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Science Advances Jun 2023The efficacy of pharmaceutical cognitive enhancers in everyday complex tasks remains to be established. Using the knapsack optimization problem as a stylized...
The efficacy of pharmaceutical cognitive enhancers in everyday complex tasks remains to be established. Using the knapsack optimization problem as a stylized representation of difficulty in tasks encountered in daily life, we discover that methylphenidate, dextroamphetamine, and modafinil cause knapsack value attained in the task to diminish significantly compared to placebo, even if the chance of finding the optimal solution (~50%) is not reduced significantly. Effort (decision time and number of steps taken to find a solution) increases significantly, but productivity (quality of effort) decreases significantly. At the same time, productivity differences across participants decrease, even reverse, to the extent that above-average performers end up below average and vice versa. The latter can be attributed to increased randomness of solution strategies. Our findings suggest that "smart drugs" increase motivation, but a reduction in quality of effort, crucial to solve complex problems, annuls this effect.
Topics: Humans; Cognition; Methylphenidate; Modafinil; Motivation; Central Nervous System Stimulants
PubMed: 37315143
DOI: 10.1126/sciadv.add4165 -
Current Topics in Behavioral... 2017This chapter reviews methylphenidate misuse, abuse, dependence, diversion, and malingering associated with its use as a prescription medication for... (Review)
Review
This chapter reviews methylphenidate misuse, abuse, dependence, diversion, and malingering associated with its use as a prescription medication for attention-deficit/hyperactivity disorder and the nonmedical use linked to its stimulant effects. Methylphenidate-induced regional elevations in brain dopamine appear to be integral to both efficacy in attention-deficit/hyperactivity disorder and potential for abuse, raising potential concerns for drug safety and prescription drug diversion costs associated with nonmedical use. Regardless, methylphenidate is an important treatment option, and detecting malingering for the purpose of illicit access to methylphenidate for subsequent misuse or diversion is a difficult challenge. Also discussed are the effects of methylphenidate in patients with comorbid substance use disorder and the potential linkage of methylphenidate use with subsequent substance abuse. The current data suggest that methylphenidate misuse and diversion are common health-care problems with a stimulant prescription drug diversion prevalence of approximately 5-10 % of high school students and 5-35 % of college students. The effectiveness and speed of action of methylphenidate are deemed desirable to enhance attention and focus performance for activities such as studying for exams, but methylphenidate is also misused recreationally. These data suggest a need for close screening and therapeutic monitoring of methylphenidate use in the treatment of attention-deficit/hyperactivity disorder.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Malingering; Methylphenidate; Prescription Drug Diversion; Substance-Related Disorders
PubMed: 26695166
DOI: 10.1007/7854_2015_426 -
Child and Adolescent Psychiatric... Jul 2022The psychostimulants-amphetamine and methylphenidate-have been in clinical use for well more than 60 years. In general, both stimulants are rapidly absorbed with... (Review)
Review
The psychostimulants-amphetamine and methylphenidate-have been in clinical use for well more than 60 years. In general, both stimulants are rapidly absorbed with relatively poor bioavailability and short half-lives. The pharmacokinetics of both stimulants are generally linear and dose proportional although substantial interindividual variability in pharmacokinetics is in evidence. Amphetamine (AMP) is highly metabolized by several oxidative enzymes forming multiple metabolites while methylphenidate (MPH) is primarily metabolized by hydrolysis to the inactive metabolite ritalinic acid. At present, pharmacogenomic testing as an aid to guide dosing and personalized treatment cannot be recommended for either agent. Few pharmacokinetically based drug-drug interactions (DDIs) have been documented for either stimulant.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Methylphenidate; Pharmacogenetics
PubMed: 35697392
DOI: 10.1016/j.chc.2022.03.003 -
MMW Fortschritte Der Medizin Jun 2022
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Methylphenidate
PubMed: 35731413
DOI: 10.1007/s15006-022-1261-9 -
The Medical Letter on Drugs and... Jan 2020
Review
Topics: Adrenergic alpha-2 Receptor Agonists; Amphetamines; Attention Deficit Disorder with Hyperactivity; Behavior Therapy; Central Nervous System Stimulants; Child; Child, Preschool; Delayed-Action Preparations; Humans; Methylphenidate; Transcutaneous Electric Nerve Stimulation
PubMed: 31999670
DOI: No ID Found -
European Review For Medical and... Jan 2019In the last decades, several cognitive-enhancing drugs have been sold onto the drug market. Methylphenidate and analogs represent a sub-class of these new psychoactive... (Review)
Review
OBJECTIVE
In the last decades, several cognitive-enhancing drugs have been sold onto the drug market. Methylphenidate and analogs represent a sub-class of these new psychoactive substances (NPS). We aimed to review the use and misuse of methylphenidate and analogs, and the risk associated. Moreover, we exhaustively reviewed the scientific data on the most recent methylphenidate analogs (methylphenidate and ethylphenidate excluded).
MATERIALS AND METHODS
Literature search was performed on methylphenidate and analogs, using specialized search engines accessing scientific databases. Additional reports were retrieved from international agencies, institutional websites, and drug user forums.
RESULTS
Methylphenidate/Ritalin has been used for decades to treat attention deficit disorders and narcolepsy. More recently, it has been used as a cognitive enhancer and a recreational drug. Acute intoxications and fatalities involving methylphenidate were reported. Methylphenidate was scheduled as an illegal drug in many countries, but NPS circumventing the ban and mimicking the psychostimulant effects of methylphenidate started being available: ethylphenidate, 3,4-dichloromethylphenidate, 3,4-dichloroethylphenidate, 4-fluoromethylphenidate, 4-fluoroethylphenidate, methylnaphthidate, ethylnaphthidate, isopropylphenidate, propylphenidate, 4-methylmethylphenidate, and N-benzylethylphenidate have been available in the past few years. Only little data is currently available for these substances. Many intoxications involving methylphenidate analogs were reported. To date, ethylphenidate was involved in 28 fatalities, although it was reportedly directly related to the cause of death in only 7 cases; 3,4-dichloroethylphenidate was involved in 1 death.
