Important Note: The following information is provided for your education. It should not be relied upon for personal diagnosis or treatment. If you believe that a particular therapy applies to you or someone you care about, be sure to consult a doctor before trying it.
   

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Previous ADHD Research: 2002-2006   
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Latest Research on ADHD
     
Pediatrics. 2008 Jul;122(1):e1-6.Related Articles, Links
Overweight in children and adolescents in relation to attention-deficit/hyperactivity disorder: results from a national sample.
Waring ME, Lapane KL.
Department of Community Health, Brown Medical School, Box G-S121, Providence, RI 02912, USA. molly_waring@brown.edu

OBJECTIVE: As the prevalence of childhood obesity increases, identifying groups of children who are at increased risk of overweight is important. The current study estimated the prevalence of overweight in children and adolescents in relation to attention-deficit/hyperactivity disorder and medication use. PATIENTS AND METHODS: This study was a cross-sectional analysis of 62 887 children and adolescents aged 5 to 17 years from the 2003-2004 National Survey of Children's Health, a nationally representative sample of children and adolescents in the United States. Attention-deficit disorder/attention-deficit/hyperactivity disorder was determined by response to the question "Has a doctor or health professional ever told you that your child has attention-deficit disorder or attention-deficit/hyperactive disorder, that is, ADD or ADHD?" Children and adolescents were classified as underweight, normal weight, at risk of overweight, or overweight according to BMI for age and gender. RESULTS: After adjustment for age, gender, race/ethnicity, socioeconomic status, and depression/anxiety, children and adolescents with attention-deficit disorder/attention-deficit/hyperactivity disorder not currently using medication had approximately 1.5 times the odds of being overweight, and children and adolescents currently medicated for attention-deficit disorder/attention-deficit/hyperactivity disorder had approximately 1.6 times the odds of being underweight compared with children and adolescents without either diagnosis. CONCLUSIONS: This study provides heightened awareness for pediatric providers about the relationship between attention-deficit disorder/attention-deficit/hyperactivity disorder, medication use, and weight status. Future work is needed to better understand the longitudinal and pharmacologic factors that influence the relationship between attention-deficit disorder/attention-deficit/hyperactivity disorder and weight status in children and adolescents.

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Am J Hum Genet. 2008 Jul;83(1):99-105. Erratum in: Am J Hum Genet. 2008 Aug;83(2):294.
Neuropsychological endophenotype approach to genome-wide linkage analysis identifies susceptibility loci for ADHD on 2q21.1 and 13q12.11.
Rommelse NN, Arias-Vásquez A, Altink ME, Buschgens CJ, Fliers E, Asherson P, Faraone SV, Buitelaar JK, Sergeant JA, Oosterlaan J, Franke B.
Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, The Netherlands.

ADHD linkage findings have not all been consistently replicated, suggesting that other approaches to linkage analysis in ADHD might be necessary, such as the use of (quantitative) endophenotypes (heritable traits associated with an increased risk for ADHD). Genome-wide linkage analyses were performed in the Dutch subsample of the International Multi-Center ADHD Genetics (IMAGE) study comprising 238 DSM-IV combined-type ADHD probands and their 112 affected and 195 nonaffected siblings. Eight candidate neuropsychological ADHD endophenotypes with heritabilities > 0.2 were used as quantitative traits. In addition, an overall component score of neuropsychological functioning was used. A total of 5407 autosomal single-nucleotide polymorphisms (SNPs) were used to run multipoint regression-based linkage analyses. Two significant genome-wide linkage signals were found, one for Motor Timing on chromosome 2q21.1 (LOD score: 3.944) and one for Digit Span on 13q12.11 (LOD score: 3.959). Ten suggestive linkage signals were found (LOD scores > or = 2) on chromosomes 2p, 2q, 3p, 4q, 8q, 12p, 12q, 14q, and 17q. The suggestive linkage signal for the component score that was found at 2q14.3 (LOD score: 2.878) overlapped with the region significantly linked to Motor Timing. Endophenotype approaches may increase power to detect susceptibility loci in ADHD and possibly in other complex disorders.

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Crit Rev Food Sci Nutr. 2008 Jun;48(6):524-37.
Attention-deficit/hyperactivity disorder (ADHD) and obesity: a systematic review of the literature.
Cortese S, Angriman M, Maffeis C, Isnard P, Konofal E, Lecendreux M, Purper-Ouakil D, Vincenzi B, Bernardina BD, Mouren MC.
AP-HP, Child and Adolescent Psychopathology Unit, Robert Debré Hospital, Paris VII University, Paris, France. samuele.cortese@gmail.com

Recent studies suggest a possible comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and obesity. To gain insight into this potential association, we performed a systematic review of the literature excluding case reports, non-empirical studies, and studies not using ADHD diagnostic criteria. Empirically based evidence suggests that obese patients referred to obesity clinics may present with higher than expected prevalence of ADHD. Moreover, all reviewed studies indicate that subjects with ADHD are heavier than expected. However, data on the prevalence of obesity in subjects with ADHD are still limited. As for the mechanisms underlying the potential association between ADHD and obesity, ADHD might lead to obesity via abnormal eating behaviors, impulsivity associated with binge eating might contribute to ADHD in obese patients, or, alternatively, both obesity and ADHD might be the expression of common underlying neurobiological dysfunctions, at least in a subset of subjects. In patients with obesity and ADHD, both conditions might benefit from common therapeutic strategies. Further empirically based studies are needed to understand the potential comorbidity between obesity and ADHD, as well as the possible mechanisms underlying this association. This might allow a more appropriate clinical management and, ultimately, a better quality of life for patients with both obesity and ADHD.

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Neuro Endocrinol Lett. 2008 Jun;29(3):320-7.
Clinical and molecular-genetic markers of ADHD in children.
Drtilkova I, Sery O, Theiner P, Uhrova A, Zackova M, Balastikova B, Znojil V.
Department of Psychiatry, Faculty Hospital and Masaryk University Brno, Czech Republic. idrtilkova@fnbrno.cz

OBJECTIVES: The objective was to make a contribution to deepening the knowledge of the etiopathogenesis of ADHD. DESIGN: In an association study design, an analysis of polymorphisms of selected genes was conducted in 119 hyperkinetic boys and a control group of boys, aged 7-13. Furthermore several psychologically determined subgroups were identified. A connection between psychological functions (endophenotypes) and genes were looked for. RESULTS: There was a statistically significant difference found in allelic and genotype frequencies of the TaqI A polymorphism of the DRD2 gene. The frequency of the allele A1 in hyperkinetic boys and the control subjects was 0.26 and 0.15, respectively (p<0.003). A statistically significant occurrence of atypical genotypes (8/10, 7/10 and 10/11) of the DAT1 gene was also found in hyperkinetic boys and a connection between the M235 polymorphism of the angiotensinogene gene and the positive family history of psychiatric illness was found in probands (p=0.031). Significant correlations between the results of some neuropsychological tests and genes for neuro-/immunomodulators (IL-6, TNF-alpha) and the gene for the brain-derived neurotrophic factor (BDNF) were found. CONCLUSION: The study showed a statistically significant prevalence of A1 allele of the DRD gene in the hyperkinetic group. We also found a significantly higher incidence of atypical DAT genotypes in the hyperkinetic group. Furthermore we found significant connections with particular gene polymorphisms which may hypothetically represent a neurodevelopmental risk factor in the etiopathogenesis of the disorder (IL-2, IL-6, TNF-alpha, BDNF). We further found a connection of the M235 polymorphism of the AGT (angiotensinogene) gene to positive family history of psychiatric illness (p=0.031). As for cognitive characteristics, we identified three subtypes with different cognitive performance profiles. This finding shows interindividual variability of cognitive style in the group of hyperkinetic boys.

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Harv Rev Psychiatry. 2008 May-Jun;16(3):151-66.
ADHD and the rise in stimulant use among children.
Mayes R, Bagwell C, Erkulwater J.
Department of Political Science, University of Richmond, Richmond, VA 23173, USA. bmayes@richmond.edu

Attention-deficit/hyperactivity disorder (ADHD) holds the distinction of being the most extensively studied pediatric mental disorder and one of the most controversial, in part because it is also the most commonly diagnosed mental disorder among minors. Currently, almost 8% of youth aged 4 to 17 years have a diagnosis of ADHD, and approximately 4.5% both have the diagnosis and are using a stimulant (methylphenidate or amphetamine) as treatment for the disorder. Yet a diagnosis of ADHD is not simply a private medical finding; it carries with it a host of policy ramifications. The enduring controversy over ADHD in the public arena therefore reflects the discomfort over what happens when science is translated into policies and rules that govern how children will be treated medically, educationally, and legally. This article (1) summarizes the existing knowledge of ADHD, (2) provides the relevant history and trends, (3) explains the controversy, (4) discusses what is and is not unique about ADHD and stimulant pharmacotherapy, (5) outlines future directions of research, and (6) concludes with a brief analysis of how two North Carolina counties have established community protocols that have improved the screening, treatment, and societal consensus over ADHD and stimulants.

