Dexmethylphenidate

Last updated

Dexmethylphenidate
Dexmethylphenidate structure.svg
Dextromethylphenidate-based-on-hydrochloride-xtal-1995-3D-balls.png
Clinical data
Trade names Focalin, Focalin XR, others
Other namesd-threo-methylphenidate (D-TMP)
AHFS/Drugs.com Monograph
MedlinePlus a603014
License data
Dependence
liability 		Physical: None[ medical citation needed ]; Psychological: High
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 11–52%
Protein binding 30%
Metabolism Liver
Elimination half-life 4 hours
Excretion Kidney
Identifiers
  • (R,R)-(+)-Methyl 2-phenyl-2-(2-piperidyl)acetate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C14H19NO2
Molar mass 233.311 g·mol−1
3D model (JSmol)
  • O=C([C@@H]([C@@H]1NCCCC1)C2=CC=CC=C2)OC

  • hydrochloride: Cl.[H][C@@](C(=O)OC)(C1=CC=CC=C1)[C@@]1([H])CCCCN1
  • InChI=1S/C14H19NO2/c1-17-14(16)13(11-7-3-2-4-8-11)12-9-5-6-10-15-12/h2-4,7-8,12-13,15H,5-6,9-10H2,1H3/t12-,13-/m1/s1 Yes check.svgY
  • Key:DUGOZIWVEXMGBE-CHWSQXEVSA-N Yes check.svgY

  • hydrochloride: InChI=1S/C14H19NO2.ClH/c1-17-14(16)13(11-7-3-2-4-8-11)12-9-5-6-10-15-12;/h2-4,7-8,12-13,15H,5-6,9-10H2,1H3;1H/t12-,13-;/m1./s1
  • Key:JUMYIBMBTDDLNG-OJERSXHUSA-N
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Dexmethylphenidate, sold under the brand name Focalin among others, is a potent central nervous system (CNS) stimulant used to treat attention deficit hyperactivity disorder (ADHD) in those over the age of five years. [3] It is taken by mouth. [3] The immediate release formulation lasts up to five hours while the extended release formulation lasts up to twelve hours. [4] It is the more active enantiomer of methylphenidate. [3]

Contents

Common side effects include abdominal pain, loss of appetite, and fever. [3] Serious side effects may include abuse, psychosis, sudden cardiac death, mania, anaphylaxis, seizures, and dangerously prolonged erection. [3] Safety during pregnancy and breastfeeding is unclear. [5] Dexmethylphenidate is a central nervous system (CNS) stimulant. [6] [3] How it works in ADHD is unclear. [3]

Dexmethylphenidate was approved for medical use in the United States in 2001. [1] It is available as a generic medication. [3] In 2020, it was the 130th most commonly prescribed medication in the United States, with more than 4 million prescriptions. [7] [8]

Medical uses

Dexmethylphenidate is used as a treatment for 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. [6]

Improvements in ADHD symptoms in children were significantly greater for dexmethylphenidate XR versus placebo. [6] It also showed greater efficacy than osmotic 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. [6]

Contraindications

Methylphenidate is contraindicated for individuals using monoamine oxidase inhibitors (e.g., phenelzine, and tranylcypromine), or individuals with agitation, tics, glaucoma, heart defects or a hypersensitivity to any ingredients contained in methylphenidate pharmaceuticals. [9]

Pregnant women are advised to only use the medication if the benefits outweigh the potential risks. [10] Not enough human studies have been conducted to conclusively demonstrate an effect of methylphenidate on fetal development. [11] In 2018, a review concluded that it has not been teratogenic in rats and rabbits, and that it "is not a major human teratogen". [12]

Adverse effects

Products containing dexmethylphenidate have a side effect profile comparable to those containing methylphenidate. [13]

Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs. Methylphenidate was ranked 13th in dependence, 12th in physical harm, and 18th in social harm. Rational harm assessment of drugs radar plot.svg
Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs. Methylphenidate was ranked 13th in dependence, 12th in physical harm, and 18th in social harm.

