Reducing Attention-deficit/hyperactivity Disorder Symptoms Research Articles

An Intervention to Promote Sleep and Reduce ADHD Symptoms

ObjectiveTo determine the effect of a sleep hygiene education module and prescriptive sleep routine for children ages 5 through 11 years with attention deficit hyperactivity disorder (ADHD). MethodsThe 20-week pilot project used a pre–/posttest design to assess sleep and ADHD symptoms. The Child Sleep Habits Questionnaire (CHSQ) and Vanderbilt Assessment Scale–Parent Form survey were provided to assess sleep and ADHD behaviors of participants at baseline and 6 weeks after implementation of the sleep hygiene routine. Fifty-three children participated in the project. Of these, 23 scored 42 or greater on the CHSQ, indicating a sleep disorder, and received the intervention. ResultsThe CHSQ and Vanderbilt scores indicated a significant improvement in sleep quality and reduction in ADHD symptoms after implementation of the sleep hygiene routine (CHSQ: p < .001, d = .928; Vanderbilt Questions 1–9: p < .001, d = .473; Vanderbilt Questions 10–18: p = .004; d = .329). ConclusionA provider-instructed sleep hygiene routine in children with ADHD improves sleep quality and reduces ADHD symptoms.

Randomized, 6-Week, Placebo-Controlled Study of Treatment for Adult Attention-Deficit/Hyperactivity Disorder: Individualized Dosing of Osmotic-Release Oral System (OROS) Methylphenidate With a Goal of Symptom Remission.

To evaluate the efficacy and safety of individualized dosing within the approved dose range for osmotic-release oral system (OROS) methylphenidate hydrochloride in adults with attention-deficit/hyperactivity disorder (ADHD). A double-blind, 6-week trial was conducted between July 2009 and February 2010 at 35 US sites. Adults with ADHD (DSM-IV diagnostic criteria) and a screening ADHD Investigator Symptom Rating Scale (AISRS) score > 24 were randomly assigned to OROS methylphenidate 18 mg or matching placebo. Treatment dose could be increased at 18 mg increments, up to 72 mg/d, until an optimal dose was achieved. AISRS score changes from baseline to end point (primary outcome) were analyzed using analysis of covariance. At baseline, the intent-to-treat population of 169 OROS methylphenidate and 172 placebo subjects (mean age = 35.8 years) had mean (standard deviation [SD]) AISRS scores of 37.8 (6.94) and 37.0 (7.51), respectively. OROS methylphenidate-treated subjects exhibited a significantly greater mean (SD) AISRS score improvement than placebo subjects (-17.1 [12.44] vs -11.7 [13.30]; P < .001). In general, OROS methylphenidate-treated subjects experienced greater improvements than placebo subjects in secondary measures of symptom frequency, cognitive function, work productivity, and quality-of-life. Little effect of OROS methylphenidate was observed in exploratory sleep assessments. The adverse event pattern was similar to previous reports of stimulants in adults with ADHD. OROS methylphenidate treatment with individualized doses titrated to achieve symptom remission demonstrated greater ADHD symptom reduction than placebo treatment. These data support the overall efficacy of OROS methylphenidate treatment in the management of adults with ADHD and provide new possibilities for additional intervention. ClinicalTrials.gov identifier: NCT00937040.

Impact of a Web-Portal Intervention on Community ADHD Care and Outcomes.

The quality of care for children with attention-deficit/hyperactivity disorder (ADHD) delivered in community-based pediatric settings is often poor. Interventions have been developed to improve community-based ADHD care but have not demonstrated that better care results in improved patient outcomes. The objective of this study was to determine whether an ADHD quality improvement (QI) intervention for community-based pediatric practices improves patient outcomes. A cluster randomized controlled trial was conducted in which 50 community-based pediatric primary care practices (213 providers) were randomized either to receive a technology-assisted QI intervention or to a control condition. The intervention consisted of 4 training sessions, office flow modification, guided QI, and an ADHD Internet portal to assist with treatment monitoring. ADHD treatment processes and parent- and teacher-rated ADHD symptoms over the first year of treatment were collected for 577 patients. Intent-to-treat analyses examining outcomes of all children assessed for ADHD were not significant (b = -1.97, P = .08). However, among the 373 children prescribed ADHD medication, there was a significant intervention effect (b = -2.42, P = .04) indicating greater reductions in parent ratings of ADHD symptoms after treatment among patients treated by intervention physicians compared with patients treated at control practices. There were no group differences on teacher ratings of ADHD symptoms. ADHD treatment care around medication was significantly better at intervention practices compared with control practices. A technology-assisted QI intervention improved some ADHD care quality and resulted in additional reductions in parent-rated ADHD symptoms among patients prescribed ADHD medications.