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Encephale. 2008 Apr;34(2):161-9. Epub 2007 Sep 5.
[Development of self-regulation and inhibition in children exhibiting attention deficit disorder with or without hyperactivity (ADHD)]
[Article in French]
Poissant H, Neault I, Dallaire S, Rouillard M, Emond V, Guay MC, Lageix P.
Centre neurosciences cognitives, université du Québec à Montréal-case postale 8888, succursale Centre-Ville-Montréal (Québec) H3C 3P8, Canada. poissant.helene@uqam.ca

INTRODUCTION: Self-regulation shares several affinities with executive functions. However, the specificity of self-regulation deficits in attention deficit/hyperactivity disorder (ADHD) remains unclear. The typical child starts around the age of four to develop a self-control mechanism along with an internal language that allows the child to modulate impulsively. Conversely, a child with ADHD seems to have greater difficulties delaying or retaining an action or response. OBJECTIVE: In this study we aim to evaluate self-regulation of comprehension in ADHD. RESULTS: Our results show that children with ADHD fail to recognize inconsistencies in presented stories at a rate ranging between 72 (eight years) and 54% (ten years). We also found a positive correlation between a better control of self-regulation and our behavioral inhibition measurement. The attentional deficits exhibited through markedly longer reaction times to continuous performance test (CPT) could be responsible for a poor ability to self-regulate. Fast reaction times were found to be associated with increased vigilance/attention that in turn would permit better self-regulation. Furthermore, our findings show that older subjects with ADHD have shorter reaction times to CPT approaching this group to the typical children. DISCUSSION: This suggests that improvement overtime in self-regulation processes may be attributed to the associated development of vigilance/attention in children with ADHD. Improved vigilance/attention would result in optimal reaction times during tasks that require self-regulation. In addition, our findings suggest that subjects with ADHD have developmental trajectories similar to those observed in healthy subjects. CONCLUSION: In the present study, the lack of a comparison group does not allow us to conclude if such trajectory is delayed compared to typical subjects. Finally, there was no significant relation between the degree of intelligence and the rate of self-regulation, which makes it possible to distinguish the two functions. However, in ADHD self-regulation is favourably influenced by age as observed in developmental studies on typical children. Thus, maturation independent of intelligence, influences self-regulation processes.

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Z Kinder Jugendpsychiatr Psychother. 2008 Mar;36(2):109-16.
[The treatment of Attention-Deficit/Hyperactivity Disorders with polyunsaturated fatty acids—an effective treatment alternative?]
[Article in German]
Frölich J, Döpfner M.
Klinik und Poliklinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters der Universität zu Köln. Praxis-dr-froelich@t-online.de

OBJECTIVES: Both omega-3 and omega-6 long-chain polyunsaturated fatty acids (PUFA) have a substantial impact on human brain development and function. However, in western industrial countries omega-3 LC-PUFA in particular are often lacking in diets. Increasing evidence indicates that LC-PUFA imbalance or deficiencies may be associated with Attention Deficit/Hyperactivity Disorder (ADHD) through involvement in the dopaminergic corico-striatal metabolism. Preliminary study result suggest that dietary supplementation with LC-PUFA might be effective in the treatment of ADHD. METHODS: This review summarizes the knowledge in terms of a hypothesized pathogenetic relationship between fatty acid metabolism and ADHD and discusses the possible clinical benefit of a primary or combined treatment with LC-PUFA. RESULTS: Actually it is unclear whether a deficit in intake or metabolism of LC-PUFA may play a major role in the pathogenesis of ADHD. Moreover treatment studies yielded conflicting results. A combination of Omega-3 and Omega-6 - fatty acids might attenuate the symptoms of ADHD significantly, thus making this dietary intake useful. CONCLUSIONS: Considerable research has to be done in the future to identify ideal therapeutic combinations and dosages of various fatty acids, and to develop reliable ways of defining those individuals to benefit from this treatment access.

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Z Kinder Jugendpsychiatr Psychother. 2008 Mar;36(2):97-106; quiz 106-7.
[Long-acting medications for the treatment of hyperkinetic disorders - a systematic review and European treatment guidelines. Part 2: a quantitative evaluation of long-acting medications]
[Article in German]
Banaschewski T, Coghill D, Santosh P, Zuddas A, Asherson P, Buitelaar J, Danckaerts M, Döpfner M, Faraone SV, Rothenberger A, Sergeant J, Steinhausen HC, Sonuga-Barke EJ, Taylor E.
Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters, Zentralinstitut für Seelische Gesundheit, Mannheim.

A panel of experts from several European countries has accomplished a systematic review of published and unpublished data on the use of long-acting medications in ADHD and hyperkinetic disorders, on the basis of which practical recommendations for the application of these medications have been developed. The current article outlines results of this analysis, comparing the effect sizes and numbers-needed to-treat for extended-release stimulant preparations and atomoxetine (ATX). It is concluded (1) that long-acting preparations should be licensed and used. (2) However, they should not completely replace short-acting medications, in view of costs as well as the greater flexibility of dosing. Individual choices of therapy are necessary. (3) Both ATX and retarded-release stimulants should be available.

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Ann N Y Acad Sci. 2008;1129:256-60.
Functional gene variation in the human norepinephrine transporter: association with attention deficit hyperactivity disorder.
Kim CH, Waldman ID, Blakely RD, Kim KS.
Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, 115 Mill St., Belmont, MA 02478, USA. kskim@mclean.harvard.edu

The norepinephrine (NE) transporter (NET) is responsible for the re-uptake of NE into presynaptic nerve terminals, thus critically regulating noradrenergic signaling and homeostasis. Since NE signaling contributes to diverse brain functions, we hypothesize that promoter variation within the human NET gene (solute carrier family 6, member 2; SLC6A2) may impact risk for NE-related disorders, including depression, attention deficit hyperactive disorder (ADHD), and autonomic dysfunction. In support of this, we recently found a functional polymorphism at -3081 position upstream of the transcription initiation site. This polymorphism displayed differential promoter function, which we showed could arise from recruitment of a transcriptional repressor. Further analyses identified Slug and Scratch as candidates involved in repression of SLC6A2 transcription generated by the -3081(T) allele. Moreover, we observed a significant association of the -3081(T) variant with ADHD. Altered transcription of SLC6A2 may therefore represent a novel risk factor for the development of ADHD.

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Ann N Y Acad Sci. 2008;1129:236-45.
Neuronal mechanisms underlying attention deficit hyperactivity disorder: the influence of arousal on prefrontal cortical function.
Brennan AR, Arnsten AF.
Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.

Neuropsychological and imaging studies indicate that attention deficit hyperactivity disorder (ADHD) is associated with alterations in prefrontal cortex (PFC) and its connections to striatum and cerebellum. Research in animals, in combination with observations of patients with cortical lesions, has shown that the PFC is critical for the regulation of behavior, attention, and affect using representational knowledge. The PFC is important for sustaining attention over a delay, inhibiting distraction, and dividing attention, while more posterior cortical areas are essential for perception and the allocation of attentional resources. The PFC in the right hemisphere is especially important for behavioral inhibition. Lesions to the PFC produce a profile of distractibility, forgetfulness, impulsivity, poor planning, and locomotor hyperactivity. The PFC is very sensitive to its neurochemical environment, and either too little (drowsiness) or too much (stress) catecholamine release in PFC weakens cognitive control of behavior and attention. Recent electrophysiological studies in animals suggest that norepinephrine enhances "signals" through postsynaptic alpha2A adrenoceptors in PFC, while dopamine decreases "noise" through modest levels of D1 receptor stimulation. alpha2A-Adrenoceptor stimulation strengthens the functional connectivity of PFC networks, while blockade of alpha2 receptors in the monkey PFC recreates the symptoms of ADHD, resulting in impaired working memory, increased impulsivity, and locomotor hyperactivity. Genetic alterations in catecholamine pathways may contribute to dysregulation of PFC circuits in this disorder. Medications may have many of their therapeutic effects by optimizing stimulation of alpha2A adrenoceptors and D1 receptors in the PFC, thus strengthening PFC regulation of behavior and attention.

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Curr Drug Saf. 2007 Jan;2(1):33-42.
Attention deficit and hyperactivity disorder: controversies of diagnosis and safety of pharmacological and nonpharmacological treatment.
Benner-Davis S, Heaton PC.
College of Pharmacy, University of Cincinnati, Cincinnati, Ohio 45267-0004, USA.

Attention-Deficit and Hyperactivity Disorder (ADHD) is a condition that presents with a variety of behavioral and social problems. The objective of this review was to examine the evidence concerning the controversies surrounding the diagnosis of ADHD and the safety of pharmacological and nonpharmacological treatment. A MEDLINE search was conducted using MeSH terms ADHD, children, treatments or behavioral therapy. The search was limited to January 1990 to present, randomized clinical trials, retrospective studies and English. Fifty-seven articles were selected for review. Controversies exist regarding the diagnosis: variations exist by gender, across countries and by method of diagnosis. These issues are currently unresolved. The interventions with the most data concerning their safety and efficacy in children were stimulant medications. Children with ADHD who took stimulant medications showed the greatest improvement in behavior when compared to other interventions such as behavior therapy or family counseling. Limitations of behavior therapy included that it is often a difficult process to continue on an ongoing basis and only a portion of the therapy stimulated the child's natural reward system. However, a combination of both stimulant medication and behavior therapy demonstrated synergistic efficacy. Care must be taken to insure that issues of gender and race, as well as the adverse effects of treatment options, are adequately taken into account by the treating clinician.

