Doses Of Methylphenidate Research Articles

Discriminating cocaine use from other sympathomimetics using wearable electrocardiographic (ECG) sensors

BackgroundOur group has established the feasibility of using on-body electrocardiographic (ECG) sensors to detect cocaine use in the human laboratory. The purpose of the current study was to test whether ECG sensors and features are capable of discriminating cocaine use from other non-cocaine sympathomimetics. MethodsEleven subjects with cocaine use disorder wore the Zephyr BioHarness™ 3 chest band under six experimental (drug and non-drug) conditions, including 1) laboratory, intravenous cocaine self-administration, 2) after a single oral dose of methylphenidate, 3) during aerobic exercise, 4) during tobacco use (N=7 who smoked tobacco), and 5) during routine activities of daily inpatient living (unit activity). Three ECG-derived feature sets served as primary outcome measures, including 1) the RR interval (i.e., heart rate), 2) a group of ECG interval proxies (i.e., PR, QS, QT and QTc intervals), and 3) the full ECG waveform. Discriminatory power between cocaine and non-cocaine conditions for each of the three outcomes measures was expressed as the area under the receiver operating characteristics (AUROC) curve. ResultsAll three outcomes successfully discriminated cocaine use from unit activity, exercise, tobacco, and methylphenidate conditions with a mean AUROC values ranging from 0.66 to 0.99 and with least squares means values all statistically different/higher than 0.5 among all subjects [F(3, 99) = 3.38, p =0.02] and among those with tobacco use [F(4, 84) = 5.39, p = 0.0007]. ConclusionsThese preliminary results support discriminatory power of wearable ECG sensors for detecting cocaine use.

Methylphenidate induces a different response in the dorsal raphe as compared to ventral tegmental area and locus coeruleus: behavioral and concomitant neuronal recordings in adult rats.

Methylphenidate (MPD) is a psychostimulant used to treat attention deficit hyperactivity disorder. MPD exerts its neurocognitive effects through increasing concentrations of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in the neuronal synapse. This study recorded from adult freely behaving rats a total of 1170 neurons, 403 from the ventral tegmental area (VTA), 409 from locus coeruleus (LC), and 356 from dorsal raphe (DR) nucleus, which are the main sources of DA, NE, and 5-HT to the mesocorticolimbic circuitry, respectively. Electrophysiological and behavioral activities were recorded simultaneously following acute and repetitive (chronic) saline or 0.6, 2.5, or 10.0mg/kg MPD. The uniqueness of this study is the evaluation of neuronal activity based on the behavioral response to chronic MPD. Animals received daily saline or MPD administration on experimental days 1-6 (ED1-6), followed by a 3-day wash-out period, and then MPD rechallenge on ED10. Each chronic MPD dose elicits behavioral sensitization in some animals, while in others, behavioral tolerance. Neuronal excitation following chronic MPD was observed in brains areas of animals exhibiting behavioral sensitization, while neuronal attenuation following chronic MPD was observed in those animals expressing behavioral tolerance. DR neuronal activity was most affected in response to acute and chronic MPD administration and responded differently compared to the neurons recorded from VTA and LC neurons at all doses. This suggests that although not directly related, DR and 5-HT are involved in the acute and chronic effects of MPD in adult rats, but exhibit a different role in response to MPD.

The effect of methylphenidate for giggle incontinence in children.

Giggle incontinence (GI) is a rare form of urinary incontinence that occurs during or immediately after laughing due to involuntary and complete bladder emptying. Few studies in the literature report that methylphenidate can be effective in treatment of this condition. The aim of this study is to characterize children with GI and evaluate their response to methylphenidate, as well as describe treatment duration, dosage of methylphenidate, relapse rates after discontinuation of medication, and side effects. Medical records and 48-hfrequency-volume charts from children treated with methylphenidate for GI in the period January 2011-July 2021 were retrospectively analyzed. Eighteen children were diagnosed with GI and fulfilled inclusion criteria. Fifteen patients were included in analysis, as 3 out of 18 children decided not to take the methylphenidate that was prescribed. In total, 14 out of the 15 GI patients treated with methylphenidate experienced clinical effect. All patients included in the study had methylphenidate prescribed in a dose range of 5-20 mg daily. Treatment duration ranged from 30 to 1001 days, with a median of 152 days (IQR 114, 243.5). Ten children experienced complete response and two of those reported symptom relapse after discontinuation of the methylphenidate. Only mild and short-lasting side effects were reported by two patients. Our study demonstrates that methylphenidate is an effective treatment in children diagnosed with GI. Side effects are mild and uncommon.

