Psychostimulant Medication Research Articles

Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized, Placebo-Controlled Trials

Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics for fear that tics will develop or worsen as a side effect of treatment. Our goal was to conduct a meta-analysis to examine the risk of new onset or worsening of tics as an adverse event of psychostimulants in randomized, placebo-controlled trials. We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). We used a fixed effects meta-analysis with risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dose, duration of treatment, recorder of side effect data, trial design, and mean age of participants on the measured risk of tics. We identified 22 studies involving 2,385 children with ADHD for inclusion in our meta-analysis. New onset tics or worsening of tic symptoms were commonly reported in the psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics associated with psychostimulant treatment was similar to that observed with placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of psychostimulant, dose, duration of treatment, recorder, and participant age did not affect risk of new onset or worsening of tics. Crossover studies were associated with a significantly greater measured risk of tics with psychostimulant use compared to parallel group trials. Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant use, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants.

Treatment of Severe Childhood Aggression (TOSCA) Studies.

[Author Affiliation]Michael G. Aman. Department of Psychiatry, Ohio State University, Columbus, Ohio.Address correspondence to: Michael G. Aman, PhD, Professor Emeritus of Psychology, The Nisonger Center (OCEDD) Ohio State University, 1581 Dodd Drive, Columbus, Ohio 43210, E-mail: Aman.1@osu.eduFor decades we have known that physical aggression in youth often has dire consequences in later life. The Treatment of Severe Childhood Aggression or TOSCA study was a departure from earlier monotherapy studies of medication treatment for aggression because it entailed an attempt to normalize behavioral outcomes through the use of combined treatment, if needed. The impetus for TOSCA was a series of risperidone studies conducted by Janssen Pharmaceutica and others (e.g., Findling et al., 2000) published in the early 2000s. When designing TOSCA, we were especially interested in risperidone's potential to dampen aggression and other disruptive behaviors. Initially, our focus was comparison of psychostimulant vs. risperidone monotherapy, both with an adjunctive parent training (PT) program. However, using the best data available, power analyses indicated that over 2,000 participants would be needed to have sufficient sensitivity to separate treatments! Eventually, we settled on a combined treatment design not only because it dealt with the statistical-power issue but also because it was ecologically valid (i.e., it followed a common clinical practice; see Farmer et al. 2011 for methodological details).TOSCA is important because it has mapped uncharted territory insofar as pediatric drug research design is concerned. To satisfy the statistical-power issues, we advocated for the complex add-on design (i.e., combined therapy) despite the fact that we, like most practitioners, were trained that simpler is better. The TOSCA design not only called for the use of combined treatments, but one of those treatments was an antipsychotic. Such agents often provoke concern because of their reputation as powerful drugs, because they can cause possible long-term movement disorders, and because of their association with metabolic syndrome. Eventually, the NIMH funded TOSCA and, in so doing, acknowledged the importance of aggression in today's society and the reality that combined pharmacotherapy has become a common practice in child and adolescent psychiatry.The TOSCA participants were 168 children with severe physical aggression (to others, to self, and/or to property) and presence of attention-deficit/hyperactivity disorder (ADHD); psychotic and bipolar disorders were excluded. All study participants received psychostimulant medication and PT in behavior management. If disruptive behavior was not normalized by 3 weeks, then either placebo or risperidone was added as co-therapy from weeks 4 through 9. Psychostimulant+PT+placebo were termed basic treatment, whereas psychostimulant+PT+risperidone were termed augmented treatment. Our earliest reports indicated that augmented treatment was more effective than basic treatment in reducing parent ratings of disruptive behavior (moderate effect size) but not clinician global ratings.Three TOSCA studies appear in this issue. Arnold et al. (2015) examined domains other than disruptive behavior as rated by parents and teachers. They found that augmented treatment resulted in a reduction to teacher-rated anxiety and further that these reductions mediated improvements in parent-rated disruptive behavior. …

The dopamine imbalance hypothesis of fatigue in multiple sclerosis and other neurological disorders.

