Treatment Of Attention-deficit/hyperactivity Disorder Symptoms Research Articles

The Therapeutic Potential of Amphetamine-like Psychostimulants.

This review delves into the therapeutic applications of amphetamine-type stimulants such as lisdexamphetamine dimesylate, mixed amphetamine salts, 3,4-methylenedioxymethamphetamine (MDMA), dextroamphetamine, and phentermine. These compounds have been investigated for their potential in treating a range of psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), drug dependence, post-traumatic stress disorder (PTSD), and obesity. Lisdexamphetamine dimesylate has shown promise in effectively treating ADHD symptoms in both children and adults. Additionally, it has been explored as a potential treatment for drug dependency and withdrawal, demonstrating encouraging results. Mixed amphetamine salts have also exhibited efficacy in reducing ADHD symptoms in adults. Future research should explore their potential use in treating bipolar disorder and cocaine dependence, considering the associated risks and benefits. MDMA-assisted psychotherapy has emerged as an innovative approach to treating PTSD, leading to sustained reductions in symptoms and even promoting post-traumatic growth. Furthermore, it has shown promise in managing anxiety related to life-threatening illnesses. Dextroamphetamine and phentermine have demonstrated efficacy in treating cocaine and opioid dependence, ADHD, and obesity. However, careful consideration and monitoring by medical professionals are essential due to the potential risks and benefits associated with them. In conclusion, amphetamine-type stimulants present a promising avenue for therapeutic interventions in various psychiatric conditions. Nevertheless, further research is necessary to comprehensively understand their mechanisms of action, dosage requirements, and long-term effects in different patient populations.

Executive Functions in Children with ADHD

Executive Functions (EFs) play an important role in everyday life, lifelong achievement, and quality of life. Patients with developmental problems are more likely to have executive dysfunctions, especially those with attention deficit hyperactivity disorder (ADHD), who often have impaired working memory, inhibitory control, and organization. Currently, many studies have shown that poor EFs are not directly related to behavioral problems and social impairments due to ADHD symptoms. However, ADHD patients with executive dysfunctions tend to have difficulties in the learning process. Therefore, evaluating EFs along with ADHD symptoms is essential. The most widely used tools for EF assessment include the Behavior Rating Inventory of Executive Function (BRIEF) and the Executive Function assessment in Mahidol University version (MU-EF). Promoting EFs should be done in conjunction with treating ADHD symptoms in ADHD patients with executive dysfunctions. This article aims to review the knowledge of EFs, EF assessment, and evidence-based interventions promoting EFs in ADHD patients, such as pharmacological treatment (Methylphenidate), cognitive training, exercise, white noise, and organization skill intervention.

Effectiveness of Specific Techniques in Behavioral Teacher Training for Childhood ADHD Behaviors: Secondary Analyses of a Randomized Controlled Microtrial

Behavioral teacher training is an effective intervention for children with attention-deficit/hyperactivity disorder (ADHD). Intervention effectiveness may be enhanced by including intervention components that carry the strongest evidence for their effectiveness. A previous article of this group showed that both antecedent- (i.e., stimulus-control) and consequent-based (i.e., contingency management) techniques were highly effective in reducing daily teacher-rated, individually selected problem behaviors in a specific situation of the child. Effects were observed up to three months post intervention. Here, we tested whether effects were also present in teacher-rated and masked DSM-based assessments that comprise the full range of ADHD and oppositional defiant disorder (ODD) symptoms, as well as on teacher-rated impairment. Teachers of 90 children with (subthreshold) ADHD (6–12 years) were randomly assigned to one of three conditions: a short (two sessions), individualized intervention consisting of either a) antecedent-based techniques or b) consequent-based techniques; or c) waitlist. Multilevel analyses showed that both sets of techniques were effective in reducing teacher-rated ADHD symptoms and impairment immediately after the intervention and up to three months later, as compared to waitlist. Masked observations of ADHD behavior were in line with teacher ratings, with effects being most pronounced for inattention. No effects on teacher-rated or masked ODD behavior were found. This study showed that antecedent- and consequent-based techniques were effective in improving classroom ADHD symptoms and impairment. Long-term changes in teacher-rated ADHD are promising. These results extend previous findings and show the potential of short individually tailored interventions in classroom settings as treatment of ADHD symptoms.

