Methylphenidate Research Articles

Behavioral and Neurophysiological Signatures of Cognitive Control in Humans and Rats.

Deficits in cognitive control are implicated in numerous neuropsychiatric disorders. However, relevant pharmacological treatments are limited, likely due to weak translational validity of applicable preclinical models used. Neural indices derived from electroencephalography (EEG) may prove useful in comparing and translating the effects of cognition-enhancing drugs between species. In the current study, we aimed to extend our previous cross-species results by examining if methylphenidate (MPH) modulates behavioral and neural indices of cognitive control in independent cohorts of humans and rats. We measured continuous EEG data from healthy adults (n=25; 14 female) and Long Evans rats (n=22; 8 female) and compared both stimulus- and response-locked event-related potentials (ERPs) and spectral power measures across species, and their MPH-related moderation following treatment with vehicle (placebo) or one of two doses of MPH. Across both species, linear mixed effects modeling confirmed the expected Flanker interference effect on behavior (e.g., accuracy) and response-related ERPs. Unexpectedly, in contrast to past work, we did not observe any task-related effects on the spectral power of rodents. Moreover, MPH generally did not modulate cognitive control of either species, although some species-specific patterns offer insight for future research. Collectively, these findings in independent human and rodent subjects replicate some of our previously reported behavioral and neurophysiological patterns partly consistent with the notion that similar neural mechanisms may regulate cognitive control in both species. Nonetheless, these results showcase an approach to accelerate translation using a coordinated between-species platform to evaluate pro-cognitive treatments.

ADHD and Risk of Precocious Puberty: Considering the Impact of MPH.

The complex association between attention-deficit/hyperactivity disorder (ADHD) and methylphenidate (MPH) with precocious puberty (PP) is still unclear. This study aims to investigate the association between ADHD, MPH, and PP. This is a nationwide cohort study including a total of 3,342,077 individuals, 186,681 with ADHD and 3,155,396 without. First, we compared the risk of PP between ADHD cases and non-ADHD cases. Second, we compared the risk of PP between MPH users and non-MPH users in patients with ADHD. Patients with ADHD were at a greater risk of PP (adjusted hazard ratio [aHR], 2.01 [95% CI, 1.91-2.11]). In our moderation analyses, the female gender was a positive additive effect modifier of the association between ADHD and PP, whereas tics and intellectual disability were negative effect modifiers. In patients with ADHD, MPH users had a significantly lower risk of PP (aHR, 0.63 [95% CI 0.57-0.70]), and females had a negative effect modification on the association between MPH and PP. Our study found that children with ADHD were at a greater risk of PP. Girls with ADHD were a group particularly vulnerable to PP. Comorbid tics or intellectual disability was associated with a lower risk of PP. Among patients with ADHD, MPH was protective against PP, especially in girls. However, these preliminary results need further validation due to the nature of them being from an electronic database study. Unmeasured confounding factors might affect the association between MPH and PP.

Scheduling of methylphenidate: Preventing misuse or impeding ADHD treatment adherence?

Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, with a chronic, and potentially debilitating course if untreated. Medication adherence is poor - negatively affecting emotional, social, educational and employment outcomes. The current Schedule 6 status of methylphenidate (MPH) drives healthcare resource utilisation and costs - a potential barrier to care. This study explored stakeholders' understanding and perceptions of the potential impact of a regulatory shift in the scheduling of MPH on treatment accessibility and adherence for ADHD. Participants from multiple stakeholder groups, involved in ADHD management in South Africa, were recruited via professional networks. A qualitative analysis of semi-structured interviews with 23 stakeholders was conducted to explore their views on the utility, benefits and risks associated with rescheduling MPH. Six key themes emerged from the interviews: 'adherence', 'accessibility', 'affordability', 'stigma', 'rescheduling of MPH' and 'risk mitigation'. Core to these themes is the role of the scheduling of MPH - which can have a protective societal role, but also acts as a barrier to care for individuals with ADHD. The current Schedule 6 status of MPH is not an effective strategy to prevent misuse and diversion but negatively impacts on treatment adherence. The positive outlook from stakeholders on rescheduling MPH holds significant implications for the ADHD landscape in South Africa. It is crucial to address stigma, facilitate fundamental change in service delivery and remove structural and practical barriers to care to improve outcomes for individuals with ADHD. A framework for ADHD treatment adherence is provided.

