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More about Methylphenidate

What is/are Methylphenidate?

Methylphenidate (ex.Ritalin) is a psychostimulant drug approved for treatment of ADHD or attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. The original patent was owned by CIBA, now Novartis Corporation. It was first licensed by the U.S. Food and Drug Administration (FDA) in 1955 for treating ADHD, prescribed from 1960, and became heavily prescribed in the 1990s, when the diagnosis of ADHD itself became more widely accepted.

ADHD and some other conditions are believed to be linked to sub-performance of the dopamine, norepinephrine, and glutamate processes in the brain, primarily in the prefrontal cortex and peripheral cortex, responsible for self-regulation functions, leading to self-regulation disorders compromising the sufferer's attention, self-control, behaviour, motivation, and executive function.

Methylphenidate acts primarily to inhibit the reuptake of dopamine and to a lesser extent norepinephrine thereby retaining these hormones longer which increases the levels of these neurotransmitters in the brain. Methylphenidate possesses some structural and pharmacological similarities to cocaine, though methylphenidate is less potent and longer in duration.

Medical uses

MPH is the most commonly prescribed psychostimulant and works by increasing the activity of the central nervous system. It produces such effects as increasing or maintaining alertness, combating fatigue, and improving attention. The short-term benefits and cost effectiveness of methylphenidate are well established, although long-term effects are unknown. The long term effects of methylphenidate on the developing brain are unknown. Methylphenidate is not approved for children under six years of age.

Methylphenidate may also be prescribed for off-label use in treatment-resistant cases of lethargy, Bipolar depression, Major Depressive Disorder, and obesity.

Attention deficit hyperactivity disorder

Methylphenidate is approved by the U.S. Food and Drug Administration (FDA) for the treatment of attention deficit hyperactivity disorder. The addition of behavioural modification therapy (e.g. cognitive behavioral therapy (CBT)) has additional benefits on treatment outcome. While stimulants such as methylphenidate increase attention and concentration, they do not improve learning and academic performance. People with ADHD have an increased risk of substance abuse, and stimulant medications reduce this risk. A meta analysis of the literature concluded that methylphenidate quickly and effectively reduces the signs and symptoms of ADHD in children under the age of 18 in the short term but found that this conclusion may be biased due to the high number of low quality clinical trials in the literature.

There have been no placebo controlled trials investigating the long term effectiveness of methylphenidate beyond 4 weeks thus the long term effectiveness of methylphenidate has not been scientifically demonstrated. Serious concerns of publication bias regarding the use of methylphenidate for ADHD have also been noted. A diagnosis of ADHD must be confirmed and the benefits and risks and proper use of stimulants as well as alternative treatments should be discussed with the parent before stimulants are prescribed. The dosage used can vary quite significantly from individual child to individual child with some children responding to quite low doses whereas other children require the higher dose range. The dose, therefore, should be titrated to an optimal level that achieves therapeutic benefit and minimal side-effects. This can range from anywhere between 5–30 mg twice daily or up to 60 mg a day. Therapy with methylphenidate should not be indefinite. Weaning off periods to assess symptoms are recommended.

Mechanisms of ADHD

The means by which methylphenidate affects people diagnosed with ADHD are not well understood. Some researchers have theorized that ADHD is caused by a dopamine imbalance in the brains of those affected. Methylphenidate is a norepinephrine and dopamine reuptake inhibitor, which means that it increases the level of the dopamine neurotransmitter in the brain by partially blocking the dopamine transporter (DAT) that removes dopamine from the synapses. This inhibition of DAT blocks the reuptake of dopamine and norepinephrine into the presynaptic neuron, increasing the amount of dopamine in the synapse. It also stimulates the release of dopamine and norepinephrine into the synapse. Finally, it increases the magnitude of dopamine release after a stimulus, increasing the salience of stimulus. An alternate explanation that has been explored is that the methylphenidate affects the action of serotonin in the brain. However, benefits with other stimulants that have a different mechanism of action indicates that support for a deficit in specific neurotransmitters is unsupported and unproven by the evidence and remains a speculative hypothesis.


Narcolepsy, a chronic sleep disorder characterized by overwhelming daytime drowsiness and sudden need for 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 controls.

Aggression and criminality in Adult ADHD

While side-effects and misuse of methylphenidate have been associated with an increased risk of aggression and psychosis, newer studies indicate that it could be useful in the treatment of ADHD in adults with a history of aggressive and criminal behavior. A large clinical study conducted in Sweden found a significant reduction of the criminality rate in males (32%) and females (42%) as compared with the rate for the same patients while not receiving medication. Some of these clinical outcomes have been confirmed in similar studies with children and adolescents.


Use of stimulants such as methylphenidate in cases of treatment resistant depression is controversial.In individuals with cancer, methylphenidate is commonly used to counteract opioid-induced somnolence, to increase the analgesic effects of opioids, to treat depression, and to improve cognitive function.Methylphenidate may be used in addition to an antidepressant for refractory major depressive disorder. It can also improve depression in several groups including stroke, cancer, and HIV-positive patients. However, benefits tend to be only partial with stimulants being, in general, less effective than traditional antidepressants and there is some suggestive evidence of a risk of habituation. Stimulants may however, have fewer side-effects than tricyclic antidepressants in the elderly and medically ill.