The effect of long-term use of methylphenidate on cardiac autonomic functions and ventricular arrhythmogenesis: a prospective case-control study.

We aimed to assess cardiac autonomic balance with heart rate variability by using 24-hour Holter electrocardiography and also to assess susceptibility to ventricular arrhythmias by using microvolt T wave alternance in children with attention deficit hyperactivity disorder. This study was conducted with age- and gender-matched groups of 40 patients taking long-acting methylphenidate for more than a year and 55 healthy controls. Heart rate variability analysis for cardiac autonomic functions and microvolt T wave alternance measurements for susceptibility to ventricular arrhythmias were evaluated by 24-hour Holter electrocardiography. The mean age 10.9 ± 2.7 years, mean duration of therapy 22.76 months, and mean methylphenidate doses were 37.64 mg/day. The study group had considerably higher rMSSD, higher HF, and a lower LF/HF ratio (respectively, p : 0.02, p : 0.001 and p : 0.01). While parasympathetic activity parameters were elevated, sympathetic activity parameters were low during the sleep period. Increase in the microvolt T wave alternance values of the study group was not found to be statistically significant (p > 0.05). In children taking long-acting methylphenidate, the autonomic balance was shown to be in favour of the parasympathetic system. Determination of the vulnerability to life-threatening ventricular arrhythmias has been evaluated for the first time in children with attention deficit hyperactivity disorder. Accordingly, microvolt T-wave alternance values give the notion that drug use is safe.

Behavioral, Neurochemical and Developmental Effects of Chronic Oral Methylphenidate: A Review.

The majority of animal studies on methylphenidate (MP) use intraperitoneal (IP) injections, subcutaneous (SC) injections, or the oral gavage route of administration. While all these methods allow for delivery of MP, it is the oral route that is clinically relevant. IP injections commonly deliver an immediate and maximum dose of MP due to their quick absorption. This quick-localized effect can give timely results but will only display a small window of the psychostimulant's effects on the animal model. On the opposite side of the spectrum, a SC injection does not accurately represent the pathophysiology of an oral exposure because the metabolic rate of the drug would be much slower. The oral-gavage method, while providing an oral route, possesses some adverse effects such as potential animal injury and can be stressful to the animal compared to voluntary drinking. It is thus important to allow the animal to have free consumption of MP, and drinking it to more accurately mirror human treatment. The use of a two-bottle drinking method allows for this. Rodents typically have a faster metabolism than humans, which means this needs to be considered when administering MP orally while reaching target pharmacokinetic levels in plasma. With this oral two-bottle approach, the pathophysiological effects of MP on development, behavior, neurochemistry and brain function can be studied. The present review summarizes these effects of oral MP which have important implications in medicine.

An exploratory analysis of the performance of methylphenidate regimens based on a PKPD model of dopamine and norepinephrine transporter occupancy.

