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European Journal of Drug Metabolism and... Feb 2017Methylphenidate (MPH) is primarily indicated for attention-deficit hyperactivity disorder and narcolepsy therapy. A marked individual variability in the dose-response... (Review)
Review
Methylphenidate (MPH) is primarily indicated for attention-deficit hyperactivity disorder and narcolepsy therapy. A marked individual variability in the dose-response has been observed, and therefore dosage must be titrated for optimal therapeutic effect with minimal toxicity. This variability has been claimed to be predominantly pharmacokinetic. Moreover, due to its similar pharmacodynamics to amphetamine, MPH has been abused and fatalities have been reported. This review aims to discuss metabolomics of MPH, namely by presenting all major and minor metabolites. Ritalinic acid is the main metabolite. In addition, minor pathways involving aromatic hydroxylation, microsomal oxidation and conjugation have also been reported to form the p-hydroxy-, oxo- and conjugated metabolites, respectively. MPH may undergo transesterification with ethanol producing ethylphenidate, which is also pharmacologically active. It is expected that knowing the metabolomics of MPH may provide further insights regarding individual contribution for MPH pharmacodynamics and toxicological effects, namely if ethanol is co-consumed.
Topics: Humans; Metabolomics; Methylphenidate
PubMed: 27438788
DOI: 10.1007/s13318-016-0362-1 -
Primary Care Mar 2023Attention-deficit hyperactivity disorder is a neurodevelopmental disorder involving dysregulation of multiple neural circuits, manifesting in symptoms such as... (Review)
Review
Attention-deficit hyperactivity disorder is a neurodevelopmental disorder involving dysregulation of multiple neural circuits, manifesting in symptoms such as inattention, impulsivity, and hyperactivity. Diagnosis requires onset of symptoms before age 12 years. However, symptoms often persist throughout lifetime, although they may change over time. The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition formally lists the clinical criteria. Management involves pharmacologic agents, such as stimulant and/or nonstimulant medications, and providers should monitor closely for any adverse effects. Nonpharmacologic interventions may be implemented and can be used in conjunction with pharmacotherapy, although medications should be at the forefront of treatment.
Topics: Child; Humans; Adolescent; Young Adult; Attention Deficit Disorder with Hyperactivity; Methylphenidate; Central Nervous System Stimulants
PubMed: 36822725
DOI: 10.1016/j.pop.2022.10.004 -
CNS Drugs Oct 2020Nootropics are drugs used to either treat or benefit cognition deficits. Among this class, methylphenidate is a popular agent, which acts through indirect dopaminergic... (Review)
Review
Nootropics are drugs used to either treat or benefit cognition deficits. Among this class, methylphenidate is a popular agent, which acts through indirect dopaminergic and noradrenergic agonism and, therefore, is proposed to enhance performance in catecholamine-dependent cognitive domains such as attention, memory and prefrontal cortex-dependent executive functions. However, investigation into the efficacy of methylphenidate as a cognitive enhancer has yielded variable results across all domains, leading to debate within the scientific community surrounding its off-label use in healthy individuals seeking scholaristic benefit or increased productivity. Through analysis of experimental data and methodological evaluation, it is apparent that there are dose-, task- and domain-dependent considerations surrounding the use of methylphenidate in healthy individuals, whereby tailored dose administration is likely to provide benefit on an individual basis dependent on the domain of cognition in which benefit is required. Additionally, it is apparent that there are subjective effects of methylphenidate, which may increase user productivity irrespective of cognitive benefit. Whilst there is not extensive study in healthy older adults, it is plausible that there are dose-dependent benefits to methylphenidate in older adults in selective cognitive domains that might improve quality of life and reduce fall risk. Methylphenidate appears to produce dose-dependent benefits to individuals with attention-deficit/hyperactivity disorder, but the evidence for benefit in Parkinson's disease and schizophrenia is inconclusive. As with any off-label use of pharmacological agents, and especially regarding drugs with neuromodulatory effects, there are inherent safety concerns; epidemiological and experimental evidence suggests there are sympathomimetic, cardiovascular and addictive considerations, which might further restrict their use within certain demographics.
