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The Journal of Nervous and Mental... Jul 2024Wolfram syndrome 1 (WS1) is a rare, autosomal recessive neurodegenerative disorder characterized by diabetes insipidus, insulin-dependent diabetes mellitus, optic...
Wolfram syndrome 1 (WS1) is a rare, autosomal recessive neurodegenerative disorder characterized by diabetes insipidus, insulin-dependent diabetes mellitus, optic atrophy, and deafness resulting from loss-of-function genetic variants in the WFS1 gene. Individuals with WS1 manifest a spectrum of neuropsychiatric disorders. Here, we report a pediatric case of WS1, which stemmed from a novel biallelic WFS1 loss-of-function genetic variant. The individual initially presented with obsessive-compulsive disorder, which was successfully managed by fluvoxamine. After 2 months, the child manifested excessive daytime sleepiness. Clinical evaluation and sleep recordings revealed a diagnosis of narcolepsy type 2. Excessive daytime sleepiness was improved with methylphenidate. To the best of our knowledge, this is the first report of narcolepsy in WS1, which possibly arose during a progressive neurodegenerative process. We emphasize the need for in-depth screening for neuropsychiatric phenotypes and sleep-related disorders in WS1, for clinical management, which significantly improves the quality of life.
Topics: Humans; Female; Wolfram Syndrome; Narcolepsy; Obsessive-Compulsive Disorder; Child; Membrane Proteins
PubMed: 38949661
DOI: 10.1097/NMD.0000000000001784 -
Physiological Reports Jun 2024Methylphenidate (MPH) has been previously shown to increase resting energy expenditure (REE) in individuals of normal weight; however, the effects on individuals living... (Randomized Controlled Trial)
Randomized Controlled Trial
Methylphenidate (MPH) has been previously shown to increase resting energy expenditure (REE) in individuals of normal weight; however, the effects on individuals living with obesity are currently unknown. Ten individuals living with obesity were randomly assigned to undergo 60 days of MPH administration with a daily dose of 0.5 mg/kg body weight or a placebo control. REE was measured before and after the 60-day intervention. There was a trend toward significance for group × time interaction on REE (p = 0.082) with a large effect size (η = 0.331), with MPH administration increasing REE compared to a decrease in placebo control. Preliminary findings from this pilot study show that MPH has the potential to counter the adaptive thermogenic process commonly seen in weight loss. This is a unique finding among pharmacotherapies, as no approved obesity drugs measurably impact REE.
Topics: Humans; Methylphenidate; Male; Female; Obesity; Pilot Projects; Energy Metabolism; Adult; Double-Blind Method; Middle Aged; Central Nervous System Stimulants
PubMed: 38924673
DOI: 10.14814/phy2.16085 -
Expert Review of Neurotherapeutics Jun 2024Stimulants, including methylphenidate and amphetamines, are the first-line pharmacological treatment of ADHD in adults. However, in patients who do not respond or poorly... (Review)
Review
INTRODUCTION
Stimulants, including methylphenidate and amphetamines, are the first-line pharmacological treatment of ADHD in adults. However, in patients who do not respond or poorly tolerate stimulants, non-stimulant medications are usually recommended.
AREAS COVERED
The authors provide a narrative review of the literature on non-stimulant treatments for adult ADHD, including controlled and observational clinical studies conducted on adult samples. Atomoxetine has been extensively studied and showed significant efficacy in treating adult ADHD. Issues related to dosing, treatment duration, safety, and use in the case of psychiatric comorbidity are summarized. Among other compounds indicated for ADHD in adults, antidepressants sharing at least a noradrenergic or dopaminergic component, including tricyclic compounds, bupropion, and viloxazine, have shown demonstratable efficacy. Evidence is also available for antihypertensives, particularly guanfacine, as well as memantine, metadoxine, and mood stabilizers, while negative findings have emerged for galantamine, antipsychotics, and cannabinoids.
EXPERT OPINION
While according to clinical guidelines, atomoxetine may serve as the only second-line option in adults with ADHD, several other nonstimulant compounds may be effectively used in order to personalize treatment based on comorbid conditions and ADHD features. Nevertheless, further research is needed to identify and test more personalized treatment strategies for adults with ADHD.
PubMed: 38915262
DOI: 10.1080/14737175.2024.2370346 -
Biological & Pharmaceutical Bulletin 2024Guanfacine, used as a medication for attention-deficit/hyperactivity disorder (ADHD), leads to a high incidence of somnolence, in contrast to methylphenidate, which...