The most common side effects associated with methylphenidate (in standard and extended-release formulations) are appetite loss, dry mouth, anxiety/nervousness, nausea, and insomnia. [15] Gastrointestinal adverse effects may include abdominal pain and weight loss. Nervous system adverse effects may include akathisia (agitation/restlessness), irritability, dyskinesia (tics), Oromandibular dystonia, [16] lethargy (drowsiness/fatigue), and dizziness. Cardiac adverse effects may include palpitations, changes in blood pressure, and heart rate (typically mild), and tachycardia (rapid heart rate). [17] Ophthalmologic adverse effects may include blurred vision caused by pupil dilatation and dry eyes, with less frequent reports of diplopia and mydriasis [ contradictory ]. [18] [19]

Smokers with ADHD who take methylphenidate may increase their nicotine 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. [20]

There is some evidence of mild reductions in height with prolonged treatment in children. [21] 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. [22] [23]

Hypersensitivity (including skin rash, urticaria, and fever) is sometimes reported when using transdermal methylphenidate. The Daytrana patch has a much higher rate of skin reactions than oral methylphenidate. [24]

Methylphenidate can worsen psychosis in people who are psychotic, and in very rare cases it has been associated with the emergence of new psychotic symptoms. [25] It should be used with extreme caution in people with bipolar disorder due to the potential induction of mania or hypomania. [26] There have been very rare reports of suicidal ideation, but some authors claim that evidence does not support a link. [21] Logorrhea is occasionally reported and visual hallucinations are very rarely reported. [18] Priapism is a very rare adverse event that can be potentially serious. [27]

U.S. Food and Drug Administration-commissioned studies in 2011 indicate that in children, young adults, and adults, there is no association between serious adverse cardiovascular events (sudden death, heart attack, and stroke) and the medical use of methylphenidate or other ADHD stimulants. [28]

Because some adverse effects may only emerge during chronic use of methylphenidate, a constant watch for adverse effects is recommended. [29]

A 2018 Cochrane review found that methylphenidate might be associated with serious side effects such as heart problems, psychosis, and death. The certainty of the evidence was stated as very low. [30]

The same review found tentative evidence that it may cause both serious and non-serious adverse effects in children. [30] [lower-alpha 1]

Overdose

The symptoms of a moderate acute overdose on methylphenidate primarily arise from central nervous system overstimulation; these symptoms include: vomiting, nausea, agitation, tremors, hyperreflexia, muscle twitching, euphoria, confusion, hallucinations, delirium, hyperthermia, sweating, flushing, headache, tachycardia, heart palpitations, cardiac arrhythmias, hypertension, mydriasis, and dryness of mucous membranes. [9] [31] A severe overdose may involve symptoms such as hyperpyrexia, sympathomimetic toxidrome, convulsions, paranoia, stereotypy (a repetitive movement disorder), rhabdomyolysis, coma, and circulatory collapse. [9] [31] [32] [lower-alpha 2] A methylphenidate overdose is rarely fatal with appropriate care. [32] Following injection of methylphenidate tablets into an artery, severe toxic reactions involving abscess formation and necrosis have been reported. [33]

Treatment of a methylphenidate overdose typically involves the administration of benzodiazepines, with antipsychotics, α-adrenoceptor agonists and propofol serving as second-line therapies. [32]

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. Add Wize Methylphenidate Warning.jpg
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.

Addiction and dependence

Methylphenidate is a stimulant with an addiction liability and dependence liability similar to amphetamine. It has moderate liability among addictive drugs; [34] [35] accordingly, addiction and psychological dependence are possible and likely when methylphenidate is used at high doses as a recreational drug. [35] When used above the medical dose range, stimulants are associated with the development of stimulant psychosis. [36]

Biomolecular mechanisms

Further information: Addiction § Biomolecular mechanisms

Methylphenidate has the potential to induce euphoria due to its pharmacodynamic effect (i.e., dopamine reuptake inhibition) in the brain's reward 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 an addiction. [35]

Interactions

Methylphenidate may inhibit the metabolism of vitamin K anticoagulants, certain anticonvulsants, and some antidepressants (tricyclic antidepressants, and selective serotonin reuptake inhibitors). Concomitant administration may require dose adjustments, possibly assisted by monitoring of plasma drug concentrations. [37] There are several case reports of methylphenidate inducing serotonin syndrome with concomitant administration of antidepressants. [38] [39] [40] [41]

When methylphenidate is coingested with ethanol, a metabolite called ethylphenidate is formed via hepatic transesterification, [42] [43] not unlike the hepatic formation of cocaethylene from cocaine 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. [44] [43]

Coingestion of alcohol (ethanol) also increases the blood plasma levels of d-methylphenidate by up to 40%. [45]

Liver toxicity from methylphenidate is extremely rare, but limited evidence suggests that intake of β-adrenergic agonists with methylphenidate may increase the risk of liver toxicity. [46]