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J Clin Psychiatry. 2008 Jan 16;:e1-e9 [Epub ahead of print]
Gender Differences in 2 Clinical Trials of Adults With Attention-Deficit/Hyperactivity Disorder: A Retrospective Data Analysis.
Robison RJ, Reimherr FW, Marchant BK, Faraone SV, Adler LA, West SA.
From the Department of Psychiatry, University of Utah, Salt Lake City (Drs. Robison and Reimherr and Mr. Marchant); SUNY Upstate Medical University, Syracuse, N.Y. (Dr. Faraone); the Department of Psychiatry and Neurology, New York University, New York (Dr. Adler); and CNS Healthcare, Orlando, Fla. (Dr. West).

INTRODUCTION: Studies show that, in childhood attention-deficit/hyperactivity disorder (ADHD), boys have the combined type with externalizing behaviors more frequently, and girls have the inattentive type with increased internalizing disorders more frequently. METHOD: This study explored gender differences in adults with ADHD in 2 large, placebo-controlled, multicenter studies conducted from 2000 to 2001. Information collected included 2 measures of ADHD, multiple psychological measures, general physical symptoms, and treatment response. RESULTS: Thirty-four percent of the subjects were female. Women were rated as more impaired on every measure of ADHD symptoms including total Conners' Adult ADHD Rating Scale-Investigator Format (CAARS-INV), total Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), and most subscales of both measures. More women (75%) had combined type compared with men (62%). Women showed a more complex presentation, with higher scores on the Hamilton Rating Scale for Anxiety (HAM-A) and the Hamilton Rating Scale for Depression, 17-item version (HAM-D(17)), more sleep problems, and more past DSM-IV Axis 1 diagnoses. Both sexes displayed substantial impairment on 3 Psychological General Well-Being Schedule factors: tension-anxiety, life satisfaction, and vitality-drive. Women experienced significantly (p = .003) greater rates of emotional dysregulation (37%) versus men (29%) as defined by a cluster of symptoms on the WRAADDS. The emotional dysregulation factor is derived by combining 3 symptoms-temper control, mood lability, and emotional overreactivity-from the Utah Criteria for ADHD in adults. These symptoms are considered associated symptoms in the DSM-IV description of ADHD. Women also experienced greater improvement (p = .011) on this symptom factor. CONCLUSION: In contrast to the results from childhood studies, women were more impaired than men on ADHD scales in our study. The higher level of emotional symptoms and more complicated presentation in women may obscure the diagnosis of ADHD. Thus, the assessments of adults with ADHD should include an exploration of the emotional dimensions of the illness.

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Nutr J. 2008 Jan 21;7(1):2 [Epub ahead of print]
Nutritional therapies for mental health disorders.
Lakhan SE, Vieira KF.

ABSTRACT: According to the Diagnostic and Statistical Manual of Mental Disorders, 4 out of the 10 leading causes of disability in the US and other developed countries are mental disorders. Major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD) are among the most common mental disorders that currently plague numerous countries and have varying incidence rates from 26 percent in America to 4 percent in China. Though some of this difference may be attributable to the manner in which individual healthcare providers diagnose mental disorders, this noticeable distribution can be also explained by studies which show that a lack of certain dietary nutrients contribute to the development of mental disorders. Notably, essential vitamins, minerals, and omega-3 fatty acids are often deficient in the general population in America and other developed countries; and are exceptionally deficient in patients suffering from mental disorders. Studies have shown that daily supplements of vital nutrients often effectively reduce patients' symptoms. Supplements that contain amino acids also reduce symptoms, because they are converted to neurotransmitters that alleviate depression and other mental disorders. Based on emerging scientific evidence, this form of nutritional supplement treatment may be appropriate for controlling major depression, bipolar disorder, schizophrenia and anxiety disorders, eating disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), addiction, and autism. The aim of this manuscript is to emphasize which dietary supplements can aid the treatment of the four most common mental disorders currently affecting America and other developed countries: major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD). Most antidepressants and other prescription drugs cause severe side effects, which usually discourage patients from taking their medications. Such noncompliant patients who have mental disorders are at a higher risk for committing suicide or being institutionalized. One way for psychiatrists to overcome this noncompliance is to educate themselves about alternative or complementary nutritional treatments. Although in the cases of certain nutrients, further research needs to be done to determine the best recommended doses of most nutritional supplements, psychiatrists can recommend doses of dietary supplements based on previous and current efficacious studies and then adjust the doses based on the results obtained.

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Pediatrics. 2008 Jan;121(1):e73-84.
A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder.
Biederman J, Melmed RD, Patel A, McBurnett K, Konow J, Lyne A, Scherer N; SPD503 Study Group.
Pediatric Psychopharmacology Department, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. jbiederman@partners.org

OBJECTIVE: With this study we assessed the efficacy and safety of an extended-release formulation of guanfacine compared with placebo for the treatment of children and adolescents with attention-deficit/hyperactivity disorder. METHODS: In this multicenter, double-blind, placebo-controlled, fixed-dosage escalation study, patients aged 6 to 17 years were randomly assigned to 1 of 3 treatment groups of guanfacine extended release (2, 3, or 4 mg/day) or placebo for 8 weeks. The primary outcome measurement was the Attention-Deficit/Hyperactivity Disorder Rating Scale IV total score. Secondary measurements included Clinical Global Impression of Improvement, Parent's Global Assessment, Conners' Parent Rating Scale-Revised: Short Form, and Conners' Teacher Rating Scale-Revised: Short Form. RESULTS: A total of 345 patients were randomly assigned to placebo (n = 86) or guanfacine extended release 2 mg (n = 87), 3 mg (n = 86), or 4 mg (n = 86) treatment groups. Least-squares mean changes from baseline to the end point in Attention-Deficit/Hyperactivity Disorder Rating Scale IV total scores were significant in all groups of children taking guanfacine extended release: -16.18 in the 2-mg group, -16.43 in the 3-mg group, and -18.87 in the 4-mg group, compared with -8.48 in the placebo group. All groups of children taking guanfacine extended release showed significant improvement on hyperactivity/impulsivity and inattentiveness subscales of the Attention-Deficit/Hyperactivity Disorder Rating Scale IV, Clinical Global Impression of Improvement, Parent's Global Assessment, Conners' Parent Rating Scale-Revised: Short Form, and Conners' Teacher Rating Scale-Revised: Short Form assessments compared with placebo. The most commonly reported treatment-emergent adverse events were headache, somnolence, fatigue, upper abdominal pain, and sedation. Small to modest changes in blood pressure, pulse rate, and electrocardiogram parameters were observed but were not clinically meaningful. CONCLUSIONS: Guanfacine extended release met the primary and secondary efficacy end points. It was well tolerated and effective compared with placebo.

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Pediatrics. 2008 Jan;121(1):e65-72.
Managing attention-deficit/hyperactivity disorder in primary care: a systematic analysis of roles and challenges.
Power TJ, Mautone JA, Manz PH, Frye L, Blum NJ.
The Center for Management of ADHD, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. power@email.chop.edu

OBJECTIVE: This study was designed to investigate the perceptions of primary care providers about their roles and the challenges of managing attention-deficit/hyperactivity disorder and to evaluate differences between providers who serve families primarily from urban versus suburban settings. METHODS: The ADHD Questionnaire was developed to assess primary care provider views about the extent to which clinical activities that are involved in the management of attention-deficit/hyperactivity disorder are appropriate and feasible in primary care. Participants were asked to rate each of 24 items of the questionnaire twice: first to indicate the appropriateness of the activity given sufficient time and resources and second to indicate feasibility in their actual practice. Informants used a 4-point scale to rate each item for appropriateness and feasibility. RESULTS: An exploratory factor analysis of primary care provider ratings of the appropriateness of clinical activities for managing attention-deficit/hyperactivity disorder identified 4 factors of clinical practice: factor 1, assessing attention-deficit/hyperactivity disorder; factor 2, providing mental health care; factor 3, recommending and monitoring approved medications; and factor 4, recommending nonapproved medications. On a 4-point scale (1 = not appropriate to 4 = very appropriate), mean ratings for items on factor 1, factor 2, and factor 3 were high, indicating that the corresponding domains of practice were viewed as highly appropriate. Feasibility challenges were identified on all factors, but particularly factors 1 and 2. A significant interaction effect, indicating differences between appropriateness and feasibility as a function of setting (urban versus suburban), was identified on factor 1. The challenges of assessing attention-deficit/hyperactivity disorder were greater for urban than for suburban primary care providers. CONCLUSIONS: Primary care providers believe that it is highly appropriate for them to have a role in the management of attention-deficit/hyperactivity disorder. Feasibility issues were particularly salient related to assessing attention-deficit/hyperactivity disorder and providing mental health care. The findings highlight the need not only for additional training of primary care providers but also for practice-based resources to assist with school communication and collaboration with mental health agencies, especially in urban practices.

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Expert Opin Investig Drugs. 2008 Jan;17(1):77-84.
An expert opinion on methylphenidate treatment for attention deficit hyperactivity disorder in pediatric patients with epilepsy.
Baptista-Neto L, Dodds A, Rao S, Whitney J, Torres A, Gonzalez-Heydrich J.
Children's Hospital of Boston, Department of Psychiatry, 300 Longwood Avenue, Boston, MA 02115, USA. lourival.baptista-neto@childrens.harvard.edu

Methylphenidate (MPH) is one of the most commonly prescribed medications to treat attention deficit hyperactivity disorder (ADHD). Despite the elevated rates of ADHD in children with epilepsy, few studies have examined the use of MPH in this population. Case reports have warned about new-onset seizures in patients treated with MPH, and drug-drug interactions between MPH and antiepileptic drugs (AEDs), as well as antidepressants. However, retrospective chart reviews, open-label trials and controlled trials of MPH in patients with epilepsy and ADHD have noted significant improvements in ADHD symptoms without an exacerbation of seizures or an adverse effect on AED serum levels. This paper reviews the chemistry and mechanisms of action of MPH, as well as preclinical, premarketing clinical trials and postmarketing data relevant to its use in patients with ADHD and epilepsy.