The Link between Pediatric Obstructive Sleep Apnea (OSA) and Attention Deficit Hyperactivity Disorder (ADHD).

Obstructive sleep apnea (OSA) is a form of sleep-disordered breathing that affects up to 9.5% of the pediatric population. Untreated OSA is associated with several complications, including neurobehavioral sequelae, growth and developmental delay, cardiovascular dysfunction, and insulin resistance. Attention-deficit/hyperactivity disorder (ADHD) is among the neurobehavioral sequelae associated with OSA. This review aims to summarize the research on the relationship between OSA and ADHD and investigate the impacts of OSA treatment on ADHD symptoms. A literature search was conducted on electronic databases with the key terms: “attention deficit hyperactivity disorder” or “ADHD”, “obstructive sleep apnea” or “OSA”, “sleep disordered breathing”, and “pediatric” or “children”. Review of relevant studies showed adenotonsillectomy to be effective in the short-term treatment of ADHD symptoms. The success of other treatment options, including continuous positive airway pressure (CPAP), in treating ADHD symptoms in pediatric OSA patients has not been adequately evaluated. Further studies are needed to evaluate the long-term benefits of surgical intervention, patient factors that may influence treatment success, and the potential benefits of other OSA treatment methods for pediatric ADHD patients.

A Meta-analysis of Mindfulness-Based Interventions in Adults with Attention-Deficit Hyperactivity Disorder: Impact on ADHD Symptoms, Depression, and Executive Functioning

Mindfulness-based interventions (MBIs) are increasingly used in adults with attention-deficit hyperactivity disorder (ADHD). The aim of the current study was to conduct a meta-analysis of the available studies on the effects of MBIs on ADHD symptoms, depression, and executive functioning in adults diagnosed with ADHD. Screening and selection of peer-reviewed literature using PRISMA-P guidelines on PsycINFO, PubMed, SCOPUS, and ERIC databases from inception to July 2019 A total of 14 studies were included in the meta-analysis, for an aggregated sample of 834 adults with ADHD. Overall, the results showed that MBIs are effective to treat ADHD symptoms in adults, as well as to reduce depression and dysexecutive problems post-intervention. MBIs are useful to improve ADHD symptoms, negative affect, and cognition in adult ADHD. The results contribute to better understanding and encourage the use of non-pharmacological treatments in ADHD.

Methylmercury, attention, and memory: baseline-dependent effects of adult d-amphetamine and marginal effects of adolescent methylmercury

Methylmercury (MeHg) is an environmental neurotoxicant known to disrupt behavior related to dopamine neurotransmission in experimental models. Such disruptions are sensitive to dopamine agonists when administered acutely after exposure to MeHg has ended or when administered concurrently with MeHg exposure. Sustained attention and short-term remembering, components of attention-deficit/hyperactivity disorder (ADHD), are partially mediated by dopamine neurotransmission. In order to observe MeHg-related alterations in sustained attention and short-term memory, as well as determine sensitivity of MeHg exposed animals to dopamine agonists commonly used in the treatment of ADHD symptoms, rats were exposed to 0, 0.5, or 5 ppm MeHg throughout adolescence and trained in a hybrid sustained attention/short term memory visual signal detection task in adulthood. Behavior was then probed with acute i.p. injections of the dopamine agonist, d-amphetamine, which improves impaired attention and inhibits short-term memory in clinical syndromes like ADHD. Acute d-amphetamine dose-dependently decreased short-term memory as well as sustained attention. While MeHg alone did not impair accuracy or memory, it did interact with d-amphetamine to produce baseline-dependent inhibition of behavior. These findings further show that changes in behavior following low-level exposure to MeHg during adolescence are augmented by dopamine agonists. Observed impairments in memory following acute d-amphetamine are consistent with previous findings.

Vitamin D Status of Children With Attention-Deficit Hyperactivity Disorder

Attention-deficit hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder, but its pathophysiology remains unclear. Vitamin D deficiency may increase risk for ADHD. A review of the literature was conducted to evaluate the vitamin D status of children with ADHD. Most of the evidence suggests that children with ADHD have significantly lower vitamin D levels than children without ADHD. Supplementation may help treat ADHD symptoms, but some investigators concluded that children with ADHD and children without ADHD do not significantly differ in vitamin D levels. However, identifying and treating vitamin D deficiency remains important for this population.

Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in children with comorbid tic disorders.

This is an update of the original Cochrane Review published in Issue 4, 2011.Attention deficit hyperactivity disorder (ADHD) is the most prevalent of the comorbid psychiatric disorders that complicate tic disorders. Medications commonly used to treat ADHD symptoms include stimulants such as methylphenidate and amphetamine; non-stimulants, such as atomoxetine; tricyclic antidepressants; and alpha agonists. Alpha agonists are also used as a treatment for tics. Due to the impact of ADHD symptoms on the child with tic disorder, treatment of ADHD is often of greater priority than the medical management of tics.However, for many decades, clinicians have been reluctant to use stimulants to treat children with ADHD and tics for fear of worsening their tics. OBJECTIVES: To assess the effects of pharmacological treatments for ADHD in children with comorbid tic disorders on symptoms of ADHD and tics. In September 2017, we searched CENTRAL, MEDLINE, Embase, and 12 other databases. We also searched two trial registers and contacted experts in the field for any ongoing or unpublished studies. We included randomized, double-blind, controlled trials of any pharmacological treatment for ADHD used specifically in children with comorbid tic disorders. We included both parallel-group and cross-over study designs. We used standard methodological procedures of Cochrane, in that two review authors independently selected studies, extracted data using standardized forms, assessed risk of bias, and graded the overall quality of the evidence by using the GRADE approach. We included eight randomized controlled trials (four of which were cross-over trials) with 510 participants (443 boys, 67 girls) in this review. Participants in these studies were children with both ADHD and a chronic tic disorder. All studies took place in the USA and ranged from three to 22 weeks in duration. Five of the eight studies were funded by charitable organizations or government agencies, or both. One study was funded by the drug manufacturer. The other two studies did not specify the source of funding. Risk of bias of included studies was low for blinding; low or unclear for random sequence generation, allocation concealment, and attrition bias; and low or high for selective outcome reporting. We were unable to combine any of the studies in a meta-analysis due to important clinical heterogeneity and unit-of-analysis issues.Several of the trials assessed multiple agents. Medications assessed included methylphenidate, clonidine, desipramine, dextroamphetamine, guanfacine, atomoxetine, and deprenyl. There was low-quality evidence for methylphenidate, atomoxetine, and clonidine, and very low-quality evidence for desipramine, dextroamphetamine, guanfacine and deprenyl in the treatment of ADHD in children with tics. All studies, with the exception of a study using deprenyl, reported improvement in symptoms of ADHD. Tic symptoms also improved in children treated with guanfacine, desipramine, methylphenidate, clonidine, and a combination of methylphenidate and clonidine. In one study, tics limited further dosage increases of methylphenidate. High-dose dextroamphetamine appeared to worsen tics in one study, although the length of this study was limited to three weeks. There was appetite suppression or weight loss in association with methylphenidate, dextroamphetamine, atomoxetine, and desipramine. There was insomnia associated with methylphenidate and dextroamphetamine, and sedation associated with clonidine. Following an updated search of potentially relevant studies, we found no new studies that matched our inclusion criteria and thus our conclusions have not changed.Methylphenidate, clonidine, guanfacine, desipramine, and atomoxetine appear to reduce ADHD symptoms in children with tics though the quality of the available evidence was low to very low.Although stimulants have not been shown to worsen tics in most people with tic disorders, they may, nonetheless, exacerbate tics in individual cases.In these instances, treatment with alpha agonists or atomoxetine may be an alternative. Although there is evidence that desipramine may improve tics and ADHD in children, safety concerns will likely continue to limit its use in this population.

The Prevalence of ADHD Patients among Pediatric Dentists in Israel and Knowledge of Dental and Behavioral Aspects of Treating Them.