Methylphenidate (MPH) is a psychostimulant which inhibits the uptake of dopamine and norepinephrine transporters, DAT and NET, and is mostly used to treat Attention Deficit/Hyperactivity Disorder. The current dose optimization is done through titration, a cumbersome approach for patients. To assess the therapeutic performance of MPH regimens, we introduce an in silico framework composed of (i) a population pharmacokinetic model of MPH, (ii) a pharmacodynamic (PD) model of DAT and NET occupancy, (iii) a therapeutic box delimited by time and DAT occupancy, and (iv) a performance score computation. DAT occupancy data was digitized (n = 152) and described with Emax models. NET occupancy was described with a KPD model. We used this integrative framework to simulate the performance of extended-release (18-99mg) and tid MPH regimens (25-40mg). Early blood samples of MPH seem to lead to higher DAT occupancy, consistent with an acute tolerance observed in clinical rating scales. An Emax model with a time-dependent tolerance was fitted to available data to assess the observed clockwise hysteresis. Peak performance is observed at 63mg. While our analysis does not deny the existence of an acute tolerance, data precision in terms of formulation and sampling times does not allow a definite confirmation of this phenomenon. This work justifies the need for a more systematic collection of DAT and NET occupancy data to further investigate the presence of acute tolerance and assess the impact of low MPH doses on its efficacy.

Methylphenidate dose–response in children with ADHD: evidence from a double-blind, randomized placebo-controlled titration trial

Methylphenidate (MPH) is highly efficacious in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Generally increased doses are found to result in better symptom control; however, it remains unclear whether this pattern can be observed at the individual level, given the large heterogeneity in individual dose–response relationships and observed placebo responses. A double-blind, randomized, placebo-controlled cross-over trial was used to compare weekly treatment with placebo and 5, 10, 15 and 20 mg of MPH twice daily on parent and teacher ratings of child ADHD symptoms and side effects. Participants were 5–13-year-old children with a DSM-5 diagnosis of ADHD (N = 45). MPH response was assessed at group and individual levels and predictors of individual dose–response curves were examined. Mixed model analysis showed positive linear dose–response curves at group level for parent and teacher rated ADHD symptoms and parent rated side effects, but not for teacher rated side effects. Teachers reported all dosages to improve ADHD symptoms compared to placebo, while parents only reported > 5 mg/dose as effective. At the individual level, most (73–88%) children, but not all, showed positive linear dose–response curves. Higher severity of hyperactive-impulsive symptoms and lower internalizing problems, lower weight, younger age and more positive opinions towards diagnosis and medication partly predicted steeper linear individual dose–response curves. Our study confirms that increased doses of MPH yield greater symptom control at a group level. However, large interindividual variation in the dose–response relationship was found and increased doses did not lead to greater symptom improvement for all children. This trial was registered in the Netherlands trial register (# NL8121).

Use of Methylphenidate to Improve Cognition in Autism Spectrum Disorder (ASD)

IntroductionMethylphenidate (MPH) is used to treat attention deficit hyperactivity disorder (ADHD) and has shown unique benefits in children and adolescents with autism spectrum disorder (ASD). In addition to improving attention, hyperactivity, and repetitive movement, it also improves cognition in ASD. Our focus is to explore the understudied benefits and safety of methylphenidate use for cognition in ASD children.Objectives1) To study the response and benefit of methylphenidate in autistic kids to improve cognition and life function.2) To assess the safety profile and risks of using methylphenidate at different doses in children with autism as a guiding tool for prescribing physicians.MethodsA literature search was conducted using relevant medical subject headings (MeSH) terms in PubMed, Medline, and PubMed Central. We identified all published articles from inception until September 30, 2022. Initial search results found 41 studies, of which 15 were excluded as they did not meet inclusion and exclusion criteria. After a thorough full-text review, we included 5 studies in our final qualitative synthesis review.ResultsMethylphenidate was found to have the unique benefit of increasing cognitive processing speed, thus improving everyday life function in ASD and ADHD children compared with only ADHD, with a clinical significance of p<0.001. Stimulants may improve the processing of social situations and interactions or social functions due to this unique response (Peled, J et al. Nordic journal of psychiatry 2020; 74(3), 163–167) A clinically significant performance gain on cognitive tasks was identified with a linear dose-response at three different doses (10 mg, 15 mg, 20 mg) of methylphenidate. ASD children with ADHD made significantly fewer omission errors, [F(3,69) = 7.21, p < 0.001], and commission errors [F(3,69) = 4.64, p = 0.005] on MPH, compared to placebo. They also showed more response at higher MPH doses, [F(3,69) = 10.45, p < 0.001]. Thus, the children were faster, more accurate, and had fewer errors at higher MPH doses (Pearson, D. A. et al. Journal of child and adolescent psychopharmacology 2020; 30(7), 414–426). There were no serious side effects or suicidality reported for low dose and a medium dose of MPH in ASD children assessed with Response Impressions and Side Effects Checklist-Kids (RISC-K), A 38-item parent rating scale (Kim, S. J. et al. Journal of autism and developmental disorders 2017; 47(8), 2307–2313).ConclusionsThe findings support the positive response of methylphenidate on cognitive function in ASD children. No serious adverse effects or suicidality were noted. Multi-center well-designed studies are recommended to determine further efficacy and safety of MPH in ASD children for cognition.Disclosure of InterestNone Declared

