Instruct: Given a question, retrieve documents that can help answer the question.
Query: Is dexmethylphenidate addictive?
Methylphenidate is a stimulant with an addiction liability and dependence liability similar to amphetamine. It has moderate liability among addictive drugs;[27][28] accordingly, addiction and psychological dependence are possible and likely when methylphenidate is used at high doses as a recreational drug.[28][29] When used above the medical dose range, stimulants are associated with the development of stimulant psychosis.[30] As with all addictive drugs, the overexpression of ΔFosB in D1-type medium spiny neurons in the nucleus accumbens is implicated in methylphenidate addiction.[29][31]
There are two major medications derived from methylphenidate's isomers: a racemic mixture of half d-threo-methylphenidate and half l-threo-methylphenidate called methylphenidate (Ritalin, Concerta), and an enantiopure formulation containing just d-threo-methylphenidate called dexmethylphenidate (Focalin).
Methylphenidate has the potential to induce euphoria due to its pharmacodynamic effect (i.e., dopamine reuptake inhibition) in the brain's reward system.[31] At therapeutic doses, ADHD stimulants do not sufficiently activate the reward system, or the reward pathway in particular, to the extent necessary to cause persistent increases in ΔFosB gene expression in the D1-type medium spiny neurons of the nucleus accumbens;[28][31][38] 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.[28][31][38] However, when methylphenidate is used at sufficiently high recreational doses through a bioavailable route of administration (e.g., insufflation or intravenous administration), particularly for use of the drug as a euphoriant, ΔFosB accumulates in the nucleus accumbens.[28][31] Hence, like any other addictive drug, regular recreational use of methylphenidate at high doses eventually gives rise to ΔFosB overexpression in D1-type neurons which subsequently triggers a series of gene transcription-mediated signaling cascades that induce an addiction.[31][38][39]
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.[52][53] In theory, D-TMP (d-threo-methylphenidate) can be anticipated to be twice the strength of the racemic product.[49][54]
Because some adverse effects may only emerge during chronic use of methylphenidate, a constant watch for adverse effects is recommended.[20]
Orally administered methylphenidate is subject to first-pass metabolism, by which the levo-isomer is extensively metabolized. By circumventing this first-pass metabolism, the relative concentrations of l-threo-methylphenidate are much higher with transdermal administration (50-60% of those of dexmethylphenidate instead of about 14-27%).
Methylphenidate is a catecholamine reuptake inhibitor that indirectly increases catecholaminergic neurotransmission by inhibiting the dopamine transporter (DAT) and norepinephrine transporter (NET),[49] which are responsible for clearing catecholamines from the synapse, particularly in the striatum and meso-limbic system.[50] Moreover, it is thought to "increase the release of these monoamines into the extraneuronal space."[51]
When methylphenidate is coingested with ethanol, a metabolite called ethylphenidate is formed via hepatic transesterification,[44][45] 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.[46][45]
The dextrorotary enantiomer of methylphenidate, known as dexmethylphenidate, is sold as a generic and under the brand names Focalin and Attenade in both an immediate-release and an extended-release form. In some circumstances it may be prescribed instead of methylphenidate, however it has no significant advantages over methylphenidate at equipotent dosages and so it is sometimes considered to be an example of an evergreened drug.
Dexmethylphenidate, sold under the trade names Focalin among others, is a potent central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy.[1]
Coingestion of alcohol (ethanol) also increases the blood plasma levels of d-methylphenidate by up to 40%.[47]
Hypersensitivity (including skin rash, urticaria, and fever) is sometimes reported. The Daytrana patch has a much higher rate of dermal reactions than oral methylphenidate.[15]
Products containing dexmethylphenidate have a side effect profile comparable to those containing methylphenidate.[5]
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.[1] Improvements in ADHD symptoms in children were significantly greater for dexmethylphenidate XR versus placebo.[1] 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.[1]
Methylphenidate is contraindicated for individuals using monoamine oxidase inhibitors (e.g., phenelzine and tranylcypromine), or individuals with agitation, tics, or glaucoma, or a hypersensitivity to any ingredients contained in methylphenidate pharmaceuticals.[2]
Treatment of a methylphenidate overdose typically involves the application of benzodiazepines, with antipsychotics, α-adrenoceptor agonists, and propofol serving as second-line therapies.[23]
Examples of drug and behavioral addictions include alcoholism, marijuana addiction, amphetamine addiction, cocaine addiction, nicotine addiction, opioid addiction, food addiction, gambling addiction, and sexual addiction. The only behavioral addiction recognized by the DSM-5 and the ICD-10 is gambling addiction. The term addiction is misused frequently to refer to other compulsive behaviors or disorders, particularly dependence, in news media.[20] An important distinction between drug addiction and dependence is that drug dependence is a disorder in which cessation of drug use results in an unpleasant state of withdrawal, which can lead to further drug use.[21] Addiction is the compulsive use of a substance or performance of a behavior that is independent of withdrawal. Addiction can occur in the absence of dependence, and dependence can occur in the absence of addiction, although the two often occur together.
USFDA-commissioned studies from 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.[19]
There is some evidence of mild reductions in height with prolonged treatment in children.[12] This has been estimated at 1cm less per year during the first three years with a total decrease of 3cm over 10 years.[13][14]
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.[48]
An addiction, by definition, includes repeated compulsive behaviors that negatively affect daily living. There are two ways to classify addictive behaviors: substance addiction and process addiction. An exercise addiction is a type of process addiction, in which an individual's mood toward a certain event becomes dependent on addictive behaviors. Many educational, occupational, and social activities are stopped due to excessive exercising. Depression may develop if exercise is neglected or may result from reoccurring physical injuries that limit exercise. Exercise addiction is often related to obsessive-compulsive disorder as exercise addicts may have obsessions or compulsions toward physical activity. Exercise addiction is also commonly associated with eating disorders as a secondary symptom of bulimia or anorexia nervosa. Approximately 39-48% of people that have an eating disorder are also addicted to exercise. When diagnosing bulimia, exercise addiction is referred to as a compensatory behavior and indicator of the underlying disorder. Research also shows exercise addiction influences not only the development of eating disorders but also their maintenance.
Methylphenidate has shown some benefits as a replacement therapy for individuals who are addicted to and dependent upon methamphetamine.[32] Methylphenidate and amphetamine have been investigated as a chemical replacement for the treatment of cocaine addiction[33][34][35][36] in the same way that methadone is used as a replacement drug for physical dependence upon heroin. Its effectiveness in treatment of cocaine or psychostimulant addiction or psychological dependence has not been proven and further research is needed.[37]
Psychologists oldest definition of addiction is that the addict has a lack of self-control. The addicted party wants to abstain, but they can't resist the temptation. Addicts lose control over their actions. It is viewed that an addict battles with their addiction and wanting abstinence and gain control over their actions.
Shopping addiction as a drug-free addiction or as a social addiction: In this theoretical perspective, not incompatible with the previous approaches, shopping addiction is usually included among the so-called “drug-free addictions”, such as addiction to gambling and, specifically, within a number of addictions grouped together as social addictions such as the addiction to Internet, video-games or mobile-phones.
The dextrorotary enantiomers are significantly more potent than the levorotary enantiomers, and some medications therefore only contain dexmethylphenidate.