药物假日与注意缺陷/多动障碍(英文)

The concept of ' drug holidays' ( defined as the structured interruption of pharmacological treatment[1] ) in the management of attention deficit hyperactivity disorder ( ADHD) is well established,but poorly researched[1] . The question is whether there is indeed a justifiable basis for the practice. In the opinion piece by Professors Du and Wang[2] ,they argue that on the balance of available evidence it is not justified. Herein lies the issue—the evidence. In reality significant numbers     

Gait in attention deficit hyperactivity disorder

Abstract Background Cognitive function and the loading of attention presumably play an important role in gait as well as in fall risk, but previous work has not demonstrated this in any cause-and-effect way. Objectives To gain insight into the relationship between gait and cognitive function, we sought: (1) To compare the gait rhythmicity (stride time variability) of children with attention deficit hyperactivity disorder (ADHD) to controls, (2) To test the hypothesis that dual tasking leads to increased stride-to-stride variability in ADHD, and (3) To test whether pharmacological treatment that relieves ADHD symptoms reduces stride-to-stride variability. Patients and Methods Gait was quantified in children with ADHD and in age-matched healthy controls under single task and dual task conditions on three occasions: off medications (both groups) and, in the ADHD group, after double blinded, randomized administration of methylphenidate (MPH) or placebo. Results At baseline, children with ADHD tended to walk with increased stride-to-stride variability compared to the controls during the single task condition (p = 0.09). During dual task walking, stride time variability was significantly reduced in the children with ADHD (p < 0.004), but not in the controls. In the children with ADHD, the placebo did not significantly affect stride-to-stride variability or the dual tasking response. In contrast, stride time variability was significantly reduced on MPH (p < 0.001) such that dual tasking no longer affected variability. Conclusions The present findings demonstrate alterations in the gait of children with ADHD, support a cause and effect link between cognitive function and gait, and suggest that enhancement of attention abilities may, in certain populations, improve gait rhythmicity.     

Genes and attention deficit hyperactivity disorder

The initial molecular genetic studies of attention deficit hyperactivity disorder (ADHD) evaluated two candidate genes (DAT and DRD4) suggested by dopamine theories of this common disorder and its treatment with stimulant medication. The initial reports of weak associations with ADHD have been replicated by many (but not all) investigators, as is expected for genes with small effects. This literature is reviewed, along with emerging literature generated by active research groups investigating additional genes that might contribute to the genetic basis of this complex disorder.     

Multicomponent attention deficits in attention deficit hyperactivity disorder

The aim of this study was to examine the specific aspects of attention, such as selective attention, sustained attention, and short-term memory in children with attention deficit hyperactivity disorder, combined subtype (ADHD-C). A total of 40 children with a diagnosis of ADHD from the 4th edition of the Diagnostic and Statistical Manual, aged 6-11 years old were compared with 40 controls matched for age and gender on a battery of tests. Short-term memory span and attention was measured by Visual Aural Digit Span Test-Revised. Stroop test and the Turkish version of Cancellation Test were used to assess selective and sustained attention, respectively. In order to check for factor structure in two groups on the test scores, principal component analysis was conducted for both groups separately. Relative to the comparison children, children with ADHD showed significant deficits on tests that are related to different aspects of attention. The results are consistent with the theories explaining the biological basis of ADHD by scattered attention networks in the brain, which have reciprocal dynamic interactions. Further comparative studies are needed to elucidate whether the cognitive processes that are known to be assessed by these tests are specific to ADHD.     

A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults

OBJECTIVE: Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, there is a paucity of controlled pharmacological trials demonstrating the effectiveness of compounds used in treatment, particularly nonstimulants. The authors report results from a controlled investigation to determine the anti-ADHD efficacy of bupropion in adult patients with DSM-IV ADHD. METHOD: This was a double-blind, placebo-controlled, randomized, parallel, 6-week trial comparing patients receiving sustained-release bupropion (up to 200 mg b.i.d.) (N=21) to patients receiving placebo (N=19). The authors used standardized structured psychiatric instruments for diagnosis of ADHD. To measure improvement, they used separate assessments of ADHD, depression, and anxiety symptoms at baseline and each weekly visit. RESULTS: Of the 40 subjects (55% male) enrolled in the study, 38 completed the study. Bupropion treatment was associated with a significant change in ADHD symptoms at the week-6 endpoint (42% reduction), which exceeded the effects of placebo (24% reduction). In analyses using a cutoff of 30% or better reduction to denote response, 76% of the subjects receiving bupropion improved, compared to 37% of the subjects receiving placebo. Similarly, in analyses using Clinical Global Impression scale scores, 52% of the subjects receiving bupropion reported being "much improved" to "very improved," compared to 11% of the subjects receiving placebo. CONCLUSIONS: These results indicate a clinically and statistically significant effect of bupropion in improving ADHD in adults. The results suggest a therapeutic role for bupropion in the armamentarium of agents for ADHD in adults, while further validating the continuity of pharmacological responsivity of ADHD across the lifespan.     