Pharmacological Treatment of Children and Adolescents Diagnosed with Attention-deficit/hyperactivity Disorder at Mental Health Services in Qatar: A Retrospective Study

Background: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common mental disorders affecting children. The consequences of ADHD could seriously impact the patient’s life, and thus parental training, behavioral therapies, and pharmacological interventions are the main therapeutic options applied. This study was conducted to explore the trends of prescribing pharmacological medications used in ADHD and identify the reasons for discontinuation of such medications. Methodology: A retrospective chart review for patients diagnosed with ADHD at Child and Adolescent Mental Health Services (CAMHS) in Qatar from January 2019 to December 2019 was carried out. Patients less than 18 years old, diagnosed with ADHD as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and were on pharmacological treatment for ADHD were suitable to be included. Patients who were not on anti-ADHD medications were excluded from the study. Results: Ninety-two patients were eligible to be included in the study. Autism Spectrum Disorder (ASD) was found to be the most coexisting condition in addition to ADHD in 16.3%. Methylphenidate was the most prescribed medication (68.5%), followed by atomoxetine (30.4%). None of the participants were found on modafinil, guanfacine, bupropion, or benzodiazepines, and none exceeded the maximum licensed dose of either methylphenidate or atomoxetine. Half (50%) of the sample on atomoxetine discontinued treatment compared to 14.2% in the methylphenidate group. Conclusion: The clinical practice of prescribing pharmacological options for ADHD was thoroughly in alignment with international guidelines. The effects of long-term use of these psychotropics in this particular group of patients on their neurobiological, behavioral, and physical health should be studied further.

Overactivated contextual visual perception and response to a single dose of methylphenidate in children with ADHD.

The pathogenesis of overactivated visual perception in attention-deficit hyperactivity disorder (ADHD) remains unclear, which is interpreted as a cognitive compensation. The existing studies have proposed that perceptual abnormalities in neurodevelopmental disorders are associated with dysfunction of the contextual knowledge system, which influences the development and formation of perception. We hypothesized that alterations in contextual states may also be responsible for inducing perceptual abnormalities in ADHD. Therefore, the present study evaluated the characteristics of pre-stimulus alpha and its response to a single dose of methylphenidate (MPH). A total of 135 Chinese children participated in the first study, including 70 children with ADHD (age = 10.61 ± 1.93years, female = 17) and 65 age- and sex-matched control children (age = 10.73 ± 1.93years, female = 20). The second clinical trial included 19 Chinese children with ADHD (age = 11.85 ± 1.72years, female = 4), with an identical visual spatial search task. Pre-stimulus alpha oscillations and P1 activity were significantly greater in children with ADHD than in the controls. Overactivated pre-stimulus alpha positively predicted P1. Both pre-stimulus alpha and P1 overactivation have beneficial effects on cognitive performance in children with ADHD. No intervening effect of a single dose of MPH on the compensatory activation of pre-stimulus alpha and P1 were observed. Our findings extended the perceptual activation to the contextual knowledge system, suggesting that compensatory perception in children with ADHD is more likely to be a top-down regulated cognitive operational process.

Effects of methylphenidate on impulsive choice and delay aversion in Lewis rats.

