Lenard A. Adler

The World Health Organization adult ADHD self-report scale (ASRS): a short screening scale for use in the general population

BACKGROUND A self-report screening scale of adult attention-deficit/hyperactivity disorder (ADHD), the World Health Organization (WHO) Adult ADHD Self-Report Scale (ASRS) was developed in conjunction with revision of the WHO Composite International Diagnostic Interview (CIDI). The current report presents data on concordance of the ASRS and of a short-form ASRS screener with blind clinical diagnoses in a community sample. METHOD The ASRS includes 18 questions about frequency of recent DSM-IV Criterion A symptoms of adult ADHD. The ASRS screener consists of six out of these 18 questions that were selected based on stepwise logistic regression to optimize concordance with the clinical classification. ASRS responses were compared to blind clinical ratings of DSM-IV adult ADHD in a sample of 154 respondents who previously participated in the US National Comorbidity Survey Replication (NCS-R), oversampling those who reported childhood ADHD and adult persistence. RESULTS Each ASRS symptom measure was significantly related to the comparable clinical symptom rating, but varied substantially in concordance (Cohens kappa in the range 0.16-0.81). Optimal scoring to predict clinical syndrome classifications was to sum unweighted dichotomous responses across all 18 ASRS questions. However, because of the wide variation in symptom-level concordance, the unweighted six-question ASRS screener outperformed the unweighted 18-question ASRS in sensitivity (68.7% v. 56.3%), specificity (99.5% v. 98.3%), total classification accuracy (97.9% v. 96.2%), and kappa (0.76 v. 0.58). CONCLUSIONS Clinical calibration in larger samples might show that a weighted version of the 18-question ASRS outperforms the six-question ASRS screener. Until that time, however, the unweighted screener should be preferred to the full ASRS, both in community surveys and in clinical outreach and case-finding initiatives.

Patterns and predictors of attention-deficit/ hyperactivity disorder persistence into adulthood : Results from the national comorbidity survey replication

BACKGROUND Despite growing interest in adult attention-deficit/hyperactivity disorder (ADHD), little is known about predictors of persistence of childhood cases into adulthood. METHODS A retrospective assessment of childhood ADHD, childhood risk factors, and a screen for adult ADHD were included in a sample of 3197 18-44 year old respondents in the National Comorbidity Survey Replication (NCS-R). Blinded adult ADHD clinical reappraisal interviews were administered to a sub-sample of respondents. Multiple imputation (MI) was used to estimate adult persistence of childhood ADHD. Logistic regression was used to study retrospectively reported childhood predictors of persistence. Potential predictors included socio-demographics, childhood ADHD severity, childhood adversity, traumatic life experiences, and comorbid DSM-IV child-adolescent disorders (anxiety, mood, impulse-control, and substance disorders). RESULTS Blinded clinical interviews classified 36.3% of respondents with retrospectively assessed childhood ADHD as meeting DSM-IV criteria for current ADHD. Childhood ADHD severity and childhood treatment significantly predicted persistence. Controlling for severity and excluding treatment, none of the other variables significantly predicted persistence even though they were significantly associated with childhood ADHD. CONCLUSIONS No modifiable risk factors were found for adult persistence of ADHD. Further research, ideally based on prospective general population samples, is needed to search for modifiable determinants of adult persistence of ADHD.

Validity of Pilot Adult ADHD Self- Report Scale (ASRS) to Rate Adult ADHD Symptoms

BACKGROUND The goal of this study was to validate the pilot Adult ADHD Self-Report Scale (pilot ASRS) versus standard clinician ratings on the ADHD Rating Scale (ADHD RS). METHOD Sixty adult ADHD patients took the self-administered ADHD RS and then raters administered the standard ADHD RS. Internal consistency of symptom scores was assessed by Cronbachs alpha. Agreement of raters was established by intra-class correlation coefficients (ICCs) between scales. RESULTS Internal consistency was high for both patient and rater-administered versions (Cronbachs alpha 0.88, 0.89, respectively). The ICC between scales for total scores was also high (0.84); ICCs for subset symptom scores were also high (both 0.83). There was acceptable agreement for individual items (% agreement: 43%-72%) and significant kappa coefficients for all items (p < 0.001). CONCLUSIONS The pilot Adult ADHD Self-Report Scale symptom checklist is a reliable and valid scale for evaluating ADHD for adults and shows a high internal consistency and high concurrent validity with the rater-administered ADHD RS.

The prevalence and effects of adult attention deficit/hyperactivity disorder on work performance in a nationally representative sample of workers.

Objective: The prevalence and workplace consequences of adult attention deficit/hyperactivity disorder (ADHD) are unknown. Methods: An ADHD screen was included in a national household survey (n = 3198, ages 18–44). Clinical reinterviews calibrated the screen to diagnoses of Diagnostic and Statistical Manual of Mental Disorders, 4th edition ADHD. Diagnoses among workers were compared with responses to the WHO Health and Work Performance Questionnaire (HPQ). Results: A total of 4.2% of workers had ADHD. ADHD was associated with 35.0 days of annual lost work performance, with higher associations among blue collar (55.8 days) than professional (12.2 days), technical (19.8 days), or service (32.6 days) workers. These associations represent 120 million days of annual lost work in the U.S. labor force, equivalent to

Structure and diagnosis of adult attention-deficit/hyperactivity disorder: analysis of expanded symptom criteria from the Adult ADHD Clinical Diagnostic Scale.