Mode of activity

Methylphenidate is a catecholamine reuptake inhibitor that indirectly increases catecholaminergic neurotransmission by inhibiting the dopamine transporter (DAT) and norepinephrine transporter (NET), [47] which are responsible for clearing catecholamines from the synapse, particularly in the striatum and meso-limbic system. [48] Moreover, it is thought to "increase the release of these monoamines into the extraneuronal space." [2]

Although four stereoisomers of methylphenidate (MPH) are possible, only the threo diastereoisomers are used in modern practice. There is a high eudysmic ratio between the SS and RR enantiomers of MPH. Dexmethylphenidate (d-threo-methylphenidate) is a preparation of the RR enantiomer of methylphenidate. [49] [50] In theory, D-TMP (d-threo-methylphenidate) can be anticipated to be twice the strength of the racemic product. [47] [51]

Compd [52] DAT (Ki)DA (IC50)NET (Ki)NE (IC50)
D-TMP1612320639
L-TMP22501600>10K980
DL-TMP1212078851

Pharmacology

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 as DL (dextro-, levo-)-TMP (threo-methylphenidate) XR (extended release) (Concerta, Ritalin LA), with flexible dosing and good tolerability. [53] [54] It has also been demonstrated to reduce ADHD symptoms in both children [55] and adults. [56] d-MPH has a similar side-effect profile to MPH [13] and can be administered without regard to food intake. [57]

See also

Notes

  1. ↑ "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." [30]
  2. ↑ 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. [32]

Related Research Articles

<span class="mw-page-title-main">Tricyclic antidepressant</span> Class of medications

Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains three rings of atoms. Tetracyclic antidepressants (TeCAs), which contain four rings of atoms, are a closely related group of antidepressant compounds.

<span class="mw-page-title-main">Attention deficit hyperactivity disorder</span> Neurodevelopmental disorder

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by executive dysfunction occasioning symptoms of inattention, hyperactivity, impulsivity and emotional dysregulation that are excessive and pervasive, impairing in multiple contexts, and otherwise age-inappropriate.

<span class="mw-page-title-main">Methylphenidate</span> Central nervous system stimulant

Methylphenidate, sold under the brand names Ritalin and Concerta among others, is a central nervous system (CNS) stimulant used medically to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, narcolepsy. It is a primary medication for ADHD ; it may be taken by mouth or applied to the skin, and different formulations have varying durations of effect, commonly ranging from 2–4 hours.

<span class="mw-page-title-main">Dextroamphetamine</span> CNS stimulant and isomer of amphetamine

Dextroamphetamine is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant.

<span class="mw-page-title-main">Clonidine</span> Medication for high blood pressure

Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal, menopausal flushing, diarrhea, spasticity, and certain pain conditions. It is used orally, by injection, or as a transdermal skin patch. Onset of action is typically within an hour with the effects on blood pressure lasting for up to eight hours.

Stimulant psychosis is a mental disorder characterized by psychotic symptoms. It involves and typically occurs following an overdose or several day 'binge' on psychostimulants; however, one study reported occurrences at regularly prescribed doses in approximately 0.1% of individuals within the first several weeks after starting amphetamine or methylphenidate therapy. Methamphetamine psychosis, or long-term effects of stimulant use in the brain, depend upon genetics and may persist for some time.

A paradoxical reaction is an effect of a chemical substance, such as a medical drug, that is opposite to what would usually be expected. An example of a paradoxical reaction is pain caused by a pain relief medication.

<span class="mw-page-title-main">Atomoxetine</span> Medication used to treat ADHD

Atomoxetine, sold under the brand name Strattera, is a medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, cognitive disengagement syndrome. It may be used alone or along with psychostimulants. It is also used as a cognitive and executive functioning enhancer to improve self-motivation, persistence, attention, inhibition, and working memory. Use of atomoxetine is only recommended for those who are at least six years old. It is taken orally. Atomoxetine is a selective norepinephrine reuptake inhibitor and is believed to work by increasing norepinephrine and dopamine levels in the brain. The effectiveness of atomoxetine is comparable to the commonly prescribed stimulant medication methylphenidate.