Fatigue is one of the most pervasive symptoms of multiple sclerosis (MS), and has engendered hundreds of investigations on the topic. While there is a growing literature using various methods to study fatigue, a unified theory of fatigue in MS is yet to emerge. In the current review, we synthesize findings from neuroimaging, pharmacological, neuropsychological, and immunological studies of fatigue in MS, which point to a specific hypothesis of fatigue in MS: the dopamine imbalance hypothesis. The communication between the striatum and prefrontal cortex is reliant on dopamine, a modulatory neurotransmitter. Neuroimaging findings suggest that fatigue results from the disruption of communication between these regions. Supporting the dopamine imbalance hypothesis, structural and functional neuroimaging studies show abnormalities in the frontal and striatal regions that are heavily innervated by dopamine neurons. Further, dopaminergic psychostimulant medication has been shown to alleviate fatigue in individuals with traumatic brain injury, chronic fatigue syndrome, and in cancer patients, also indicating that dopamine might play an important role in fatigue perception. This paper reviews the structural and functional neuroimaging evidence as well as pharmacological studies that suggest that dopamine plays a critical role in the phenomenon of fatigue. We conclude with how specific aspects of the dopamine imbalance hypothesis can be tested in future research.

Current evidence and future directions for research with omega-3 fatty acids and attention deficit hyperactivity disorder.

Nutritional insufficiencies of nutrients such as omega-3 highly unsaturated fatty acids (HUFAs), vitamins and minerals have been linked to suboptimal developmental outcomes including attention deficit hyperactivity disorder (ADHD). Although the predominant treatment is currently psychostimulant medications, randomized clinical trials with omega-3 HUFAs have reported small-to-modest effects in reducing symptoms of ADHD in children despite arguable individual methodological and design misgivings. This review presents, discusses and critically evaluates data and findings from meta-analytic and systematic reviews and clinical trials published within the last 12 months. Recent trajectories of this research are discussed, such as comparing eicosapentaenoic acid and docosahexaenoic acid and testing the efficacy of omega-3 HUFAs as an adjunct to methylphenidate. Discussion includes highlighting limitations and potential future directions such as addressing variable findings by accounting for other nutritional deficiencies and behavioural food intolerances. The authors conclude that given the current economic burden of ADHD, estimated in the region of $77 billion in the USA alone, in addition to the fact that a proportion of patients with ADHD are either treatment resistant, nonresponders or withdraw from medication because of adverse side-effects, the investigation of nonpharmacological interventions including omega-3 HUFAs in clinical practice warrants extrapolating.

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.

Exploring parental country of birth differences in the use of psychostimulant medications for ADHD: a whole‐population linked data study

ObjectiveTo explore parental country of birth differences in the use of stimulants for attention deficit hyperactivity disorder (ADHD) in Western Australian (WA) children and adolescents. MethodsStatutory WA stimulant notification and dispensing records from 2003 to 2007 were linked to whole‐population state data from 1980 to 2007. Parental attributes were obtained through the WA Family Connections genealogical linkage system. Using multivariate logistic and linear regression, the differences in WA stimulant use for ADHD by parental country of birth, socioeconomic status and geographical remoteness were examined. ResultsOf 671,231 people born in WA between 1980 and 2007, 13,555 (2%) used stimulants for ADHD. Of these, 734 (5%) had parents born in Africa, Asia, the Middle East or South America, and 12,006 (87%) had parents born in Australia, North America and Europe. Children and adolescents with parents born in traditionally non‐Anglophonic countries were less likely to be treated with stimulants (OR=0.17, 95%CI 0.14–0.21) than those with parents born in Anglophonic countries. Socioeconomic advantage and residential remoteness were also significant independent predictors of a decreased likelihood of stimulant use. ConclusionsThe results highlight the importance of improving knowledge about cultural differences in access to and attitudes towards the diagnosis of ADHD and different approaches to its treatment.