Topics: Aged; Animals; Attention; Central Nervous System Stimulants; Cognition; Cognition Disorders; Dose-Response Relationship, Drug; Humans; Memory; Methylphenidate; Nootropic Agents
PubMed: 32794136
DOI: 10.1007/s40263-020-00758-w -
Neuropsychopharmacology : Official... Feb 2021The ability to maximize rewards and minimize the costs of obtaining them is vital to making advantageous explore/exploit decisions. Exploratory decisions are theorized... (Randomized Controlled Trial)
Randomized Controlled Trial
The ability to maximize rewards and minimize the costs of obtaining them is vital to making advantageous explore/exploit decisions. Exploratory decisions are theorized to be greater among individuals with attention-deficit/hyperactivity disorder (ADHD), potentially due to deficient catecholamine transmission. Here, we examined the effects of ADHD status and methylphenidate, a common ADHD medication, on explore/exploit decisions using a 6-armed bandit task. We hypothesized that ADHD participants would make more exploratory decisions than controls, and that MPH would reduce group differences. On separate study days, adults with (n = 26) and without (n = 23) ADHD completed the bandit task at baseline, and after methylphenidate or placebo in counter-balanced order. Explore/exploit decisions were modeled using reinforcement learning algorithms. ADHD participants made more exploratory decisions (i.e., chose options without the highest expected reward value) and earned fewer points than controls in all three study days, and methylphenidate did not affect these outcomes. Baseline exploratory choices were positively associated with hyperactive ADHD symptoms across all participants. These results support several theoretical models of increased exploratory choices in ADHD and suggest the unexplained variance in ADHD decisions may be due to less value tracking. The inability to suppress actions with little to no reward value may be a key feature of hyperactive ADHD symptoms.
Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Methylphenidate; Reinforcement, Psychology; Reward
PubMed: 33040092
DOI: 10.1038/s41386-020-00881-8 -
American Journal of Health-system... Jul 2014Current literature on the safety and efficacy of various intermediate- and long-acting preparations of methylphenidate and dexmethylphenidate for pediatric... (Review)
Review
PURPOSE
Current literature on the safety and efficacy of various intermediate- and long-acting preparations of methylphenidate and dexmethylphenidate for pediatric attention-deficit/hyperactivity disorder (ADHD) is reviewed.
SUMMARY
The efficacy of methylphenidate in controlling ADHD symptoms is firmly established. Given the drug's relatively short half-life in pediatric patients (about 2.5 hours), a number of intermediate- and long-acting products have been developed; these extended-release methylphenidate products provide the same efficacy as immediate-release (IR) formulations, with the convenience of less frequent dosing. Intermediate-acting methylphenidate preparations have effects lasting as long as 8 hours, but peak concentrations are not attained for up to 5 hours, and many patients may require twice-daily dosing. Long-acting methylphenidate products developed to address these challenges include a controlled-release tablet and bimodal-delivery capsules containing mixtures of IR and extended-release beads (durations of effect, 8-12 hours). Options for patients with difficulty swallowing tablets or capsules include a once-daily transdermal delivery system and a once-daily liquid formulation. Dexmethylphenidate (the more pharmacologically active d-isomer of racemic methylphenidate) can provide efficacy comparable to that of IR methylphenidate at half the dose; an extended-release form of dexmethylphenidate can provide less fluctuation in peak and trough concentrations than the IR form. Methylphenidate and dexmethylphenidate products in capsule form can be opened and sprinkled on applesauce.
CONCLUSION
The various formulations of IR and intermediate- and extended-release methylphenidate and dexmethylphenidate can be useful options in satisfying patients' individual needs in the management of ADHD. All are equally efficacious in controlling ADHD symptoms.
Topics: Attention Deficit Disorder with Hyperactivity; Capsules; Central Nervous System Stimulants; Child; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Humans; Methylphenidate; Tablets
PubMed: 24973373
DOI: 10.2146/ajhp130638 -
South Dakota Medicine : the Journal of... May 2023Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood. Children and adolescents with ADHD are at increased risk for...
Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood. Children and adolescents with ADHD are at increased risk for behavioral issues, academic issues, substance abuse issues, and legal problems. Approximately 50% of cases of childhood ADHD will persist into adulthood where it can impact employment, organizational skills, and frustration tolerance. Use of amphetamine and methylphenidate stimulant medications have shown to have the best outcomes, and are considered first line treatments. It is important to monitor stimulant use closely in individuals with substance abuse concerns, however, studies in adolescents with both substance abuse histories and ADHD tend to support their use and benefits. It is important to identify other co-morbid conditions that a patient with ADHD may be struggling with and treat those accordingly. Providers should re-evaluate the symptoms and clinical presentation of patients that show minimal or no improvement with treatment to ensure a proper diagnosis has been made.
Topics: Humans; Adolescent; Child; Attention Deficit Disorder with Hyperactivity; Amphetamine; Methylphenidate; Employment; Attention
PubMed: 37603873
DOI: No ID Found -
The Lancet. Psychiatry Oct 2023
Topics: Adolescent; Child; Humans; Methylphenidate; Attention Deficit Disorder with Hyperactivity; World Health Organization
PubMed: 37739581
DOI: 10.1016/S2215-0366(23)00292-4 -
Nature Communications Nov 2023The faster a drug enters the brain, the greater its addictive potential, yet the brain circuits underlying the rate dependency to drug reward remain unresolved. With...