<span class="mw-page-title-main">Adderall</span> Drug mixture used mainly to treat ADHD and narcolepsy

Adderall and Mydayis are trade names for a combination drug called mixed amphetamine salts containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio between dextroamphetamine and levoamphetamine, the two enantiomers of amphetamine. Both enantiomers are stimulants, but differ enough to give Adderall an effects profile distinct from those of racemic amphetamine or dextroamphetamine, which are marketed as Evekeo and Dexedrine/Zenzedi, respectively. Adderall is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used illicitly as an athletic performance enhancer, cognitive enhancer, appetite suppressant, and recreationally as a euphoriant. It is a central nervous system (CNS) stimulant of the phenethylamine class.

A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission.

Adult Attention Deficit Hyperactivity Disorder is the persistence of attention deficit hyperactivity disorder (ADHD) in adults. It is a neurodevelopmental disorder, meaning symptoms must have been present in childhood except for when ADHD occurs after traumatic brain injury. Specifically, for ADHD, multiple symptoms must have been present before the age of 12, according to DSM-5 diagnostic criteria. This cutoff age of 12 is a change from the previous requirement of symptom onset before the age of 7 in the DSM-IV to add flexibility in the diagnosis of adults. ADHD was previously thought to be a childhood disorder that improved with age, but recent research has disproved this. Approximately two-thirds of childhood cases of ADHD continue into adulthood, with varying degrees of symptom severity that change over time, and continue to significantly affect individuals' daily functioning in multiple domains.

<span class="mw-page-title-main">Pemoline</span> Stimulant, used in the treatment of ADHD

Pemoline, sold under the brand name Cylert among others, is a stimulant medication which has been used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. It has been discontinued in most countries due to rare but serious problems with liver toxicity. The medication was taken by mouth.

<span class="mw-page-title-main">Viloxazine</span> Medication used to treat ADHD

Viloxazine, sold under the brand name Qelbree and formerly as Vivalan among others, is a selective norepinephrine reuptake inhibitor medication which is used in the treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. It was marketed for almost 30 years as an antidepressant for the treatment of depression before being discontinued and subsequently repurposed as a treatment for ADHD. Viloxazine is taken orally. It was used as an antidepressant in an immediate-release form and is used in ADHD in an extended-release form.

<span class="mw-page-title-main">Guanfacine</span> Medication used for high blood pressure and ADHD

Guanfacine, sold under the brand name Tenex (immediate-release) and Intuniv (extended-release) among others, is an oral alpha-2a agonist medication used to treat attention deficit hyperactivity disorder (ADHD) and high blood pressure. Guanfacine is FDA-approved for monotherapy treatment of ADHD, as well as being used for augmentation of other treatments, such as stimulants. Guanfacine is also used off-label to treat tic disorders, anxiety disorders and PTSD.

Attention deficit hyperactivity disorder predominantly inattentive, is one of the three presentations of attention deficit hyperactivity disorder (ADHD). In 1987–1994, there were no subtypes and thus it was not distinguished from hyperactive ADHD in the Diagnostic and Statistical Manual (DSM-III-R).

<span class="mw-page-title-main">Attention deficit hyperactivity disorder controversies</span>

Despite the scientifically well-established nature of attention deficit hyperactivity disorder (ADHD), its diagnosis, and its treatment, each of these has been controversial since the 1970s. The controversies involve clinicians, teachers, policymakers, parents, and the media. Positions range from the view that ADHD is within the normal range of behavior to the hypothesis that ADHD is a genetic condition. Other areas of controversy include the use of stimulant medications in children, the method of diagnosis, and the possibility of overdiagnosis. In 2009, the National Institute for Health and Care Excellence, while acknowledging the controversy, stated that the current treatments and methods of diagnosis are based on the dominant view of the academic literature.

<span class="mw-page-title-main">Lisdexamfetamine</span> Central nervous system stimulant prodrug

Lisdexamfetamine, most commonly sold under the brand name Vyvanse and Elvanse among others, is a stimulant medication that is used to treat attention deficit hyperactivity disorder (ADHD) in children and adults, and for moderate-to-severe binge eating disorder in adults. Lisdexamfetamine is taken by mouth. Its effects generally begin within two hours and last for up to 14 hours. In the United Kingdom, it is usually less preferred to methylphenidate for the treatment of children.

Attention deficit hyperactivity disorder management options are evidence-based practices with established treatment efficacy for ADHD.

<span class="mw-page-title-main">Isopropylphenidate</span> Stimulant designer drugs

Isopropylphenidate is a piperidine based stimulant drug, closely related to methylphenidate, but with the methyl ester replaced by an isopropyl ester. It has similar effects to methylphenidate but with a longer duration of action, and was banned in the UK as a Temporary Class Drug from April 2015 following its unapproved sale as a designer drug.

