Methylphenidate
Methylphenidate, sold under the brand name Ritalin and Concerta, among others, is a central nervous system stimulant used in the treatment of attention deficit hyperactivity disorder and narcolepsy. It may be taken by mouth or applied to the skin, and different formulations have varying durations of effect. For ADHD, the effectiveness of methylphenidate is comparable to atomoxetine but modestly lower than amphetamine. However, methylphenidate is preferred as a first-line treatment in children, while amphetamine is preferred in adults. Methylphenidate reduces core ADHD symptoms and may do so in part by enhancing executive functions, such as working memory, sustained attention, and inhibitory control.
At therapeutic doses, methylphenidate increases alertness and concentration and reduces hyperactivity and impulsive behavior in individuals with ADHD. Common side effects include loss of appetite, weight loss, trouble sleeping, and small increases in heart rate and blood pressure. Long-term treatment in children has been associated with slightly slower growth. Methylphenidate can be misused; dependence and withdrawal are mainly reported with high-dose or non-medical use and are uncommon at therapeutic doses.
Methylphenidate is believed to work by blocking the reuptake of dopamine and norepinephrine by neurons. It is a central nervous system stimulant of the phenethylamine and piperidine classes. It is available as a generic medication. In 2023, it was the 50th most commonly prescribed medication in the United States, with more than 13million prescriptions.
Uses
Medical
Methylphenidate is most commonly used to treat ADHD and narcolepsy.Attention deficit hyperactivity disorder
Methylphenidate is used for the treatment of attention deficit hyperactivity disorder. The dosage may vary and is titrated to effect, with some guidelines recommending initial treatment with a low dose. Methylphenidate is available in both immediate-release and modified-release formulations. Methylphenidate is not approved for children under six years of age.The International Consensus Statement on ADHD shows that the results from systematic reviews, meta-analyses and large scale studies are clear: methylphenidate is safe and among the most efficacious drugs in all of medicine; treatment in the long-term substantially reduces accidental injuries, traumatic brain injury, substance abuse, cigarette smoking, educational underachievement, bone fractures, sexually transmitted infections, depression, suicide, criminal activity, teenage pregnancy, vehicle crashes, burn injuries and overall-cause mortality, and eliminates the increased risk for obesity.
One committee from the World Health Organization responsible for the World Health Organization Essential Medicines List rejected an application in 2019, and a second application endorsed by 51 professional medical groups in 2021, for methylphenidate's inclusion due to uncertainty about its efficacy and safety. However, in November 2023, the WHO Mental Health Gap Action Programme Guidelines for mental, neurological, and substance use disorders recommended that methylphenidate should be considered for children aged 6 years and older who have ADHD, noting specifically that, "methylphenidate treatment shows substantial effects on symptom reduction", in addition to other WHO publications. In 2024, the European Society for Child and Adolescent Psychiatry and the American Academy of Paediatrics endorsed the inclusion of methylphenidate in the WHO EML. A new application for methylphenidate's inclusion is currently pending review, having sparked debate in the comment process among researchers engaged in the evaluation of the evidence-base.
Safety and efficacy data have been reviewed extensively by medical regulators, the developers of evidence-based national guidelines, and government agencies who have endorsed these guidelines. These professional groups unanimously conclude, based on the scientific evidence, that methylphenidate is safe and effective and should be considered as a first-line treatment for ADHD.
Since the diagnosis of ADHD has increased around the world, methylphenidate may be misused as a "study drug" by students, which may be harmful. This also applies to people who may be experiencing a different issue and are misdiagnosed with ADHD. People in this category are prone to experience the adverse effects of the drug, which can worsen their condition.
Long-term meta-analyses and systematic reviews show that the medications used to treat ADHD are not associated with observed deficits in brain structure, but with improved brain development and functioning, most prominently in inferior frontal and striatal regions. The most comprehensive meta-analysis available found "no statistically significant association between ADHD medications and the risk of cardiovascular event among children and adolescents, young and middle-aged adults, or older adults"; as do other systematic reviews and meta-analyses.