Guanfacine, used as a medication for attention-deficit/hyperactivity disorder (ADHD), leads to a high incidence of somnolence, in contrast to methylphenidate, which leads to a high incidence of insomnia. The impact of somnolence on continuing guanfacine treatment is unclear. Therefore, we investigated the reasons for discontinuing guanfacine and analyzed the factors associated with discontinuation caused by somnolence. We surveyed 96 patients under guanfacine from July 2017 to December 2021 at the Saga University Hospital. Patients who discontinued guanfacine by the end date of our study were divided into a median early and late group. We compared the reasons for discontinuation in both groups. Of all patients, 47 continued and 49 discontinued guanfacine. A higher percentage of patients discontinued guanfacine caused by somnolence for ≤70 d than for >70 d of treatment (44.0 vs. 8.3%; p = 0.008). When stratified by the concomitant use of other ADHD drugs, somnolence resulted in a higher discontinuation rate for ≤70 d than for >70 d of treatment without concomitant use (55.0 vs. 7.1%; p = 0.009). Nonetheless, concomitant use resulted in no difference. In conclusion, somnolence affects the early discontinuation of guanfacine as an ADHD drug. The combination of methylphenidate or atomoxetine may decrease withdrawal caused by somnolence.
Topics: Guanfacine; Humans; Attention Deficit Disorder with Hyperactivity; Male; Female; Child; Adolescent; Sleepiness; Adrenergic alpha-2 Receptor Agonists; Methylphenidate
PubMed: 38910124
DOI: 10.1248/bpb.b24-00147 -
Annals of General Psychiatry Jun 2024This study aimed to assess the incidence of EEG abnormalities (EEG-ab) in children diagnosed with ADHD, investigate the risk of epileptic seizures (SZ) and maintenance...
PURPOSE
This study aimed to assess the incidence of EEG abnormalities (EEG-ab) in children diagnosed with ADHD, investigate the risk of epileptic seizures (SZ) and maintenance on methylphenidate (MPH) over a three-year period.
METHODS
A total of 517 ADHD children aged 6-14 years were included. Baseline assessments included the identification of EEG-ab, ADHD inattentive subtype (ADHD-I), comorbid epilepsy, the use of antiepileptic drugs (AEDs) and the use of MPH. At the 3-year follow-up, assessments included the presence of EEG-ab, maintenance on MPH, AED usage, SZ risk in cases with EEG-epileptiform abnormalities (EEG-epi-ab), compared with control ADHD cases without EEG-epi-ab matched for age and gender.
RESULTS
EEG-ab were identified in 273 (52.8%) cases. No statistically significant differences were observed between the EEG-ab and EEG-non-ab groups in terms of age, gender, ADHD-I type or initial use of MPH. EEG non-epileptiform abnormalities (EEG-non-epi-ab) were found in 234 out of 478 (49%) cases without EEG-epi-ab. Notably, EEG-non-epi-ab occurred more frequently in the group of 39 cases with EEG-epi-ab (30/39 (76.9%) vs. 9/39, (21.3%), a subset selected for 3-year follow-up. At 3-year-follow-up no statistically significant difference was found in maintenance on MPH in ADHD cases with and without EEG-epi-ab. Nobody of ADHD cases without comorbid epilepsy or with comorbid epilepsy with achieved SZ freedom developed new SZ. Only 3 children with drug resistant epilepsy experienced SZs, without increase in SZ frequency. The disappearance rate of EEG-epi-ab was higher than that EEG-non-epi-ab (71.8% vs. 33.3%).
CONCLUSIONS
Children with and without EEG-ab exhibited similar patterns of MPH use (initial use, positive response, and maintenance on MPH). The presence of comorbid epilepsy and EEG-ab, with or without EEG-epi-ab, was not associated with an increased risk of SZ despite the use of MPH.
PubMed: 38907242
DOI: 10.1186/s12991-024-00510-4 -
Journal of Developmental and Behavioral...DL is an 8-year-old Mexican boy with a posterior atrial septal defect and partial anomalous pulmonary venous return of the right lower pulmonary vein with resultant...
Complex ADHD Challenging Case: Managing Co-Occurring Attention-Deficit Hyperactivity Disorder and Congenital Heart Disease with a Limited Medication Formulary: A Case from Mexico.