Critical appraisal of omega-3 fatty acids in attention-deficit/hyperactivity disorder treatment.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. The classical treatment of ADHD where stimulant medication is used has revealed severe side effects and intolerance. Consequently, the demand to search for alternative treatment has increased rapidly. When comparing levels of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in ADHD patients with those in age-matching controls, lower levels are found in ADHD patients’ blood. ω-3 PUFAs are essential nutrients and necessary for a proper brain function and development. Additionally, there are strong indications that ω-3 PUFA supplements could have beneficial effects on ADHD. However, the results of ω-3 PUFA supplementation studies show a high variability. Therefore, we reviewed recent studies published between 2000 and 2015 to identify effective treatment combinations, the quality of design, and safety and tolerability of ω-3-containing food supplements. We searched the databases MEDLINE, PubMed, and Web of Science with keywords such as “ADHD” and “ω-3/6 PUFA” and identified 25 studies that met the inclusion and exclusion criteria. The results of these ω-3 PUFA studies are contradictory but, overall, show evidence for a successful treatment of ADHD symptoms. Tolerability of the given supplements was high, and only mild side effects were reported. In conclusion, there is evidence that a ω-3 PUFA treatment has a positive effect on ADHD. It should be added that treatment could be more effective in patients with mild forms of ADHD. Moreover, the dosage of stimulant medication could be reduced when used in combination with ω-3 PUFA supplements. Further studies are necessary to investigate underlying mechanisms that can lead to a reduction of ADHD symptoms due to ω-3 PUFA treatments and also to determine the optimal concentrations of ω-3 PUFAs, whether used as single treatment or in combination with other medication.

Mindfulness-Based Cognitive Therapy and the Adult ADHD Brain: A Neuropsychotherapeutic Perspective.

Attention-deficit/hyperactivity disorder (ADHD) is a recognized serious mental disorder that often persists into adulthood. The symptoms and impairments associated with ADHD often cause significant mental suffering in affected individuals. ADHD has been associated with abnormal neuronal activity in various neuronal circuits, such as the dorsofrontostriatal, orbitofrontostriatal, and frontocerebellar circuits. Psychopharmacological treatment with methylphenidate hydrochloride is recommended as the first-line treatment for ADHD. It is assumed that medication ameliorates ADHD symptoms by improving the functioning of the brain areas affected in the condition. However, side effects, contraindications, or non-response can limit the effectiveness of a psychopharmacological treatment for ADHD. It is therefore necessary to develop non-pharmacological interventions that target neuronal mechanisms associated with the condition in the same way as pharmacological treatment. We think that mindfulness meditation employed as a neuropsychotherapeutic intervention could help patients with ADHD to regulate impaired brain functioning and thereby reduce ADHD symptoms. In this paper, we highlight the mechanisms of such mindfulness meditation, and thus provide a rationale for further research and treatment development from a neuropsychotherapeutic perspective. We conclude that mindfulness meditation employed as a neuropsychotherapeutic intervention in therapy is a promising treatment approach in ADHD.

Effects of Narrative Therapy and Computer-Assisted Cognitive Rehabilitation on the Reduction of ADHD Symptoms in Children

BACKGROUND AND OBJECTIVE: Attention deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral condition in children, which adversely affects the psychological function of children in educational, social, and emotional areas. Use of non-pharmacological treatment methods, such as narrative therapy and computerassisted cognitive rehabilitation, is necessary for ADHD patients due to lack of side effects and concerns regarding medication therapy. This study aimed to evaluate the effects of narrative therapy and computer-assisted cognitive rehabilitation on the symptoms of ADHD in children. METHODS: This quasi-experimental study was conducted in Sari, Iran during June-February 2015 using the pretestposttest approach with a control group. In total, 30 children aged 7-12 years diagnosed with ADHD were selected and divided into three groups. Children of the first group received eight sessions of narrative therapy, while the second group received 10 sessions of computer-assisted cognitive rehabilitation, and the third group received no training. Data were collected using the Raven’s colored matrices, Conners' Parent Rating Scale (CPRS-48), and CogniPlus software. FINDINGS: Mean post-test scores of ADHD symptoms were 20.1±5.21 and 20±3.55 in the narrative therapy and computer-assisted cognitive rehabilitation groups, respectively; however, no significant difference was observed between the groups in this regard. Moreover, these scores were 37.4±9.84 and 38.95±9.06 in the control group, which showed a significant difference compared to the experimental groups (p<0.05). CONCLUSION: According to the results of this study, narrative therapy and computer-assisted cognitive rehabilitation could remarkably reduce ADHD symptoms in children.