<span class="mw-page-title-main">Serdexmethylphenidate/dexmethylphenidate</span> A combination of CNS Stimulants

Serdexmethylphenidate/dexmethylphenidate, sold under the brand name Azstarys, is a fixed-dose combination medication containing serdexmethylphenidate, a prodrug of dexmethylphenidate, and dexmethylphenidate, a d-threo enantiomer of racemic methylphenidate, which is used to treat attention deficit hyperactivity disorder (ADHD) in people aged six years and older.

References

  1. 1 2 "Focalin- dexmethylphenidate hydrochloride tablet". DailyMed. 24 June 2020. Retrieved 15 November 2020.
  2. 1 2 "Focalin XR- dexmethylphenidate hydrochloride capsule, extended release". DailyMed. 27 June 2020. Retrieved 15 November 2020.
  3. 1 2 3 4 5 6 7 8 "Dexmethylphenidate Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 15 April 2019.
  4. ↑ Mosby's Drug Reference for Health Professions - E-Book. Elsevier Health Sciences. 2013. p. 455. ISBN   9780323187602.
  5. ↑ "Dexmethylphenidate Use During Pregnancy". Drugs.com. Retrieved 15 April 2019.
  6. 1 2 3 4 Moen MD, Keam SJ (December 2009). "Dexmethylphenidate extended release: a review of its use in the treatment of attention-deficit hyperactivity disorder". CNS Drugs. 23 (12): 1057–83. doi:10.2165/11201140-000000000-00000. PMID   19958043. S2CID   24975170.
  7. ↑ "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  8. ↑ "Dexmethylphenidate Hydrochloride - Drug Usage Statistics". ClinCalc. Archived from the original on 12 April 2020. Retrieved 7 October 2022.
  9. 1 2 3 "Daytrana- methylphenidate patch". DailyMed. 15 June 2021. Retrieved 26 March 2022.
  10. ↑ "Methylphenidate: Use During Pregnancy and Breastfeeding". Drugs.com. Archived from the original on 2 January 2018.
  11. ↑ Humphreys C, Garcia-Bournissen F, Ito S, Koren G (July 2007). "Exposure to attention deficit hyperactivity disorder medications during pregnancy". Canadian Family Physician. 53 (7): 1153–1155. PMC   1949295 . PMID   17872810.
  12. ↑ Ornoy A (February 2018). "Pharmacological Treatment of Attention Deficit Hyperactivity Disorder During Pregnancy and Lactation". Pharmaceutical Research. 35 (3): 46. doi:10.1007/s11095-017-2323-z. PMID   29411149. S2CID   3663423.
  13. 1 2 Keating GM, Figgitt DP (2002). "Dexmethylphenidate". Drugs. 62 (13): 1899–904, discussion 1905–8. doi:10.2165/00003495-200262130-00009. PMID   12215063. S2CID   249894173.
  14. ↑ Nutt D, King LA, Saulsbury W, Blakemore C (March 2007). "Development of a rational scale to assess the harm of drugs of potential misuse". Lancet. 369 (9566): 1047–1053. doi:10.1016/S0140-6736(07)60464-4. PMID   17382831. S2CID   5903121.
  15. ↑ Coghill D, Banaschewski T, Zuddas A, Pelaz A, Gagliano A, Doepfner M (September 2013). "Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies". BMC Psychiatry. Springer Science and Business Media LLC. 13 (1): 237. doi: 10.1186/1471-244x-13-237 . PMC   3852277 . PMID   24074240.
  16. ↑ Rissardo JP, Caprara AL (2020). "Oromandibular dystonia secondary to methylphenidate: A case report and literature review". Int Arch Health Sci. 7: 108–111. doi: 10.4103/iahs.iahs_71_19 (inactive 1 August 2023). Archived from the original on 15 November 2021. Retrieved 15 November 2021– via Gale Academic OneFile.{{cite journal}}: CS1 maint: DOI inactive as of August 2023 (link)
  17. ↑ "Ritalin LA (methylphenidate hydrochloride) extended-release capsules" (PDF). Novartis. Archived from the original (PDF) on 20 July 2011.
  18. 1 2 de Sousa A, Kalra G (January 2012). "Drug therapy of attention deficit hyperactivity disorder: current trends". Mens Sana Monographs. 10 (1): 45–69. doi: 10.4103/0973-1229.87261 . PMC   3353606 . PMID   22654382.