Bioinformatics and experimental validation were combined to explore lactylation-related biomarkers in HBV-associated acute liver failure.

Currently, hepatitis B virus-related acute liver failure (HBV-ALF) has limited treatment options. Studies have shown that histone lactylation plays a role in the progression of liver-related diseases. Therefore, it is essential to explore lactylation-related gene (LRGs) biomarkers in HBV-ALF to provide new information for the treatment of HBV-ALF. Two HBV-ALF-related datasets (GSE38941 and GSE14668) and 65 LRGs were used. First, the differentially expressed genes (DEGs) were derived from differential expression analysis, the key module genes from weighted gene co-expression network analysis; and LRGs were used to intersect to obtain the candidate genes. Subsequently, the feature genes obtained from least absolute shrinkage and selection operator regression analysis and support vector machine analysis were intersected to obtain the candidate key genes. Among them, genes with consistent and significant expression trends in both GSE38941 and GSE14668 were used as biomarkers. Subsequently, biomarkers were analyzed for functional enrichment, immune infiltration, and sensitive drug prediction. In this study, five candidate genes (PIGM, PIGA, EGR1, PIGK, and PIGL) were identified by intersecting 6461 DEGs and 2496 key module genes with 65 LRGs. We then screened four candidate key genes from the machine learning algorithm, among which PIGM and PIGA were considered biomarkers in HBV-ALF. Moreover, the results of enrichment analysis showed that the significant enrichment signaling pathways for biomarkers included allograft rejection and valine, leucine, and isoleucine degradation. Thereafter, 11 immune cells differed significantly between groups, with resting memory CD4+ T cells having the strongest positive correlation with biomarkers. Methylphenidate hydrochloride is a potential therapeutic drug for PIGM. Two genes, PIGM and PIGA, were identified as biomarkers related to LRGs in HBV-ALF, providing a basis for understanding HBV-ALF pathogenesis.

Association between methylphenidate use and long-term cardiovascular risk in paediatric patients with attention deficit and hyperactivity disorder

BackgroundThere have been concerns about the potential cardiovascular (CV) adverse effects associated with methylphenidate (MTH) use. However, only limited evidence exists on the long-term safety of MTH.ObjectiveTo evaluate whether MTH...

Intranasal transfersomal based in situ gel for augmenting methylphenidate bioavailability and brain delivery: In vitro and in vivo evaluation

Methylphenidate, a CNS stimulant drug, has poor oral bioavailability due to extensive first-pass effect. In this study, Methylphenidate loaded transfersomes based in situ gel (MPH-TFs Gel) was prepared for brain targeting through intranasal (IN) drug delivery. Methylphenidate transfersomes (MPH-TFs) were prepared using the thin film hydration method. Box-Behnken Design expert software was utilized for the optimization by assessing the effect of independent variables phospholipon 90-G, Tween-80, and Methylphenidate (MPH) on particle size (PS), zeta potential (ZP), Polydispersity index (PDI), and Entrapment Efficiency (EE). The observed mean particle size of the optimized MPH-TFs was found to be 139.7 ± 3.75 nm, mono dispersion with PDI (0.208 ± 0.002), negatively charged (−27.9 ± 0.287 mV) and had an excellent entrapment efficiency (86 ± 3 %). Fourier-Transform Infrared (FTIR) spectra have depicted the compatibility of the components. X-r Diffraction analysis showed the conversion of crystalline structure methylphenidate to amorphous. The optimized MPH-TFs were then subsequently incorporated into an already optimized MPH-TFs Gel. MPH-TFs Gel was then characterized for its physicochemical properties, in vitro and in vivo studies. In vitro release and ex vivo permeation analysis showed sustained release and improved permeation of the MPH-TFs Gel, respectively. Additionally, histopathological studies of nasal membrane affirmed the safety of MPH-TFs Gel after intranasal application. In vivo pharmacokinetic study demonstrated improved brain bioavailability of MPH-TFs Gel compared to orally administered Methylphenidate solution (MPH-Sol).