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J Nerv Ment Dis. 2007 Dec;195(12):1013-9.
Structured group psychotherapy in adults with attention deficit hyperactivity disorder: results of an open multicentre study.
Philipsen A, Richter H, Peters J, Alm B, Sobanski E, Colla M, Münzebrock M, Scheel C, Jacob C, Perlov E, Tebartz van Elst L, Hesslinger B.
Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Freiburg, Germany. alexandra.philipsen@uniklinik-freiburg.de

Attention deficit hyperactivity disorder (ADHD) is a serious mental disorder that often persists in adulthood. In a pilot study, a structured skills training group program for adult ADHD led to significant symptomatic improvements. The present study evaluated the program's effectiveness, feasibility, and patient acceptability in a multicenter setting. Seventy-two adult ADHD patients were assigned to 13 two-hour weekly sessions at 4 different therapy sites. The therapy was well tolerated and led to significant improvements of ADHD, depressive symptoms, and personal health status (p < 0.001). The factors treatment site and medication did not contribute to the overall improvement. Patients regarded the program topics "behavioral analyses," "mindfulness," and "emotion regulation" as the most helpful. In this multicenter study, the therapy program showed therapist-independent effects and seemed to be disorder-specific. This warrants the effort of organizing further controlled studies.

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Pediatr Dent. 2007 Nov-Dec;29(6):507-13.
Pharmacologic behavior management of pediatric dental patients diagnosed with attention deficit disorder/attention deficit hyperactivity disorder.
Kerins CA, McWhorter AG, Seale NS.
Department of Pediatric Dentistry, Baylor College of Dentistry, Texas A&M University Health Science Center, Dallas, USA. ckerins@bcd.tamhsc.edu

PURPOSE: The purpose of this study was to conduct a survey of Texas pediatric dentists to determine: (1) the percentage of patients they treat with attention deficit disorder (ADD)/attention deficit hyperactivity disorder (ADHD); (2) the behavior management techniques that are utilized to treat their patients who suffer from ADD/ADHD; and (3) the relative success rates of these techniques in their practices. METHODS: A 17-question, single-answer, multiple choice survey was mailed to 343 Texas pediatric dentists. The mailing list was obtained from American Academy of Pediatric Dentistry and Texas Academy of Pediatric Dentistry member rosters. One mailing was sent, including a self-addressed stomped envelope, for returned responses. RESULTS: A 54% response rate (186 surveys) revealed that nitrous oxide was the most frequently used pharmacologic behavior management technique; however, demerol/promethazine/nitrous oxide was rated as effective most often for treating ADD/ADHD patients. CONCLUSIONS: Practitioners believe the incidence of attention deficit disorder/attention deficit hyperactivity disorder is increasing, and they are familiar with the medications used to treat the conditions. Texas pediatric dentists are using a variety of sedation techniques and are interested in developing guidelines for sedation of these patients.

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J Manag Care Pharm. 2007 Nov;13(9 Suppl B):S2-S13; quiz S14-S16.
Changes and challenges: managing ADHD in a fast-paced world.
Manos MJ, Tom-Revzon C, Bukstein OG, Crismon ML.
Children's Hospital, 9500 Euclid Ave., Desk A120, Cleveland, OH 44195,USA. manosm@ccf.org

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) impairs the lives of both children and adults. Undiagnosed and untreated, ADHD may have serious lifelong consequences. Research has identified diagnostic clues, neurotransmitter pathways, and psychiatric comorbidities related to ADHD, as well as effective pharmacologic, behavioral, and psychosocial interventions. Stimulant agents have been the foundation of ADHD therapy for more than 50 years. Availability of new extended-release (XR or ER) and longer-acting (LA) formulations and novel agents allows for wider and more individualized treatment choices. Side effects of stimulants are generally mild, short lived, and responsive to adjustments in dosage or timing. Outcomes in ADHD treatment can be improved with the use of clear treatment guidelines and tools to aid clinicians in implementing them efficiently and effectively. The Texas Children's Medication Algorithm Project (CMAP) provides a system of algorithm-driven treatment decisions that is evidence based and easy to implement. OBJECTIVE: To (1) review the psychological components of attention, the neurotransmitter pathways associated with ADHD, and the array of therapeutic options for ADHD, with an emphasis on the most recent introductions to the therapeutic armamentarium; (2) discuss the rare psychiatric and cardiovascular side effects associated with stimulants; (3) review abuse liability, comorbidities, and suggested approaches to these issues; and (4) review the development and use of CMAP and offer resources for its implementation in clinical practice. CONCLUSION: The pathophysiology of ADHD is linked to dysfunction of fronto-subcortical networks and dysregulation of dopaminergic, noradrenergic, and nicotinic neurotransmitter systems. An additive effect of multiple genes as well as environmental influences contributes to the clinical picture. Treatment with stimulants and nonstimulants has proven effective in different subgroups,
with the effectiveness of specific agents most likely related to the primary neurotransmitter involved. Availability of XR, ER, LA, and transdermal stimulant formulations, as well as alternative nonstimulant agents, offers new options for the pharmacotherapy of ADHD. Major concerns associated with abuse liability of stimulants have been allayed by the availability of ER formulations, which have reduced reinforcing effects associated with short-acting preparations. Medication outcomes in ADHD can be enhanced by the use of evidence-based algorithms such as CMAP. Keys to success are adequate initial assessment and diagnosis, the use of sustained-release products, sufficient dose titration, and the use of clinical rating scales with feedback from caregivers and teachers. Optimal treatment outcomes can be achieved by appropriate pharmacotherapy combined with psychosocial interventions.

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Clin Child Psychol Psychiatry. 2007 Oct;12(4):511-24.
Parent management training as a treatment for children with oppositional defiant disorder referred to a mental health clinic.
Costin J, Chambers SM.
Eastern Health Child and Adolescent Mental Health Service, Victoria, Australia. Jan.Costin@maroondah.org.au

Parent Management Training (PMT) has been shown to be an empirically supported intervention in ameliorating antisocial behaviour problems. Less evidence is available to demonstrate the effectiveness of PMT in routine public-health-oriented community-based settings where the presence of comorbid disorders complicates the picture. The current study was undertaken to investigate the effectiveness of PMT as a treatment for primary school-age children with Oppositional Defiant Disorder (ODD) and comorbid disorders offered by clinical staff as part of clinical practice. An Australian sample of 94 parents of children diagnosed with ODD by structured interview was provided with eight sessions of PMT. Measures used to assess changes in child behaviour symptoms were the Eyberg Child Behavior Inventory, the Parent Stress Index Child Domain, and the Child Behavior Checklist. Clinically relevant and statistically significant outcome results were found at posttreatment and at 5 months follow-up. There was a reduction in child symptomatology but no evidence of any effect of comorbidity on outcome. These findings are important for the clinical field as they show that PMT is a robust intervention suitable for routine clinical practice even when comorbid disorders are present in addition to ODD.

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J Am Acad Child Adolesc Psychiatry. 2007 Oct;46(10):1263-1271.
Effectiveness of Behavioral Parent Training for Children With ADHD in Routine Clinical Practice: A Randomized Controlled Study.
van den Hoofdakker BJ, van der Veen-Mulders L, Sytema S, Emmelkamp PM, Minderaa RB, Nauta MH.
Ms. van den Hoofdakker, Ms. van der Veen-Mulders, and Drs. Sytema, Minderaa, and Nauta are with the Department of Psychiatry, University Medical Center Groningen, University of Groningen, The Netherlands; and Dr. Emmelkamp is with the Department of Clinical Psychology, University of Amsterdam, The Netherlands.

OBJECTIVE:: To investigate the effectiveness of behavioral parent training (BPT) as adjunct to routine clinical care (RCC). METHOD:: After a first phase of RCC, 94 children with attention-deficit/hyperactivity disorder (ADHD) ages 4-12, all referred to a Dutch outpatient mental health clinic, were randomly assigned to 5 months of BPT plus concurrent RCC (n = 47) or to 5 months of RCC (n = 47) alone. BPT consisted of 12 sessions in group format; RCC included family support and pharmacotherapy when appropriate. Exclusionary criteria were minimized, and children with and without medication could participate. Parent-reported behavioral problems, ADHD symptoms, internalizing problems, and parenting stress were assessed before and after treatment. Follow-up assessment of the BPT + RCC group was completed 25 weeks post-BPT intervention. Repeated-measures analyses of variance were carried out on an intention-to-treat basis. RESULTS:: Both groups showed improvements over time on all measures. BPT + RCC was superior to RCC alone in reducing behavioral (p = .017) and internalizing (p = .042) problems. No outcome differences were found in ADHD symptoms (p = .161) and parenting stress (p = .643). These results were equal for children with and without medication. Children allocated to RCC alone received more polypharmaceutical treatment. CONCLUSIONS:: Adjunctive BPT enhances the effectiveness of routine treatment of children with ADHD, particularly in decreasing behavioral and internalizing problems, but not in reducing ADHD symptoms or parenting stress. Furthermore, adjunctive BPT may limit the prescription of polypharmaceutical treatment.

