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Journal of Child and Adolescent... Apr 2024This study aimed to examine switch from first-line methylphenidate (MPH) to lisdexamfetamine (LDX) in school-aged children with attention-deficit/hyperactivity disorder... (Observational Study)
Observational Study
This study aimed to examine switch from first-line methylphenidate (MPH) to lisdexamfetamine (LDX) in school-aged children with attention-deficit/hyperactivity disorder (ADHD). This is a retrospective observational study based on systematic review of patient records of all children (7-13 years) diagnosed with ADHD and referred to a Danish specialized outpatient clinic. The study included 394 children switching from MPH to LDX as either second-line or third-line treatment (atomoxetine [ATX] as second-line treatment) during the study period from April 1, 2013, to November 5, 2019. One in five children switched from MPH to LDX at some point during the study period. The most frequent reasons for switching to LDX were adverse effects (AEs; 70.0% for MPH, 68.3% for ATX) and lack of efficiency (52.0% for MPH, 72.7% for ATX). Top five AEs of LDX were decreased appetite (62.4%), insomnia (28.7%), irritability/aggression (26.1%), weight decrease (21.1%), and mood swings (13.9%). MPH and LDX had similar AE profiles, yet most AEs were less frequent after switching to LDX. At the end of the study period, the majority were prescribed LDX as second-line rather than third-line treatment (86.1% in 2019). However, the likelihood of LDX as second-line treatment decreased with the number of psychiatric comorbidities, ADHD symptom severity as assessed by parents, and if AEs were a reason for MPH discontinuation. Among children observed for at least 1 year after initiation of LDX, 41.3% continued LDX treatment for a year or longer. LDX continuation was less likely if AEs were a reason for MPH discontinuation. Similarly to MPH and ATX, the most frequent reasons for LDX discontinuation were AEs (74.4%) and lack of efficiency (34.7%). The findings support LDX as an important option in the personalized treatment of children with ADHD and may support prescribers in the clinical decision-making on switching medication.
Topics: Child; Humans; Attention Deficit Disorder with Hyperactivity; Lisdexamfetamine Dimesylate; Cohort Studies; Methylphenidate; Atomoxetine Hydrochloride; Ambulatory Care Facilities; Denmark
PubMed: 38608011
DOI: 10.1089/cap.2023.0077 -
Soa--ch'ongsonyon Chongsin Uihak =... Apr 2024The purpose of this study was to examine the patterns of use of oral aripiprazole treatment in children and adolescents diagnosed with autism spectrum disorder (ASD) at...
OBJECTIVES
The purpose of this study was to examine the patterns of use of oral aripiprazole treatment in children and adolescents diagnosed with autism spectrum disorder (ASD) at a university medical center in Korea.
METHODS
We retrospectively reviewed the medical records of 164 outpatient children and adolescents diagnosed with ASD by child and adolescent psychiatrists. Patient demographic characteristics, clinical features, age and dose of aripiprazole treatment, associated adverse events, and concomitant medications, etc. were evaluated.
RESULTS
Aripiprazole treatment was initiated at a mean age of 7.64 years, at a mean initial dose of 1.15 mg. Methylphenidate was often co-administered with aripiprazole. The most commonly reported adverse effects were increased appetite and weight gain, which in some cases led to discontinuation of medication.
CONCLUSION
A follow-up study is warranted to evaluate the efficacy and safety of aripiprazole treatment in Korean children and adolescents diagnosed with ASD, and it is crucial to consider their clinical characteristics and response to treatment in the evaluation.
PubMed: 38601108
DOI: 10.5765/jkacap.230057 -
Journal of Attention Disorders Jun 2024DR/ER-MPH (formerly HLD200) is an evening-dosed delayed-release and extended-release methylphenidate approved for the treatment of ADHD in patients ≥6 years.... (Randomized Controlled Trial)
Randomized Controlled Trial
A Post-Hoc Analysis of Emotional Lability With Delayed-Release/Extended-Release Methylphenidate in Children Aged 6 to 12 Years of Age Participating in Two Phase 3 Clinical Trials.
OBJECTIVE
DR/ER-MPH (formerly HLD200) is an evening-dosed delayed-release and extended-release methylphenidate approved for the treatment of ADHD in patients ≥6 years. analyses of two pivotal Phase 3 trials: HLD200-107 (NCT02493777) and HLD200-108 (NCT02520388) evaluated emotional lability (EL) with DR/ER-MPH treatment.
METHODS
Differences in Conners Global Index-Parent (CGI-P) EL subscale scores and age- and gender-adjusted -scores over an open-label titration phase (HLD200-107) and between treatment and placebo groups at endpoint (HLD200-108) were evaluated.
RESULTS
In HLD200-107 ( = 117) mean CGI-P EL subscale scores improved from 5.3 to 1.3 ( < .0001) after 6 weeks; in HLD200-108 significant improvements were observed in the treatment group ( = 81) versus placebo ( = 80; 3.11 vs. 4.08; = .0053). -scores showed an improvement with DR/ER-MPH treatment in both trials. Few emotional adverse events (AEs) were reported.