Generation of induced pluripotent stem cells from ADHD patients who do or do not respond to Methylphenidate treatment

As a neurodevelopmental multifactorial disorder whose prevalence has been increasing worldwide, attention-deficit hyperactivity disorder (ADHD) is considered a public health concern. Methylphenidate (MPH) is the drug of choice for ADHD; however, not all patients respond fully to this treatment. Therefore, exploring the underlying molecular mechanisms involved in ADHD and potential novel therapeutic targets is crucial. Here, we generated induced pluripotent stem cells (iPSCs) from Peripheral Blood Mononuclear Cells (PBMCs) retrieved from four ADHD patients (two MPH responders and two non-responders) using Sendai virus. These lines might be helpful for the in vitro investigation of ADHD pathophysiology in a patient-specific manner.

Methylphenidate Exposing During Neurodevelopment Alters Amino Acid Profile, Astrocyte Marker and Glutamatergic Excitotoxicity in the Rat Striatum.

There is a public health concern about the use of methylphenidate (MPH) since the higher prescription for young individuals and non-clinical purposes is addressed to the limited understanding of its neurochemical and psychiatric consequences. This study aimed to evaluate the impact of early and chronic MPH treatment on the striatum focusing on amino acid profile, glutamatergic excitotoxicity, redox status, neuroinflammation and glial cell responses. Male Wistar rats were treated with MPH (2.0mg/kg) or saline solution from the 15th to the 44th postnatal day. Biochemical and histological analyses were conducted after the last administration. MPH altered the amino acid profile in the striatum, increasing glutamate and ornithine levels, while decreasing the levels of serine, phenylalanine, and branched-chain amino acids (leucine, valine, and isoleucine). Glutamate uptake and Na+,K+-ATPase activity were decreased in the striatum of MPH-treated rats as well as increased ATP levels, as indicator of glutamatergic excitotoxicity. Moreover, MPH caused lipid peroxidation and nitrative stress, increased TNF alpha expression, and induced high levels of astrocytes, and led to a decrease in BDNF levels. In summary, our results suggest that chronic early-age treatment with MPH induces parallel activation of damage-associated pathways in the striatum and increases its vulnerability during the juvenile period. In addition, data presented here contribute to shedding light on the mechanisms underlying MPH-induced striatal damage and its potential implications for neurodevelopmental disorders.

Enhancing pediatric attention-deficit hyperactivity disorder treatment: exploring the gut microbiota effects of French maritime pine bark extract and methylphenidate intervention.

The pathogenesis of Attention-Deficit Hyperactivity Disorder (ADHD) is thought to be multifactorial, with a potential role for the bidirectional communication between the gut microbiome and brain development and function. Since the "golden-standard" medication therapy with methylphenidate (MPH) is linked to multiple adverse effects, there is a need for alternative treatment options such as dietary polyphenols. These secondary plant metabolites exert antioxidant and anti-inflammatory effects, but much less is known about their impact on the gut microbiota. Since polyphenols are believed to modulate gut microbial composition, interventions might be advantageous in ADHD therapy. Therefore, intervention studies with polyphenols in ADHD therapy investigating the gut microbial composition are highly relevant. Besides the primary research questions addressed previously, this study explored a potential prebiotic effect of the polyphenol-rich French Maritime Pine Bark Extract (PBE) compared to MPH and a placebo in pediatric ADHD patients by studying their impact on the gut microbiota via amplicon sequencing of the full length 16S rRNA gene ribosomal subunit (V1-V9). One interesting finding was the high relative abundance of Bifidobacteria among all patients in our study cohort. Moreover, our study has identified that treatment (placebo, MPH and PBE) explains 3.94% of the variation in distribution of microbial taxa (adjusted p-value of 0.011). Our small sample size (placebo: n = 10; PBE: n = 13 and MPH: n = 14) did not allow to observe clear prebiotic effects in the patients treated with PBE. Notwithstanding this limitation, subtle changes were noticeable and some limited compositional changes could be observed. doi: 10.1186/S13063-017-1879-6.

The Effects of Chronic Psychostimulant Administration on Bone Health: A Review.