Relationships Between Functional Outcomes and Symptomatic Improvement in Atomoxetine-Treated Adult Patients with Attention-Deficit/Hyperactivity Disorder: Post Hoc Analysis of an Integrated Database.

Atomoxetine treatment is associated with improvements in functional outcomes in patients with attention-deficit/hyperactivity disorder (ADHD), although relationships between improvements in these outcomes and reductions in ADHD symptoms have not been comprehensively investigated in adults. The aim of this study was to assess relationships between functional outcomes and ADHD symptoms (primary objective), and to assess time courses of changes in functional outcomes from baseline to weeks 10 and 24 (secondary objective). We analyzed data pooled from seven Eli Lilly-sponsored placebo-controlled trials of atomoxetine in adults with ADHD that had Conners' Adult ADHD Rating Scales-Investigator Rated: Screening Version (CAARS-Inv:SV) total scores and functional outcome data at baseline and at week 10. Two trials also had these data at week 24. Patients were included in these pooled analyses if they had a CAARS-Inv:SV total score at baseline and at one or more post-baseline visits at weeks 10 or 24, or had post-baseline scores that would allow missing scores at weeks 10 or 24 to be imputed. To address the primary objective, changes in functional outcomes during treatment with atomoxetine versus placebo were assessed using last observation carried forward (LOCF) analysis of covariance (ANCOVA) and mixed-effects model repeated measures (MMRM) analysis, and correlations between score changes in CAARS-Inv:SV total and functional outcomes were assessed using Spearman's rank correlation coefficient (r) at weeks 10 and 24. The secondary objective was addressed using MMRM. At baseline, patients generally had moderately severe or worse ADHD symptoms (based on CAARS-Inv:SV total scores) and impaired functional outcomes (based on Adult ADHD Quality-of-Life [AAQoL], Behavior Rating Inventory of Executive Function-Adult Version [BRIEF-A], Sheehan Disability Scale [SDS], and 36-item Short-Form Health Survey [SF-36] scores). These baseline characteristics were comparable in the atomoxetine and placebo groups. For atomoxetine versus placebo, statistically significant improvements were detected in AAQoL total and subscores at weeks 10 and 24, and in BRIEF-A Self-Report scores at week 10, but not in BRIEF-A Informant Report or SDS scores at week 10 (no BRIEF-A or SDS data were available at week 24), and not in SF-36 at weeks 10 or 24. All functional improvements were gradual. During treatment with atomoxetine, there were moderate correlations between reductions in CAARS-Inv:SV total scores and increases in AAQoL total and subscores at weeks 10 and 24 (r range -0.58 to -0.39; n=394-545), and also with reductions in BRIEF-A Self-Report at week 10 (r=0.49; n=256). With placebo, moderate correlations were also found between reductions in CAARS-Inv:SV total scores and increases in AAQoL total and subscores at weeks 10 and 24 (r range -0.56 to -0.28; n=321-542), and with reductions in BRIEF-A Self-Report at week 10 (r=0.49; n=271). However, correlations between changes in CAARS-Inv:SV and BRIEF-A Informant at week 10 were low for atomoxetine-treated patients (r=0.25; n=65), moderate with placebo (r=0.42; n=72), and there were low/no correlations between changes in CAARS-Inv:SV and functional outcome rating scales that are not specific to ADHD; that is, for atomoxetine-treated patients, SDS total r=0.19 (n=32 at week 10) and SF-36 r range -0.20 to -0.01 (n=51 at week 10, n=183 at week 24). Atomoxetine-treated adult patients experienced improvements in functional outcomes (AAQoL and BRIEF-A Self-Report) that correlated with reductions in ADHD symptoms. Although atomoxetine improved both the ADHD symptoms and functional outcomes, the correlation between symptoms and functional outcomes was low to moderate, suggesting that they measure overlapping but different aspects of the disorder. Hence, clinicians should assess not just ADHD symptoms, but also the functional impairments.