CONCLUSION
DR/ER-MPH treatment resulted in statistically significant improvements in EL to the level of non-ADHD peers as contextualized by -scores.
Topics: Humans; Methylphenidate; Delayed-Action Preparations; Child; Male; Female; Central Nervous System Stimulants; Attention Deficit Disorder with Hyperactivity; Double-Blind Method; Treatment Outcome; Affective Symptoms
PubMed: 38600754
DOI: 10.1177/10870547241243155 -
The Journal of Pediatric Pharmacology... Apr 2024Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood with approximately 6 million children (age 3 to 17...
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood with approximately 6 million children (age 3 to 17 years) ever diagnosed based on data from 2016-2019. ADHD is characterized by a constant pattern of inattention and/or hyperactivity-impulsivity symptoms that interferes with development or functioning. Specific criteria from the assist with the diagnosis with multiple guidelines available providing non-pharmacologic and pharmacologic recommendations for the treatment of ADHD in the pediatric population. While all guidelines similarly recommend behavioral and/or stimulant therapy as first-line therapy based on age, not all stimulant products are equal. Their differing pharmacokinetic profiles and formulations are essential to understand in order to optimize efficacy and safety for patients. Additionally, new stimulant products and non-stimulant medications continue to be approved for use of ADHD in the pediatric population and it is important to know their differences in formulation, efficacy, and safety to other products currently available. Lastly, due to drug shortages, it is important to understand product similarities and differences to select alternative therapy for patients.
PubMed: 38596418
DOI: 10.5863/1551-6776-29.2.107 -
Cureus Mar 2024Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is commonly diagnosed during childhood. Patients present with hyperactive-impulsive...
Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is commonly diagnosed during childhood. Patients present with hyperactive-impulsive behavior and/or inappropriate inattention which may persist through adulthood. Central nervous system stimulants have been used to manage patients with ADHD. Methylphenidate which is used as a first-line therapy has been shown to have adverse cardiovascular effects in these patients. This is a case of a young male with a history of ADHD since childhood on methylphenidate who was diagnosed with acute non-ischemic heart failure with an ejection fraction of 15-20%. Methylphenidate-induced heart failure is the rare adverse effect seen in ADHD patients who are on this medication. Our patient was started on goal-directed medical therapy for heart failure and was discharged with an implantable cardioverter defibrillator (LifeVest®, ZOLL, Pittsburgh, PA) because of his persistently low left ventricular ejection fraction. It is important for physicians to always consider heart failure as a possible cardiovascular adverse effect when starting patients on methylphenidate for the management of ADHD.
PubMed: 38586757
DOI: 10.7759/cureus.55604 -
Trials Apr 2024Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the...
5-EPIFAT trial protocol: a multi-center, randomized, placebo-controlled trial of the efficacy of pharmacotherapy for fatigue using methylphenidate, bupropion, ginseng, and amantadine in advanced cancer patients on active treatment.
BACKGROUND
Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer.
METHODS
The 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0-10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups.
DISCUSSION
The findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines.
TRIAL REGISTRATION
IRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.
Topics: Adult; Humans; Amantadine; Bupropion; Fatigue; Methylphenidate; Multicenter Studies as Topic; Neoplasms; Panax; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38570861
DOI: 10.1186/s13063-024-08078-w -
Psychiatria Polska Dec 2023In this article, we present the case of an adult patient, whose main problem is episodes of fantasizing and rocking lasting up to 12 hours a day and completely...
In this article, we present the case of an adult patient, whose main problem is episodes of fantasizing and rocking lasting up to 12 hours a day and completely preventing school development. The nature of the disorder in the patient is related to the sinking into fantasies, and not typical obsessions as in OCD. The patient was previously treated with drugs from the SSRI group, neuroleptics (without aripiprazole) and methylphenidate. Only methylphenidate showed some improvement; however, it made the patient feel ‟stiff in thinking". The patient was hospitalized because of a suicide attempt, which, as it later turned out, was self-harm with no intention of killing himself. During hospitalization, a differential diagnosis was performed and the diagnosis of Asperger's syndrome was made, which was accompanied by immersion in the world of one's fantasies and stereotypical behavior. The patient was administered aripiprazole at a dose of 15 mg/d and after three weeks, a significant improvement in health was achieved, including a reduction in the duration of episodes from several hours to several dozen seconds. The drug is well tolerated by the patient. The patient was discharged from the hospital and continues his school education. In the article, we present single case reports in which similar spectacular results were achieved in similar cases. We also describe a possible physiological explanation for this response to this drug.
Topics: Adult; Humans; Asperger Syndrome; Aripiprazole; Antipsychotic Agents; Suicide, Attempted; Methylphenidate
PubMed: 38564518
DOI: 10.12740/PP/152316 -
MedRxiv : the Preprint Server For... Jun 2024Widely prescribed for Attention-Deficit/Hyperactivity Disorder (ADHD), stimulants (e.g., methylphenidate) have been studied for their chronic effects on the brain in...