  19. ↑ Jaanus SD (1992). "Ocular side effects of selected systemic drugs". Optometry Clinics. 2 (4): 73–96. PMID   1363080.
  20. ↑ Bron TI, Bijlenga D, Kasander MV, Spuijbroek AT, Beekman AT, Kooij JJ (June 2013). "Long-term relationship between methylphenidate and tobacco consumption and nicotine craving in adults with ADHD in a prospective cohort study". European Neuropsychopharmacology. 23 (6): 542–554. doi:10.1016/j.euroneuro.2012.06.004. PMID   22809706. S2CID   23148548.
  21. 1 2 Cortese S, Holtmann M, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, et al. (March 2013). "Practitioner review: current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents". Journal of Child Psychology and Psychiatry, and Allied Disciplines. 54 (3): 227–246. doi:10.1111/jcpp.12036. PMID   23294014.
  22. ↑ Poulton A (August 2005). "Growth on stimulant medication; clarifying the confusion: a review". Archives of Disease in Childhood. 90 (8): 801–806. doi:10.1136/adc.2004.056952. PMC   1720538 . PMID   16040876.
  23. ↑ Hinshaw SP, Arnold LE (January 2015). "ADHD, Multimodal Treatment, and Longitudinal outcome: Evidence, paradox, and challenge". Wiley Interdisciplinary Reviews. Cognitive Science. 6 (1): 39–52. doi:10.1002/wcs.1324. PMC   4280855 . PMID   25558298.
  24. ↑ Findling RL, Dinh S (March 2014). "Transdermal therapy for attention-deficit hyperactivity disorder with the methylphenidate patch (MTS)". CNS Drugs. 28 (3): 217–228. doi:10.1007/s40263-014-0141-y. PMC   3933749 . PMID   24532028.
  25. ↑ Kraemer M, Uekermann J, Wiltfang J, Kis B (July 2010). "Methylphenidate-induced psychosis in adult attention-deficit/hyperactivity disorder: report of 3 new cases and review of the literature". Clinical Neuropharmacology. 33 (4): 204–206. doi:10.1097/WNF.0b013e3181e29174. PMID   20571380. S2CID   34956456.
  26. ↑ Wingo AP, Ghaemi SN (2008). "Frequency of stimulant treatment and of stimulant-associated mania / hypomania in bipolar disorder patients". Psychopharmacology Bulletin. 41 (4): 37–47. PMID   19015628.
  27. ↑ "Methylphenidate ADHD medications: Drug safety communication – risk of long-lasting erections". U.S. Food and Drug Administration (FDA). 17 December 2013. Archived from the original on 17 December 2013. Retrieved 17 December 2013.
  28. ↑ "FDA drug safety communication: Safety review update of medications used to treat attention-ceficit / hyperactivity disorder (ADHD) in children and young adults". U.S. Food and Drug Administration (FDA). 20 December 2011. Archived from the original on 30 October 2013. Retrieved 4 November 2013.Cooper WO, Habel LA, Sox CM, Chan KA, Arbogast PG, Cheetham TC, et al. (November 2011). "ADHD drugs and serious cardiovascular events in children and young adults". The New England Journal of Medicine. 365 (20): 1896–1904. doi:10.1056/NEJMoa1110212. PMC   4943074 . PMID   22043968. "FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in adults". U.S. Food and Drug Administration (FDA). 15 December 2011. Archived from the original on 30 October 2013. Retrieved 4 November 2013.Habel LA, Cooper WO, Sox CM, Chan KA, Fireman BH, Arbogast PG, et al. (December 2011). "ADHD medications and risk of serious cardiovascular events in young and middle-aged adults". JAMA. 306 (24): 2673–2683. doi:10.1001/jama.2011.1830. PMC   3350308 . PMID   22161946.
  29. ↑ Gordon N (1999). "Attention deficit hyperactivity disorder: Possible causes and treatment". International Journal of Clinical Practice. 53 (7): 524–528. doi:10.1111/j.1742-1241.1999.tb11794.x. PMID   10692738. S2CID   27462347.
  30. 1 2 3 Storebø OJ, Pedersen N, Ramstad E, Kielsholm ML, Nielsen SS, Krogh HB, et al. (May 2018). "Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies". The Cochrane Database of Systematic Reviews (Systematic Review). 5 (5): CD012069. doi:10.1002/14651858.CD012069.pub2. PMC   6494554 . PMID   29744873.
