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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 -
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 -
Revista Paulista de Pediatria : Orgao... 2023The aim of this study was to analyze the effect of the pharmacological treatment on the sleep patterns of children with attention deficit hyperactivity disorder (ADHD).
OBJECTIVE
The aim of this study was to analyze the effect of the pharmacological treatment on the sleep patterns of children with attention deficit hyperactivity disorder (ADHD).
DATA SOURCE
A high-sensitivity electronic search was performed in the following databases: Cochrane Library, MEDLINE via PubMed, LILACS via the Regional Health Portal (BVS), Embase, Scopus, CINAHL, and Web of Science, as recommended by the Cochrane Handbook, and which has undergone peer review according to the PRESS Guide.
DATA SYNTHESIS
The studies contemplated the use of the drugs atomoxetine, guanfacine, methylphenidate, dasotraline, L-theanine, and lisdexamfetamine. They showed efficiency in reducing the symptoms of ADHD, although all, except atomoxetine, affected sleep quality, such as by reducing total rapid eye movement (REM), non-REM phase, slow-wave sleep time, and longer sleep-onset latency.
CONCLUSIONS
The drugs used in the treatment of ADHD seem to have negative repercussions on the sleep quality of children, with the drug atomoxetine showing lesser effects on this variable.
Topics: Child; Humans; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Central Nervous System Stimulants; Methylphenidate; Sleep
PubMed: 37255110
DOI: 10.1590/1984-0462/2023/41/2022065 -
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 -
Journal of Analytical Toxicology Sep 2021Methylphenidate (MPH) is a medication used to combat attention-deficit/hyperactivity disorder by speeding up brain activity. MPH has two chiral centers; however,...
Methylphenidate (MPH) is a medication used to combat attention-deficit/hyperactivity disorder by speeding up brain activity. MPH has two chiral centers; however, d-threo-MPH is responsible for its effects. Few studies have analyzed MPH and its metabolites, ritalinic acid (RA) and ethylphenidate (EPH), in blood. Stability studies are crucial in a forensic setting to provide insight on ideal storage conditions and analysis time. In this study, d,l-MPH, d,l-EPH and RA were analyzed at two concentrations (15 and 150 ng/mL) over 5 months at room temperature (∼25°C), refrigerated (4°C), frozen (-20°C) and elevated (35°C) temperatures. Analytes were analyzed using a validated liquid chromatography--mass spectrometry method. RA concentrations increased 53% at 25°C after 24 h, while d- and l-MPH concentrations dropped 18.1 and 20.6%, respectively. Additionally, d- and l-EPH concentrations decreased 22.3 and 28.8%, respectively. All analytes were stable at 4°C for 1 week (±17% change). At -20°C, all analytes were stable for 5 months. At 35°C, l-EPH remained stable for 24 h (14.4% loss) at the high concentration, while RA increased 244%. Losses of 64.1, 68.7 and 27.2% were observed for d- MPH, l-MPH and d-EPH, respectively. Due to this, a follow-up study was designed to assess the breakdown of MPH. The short-term experiment assessed d,l-MPH at two concentrations for 1 month in the same conditions. As MPH decreased, RA concentrations rose. At 25°C, it took 2 weeks for MPH to metabolize completely into RA. In refrigerated and frozen temperatures, MPH did not completely metabolize to RA. In elevated temperatures, MPH broke down to RA within 2 weeks. Due to this, it was concluded that d,l-MPH breaks down in the blood to its metabolite RA and may make data interpretation difficult if samples are not properly stored. The optimal storage for these analytes is recommended at -20°C.
Topics: Chromatography, Liquid; Follow-Up Studies; Mass Spectrometry; Methylphenidate
PubMed: 34086899
DOI: 10.1093/jat/bkab063 -
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 -
Journal of Attention Disorders Oct 2023To report the characteristics associated with response to methylphenidate (MPH) in children and adolescents with ADHD. (Review)
Review
OBJECTIVE
To report the characteristics associated with response to methylphenidate (MPH) in children and adolescents with ADHD.
METHODS
Studies reporting potentials predictors of response to MPH were searched in Medline and Embase from January 1998 to March 2022. Narrative synthesis was performed.
RESULTS
Fifty-seven reports of 46 studies totaling 6,656 ADHD patients were included. No association appears between response to MPH and age, gender, MPH dosage, ADHD subtype, comorbidities nor socioeconomic status when considering a specific patient. No conclusion could be drawn about body weight, ADHD severity, intelligence quotient, and parental symptoms of depression or ADHD.
CONCLUSIONS
None of these potential predictors have proven their usefulness to predict response to MPH on an individual basis in clinical practice. In research, potential predictors should be measured, their association with response to MPH assessed, in order to control for confounding variables when modeling response to MPH.
Topics: Humans; Child; Adolescent; Methylphenidate; Central Nervous System Stimulants; Attention Deficit Disorder with Hyperactivity; Intelligence Tests; Parents; Treatment Outcome
PubMed: 37243373
DOI: 10.1177/10870547231177234 -
Medicine Jul 2020Various psychotropic drugs may affect the hematological and biochemical profiles of plasma and its metabolism. Carbamazepine, the most well-known psychotropic drug, can...
Various psychotropic drugs may affect the hematological and biochemical profiles of plasma and its metabolism. Carbamazepine, the most well-known psychotropic drug, can cause substantial hyponatremia. Methylphenidate, a piperidine derivative structurally related to amphetamines, acts as a central nervous system stimulant. The current study evaluated whether methylphenidate affects hematological and biochemical parameters of patients diagnosed with attention deficit hyperactivity disorder.Patients undergoing treatment for attention deficit hyperactivity disorder at our Adolescent Psychiatric Clinic were enrolled in the study. Blood samples for complete blood count and common biochemical analyses were collected before patients started methylphenidate and after 3 months of continuous treatment.Participants included 64 patients comprised the study cohort. There were 48 (75%) males and 16 (25%) females, with a median age of 16 years (range 11-31). The total median potassium level decreased by 0.6 mg/dL (P < .0001), while glucose rose by 15 mg/dL (P < .0001), sodium decreased in 0.7meq/L, (P = .006). The white blood count rose by 1350 cells/μL (P < .033) due to neutrophilia, lymphocytosis and eosinophilia. Hemoglobin rose slightly by 0.1 (P = .041). Changes in calcium, phosphorus, protein, albumin, and liver enzyme levels were not significant.The results indicate that methylphenidate may cause hypokalemia and elevated glucose, leukocyte, neutrophil, lymphocyte and eosinophil counts.
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cohort Studies; Female; Humans; Hypoglycemia; Leukocytes; Male; Methylphenidate; Neutrophils; Young Adult
PubMed: 32629693
DOI: 10.1097/MD.0000000000020931