There are no clear guidelines for managing the dental treatment of children with attention deficit hyperactivity disorder (ADHD). The use of sedation in combination with chronic ADHD medication use is also not well defined. This study surveyed the prevalence of ADHD children, management techniques and knowledge of pharmacologic therapies of these children among Israeli dentists. A specially designed questionnaire was distributed to all Israeli dentists attending a national conference in 2016. Of the 160 dentists who attended the conference, 96 completed the survey (60% response rate), and they included 46 (51%) pediatric dental specialists and 50 (49%) general dental practitioners. The medications Ritalin and Concerta were most familiar to the respondents (98.9%). Eighty-seven (91.1%) of the practitioners responded that their ADHD patients take their usual doses of any drug for treating ADHD symptoms, regardless of whether or not the dentists intended to use sedatives. The practitioners invented their own behavior management techniques with varying degrees of success. There are no specific guidelines for the most effective pharmacologic protocol (co-administration of ADHD drugs and dental sedatives) or behavior management techniques for the provision of optimal dental care to children with ADHD.

A review of the efficacy of atomoxetine in the treatment of attention-deficit hyperactivity disorder in children and adult patients with common comorbidities.

Attention-deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder that is often diagnosed during childhood, but has also increasingly been recognized to occur in adults. Importantly, up to 52% of children (including adolescents) and 87% of adults with ADHD also have a comorbid psychiatric disorder. The presence of a comorbid disorder has the potential to impact diagnosis and could affect treatment outcomes. Atomoxetine is a nonstimulant treatment for ADHD. Despite numerous published studies regarding efficacy of atomoxetine in the treatment of ADHD in patients with comorbid disorders, there is limited information about the impact of individual common comorbid disorders on the efficacy of atomoxetine for ADHD, especially with regard to adults. Moreover, a cumulative review and assessment of these studies has not been conducted. For this reason, we performed a literature review to find, identify, and cumulatively review clinical studies that examined the efficacy of atomoxetine in the treatment of patients with ADHD and comorbid psychiatric disorders. We found a total of 50 clinical studies (37 in children; 13 in adults) that examined the efficacy of atomoxetine in patients with ADHD and a comorbid disorder. The comorbidities that were studied in children or in adults included anxiety, depression, and substance use disorder. Overall, the presence of comorbidity did not adversely impact the efficacy of atomoxetine in treatment of ADHD symptoms in both patient populations. In the studies identified and assessed in this review, atomoxetine did not appear to exacerbate any of the comorbid conditions and could, therefore, be an important therapy choice for the treatment of ADHD in the presence of comorbid disorders.

Effects of methylphenidate on the impairment of spontaneous alternation behavior in mice intermittently deprived of REM sleep

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. We have previously shown that abnormal behaviors elicited by intermittent rapid eye movement (REM) sleep deprivation stress may fulfill the profile of a model of ADHD. It is well known that the impairment of spontaneous alternation behavior (SAB) in the Y-maze indicates inattentive features of ADHD model animals. On the other hand, it has been reported that nitric oxide (NO) in the hippocampus is required for SAB. In this study, using mice, we investigated whether intermittent REM sleep deprivation stress causes changes in SAB and the expression of NO synthase (NOS) mRNA and in the levels of NO metabolites in the hippocampus. Mice were deprived of REM sleep intermittently by the small-platform method (20 h/day) for 3 days. The SAB, the level of nitrite and expression of endothelial NOS (eNOS) and inducible NOS (iNOS) mRNA in the hippocampus, but not neuronal NOS (nNOS), were significantly decreased by intermittent REM sleep deprivation stress. The decreased levels of SAB, nitrite and iNOS mRNA were significantly increased by methylphenidate treatment, which is used clinically to treat ADHD symptoms. Moreover, these improvement effects of methylphenidate on SAB and the nitrite level were decreased by the administration of selective iNOS and eNOS inhibitors. However, the eNOS inhibitor decreased both nitrate and total NOx levels of the hippocampus in saline treated intermittent REM sleep-deprived mice. These results suggest that the impairment of SAB induced by intermittent REM sleep deprivation stress may serve as a model of the inattention symptom in ADHD. Further, the ameliorating effects of methylphenidate on the impairment of SAB may be mediated through NO production mainly by iNOS in the hippocampus of mice.