Neurobiology of attention deficit hyperactivity disorder

This article addresses the current understanding of the neurobiological bases of attention deficit hyperactivity disorder (ADHD), focusing on empiric research findings that connect genetic and environmental factors to structural and functional brain abnormalities, ultimately leading to a set of age-dependent behavioral manifestations. Section one presents evidence for genetic risk factors for ADHD and discusses the role of potential environmental factors in the etiology of the disorder. Section two focuses on brain imaging studies and how they have helped generate different hypotheses regarding the pathophysiology of ADHD. Finally, the article addresses the longitudinal course of symptoms in ADHD from infancy to adulthood in an attempt to place biological findings for this complex brain disorder in the context of maturation and development.     

Genetics of attention deficit hyperactivity disorder

Results of behavioral genetic and molecular genetic studies have converged to suggest that both genetic and nongenetic factors contribute to the development of attention deficit hyperactivity disorder (ADHD). Family, twin, and adoption studies provide compelling evidence that genes play a strong role in mediating susceptibility to ADHD. In contrast to a handful of genome-wide scans conducted thus far, many candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder. Yet, even these associations are small and consistent with the idea that the genetic vulnerability to ADHD is mediated by many genes of small effects. These small effects emphasize the need for future candidate gene studies to implement strategies that will provide enough statistical power to detect such small effects.     

Atypical outcome in attention deficit hyperactivity disorder

This report describes the course of psychiatric illness in two boys. Both presented with attention deficit hyperactivity disorder (ADHD) in midchildhood; after puberty, one boy developed a schizophrenic illness while the other boy developed a major affective illness. Although the major ADHD outcome studies have found no link between the childhood occurrence of ADHD and psychosis in adulthood, occasionally such a link may exist. The theoretical and practical implications of this finding are discussed. It should be noted, however, that such outcome is highly atypical and very rare.     

Psychosocial interventions in attention deficit hyperactivity disorder

This brief overview of psychosocial treatment approaches to attention deficit hyperactivity disorder (ADHD) concentrates on the two that receive the greatest research support, parent training in child behavior management and teacher training in classroom management. Cognitive-behavioral training of children who have ADHD has little evidence of efficacy and group social skills training has mixed or limited evidence of effectiveness. Research should focus on more theoretically driven psychosocial treatment approaches, on potential side effects or adverse events associated with this form of intervention, and on the complex pathways that affect impairment in major life activities that could guide subsequent treatment design for such impairments.     

Raising attention to attention deficit hyperactivity disorder in schizophrenia

Schizophrenia and attention deficit hyperactivity disorder (ADHD) are two psychiatric disorders with a negative impact on quality of life of individuals affected. Although they are classified into distinct disorders categories, attentional dysfunction is considered as a core feature in both conditions, either at the clinical then pathophysiological level. Beyond the obvious clinical overlap between these disorders, the Research Domain Criteria approach might offer an interesting perspective for disentangling common circuits underpinning both disorders. Hence, we review evidences regarding the overlap between schizophrenia and ADHD, at the clinical level, and at the level of underlying brain mechanisms. The evidence regarding the influence of environmental risk factors in the emergence of both disorders, and their developmental trajectories is also reviewed. Among these, we will try to elucidate the complex relationship between stimulants use and psychotic symptoms, discussing the potential role of ADHD medication in inducing psychosis or in exacerbating it. We aim that, taken together, these findings may promote further investigation with important implications both for clinicians and research. In fact, considering the amounting evidence on the overlap between schizophrenia and ADHD, the delineation of their boundaries might help in the decision for diagnosis and treatment. Moreover, it may help to promote interventions focused on the prevention of both schizophrenia and ADHD, by the reduction of recognized environmental risk factors.     

Dexmethylphenidate extended-release capsules for attention deficit hyperactivity disorder

Medications for attention deficit hyperactivity disorder (ADHD) currently represent the ninth largest segment of the CNS market by sales, with 2.4 billion USD spent annually on this condition and 40% annual growth. Stimulant medications remain the most effective ADHD therapies and provide robust improvement in ADHD symptoms in both youth and adults. Current prescribing practices favor extended release preparations due to increased convenience, compliance and tolerability with once-daily dosing. Dexmethylphenidate extended release is a long-acting preparation of the ADHD medication Focalin (dexmethylphenidate immediate release) and was approved for marketing by the US Food and Drug administration in June 2005. Dexmethylphenidate consists of the single dextro-isomer form of d,l-methylphenidate commonly marketed as Ritalin. Dexmethylphenidate extended release utilizes spheroidal oral drug absorption system technology to achieve a 50% immediate medication delivery and 50% delayed release of dexmethylphenidate approximately 4 h after ingestion. Placebo-controlled, clinical trials in children and adults with ADHD have demonstrated efficacy for behavioral and academic ratings, with an analog classroom study showing medication effects up to 12 h after dosing. Dexmethylphenidate extended release was generally well tolerated with a side-effect profile similar to other stimulants. The most common reported side effects include diminished appetite and insomnia. Given its duration of effect, favorable tolerability and flexibility in dosing, dexmethylphenidate extended release is likely to gain considerable use as an ADHD treatment.     

