Working memory (WM) capacity is the ability to retain and manipulate information during a short period of time. This ability underlies complex reasoning and has generally been regarded as a ®xed trait of the individual. Children with attention de®cit hyperactivity disorder (ADHD) represent one group of subjects with a WM de®cit, attributed to an impairment of the frontal lobe. In the present study, we used a new training paradigm with intensive and adaptive training of WM tasks and evaluated the effect of training with a double blind, placebo controlled design. Training signi®cantly enhanced performance on the trained WM tasks. More importantly, the training signi®cantly improved performance on a nontrained visuo-spatial WM task and on Raven's Progressive Matrices, which is a nonverbal complex reasoning task. In addition, motor activity ± as measured by the number of head movements during a computerized test ± was signi®cantly reduced in the treatment group. A second experiment showed that similar training-induced improvements on cognitive tasks are also possible in young adults without ADHD. These results demonstrate that performance on WM tasks can be signi®cantly improved by training, and that the training effect also generalizes to nontrained tasks requiring WM. Training improved performance on tasks related to prefrontal functioning and had also a signi®cant effect on motor activity in children with ADHD. The results thus suggest that WM training potentially could be of clinical use for ameliorating the symptoms in ADHD.

It would not be appropriate to develop ADHD-services where clinicians would only have expertise in ADHD as such. Anyone working with children, adolescents and adults with ADHD would need to have training in general neuropsychiatry. Further research in this field is urgently needed.

This study evaluated the efficacy and safety of lisdexamfetamine dimesylate (LDX) compared with placebo in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in Europe. Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference arm. Patients (6-17 years old) with a baseline ADHD Rating Scale version IV (ADHD-RS-IV) total score ≥ 28 were randomized (1:1:1) to dose-optimized LDX (30, 50, or 70 mg/day), OROS-MPH (18, 36, or 54 mg/day) or placebo for 7 weeks. Primary and key secondary efficacy measures were the investigator-rated ADHD-RS-IV and the Clinical Global Impressions-Improvement (CGI-I) rating, respectively. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs. Of 336 patients randomized, 196 completed the study. The difference between LDX and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -18.6 (95% confidence interval [CI]: -21.5 to -15.7) (p<0.001; effect size, 1.80). The difference between OROS-MPH and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -13.0 (95% CI: -15.9 to -10.2) (p<0.001; effect size, 1.26). The proportions (95% CI) of patients showing improvement (CGI-I of 1 or 2) at endpoint were 78% (70-86), 14% (8-21), and 61% (51-70) for LDX, placebo, and OROS-MPH. The most common TEAEs for LDX were decreased appetite, headache, and insomnia. Mean changes in vital signs were modest and consistent with the known profile of LDX. LDX was effective and generally well tolerated in children and adolescents with ADHD.