(1) Background: Methylphenidate (MP) and amphetamine (AMP) are psychostimulants that are widely prescribed to treat Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy. In recent years, 6.1 million children received an ADHD diagnosis, and nearly 2/3 of these children were prescribed psychostimulants for treatment. The purpose of this review is to summarize the current literature on psychostimulant use and the resulting effects on bone homeostasis, biomechanical properties, and functional integrity. (2) Methods: Literature searches were conducted from Medline/PubMed electronic databases utilizing the search terms "methylphenidate" OR "amphetamine" OR "methylphenidate" AND "bone health" AND "bone remodeling" AND "osteoclast" AND "osteoblast" AND "dopamine" from 01/1985 to 04/2023. (3) Results: Of the 550 publications found, 44 met the inclusion criteria. Data from identified studies demonstrate that the use of MP and AMP results in decreases in specific bone properties and biomechanical integrity via downstream effects on osteoblasts and osteoclast-related genes. (4) Conclusions: The chronic use of psychostimulants negatively affects bone integrity and strength as a result of increased osteoclast activity. These data support the need to take this into consideration when planning the treatment type and duration for bone fractures.

The effect of a single dose of methylphenidate on attention in children and adolescents with ADHD and comorbid Oppositional Defiant Disorder.

The co-occurrence Oppositional Defiant Disorder (ODD) in children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) has been associated to difficulties in regulating adverse states, elevated functional impairment, deficits in Executive Functions and high risk for psychopathology. Recent studies have shown that ODD is a negative predictor of a positive response to methylphenidate (MPH) treatment for ADHD symptoms in children and adolescents and that patients with a diagnosis of comorbid ADHD and ODD are less likely to respond favorably to pharmacological treatment with MPH. We conducted a naturalistic study to understand the clinical characteristics of drug-naïve children and adolescents with ADHD that influence the response to MPH by measuring the effect on attention. Specifically, we investigated whether a single dose of MPH differently affects the performance of 53 children and adolescents with ADHD with or without ODD comorbidity. In addition, participant characteristics such as symptom severity, functional impairment, and associated behavioral and emotional symptoms at baseline were examined to better understand what aspects affect the response to MPH. We found that a single dose of MPH improved the attention of children and adolescents with ADHD without ODD more than those with comorbid ADHD and ODD, resulting in reduced reaction times. Our findings indicated that children and adolescents with comorbid ADHD and ODD and those with ADHD alone did not exhibit differences in measures of attention prior to taking MPH, nor in demographic variables (age, intelligence quotient, gender), clinical characteristics related to symptom severity, and adaptive behaviors. However, we observed differences between the two groups in certain behavioral aspects, including the Dysregulation Profile and disruptive behaviors. Assessing symptoms in combination with the presence of ADHD can be beneficial in determining which individuals would derive the greatest benefits from treatment.

A matching-adjusted indirect comparison of centanafadine versus lisdexamfetamine, methylphenidate and atomoxetine in adults with attention-deficit/hyperactivity disorder: long-term safety and efficacy.

Aim: To compare long-term safety and efficacy outcomes of centanafadine versus lisdexamfetamine dimesylate (lisdexamfetamine), methylphenidate hydrochloride (methylphenidate) and atomoxetine hydrochloride (atomoxetine), respectively, in adults with attention-deficit/hyperactivity disorder (ADHD) using matching-adjusted indirect comparisons (MAICs). Patients & methods: Patient-level data from a centanafadine trial (NCT03605849) and published aggregate data from a lisdexamfetamine trial (NCT00337285), a methylphenidate trial (NCT00326300) and an atomoxetine trial (NCT00190736) were used. Patient characteristics were matched in each comparison using propensity score weighting. Study outcomes were assessed up to 52weeks and included safety (rates of adverse events [AEs]) and efficacy (mean change from baseline in the Adult ADHD Investigator Symptom Rating Scale [AISRS] or ADHD Rating Scale [ADHD-RS] score). Results: In all comparisons of matched populations, risks of AEs were statistically significantly lower with centanafadine or non-different between centanafadine and comparator; the largest differences in AE rates included upper respiratory tract infection (risk difference in percentage points: 18.75), insomnia (12.47) and dry mouth (12.33) versus lisdexamfetamine; decreased appetite (20.25), headache (18.53) and insomnia (12.65) versus methylphenidate; and nausea (26.18), dry mouth (25.07) and fatigue (13.95) versus atomoxetine (all p<0.05). Centanafadine had a smaller reduction in the AISRS/ADHD-RS score versus lisdexamfetamine (6.15-point difference; p<0.05) and no statistically significant difference in the change in AISRS score versus methylphenidate (1.75-point difference; p=0.13) and versus atomoxetine (1.60-point difference; p=0.21). Conclusion: At up to 52weeks, centanafadine showed significantly lower incidence of several AEs than lisdexamfetamine, methylphenidate and atomoxetine; efficacy was lower than lisdexamfetamine and non-different from methylphenidate and atomoxetine.