Attention-deficit/hyperactivity disorder (ADHD), a common behavioral disorder in children and young adults, is characterized by symptoms of impulsivity, inattention, and hyperactivity. The purpose of this study was to evaluate the Lewis rat strain as a model of ADHD by testing their impulsive choices. Lewis rats were compared to their source strain, the Wistar rat, on an impulsive choice task. Rats completed the tasks on and off methylphenidate, a commonly prescribed medication for ADHD. Off methylphenidate, Lewis rats made more impulsive choices than Wistar rats. Analyses of acquisition of choice behavior suggested that both strains were able to discriminate reward sizes, but Lewis rats still chose the smaller-sooner option more than the larger-later (LL) option when the delays to reward were the same. This may be due to an aversion to the LL lever, which was associated with the longest delays to reward. Higher doses of methylphenidate increased LL choices in Lewis rats but decreased LL choices in Wistar rats. Altogether, these results suggest Lewis rats may be a viable model for ADHD in individuals whose symptoms are characterized by impulsive choices.

Methylphenidate is more effective to improve inhibitory control and working memory compared to tDCS in children and adolescents with attention deficit/hyperactivity disorder: a proof-of-concept study.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by an inappropriate, pervasive and persistent pattern of inattention, hyperactivity, and/or impulsivity and associated with substantial functional impairment. Despite considerable advances in the understanding and management of ADHD, some patients do not respond well to methylphenidate (MPH), the first-choice pharmacological treatment. Over the past decades, among non-invasive brain stimulation techniques, transcranial direct current stimulation (tDCS) has proven to be an effective and safe technique to improve behavior and cognition in children with neurodevelopmental disorders, including ADHD, by modifying cortical excitability. However, the effect of tDCS has never been directly compared with that of the MPH. The present randomized sham-controlled trial evaluated the effect of a single session of anodal tDCS compared with the administration of a single dose of MPH in children and adolescents with ADHD. After completing baseline assessment (T0), 26 children and adolescents with ADHD were exposed to 3 conditions with a 24-h interval-sessions: (A) a single session of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC); (B) a single session of sham tDCS over the left DLPFC; (C) a single dose of MPH. Our results showed that after administering a single dose of MPH, children and adolescents with ADHD improved inhibitory control and visual-spatial WM compared with baseline, anodal, and sham tDCS. However, a single session of active tDCS over the left DLPFC was not effective compared with either baseline or sham tDCS. In conclusion, our protocol in ADHD involving a single tDCS session did not demonstrate consistent improvements in neurocognitive features compared with baseline, sham tDCS, or single MPH administration. Different protocols need to be developed to further test the effectiveness of tDCS in improving ADHD symptoms.

Methylphenidate improves cognitive function and health-related quality of life in survivors of childhood brain tumours

ABSTRACT Objectives: The growing population of survivors of childhood brain tumors present the challenge of long-term quality of survival. The domains most affected by tumor and treatment are those implicated in development of typical intellectual functions: attention, working memory, and processing speed, with consequent effects upon function and quality of life. In this paper we present service evaluation data on the 12-month effect upon processing speed, visual and auditory attentional domains in 29 patients receiving methylphenidate aged 5-16 years (Mean=10.6). Methods: Patients received immediate-release methylphenidate and were converted to modified-release as appropriate. Mean optimal dose of immediate-release methylphenidate was 0.34 mg/kg per dose (range 0.2-0.67). Results: Patients showed a significant positive impact of methylphenidate on attention in all tests of selective visual attention from the Test of Everyday Attention for Children 2. A significant improvement was also shown on response time. Significant change was not found on psychometric measures of sustained auditory or visual attention, or selective auditory attention. Ratings of Health-Related Quality of Life showed a positive benefit of methylphenidate at 12 months. Side effects were minimal and not statistically significant. Conclusions: Survivors of childhood brain tumor with attentional and processing speed deficit show clinical benefit from methylphenidate.