Lisdexamfetamine: A Review in ADHD in Adults.

Lisdexamfetamine dimesylate (lisdexamfetamine) is a long-acting amfetamine prodrug with a convenient once-daily oral regimen that offers the potential for improved adherence and reduced abuse compared with short-acting preparations of amfetamines. Lisdexamfetamine (as Elvanse Adult(®); Tyvense Adult™) has been approved for use in adults with attention-deficit hyperactivity disorder (ADHD) under the EU decentralization procedure, with the first approvals in the UK, Sweden and Denmark. This approval reflects the results of three short-term trials in adults with ADHD in which fixed- or flexible-dose lisdexamfetamine produced significantly greater improvements than placebo in ADHD symptoms, overall functioning, executive functioning (including in patients with significant pre-existing impairment) and quality of life. Of note, a post hoc analysis of one of these studies suggested that the response to lisdexamfetamine was generally similar in treatment-naïve patients and those who had already received-and not responded satisfactorily to-previous ADHD therapies, including methylphenidate (MPH). Two further studies demonstrated the longer-term effectiveness of flexible-dose lisdexamfetamine in reducing ADHD symptoms, albeit maintenance of efficacy required ongoing treatment with the drug. Lisdexamfetamine was generally well tolerated in clinical trials, with an adverse event profile typical of that reported for other long-acting stimulants. Head-to-head comparisons with other long-acting agents, notably MPH and atomoxetine, are lacking. Nonetheless, on the basis of the available data, lisdexamfetamine provides a useful alternative option for the treatment of adults with ADHD, including those who have not responded adequately to previous ADHD therapies, including MPH.

Neural Correlates of Symptom Improvement Following Stimulant Treatment in Adults with Attention-Deficit/Hyperactivity Disorder.

The purposes of this study were to examine the impact of 3 weeks of amphetamine administration on intrinsic connectome-wide connectivity patterns in adults with attention-deficit/hyperactivity disorder (ADHD) and explore the association between stimulant-induced symptom improvement and functional connectivity alteration. Participants included 19 adults (age 20-55 years) diagnosed with ADHD using the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria per the Adult Clinician Diagnostic Scale taking part in amphetamine trials. For each patient, two 6-minute resting-state functional magnetic resonance imaging (R-fMRI) scans were acquired at baseline and after treatment. A fully data-driven multivariate analytic approach (i.e., multivariate distance matrix regression [MDMR]) was applied to R-fMRI data to characterize the distributed pharmacological effects in the entire functional connectome. Clinical efficacy was assessed using ADHD rating scale with adult prompts and the Adult Self-Report Scale v1.1 Symptom Checklist. We linked stimulant-induced functional connectivity changes to symptom amelioration using Spearman's correlation. Three weeks of administration of a stimulant significantly reduced ADHD symptoms. MDMR-based analyses on R-fMRI data highlighted the left dorsolateral prefrontal cortex (DLPFC, a key cognitive control region) and the medial prefrontal cortex (MPFC, the anterior core of default network) whose distributed patterns of functional connectivity across the entire brain were altered by psychostimulants. Follow-up intrinsic functional connectivity revealed that stimulants specifically decreased the positive functional connectivity between DLPFC-insula, DLPFC-anterior cingulate cortex, and MPFC-insula. Importantly, these functional connectivity changes are associated with symptom improvement. These results suggested that ADHD is associated with increased functional integration or decreased functional segregation between core regions of cognitive control, default, and salience networks. The apparent normalization of intrinsic functional interaction in these circuits (i.e., increased functional segregation) may underlie the clinical benefits produced by 3 weeks of amphetamine treatment.

Mediation and Moderation of Outcome in a Training Intervention for Adolescents With Attention-Deficit/Hyperactivity Disorder

Objective: A training intervention that aims to improve the problem-solving and organization skills of adolescents with attention-deficit/hyperactivity disorder (ADHD) has been investigated. Aim of this study was to examine the mechanisms of change that occurred during the intervention in an empirical trial. Method: Forty-nine adolescents with ADHD aged 12–17 years took part in the intervention. The primary outcome of the intervention was the reduction of ADHD symptoms. To understand how the intervention facilitated the improvement of the outcome, we conducted mediation and moderation analyses. As potential mediators, improvement in academic enablers and meta- and neurocognitive functioning were investigated. Age, gender, and medication status were analyzed as potential moderators of the outcome. Results: An improvement in academic enablers partially mediated symptom reductions. There were no effects of moderation. Conclusions: Enhancing academic skills can reduce ADHD symptom severity. The training intervention examined in this study is a promising treatment for adolescents with ADHD.