Differences in the Interleukin Profiles in Inattentive ADHD Prepubertal Children Are Probably Related to Conduct Disorder Comorbidity.

Inflammatory cytokines are involved in attention deficit hyperactivity disorder (ADHD), a highly prevalent neurodevelopmental disorder. To quantify the baseline levels of pro- and anti-inflammatory cytokines and their changes after methylphenidate (MPH), a total of 31 prepubertal children with ADHD were recruited and subclassified into only two ADHD presentations-ADHD attention deficit (n = 13) or ADHD combined (n = 18). The children were also screened for oppositional defiant conduct disorder (ODCD) and anxiety disorder. Blood samples were drawn at 09:00 and after 4.63 ± 1.87 months of treatment. Four pro-inflammatory cytokines (interleukin-1beta (IL-1β), IL-5, IL-6, tumor necrosis factor-alpha (TNF-α)) and three anti-inflammatory cytokines (IL-4, IL-10, IL-13) were measured using a Luminex® assay. For statistics, a factorial analysis was performed in Stata 15.1. Overall, there were no statistically significant differences in the interleukin (IL) values induced by treatment. When grouped by presentation, the differences were present almost exclusively in ADHD-AD, usually with a profile opposite to that observed in ADHD-C, and with interactions between comorbid factors, with IL-1β (p = 0.01) and IL-13 (p = 0.006) being the ones reaching the greatest statistical significance. These differences are probably related to the ODCD factor, and they disappear after treatment. In conclusion, the changes observed in cytokine levels in prepubertal children only in the ADHD-AD presentation are probably related to comorbidities (specifically ODCD) and are mitigated after treatment.

Attenuated responses to attention-modulating drugs in the neuroligin-3R451C mouse model of autism.

Attention deficits are frequently reported within the clinical autism population. Despite not being a core diagnostic feature, some aetiological theories place atypical attention at the centre of autism development. Drugs used to treat attention dysfunction are therefore increasingly prescribed to autistic patients, though currently off-label with uncertain efficacy. We utilised a rodent-translated touchscreen test of sustained attention in mice carrying an autism-associated R451C mutation in the neuroligin-3 gene (Nlgn3R451C). In doing so, we replicated their cautious but accurate response profile and probed it using two widely prescribed attention-modulating drugs: methylphenidate (MPH) and atomoxetine (ATO). In wild-type mice, acute administration of MPH (3 mg/kg) promoted impulsive responding at the expense of accuracy, while ATO (3 mg/kg) broadly reduced impulsive responding. These drug effects were absent in Nlgn3R451C mice, other than a small reduction in blank touches to the screen following ATO administration. The absence of drug effects in Nlgn3R451C mice likely arises from their altered behavioural baseline and underlying neurobiology, highlighting caveats to the use of classic attention-modulating drugs across disorders and autism subsets. It further suggests that altered dopaminergic and/or norepinephrinergic systems may drive behavioural differences in the Nlgn3R451C mouse model of autism, supporting further targeted investigation.

Catecholaminergic Modulation of Metacontrol Is Reflected by Changes in Aperiodic EEG Activity.

