leads to predictable differences in their behavioral characteristics, such as specificity

Behaviors characteristic of ADHD are common among preschool children, and as such, their clinical significance is oftentimes difficult to ascertain. Thus a focus on impairment is essential in determining the clinical significance of these behaviors. In order to explore the impact of impairment criteria on rates of diagnoses in inattentive/hyperactive children aged 36 through 60-months-old, we first developed, and psychometrically evaluated, the Children's Problem Checklist (CPC) which was designed to assess psychosocial impairment associated with ADHD in a community sample of preschoolers (n = 394), and found its reliability and validity to be acceptable. We then examined the impact of the inclusion of various CPC-determined impairment criteria, over and above symptom criteria measured by the ADHD-RS-IV, using various cut points ranging from the 75th to 90th percentile of our community sample. This reduced the number of children meeting criteria for ADHD by 46-77%. These findings are discussed in terms of the importance of using impairment criteria, rather than just severity of inattention, impulsivity and hyperactivity, when diagnosing ADHD in preschool children.