Narcolepsy
, a chronic sleep disorder characterized by overwhelming daytime drowsiness and uncontrollable sleep, is treated primarily with stimulants. Methylphenidate is considered effective in increasing wakefulness, vigilance, and performance. Methylphenidate improves measures of somnolence on standardized tests, such as the Multiple Sleep Latency Test, but performance does not improve to levels comparable to healthy people.Other medical uses
Methylphenidate may also be prescribed for off-label use in treatment-resistant cases of bipolar disorder and major depressive disorder. It can also improve depression in several groups, including stroke, cancer, and HIV-positive patients. There is weak evidence in favor of methylphenidate's effectiveness for depression, including providing additional benefit in combination with antidepressants. In individuals with terminal cancer, methylphenidate can be used to counteract opioid-induced somnolence, to increase the analgesic effects of opioids, to treat depression, and to improve cognitive function. A 2021 systematic review and meta-analysis found that all studies on geriatric depression reported positive results of methylphenidate use; the review recommended short-term use in combination with citalopram. A 2018 review found low-quality evidence supporting its use to treat apathy as seen in Alzheimer's disease, in addition to slight benefits for cognition and cognitive performance.Enhancing performance
Methylphenidate's efficacy as an athletic performance enhancer, cognitive enhancer, aphrodisiac, and euphoriant is supported by research. However, the manner in which methylphenidate is used for these purposes can result in severe unintended side effects.A 2015 review found that therapeutic doses of amphetamine and methylphenidate result in modest improvements in cognition, including working memory, episodic memory, and inhibitory control, in normal healthy adults; the cognition-enhancing effects of these drugs are known to occur through the indirect activation of both dopamine receptor D1 and adrenoceptor α2 in the prefrontal cortex. Methylphenidate and other ADHD stimulants also improve task saliency and increase arousal. Stimulants such as amphetamine and methylphenidate can improve performance on difficult and boring tasks, and are used by some students as a study and test-taking aid. Based upon studies of self-reported illicit stimulant use, performance-enhancing use rather than use as a recreational drug, is the primary reason that students use stimulants.
Excessive doses of methylphenidate, above the therapeutic range, could interfere with working memory and cognitive control. Methylphenidate increases stamina and endurance in humans primarily through reuptake inhibition of dopamine in the central nervous system. Similar to the loss of cognitive enhancement when using large amounts, large doses of methylphenidate could induce side effects that impair athletic performance, such as rhabdomyolysis and hyperthermia. While literature suggests it might improve cognition, there isn't evidence that its use as a study aid without an ADHD diagnosis improves one's GPA.
Available forms
The most common formulations of methylphenidate are based on its hydrochloride salt and are available as both immediate-release and extended-release oral dosage forms, as well as transdermal patches. Methylphenidate is a chiral compound with two stereocenters; clinical use overwhelmingly utilizes the racemate threo diastereomer, with the pharmacologically active component being the d-threo-methylphenidate enantiomer. Additionally, dexmethylphenidate is the single d-threo enantiomer formulation approved for medicinal use. There is some evidence that dexmethylphenidate has better bioavailability and a longer duration of action than methylphenidate.Immediate-release
In the Ritalin tablets series, the volume of distribution was 2.65±1.11 L/kg for d-methylphenidate and 1.80±0.91 L/kg for l-methylphenidate subsequent to swallowing. Following administration of Concerta, plasma concentrations of the l-isomer were approximately the plasma concentrations of the d-isomer.Methylphenidate was originally available as an immediate-release racemic mixture formulation under the Novartis brand name Ritalin, although a variety of generics are available, some under other brand names. Generic brand names include Ritalina, Rilatine, Attenta, Medikinet, Metadate, Methylin, Penid, Tranquilyn, and Rubifen.