"Metacontrol" describes the ability to maintain an optimal balance between cognitive control styles that are either more persistent or more flexible. Recent studies have shown a link between metacontrol and aperiodic EEG patterns. The present study aimed to gain more insight into the neurobiological underpinnings of metacontrol by using methylphenidate (MPH), a compound known to increase postsynaptic catecholamine levels and modulate cortical noise. In a double-blind, randomized, placebo-controlled study design, we investigated the effect of MPH (0.5mg/kg) on aperiodic EEG activity during a flanker task in a sample of n = 25 neurotypical adults. To quantify cortical noise, we employed the fitting oscillations and one over f algorithm. Compared with placebo, MPH increased the aperiodic exponent, suggesting that it reduces cortical noise in 2 ways. First, it did so in a state-like fashion, as the main effect of the drug was visible and significant in both pre-trial and within-trial periods. Second, the electrode-specific analyses showed that the drug also affects specific processes by dampening the downregulation of noise in conditions requiring more control. Our findings suggest that the aperiodic exponent provides a neural marker of metacontrol states and changes therein. Further, we propose that the effectiveness of medications targeting catecholaminergic signaling can be evaluated by studying changes of cortical noise, fostering the idea of using the quantification of cortical noise as an indicator in pharmacological treatment.

Differential Impact of Serotonin Signaling Methylphenidate on Young versus Adult: Insights from Behavioral and Dorsal Raphe Nucleus Neuronal Recordings from Freely Behaving Rats.

Methylphenidate (MPD) remains a cornerstone pharmacological intervention for managing ADHD, yet its increasing usage among ordinary youth and adults outside clinical contexts necessitates a thorough investigation into its developmental effects. This study seeks to simultaneously investigate the behavioral and neuronal changes within the dorsal raphe (DR) nucleus, a center of serotonergic neurons in the mammalian brain, before and after the administration of varying doses of acute and chronic MPD in freely behaving young and adult rats implanted with DR recording electrodes. Wireless neuronal and behavioral recording systems were used over 10 consecutive experimental days. Eight groups were examined: saline, 0.6, 2.5, and 10.0 mg/kg MPD for both young and adult rats. Six daily MPD injections were administered on experimental days 1 to 6, followed by a three-day washout period and MPD re-administration on experimental day 10 (ED10). The analysis of neuronal activity recorded from 504 DR neurons (DRNs) in young rats and 356 DRNs in adult rats reveals significant age-dependent differences in acute and chronic MPD responses. This study emphasizes the importance of aligning electrophysiological evaluations with behavioral outcomes following extended MPD exposure, elucidating the critical role of DRNs and serotonin signaling in modulating MPD responses and delineating age-specific variations in young versus adult rat models.

Effectiveness of pharmacological interventions for managing ADHD symptoms in individuals with autism spectrum disorder: A systematic review and meta-analysis

ObjectivesThis systematic review sought to provide evidence for the effectiveness of common pharmacological interventions used for treating attention deficit hyperactivity disorder (ADHD) symptoms in the autism spectrum disorder (ASD) population, considering studies attempting to find safe and effective drugs. MethodsWe searched for randomized controlled trials describing the effectiveness and/or safety profile of pharmacological interventions for treating ASD and ADHD or ASD with ADHD symptoms using three bibliographic databases: PubMed, Cochrane Library, and Embase. We have chosen ADHD symptoms measured by any clinical scale as the primary outcome. As additional outcomes, we have used other symptoms of aberrant behavior measured by the aberrant behavior checklist, satisfaction with treatment, and peer satisfaction. ResultsTwenty-two publications met the inclusion criteria for the systematic review and eight for the meta-analysis. In our investigation, we found a few articles using clonidine, modafinil, and bupropion as interventions when compared to methylphenidate (MPH). Our meta-analysis showed that MPH had positive changes compared to placebo in symptoms such as hyperactivity, irritability, or inattention. However, no effect was found in stereotyped symptoms, and our data's quantitative analysis revealed a large effect of MPH-induced adverse effects on the dropout rate. On the other hand, atomoxetine initiation had positive effects when compared to placebo on symptoms of hyperactivity and inattention. We have found no effect of atomoxetine on stereotypes or irritability. Furthermore, atomoxetine did not influence side effects that caused dropouts from studies. ConclusionOur results indicated that atomoxetine has a modest effect on hyperactivity and inattention symptoms, with a relatively benign profile of side effects. MPH appears to be effective in handling hyperactivity, inattention, and irritability symptoms. However, our results on atomoxetine revealed increased dropouts due to adverse effects when compared to MPH or placebo. Evidence for other substances such as guanfacine, clonidine, bupropion, or modafinil is either preliminary or nonexistent.