A randomized controlled clinical trial of real-time functional magnetic resonance imaging neurofeedback for adolescents with attention deficit hyperactivity disorder (ADHD)

A randomized controlled clinical trial of real-time functional magnetic resonance imaging neurofeedback for adolescents with attention deficit hyperactivity disorder (ADHD)

Clinically Significant Symptom Reduction in Children with Attention-Deficit/Hyperactivity Disorder Treated with Micronutrients: An Open-Label Reversal Design Study.

The purpose of this study was to investigate the clinical effect and safety of a broad spectrum, 36 ingredient micronutrient (vitamins and minerals) in treating children with attention-deficit/hyperactivity disorder (ADHD). This open-label, on-off-on-off (reversal design) study followed 14 participants (8-12 years of age) with ADHD, diagnosed using standardized instruments, for 6 months with no dropouts. Following baseline assessment, including hematology and biochemistry screening, participants began an 8 week treatment phase with micronutrients titrated up to maximum dose (15 capsules/day). Treatment was withdrawn for 4 weeks, reinstated for a further 8 weeks, and then withdrawn for 4 weeks. Primary outcomes included the Conners' Parent Rating Scale, the Clinical Global Impressions Scale (CGI), and the Strengths and Difficulties Questionnaire - Parent version (SDQ). Secondary outcomes were mood and global functioning. Modified Brinley plots revealed a reduction in ADHD symptoms, improved mood, and improved overall functioning during intervention phases, and deterioration in ADHD symptoms, mood, and overall functioning during the withdrawal phases. Reliable change analyses, Cohen's d and percent superiority effect sizes, 95% confidence intervals and t tests confirmed clinically and statistically significant change between the intervention and withdrawal phases, with large effect sizes observed pre- to post-exposure of micronutrients (d = 1.2-2.2) on ADHD symptoms during intervention phases. Seventy-one percent of participants showed at least a 30% decrease in ADHD symptoms by the end of the second treatment phase, and 79% were identified as "much improved" or "very much improved" at the end of the second phase (5 months) based on the clinician-rated CGI when considering functioning generally. The SDQ showed that these benefits occurred across other areas of functioning including emotional symptoms, conduct problems, and prosocial behaviours. The children's self-reports confirmed the improvements. Excellent adherence to treatment occurred throughout, side effects were mild and transitory, and no safety issues were identified through blood analyses. This study demonstrates the clinical benefit, feasibility, and safety of broad-spectrum micronutrients in the treatment of childhood ADHD. Replications utilizing double-blind placebo-controlled studies are warranted. Trial is registered with the Australia and New Zealand Clinical Trial Registry: ACTRN12612000645853.

Pharmacokinetics and Exposure-Response Relationships of Dasotraline in the Treatment of Attention-Deficit/Hyperactivity Disorder in Adults.

Background and ObjectivesDasotraline is a novel inhibitor of dopamine and norepinephrine reuptake currently being investigated in clinical studies for the treatment of attention-deficit/hyperactivity disorder (ADHD). Uniquely, relative to current ADHD medications, dasotraline has a slow absorption and long elimination half-life. Here we relate the pharmacokinetics and pharmacodynamics of dasotraline to reduction in ADHD symptoms based on simulated clinical trial outcomes.MethodsDasotraline pharmacokinetics were analyzed by population pharmacokinetic methodologies using data collected from 395 subjects after single or multiple oral dose administrations ranging from 0.2 to 36 mg (three phase I studies and one phase II ADHD study). Population pharmacokinetic and pharmacodynamic models related individual dasotraline exposures to norepinephrine metabolite 3,4-dihydroxyphenylglycol (DHPG) concentrations, ADHD symptoms, and study discontinuation (probability of dropout).ResultsDasotraline pharmacokinetics were described by a one-compartment model with dual (linear plus nonlinear) elimination. In an ADHD population treated with dasotraline 4 or 8 mg/day, dasotraline was characterized by a mean apparent half-life of 47 h and plasma concentrations reached steady-state by 10 days of dosing. A population pharmacokinetic and pharmacodynamic model of DHPG indicated clinically significant norepinephrine transporter inhibition was achieved as a function of time-matched dasotraline concentrations. Dasotraline exposure reduced ADHD symptoms in a sigmoid Emax time-course model. Clinical trial simulations described the effects of dose, duration, and sample size on clinical outcomes.ConclusionThese results related dasotraline pharmacokinetics to pharmacological activity in ADHD, and support the novel concept that maintaining constant, steady-state dopamine and norepinephrine reuptake inhibition throughout a 24-h dosing interval is a novel pharmacological approach to the management of ADHD symptoms.Clinicaltrials.gov identifier: NCT01692782.Electronic supplementary materialThe online version of this article (doi:10.1007/s40261-015-0358-7) contains supplementary material, which is available to authorized users.

