Faculty Bibliography

The validity of the six-question World Health Organization Adult ADHD Self-Report Scale (ASRS) Screener was assessed in a sample of subscribers to a large health plan in the US. A convenience subsample of 668 subscribers was administered the ASRS Screener twice to assess test-retest reliability and then a third time in conjunction with a clinical interviewer for DSM-IV adult ADHD. The data were weighted to adjust for discrepancies between the sample and the population on socio-demographics and past medical claims. Internal consistency reliability of the continuous ASRS Screener was in the range 0.63-0.72 and test-retest reliability (Pearson correlations) in the range 0.58-0.77. A four-category version The ASRS Screener had strong concordance with clinician diagnoses, with an area under the receiver operating characteristic curve (AUC) of 0.90. The brevity and ability to discriminate DSM-IV cases from non-cases make the six-question ASRS Screener attractive for use both in community epidemiological surveys and in clinical outreach and case-finding initiatives

OBJECTIVE: Despite appropriate treatment with selective serotonin reuptake inhibitors (SSRIs), many depressed patients do not attain remission. Addition of a noradrenergic intervention in patients poorly or partially responsive to SSRIs may improve outcomes, but few well-controlled studies testing this hypothesis have been reported. METHOD: Patients with major depressive disorder (confirmed by the Structured Clinical Interview for DSM-IV) were treated with sertraline at doses up to 200 mg/day in this study, conducted from June 18, 2003, to January 28, 2005. Patients who continued to experience depressive signs and symptoms after 8 weeks were randomly assigned to have atomoxetine 40 to 120 mg/day or placebo added to sertraline for a further 8 weeks. RESULTS: Of 276 patients starting the study, 146 with persistent depressive symptoms after 8 weeks of sertraline treatment (mean [SD] final sertraline dose: 161.1 [43.4] mg/day) were randomly assigned to addition of atomoxetine or placebo. After 8 additional weeks, there was no difference between treatment groups in mean change in symptom severity or in the proportion of patients whose symptoms remitted (sertraline/ atomoxetine 29/72 [40.3%], sertraline/placebo 28/74 [37.8%], p = .865). Secondary analyses that separated the subgroups with improvements in symptoms that did not reach remission (partial responders) and those with little or no improvement (nonresponders) also showed no effect of atomoxetine. The number of patients discontinuing because of adverse events did not differ between groups. CONCLUSION: In depressed patients with persistent symptoms after an initial trial of sertraline, addition of atomoxetine did not improve response more than placebo

Attention-deficit/hyperactivity disorder (ADHD) is a clinical disorder that may be confused with other medical and psychiatric conditions, due to overlapping symptoms. Often, symptoms suggestive of ADHD may be explained by other diagnoses. Medical 'mimics' one should consider when diagnosing a patient with ADHD include sleep deprivation, chronic and acute illness, medication effects, cognitive deficits, and other psychiatric disorders such as Asperger's syndrome, substance use disorders, and mood disorders. ADHD in both children and adults is also associated with academic performance problems, such as learning disabilities and executive functioning deficits. Learning disabilities such as math and spelling deficits are more common in children, although both age groups experience difficulties with reading and listening comprehension. Executive deficits in response inhibition and working memory have been demonstrated to be predictive of impairment in virtually every major life activity. Evaluation of both children and adults with ADHD requires screening for comorbid medical, psychiatric, and learning disorders; executive functioning; and history of school impairment. In this monograph, Russell A. Barkley, PhD, reviews the comorbidity of adult attention-deficit/hyperactivity disorder (ADHD) and learning and executive function disorders. Next, Timothy E. Wilens, MD, discusses differential diagnosis of ADHD as well as the prevalence of psychiatric comorbidity in adult ADHD. Finally, Lenard A. Adler, MD, reviews Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnostic criteria for adult ADHD and reviews the diagnostic and symptom assessment instruments available for the evaluation of ADHD in this population. (journal abstract)

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a disorder characterized by hyperactivity, impulsiveness, and inattention that affects 4% of adults. Atomoxetine hydrochloride is an FDA-approved treatment for adult ADHD, but no studies have clarified whether there are advantages to once versus twice daily dosing. METHODS: This randomized, double-blind, multicenter study compared safety and tolerability of 80 mg atomoxetine QD versus 40 mg atomoxetine BID in 218 adults with ADHD. Treatment-emergent adverse events (TEAEs), laboratory values, vital signs, weight, electrocardiograms, scores on the Arizona Sexual Experiences Scale, and efficacy (using the Conners' ADHD Rating Scale-Investigator Rated: Screening Version) were assessed. RESULTS: The overall incidence for any one TEAE was low. There was no significant treatment group difference in likelihood of patients experiencing >/=1 of the four most commonly observed TEAEs (dry mouth, insomnia, nausea, and erectile dysfunction). Frequency of nausea was significantly lower in the 40 mg BID group (16.4%) than the 80 mg QD group (32.4%; p = .007). There were no unexpected safety results. Although both QD and BID treatments were efficacious, the reduction in scores was greater for BID treatment. CONCLUSIONS: Data indicate both dosing strategies are safe, well tolerated, and efficacious in the treatment of adult ADHD. Changes in dosing strategy are unlikely to be accompanied by safety risks, implying that there is room for prescribers to use discretion and to base dosing strategies on individual factors