19.5 billion lost human capital. Conclusions: ADHD is a common and costly workplace condition. Effectiveness trials are needed to estimate the region of interest of workplace ADHD screening and treatment programs.

Efficacy and Safety of Dexmethylphenidate Extended-Release Capsules in Adults with Attention-Deficit/Hyperactivity Disorder

CONTEXT Controversy exists about the appropriate criteria for a diagnosis of adult attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE To examine the structure and symptoms most predictive of DSM-IV adult ADHD. DESIGN The data are from clinical interviews in enriched subsamples of the National Comorbidity Survey Replication (n = 131) and a survey of a large managed health care plan (n = 214). The physician-administered Adult ADHD Clinical Diagnostic Scale (ACDS) was used to assess childhood ADHD and expanded symptoms of current adult ADHD. Analyses examined the stability of symptoms from childhood to adulthood, the structure of adult ADHD, and the adult symptoms most predictive of current clinical diagnoses. SETTING The ACDS was administered telephonically by clinical research interviewers with extensive experience in the diagnosis and treatment of adult ADHD. PARTICIPANTS An enriched sample of community respondents. MAIN OUTCOME MEASURE Diagnoses of DSM-IV /ACDS adult ADHD. RESULTS Almost half of the respondents (45.7%) who had childhood ADHD continued to meet the full DSM-IV criteria for current adult ADHD, with 94.9% of these patients having current attention-deficit disorder and 34.6% having current hyperactivity disorder. Adult persistence was much greater for inattention than for hyperactivity/impulsivity. Additional respondents met the full criteria for current adult ADHD despite not having met the full childhood criteria. A 3-factor structure of adult symptoms included executive functioning (EF), inattention/hyperactivity, and impulsivity. Stepwise logistic regression found EF problems to be the most consistent and discriminating predictors of adult DSM-IV /ACDS ADHD. CONCLUSIONS These findings document the greater persistence of inattentive than of hyperactive/impulsive childhood symptoms of ADHD in adulthood but also show that inattention is not specific to ADHD because it is strongly associated with other adult mental disorders. In comparison, EF problems are more specific and consistently important predictors of DSM-IV adult ADHD despite not being in the DSM-IV, suggesting that the number of EF symptoms should be increased in the DSM-V/ICD-11.

Atomoxetine treatment of adults with ADHD and comorbid alcohol use disorders

BACKGROUND This multicenter, randomized, fixed-dose, double-blind, placebo-controlled study evaluated efficacy of extended-release dexmethylphenidate (d-MPH-ER) in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS Randomized adults with ADHD (n=221) received once-daily d-MPH-ER 20 mg, 30 mg, or 40 mg or placebo for 5 weeks. The primary efficacy variable was change from baseline to final visit in DSM-IV ADHD Rating Scale (ADHD-RS) total score. Secondary efficacy parameters included the proportion of patients with improvement>or=30% in ADHD-RS total score and final scores on Clinical Global Impressions-Improvement (CGI-I) scale. RESULTS Of 218 evaluable patients, 184 completed the study. All d-MPH-ER doses were significantly superior to placebo in improving ADHD-RS total scores. Placebo scores improved by 7.9; d-MPH-ER, 20 mg, improved by 13.7 (p=.006); d-MPH-ER, 30 mg, improved by 13.4 (p=.012); and d-MPH-ER, 40 mg, improved by 16.9 (p<.001). Overall distribution of CGI-I ratings at final visit was significantly better with each d-MPH-ER dosage than with placebo. There were no unexpected safety or tolerability concerns, based on experience with racemic methylphenidate (MPH) in adults and dexmethylphenidate (d-MPH) in children. CONCLUSIONS Once-daily d-MPH-ER at 20 mg, 30 mg, or 40 mg is a safe and effective treatment for adults with ADHD.

ABT-089, A Neuronal Nicotinic Receptor Partial Agonist, for the Treatment of Attention-Deficit/Hyperactivity Disorder in Adults: Results of a Pilot Study

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.

Neuroleptic-induced akathisia: a review

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 Conners 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.

Efficacy and safety of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, double-blind, parallel group, dose-escalation study.

Neuroleptic-induced akathisia (NIA) is a relatively common side effect of neuroleptics, in which patients complain of a subjective sense of restlessness usually referable to the legs and have characteristic motor movements. This paper will review: 1) history of spontaneously occurring syndromes of pathologic restlessness and NIA, 2) the clinical significance of NIA, 3) issues concerning the diagnosis and quantification of NIA, 4) treatments of NIA and 5) possible future directions for research in this area. Special attention will be paid to newer treatments for this syndrome, specifically beta-blockers.