methylphenidate
Research Papers
Showing 6 of 11Brainmarker-I Differentially Predicts Remission to Various Attention-Deficit/Hyperactivity Disorder Treatments: A Discovery, Transfer, and Blinded Validation Study
BACKGROUND: Attention-deficit/hyperactivity disorder is characterized by neurobiological heterogeneity, possibly explaining why not all patients benefit from a given treatment. As a means to select the right treatment (stratification), biomarkers may aid in personalizing treatment prescription, thereby increasing remission rates. METHODS: The biomarker in this study was developed in a heterogeneous clinical sample (N = 4249) and first applied to two large transfer datasets, a priori stratifying young males (<18 years) with a higher individual alpha peak frequency (iAPF) to methylphenidate (N = 336) and those with a lower iAPF to multimodal neurofeedback complemented with sleep coaching (N = 136). Blinded, out-of-sample validations were conducted in two independent samples. In addition, the association between iAPF and response to guanfacine and atomoxetine was explored. RESULTS: Retrospective stratification in the transfer datasets resulted in a predicted gain in normalized remission of 17% to 30%. Blinded out-of-sample validations for methylphenidate (n = 41) and multimodal neurofeedback (n = 71) corroborated these findings, yielding a predicted gain in stratified normalized remission of 36% and 29%, respectively. CONCLUSIONS: This study introduces a clinically interpretable and actionable biomarker based on the iAPF assessed during resting-state electroencephalography. Our findings suggest that acknowledging neurobiological heterogeneity can inform stratification of patients to their individual best treatment and enhance remission rates.
View Full Paper →Practical considerations for the evaluation and management of Attention Deficit Hyperactivity Disorder (ADHD) in adults
Attention deficit with or without hyperactivity disorder (ADHD) is one of the most frequent neuropsychiatric disorders, and affects 2-4% of adults. In contrast with many European countries, the identification and management of adult ADHD remains underdeveloped in France, and a subject of controversy. This review provides a practical update on current knowledge about ADHD in adults for French-speaking professionals who have to detect or manage adult patients with ADHD. ADHD is classified as a neurodevelopmental disorder in the recent update of the international diagnostic classification. While symptoms and impairment due to ADHD are frequently severe during childhood, they often evolve as children grow older, with frequent persistent disabilities in adulthood. In adulthood, the clinical presentation, as in childhood, involves the symptom triad of inattention, hyperactivity and impulsivity. However, differences are noted: hyperactivity is more often internalized, symptoms of inattention may be masked by anxiety symptoms or obsessive-like compensation strategies. ADHD is often diagnosed during childhood, but it is not rare for the diagnosis to be made later. Failure to recognise symptoms resulting in misdiagnosis, or alternatively well-developed compensation factors could be two underlying reasons for the long delay until diagnosis. Other symptoms, such as emotional deregulation or executive function-related symptoms are also usually observed in adults. In addition, in adults, ADHD is often associated with other psychiatric disorders (in 80% of cases); this makes the diagnosis even more difficult. These disorders encompass a broad spectrum, from mood disorders (unipolar or bipolar), to anxiety disorders, and other neurodevelopmental disorders and personality disorders, especially borderline and antisocial personality disorder. Substance-use disorders are very common, either as a consequence of impulsivity and emotional dysregulation or as an attempt at self-treatment. Sleep disorders, especially restless leg syndrome and hypersomnolence, could share common pathophysiological mechanisms with ADHD. ADHD and comorbidity-related symptoms are responsible for serious functional impairment, in various domains, leading to academic, social, vocational, and familial consequences. The impact on other psychiatric disorders as an aggravating factor should also be considered. The considerable disability and the poorer quality of life among adults with ADHD warrant optimal evaluation and management. The diagnostic procedure for ADHD among adults should be systematic. Once the positive diagnosis is made, the evaluation enables characterisation of the levels of severity and impairment at individual level. A full examination should also assess medical conditions associated with ADHD, to provide personalized care. In recent years, a growing number of assessment tools have been translated and validated in French providing a wide range of structured interviews and standardized self-report questionnaires for the evaluation of core and associated ADHD symptoms, comorbidities and functional impairment. The treatment of ADHD in adults is multimodal, and aims to relieve the symptoms, limit the burden of the disease, and manage comorbidities. The most relevant and validated psychological approaches are psycho-education, cognitive-behavioural therapy and "third wave therapies" with a specific focus on emotional regulation. Cognitive remediation and neurofeedback are promising strategies still under evaluation. Medications, especially psychostimulants, are effective for alleviating ADHD symptoms with a large effect size. Their safety and tolerance are satisfactory, although their long-term clinical benefit is still under discussion. In France, methylphenidate is the only stimulant available for the treatment of ADHD. Unfortunately, there is no authorization for its use among adults except in continuation after adolescence. Hence the prescription, which is subject to the regulations on narcotics, is off-label in France. This article aims to provide practical considerations for the management of ADHD and associated disorders in adults, in this particular French context.