Does Guanfacine Extended Release Impact Functional Impairment in Children with Attention-Deficit/Hyperactivity Disorder? Results from a Randomized Controlled Trial.

BackgroundIn clinical trials of medications to treat attention-deficit/hyperactivity disorder (ADHD) in children, effects on functional impairment have been less well-studied than changes in ADHD symptoms.ObjectiveData regarding functional impairment were analyzed from a multicenter, double-blind, placebo-controlled study of guanfacine extended release (GXR) in children with ADHD, using the Weiss Functional Impairment Rating Scale–Parent Report (WFIRS-P). The correspondence of changes in WFIRS-P scores with symptomatic and global response to GXR treatment was also examined, with treatment response defined by scores on both the ADHD Rating Scale IV (ADHD-RS-IV) and the Clinical Global Impressions–Improvement Scale (CGI-I).MethodsIn this 8-week, double-blind, placebo-controlled, dose optimization study at 47 sites across the USA and Canada, children aged 6–12 years with a diagnosis of ADHD [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria, and an ADHD-RS-IV score ≥28 and CGI–Severity of Illness Scale score ≥4 at baseline], were randomized 1:1:1 into three groups: GXR am [GXR (1–4 mg/day) in the morning, placebo in the evening], GXR pm [placebo in the morning, GXR (1–4 mg/day) in the evening], or twice-daily placebo. Parents rated their children on the WFIRS-P at screening, baseline, the end of dose optimization, and at the final on-treatment assessment.ResultsThe efficacy population was composed of 333 subjects (GXR am: n = 107; GXR pm: n = 114; placebo: n = 112). At the final on-treatment assessment, there were significant improvements from baseline in the placebo-adjusted difference in least-squares (LS) mean (95 % confidence interval) WFIRS-P Total scores for both GXR treatment groups combined [GXR all-active: −0.16 (−0.25, −0.07), effect size (ES) = 0.448, P <0.001] and separately [GXR am: −0.15 (−0.26, −0.05), ES = 0.417, P = 0.004; GXR pm: −0.18 (−0.28, −0.07), ES = 0.478, P = 0.001]. Significant improvements in WFIRS-P domain scores for Family, Learning and School (including Academic Performance and Behavior in School), Social, and Risky Behavior were found for both GXR cohorts compared with placebo. However, the Life Skills and Self-Concept domain scores of the WFIRS-P did not improve with GXR treatment. Post hoc stratification by responder status revealed that significant (P <0.001) improvements in WFIRS-P Total and all domain scores were associated with symptomatic treatment response in the GXR all-active group.ConclusionsGXR treatment in children with ADHD was associated with reductions in WFIRS-P functional impairment scores compared with placebo, regardless of time of GXR administration. Changes in WFIRS-P scores were congruent with clinical response, as determined by both ADHD symptom reduction and CGI-I scores.ClinicalTrials.gov identifierNCT00997984.

Efficacy, safety and variability in pharmacotherapy for adults with attention deficit hyperactivity disorder: a meta-analysis and meta-regression in over 9000 patients.