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Int J Clin Pract. 2007 Oct;61(10):1730-8.
Clinical assessment and treatment of ADHD in children.
Smoot LC, Boothby LA, Gillett RC.
Auburn University, Auburn, AL, USA.

Attention-deficit/hyperactivity disorder is a highly diagnosed psychiatric disorder in children. This widespread and complex condition requires extensive evaluation involving clinicians, parents and teachers. Proper management involves individual assessment and treatment. Psychostimulants remain the primary medication of choice as they have been shown to be efficacious for this condition. Newer, long-acting medications are providing expanded options for children and their caregivers. Failure to assess and treat can lead to serious long-term effects later in life.

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Eur Child Adolesc Psychiatry. 2007 Sep 14; [Epub ahead of print]
Treatment of attention deficit hyperactivity disorder in children : Predictors of treatment outcome.
van der Oord S, Prins PJ, Oosterlaan J, Emmelkamp PM.
Dept. of Clinical Psychology, University of Amsterdam, Roeterstraat 15, Amsterdam, 1018, WB, The Netherlands, s.vanderoord@uva.nl.

OBJECTIVE: The present study investigated the predictive power of anxiety, IQ, severity of ADHD and parental depression on the outcome of treatment in children with ADHD. METHOD: Fifty children with ADHD (ages 8-12) were randomized to a 10-week treatment of methylphenidate or to a treatment of methylphenidate combined with multimodal behavior therapy. Prior to treatment predictors were assessed. Outcome was assessed separately for parents and teachers on a composite measure of inattentive, hyperactive, oppositional- and conduct disorder symptoms. RESULTS: There was neither a significant difference between the two treatments at baseline nor did treatment condition predict outcome. Therefore the data were collapsed across the two treatments. A combination of anxiety and IQ predicted teacher-rated outcome, explaining 18% of the variance. Higher anxiety and higher IQ's indicated better treatment outcome. There were no significant predictors of the parent-rated outcome. CONCLUSION: This study showed a small but significant predictive effect of IQ and anxiety on treatment outcome in children with ADHD. CLINICAL IMPLICATIONS: This study supports the idea that for the treatment of ADHD children with comorbid anxiety and higher IQ respond better to the two most used treatments for ADHD.

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Expert Opin Emerg Drugs. 2007 Sep;12(3):423-34.
Emerging drugs for attention-deficit/hyperactivity disorder.
Weisler RH.
Duke University Medical Center, Durham, NC, USA. rweisler@aol.com

Symptoms of attention-deficit/hyperactivity disorder (ADHD) are heterogeneous and often accompanied by comorbid psychiatric disorders. Although symptoms tend to lessen with age, many patients continue to be affected by the disorder into adulthood. Although many medications are available to treat ADHD, it is unlikely that a single medication will ever be developed to work for all patients. Recent advances, such as long-acting, extended-release formulations and transdermal delivery systems, have lengthened the duration of effectiveness, which has increased compliance and eliminated the need for additional medication dosing during the school or work day. Additional safe, well-tolerated, long-acting medications with further reduced potential for diversion and abuse are needed. Catecholamine pathways and their effect on executive functions and ADHD symptom control have been productive areas of research. Potential therapies such as adrenergic receptor agonists, glutamatergic agents, GABA receptor antagonists and nicotine receptor agonists are being explored as future pharmacotherapies for ADHD.

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BMC Psychiatry. 2007 Sep 14;7(1):49 [Epub ahead of print]
Comparative acute efficacy and tolerability of OROS and immediate release formulations of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder.
Biederman J, Mick EO, Surman C, Doyle R, Hammerness P, Michel E, Martin J, Spencer TJ.

ABSTRACT: BACKGROUND: The main aim of this study was to compare the safety and efficacy of IR MPH administered three times daily to those of once daily OROS-MPH. METHODS: Subjects were outpatient adults satisfying full diagnostic criteria for DSM-IV ADHD between 19 and 60 years of age. Data from two independently conducted 6-week placebo controlled, randomized clinical trials of IR-MPH (tid) and of OROS-MPH were pooled to create three study groups: Placebo (N=116), IR-MPH (tid) (N=102) and OROS-MPH (N=67). RESULTS: Eight-five percent (N=99) of placebo treated subjects, 77% (N=79) of the IR-MPH (tid) treated subjects, and 82% (N=55) of the OROS-MPH treated subjects completed the 6-week trial. Total daily doses at endpoint were 80.9+/-31.9 mg, 74.8+/-26.2 mg, and 95.4+/-26.3 mg in the OROS-MPH, IR-MPH (tid), and placebo groups, respectively. At endpoint, 66% (N=44) of subjects receiving OROS-MPH and 70% (N=71) of subjects receiving IR-MPH (tid) were considered responders compared with 31% (N=36) on placebo. CONCLUSION: Comparison of data from two similarly designed, large, randomized, placebo-controlled, trials, showed that equipotent daily doses of once daily OROS-MPH had similar efficacy to that of TID administered IR MPH. Trial Registration. The trial of OROS-MPH was registered at clinicaltrials.gov (identifier #NCT00181571) but the trial of IR-MPH was funded by the NIH and was conducted before registration was required or available.

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Arch Pediatr Adolesc Med. 2007 Sep;161(9):857-64.
Prevalence, Recognition, and Treatment of Attention-Deficit/Hyperactivity Disorder in a National Sample of US Children.
Froehlich TE, Lanphear BP, Epstein JN, Barbaresi WJ, Katusic SK, Kahn RS.
Cincinnati Children's Hospital Medical Center, Mail Location 4002, 3333 Burnet Ave, Cincinnati, OH 45229. tanya.froehlich@cchmc.org.

OBJECTIVE: To determine the US national prevalence of attention-deficit/hyperactivity disorder (ADHD) and whether prevalence, recognition, and treatment vary by socioeconomic group. DESIGN: Cross-sectional survey. SETTING: Nationally representative sample of the US population from 2001 to 2004. PARTICIPANTS: Eight- to 15-year-old children (N = 3082) in the National Health and Nutrition Examination Survey. MAIN OUTCOME MEASURES: The Diagnostic Interview Schedule for Children (caregiver module) was used to ascertain the presence of ADHD in the past year based on Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) criteria. Prior diagnosis of ADHD by a health professional and ADHD medication use were assessed by caregiver report. RESULTS: Of the children, 8.7% met DSM-IV criteria for ADHD. The poorest children (lowest quintile) were more likely than the wealthiest (highest quintile) to fulfill criteria for ADHD (adjusted odds ratio [AOR], 2.3; 95% confidence interval [CI], 1.4-3.9). Among children meeting DSM-IV ADHD criteria, 47.9% had a prior diagnosis of ADHD and 32.0% were treated consistently with ADHD medications during the past year. Girls were less likely than boys to have their disorder identified (AOR, 0.3; 95% CI, 0.1-0.8), and the wealthiest children were more likely than the poorest to receive regular medication treatment (AOR, 3.4; 95% CI, 1.3-9.1). CONCLUSIONS: Of US children aged 8 to 15 years, 8.7%, an estimated 2.4 million, meet DSM-IV criteria for ADHD. Less than half of children meeting DSM-IV criteria report receiving either a diagnosis of ADHD or regular medication treatment. Poor children are most likely to meet criteria for ADHD yet are least likely to receive consistent pharmacotherapy.

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J Child Adolesc Psychopharmacol. 2007 Aug;17(4):433-46.
Venlafaxine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder.
Findling RL, Greenhill LL, McNamara NK, Demeter CA, Kotler LA, O'riordan MA, Myers C, Reed MD.
Department of Psychiatry, University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, Ohio., Department of Pediatrics, University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, Ohio.

Objective: The objectives of this pilot study were to explore the changes in symptom severity, tolerability, and the pharmacodynamics of venlafaxine treatment in youths with attention-deficit/hyperactivity disorder (ADHD). Methods: This was a 2-week, open-label, outpatient trial of venlafaxine in children and adolescents, ages 5-17 years, with ADHD. Three dosing strata, 0.5, 1.0, and 2.0 mg/kg per day, were examined. ADHD symptom severity and improvement assessments included the ADHD Rating Scale (ARS-IV) and the Clinical Global Impressions Scale (CGI). During this study, venlafaxine, O-desmethylvenlafaxine (ODV), norepinephrine, and serotonin concentrations were obtained. Results: Thirty-eight participants (33 males) were treated in this trial. Overall, parent-completed and teacher-completed ARS-IV total scores showed a statistically significant positive change at the end of the study when compared to baseline (p < 0.05). Significant increases in plasma venlafaxine concentrations were observed at day 15 when compared to day 8 (p = 0.04). In addition, plasma norepinephrine and serotonin concentrations were found to be significantly decreased from baseline at end of study (p < 0.05). Four patients ended participation in the study prematurely: lost to follow up (n = 2), withdrawal of consent (n = 1), and worsening of ADHD symptoms after 8 days of treatment (n = 1). There were no discontinuations due to other adverse events. Conclusions: Venlafaxine appeared to offer some benefit and appears to be relatively safe for the short-term treatment of ADHD in this open-label trial. The pharmacodynamics of venlafaxine in youths are consistent with serotonergic and neuradrenergic modulation.