  31. 1 2 Heedes G, Ailakis J. "Methylphenidate hydrochloride (PIM 344)". INCHEM. International Programme on Chemical Safety. Archived from the original on 23 June 2015. Retrieved 23 June 2015.
  32. 1 2 3 4 Spiller HA, Hays HL, Aleguas A (July 2013). "Overdose of drugs for attention-deficit hyperactivity disorder: Clinical presentation, mechanisms of toxicity, and management". CNS Drugs. 27 (7): 531–543. doi: 10.1007/s40263-013-0084-8 . PMID   23757186. S2CID   40931380.
  33. ↑ Bruggisser M, Bodmer M, Liechti ME (2011). "Severe toxicity due to injected but not oral or nasal abuse of methylphenidate tablets". Swiss Medical Weekly. 141: w13267. doi: 10.4414/smw.2011.13267 . PMID   21984207.
  34. ↑ Morton WA, Stockton GG (October 2000). "Methylphenidate Abuse and Psychiatric Side Effects". Primary Care Companion to the Journal of Clinical Psychiatry. 2 (5): 159–164. doi:10.4088/PCC.v02n0502. PMC   181133 . PMID   15014637.
  35. 1 2 3 Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and addictive disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A foundation for clinical neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 368. ISBN   9780071481274.
  36. ↑ Auger RR, Goodman SH, Silber MH, Krahn LE, Pankratz VS, Slocumb NL (June 2005). "Risks of high-dose stimulants in the treatment of disorders of excessive somnolence: A case-control study". Sleep. 28 (6): 667–672. doi: 10.1093/sleep/28.6.667 . PMID   16477952.
  37. ↑ "Concerta- methylphenidate hydrochloride tablet, extended release". DailyMed. 1 July 2021. Archived from the original on 26 March 2017. Retrieved 26 March 2022.
  38. ↑ Ishii M, Tatsuzawa Y, Yoshino A, Nomura S (April 2008). "Serotonin syndrome induced by augmentation of SSRI with methylphenidate". Psychiatry and Clinical Neurosciences. 62 (2): 246. doi: 10.1111/j.1440-1819.2008.01767.x . PMID   18412855. S2CID   5659107.
  39. ↑ Türkoğlu S (2015). "Serotonin syndrome with sertraline and methylphenidate in an adolescent". Clinical Neuropharmacology. 38 (2): 65–66. doi:10.1097/WNF.0000000000000075. PMID   25768857. S2CID   38523209.
  40. ↑ Park YM, Jung YK (May 2010). "Manic switch and serotonin syndrome induced by augmentation of paroxetine with methylphenidate in a patient with major depression". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 34 (4): 719–720. doi:10.1016/j.pnpbp.2010.03.016. PMID   20298736. S2CID   31984813.
  41. ↑ Bodner RA, Lynch T, Lewis L, Kahn D (February 1995). "Serotonin syndrome". Neurology. 45 (2): 219–223. doi:10.1212/wnl.45.2.219. PMID   7854515. S2CID   35190429.
  42. ↑ Patrick KS, González MA, Straughn AB, Markowitz JS (January 2005). "New methylphenidate formulations for the treatment of attention-deficit/hyperactivity disorder". Expert Opinion on Drug Delivery. 2 (1): 121–143. doi:10.1517/17425247.2.1.121. PMID   16296740. S2CID   25026467.
  43. 1 2 Markowitz JS, DeVane CL, Boulton DW, Nahas Z, Risch SC, Diamond F, Patrick KS (June 2000). "Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and ethanol". Drug Metabolism and Disposition. 28 (6): 620–624. PMID   10820132.
  44. ↑ Markowitz JS, Logan BK, Diamond F, Patrick KS (August 1999). "Detection of the novel metabolite ethylphenidate after methylphenidate overdose with alcohol coingestion". Journal of Clinical Psychopharmacology. 19 (4): 362–366. doi:10.1097/00004714-199908000-00013. PMID   10440465.
  45. ↑ Patrick KS, Straughn AB, Minhinnett RR, Yeatts SD, Herrin AE, DeVane CL, et al. (March 2007). "Influence of ethanol and gender on methylphenidate pharmacokinetics and pharmacodynamics". Clinical Pharmacology and Therapeutics. 81 (3): 346–353. doi:10.1038/sj.clpt.6100082. PMC   3188424 . PMID   17339864.