Adolescent exposure to cocaine, amphetamine, and methylphenidate cross-sensitizes adults to methamphetamine with drug- and sex-specific effects

The increasing availability, over-prescription, and misuse and abuse of ADHD psychostimulant medications in adolescent populations necessitates studies investigating the long-term effects of these drugs persisting into adulthood. Male and female C57Bl/6J mice were exposed to amphetamine (AMPH) (1.0 and 10mg/kg), methylphenidate (MPD) (1.0 and 10mg/kg), or cocaine (COC) (5.0mg/kg) from postnatal day 22 to 31, which represents an early adolescent period. After an extended period of drug abstinence, adult mice were challenged with a subacute methamphetamine (METH) dose (0.5mg/kg), to test the long-term effects of adolescent drug exposures on behavioral cross-sensitization using an open field chamber. There were no sex- or dose-specific effects on motor activity in adolescent, saline-treated controls. However, AMPH, MPD, and COC adolescent exposures induced cross-sensitization to a subacute METH dose in adulthood, which is a hallmark of addiction and a marker of long-lasting plastic changes in the brain. Of additional clinical importance, AMPH-exposed male mice demonstrated increased cross-sensitization to METH in contrast to the female-specific response observed in MPD-treated animals. There were no sex-specific effects after adolescent COC exposures. This study demonstrates differential drug, dose, and sex-specific alterations induced by early adolescent psychostimulant exposure, which leads to behavioral alterations that persist into adulthood.

Treatment compliance or medication adherence in children and adolescents on ADHD medication in clinical practice: results from the COMPLY observational study.

Although the efficacy and tolerability of ADHD medications have been investigated fairly extensively, there are very few data comparing the different types of medication (e.g. psychostimulants, non-stimulants) in terms of medication adherence. The primary research objective of the COMPLY observational study was to evaluate medication adherence (i.e. compliance) over 1 year in children and adolescents with ADHD in a routine clinical setting. COMPLY was a prospective 12-month, observational, open-label study that included children and adolescents, aged 6-17 years, with ADHD. Medication adherence (i.e. compliance) was measured using the Pediatric Compliance Self-Rating (PCSR) instrument and using items 1-4 of the Medication Adherence Rating Scale (MARS). A total of 504 patients were enrolled. At baseline, 252 patients (50.0 %) were prescribed non-stimulant (atomoxetine) medication and 247 patients (49.0 %) were prescribed psychostimulant medication. Both types of medication were prescribed concomitantly in five patients (1.0 %). After 12 months, 123 patients (48.8 %) were taking atomoxetine and 176 patients (71.3 %) were taking psychostimulants. Adherence (PCSR score ≥ 5) was present in both groups (atomoxetine: 67.5 %; psychostimulant: 74.2 %) throughout the observation period. MARS scores declined over time in both groups (atomoxetine: from 3.7 to 2.9; psychostimulant: from 3.6 to 3.1), indicating a deterioration in adherence. There was no statistically significant difference in terms of medication adherence between the two groups.

The Association Between Attention Deficit Hyperactivity Disorder and Nicotine Use Among Adolescents and Young Adults

Previous research indicates that youths with attention deficit hyperactivity disorder (ADHD) are more susceptible to nicotine use compared to those without ADHD, and one explanation for this association is the self-medication theory. The present study examines nicotine use in a prospective sample derived from a community sampling procedure rather than a clinical setting. Nicotine use was measured through young adulthood (mean ages: 18, 20, and 22), and three groups were compared based on childhood status: ADHD only, ADHD externalizers, and control groups. Results indicated that at all three data points, individuals with childhood ADHD plus an externalizing disorder reported higher nicotine use on all variables compared to the ADHD group absent of an externalizing disorder and the comparison group of non-ADHD youths. The group differences were significant even after controlling for possible confounding variables (age, gender, and current treatment with psychostimulant medication). Study results are discussed in light of the self-medication hypothesis and of the importance of including nicotine prevention programs for adolescents and young adults with ADHD and externalizing problems.