Substance dependence

Although possible, substance dependence is rare with Methylphenidate. Methylphenidate has shown some benefits as a replacement therapy for individuals dependent on methamphetamine. Cocaine and methamphetamine block the protein DAT, over time causing DAT upregulation and lower cytoplasmic dopamine levels in their absence. Methylphenidate and amphetamine have been investigated as a chemical replacement for the treatment of cocaine dependence in the same way that methadone is used as a replacement for heroin. Its effectiveness in treatment of cocaine or other psychostimulant dependence has not been proven and further research is needed.

Early research began in 2007–2008 by Pharmacokinetics and Biopharmaceutics Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, in University of Maryland, Baltimore, Maryland, first published, 19 September 2007 in the United States on the effectiveness of methylphenidate as a substitute agent in refractory cases of cocaine dependence, owing to methylphenidate's longer half life, and reduced vasoconstrictive effects.[63][64] This replacement therapy is used in other classes of drugs such as opiates for maintenance and gradual withdrawal such as methadone, suboxone, etc. A second generation of N-substituted 3α-[bis(4′-fluorophenyl)methoxy]-tropanes (GA 1–69, JHW 005 and JHW 013) binds with high affinity to the dopamine transporter (DAT) and are highly selective toward DAT compared to muscarinic receptor binding (M1). The objective of this study was to characterize brain distribution, pharmacokinetics, and pharmacodynamics [extracellular brain dopamine levels] of three novel N-substituted benztropine (BZT) analogs in male Sprague–Dawley rats. The BZT analogs displayed a higher distribution (Vd = 8.69–34.3 vs. 0.9 L/kg) along with longer elimination (t1/2: 4.1–5.4 vs. 0.5 h) than previously reported for cocaine. Brain-to-plasma partition coefficients were 1.3–2.5 vs. 2.1 for cocaine. The effect of the BZT analogs on extracellular brain dopamine levels ranged from minimal effects (GA 1–69) to several fold elevation (∼850% of basal DA for JHW 013) at the highest dose evaluated. PK/PD analysis of exposure–response data resulted in lower IC50 values for the BZT analogs compared to cocaine indicating their higher potency to inhibit dopamine reuptake (0.1–0.3 vs. 0.7 mg/L). These BZT analogs possess significantly different PK and PD profiles as compared to cocaine suggesting that further evaluation as cocaine abuse therapeutics is warranted. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 1993–2007, 2008.


Animal studies using rats with ADHD-like behaviours were used to assess the safety of methylphenidate on the developing brain and found that psychomotor impairments, structural and functional parameters of the dopaminergic system were improved with treatment. This animal data suggests that methylphenidate supports brain development and hyperactivity in children diagnosed with ADHD. However, in normal control animals methylphenidate caused long lasting changes to the dopaminergic system suggesting that if a child is misdiagnosed with ADHD they may be at risk of long lasting adverse effects to brain development. Animal tests found that rats given methylphenidate grew up to be more stressed and emotional. It is unclear due to lack of follow-up study whether this occurs in ADHD like animals and whether it occurs in humans. However, long lasting benefits of stimulant drugs have not been found in humans.

Adverse effects

Some adverse effects may emerge during chronic use of methylphenidate so a constant watch for adverse effects is recommended.[68] Some adverse effects of stimulant therapy may emerge during long-term therapy, but there is very little research of the long-term effects of stimulants.[69][70] The most common side effects of methylphenidate are nervousness, drowsiness and insomnia. Other adverse reactions include:

  •     Abdominal pain
  •     Akathisia (restlessness)
  •     Alopecia (loss of hair)
  •     Angina (chest pain)
  •     Appetite loss
  •     Anxiety/Nervousness
  •     Blood pressure and pulse changes (both up and down)
  •     Cardiac arrhythmia
  •     Depression
  •     Diaphoresis (sweating)
  •     Dizziness
  •     Dyskinesia (uncontrollable tics)
  •     Euphoria or dysphoria
  •     Headache
  •     Hypersensitivity (including skin rash, urticaria, fever, arthralgia, exfoliative dermatitis, erythema multiforme, necrotizing vasculitis, and thrombocytopenic purpura)
  •     Irritability
  •     Lethargy
  •     Libido increased or decreased
  •     Mania or hypomania
  •     Nausea
  •     Palpitations
  •     Pupil dilation
  •     Psychosis and psychiatric disorders - stimulants above the recommended dose level are associated with higher levels of psychosis, substance misuse and psychiatric admissions.[73]
  •     Short-term weight loss
  •     Somnolence
  •     Stunted growth
  •     Suicidal ideation
  •     Tachycardia (rapid resting heart rate)
  •     Xerostomia (dry mouth)

On March 22, 2006, the FDA Pediatric Advisory Committee decided that medications using methylphenidate ingredients do not need black box warnings about their risks, noting that "for normal children, these drugs do not appear to pose an obvious cardiovascular risk." Previously, 19 possible cases had been reported of cardiac arrest linked to children taking methylphenidate and the Drug Safety and Risk Management Advisory Committee to the FDA recommend a "black-box" warning in 2006 for stimulant drugs used to treat attention deficit/hyperactivity disorder.