Open assessment of the therapeutic and rate-dependent effects of brain balance center® and interactive metronome® exercises on children with attention deficit hyperactivity disorder

The aim of this open study was to delineate domains of benefit and effect size measures to design an appropriately powered randomized control trial to assess the efficacy of Brain Balance@ exercises and Interactive Metronome@ training (BB/IM) on ADHD symptoms in children. Participants underwent an extensive 15-week, 5 time per week, at-home training program. Results were assessed in 16 youths with ADHD (14M/2F, 10.8±1.7 years) who completed the program and compared to 8 typically developing controls (4M/F4, 11.0±1.8 years). BB/IM was associated with a significant reduction of 8.3 and 8.2 points on the Conner's Parent Rating Scale – Revised and the ADHD Rating Scale – IV. BB/IM was not associated with improvement on the Quotient ADHD System but with rate-dependent effects on hyperactivity and attention that were similar to previously reported effects of low dose methylphenidate. Both therapeutic and rate-dependent effects were observed on the Tower of London. The study provides information that could be used to design a randomized control trial, which is required for proof of efficacy. A key limitation is that 59% of the 39 enrolled participants with ADHD dropped out of the study and a new study should include multiple ratings during the course of treatment.

The Influence of Cannabidiol on the Pharmacokinetics of Methylphenidate in Healthy Subjects

Introduction: Cannabidiol (CBD) is a widely utilized nonpsychoactive cannabinoid available as an over-the-counter supplement, a component of medical cannabis, and a prescriptive treatment of childhood epilepsies. In vitro studies suggest CBD may inhibit a number of drug-metabolizing enzymes, including carboxylesterase 1 (CES1). The aim of this study was to evaluate effect of CBD on the disposition of the CES1 substrate methylphenidate (MPH). Methods: In a randomized, placebo-controlled, crossover study, 12 subjects ingested 750 mg of CBD solution, or alternatively, a placebo solution twice daily for a 3-day run-in period followed by an additional CBD dose (or placebo) and a single 10 mg dose of MPH and completed serial blood sampling for pharmacokinetic analysis. MPH and CBD concentrations were measured by liquid chromatography with tandem mass spectrometry. Results: The Cmax (mean ± CV) for the CBD group and placebo group was 13.5 ± 43.7% ng/mL and 12.2 ± 36.4% ng/mL, respectively. AUCinf (ng/mL*h) for the CBD group and placebo group was 70.7 ± 32.5% and 63.6 ± 25.4%, respectively. The CBD AUC0-8h (mean ± CV) was 1,542.2 ± 32% ng/mL*h, and Cmax was 389.2 ± 39% ng/mL. When compared to MPH only, the geometric mean ratio (CBD/control, 90% CI) for AUCinf and Cmax with CBD co-administration was 1.09 (0.89, 1.32) and 1.08 (0.85, 1.37), respectively. Discussion/Conclusion: Although the upper bound of bioequivalence was not met, the mean estimates of AUC and Cmax ratios were generally small and unlikely to be of clinical significance.

Evaluating the relationship between Ex3 vNTR and rs3758653 polymorphisms in DRD4 genes in children with attention deficit hyperactivity disorder with respect to the dose of methylphenidate