OBJECTIVE: Despite growing interest in adult attention deficit hyperactivity disorder (ADHD), little is known about its prevalence or correlates. METHOD: A screen for adult ADHD was included in a probability subsample (N=3,199) of 18-44-year-old respondents in the National Comorbidity Survey Replication, a nationally representative household survey that used a lay-administered diagnostic interview to assess a wide range of DSM-IV disorders. Blinded clinical follow-up interviews of adult ADHD were carried out with 154 respondents, oversampling those with positive screen results. Multiple imputation was used to estimate prevalence and correlates of clinician-assessed adult ADHD. RESULTS: The estimated prevalence of current adult ADHD was 4.4%. Significant correlates included being male, previously married, unemployed, and non-Hispanic white. Adult ADHD was highly comorbid with many other DSM-IV disorders assessed in the survey and was associated with substantial role impairment. The majority of cases were untreated, although many individuals had obtained treatment for other comorbid mental and substance-related disorders. CONCLUSIONS: Efforts are needed to increase the detection and treatment of adult ADHD. Research is needed to determine whether effective treatment would reduce the onset, persistence, and severity of disorders that co-occur with adult ADHD

OBJECTIVE: The objective of this study was to determine if measures of broad clinical psychopathology or neuropsychological performance could aid in the prediction of therapeutic response to the highly selective norepinephrine transporter inhibitor, atomoxetine, among adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: We analyzed data from 2 double-blind, placebo-controlled, parallel design studies of adult patients (Study I, N = 280; Study II, N = 256) with DSM-IV-defined ADHD who were recruited by referral and advertising. Subjects were randomly assigned to 10 weeks of treatment with atomoxetine or placebo and were assessed with Conners' Adult ADHD Rating Scales (CAARS), the General Well-Being Schedule (GWB), the Sheehan Disability Scale, the Stroop Color-Word Test (SCWT), and the Structured Clinical Interview for DSM-IV (SCID) before and after treatment. RESULTS: Therapeutic improvement on atomoxetine as evidenced by reduced CAARS scores was reliably predicted by the presence of a lifetime comorbid diagnosis of depression or post-traumatic stress disorder at baseline, while improvement on subscales of the GWB and Sheehan Disability Scale were predicted by these and other SCID endorsements, such as alcohol and substance use, as well as demographics such as age and gender. In light of the exploratory nature of this work and the many comparisons that were examined in the corresponding regression models, these findings should be regarded as tentative pending replication and extension in another dataset. CONCLUSION: From these findings, we conclude that the variable responsiveness of individuals to atomoxetine cannot be largely accounted for by differences in broad-spectrum psychopathology or neuropsychological indicators of attentional capacity

BACKGROUND: This pilot study was designed to evaluate ABT-089, a neuronal nicotinic receptor partial agonist, as treatment for adult attention-deficit/hyperactivity disorder (ADHD). METHODS: Adults with ADHD received placebo, 2 mg, 4 mg, or 20 mg of ABT-089 for 2 weeks each in a randomized, double-blind, placebo-controlled, 4 x 4 Latin square design for a total of 8 weeks. In addition to the primary outcome, the Conner's Adult ADHD Rating Scale (CAARS), secondary rating scales, and neuropsychological and safety assessments were completed. RESULTS: A total of 11 adults with well-characterized ADHD completed this crossover study. ABT-089 b.i.d. was superior to placebo for the CAARS Total Symptom Score, which was the primary endpoint (placebo: 38.0 +/- 1.9; 2 mg b.i.d.: 32.2 +/- 1.9, one-tail p = .021; 4 mg b.i.d.: 33.2 +/- 1.9, p = .047; 20 mg b.i.d.: 33.5 +/- 1.9, p = .056). ABT-089 was also superior to placebo for the CAARS ADHD Index and Hyperactive/Impulsive scores and the Clinical Global Impression-ADHD Severity score. On the clinical efficacy endpoints, CAARS Total Symptom Score and CAARS Hyperactive/Impulsive score, a shallow inverted U-shaped dose-response curve was observed; however, the dose-response curve for attention and memory effects as measured by computerized cognitive testing seemed dose-linear. No clinically meaningful findings in safety assessments or side effect profile were observed. CONCLUSIONS: Data from this pilot study suggest that ABT-089 might be effective in treating adult ADHD and that it is well tolerated. On the basis of these promising results, larger, parallel-group ABT-089 studies of longer duration are warranted