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J Child Adolesc Psychopharmacol. 2007 Aug;17(4):421-32.
Long-Acting Methylphenidate has an Effect on Aggressive Behavior in Children with Attention-Deficit/Hyperactivity Disorder.
Sinzig J, Dopfner M, Lehmkuhl G; German Methylphenidate Study Group.
Department for Psychiatry and Psychotherapy of Children & Adolescents at the University of Cologne, Germany.

Introduction: Aggression is frequently observed in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). The aim of this study was to assess the efficacy with regard to oppositional and aggressive behavior of a new long-acting methylphenidate preparation (Medikinet retard((R)), MPH-MR), with equal portions of the immediate-release and the sustained-release active substance, and especially to look at correlations between either teacher or parent assessment of aggression and ADHD sub-symptomatology. Methods: Eighty five children and adolescents (6-16 years) were investigated in a double-blind, randomized, clinical trial over 5 weeks under a treatment with MPH-MR using symptom checklists for ADHD, oppositional-defiant and conduct disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). Results: A total of 64.9% of the children showed oppositional defiant disorder/conduct disorder (ODD/CD) symptoms. A statistically significant effect was found in the group treated with MPH (verum-group). On the basis of Cohen's criteria, high effects were found for aggressive symptoms in school (d = 1.0), but not in the afternoon (d = 0.4). There were also lower effect sizes for more severe aggressive symptoms. We found characteristic correlations between ODD/CD symptoms and the ADHD subscale hyperactivity/impulsivity compared to the subscale inattention. Conclusions: Long-acting MPH is effective in the treatment of oppositional-defiant and aggressive behavior, especially concerning milder symptoms. The expected correlation between impulsivity and aggressiveness could be confirmed.

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J Child Adolesc Psychopharmacol. 2007 Aug;17(4):407-20.
Efficacy and safety of atomoxetine in adolescents with attention-deficit/hyperactivity disorder and major depression.
Bangs ME, Emslie GJ, Spencer TJ, Ramsey JL, Carlson C, Bartky EJ, Busner J, Duesenberg DA, Harshawat P, Kaplan SL, Quintana H, Allen AJ, Sumner CR.
Lilly Research Laboratories, Indianapolis, Indiana.

This double-blind study examined efficacy and safety of atomoxetine (ATX; </=1.8mg/kg per day) in adolescents aged 12-18 with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnoses of both attention-deficit/hyperactivity disorder (ADHD) and co-morbid major depressive disorder (MDD). Diagnoses were confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version and persistently elevated scores on the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, Parent version, Investigator-administered and -scored (ADHDRS-IV-Parent:Inv, >/=1.5 standard deviations above age and gender norms) and Children's Depression Rating Scale-Revised (CDRS-R, >/= 40). Patients were treated for approximately 9 weeks with ATX (n = 72) or placebo (n = 70). Mean decrease in ADHDRS-IV-Parent:Inv total score was significantly greater in the ATX group (-13.3 +/- 10.0) compared with the placebo group (-5.1 +/- 9.9; p < 0.001). Mean CDRS-R score improvement was not significantly different between groups (ATX, -14.8 +/- 13.3; placebo, -12.8 +/- 10.4). Rates of treatment-emergent mania did not differ between groups (ATX, 0.0%; placebo, 1.5%). ATX treatment was associated with significantly more nausea and decreased appetite (p = 0.002; p = 0.003). No spontaneously reported adverse events involving suicidal ideation or suicidal behavior occurred in either group. ATX was an effective and safe treatment for ADHD in adolescents with ADHD and MDD. However, this trial showed no evidence for ATX of efficacy in treating MDD.

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Expert Opin Pharmacother. 2007 Apr;8(6):745-58.
Review of long-acting stimulants in the treatment of attention deficit hyperactivity disorder.
Weisler RH.
Duke University Medical Center, Durham, NC, USA. rweisler@aol.com

A number of long-acting medications for the treatment of attention deficit hyperactivity disorder (ADHD) have recently been developed and approved for use in the US. These compounds are intended to optimize and maintain ADHD symptom control throughout the day, while eliminating problems associated with short-acting medications, such as the need for in-school, midday or multiple daily doses. Recent reports confirm that the safety and tolerability of long-acting medications are similar to those of short-acting medications, although long-acting medications appear to have a lower risk of abuse and diversion and may be associated with significant improvements in medication adherence. Distinctions can be made among the long-acting medications with regard to the onset, magnitude and duration of their clinical effects. Recognition of these differences is important for individualizing treatment for patients with ADHD.

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Ann Thorac Surg. 2007 Apr;83(4):1425-30.
Attentional dysfunction in children after corrective cardiac surgery in infancy.
Hövels-Gürich HH, Konrad K, Skorzenski D, Herpertz-Dahlmann B, Messmer BJ, Seghaye MC.
Department of Pediatric Cardiology, Aachen University of Technology, Aachen, Germany. hhoevels-guerich@ukaachen.de

BACKGROUND: Attentional dysfunction in children after corrective cardiac surgery in infancy has rarely been evaluated and is the topic of the present work. METHODS: Forty unselected children, 20 with tetralogy of Fallot and hypoxemia and 20 with ventricular septal defect and cardiac insufficiency, operated on at a mean age 0.7 (SD 0.3) years with deep hypothermic circulatory arrest and low flow cardiopulmonary bypass, were evaluated at mean age 7.4 (SD 1.6) years by the computerized form of the Attention Network Test providing performance measures of three networks of attention: alerting, orienting, and executive control. Parental ratings of attentional dysfunction were derived from the Child Behavior Checklist. Results were compared with healthy controls, between patient groups, and correlated with perioperative risk factors and current neurodevelopmental status. RESULTS: Executive control was reduced in the tetralogy of Fallot group, alerting and orienting were found normal and not different between patient groups. Durations of aortic cross clamping inversely correlated with orienting; durations of cardiopulmonary bypass correlated with mean reaction time and inversely correlated with executive control. Motor function and acquired abilities correlated with executive control and orienting. Parent-reported problems on the Child Behavior Checklist inversely correlated with executive control and mean accuracy. CONCLUSIONS: Children with preoperative hypoxemia in infancy due to cyanotic cardiac defects are at increased risk for attentional dysfunction in the field of executive control, compared with normal children and with those who have acyanotic heart defects. Besides unfavorable perioperative influences, preoperative hypoxemia is considered responsible for additional damage to the highly oxygen sensitive regions of the prefrontal cortex and striate body assumed to be associated with the executive control network of attention.

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MMW Fortschr Med. 2007 Mar 8;149(10):39-40.
[My child is so restless]
[Article in German]
Schlamp D.
Heckscher-Klinik für Kinder- und Jugendpsychiatrie und Psychotherapie, München. dieter.schlamp@heckscher-klinik.de

Hyperkinetic or attention deficit hyperactivity disorders (ADHD) are characterized by three symptoms: attention deficit, hyperactivity and impulsiveness. For some patients, intensive, continuous counselling or behaviour therapy leads to adequate success. If this is not effective, drug treatment using stimulants such as methylphenidate or the selective norepinephrine reuptake inhibitor atomoxetine is indicated.

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Dis Mon. 2007 Feb;53(2):70-131.
Attention deficit hyperactivity disorder across the lifespan: the child, adolescent, and adult.
Greydanus DE, Pratt HD, Patel DR.
Pediatrics and Human Development, Michigan State University College of Human Medicine, Sindecuse College Health Center, USA.

Management of a child, adolescent, college student, or adult with ADD/ADHD (ADHD) is reviewed with emphasis on pharmacologic approaches in the adult. Psychological treatment includes psychotherapy, cognitive-behavior therapy, support groups, parent training, biofeedback, meditation, and social skills training. Medications are reviewed that research has revealed can improve the core symptomatology of a child or adolescent with ADHD. These medications include stimulants (psychostimulants), antidepressants, alpha-2 agonists, and a norepinephrine reuptake inhibitor. Psychopharmacology approved and/or used in pediatric patients are also used in adults with ADHD, though most are not officially FDA-approved. It is emphasized that ADHD management should include a multi-modal approach, involving appropriate educational interventions, appropriate psychological management of the patient of any age, and judicious use of medications. Such an approach is recommended to benefit those with ADHD achieve their maximum potential across the human life span.

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J Child Adolesc Psychopharmacol. 2007 Feb;17(1):35-49.
Preliminary evidence of beneficial effects of methylphenidate on listening comprehension in children with attention-deficit/hyperactivity disorder.
McInnes A, Bedard AC, Hogg-Johnson S, Tannock R.
Faculty of Education, University of Windsor, Windsor, Ontario, Canada.

OBJECTIVE: The effect of methylphenidate (MPH) on listening comprehension for information passages, and on working memory, was examined in a clinical sample of 16 children with attention-deficit/hyperactivity disorder (ADHD). METHOD: Drug effects on comprehension of spoken language at the levels of single sentences and passages, and on verbal and visual-spatial working memory (WM) skills were assessed over a 4-day placebo-controlled, double-blind, crossover treatment trial of MPH at low, medium, and high doses. Concurrent behavior ratings were also completed. Data were analyzed at both group and individual levels; individual improvements using average change scores were analyzed to explore interrelationships among comprehension, WM, and behavioral responses to MPH. RESULTS: There was a significant effect of drug on comprehension of inferences from challenging listening passages (F = 3.1, p ,0.05), and on visual-spatial working memory performance (F = 3.3, p ,0.05), with significant linear dose-response relationships evident for both domains. Individual improvements in comprehension using averaged placebo-dose change scores were not related to improvements in behavior with MPH, or to improvements in WM in this sample. CONCLUSIONS: Findings provide preliminary evidence that MPH affects higher-level language comprehension skills, which require sustained attention and mental effort. If generalizable to classroom listening skills, these findings have implications for clinicians and teachers involved with children with ADHD.