Treatment strategies for ADHD in preschool and school-age children.

This review presents current best-evidence treatment options for children with attention-deficit hyperactivity disorder (ADHD), including a review of current literature on the efficacy and safety of psychostimulant medications, particularly methylphenidate, used in treating preschoolers and school-age children with ADHD.

Implementation of a self-monitoring application to improve on-task behavior: A high school pilot study.

Technological innovations offer promise for improving intervention implementation in secondary, inclusive classrooms. A withdrawal design was employed with two high school students in order to assess the effectiveness of a technologically-delivered, self-monitoring intervention in improving on-task behavior in a science classroom. Two students ages 14 and 15 with diagnoses of specific learning disability (student 1) and attention deficit hyperactivity disorder (ADHD: student 2) were selected by case manager referral due to difficulties with on-task behavior despite long-term administration of psychostimulant medication. After baseline data were collected, both students were trained in the use of a self-monitoring application (I-Connect) delivered via a handheld tablet. On-task prompts were delivered at five min intervals in an ABAB withdrawal design. The intervention resulted in positive, stable improvements in the primary dependent variable of on-task behavior for both students and less clear improvement in the generalization variable of disruptive behavior.

Associations of sleep disturbance with ADHD: implications for treatment.

Attention-deficit/hyperactivity disorder (ADHD) is commonly associated with disordered or disturbed sleep. The relationships of ADHD with sleep problems, psychiatric comorbidities and medications are complex and multidirectional. Evidence from published studies comparing sleep in individuals with ADHD with typically developing controls is most concordant for associations of ADHD with: hypopnea/apnea and peripheral limb movements in sleep or nocturnal motricity in polysomnographic studies; increased sleep onset latency and shorter sleep time in actigraphic studies; and bedtime resistance, difficulty with morning awakenings, sleep onset difficulties, sleep-disordered breathing, night awakenings and daytime sleepiness in subjective studies. ADHD is also frequently coincident with sleep disorders (obstructive sleep apnea, peripheral limb movement disorder, restless legs syndrome and circadian-rhythm sleep disorders). Psychostimulant medications are associated with disrupted or disturbed sleep, but also ‘paradoxically’ calm some patients with ADHD for sleep by alleviating their symptoms. Long-acting formulations may have insufficient duration of action, leading to symptom rebound at bedtime. Current guidelines recommend assessment of sleep disturbance during evaluation of ADHD, and before initiation of pharmacotherapy, with healthy sleep practices the first-line option for addressing sleep problems. This review aims to provide a comprehensive overview of the relationships between ADHD and sleep, and presents a conceptual model of the modes of interaction: ADHD may cause sleep problems as an intrinsic feature of the disorder; sleep problems may cause or mimic ADHD; ADHD and sleep problems may interact, with reciprocal causation and possible involvement of comorbidity; and ADHD and sleep problems may share a common underlying neurological etiology.

Multimodal MR imaging of brain iron in attention deficit hyperactivity disorder: a noninvasive biomarker that responds to psychostimulant treatment?

To comprehensively assess brain iron levels in typically developing control subjects and patients with attention deficit hyperactivity disorder (ADHD) when psychostimulant medication history is accounted for. This prospective study was approved by the institutional review board, and informed consent was obtained. Brain iron was indexed noninvasively by using magnetic resonance (MR) imaging relaxation rates (R2, R2*, R2') and magnetic field correlation (MFC) in the globus pallidus, putamen, caudate nucleus, and thalamus for 22 patients with ADHD (12 medication-naïve patients and 10 with a history of psychostimulant treatment) and 27 control subjects (age range, 8-18 years). Serum iron measures were also collected. Subgroup differences were analyzed with data-appropriate omnibus tests followed by post hoc pairwise comparisons; false discovery rate correction was conducted to control for multiple comparisons. Medication-naïve ADHD patients had significantly lower striatal and thalamic MFC indexes of brain iron than did control subjects (putamen, P = .012; caudate nucleus, P = .008; thalamus, P = .012) and psychostimulant-medicated ADHD patients (putamen, P = .006; caudate nucleus, P = .010; thalamus, P = .021). Conversely, the MFC indexes in medicated patients were comparable to those in control subjects. No significant differences were detected with R2, R2*, R2', or serum measures. Lower MFC indexes of striatal and thalamic brain iron in medication-naïve ADHD patients and lack of differences in psychostimulant-medicated patients suggest that MFC indexes of brain iron may represent a noninvasive diagnostic biomarker that responds to psychostimulant treatment.