The faster a drug enters the brain, the greater its addictive potential, yet the brain circuits underlying the rate dependency to drug reward remain unresolved. With simultaneous PET-fMRI we linked dynamics of dopamine signaling, brain activity/connectivity, and self-reported 'high' in 20 adults receiving methylphenidate orally (results in slow delivery) and intravenously (results in fast delivery) (trial NCT03326245). We estimated speed of striatal dopamine increases to oral and IV methylphenidate and then tested where brain activity was associated with slow and fast dopamine dynamics (primary endpoint). We then tested whether these brain circuits were temporally associated with individual 'high' ratings to methylphenidate (secondary endpoint). A corticostriatal circuit comprising the dorsal anterior cingulate cortex and insula and their connections with dorsal caudate was activated by fast (but not slow) dopamine increases and paralleled 'high' ratings. These data provide evidence in humans for a link between dACC/insula activation and fast but not slow dopamine increases and document a critical role of the salience network in drug reward.
Topics: Adult; Humans; Behavior, Addictive; Brain; Dopamine; Methylphenidate; Reward; Clinical Trials as Topic
PubMed: 37938560
DOI: 10.1038/s41467-023-41972-6 -
Journal of the American Academy of... May 2022The first paper indicating that a central nervous system stimulant (amphetamine) could be beneficial for children with attention-deficit/hyperactivity disorder... (Meta-Analysis)
Meta-Analysis
The first paper indicating that a central nervous system stimulant (amphetamine) could be beneficial for children with attention-deficit/hyperactivity disorder (ADHD)-like behavioral symptoms appeared in 1937. Over the subsequent 80 years, a range of additional stimulant (methylphenidate) and nonstimulant (atomoxetine, clonidine, guanfacine, and, most recently, viloxazine) drugs have been approved to treat children and adolescents with ADHD. These drug treatments have been the subject of a large number of randomized controlled trails (RCTs). A network meta-analysis found that using clinician ratings, amphetamine, methylphenidate, and atomoxetine were all significantly superior to a placebo. These findings suggest that in the short-term at least, these treatments are effective-data are sparse on the efficacy of longer-term drug treatment. However, there are longstanding worries about the use of such drug treatments with children. In particular there are concerns over possible adverse impact on growth. There are also less tangible, but important, concerns of parents as the whether it is appropriate to subject their children to the modification of behavior by drugs. For these reasons, there is an urgent need to develop nonpharmacological treatments for children and adolescents with ADHD. One such nonpharmacological treatment is dietary supplementation with micronutrients. In this issue of the Journal, Johnstone et al. present a study of micronutrients showing that, under the stringent conditions of an RCT, micronutrients substantially benefit the well-being of young people with ADHD and irritability (risk ratio [RR] = 2.97; 97.5% CI = 1.50-5.90).
Topics: Adolescent; Amphetamines; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Humans; Methylphenidate; Micronutrients
PubMed: 34416292
DOI: 10.1016/j.jaac.2021.08.008 -
Current Neuropharmacology 2019This brief review deals with the various issues that contributed to the creation of the new Diagnostic and Statistical Manual condition of hoarding disorder (HD) and... (Review)
Review
This brief review deals with the various issues that contributed to the creation of the new Diagnostic and Statistical Manual condition of hoarding disorder (HD) and attempts at reviewing its pharmacotherapy. It appears that after the newly founded diagnosis appeared in the literature as an autonomous entity, distinct from obsessive-compulsive disorder, drug trials are not being conducted and the disorder is left in the hands of psychotherapists, who on their part, report fair results in some core dimensions of HD. The few trials on HD specifically regard the serotonin-noradrenaline reuptake inhibitor venlafaxine, and, possibly due to the suggestion of a common biological background of HD with attention-deficit/hyperactivity disorder, the psychostimulant methylphenidate and the noradrenaline reuptake inhibitor atomoxetine. For all these drugs, positive results have been reported, but the evidence level of these studies is low, due to small samples and non-blind designs. Regretfully, there are currently no future studies aiming at seriously testing drugs in HD.
Topics: Atomoxetine Hydrochloride; Hoarding Disorder; Humans; Methylphenidate; Obsessive-Compulsive Disorder; Selective Serotonin Reuptake Inhibitors
PubMed: 30678629
DOI: 10.2174/1570159X17666190124153048