View Full Paper →An RCT into the effects of neurofeedback on neurocognitive functioning compared to stimulant medication and physical activity in children with ADHD
Neurofeedback (NFB) is a potential alternative treatment for children with ADHD that aims to optimize brain activity. Whereas most studies into NFB have investigated behavioral effects, less attention has been paid to the effects on neurocognitive functioning. The present randomized controlled trial (RCT) compared neurocognitive effects of NFB to (1) optimally titrated methylphenidate (MPH) and (2) a semi-active control intervention, physical activity (PA), to control for non-specific effects. Using a multicentre three-way parallel group RCT design, children with ADHD, aged 7-13, were randomly allocated to NFB (n = 39), MPH (n = 36) or PA (n = 37) over a period of 10-12 weeks. NFB comprised theta/beta training at CZ. The PA intervention was matched in frequency and duration to NFB. MPH was titrated using a double-blind placebo controlled procedure to determine the optimal dose. Neurocognitive functioning was assessed using parameters derived from the auditory oddball-, stop-signal- and visual spatial working memory task. Data collection took place between September 2010 and March 2014. Intention-to-treat analyses showed improved attention for MPH compared to NFB and PA, as reflected by decreased response speed during the oddball task [η p2 = 0.21, p < 0.001], as well as improved inhibition, impulsivity and attention, as reflected by faster stop signal reaction times, lower commission and omission error rates during the stop-signal task (range η p2 = 0.09-0.18, p values <0.008). Working memory improved over time, irrespective of received treatment (η p2 = 0.17, p < 0.001). Overall, stimulant medication showed superior effects over NFB to improve neurocognitive functioning. Hence, the findings do not support theta/beta training applied as a stand-alone treatment in children with ADHD.
View Full Paper →Learning curves of theta/beta neurofeedback in children with ADHD
Neurofeedback is widely applied as non-pharmacological intervention aimed at reducing symptoms of ADHD, even though efficacy has not been unequivocally established. Neuronal changes during the neurofeedback intervention that resemble learning can provide crucial evidence for the feasibility and specificity of this intervention. A total of 38 children (aged between 7 and 13 years) with a DSM-IV-TR diagnosis of ADHD, completed on average 29 sessions of theta (4-8 Hz)/beta (13-20 Hz) neurofeedback training. Dependent variables included training-related measures as well as theta and beta power during baseline and training runs for each session. Learning effects were analyzed both within and between sessions. To further specify findings, individual learning curves were explored and correlated with behavioral changes in ADHD symptoms. Over the course of the training, there was a linear increase in participants' mean training level, highest obtained training level and the number of earned credits (range b = 0.059, -0.750, p < 0.001). Theta remained unchanged over the course of the training, while beta activity increased linearly within training sessions (b = 0.004, 95% CI = [0.0013-0.0067], p = 0.005) and over the course of the intervention (b = 0.0052, 95% CI = [0.0039-0.0065], p < 0.001). In contrast to the group analyses, significant individual learning curves were found for both theta and beta over the course of the intervention in 39 and 53%, respectively. Individual learning curves were not significantly correlated with behavioral changes. This study shows that children with ADHD can gain control over EEG states during neurofeedback, although a lack of behavioral correlates may indicate insufficient transfer to daily functioning, or to confounding reinforcement of electromyographic activity. CLINICAL TRIALS REGISTRATION: This trial is registered at the US National Institutes of Health (ClinicalTrials.gov, ref. no: NCT01363544); https://clinicaltrials.gov/show/NCT01363544 .