ADHD & Pharmacotherapy: Past, Present and Future: A Review of the Changing Landscape of Drug Therapy for Attention Deficit Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) is the most common neurobiological disorder in children, with a prevalence of ~6-7%1,2 that has remained stable for decades2. The social and economic burden associated with patients3, families, and broader systems (healthcare/educational) is substantial, with the annual economic impact of ADHD exceed $30 billion in the US alone4. Efficacy of pharmacotherapy in treating ADHD symptoms has generally been considerable with at least ¾ of individuals benefitting from pharmacotherapy, typically in the form of stimulants5. In this review, we begin by briefly reviewing the history of pharmacotherapy in relation to ADHD, before focusing (primarily) on the state-of-the-field on themes such as biophysiology, pharmacokinetics, and pharmacogenomics. We conclude with a summary of emerging clinical and research studies, particularly the potential role for precision therapy in matching ADHD patients and drug types.

The effects of a Self-Alert Training (SAT) program in adults with ADHD.

Attention-Deficit/Hyperactivity Disorder (ADHD), a neuropsychiatric condition characterized by attention and impulsivity problems, is one of the most common behavioral disorders. The first line of treatment for ADHD is psychostimulant medication, but this has limited effectiveness, particularly in adults, and is often associated with adverse side-effects. Thus, it is imperative that new non-pharmaceutical approaches to treatment are developed. This study aims to evaluate the impact of a non-pharmacological Self-Alert Training (SAT) intervention on ADHD symptom prevalence, psychological and cognitive functioning, and on everyday functional impairment in adults with ADHD. Fifty-one adult participants with a current diagnosis of ADHD were randomized to either SAT or a Control Training (CT) program. They were assessed at baseline, immediately following the 5-week training period, and after 3-months using ADHD symptoms scales, as well as a series of neuropsychological tests and psychological questionnaires. Subjective ratings of everyday life attention and memory problems were also collected. The SAT group showed significant improvements in ADHD inattentive and impulsive symptoms, depressive symptoms and in self-efficacy ratings compared to the CT group at both post-training and at the 3-month assessment. Pre-post improvements in SAT participants on untrained cognitive tasks measuring selective attention and executive functions were also observed. Finally, the SAT group reported improved subjective ratings of everyday life attention at both assessment points. This pattern of results suggests that SAT may be beneficial in treating ADHD symptoms as well as psychological and cognitive impairments in adult ADHD. A large-scale randomized controlled trial (RCT) is needed.

A randomized, placebo-controlled, double-blind study of sapropterin to treat ADHD symptoms and executive function impairment in children and adults with sapropterin-responsive phenylketonuria.

Symptoms of attention deficit-hyperactivity disorder (ADHD), particularly inattention, and impairments in executive functioning have been reported in early and continuously treated children, adolescents, and adults with phenylketonuria (PKU). In addition, higher blood phenylalanine (Phe) levels have been correlated with the presence of ADHD symptoms and executive functioning impairment. The placebo-controlled PKU ASCEND study evaluated the effects of sapropterin therapy on PKU-associated symptoms of ADHD and executive and global functioning in individuals who had a therapeutic blood Phe response to sapropterin therapy. The presence of ADHD inattentive symptoms and executive functioning deficits was confirmed in this large cohort of 206 children and adults with PKU, of whom 118 responded to sapropterin therapy. In the 38 individuals with sapropterin-responsive PKU and ADHD symptoms at baseline, sapropterin therapy resulted in a significant improvement in ADHD inattentive symptoms in the first 4 weeks of treatment, and improvements were maintained throughout the 26 weeks of treatment. Sapropterin was well-tolerated with a favorable safety profile. The improvements in ADHD inattentive symptoms and aspects of executive functioning in response to sapropterin therapy noted in a large cohort of individuals with PKU indicate that these symptoms are potentially reversible when blood Phe levels are reduced.

Broad-spectrum micronutrient treatment for attention-deficit/hyperactivity disorder: rationale and evidence to date.

Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric illness, which often co-occurs with other common psychiatric problems. Although empirical evidence supports the short-term efficacy of pharmacological and behavioural treatments, families often search for alternative treatment methods because of concerns about side effects and safety, cost and access, as well as fears about long-term exposure to psychotropic medications. This review presents the published evidence on use of broad-spectrum micronutrients to treat ADHD symptoms. This approach makes physiological sense in that nutrients are required for many critical biochemical reactions to occur, ranging from manufacturing neurotransmitters, to providing the mitochondria with essential nutrients for energy production, to assisting the gut to heal from inflammation. Multi-nutrient treatment approaches are an intriguing yet under-researched area; all but one of the trials conducted in the last decade have shown benefit for the treatment of ADHD symptoms, and the one negative trial likely used doses too low to effect change. However, the methodologies have varied widely from case-controlled studies to open-label trials to one randomized controlled trial. Sample sizes have typically been modest, although the effect sizes have tended to be medium to large. What is required now is replication, as well as investigation into the optimal ingredient range and optimal doses of nutrients. We discuss the proven and potential benefits of the broad-spectrum nutrient approach, considering the heterogeneous nature of ADHD.