DL is an 8-year-old Mexican boy with a posterior atrial septal defect and partial anomalous pulmonary venous return of the right lower pulmonary vein with resultant right heart dilation with normal right ventricular systolic and diastolic function and no arrhythmias. Surgical repair was deferred, and DL's condition was being medically managed with furosemide 0.5 mg/kg BID and spironolactone 0.5 mg/kg BID.DL presents for developmental assessment due to poor performance in school following a lifting of COVID-19 pandemic restrictions and return to in-person classes. He has been attending full-time classes for 3 months without improvements in math, reading, and writing skills. Current attentional concerns at school include an inability to complete tasks without getting distracted by minimal stimuli and highly impulsive behavior.At the first assessment, DL was performing below grade expectations (e.g., reading by syllable without text comprehension, demonstrating preoperational addition and subtraction skills, inability to take dictation)-all of which was viewed as negatively impacted by attentional deficits. DL met DSM-5 criteria for ADHD, predominantly inattentive type. He was started on 10-mg immediate-release methylphenidate PO at 8 am with breakfast and a second dose of 10-mg immediate-release methylphenidate PO 4 hours after the first dose.After a month, at the first follow-up consultation, improvement in attention span, impulsivity, and school performance were observed, including reading skills and math proficiency. However, DL's mother raised concerns about circumoral cyanosis and acrocyanosis in the fingers of both hands after playing outside. These signs were not previously observed. During physical examination at the same visit, heart rate, blood pressure, and oximetry were within baseline ranges and his cardiac examination was unchanged. DL's dosage of methylphenidate was lowered to 10-mg immediate-release methylphenidate PO QD in the mornings with breakfast (8 am).DL did not return to clinic for another 2 months, having discontinued the medication after 2 months of treatment given financial limitations. His mother reported that DL's exertional circumoral cyanosis and acrocyanosis resolved while he was off medication. However, she observed an increase in inattentive symptoms and impulsivity and decline in his academic skills. She asked if our team was able continue the treatment despite the drug side effects, since she believed the benefits outweighed the disadvantages.Given these concerns, the team requested an updated cardiology assessment. The Cardiologist recommended discontinuation of methylphenidate and recommended follow-up with cardiothoracic surgery for reassessment of the surgical timeline.Given the limited treatment options in Mexico, what would you do next as the treating developmental-behavioral clinician…?
Topics: Humans; Male; Attention Deficit Disorder with Hyperactivity; Child; Heart Defects, Congenital; Mexico; COVID-19; Central Nervous System Stimulants; Methylphenidate
PubMed: 38905008
DOI: 10.1097/DBP.0000000000001280 -
Journal of Developmental and Behavioral... Jun 2024Attention-deficit hyperactive disorder (ADHD) is one of the most common psychiatric disorders among children, with estimated prevalence of 7% to 15% worldwide. The aim...
OBJECTIVE
Attention-deficit hyperactive disorder (ADHD) is one of the most common psychiatric disorders among children, with estimated prevalence of 7% to 15% worldwide. The aim of this analysis was to update and summarize trends in diagnosis, demographics, and drug utilization of pediatric patients with ADHD.
METHODS
We used the Agency for Health care Research and Quality Medical Expenditure Panel Survey (MEPS), a survey of US individuals, families, their medical providers, and employers, using datasets from 2016 to 2019. The data sources from the MEPS database included the full-year consolidated files, medical conditions files, prescribed-medicines files, and condition-event link files for each year. We summarized trends in the proportion of children, ages 17 years and younger, with a diagnosis of ADHD, demographic information and a prescription for medication known to treat ADHD. In addition, we further stratified ADHD medication use by stimulant/nonstimulant categories.
RESULTS
There was a 1.6% and 4.7% absolute increase in children with an ADHD diagnosis and those prescribed ADHD medications, respectively, from 2016 to 2019. Most of these children were male, non-Hispanic, and on public insurance. Of the children prescribed an ADHD medication and concomitant behavioral medications, stimulants-only use was the highest (60%-67%), followed by stimulants/nonstimulants (13%-15%), stimulant/antidepressants (6%-9%), and nonstimulants only (5%-9%). The proportion of patients with ADHD in the high-income and near-poor categories increased by 4% from 2016 to 2019.
CONCLUSION
Diagnosis of ADHD among children is trending upward in the United States. Central nervous system stimulants, especially methylphenidate formulations, are the most prescribed ADHD medications for children 17 years and younger.
