Ritalin
Onofre Alamillo
Common adverse reactions of methylphenidate include euphoria, dilated pupils, tachycardia, palpitations, headache, insomnia, anxiety, hyperhidrosis, weight loss, decreased appetite, dry mouth, nausea, and abdominal pain.[9] Withdrawal symptoms may include chills, depression, drowsiness, dysphoria, exhaustion, headache, irritability, lethargy, nightmares, restlessness, suicidal thoughts, and weakness.[2]
Methylphenidate is believed to work by blocking the reuptake of dopamine and norepinephrine by neurons.[24][25] It is a central nervous system (CNS) stimulant of the phenethylamine and piperidine classes. It is available as a generic medication.[26] In 2021, it was the 43rd most commonly prescribed medication in the United States, with more than 15.2 million prescriptions.[27][28]
The name "Ritalin" derives from Marguerite "Rita" Panizzon, the wife of Leandro Panizzon, who first synthesized the drug in 1944. Rita was the first person to take methylphenidate, and described its effects to her husband.[29]
Methylphenidate is used for the treatment of attention deficit hyperactivity disorder.[31] The dosage may vary and is titrated to effect, with some guidelines recommending initial treatment with a low dose.[32] Methylphenidate is available in both immediate-release and extended-release (XR) formulations to provide a sustained release of the drug.[33][34] Methylphenidate is not approved for children under six years of age.[35][36]
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 efficacious, but also among the most efficacious drugs in all of medicine; treatment in the long-term significantly reduces or eliminates the elevated risks for obesity, 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.[37]
One committee from the World Health Organization (WHO) 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.[38][39] However, in November 2023, the WHO Mental Health Gap Action Programme Guidelines for mental, neurological, and substance use disorders makes a clear recommendation 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",[40] in addition to other WHO publications.[41]
Safety and efficacy data have been reviewed extensively by medical regulators (e.g., the US Food and Drug Administration and the European Medicines Agency), the developers of evidence-based national guidelines (e.g., the UK National Institute for Health and Care Excellence and the American Academy of Pediatrics), and government agencies who have endorsed these guidelines (e.g., the Australian National Health and Medical Research Council). 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.[37]
Since ADHD diagnosis has increased around the world, methylphenidate may be misused as a "study drug" by some populations, which may be harmful.[42] This also applies to people who may be experiencing a different issue and are misdiagnosed with ADHD.[42] People in this category can then experience negative side-effects of the drug, which worsen their condition.[42]
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.[37] The most comprehensive meta-analysis available (19 studies with over 3.9 million participants) found "no statistically significant association between ADHD medications [including methylphenidate] and the risk of cardiovascular event among children and adolescents, young and middle-aged adults, or older adults".;[43] as do other systematic reviews and meta-analyses.[44][45][46]
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.[47] Methylphenidate improves measures of somnolence on standardized tests, such as the Multiple Sleep Latency Test (MSLT), but performance does not improve to levels comparable to healthy people.[48]
Methylphenidate may also be prescribed for off-label use in treatment-resistant cases of bipolar disorder and major depressive disorder.[49] It can also improve depression in several groups, including stroke, cancer, and HIV-positive patients.[50] There is weak evidence in favor of methylphenidate's effectiveness for depression,[51] including providing additional benefit in combination with antidepressants.[52] 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.[53] 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.[54] 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.[55]
Methylphenidate's efficacy as an athletic performance enhancer, cognitive enhancer, aphrodisiac, and euphoriant is supported by research.[56][57][58][59][60][61][62][63][64] However, the manner in which methylphenidate is used for these purposes (high dosages, alternate routes of administration, during sleep deprivation, etc.) can result in severe unintended side effects.[65][66][64]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;[67][a][68][b]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.[67] Methylphenidate and other ADHD stimulants also improve task saliency and increase arousal.[69][70] Stimulants such as amphetamine and methylphenidate can improve performance on difficult and boring tasks,[69][c][70][71] and are used by some students as a study and test-taking aid.[42][72] 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.[73]
Excessive doses of methylphenidate, above the therapeutic range, can interfere with working memory and cognitive control.[69][70] Like amphetamine and bupropion, methylphenidate increases stamina and endurance in humans primarily through reuptake inhibition of dopamine in the central nervous system.[74] Similar to the loss of cognitive enhancement when using large amounts, large doses of methylphenidate can induce side effects that impair athletic performance, such as rhabdomyolysis and hyperthermia.[12] While literature suggests it might improve cognition, most authors agree that using the drug as a study aid when an ADHD diagnosis is not present does not actually improve GPA.[42] Moreover, it has been suggested that students who use the drug for studying may be self-medicating for potentially deeper underlying issues.[42]
Pregnant women are advised to only use the medication if the benefits outweigh the potential risks.[75] Not enough human studies have been conducted to conclusively demonstrate an effect of methylphenidate on fetal development.[76] In 2018, a review concluded that it has not been teratogenic in rats and rabbits, and that it "is not a major human teratogen".[77]
The most common side effects associated with methylphenidate (in standard and extended-release formulations) are appetite loss, dry mouth, anxiety/nervousness, nausea, and insomnia.[79] Gastrointestinal adverse effects may include abdominal pain and weight loss. Nervous system adverse effects may include akathisia (agitation/restlessness), irritability, dyskinesia (tics), 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).[80] Ophthalmologic adverse effects may include blurred vision caused by pupil dilatation and dry eyes, with less frequent reports of diplopia and mydriasis.[contradictory][81][82]
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.[83]
There is some evidence of mild reductions in height with prolonged treatment in children.[84] 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.[85][86]
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.[87]
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.[88] It should be used with extreme caution in people with bipolar disorder due to the potential induction of mania or hypomania.[89] There have been very rare reports of suicidal ideation, but some authors claim that evidence does not support a link.[84] Logorrhea is occasionally reported and visual hallucinations are very rarely reported.[81] Priapism is a very rare adverse event that can be potentially serious.[90]
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