Use of Serotonin Norepinephrine Reuptake Inhibitors in the Treatment of Attention-Deficit Hyperactivity Disorder in Pediatrics

To review the current literature on the efficacy and safety of serotonin norepinephrine reuptake inhibitors in the treatment of attention-deficit hyperactivity disorder (ADHD) in the pediatric population. A literature search from 1996 to August 2013 was conducted using MEDLINE, CINAHL, and EMBASE databases. Search terms included attention-deficit hyperactivity disorder, serotonin norepinephrine reuptake inhibitor, pediatric attention-deficit hyperactivity disorder, venlafaxine, duloxetine, desvenlafaxine, milnacipran, and nefazodone. Relevant articles on duloxetine and venlafaxine for the treatment of pediatric ADHD were reviewed; 5 studies on venlafaxine and 1 study on duloxetine were evaluated. Studies included open-label and randomized, double-blind trials. Case studies in pediatric populations and all studies in adult populations were excluded. Patients 6 to 17 years old were evaluated in the venlafaxine and duloxetine studies. Trials on venlafaxine, ranging from 2 to 6 weeks, showed patient improvement as measured by the Conners Rating Scale and ADHD Rating Scale. Venlafaxine was initiated at 12.5 to 25 mg/d and titrated up to 1.4 to 3.8 mg/kg/d to a maximum of 150 mg/d. Duloxetine showed minimal efficacy in treating ADHD symptoms at doses of 60 mg/d at 6 weeks. The most common side effects for venlafaxine and duloxetine included drowsiness and decreased appetite, respectively. Data for venlafaxine and duloxetine are limited. However, venlafaxine may be considered as an alternative agent when patients cannot tolerate or fail stimulants, tricyclic antidepressants, or bupropion. Duloxetine has been studied in children; however, with only 1 study available, it is difficult to recommend.

A Systematic Review of Combination Therapy with Stimulants and Atomoxetine for Attention-Deficit/Hyperactivity Disorder, Including Patient Characteristics, Treatment Strategies, Effectiveness, and Tolerability

The purpose of this article was to systematically review the literature on stimulant and atomoxetine combination therapy, in particular: 1) Characteristics of patients with attention-deficit/hyperactivity disorder (ADHD) given combination therapy, 2) treatment strategies used, 3) efficacy and effectiveness, and 4) safety and tolerability. Literature databases (MEDLINE(®), EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, and SciVerse Scopus) were systematically searched using prespecified criteria. Publications describing stimulant and atomoxetine combination therapy in patients with ADHD or healthy volunteers were selected for review. Exclusion criteria were comorbid psychosis, bipolar disorder, epilepsy, or other psychiatric/neurologic diseases that could confound ADHD symptom assessment, or other concomitant medication(s) to treat ADHD symptoms. Of the 16 publications included for review, 14 reported findings from 3 prospective studies (4 publications), 7 retrospective studies, and 3 narrative reviews/medication algorithms of patients with ADHD. The other two publications reported findings from two prospective studies of healthy volunteers. The main reason for prescribing combination therapy was inadequate response to previous treatment. In the studies of patients with ADHD, if reported, 1) most patients were children/adolescents and male, and had a combined ADHD subtype; 2) methylphenidate was most often used in combination with atomoxetine for treatment augmentation or switch; 3) ADHD symptom control was improved in some, but not all, patients; and 4) there were no serious adverse events. Published evidence of the off-label use of stimulant and atomoxetine combination therapy is limited because of the small number of publications, heterogeneous study designs (there was only one prospective, randomized controlled trial), small sample sizes, and geographic bias. Existing evidence suggests, but does not confirm, that this drug combination may benefit some, but not all, patients who have tried several ADHD medications without success.

