Dexmethylphenidate was approved for medical use in the United States in 2001.[2] It is available as ageneric medication.[4] In 2022, it was the 109th most commonly prescribed medication in the United States, with more than 5million prescriptions.[7][8]
Dexmethylphenidate is used as a treatment forattention deficit hyperactivity disorder (ADHD), usually along with psychological, educational, behavioral or other forms of treatment. It is proposed that stimulants help ameliorate the symptoms of ADHD by making it easier for the user to concentrate, avoid distraction, and control behavior. Placebo-controlled trials have shown that once-daily dexmethylphenidate XR was effective and generally well tolerated.[9]
Improvements in ADHD symptoms in children were significantly greater for dexmethylphenidate XR versus placebo.[9] It also showed greater efficacy thanosmotic controlled-release oral delivery system (OROS) methylphenidate over the first half of the laboratory classroom day but assessments late in the day favoured OROS methylphenidate.[9]
Pregnant women are advised to only use the medication if the benefits outweigh the potential risks.[11] Not enough human studies have been conducted to conclusively demonstrate an effect of methylphenidate onfetal development.[12] In 2018, a review concluded that it has not beenteratogenic in rats and rabbits, and that it "is not a major human teratogen".[13]
Products containing dexmethylphenidate have a side effect profile comparable to those containing methylphenidate.[14]
Addiction experts in psychiatry, chemistry, pharmacology,forensic science, epidemiology, and the police and legal services engaged indelphic analysis regarding 20 popular recreational drugs. Methylphenidate was ranked 13th in dependence, 12th in physical harm, and 18th in social harm.[15]
Results from a 2024 systematic review showed that methylphenidate significantly improves ADHD symptoms and broadband measures but can cause appetite suppression and other adverse events in children and adolescents.[21] Smokers with ADHD who take methylphenidate may increase theirnicotine dependence, and smoke more often than before they began using methylphenidate, with increased nicotine cravings and an average increase of 1.3 cigarettes per day.[22]
There is some evidence of mild reductions in height with prolonged treatment in children.[23] This has been estimated at 1 centimetre (0.4 in) or less per year during the first three years with a total decrease of 3 centimetres (1.2 in) over 10 years.[24][25]
Hypersensitivity (includingskin rash,urticaria, andfever) is sometimes reported when using transdermal methylphenidate. TheDaytrana patch has a much higher rate of skin reactions than oral methylphenidate.[26]
Methylphenidate can worsenpsychosis in people who are psychotic, and in very rare cases it has been associated with the emergence of new psychotic symptoms.[27] It should be used with extreme caution in people withbipolar disorder due to the potential induction ofmania orhypomania.[28] There have been very rare reports ofsuicidal ideation, but some authors claim that evidence does not support a link.[23]Logorrhea is occasionally reported and visualhallucinations are very rarely reported.[18]Priapism is a very rare adverse event that can be potentially serious.[29]
U.S. Food and Drug Administration-commissioned studies in 2011 indicate that in children, young adults, and adults, there is no association between serious adversecardiovascular events (sudden death,heart attack, andstroke) and the medical use of methylphenidate or other ADHD stimulants.[30]
Because some adverse effects may only emerge during chronic use of methylphenidate, a constant watch for adverse effects is recommended.[31]
A 2018Cochrane review found tentative evidence that it may cause non-serious adverse events in children, but found no increase in serious adverse events.[32][a]
Packaging of a formulation of methylphenidate advises against crushing the tablets. It is placed under Schedule X of the Indian drug scheduling system. Schedule X medications typically hold abusable medications such as barbiturates or stimulants such as amphetamines.
Methylphenidate is a stimulant with an addiction liability and dependence liability similar toamphetamine. It has moderate liability amongaddictive drugs;[37][38] accordingly,addiction andpsychological dependence are possible and likely when methylphenidate is used as a recreational drug.[38] When used above the medical dose range, stimulants are associated with the development ofstimulant psychosis.[39]
Methylphenidate has the potential to induceeuphoria due to itspharmacodynamic effect (i.e.,dopamine reuptake inhibition) in the brain'sreward system. At therapeutic doses, ADHD stimulants do not sufficiently activate the reward system; consequently, when taken as directed in doses that are commonly prescribed for the treatment of ADHD, methylphenidate use lacks the capacity to cause anaddiction.[38]
When methylphenidate is coingested withethanol, a metabolite calledethylphenidate is formed viahepatictransesterification,[44][45] not unlike the hepatic formation ofcocaethylene fromcocaine and ethanol. The reduced potency of ethylphenidate and its minor formation means it does not contribute to the pharmacological profile at therapeutic doses, and even in overdose cases, ethylphenidate concentrations remain negligible.[46][45]
Coingestion ofalcohol also increases the blood plasma levels of d-methylphenidate by up to 40%.[47]
Liver toxicity from methylphenidate is extremely rare, but limited evidence suggests that intake ofβ-adrenergic agonists with methylphenidate may increase the risk of liver toxicity.[48]
Dexmethylphenidate has a 4–6 hour duration of effect. A long-acting formulation, Focalin XR, which spans 12 hours is also available and has been shown to be as effective asDL (dextro-, levo-)-TMP (threo-methylphenidate) XR (extended release) (Concerta, Ritalin LA), with flexible dosing and good tolerability.[49][50] It has also been demonstrated to reduce ADHD symptoms in both children[51] and adults.[52] d-MPH has a similar side-effect profile to MPH[14] and can be administered without regard to food intake.[53]
CTx-1301 is an experimental medication that is an extended-release formulation of dexmethylphenidate that has a half life more than an hour longer than extended-release dexmethylphenidate (d-MPH-ER). It is under development for ADHD.[54][55][56][57][58]
Although fourstereoisomers ofmethylphenidate (MPH) are possible, only thethreodiastereoisomers are used in modern practice. There is a higheudysmic ratio between the SS and RRenantiomers of MPH. Dexmethylphenidate (d-threo-methylphenidate) is a preparation of the RR enantiomer of methylphenidate.[61][62] In theory,D-TMP (d-threo-methylphenidate) can be anticipated to be twice the strength of theracemic product.[59][63]
^"Our findings suggest that methylphenidate may be associated with a number of serious adverse events as well as a large number of non-serious adverse events in children" "Concerning adverse events associated with the treatment, our systematic review of randomised clinical trials (RCTs) demonstrated no increase in serious adverse events, but a high proportion of participants suffered a range of non-serious adverse events."[32]
^The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. ... However, fatalities are rare with appropriate care.[35]
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