PubMed: 38904656
DOI: 10.1097/DBP.0000000000001296 -
Postgraduate Medicine Jun 2024With more than 30 available stimulant medications, choosing among therapeutic options for attention-deficit/hyperactivity disorder (ADHD) has become increasingly complex... (Review)
Review
With more than 30 available stimulant medications, choosing among therapeutic options for attention-deficit/hyperactivity disorder (ADHD) has become increasingly complex and patient specific. All ADHD stimulants owe their action to variants of either amphetamine or methylphenidate, yet formulation and delivery system differences create unique pharmacokinetic and clinical profiles for each medication. A benefit of the diversity within ADHD pharmacotherapy is that it facilitates tailoring treatment to meet patient needs. Historically, there has been a constant among long-acting stimulant options, regardless of formulation, which was morning dosing. The introduction of delayed-release and extended-release methylphenidate (DR/ER-MPH) is the first long-acting stimulant that patients take in the evening, with the clinical effect delayed until awakening in the morning. This paradigm shift has generated questions among clinicians and continued interest in real-world experience and data. This review used available clinical data, real-world evidence, emerging analyses, and clinical experience to evaluate the characteristics of DR/ER-MPH and its clinical utility within the greater context of ADHD medications and to provide clinicians with practical guidance on the use of DR/ER-MPH in children, adolescents, and adults with ADHD.
PubMed: 38904469
DOI: 10.1080/00325481.2024.2370230 -
Behavioral and Brain Functions : BBF Jun 2024The Default Mode Network (DMN) is a central neural network, with recent evidence indicating that it is composed of functionally distinct sub-networks. Methylphenidate... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The Default Mode Network (DMN) is a central neural network, with recent evidence indicating that it is composed of functionally distinct sub-networks. Methylphenidate (MPH) administration has been shown before to modulate impulsive behavior, though it is not yet clear whether these effects relate to MPH-induced changes in DMN connectivity. To address this gap, we assessed the impact of MPH administration on functional connectivity patterns within and between distinct DMN sub-networks and tested putative relations to variability in sub-scales of impulsivity.
METHODS
Fifty-five right-handed healthy adults underwent two resting-state functional MRI (rs-fMRI) scans, following acute administration of either MPH (20 mg) or placebo, via a randomized double-blind placebo-controlled design. Graph modularity analysis was implemented to fractionate the DMN into distinct sub-networks based on the impact of MPH (vs. placebo) on DMN connectivity patterns with other neural networks.
RESULTS
MPH administration led to an overall decreased DMN connectivity, particularly with the auditory, cinguloopercular, and somatomotor networks, and increased connectivity with the parietomedial network. Graph analysis revealed that the DMN could be fractionated into two distinct sub-networks, with one exhibiting MPH-induced increased connectivity and the other decreased connectivity. Decreased connectivity of the DMN sub-network with the cinguloopercular network following MPH administration was associated with elevated impulsivity and non-planning impulsiveness.
CONCLUSION
Current findings highlight the intricate effects of MPH administration on DMN rs-fMRI connectivity, uncovering its opposing impact on distinct DMN sub-divisions. MPH-induced dynamics in DMN connectivity patterns with other neural networks may account for some of the effects of MPH administration on impulsive behavior.
Topics: Humans; Methylphenidate; Adult; Male; Magnetic Resonance Imaging; Female; Central Nervous System Stimulants; Default Mode Network; Young Adult; Double-Blind Method; Nerve Net; Impulsive Behavior; Connectome; Brain; Neural Pathways
PubMed: 38902791
DOI: 10.1186/s12993-024-00242-1 -
Neuropsychopharmacology : Official... Jun 2024Disorders of motivation such as apathy syndrome are highly prevalent across neurological disorders but do not yet have an agreed treatment approach. The use of...
Disorders of motivation such as apathy syndrome are highly prevalent across neurological disorders but do not yet have an agreed treatment approach. The use of translational behavioural models can provide a route through which to meaningfully screen novel drug targets. Methods that utilise food deprivation in contrived environments may lack the sensitivity to detect deficits in self-initiated behaviour, and may have limited translation to normal behaviour. Animals monitored in more naturalistic environments may display more ethologically-relevant behaviours of greater translational value. Here, we aimed to validate a novel, non-food or water motivated effort-based foraging task as a measure of motivational state in mice. In this task, the mouse can freely choose to exert effort to forage nesting material and shuttle it back to a safe and enclosed environment. The amount of nesting material foraged is used as a readout of motivational state. Acute dopaminergic modulation with haloperidol, amphetamine and methylphenidate, and two phenotypic models known to induce motivational deficits (healthy ageing and chronic administration of corticosterone) were used to validate this task. Consistent with other effort-based decision-making tasks we find that foraging behaviour is sensitive to acute modulation of dopaminergic transmission. We find that both phenotypic models induce differing deficits in various aspects of foraging behaviour suggesting that the task may be used to parse different behavioural profiles from distinct disease phenotypes. Thus, without requiring extended training periods or physiological deprivation, this task may represent a refined and translational preclinical measure of motivation.
PubMed: 38898205
DOI: 10.1038/s41386-024-01899-y