The impact of methylphenidate on seizure frequency and severity in children with attention‐deficit–hyperactivity disorder and difficult‐to‐treat epilepsies

Difficult-to-treat epilepsies and attention-deficit-hyperactivity disorder (ADHD) often co-occur. Because of concerns about the use of stimulants in children with this comorbidity, the impact of ADHD treatment on seizure frequency and severity is not known. This pilot study evaluated the safety and efficacy of methylphenidate in this population. After a 3 month period in which antiepileptic drugs were adjusted, 22 patients recruited from a specialist outpatient clinic for severe epilepsy (16 males, six females; mean age 11 y 2 mo, SD 3 y 2 mo) received methylphenidate for 3 months in an open label, non-controlled trial; four with generalized or multifocal (symptomatic/cryptogenic) epilepsy, one with generalized (idiopathic) epilepsy, 17 with partial (symptomatic/cryptogenic) epilepsy; five with partial seizures only, 17 with primarily or secondarily generalized seizures). Epilepsy, ADHD symptoms, and side effects were assessed using the Swanson, Nolan, and Pelham Questionnaire, the Child Behavior Checklist, the Hague Seizure Severity Scale, and the Side Effects Rating Scale. Methylphenidate significantly improved ADHD. After 3 months of treatment, 73% of patients no longer had clinically significant symptoms. Methylphenidate also reduced seizure severity (9-point median decrease on the Hague Seizure Severity Scale). Seizure frequency increased in four out of 22 patients, but only one patient withdrew from the study for this reason. Most patients experienced no major side effects. These data are among the first showing that low doses of methylphenidate are safe and effective to treat ADHD symptoms in patients with difficult-to-treat epilepsies. Randomized controlled trials are needed to replicate the findings.

Systematic Review and Meta-analysis of Pharmacological Treatment of the Symptoms of Attention-Deficit/Hyperactivity Disorder in Children with Pervasive Developmental Disorders

Many children with pervasive developmental disorders (PDD) exhibit behaviors and symptoms of attention-deficit/hyperactivity disorder (ADHD). We sought to determine the relative efficacy of medications for treating ADHD symptoms in children with PDD by identifying all double-blind, randomized, placebo-controlled trials examining the efficacy of medications for treating ADHD symptoms in children with PDD. We located seven trials involving 225 children. A random effects meta-analysis of four methylphenidate trials showed methylphenidate to be effective for treating ADHD symptoms in children with PDD (ES=.67). Several adverse events were greater for children were taking methylphenidate compared to placebo. An individual trial of clonidine and two trials of atomoxetine suggest these agents may also be effective in treating ADHD symptoms in children with PDD.

An influence of delayed reinforcement on the effectiveness of psychostimulants to enhance indices of attention under a five-choice serial reaction time procedure in male rats.

The five-choice serial reaction time (5-CSRT) procedure has been considered a translational tool for assessments of the psychopharmacology of attention in preclinical research. Because greater sensitivity to delayed reinforcement may promote the development of attention-deficit/hyperactivity disorder (ADHD) symptoms, effects of reinforcer delay and psychostimulants on performances under a 5-CSRT procedure were determined. Male rats were trained to respond under a 5-CSRT procedure with different delay-of-reinforcement conditions (0, 2, 4, 8, 16 s), and effects of d-amphetamine, methylphenidate, and morphine (as a negative control) were assessed at 0- and 16-s delays. Under nondrug conditions, as the delay increased both response latency and the number of trials in which a response did not occur (omissions) increased, and the percent correct on trials when responses were emitted decreased. Only modest increases in the percent correct were found with psychostimulants during the 0-s delay condition; however, more substantial enhancements were found with a 16-s delay. Consistent effects of both psychostimulants at either delay on omissions and response latency were not observed. Morphine increased omissions and response latency at both delays and decreased the percent correct (16-s delay). Generally, responses during the intertrial interval were not systematically affected under any condition. The current results demonstrate that measures of attention in a 5-CSRT procedure are sensitive to changes in the delay to reinforcer delivery. More important, psychostimulants significantly enhanced a measure of attention only when reinforcers were delayed, which may be reflective of the psychopharmacological mechanisms involved with clinical treatment of ADHD symptoms.