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J Child Adolesc Psychopharmacol. 2007 Feb;17(1):19-33.
A pilot evaluation of the safety, tolerability, pharmacokinetics, and effectiveness of memantine in pediatric patients with attention-deficit/hyperactivity disorder combined type.
Findling RL, McNamara NK, Stansbrey RJ, Maxhimer R, Periclou A, Mann A, Graham SM.
Department of Psychiatry, Case Western Reserve University and Division of Child & Adolescent Psychiatry, University Hospitals of Cleveland, Cleveland, Ohio 44106-5080, USA. Robert.Findling@uhhs.com

BACKGROUND: Disturbances in N-methyl-D-aspartate (NMDA) receptor activity may play a role in attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: This study is a preliminary evaluation of the safety, pharmacokinetics, and effectiveness of the NMDA receptor antagonist memantine in pediatric ADHD. METHODS: An open-label, dose-finding, 8-week, trial in outpatients 6-12 years old with ADHD combined type. Memantine oral solution (2 mg/mL) was titrated to 10 mg/day (n = 8) or 20 mg/day (n = 8). Safety data and blood samples for pharmacokinetic analyses were collected. The ADHD Rating Scale-IV (ADHD-IV) and Clinical Global Impression of Severity (CGI-S) scale measured the effectiveness of memantine. RESULTS: There were no discontinuations due to adverse events (AEs), serious AEs, deaths, or suicides. Most AEs were mild and occurred during the first week of treatment. The 20 mg/day memantine dose was associated with a higher rate of completion and larger mean improvement on the ADHD-IV and CGI-S than 10 mg/day memantine. Pharmacokinetic analyses suggest response to memantine may be dose-dependent beyond an initial threshold concentration. CONCLUSIONS: This pilot study suggests that a memantine dose of 20 mg/day may be a safe and possibly effective treatment for pediatric ADHD. Further investigations of memantine in ADHD appear to be warranted.

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J Clin Psychiatry. 2007 Feb;68(2):268-77.
Efficacy of a novel biphasic controlled-release methylphenidate formula in adults with attention-deficit/hyperactivity disorder: results of a double-blind, placebo-controlled crossover study.
Jain U, Hechtman L, Weiss M, Ahmed TS, Reiz JL, Donnelly GA, Harsanyi Z, Darke AC.
Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

OBJECTIVE: To evaluate the efficacy and safety of a new biphasic multilayer-release (MLR) methylphenidate formulation in a double-blind, placebo-controlled crossover study of adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: Adults 18 to 60 years of age with a DSM-IV diagnosis of ADHD entered a no-medication baseline week and were then randomly assigned to once-daily MLR methylphenidate or matching placebo. Patients were titrated to optimal effect over 1 to 3 weeks followed by 2 weeks of treatment on a stable dose. The same titration protocol was repeated with the alternate treatment. Clinical Global Impressions scale (CGI) and Conners' Adult ADHD Rating Scales (Self-rated, CAARS-S, and Observer-rated, CAARS-O) were collected at weekly clinic visits. The study was conducted between October 2003 and April 2004. RESULTS: Fifty patients were randomly assigned to treatment, and 39 were analyzed in a per-protocol population (23 men, 16 women; mean age = 37.9 years). CGI-Improvement scores of subjects taking MLR methylphenidate were significantly improved compared with placebo (Global Improvement: 2.6 vs. 3.7; p = .0015). MLR methylphenidate produced improvements over placebo on the ADHD Index T scores of the CAARS-S (12.2 vs. 5.4 [change from baseline score]; p = .0083) and the CAARS-O (10.9 vs. 6.6 [change from baseline score]; p = .1404). The most frequent adverse events for MLR methylphenidate and placebo were headache (26% and 24%, respectively), anorexia (22% and 6%), insomnia (22% and 8%), nervousness (20% and 4%), and nausea (16% and 8%). There were no serious adverse events. CONCLUSIONS: Once-daily MLR methylphenidate produces significant improvements in ADHD symptoms and situational behavior in adult patients with ADHD, with a prolonged duration of effect and minimal side effects, thus having the potential to improve compliance and, therefore, treatment outcomes in routine clinical use.

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J Am Acad Child Adolesc Psychiatry. 2007 Feb;46(2):233-41.
Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia.
Van der Heijden KB, Smits MG, Van Someren EJ, Ridderinkhof KR, Gunning WB.
Epilepsy Center Kempenhaeghe, Heeze, The Netherlands.

OBJECTIVE: To investigate the effect of melatonin treatment on sleep, behavior, cognition, and quality of life in children with attention-deficit/hyperactivity disorder (ADHD) and chronic sleep onset insomnia. METHOD: A total of 105 medication-free children, ages 6 to 12 years, with rigorously diagnosed ADHD and chronic sleep onset insomnia participated in a randomized, double-blind, placebo-controlled trial using 3 or 6 mg melatonin (depending on body weight), or placebo for 4 weeks. Primary outcome parameters were actigraphy-derived sleep onset, total time asleep, and salivary dim light melatonin onset. RESULTS: Sleep onset advanced by 26.9 +/- 47.8 minutes with melatonin and delayed by 10.5 +/- 37.4 minutes with placebo (p < .0001). There was an advance in dim light melatonin onset of 44.4 +/- 67.9 minutes in melatonin and a delay of 12.8 +/- 60.0 minutes in placebo (p < .0001). Total time asleep increased with melatonin (19.8 +/- 61.9 minutes) as compared to placebo (-13.6 +/- 50.6 minutes; p = .01). There was no significant effect on behavior, cognition, and quality of life, and significant adverse events did not occur. CONCLUSION: Melatonin advanced circadian rhythms of sleep-wake and endogenous melatonin and enhanced total time asleep in children with ADHD and chronic sleep onset insomnia; however, no effect was found on problem behavior, cognitive performance, or quality of life.

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J Clin Psychiatry. 2007 Jan;68(1):93-101.
A double-blind, placebo-controlled, crossover study of osmotic release oral system methylphenidate in adults with ADHD with assessment of oppositional and emotional dimensions of the disorder.
Reimherr FW, Williams ED, Strong RE, Mestas R, Soni P, Marchant BK.
Mood Disorders Clinic, Department of Psychiatry, University of Utah Health Sciences Center, Salt Lake City, UT 84132, USA. fred.reimberr@hsc.utah.edu

BACKGROUND: The realization that attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood has led to increased frequency of diagnosis and treatment in adults. Osmotic release oral system (OROS) methylpheni-date is a long-acting stimulant demonstrated to be effective in the treatment of children and adolescents with ADHD. METHOD: Forty-seven adults entered and 41 completed this double-blind, placebo-controlled, crossover trial of OROS methylphenidate. Each double-blind arm lasted 4 weeks; data were collected from August 2004 through December 2005. Subjects met both DSM-IV-TR and Utah Criteria for ADHD in adults. Outcome measures included the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), the adult ADHD-Rating Scale (ADHD-RS), and the Clinical Global Impressions-Improvement scale (CGI-I). At baseline, subjects were categorized as having significant emotional symptoms with the WRAADDS and/or significant oppositional-defiant symptoms using a self-report scale assessing the DSM-IV criteria for oppositional defiant disorder. RESULTS: 17% of the sample (N = 8) had ADHD alone, 38% (N = 18) had ADHD plus significant emotional symptoms, and 40% (N = 19) had ADHD with both significant emotional and oppositional symptoms. At a mean +/- SD dose of 64.0 +/- 23.3 (0.75 mg/kg), OROS methylphenidate proved superior to placebo for all clinical measures: total WRAADDS score decrease of 42% versus 13%, respectively, p < .001 and total ADHD-RS score decrease of 41% versus 14%, respectively, p = .003, plus the subscales addressing inattention, hyperactivity/ impulsivity, and emotional dysregulation. CONCLUSIONS: OROS methylphenidate proved effective in treating adult ADHD. ADHD alone was relatively uncommon. Over 80% of our patients had ADHD with a combination of emotional and/or oppositional symptoms.

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Environ Health Perspect. 2006 Dec;114(12):1904-9.
Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children.
Braun JM, Kahn RS, Froehlich T, Auinger P, Lanphear BP.
College of Nursing, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Free full text at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17185283.

OBJECTIVE: The purpose of this study was to examine the association of exposures to tobacco smoke and environmental lead with attention deficit hyperactivity disorder (ADHD). METHODS: Data were obtained from the National Health and Nutrition Examination Survey 1999-2002. Prenatal and postnatal tobacco exposure was based on parent report; lead exposure was measured using blood lead concentration. ADHD was defined as having current stimulant medication use and parent report of ADHD diagnosed by a doctor or health professional. RESULTS: Of 4,704 children 4-15 years of age, 4.2% were reported to have ADHD and stimulant medication use, equivalent to 1.8 million children in the United States. In multivariable analysis, prenatal tobacco exposure [odds ratio (OR) = 2.5; 95% confidence interval (CI), 1.2-5.2] and higher blood lead concentration (first vs. fifth quintile, OR = 4.1; 95% CI, 1.2-14.0) were significantly associated with ADHD. Postnatal tobacco smoke exposure was not associated with ADHD (OR = 0.6; 95% CI, 0.3-1.3; p = 0.22). If causally linked, these data suggest that prenatal tobacco exposure accounts for 270,000 excess cases of ADHD, and lead exposure accounts for 290,000 excess cases of ADHD in U.S. children. CONCLUSIONS: We conclude that exposure to prenatal tobacco and environmental lead are risk factors for ADHD in U.S. children.