Background. Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders starting at an early age with symptoms of attention deficit hyperactivity disorder and impulsivity. This study aimed to investigate the molecular alterations of the DRD4 gene, which have been linked to ADHD in previous studies with respect to the dose of methylphenidate. Methods. The study population included all ADHD patients needing drug therapy aged 5-18 years referred to Bozorgmehr psychiatric clinic in Tabriz in 2017 for one year. After diagnosis, symptoms severity was assessed using the Conners Scale for ADHD Assessment. Then, 4 ml of blood was collected from each individual and DNA was extracted using salting out method. After performing polymerase chain reaction (PCR), the products were separated using specific restriction enzymes and then polymorphisms of Ex3 VNTR and rs3758653 of DRD4 gene were analyzed in 2% agarose gel. The last dose to achieve the therapeutic response was recorded in mg/kg. Then, we investigated the relationship between the doses of drug used to achieve the therapeutic response and the existence of the mentioned polymorphisms. Results. There was no significant relationship between treatment response and type of polymorphism. Also, there was no significant relationship between the average dose of drug and the polymorphisms of three replicates, four replicates, six replicates, and more than six replicates in EX3VNTR in DRD4 gene. In addition, we witnessed no statistically significant relationship between the mean drug dose and CC, TC, and TT genotypes in DRD4rs3758653. Conclusion. There was no significant relationship between treatment response and type of polymorphism. There was no significant relationship between the average dose of drug and the polymorphisms of three replicate, four replicates, six replicates and more than six replicates in EX3VNTR in DRD4 gene. Between mean drug dose and CC, TC and TT genotypes in DRD4rs3758653, there was no statistically significant relationship. Practical Implications. Determining the reduction of ADHD symptoms by taking methylphenidate and evaluating the relationship between presence or absence of DRD4 polymorphisms and the dosage of drug to achieve a better response to treatment can collect enough evidence to determine the dose of methylphenidate according to the molecular analysis of DRD4 gene in patients with ADHD. This can reduce doctor visits, save time, and decrease the drug side effects.

Ignore the glitch but mind the switch: Positive effects of methylphenidate on cognition in attention deficit hyperactivity disorder are related to prediction gain

Neuropsychological symptoms such as inattention and distractibility constitute a core characteristic of attention deficit hyperactivity disorder (ADHD). Here, we tested the hypothesis that attentional dysfunctions result from a deficit in neural gain modulation, which translates into difficulty in predictively weighting relevant sensory input while ignoring distraction.We compared thirty-seven hitherto untreated adults diagnosed with ADHD and thirty-eight healthy participants with a serial switch-drift task that requires internal models of predictable digit sequences to be either updated or stabilized. Switches between sequences that had to be indicated by key presses and digit omissions within a sequence (drifts) that should be ignored varied by stimulus-bound surprise quantified as Shannon information. To investigate whether catecholaminergic modulation by increasing extracellular norepinephrine and dopamine levels leads to an amelioration in prediction gain, participants were tested twice, with patients receiving a single dose of methylphenidate, a norepinephrine/dopamine reuptake inhibitor, in the second session.Patients and controls differed in both updating and stabilizing, depending on the respective event surprise. Specifically, patients showed difficulty in detecting expectable switches, while having greater difficulty to ignore surprising distractions.Thus, underconfident prior beliefs in ADHD may fail to appropriately weight expected relevant input, whereas the gain of neural responses to unexpected irrelevant distractors is increased. Methylphenidate improved both flexibility and stability of prediction and had a positive effect on selective responding over time. Our results suggest that ADHD is associated with an impairment in the use of prior expectations to optimally weight sensory inputs, which is improved by increasing catecholaminergic neurotransmission.

Long-term Methylphenidate Monotherapy for Parkinson’s: Biochemistry Analysis and 17 Year Case Study

Background: Information in this study can improve the health and quality of life of over ten million people with Parkinson’s. This paper presents long-term treatment of Parkinson’s with Methylphenidate that was found safe and effective to use instead of traditional anti-Parkinsonians such as Carbidopa-Levodopa and Pramipexole that cause augmentation (neural damage), excessive sedation, sudden passing out and slowed cognition. Methylphenidate strengthens and protects neural tissues and sustains normal alertness and cognition. Methods: This article analyzes the neurobiochemistry of Methylphenidate-therapy vs. AntiParkinsonian-therapy based on this author’s review of over 400 published studies and guidelines. This article also presents a Case Study involving a case-subject who has a very severe Parkinson’s disorder with a well-documented nine years of AntiParkinsonian-therapy followed by eight years of Methylphenidate-therapy. The case-subject is a 66 year-old male with a PhD who is a published Neurobiochemistry Researcher. At age-55 he was medically documented as disabled and needing medications to function. At age-58 his illness and the adverse effects of APs jointly caused total disability for which there was no known remedy. Thus he conceived and designed the world’s first long-term Methylphenidate treatment of Parkinson’s and implemented it with the cooperation of a prescribing Physician. Results: Adjunctive 30 mg doses of diurnal Methylphenidate overcame adverse effects of AntiParkinsonians. 20 mg doses of diurnal Methylphenidate monotherapy controlled Parkinson’s illness better than AntiParkinsonians. A 3-hour dosing schedule resulted in smooth and uninterrupted efficacy between and across doses of Methylphenidate. Sequential doses every three hours extended efficacy duration to 16 hours. Continued high-dose AntiParkinsonians at bedtime gave good sleep. Conclusion: This author recommends that clinicians use these findings to replace diurnal AntiParkinsonians with diurnal Methylphenidate in order to provide safer and more effective long-term treatment of Parkinson’s illnesses.