CONCLUSIONS
The rapid expansion of methylphenidate analogs onto the drug market in the past few years makes likely the occurrence of intoxications and fatalities in the next years. Careful monitoring and systematic control of methylphenidate analogs should be undertaken to reduce the uprising threat, and education efforts should be made among high-risk populations.
Topics: Central Nervous System Stimulants; Drug and Narcotic Control; Humans; Illicit Drugs; Methylphenidate; Nootropic Agents; Prescription Drug Misuse
PubMed: 30657540
DOI: 10.26355/eurrev_201901_16741 -
Psychopharmacology Oct 2023Working memory deficits and associated neurofunctional abnormalities are frequently reported in attention-deficit/hyperactivity disorder (ADHD). Methylphenidate and... (Randomized Controlled Trial)
Randomized Controlled Trial
RATIONALE
Working memory deficits and associated neurofunctional abnormalities are frequently reported in attention-deficit/hyperactivity disorder (ADHD). Methylphenidate and atomoxetine improve working memory performance and increase activation of regions under-functioning in ADHD. Additionally, methylphenidate has been observed to modulate functional networks involved in working memory. No research, however, has examined the effects of atomoxetine or compared the two drugs.
OBJECTIVES
This study aimed to test methylphenidate and atomoxetine effects on functional connectivity during working memory in boys with ADHD.
METHODS
We tested comparative effects of methylphenidate and atomoxetine on functional connectivity during the n-back task in 19 medication-naïve boys with ADHD (10-15 years old) relative to placebo and assessed potential normalisation effects of brain dysfunctions under placebo relative to 20 age-matched neurotypical boys. Patients were scanned in a randomised, double-blind, cross-over design under single doses of methylphenidate, atomoxetine, and placebo. Controls were scanned once, unmedicated.
RESULTS
Patients under placebo showed abnormally increased connectivity between right superior parietal gyrus (rSPG) and left central operculum/insula. This hyperconnectivity was not observed when patients were under methylphenidate or atomoxetine. Furthermore, under methylphenidate, patients showed increased connectivity relative to controls between right middle frontal gyrus (rMFG) and cingulo-temporo-parietal and striato-thalamic regions, and between rSPG and cingulo-parietal areas. Interrogating these networks within patients revealed increased connectivity between both rMFG and rSPG and right supramarginal gyrus under methylphenidate relative to placebo. Nonetheless, no differences across drug conditions were observed within patients at whole brain level. No drug effects on performance were observed.
CONCLUSIONS
This study shows shared modulating effects of methylphenidate and atomoxetine on parieto-insular connectivity but exclusive effects of methylphenidate on connectivity increases in fronto-temporo-parietal and fronto-striato-thalamic networks in ADHD.
Topics: Male; Humans; Child; Adolescent; Methylphenidate; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Brain; Frontal Lobe; Central Nervous System Stimulants; Magnetic Resonance Imaging
PubMed: 37500785
DOI: 10.1007/s00213-023-06422-7 -
The Lancet. Psychiatry Feb 2024
Topics: Child; Adolescent; Humans; Methylphenidate; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; World Health Organization
PubMed: 38245024
DOI: 10.1016/S2215-0366(23)00437-6 -
Psychiatria Danubina 2021
Topics: Ecchymosis; Humans; Methylphenidate; Postoperative Complications
PubMed: 33857043
DOI: 10.24869/psyd.2021.65 -
European Child & Adolescent Psychiatry Jul 2021For patients with attention deficit hyperactivity disorder and comorbid conduct-dissocial disorder, a combination therapy of the psychostimulant methylphenidate and the... (Review)
Review
For patients with attention deficit hyperactivity disorder and comorbid conduct-dissocial disorder, a combination therapy of the psychostimulant methylphenidate and the antipsychotic risperidone may be prescribed. Case reports describe the occurrence of movement disorders under this combination therapy, but clinical trials had limited power to detect these events. This study aimed (1) to summarise published case reports and (2) to analyse pharmacovigilance data consisting of adverse drug event reports to elucidate these reactions. PubMed, Embase, and APA PsycInfo were used to retrieve case reports. For the pharmacovigilance data, aggregated information on individual case safety reports (ICSRs) within the database of suspected adverse drug events by the WHO were analysed. ICSRs were assessed for disproportionality in reporting. Thirteen published case reports (62% male) on movement disorders were identified, with ages between 5 and 15 years. Seven reports (54%) described incidents when risperidone was tapered down or switched to methylphenidate. From the WHO, we identified 25,556 ICSRs (16,118 for methylphenidate, 8,614 for risperidone, and 824 for both). Of these, 953 (5.9%), 1356 (15.7%), and 159 (19.3%) ICSRs reported movement disorders in association with methylphenidate, risperidone or both, respectively. The analyses on disproportionality showed an increased number of ICSRs with movement disorders when the two drugs were coded in combination. The potential of movement disorders as adverse effects might be amplified when methylphenidate and risperidone are used in combination. The results from the literature underline the necessity of caution and patient monitoring when risperidone dosing is modified during methylphenidate therapy.
Topics: Attention Deficit Disorder with Hyperactivity; Combined Modality Therapy; Comorbidity; Conduct Disorder; Databases, Factual; Humans; Methylphenidate; Movement Disorders; Pharmacovigilance; Risperidone; World Health Organization
PubMed: 32621088
DOI: 10.1007/s00787-020-01589-2