An open-label trial of tomoxetine in pediatric attention deficit hyperactivity disorder.

OBJECTIVE: To collect pilot data assessing the safety, tolerability, and efficacy of tomoxetine, a nonstimulant norepinephrine enhancer, in pediatric attention deficit hyperactivity disorder (ADHD). METHODS: An open-label trial of tomoxetine in pediatric ADHD was conducted as part of a multisite clinical trial. Following a baseline assessment, an ascending dose titration was completed during 10 weekly visits. RESULTS: Ten subjects were enrolled at baseline, with eight completing the study. Seven of the eight remaining subjects met efficacy criteria. Significant decreases in symptom severity ratings by parents and study investigators were found. The medication was well tolerated, with transient appetite suppression the most frequently reported side effect. However, subjects' weights remained stable across study visits. DISCUSSION: These preliminary findings suggest that tomoxetine may hold promise as a treatment for pediatric ADHD.     

Atomoxetine for attention deficit hyperactivity disorder in mental retardation

The study objective was to assess the efficacy and tolerability of atomoxetine in the treatment of attention deficit hyperactivity disorder symptoms in patients with mental retardation. In a 16-week, open-label, prospective study, 48 children with mental retardation and attention deficit hyperactivity disorder were recruited; the patients received atomoxetine, with a single final dose of 1.2 mg/kg per day reached at 3 weeks. The measure of efficacy was scores on Clinical Global Impression Severity scale (CGI-S), Conners, and Attention Deficit Hyperactivity Disorder Rating Scale ADHDRS-IV. A statistically significant difference was documented between the mean CGI-S scores before and after treatment: baseline CGI-S = 5.31 (S.D. = 0.85); post-treatment CGI-S = 4.13 (S.D. = 0.97), with a difference of 1.18 points (S.D. = 0.84) and a 95% confidence interval for the difference of 0.92-1.43 (P < 0.001). A statistically significant reduction (P < 0.01) was observed with respect to all the variables of the ADHDRS-IV and Conners scales. Slightly less than one third of the patients (31%) presented adverse events, the majority of which were mild, with irritability being the most frequent event. Atomoxetine appears to be to useful in improving attention deficit hyperactivity disorder symptoms in mentally retarded patients. Larger, randomized, controlled, double-blind studies are required to confirm the efficacy observed in this first study.     

Frontiers between attention deficit hyperactivity disorder and bipolar disorder

The co-occurrence of attention deficit hyperactivity disorder (ADHD) and bipolar disorder has received much recent attention in the literature. The authors review the literature examining associations between ADHD and bipolar disorder in children, and data concerning severe irritability in youth with ADHD. This article focuses on (1) population-based studies examining ADHD and bipolar disorder or ADHD and co-occurring irritability, (2) the co-occurrence and prospective relationships of ADHD and bipolar disorder in clinical samples, (3) phenomenology and assessment of bipolar disorder and ADHD, (4) treatment of comorbid ADHD and bipolar disorder, (5) family and genetic studies of ADHD and bipolar disorder, and (6) pathophysiologic comparisons between children with ADHD and irritability and bipolar disorder. We draw on the research to make clinical recommendations and highlight important directions for future research.     

Response to methylphenidate in children with attention deficit hyperactivity disorder and manic symptoms in the multimodal treatment study of children with attention deficit hyperactivity disorder titration trial

OBJECTIVE: Recent reports raise concern that children with attention deficit hyperactivity disorder (ADHD) and some manic symptoms may worsen with stimulant treatment. This study examines the response to methylphenidate in such children. METHODS: Data from children participating in the 1-month methylphenidate titration trial of the Multimodal Treatment Study of Children with ADHD were reanalyzed by dividing the sample into children with and without some manic symptoms. Two "mania proxies" were constructed using items from the Diagnostic Interview Schedule for Children (DISC) or the Child Behavior Checklist (CBCL). Treatment response and side effects are compared between participants with and without proxies. RESULTS: Thirty-two (11%) and 29 (10%) participants fulfilled criteria for the CBCL mania proxy and DISC mania proxy, respectively. Presence or absence of either proxy did not predict a greater or lesser response or side effects. CONCLUSION: Findings suggest that children with ADHD and manic symptoms respond robustly to methylphenidate during the first month of treatment and that these children are not more likely to have an adverse response to methylphenidate. Further research is needed to explore how such children will respond during long-term treatment. Clinicians should not a priori avoid stimulants in children with ADHD and some manic symptoms.     

Genetic influences on attention deficit hyperactivity disorder

In this article we review behavioral and molecular genetics studies of attention deficit hyperactivity disorder (ADHD). Family, twin, and adoption studies, along with segregation analyses and molecular genetic studies, all support the hypothesis that both genetic and environmental factors contribute to the etiology of ADHD. Despite this strong evidence for the familial transmission of ADHD, the mode of transmission requires further clarification. In addition, because ADHD appears to be genetically heterogeneous, more work is needed to delineate genetically homogeneous subtypes and describe the range of expression of their underlying genotypes.