Widely prescribed for Attention-Deficit/Hyperactivity Disorder (ADHD), stimulants (e.g., methylphenidate) have been studied for their chronic effects on the brain in prospective designs controlling dosage and adherence. While controlled approaches are essential, they do not approximate real-world stimulant exposure contexts where medication interruptions, dosage non-compliance, and polypharmacy are common. Brain changes in real-world conditions are largely unexplored. To fill this gap, we capitalized on the observational design of the Adolescent Brain Cognitive Development (ABCD) study to examine effects of stimulants on large-scale bilateral cortical networks' resting-state functional connectivity (rs-FC) with 6 striatal regions (left and right caudate, putamen, and nucleus accumbens) across two years in children with ADHD. Bayesian hierarchical regressions revealed associations between stimulant exposure and change in rs-FC of multiple striatal-cortical networks, affiliated with executive and visuo-motor control, which were not driven by general psychotropic medication. Of these connections, three were selective to stimulants versus stimulant naive: reduced rs-FC between caudate and frontoparietal network, and between putamen and frontoparietal and visual networks. Comparison with typically developing children in the ABCD sample revealed stronger rs-FC reduction in stimulant-exposed children for putamen and frontoparietal and visual networks, suggesting a normalizing effect of stimulants. 14% of stimulant-exposed children demonstrated reliable reduction in ADHD symptoms, and were distinguished by stronger rs-FC reduction between right putamen and visual network. Thus, stimulant exposure for a two-year period under real-world conditions modulated striatal-cortical functional networks broadly, had a normalizing effect on a subset of networks, and was associated with potential therapeutic effects involving visual attentional control.
PubMed: 38562872
DOI: 10.1101/2024.03.18.24304470 -
Current Research in Toxicology 2024Full treatment of the second most common neurodegenerative disorder, Parkinson's disease (PD), is still considered an unmet need. As the psychostimulants, amphetamine...
Full treatment of the second most common neurodegenerative disorder, Parkinson's disease (PD), is still considered an unmet need. As the psychostimulants, amphetamine (AMPH) and methylphenidate (MPH), were shown to be neuroprotective against stroke and other neuronal injury diseases, this study aimed to evaluate their neuroprotective potential against two dopaminergic neurotoxicants, 6-hydroxydopamine (6-OHDA) and paraquat (PQ), in differentiated human dopaminergic SH-SY5Y cells. Neither cytotoxicity nor mitochondrial membrane potential changes were seen following a 24-hour exposure to either therapeutic concentration of AMPH or MPH (0.001-10 μM). On the other hand, a 24-hour exposure to 6-OHDA (31.25-500 μM) or PQ (100-5000 μM) induced concentration-dependent mitochondrial dysfunction, assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and lysosomal damage, evaluated by the neutral red uptake assay. The lethal concentrations 25 and 50 retrieved from the concentration-toxicity curves in the MTT assay were 99.9 µM and 133.6 µM for 6-OHDA, or 422 µM and 585.8 µM for PQ. Both toxicants caused mitochondrial membrane potential depolarization, but only 6-OHDA increased reactive oxygen species (ROS). Most importantly, PQ-induced toxicity was partially prevented by 1 μM of AMPH or MPH. Nonetheless, neither AMPH nor MPH could prevent 6-OHDA toxicity in this experimental model. According to these findings, AMPH and MPH may provide some neuroprotection against PQ-induced neurotoxicity, but further investigation is required to determine the exact mechanism underlying this protection.
PubMed: 38562456
DOI: 10.1016/j.crtox.2024.100165 -
Journal of Primary Health Care Mar 2024Introduction Attention deficit and hyperactivity disorder (ADHD) is a common neurodevelopmental disorder affecting about 7% of those aged up to 12 years, 5% of...
Introduction Attention deficit and hyperactivity disorder (ADHD) is a common neurodevelopmental disorder affecting about 7% of those aged up to 12 years, 5% of teenagers and 3% of adults. It is associated with poor academic performance, substance abuse, criminality, poor social functioning and other negative outcomes. Psychotherapeutic treatment is moderately successful, whereas pharmacotherapy with stimulant medication is more efficacious and is recommended in many international guidelines. Anecdotal evidence suggests underuse of these medications in Aotearoa, New Zealand. Aim To estimate how many patients with ADHD are prescribed psychostimulants in Aotearoa, New Zealand. Methods National prescribing data for dexamphetamine and methylphenidate in 2022 were obtained and matched against estimated prevalence of ADHD by age. Results There is a significant treatment gap for which inability to access first-line medication is likely to be the predominant explanation. Discussion The data suggest failure of our health system to provide reasonable health care for a significant number of people with ADHD, and results in inequity in outcomes. New approaches are needed that will increase access to first-line medication, yet maintain appropriateness of diagnosis and limit risk of medication diversion.
Topics: Adult; Adolescent; Humans; Aged; Attention Deficit Disorder with Hyperactivity; New Zealand; Central Nervous System Stimulants; Methylphenidate; Substance-Related Disorders
PubMed: 38546775
DOI: 10.1071/HC23126