Former Training Relieves the Later Development of Behavioral Inflexibility in an Animal Model Overexpressing the Dopamine Transporter

A range of dopamine-dominating neuropsychiatric disorders present with cognitive deficits. In accordance, the dopamine transporter overexpressing rat model (DAT-tg rat) displays cognitive deficits by means of behavioral inflexibility and learning disabilities. It remains to be investigated when cognitive deficits emerge, due to the inherent DA irregularities, during the life course of the DAT-tg rat and what may relieve symptoms. The Morris water maze (MWM) was used to assess cognitive abilities in three cohorts of DAT-tg rats. In the first cohort, the development of cognitive deficits was assessed by repeatedly testing animals in the MWM at postnatal day (PND) 35, 60, and 90. In the second and third cohort, pharmacological interventions and transcranial direct current stimulation (tDCS) were tested in adult animals to understand what drives, and thus relieves, the deficits. Minor differences were observed between DAT-tg rats and control rats at PND 35 and 60, whereas cognitive deficits fully emerged at PND 90. A high dosage of methylphenidate diminished both behavioral inflexibility and improved learning abilities in adult rats. Interestingly, rats subjected early in life to the MWM also displayed improved behavioral flexibility as compared to rats naïve to the paradigm. Cognitive deficits gradually develop over time and fully emerge in adulthood. Pharmacological modulation of the ubiquitous DAT overexpression overall improves deficits in adult rats, whereas early training decreases later development of behavioral inflexibility. Thus, former training may constitute a preventive avenue that alters some aspects of cognitive deficits resulting from inherent DA abnormalities.

Investigating the effects of age, IQ, dosing, and anthropometric measures on the treatment persistence in long-term methylphenidate use

Objectives This study aimed to determine anthropometric and clinical correlates of persistence to methylphenidate (MPH) treatment in Turkish youth with attention-deficit hyperactivity disorder (ADHD). Methods Data from medical records of 518 children and adolescents with ADHD were recorded between March 2012 and January 2022. Clinical variables of patients persistent to MPH ≥ 2 years were compared with those of the non-persistent group. Children and adolescent age groups were compared using Kaplan–Meier estimates for treatment drop-outs. Cox regression analysis until the treatment drop-out was implemented to calculate hazard ratios (HRs) for gender, age, full-scale IQ, and anthropometric measures. Weight, height, and body mass index (BMI) z-scores were calculated per national guidelines. Results Persistent and non-persistent study groups had similar full-scale IQ, weight, height, and BMI z-scores at treatment onset. The mean MPH dose was significantly higher in the persistent group compared to the non-persistent counterparts (31.43 ± 10.70 vs. 24.28 ± 9.60 mg/d, p < 0.001, d = 0.70). Compared to children, the adolescents showed earlier treatment drop-outs in males (p < 0.001) but not in females (p = 0.110). Younger age showed a positive effect on treatment persistence. Conversely, baseline BMI and IQ scores were not associated with long-term persistence. Discussion Our study demonstrated lower daily doses and older age-onset were associated with early drop-outs in MPH treatment. These findings supported the notion that effective dosing strategies at younger ages could increase the sustainability of the treatment with MPH in the Turkish population.