Stimulant treatment of ADHD and cigarette smoking: a meta-analysis.

Individuals with attention-deficit/hyperactivity disorder (ADHD) have a significantly higher risk of cigarette smoking. The nature of the relationship between smoking and psychostimulant medications commonly used to treat ADHD is controversial. Our objective was to examine the relationship between stimulant treatment of ADHD and cigarette smoking by using meta-analysis, and to identify study and sample characteristics that moderate this relationship. Literature searches on PubMed and PsycInfo databases identified published studies for inclusion. Included studies compared cigarette smoking outcomes for stimulant-treated and untreated ADHD individuals. Seventeen studies met inclusion criteria, and 14 (total n = 2360) contained sufficient statistical information for inclusion in the meta-analysis. Two authors extracted odds ratios or frequencies of smokers in the treatment or nontreatment groups, and coded study characteristics including sample source, percentage of male participants, follow-up length, treatment consistency, type of smoking measure, prospective study, and controlling for comorbidities. Meta-analysis revealed a significant association between stimulant treatment and lower smoking rates. Meta-regression indicated that effect sizes were larger for studies that used clinical samples, included more women, measured smoking in adolescence rather than adulthood, conceptualized stimulant treatment as consistent over time, and accounted for comorbid conduct disorder. Nearly all studies were naturalistic, precluding causal inferences. Available data were insufficient to examine additional influences of patient demographics, treatment effectiveness, or other comorbidities. Consistent stimulant treatment of ADHD may reduce smoking risk; the effect was larger in samples with more severe psychopathology. Implications for further research, treatment of ADHD, and smoking prevention are discussed.

Neural activation during response inhibition in adult attention-deficit/hyperactivity disorder: Preliminary findings on the effects of medication and symptom severity

Studies of adults with attention-deficit/hyperactivity disorder (ADHD) have suggested that they have deficient response inhibition, but findings concerning the neural correlates of inhibition in this patient population are inconsistent. We used the Stop-Signal task and functional magnetic resonance imaging (fMRI) to compare neural activation associated with response inhibition between adults with ADHD (N=35) and healthy comparison subjects (N=62), and in follow-up tests to examine the effect of current medication use and symptom severity. There were no differences in Stop-Signal task performance or neural activation between ADHD and control participants. Among the ADHD participants, however, significant differences were associated with current medication, with individuals taking psychostimulants (N=25) showing less stopping-related activation than those not currently receiving psychostimulant medication (N=10). Follow-up analyses suggested that this difference in activation was independent of symptom severity. These results provide evidence that deficits in inhibition-related neural activation persist in a subset of adult ADHD individuals, namely those individuals currently taking psychostimulants. These findings help to explain some of the disparities in the literature, and advance our understanding of why deficits in response inhibition are more variable in adult, as compared with child and adolescent, ADHD patients.