  46. ↑ Roberts SM, DeMott RP, James RC (1997). "Adrenergic modulation of hepatotoxicity". Drug Metabolism Reviews. 29 (1–2): 329–353. doi:10.3109/03602539709037587. PMID   9187524.
  47. 1 2 Markowitz JS, Patrick KS (June 2008). "Differential pharmacokinetics and pharmacodynamics of methylphenidate enantiomers: does chirality matter?". Journal of Clinical Psychopharmacology. 28 (3 Suppl 2): S54-61. doi:10.1097/JCP.0b013e3181733560. PMID   18480678.
  48. ↑ Schweri MM, Skolnick P, Rafferty MF, Rice KC, Janowsky AJ, Paul SM (October 1985). "[3H]Threo-(+/-)-methylphenidate binding to 3,4-dihydroxyphenylethylamine uptake sites in corpus striatum: correlation with the stimulant properties of ritalinic acid esters". Journal of Neurochemistry. 45 (4): 1062–70. doi:10.1111/j.1471-4159.1985.tb05524.x. PMID   4031878. S2CID   28720285.
  49. ↑ Ding YS, Fowler JS, Volkow ND, Dewey SL, Wang GJ, Logan J, et al. (May 1997). "Chiral drugs: comparison of the pharmacokinetics of [11C]d-threo and L-threo-methylphenidate in the human and baboon brain". Psychopharmacology. 131 (1): 71–8. doi:10.1007/s002130050267. PMID   9181638. S2CID   26046917.
  50. ↑ Ding YS, Gatley SJ, Thanos PK, Shea C, Garza V, Xu Y, et al. (September 2004). "Brain kinetics of methylphenidate (Ritalin) enantiomers after oral administration". Synapse. 53 (3): 168–75. CiteSeerX   10.1.1.514.7833 . doi:10.1002/syn.20046. PMID   15236349. S2CID   11664668.
  51. ↑ Davids E, Zhang K, Tarazi FI, Baldessarini RJ (February 2002). "Stereoselective effects of methylphenidate on motor hyperactivity in juvenile rats induced by neonatal 6-hydroxydopamine lesioning". Psychopharmacology. 160 (1): 92–8. doi:10.1007/s00213-001-0962-5. PMID   11862378. S2CID   8037050.
  52. ↑ Williard RL, Middaugh LD, Zhu HJ, Patrick KS (February 2007). "Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity". Behavioural Pharmacology. 18 (1): 39–51. doi:10.1097/FBP.0b013e3280143226. PMID   17218796. S2CID   20232871.
  53. ↑ McGough JJ, Pataki CS, Suddath R (July 2005). "Dexmethylphenidate extended-release capsules for attention deficit hyperactivity disorder". Expert Review of Neurotherapeutics. 5 (4): 437–41. doi:10.1586/14737175.5.4.437. PMID   16026226. S2CID   6561452.
  54. ↑ Silva R, Tilker HA, Cecil JT, Kowalik S, Khetani V, Faleck H, Patin J (2004). "Open-label study of dexmethylphenidate hydrochloride in children and adolescents with attention deficit hyperactivity disorder". Journal of Child and Adolescent Psychopharmacology. 14 (4): 555–63. doi:10.1089/cap.2004.14.555. PMID   15662147.
  55. ↑ Arnold LE, Lindsay RL, Conners CK, Wigal SB, Levine AJ, Johnson DE, et al. (Winter 2004). "A double-blind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention deficit hyperactivity disorder". Journal of Child and Adolescent Psychopharmacology. 14 (4): 542–54. doi:10.1089/cap.2004.14.542. PMID   15662146.
  56. ↑ Spencer TJ, Adler LA, McGough JJ, Muniz R, Jiang H, Pestreich L (June 2007). "Efficacy and safety of dexmethylphenidate extended-release capsules in adults with attention-deficit/hyperactivity disorder". Biological Psychiatry. 61 (12): 1380–7. doi: 10.1016/j.biopsych.2006.07.032 . PMID   17137560. S2CID   45976373.
  57. ↑ Teo SK, Scheffler MR, Wu A, Stirling DI, Thomas SD, Stypinski D, Khetani VD (February 2004). "A single-dose, two-way crossover, bioequivalence study of dexmethylphenidate HCl with and without food in healthy subjects". Journal of Clinical Pharmacology. 44 (2): 173–8. doi:10.1177/0091270003261899. PMID   14747426. S2CID   20694072.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.