Faculty Bibliography

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 >/=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

Attention-deficit/hyperactivity (ADHD) is a lifelong condition that begins in childhood and continues with adult manifestations related to the core symptoms. Approximately 50% to 75% of children with ADHD continue to meet criteria for the disorder as adolescents and adults. Adults with the disorder increasingly present primary care physicians,psychiatrists, and other practitioners for diagnosis and treatment. Understanding the diagnosis of ADHD in adults requires knowledge of age-dependent decline of symptoms over time. Retrospective recall of symptoms and impairment are valid methods of diagnosing the disorder. ADHD is also a brain disorder with a strong neurobiological basis, compiles etiology, and genetic component. Genetic and environmental vulnerabilities give rise to abnormalities in the brain and subsequent behavioral and cognitive deficits, which may produce the symptoms associated with ADHD. Magnetic resonance imaging studies of ADHD have provided evidence that abnormalities in the brain are caused by the disorder itself rather than treatment of the disorder. Psychiatric commodities is common among patients with ADHD and tends to complicate treatment. Acute and long-term use of long-acting stimulant formulations (methylphenidate and amphetamine compounds)have shown robust efficacy and tolerability consistent with the treatment responses establishes in children with ADHD, Non-stimulant medication have demonstrated efficacy as well, and may be preferred in patients with tic abd substance use disorders. In this expert roundtable supplement, Timothy E. Wilens, MD, reviews the epidemiology and clinical presentation of adult ADHD. Next, Joseph Biederman, MD, provides an overview of recent advances in the neurobiology of ADHD. Thomas J. Spencer, MD, reviews stimulant treatment of adult ADHD, and Lenard A. Adler concludes with a discussion of non-stimulant trials in adults ADHD. (journal abstract)

Attention-deficit/hyperactivity disorder (ADHD) is a lifelong condition that begins in childhood and continues with adult manifestations related to the core symptoms. Approximately 50% to 75% of children with ADHD continue to meet criteria for the disorder as adolescents and adults. Adults with the disorder increasingly present to primary care physicians, psychiatrists, and other practitioners for diagnosis and treatment. Understanding the diagnosis of ADHD in adults requires knowledge of age-dependent decline of symptoms over time. Retrospective recall of symptoms and impairment are valid methods of diagnosing the disorder. ADHD is also a brain disorder with a strong neurobiologic basis, complex etiology, and genetic component. Genetic and environmental vulnerabilities give rise to abnormalities in the brain and subsequent behavioral and cognitive deficits, which may produce the symptoms associated with ADHD. Magnetic resonance imaging studies of ADHD have provided evidence that abnormalities in the brain are caused by the disorder itself rather than treatment of the disorder. Psychiatric comorbidity is common among patients with ADHD and tends to complicate treatment. Acute and long-term use of long-acting stimulant formulations (methylphenidate and amphetamine compounds) have shown robust efficacy and tolerability consistent with the treatment response established in children with ADHID. Non-stimulant medications have demonstrated efficacy as well, and may be preferred in patients with tic and substance use disorders. In this expert roundtable supplement, Timothy E. Wilens, MID, reviews the epidemiology and clinical presentation of adult ADHD. Next, Joseph Biederman, MID, provides an overview of recent advances in the neurobiology of ADHD. Thomas J. Spencer, MID, reviews stimulant treatment of adult ADHID, and Lenard A. Adler concludes with a discussion of non-stimulant trials in adult ADHD

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

BACKGROUND: Identify a group of adults with 'undiagnosed' attention deficit hyperactivity disorder (ADHD) and compare their personal and family medical histories, psychosocial profiles, functional impairment and quality of life with non-ADHD controls. Additionally, compare adults with undiagnosed and diagnosed ADHD to investigate possible reasons why the undiagnosed avoid clinical detection. METHOD: ICD-9 codes for ADHD in administrative claims records and responses to a telephone-administered adult ADHD screener [the Adult ADHD Self-Report Scale (ASRS)] were used to classify approximately 21000 members of two large managed health-care plans as 'undiagnosed' (no coded diagnosis; ASRS positive) or 'non-ADHD' controls (no coded diagnosis; ASRS negative). Patients identified as 'undiagnosed' ADHD were compared with samples of non-ADHD controls and 'diagnosed' ADHD patients (ICD-9 coded ADHD diagnoses) on the basis of demographics, socio-economic status, past and present mental health conditions, and self-reported functional and psychosocial impairment and quality of life. RESULTS: A total of 752 'undiagnosed' ADHD subjects, 199 'non-ADHD' controls and 198 'diagnosed' ADHD subjects completed a telephone interview. Overall, the 'undiagnosed' ADHD cohort demonstrated higher rates of co-morbid illness and greater functional impairment than 'non-ADHD' controls, including significantly higher rates of current depression, and problem drinking, lower educational attainment, and greater emotional and interpersonal difficulties. 'Undiagnosed' ADHD subjects reported a different racial composition and lower educational attainment than 'diagnosed' ADHD subjects. CONCLUSION: Individuals with 'undiagnosed' ADHD manifest significantly greater functional and psychosocial impairment than those screening negative for the disorder, suggesting that ADHD poses a serious burden to adults even when clinically unrecognized

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