The factors underlying the variability in the results of randomized, placebo-controlled clinical trials (RPCCT) assessing pharmacological interventions for adults with attention deficit hyperactivity disorder (ADHD) are not fully understood. A systematic review and meta-analysis of RPCCT comparing pharmacological treatment and placebo in adults with ADHD was carried out. The study outcomes were all-cause treatment discontinuation, efficacy on ADHD symptoms, and safety. Patient-, intervention-, and study design-related covariates were collected. Meta-regression methods were applied. Forty-four studies involving 9952 patients were included. All-cause treatment discontinuation was slightly higher with pharmacological treatment than with placebo (odds ratio (OR) = 1.18; 95% confidence interval (CI) 1.02, 1.36; p = 0.003). A better outcome on all-cause treatment discontinuation was observed in studies that provided concomitant psychotherapy when compared to those that did not (rate of OR (ROR) = 0.68, p = 0.048). Pharmacological treatment was efficacious for reducing ADHD symptoms (standardized mean difference (SMD) = 0.45; 95% CI 0.37, 0.52; p < 0.00001), with stronger intervention effects found in studies investigating stimulant drugs (difference of SMD (Diff SMD) = 0.18, p = 0.017), in shorter studies (Diff SMD = -0.01, p = 0.044), and when clinician-rated scales were used (Diff SMD = 0.44, p < 0.0001). Pharmacological treatment was associated with more frequent adverse events (AEs) (OR = 2.29; 95% CI 1.97, 2.66; p = 0.006). Studies with a lead-in phase and with a higher proportion of patients previously treated with stimulants were associated with a better safety outcome (ROR = 0.59, p = 0.017; ROR = 0.98, p = 0.036, respectively). Pharmacological treatment provides mild symptom improvement but is associated with frequent AEs and higher treatment discontinuation than placebo, particularly when no concomitant psychotherapy is administered. Stimulants appear more efficacious than non-stimulant drugs and the former should be preferred over the latter. The efficacy of pharmacological treatment should be monitored over time because it may decrease progressively.

The therapeutic potential of working memory training for treating mental disorders.

The therapeutic potential of working memory training for treating mental disorders.

An update on pharmacotherapy for autism spectrum disorder in children and adolescents.

Although there is no known efficacious pharmacotherapy for core symptoms of autism spectrum disorder (ASD), psychotropic medications are commonly prescribed for behavioral/emotional symptoms associated with ASD. We reviewed current evidence-based pharmacotherapy options and updates from recent noteworthy studies. Atypical antipsychotics, particularly risperidone and aripiprazole, are effective in reducing irritability, stereotypy and hyperactivity. Metabolic adverse events, including weight gain and dyslipidemia, are common. Methylphenidate is effective in reducing attention-deficit hyperactivity disorder (ADHD) symptoms. Atomoxetine and alpha-2 agonists appear effective in reducing ADHD symptoms. Selective serotonin reuptake inhibitors are not effective in improving repetitive behaviors in children with ASD, and frequently cause activating adverse events. Efficacy of antiepileptic drugs is inconclusive. Overall, efficacy and tolerability of pharmacotherapy in children with ASD are less favorable than data seen in typically developing children with similar symptoms. Newer agents, including glutamatergic agents and oxytocin, appear promising albeit with mixed results. Current evidence-based pharmacotherapy options in children with ASD are very limited, and many have substantial adverse events. Clinicians should use pharmacotherapy as a part of comprehensive treatment, and judiciously weigh risks and benefits. New pharmacotherapy options for core symptoms as well as co-occurring symptoms of ASD are in urgent need.

Comparative Efficacy of Atomoxetine, Lisdexamfetamine, Bupropion and Methylphenidate in Treatment of Attention Deficit Hyperactivity Disorder in Children and Adolescents: a Metaanalysis with Focus On Bupropion

Introduction Pharmacotherapy is essential for the treatment of children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD). There are only two metaanalyzes available in the literature where bupropion (BUP) was also included and compared to atomoxetine (ATX) and methylphenidate (MPH) in the treatment of ADHD in youths. Objectives There is a lack of comparative effectiveness research among ADHD medications in terms of efficacy, where BUP is compared with ATX, lisdexamfetamine (LDX) and MPH. Aim The main aim of this work was to compare the efficacy of these drugs in children and adolescents using a metaanalysis. Methods A literature search was conducted to identify double-blind, placebo-controlled, noncrossover studies of ADHD. A systematic electronic literature search of PubMed (1975–April 2014) and clinicaltrials.gov with full text (1981–April 2014) was conducted. Drug efficacy was calculated based on the standardized mean difference (SMD). Treatment score was the primary endpoint. Results 28 articles and 27 trials met inclusion criteria and were sufficient for inclusion in the metaanalysis. BUP 0.32 (95% CI, -0.05, 0.69) showed small efficacy, ATX 0.68 (95% CI, 0.59, 0.76), and MPH 0.75 (95% CI, 0.52, 0.98) showed modest efficacy in reducing ADHD symptoms and LDX showed high efficacy 1.28 (95% CL, 0.71, 1.84). Conclusions The results suggest that LDX has the best efficacy and has promising potential for treating children and adolescents with ADHD. Effect sizes should not be the only evidence for clinicians when choosing ADHD medication. More research is needed for a better clinical evaluation of BUP.