View Full Paper →Multimodal treatment in children and adolescents with attention-deficit/hyperactivity disorder: a 6-month follow-up
Background: Different treatment approaches aimed at reducing attention-deficit/hyperactivity disorder (ADHD) core symptoms are available. However, factors such as intolerance, side-effects, lack of efficacy, high new technology costs, and placebo effect have spurred on an increasing interest in alternative or complementary treatment. Aim: The aim of this study is to explore efficacy of multimodal treatment consisting of standard stimulant medication (methylphenidate) and neurofeedback (NF) in combination, and to compare it with the single treatment in 6-month follow-up in ADHD children and adolescents. Methods: This randomized controlled trial with 6-month follow-up comprised three treatment arms: multimodal treatment (NF + MED), MED alone, and NF alone. A total of 130 ADHD children/adolescents participated, and 62% completed the study. ADHD core symptoms were recorded pre-/post-treatment, using parents’ and teachers’ forms taken from Barkley’s Defiant Children: A Clinician’s Manual for Assessment and Parent Training, and a self-report questionnaire. Results: Significant ADHD core symptom improvements were reported 6 months after treatment completion by parents, teachers, and participants in all three groups, with marked improvement in inattention in all groups. However, no significant improvements in hyperactivity or academic performance were reported by teachers or self-reported by children/adolescents, respectively, in the three groups. Changes obtained with multimodal treatment at 6-month follow-up were comparable to those with single medication treatment, as reported by all participants. Conclusions: Multimodal treatment using combined stimulant medication and NF showed 6-month efficacy in ADHD treatment. More research is needed to explore whether multimodal treatment is suitable for ADHD children and adolescents who showed a poor response to single medication treatment, and for those who want to reduce the use of stimulant medication.
View Full Paper →Behavioral Effects of Neurofeedback Compared to Stimulants and Physical Activity in Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial
Objective: The efficacy of neurofeedback as a treatment for attention-deficit/hyperactivity disorder (ADHD), and whether neurofeedback is a viable alternative for stimulant medication, is still an intensely debated subject. The current randomized controlled trial compared neurofeedback to (1) optimally titrated methylphenidate and (2) a semi-active control intervention, physical activity, to account for nonspecific effects. Methods: A multicenter 3-way parallel-group study with balanced randomization was conducted. Children with a DSMIV- TR diagnosis of ADHD, aged 7.13 years, were randomly allocated to receive neurofeedback (n = 39), methylphenidate (n = 36), or physical activity (n = 37) over a period of 10.12 weeks. Neurofeedback comprised theta/beta training on the vertex (Cz). Physical activity consisted of moderate to vigorous intensity exercises. Neurofeedback and physical activity were balanced in terms of number (~30) and duration of sessions. A double-blind pseudorandomized placebo-controlled crossover titration procedure was used to determine an optimal dose in the methylphenidate intervention. Parent and teacher ratings on the Strengths and Difficulties Questionnaire (SDQ) and Strengths and Weaknesses of ADHD Symptoms and Normal Behavior (SWAN) were used to assess intervention outcomes. Data collection took place between September 2010 and March 2014. Results: Intention-to-treat analyses revealed an improvement in parent-reported behavior on the SDQ and the SWAN Hyperactivity/Impulsivity scale, irrespective of received intervention (νp2 = 0.21.0.22, P ≤ .001), whereas the SWAN Inattention scale revealed more improvement in children who received methylphenidate than neurofeedback and physical activity (νp2 = 0.13, P ≤ .001). Teachers reported a decrease of ADHD symptoms on all measures for methylphenidate, but not for neurofeedback or physical activity (range of νp2 = 0.14.0.29, P < .001). Conclusions: The current study found that optimally titrated methylphenidate is superior to neurofeedback and physical activity in decreasing ADHD symptoms in children with ADHD
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