Gender differences in adults with ADHD, pretreatment and following treatment with atomoxetine under double-blind conditions

posterBoys more frequently have externalizing disorders (conduct and oppositional defiant disorder). Girls are more frequently inattentive type with increased internalizing disorders. NIMH-sponsored, multicenter MTA Study did not show these differences. This study explored gender differences in a clinical trial of ADHD adults evaluated with a wide variety of psychological measures

Six month, open-trial of bupropion SR in comparison to methylphenidate in the treatment of adults with ADHD

posterABSTRACT Objective: ADHD has become increasingly diagnosed and treated in adults. Treatment modalities have grown to include several antidepressants as well as stimulant medications. This study was designed to evaluate the effectiveness of bupropion SR compared to methylphenidate in an extended open-label study following a previously reported six-week, double-blind placebo-controlled trial of bupropion SR (1). Methods: Sixty subjects were selected using the Utah Criteria and DSM-IV for ADHD. Sixty percent were assigned to bupropion SR and 40% to placebo in a double-blind manner. Nonresponders to bupropion (n=22) were treated with methylphenidate in an open manner. Patients treated with placebo were treated with bupropion SR. Results: Response rate to bupropion SR in patients (n=38) treated in either the double-blind study or the open study was 43% as defined by a 40% improvement in the Wender Reimherr Adult Attention Deficit Disorder Scale (WRAADDS). In nonresponders subsequently treated with methylphenidate (n=16) the response measured in the same manner was 63% (p<ns). Conversely, in patients who continued in treatment for an extended 4-6 month time period, WRAADDS scores improved 65% over baseline with bupropion SR (n=10) and 59% with methylphenidate (n=8) Discussion: We found a lower frequency of response in adult ADHD with bupropion SR as opposed to methylphenidate. However, treatment with either medication produced equivalent levels of improvement at the 4 to 6 month evaluation in the subpopulation continuing on medication. Despite the increasing recognition of adult ADHD, there is a paucity of data on its treatment. Information on long-term outcome in adults is even more limited. Although the stimulants have been shown to be effective in adult ADHD, the multiple dosing, scheduled prescribing restrictions, anxiogenic properties, and abuse potential limit their usefulness in subgroups of adults. Despite the emergence of bupropion as a second-line agent for pediatric ADHD, data in ADHD adults are limited. There is a perception that stimulants produce a greater degree of improvement in the symptoms of ADHD than non-stimulants such as bupropion. We now report findings on an open-label, extended study of bupropion SR in comparison with methylphenidate

Emotional dysregulation in adult ADHD and response to atomoxetine

posterABSTRACT Objective: Agreement on the symptoms of adult ADHD remains problematic. The Wender- Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) contains three items which could be considered signs of emotional dysregulation: temper, affective lability and emotional over-reactivity. Previously published data were reexamined to assess: 1) the pervasiveness of these symptoms; 2) if their presence predicted a favorable response to atomoxetine; and 3) was their response to atomoxetine similar to other ADHD symptoms. Method: This placebo-controlled, double-blind study was conducted concurrently at 31 outpatient sites. Patients met DSM-IV criteria for ADHD, confirmed using the Conners' Adult ADHD Diagnostic Interview. Outcome was assessed using the Conners' Adult ADHD Rating Scale (CAARS) and the WRAADDS. Emotional dysregulation was operationally defined as scores of 7 or more on the three scales. Results: Emotional dysregulation affected 31% of the population. There was a significant interaction between treatment and emotional dysregulation on improvement of the CAARS (p=.031). These emotional factors displayed a treatment effect (p<.001) similar to the CAARS. Conclusions: Patient outcome was related to emotional dysregulation as defined using the WRAADDS. These emotional symptoms showed treatment effects that were statistically significant and similar in size to the traditional signs of hyperactivity/impulsivity and inattention. In the past, ADHD was known as MBD and included emotional and personality dimensions. It is uncertain whether these dimensions should be viewed as part of an ADHD spectrum or independent comorbid diagnoses. Recent studies with atomoxetine in adults were carefully designed to exclude other comorbid adult psychiatric diagnoses and used both the CAARS and WRAADDS to assess outcome. Three factors on the WRAADDS appear to measure emotional dysregulation while the other four factors measure DSM-IV criteria. These factors were used to assess the frequency of emotional dysregulation in adult ADHD. We then examined the attributes of these patients and effects of atomoxetine in these patients both on emotional dysregulation and DSM-IV criteria symptoms of ADHD

Neuropsychological functioning and OROS® methylphenidate in an Adult Attention-Deficit/Hyperactivity Disorder (ADHD) population

posterObjective: Neuropsychological tests have been used in attention-deficit/hyperactivity disorder (ADHD) to compare ADHD patients with normal subjects, to assess drug-placebo differences in clinical trials and to identify appropriate medication levels via test dose paradigms. While clinical studies have generally been positive1 with moderate effect sizes, outcomes have been inconsistent, particularly in adults. This analysis examined a neurocognitive battery in a sample of adult ADHD subjects during a clinical trial of OROS® methylphenidate (OROS MPH; Concerta®).2 Methods:This 8-week crossover study utilized OROS MPH in 41 subjects who met DSM-IV criteria and the Utah Criteria for ADHD. ADHD symptoms were assessed using the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS)3 and the ADHD-Rating Scale (ADHD-RS). (The primary efficacy and safety results were previously reported.2) The CNS Vital Signs (CNSVS) is a computer-based neurocognitive battery with tests of Verbal and Visual Memory, Finger Tapping, Symbol Digit Coding (SDC), the Stroop Test, the Shifting Attention Test (SAT), and the Continuous Performance Test (CPT). The developer has reported average scores for both normal and ADHD subjects on these tests.4 Baseline scores on this population were compared with the normative data. The impact of treatment (OROS MPH vs placebo) on test scores was assessed via paired t-tests. Results: OROS MPH was superior to placebo for all clinical ADHD measures, including total WRAADDS (44% vs 13% improvement; P=0.001), plus the subscales addressing inattention, hyperactivity/impulsivity, and emotional dysregulation. At baseline, our ADHD patients had CNSVS scores midway between the developer's ADHD and normal samples. However, on errors in the Stroop and CTP commission errors, the ADHD patients scored worse than either comparison group. Although OROS MPH was usually associated with better scores than placebo, this difference only achieved significance for 4 of the tests: SDC number correct (P=0.041), Stroop complex reaction time (P=0.009), SAT number correct (P=0.018), and CPT reaction time (P=0.034). Conclusions: Baseline scores were consistently worse than the test developer's normative data, and endpoint scores on OROS MPH were consistently better than placebo. The tests that reached or approached significance were all test scores that had previously reached significance in test dose paradigms. The longer period between testing in this clinical trial (4 weeks) compared with a test dose paradigm (1 hour) may contribute to the weaker relationship. Conversely, actual clinical trials in adults with ADHD have frequently failed to find drug-placebo differences on cognitive testing