Add-On Bifidobacterium Bifidum Supplement in Children with Attention-Deficit/Hyperactivity Disorder: A 12-Week Randomized Double-Blind Placebo-Controlled Clinical Trial.

We conducted a 12-week randomized double-blind placebo-controlled clinical trial to investigate the potential impact of Bifidobacterium bifidum (Bf-688) supplementation on attention-deficit/hyperactivity disorder (ADHD). Children with ADHD who were already receiving a stable dose of methylphenidate (MPH) treatment were enrolled and were randomly assigned to two groups: one receiving add-on Bf-688 (daily bacterial count of 5 × 109 CFUs) (n = 51) and the other receiving a placebo (n = 51). All participants underwent assessments using Conners' Continuous Performance Test (CPT) and Conners' Continuous Auditory Test of Attention (CATA). Additionally, fecal samples were collected at the beginning of the trial (week 0) and at the endpoint (week 12). Remarkably, the group receiving Bf-688 supplementation, but not the placebo group, exhibited significant improvements in omission errors in CPT as well as Hit reaction time in both CPT and CATA. Gut microbiome analysis revealed a significant increase in the Firmicutes to Bacteroidetes ratio (F/B ratio) only in the Bf-688 group. Furthermore, we identified significant negative correlations between N-Glycan biosynthesis and Hit reaction time in both CPT and CATA. Our results demonstrate that the probiotic Bf-688 supplement can enhance neuropsychological performance in children with ADHD, possibly by altering the composition of the gut microbiota, ultimately leading to reduced N-Glycan biosynthesis.

Assessment of centanafadine in adults with ADHD: a matching adjusted indirect comparison versus methylphenidate hydrochloride extended release (Concerta)

Objective To compare safety and efficacy of centanafadine versus methylphenidate hydrochloride extended release (ER; Concerta) in adults with ADHD. Methods Without head-to-head trials, anchored matching-adjusted indirect comparisons (MAIC) of adverse event rates reported across trials and mean change from baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) score between centanafadine and methylphenidate hydrochloride ER were conducted. Pooled patient-level data from two centanafadine trials (NCT03605680/NCT03605836) and aggregate data from one published methylphenidate hydrochloride ER trial (NCT00937040) were used. Characteristics of individual patients from the centanafadine trials were matched to aggregate baseline characteristics from the methylphenidate hydrochloride ER trial using propensity score weighting. A sensitivity analysis assessed the robustness of the results to the capping of extreme weights (i.e. >99th percentile). Results Compared with methylphenidate hydrochloride ER, centanafadine was associated with significantly lower risk of dry mouth (risk difference [RD] in percentage points: −11.95), initial insomnia (−11.10), decreased appetite (−8.05), anxiety (−5.39), palpitations (−5.25), and feeling jittery (−4.73) though a significantly smaller reduction in AISRS score (4.16-point). In the sensitivity analysis, the safety results were consistent with the primary analysis but there was no significant difference in efficacy between centanafadine and methylphenidate hydrochloride ER. Conclusion In this MAIC, centanafadine had better safety and possibly lower efficacy than methylphenidate hydrochloride ER. While safety results were robust across analyses, there was no efficacy difference between centanafadine and methylphenidate hydrochloride ER in the sensitivity analysis. Considering its favorable safety profile, centanafadine may be preferred among patients for whom treatment-related adverse events are a concern.

Bilateral cataract related to the use of methylphenidate in a 10-year-old girl

The purpose of the case report is to highlight the fact that the use of methylphenidate (MPH) treatment for attention deficit hyperactivity disorder (ADHD) causes bilateral cataracts. A 10-year-old girl was referred to us for blurred vision using MPH 30 mg/day for four years. A complete cataract in the right eye with a perception of light visual acuity (VA) and a posterior subcapsular cataract in the left eye with 6/20 VA were observed. After cataract surgery, VA was 20/20 in both eyes. Increasing norepinephrine and dopamine levels in the aqueous with the use of MPH may induce the inflammation that causes cataract.