Reducing Creativity With Psychostimulants May Debilitate Mental Health and Well-Being

Recently, healthy individuals have been using psychostimulants for cognitive enhancement purposes. Psychostimulant medications may increase wakefulness, but as a tradeoff, they may constrict cognitive flexibility and reduce creativity in healthy individuals with no psychiatric disorders. In this perspective, the author addresses the ethical and prudential issues that arise from impairing creativity with psychostimulants. As there is a strong relationship between creativity and positive mental health, the author argues that creativity is an important character strength. Hence, reducing it with psychostimulants will impair an intrinsically and instrumentally valuable trait, which will in the long term reduce well-being and negatively impact the positive mental health of the healthy individual and the flourishing of society. The author concludes that using psychostimulants as a form of cognitive enhancement in healthy adults is imprudent and morally suspect for society.PERSPECTIVES is a special feature included in this issue of Journal of Creativity in Mental Health that provides mental health professionals with an opportunity to discuss their positions on a variety of creativity-related topics.In this article, Dr. Mohamed shares his view of the ethical and prudential issues that arise from impairing creativity with psychostimulants.Dr. Ahmed Dahir Mohamed is a chartered psychologist member of the British Psychological Society. His Ph.D., which was awarded in 2013 by the Department of Psychiatry at the University of Cambridge, was in the area of cognitive enhancement. Using modafinil as a pharmacological probe, his work explored how drugs like modafinil, Adderall, and methylphenidate (Ritalin) affect cognitive and affective functions in healthy individuals with no psychiatric disorders. His work has been published in highly regarded academic journals including the International Journal of Neuropsychopharmacology, The American Journal of Bioethics: Neuroscience, The Journal of Ethics in Mental Health, and The British Journal of Counselling and Psychotherapy. Dr. Mohamed was the previous winner of the Nuffield Science Bursary Award for outstanding research in psychology and the Wellcome Trust Doctoral Neuroscience studentship award. In 2013, Dr. Mohamed became an Elected Life Academic Member of Clare Hall at the University of Cambridge. Dr. Mohamed is currently editing an Oxford University Press handbook entitled Rethinking Cognitive Enhancement: The Neuroscience and Ethics of Cognitive and Physical Enhancement.This article is based on an invited lecture given at the St. Cross Ethics Seminars at Oxford. Dr Mohamed was a visiting academic scholar at St. Cross College and a recognized DPhil student at the Oxford Centre for Neuroethics at the University of Oxford.

EPA-0154 – Influence of psychostimulants on temperament and character profiles in adult adhd patients

Several Clinical studies have shown specific Temperament and Character Profiles in adult ADHD patients. In all studies drug naive patients were included. The present study was set up to assess whether adult ADHD patients referred to an outpatient clinic would show altered temperament and character profiles after they were put on psychostimulant medication. During 18 months patients were recruited randomly from two out patient Clinics in Western Brabant, The Netherlands. ADHD symptoms were rated with the ASRS-Dutch version and temperament and character with the VTCI, a shortened Dutch translation of the TCI. Patients were assessed just before the first prescription of psychostimulants (T0) and after subjective clinical effect of the medication (T1). 48 patients gave informed consent and in total 38 completed the study. Significant differences between T1 and T0 were found for Novelty Seeking, Harm Avoidance, Self- Directedness and Self-Transcendence. Adult ADHD patients can experience significant differences in temperament and character profiles after taking psychostimulant medication, suggesting different attitudes in daily life like carefulness, resilience, selfimage and sense of belonging are encouraged. It is important to discuss these issues with ADHD patients.

Effectiveness of Osmotic-Controlled Release Oral Delivery System Methylphenidate in the Treatment of Stuttering that Combined with Attention-Deficit/Hyperactivity Disorder: A Case Report

Attention-Deficit/Hyperactivity Disorder (ADHD) is the most common neurodevelopmental disorder in children that shows comorbidity with several psychopathology included stuttering. The prefrontal cortex is the area of brain that sends and receives projections from virtually all cortical sensory systems, motor systems, and many subcortical structures. It has been shown that psychostimulant medication increases activation of the inferior prefrontal cortex and the basal ganglia. Both functional neuroimaging and neuropsychological studies show that psychostimulant medication improves executive functions. Verbal fluency is also considered as one of the executive functions. In this article, we report osmotic-controlled release oral delivery system (OROS) methylphenidate treatment effectiveness of stuttering that combined with ADHD.