Group Therapy for Adolescents With Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial

To determine the efficacy of group cognitive-behavioral therapy (CBT) on adolescents with attention-deficit/hyperactivity disorder (ADHD) who were in pharmacological treatment but still had persistent symptoms. We conducted a multicenter, randomized, rater-blinded, controlled trial between April 2012 and May 2014 in a cohort of 119 adolescents (15-21 years of age). Participants were randomly assigned to 12 manualized group CBT sessions (n= 45) or a waiting list control group (n= 44). Primary outcomes were assessed by a blinded evaluator (ADHD Rating Scale [ADHD-RS], Clinical Global Impression Scale for Severity [CGI-S], Global Assessment of Functioning [GAF]) before and after treatment, as well as by self-report and parent informant ratings. Of the initial 119 participants enrolled, 89 completed treatment. A mixed-effects model analysis revealed that participants who were assigned to the group CBT sessions experienced significantly reduced ADHD symptoms compared to the control group (ADHD-RS Adolescent:-7.46, 95% CI=-9.56 to-5.36, p< .001, d=7.5; ADHD-RS Parents:-9.11, 95% CI=-11.48 to-6.75, p< .001, d= 8.38; CGI-S Self-Report:-0.68, 95% CI=-0.98 to-0.39, p< .001, d= 3.75; CGI-S Clinician:-0.79, 95% CI=-0.95 to-0.62, p< .001; d=7.71). Functional impairment decreased significantly inthe CBT group according to parents (Weiss Functional Impairment Scale-4.02, 95% CI=-7.76 to-0.29, p< .05, d= 2.29) and according to the blinded evaluator (GAF:-7.58, 95% CI=-9.1 to-6.05, p< .001, d= 7.51). Group CBT associated with pharmacological treatment is an efficacious intervention for reducing ADHD symptoms and functional impairment in adolescents. Clinical trial registration information-CBT Group for Adolescents With ADHD: a Randomized Controlled Trial; http://clinicaltrials.gov/; NCT02172183.

Near-infrared spectroscopy (NIRS) neurofeedback as a treatment for children with attention deficit hyperactivity disorder (ADHD)-a pilot study.

In this pilot study near-infrared spectroscopy (NIRS) neurofeedback was investigated as a new method for the treatment of Attention Deficit-/Hyperactivity Disorder (ADHD). Oxygenated hemoglobin in the prefrontal cortex of children with ADHD was measured and fed back. 12 sessions of NIRS-neurofeedback were compared to the intermediate outcome after 12 sessions of EEG-neurofeedback (slow cortical potentials, SCP) and 12 sessions of EMG-feedback (muscular activity of left and right musculus supraspinatus). The task was either to increase or decrease hemodynamic activity in the prefrontal cortex (NIRS), to produce positive or negative shifts of SCP (EEG) or to increase or decrease muscular activity (EMG). In each group nine children with ADHD, aged 7–10 years, took part. Changes in parents’ ratings of ADHD symptoms were assessed before and after the 12 sessions and compared within and between groups. For the NIRS-group additional teachers’ ratings of ADHD symptoms, parents’ and teachers’ ratings of associated behavioral symptoms, childrens’ self reports on quality of life and a computer based attention task were conducted before, 4 weeks and 6 months after training. As primary outcome, ADHD symptoms decreased significantly 4 weeks and 6 months after the NIRS training, according to parents’ ratings. In teachers’ ratings of ADHD symptoms there was a significant reduction 4 weeks after the training. The performance in the computer based attention test improved significantly. Within-group comparisons after 12 sessions of NIRS-, EEG- and EMG-training revealed a significant reduction in ADHD symptoms in the NIRS-group and a trend for EEG- and EMG-groups. No significant differences for symptom reduction were found between the groups. Despite the limitations of small groups and the comparison of a completed with two uncompleted interventions, the results of this pilot study are promising. NIRS-neurofeedback could be a time-effective treatment for ADHD and an interesting new option to consider in the treatment of ADHD.