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Curr Med Res Opin. 2006 Dec;22(12):2557-66.
Does OROS-methylphenidate improve core symptoms and deficits in executive function? Results of an open-label trial in adults with attention deficit hyperactivity disorder.
Fallu A, Richard C, Prinzo R, Binder C.
Clinique Woodward, Sherbrooke, Quebec, Canada. cliniquewoodward@videotron.ca

OBJECTIVE: This pilot, uncontrolled, open-label study evaluated the safety/tolerability and potential effectiveness of OROS-methylphenidate (OROS-MPH) in adult attention deficit hyperactivity disorder (ADHD). METHODS: Adults with DSM-IV-defined ADHD were enrolled in this 38-day study. Retrospective childhood diagnosis was made using the Wender Utah Rating Scale. Eligible patients required a baseline Conners Adult ADHD Rating Scale (CAARS) score > or = 24, Clinical Global Impression of Severity (CGI-S) score > or = 4 (at least moderate illness), and Montgomery-Asberg Depression Rating Scale (MADRS) score < or = 16. Safety/tolerability measurements included adverse event reporting, vital signs, electrocardiograms (ECGs), weight, physical examination. Primary effectiveness evaluated changes in CAARS scores. Secondary effectiveness parameters included executive function. RESULTS: Thirty-two patients formed the safety analysis; however, 30 comprised the effectiveness analysis since two patients did not meet diagnostic inclusion criteria. No serious adverse events were reported and there were no early withdrawals due to adverse events. There were no clinically significant changes in endpoint ECGs, physical examination, or blood pressure. Mean pulse rate increased by 5.9 beats/min (p = 0.003) and mean body weight decreased by 2.2 kg at endpoint (p < 0.0001). Total CAARS scores decreased significantly at endpoint as well as the inattention (p < 0.0001) and hyperactivity/impulsivity symptom subscales (p < 0.0001) separately. Statistically significant improvements were observed in executive function and all other secondary measures, including the CAARS self report, CGI-S/CGI-I, Subject Satisfaction with treatment and the Sheehan Disability Scale (SDS). Mean dose of OROS-MPH = 52.3 +/- 14.0 mg. Modal dose = 54 mg. Study limitations include: the lack of placebo control in the study design leading to potential observer bias, the exclusion of adults with unstable psychiatric and other medical conditions which is less reflective of clinical practice, and the short study duration. CONCLUSIONS: This uncontrolled, open-label trial suggests that OROS-MPH is well tolerated, providing core symptom control with the added benefit of improving executive function. However, future larger, randomized, controlled trials are required.

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Neurosci Biobehav Rev. 2006;30(8):1225-45.
Cognitive effects of immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder.
Pietrzak RH, Mollica CM, Maruff P, Snyder PJ.
Department of Psychology, Clinical Division, University of Connecticut, 406 Babbidge Road, Unit 1020, Storrs, CT 06269-1020, USA.

A growing body of literature has examined the cognitive effects of immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). However, a clear understanding of the types and magnitude of such effects are difficult to discern from such a large and varied collection of published reports. This review evaluated a total of 40 relevant placebo-controlled studies published since Rapport and Kelly's [1993. Psychostimulant effects on learning and cognitive function. In: Matson, J.L. (Ed.), Handbook of Hyperactivity in Children. Allyn & Bacon, Boston, pp. 97-136] original review of cognitive effects of methylphenidate in children with ADHD. Of these published studies, 63.5% identified some improvement in cognitive function following methylphenidate treatment. Methylphenidate improved performance on saccadic eye movement, planning/cognitive flexibility, attention/vigilance, and inhibitory control tasks in 83.3%, 71.4%, 70.6%, and 69.7% of studies, respectively. A total 58.3% and 50% of studies that evaluated the effect of methylphenidate on tasks of memory and working memory/divided attention, respectively, noted improvement. Variability of findings across studies may be explained by differential effects of methylphenidate on brain function, intra- and inter-individual variability in medication response, methodological limitations, and problems associated with repeated neuropsychological assessment and metric properties of commonly utilised neuropsychological instruments.

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Expert Opin Pharmacother. 2006 Dec;7(18):2547-57.
Dexmethylphenidate extended-release capsules for the treatment of attention deficit hyperactivity disorder.
Kowalik S, Minami H, Silva R.
New York University School of Medicine, New York, USA.

Dexmethylphenidate is a chirally pure d-isomer of the racemic mixture of methylphenidate. The extended-release form of this compound was developed using proprietary Spheroidal Oral Drug Absorption System technology. The product is approved for the treatment of attention deficit hyperactivity disorder in individuals as young as 6 years old. It represents the first methylphenidate product approved for use in adults. The agent's delivery system is designed to provide an initial release of medication immediately after dosing, with a second release approximately 4 h later. Blood levels first peak at approximately 1.5 h, and the second peak is noted at an average of 6.5 h post-dose. Laboratory classroom studies have demonstrated clinically and statistically meaningful efficacy throughout a 12-h day. Pharmacokinetics, safety and efficacy data are reviewed.

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J Clin Psychopharmacol. 2006 Dec;26(6):648-52.
Quality of life assessment in adult patients with attention-deficit/hyperactivity disorder treated with atomoxetine.
Adler LA, Sutton VK, Moore RJ, Dietrich AP, Reimherr FW, Sangal RB, Saylor KE, Secnik K, Kelsey DK, Allen AJ.
Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA. lenard.adler@med.nyu.edu

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has its onset during childhood and is estimated to affect 3% to 7% of school-aged children. Unfortunately, the disorder frequently persists into adult life. The burden of this disorder is considerable and is often characterized by academic (or occupational) impairment and dysfunction within the family and society. Despite the existence of research demonstrating the effects of ADHD on certain aspects of life, the clinical trials of treatments for this disorder have focused primarily on efficacy and safety. METHODS: Atomoxetine was approved in the United States in November 2002 for the treatment of ADHD in children, adolescents, and adults. The present study uses data from a clinical trial of atomoxetine in adult patients with ADHD that incorporated a measure of health-related quality of life (the Medical Outcomes Study 36-item short-form health survey [SF-36]) as part of the overall assessment of the success of this relatively new treatment. The primary outcome measure for ADHD symptoms was the Conners Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS) ADHD total symptom score. RESULTS: In agreement with previous studies, adult patients with ADHD treated with atomoxetine at typical doses showed significant amelioration of ADHD symptoms, as measured on the CAARS. At baseline, the measures of overall mental health (one aspect of quality of life) of adult patients with ADHD were below the average level, as measured on the SF-36. Treatment with atomoxetine significantly improved the measures of mental health and ameliorated the ADHD symptoms. In addition, the 2 measures were correlated. CONCLUSIONS: These data suggest that pharmacological intervention with atomoxetine not only ameliorates ADHD symptoms in adult patients but also improves their perceived quality of life.

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J Clin Psychiatry. 2006 Oct;67(10):1527-35.
An open trial of light therapy in adult attention-deficit/hyperactivity disorder.
Rybak YE, McNeely HE, Mackenzie BE, Jain UR, Levitan RD.
Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. irybak@uwo.ca

OBJECTIVE: In adults with attention-deficit/ hyperactivity disorder (ADHD), a delayed sleep/ activity rhythm and/or seasonal mood symptoms may contribute significantly to core pathology and disability. This study examined whether a chronobiologically based treatment, i.e., morning bright light therapy (LT), might have utility as an adjunctive treatment for adult ADHD in the fall/ winter period. METHOD: Twenty-nine adults with DSM-IV ADHD were administered a standard 3-week open trial of LT during the fall or winter months. Primary outcome measures included percentage reduction on the Brown Adult ADD Scale and the Conners' Adult ADHD Scale. Secondary measures were decrease in depression scores according to the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorder version; improvements on various neuropsychological tests; and shift toward an earlier circadian preference as measured by the Horne-Ostberg Morningness-Eveningness questionnaire. Regression analyses determined which variables at baseline best predicted improvement on a given outcome measure and which variables changed in parallel with one another. The study was conducted from November 2003 through February 2004. RESULTS: Morning bright light therapy was associated with a significant decrease in both subjective and objective measures of core ADHD pathology, improved mood symptoms, and a significant phase advance in circadian preference. Multiple regression showed that the shift toward an earlier circadian preference with LT was the strongest predictor of improvement on both subjective and objective ADHD measures. Neither baseline global seasonality scores nor baseline depression scores strongly predicted LT effects on most measures of ADHD. CONCLUSION: These findings suggest that during the fall/winter period, LT may be a useful adjunct in many adults with ADHD. Strikingly, the strongest correlate of improvement in core ADHD pathology was a phase advance in circadian preference rather than alleviation of comorbid seasonal affective disorder, suggesting important clinical benefits of LT beyond the treatment of seasonal affective disorder.
  
Previous ADHD Research: 2002-2006   
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