Effects of Stimulants on Brain Function in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis

BackgroundPsychostimulant medication, most commonly the catecholamine agonist methylphenidate, is the most effective treatment for attention-deficit/hyperactivity disorder (ADHD). However, relatively little is known on the mechanisms of action. Acute effects on brain function can elucidate underlying neurocognitive effects. We tested methylphenidate effects relative to placebo in functional magnetic resonance imaging (fMRI) during three disorder-relevant tasks in medication-naïve ADHD adolescents. In addition, we conducted a systematic review and meta-analysis of the fMRI findings of acute stimulant effects on ADHD brain function.MethodsThe fMRI study compared 20 adolescents with ADHD under either placebo or methylphenidate in a randomized controlled trial while performing stop, working memory, and time discrimination tasks. The meta-analysis was conducted searching PubMed, ScienceDirect, Web of Knowledge, Google Scholar, and Scopus databases. Peak coordinates of clusters of significant effects of stimulant medication relative to placebo or off medication were extracted for each study.ResultsThe fMRI analysis showed that methylphenidate significantly enhanced activation in bilateral inferior frontal cortex (IFC)/insula during inhibition and time discrimination but had no effect on working memory networks. The meta-analysis, including 14 fMRI datasets and 212 children with ADHD, showed that stimulants most consistently enhanced right IFC/insula activation, which also remained for a subgroup analysis of methylphenidate effects alone. A more lenient threshold also revealed increased putamen activation.ConclusionsPsychostimulants most consistently increase right IFC/insula activation, which are key areas of cognitive control and also the most replicated neurocognitive dysfunction in ADHD. These neurocognitive effects may underlie their positive clinical effects.

Guanfacine Extended Release: A Novel Treatment for Attention-Deficit/Hyperactivity Disorder in Children and Adolescents

BackgroundGuanfacine extended release (GXR) has reported efficacy for the treatment of attention-deficit/hyperactivity disorder (ADHD) as monotherapy and adjunctive therapy to psychostimulant medications. ObjectiveThe objective of this article was to review the efficacy, safety profile, mechanism of action, pharmacokinetics, and appropriate dosing of GXR in children and adolescents with ADHD. MethodsPertinent English-language literature was identified from searches of MEDLINE (1950–February 2012), BIOSIS (1969–February 2012), and EMBASE (1974–February 2012). Search terms included guanfacine, guanfacine extended release, attention deficit disorder with hyperactivity, ADHD, nonstimulant, and alpha-2 adrenergic receptor. Of the 49 publications identified, 12 are reviewed herein. Citations from identified articles were reviewed for additional references. Abstracts and posters presented at recent scientific meetings and data included in the prescribing information were also reviewed. ResultsStudies of GXR have demonstrated efficacy as once-daily monotherapy as well as adjunctive therapy to psychostimulants for ADHD in short-term trials. The safety profile of GXR is consistent with that of a centrally acting α2A-adrenoceptor agonist. Somnolence, sedation, and hypersomnia adverse events (AEs), although frequent, are typically mild to moderate and tend to diminish with continued treatment. However, 1 long-term, open-label study found that 22 serious treatment-emergent AEs occurred in 16 (6.2%) of 259 subjects, and another found that 26% of subjects discontinued therapy due to AEs. The cardiovascular effects, of GXR are consistent with guanfacine’s known effects, and are generally modest in nature. The mechanism of action of GXR in ADHD is unknown. Because the pharmacokinetics of immediate-release guanfacine differ from GXR, dose substitution on a milligram-for-milligram basis is inappropriate. Clinical trials analyzed according to weight-adjusted doses suggest a dose-response relationship for efficacy. Doses >4 mg/d cannot be recommended due to lack of study data at those doses. ConclusionsCurrent evidence indicates that GXR is an effective treatment option for children and adolescents with ADHD. AEs are typically mild to moderate, although severe AEs and discontinuations due to AEs have been observed.