Historical concerns related to child growth and cancer risk have existed, and these are still monitored and studied, however current scientific consensus is that the evidence of studies suggests these are either dubious or low-significance risks. (See : Previous health concerns now considered doubtful or largely minor)

Treatment emergent psychosis

On occasion, treatment emergent psychosis can occur during long-term therapy with methylphenidate. Regular psychiatric monitoring of people who are taking methylphenidate for adverse effects such as psychotic symptomatology has been recommended. In the majority of unremarkable isolated cases methylphenidate overdose is asymptomatic or only incurs minor symptoms even in children under six years of age Normally any reaction will show within three hours. However, injection (particularly arterial) has sometimes led to toxic necrosis and amputation at the point of injection.Emergency treatment is recommended beyond certain overdose levels, in cases of attempted suicide, and in those using monoamine oxidase inhibitors (MAOIs).

Long-term effects

It was documented in 2000, by Zito et al. "that at least 1.5% of children between the ages of two and four are medicated with stimulants, anti-depressants and anti-psychotic drugs, despite the paucity of controlled scientific trials confirming safety and long-term effects with preschool children."

The effects of long-term methylphenidate treatment on the developing brains of children with ADHD is the subject of study and debate. Although the safety profile of short-term methylphenidate therapy in clinical trials has been well established, repeated use of psychostimulants such as methylphenidate is less clear. There are no well defined withdrawal schedules for discontinuing long-term use of stimulants. There is limited data that suggests there are benefits to long-term treatment in correctly diagnosed children with ADHD, with overall modest risks. Short-term clinical trials lasting a few weeks show an incidence of psychosis of about 0.1%. A small study of just under 100 children that assessed long-term outcome of stimulant use found that 6% of children became psychotic after months or years of stimulant therapy. Typically, psychosis would abate soon after stopping stimulant therapy. As the study size was small, larger studies have been recommended. The long-term effects on mental health disorders in later life of chronic use of methylphenidate is unknown. Concerns have been raised that long-term therapy might cause drug dependence, paranoia, schizophrenia and behavioral sensitisation, similar to other stimulants. Psychotic symptoms from methylphenidate can include hearing voices, visual hallucinations, urges to harm oneself, severe anxiety, euphoria, grandiosity, paranoid delusions, confusion, increased aggression and irritability. Methylphenidate psychosis is unpredictable in whom it will occur. Family history of mental illness does not predict the incidence of stimulant toxicosis in children with ADHD. High rates of childhood stimulant use is found in patients with a diagnosis of schizophrenia and bipolar disorder independent of ADHD. Individuals with a diagnosis of bipolar or schizophrenia who were prescribed stimulants during childhood typically have a significantly earlier onset of the psychotic disorder and suffer a more severe clinical course of psychotic disorder. Knowledge of the effects of chronic use of methylphenidate is poorly understood with regard to persisting behavioral and neuroadaptational effects.

Juvenile rhesus monkeys chronically administered twice daily methylphenidate doses that cause plasma levels similar to those of higher pharmalogical doses in humans show no apparent lasting effects.[95] Measures tested included D2-like dopamine receptor density, dopamine transporter density, amphetamine-induced dopamine release responsiveness, cognitive performance, and growth.

This article uses material from the Wikipedia article Methylphenidate, which is released under the Creative Commons Attribution-Share-Alike License 3.0.

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Reviews for Methylphenidate

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jaguar is a member of the Pharmacy Reviewer forum
Total Posts: 1
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Finding the right Concerta dosage

My daughter takes Concerta now for 18 months. I was very skeptical in the beginning if it would help her to concentrate better (ADHS). It took us a while to find the right dosage. We slowly increased until we had a dosage that was too high. Stepping one step back brought the right results. In school holidays she abruptly stopped taking Concerta which wasn't a good idea. I would say that it has a high dependency potential but it should be reduced slowly and gradually in order to avoid feeling tired and without any drive. I was long time hesitant if we should go this way but looking back I am overall happy that I agreed to my daughter taking Concerta as her concentration abilities went significantly up.

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6 months - 2 years
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My energy level improves

My energy level improves,however I'm bipolar and it was given to me to help my depression.

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1 month - 6 months
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goonandwalkitout is a member of the Pharmacy Reviewer forum
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Little helpers.

I've taken Ritalin off and on for most of my life. I have ADHD even now as an adult. As far as stimulation goes, there are much stronger out there with less nasty side effects. As for their effect on my attention span, they again work decently enough, but there are much better out there. If you are a parent wondering which ADHD drug would be good for your younger children, Ritalin may be the medicine you'd like to ask your doctor about.

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6 months - 2 years
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Heavy Addiction Potential

I felt a boost of energy in the morning and increased focus, but felt that it wore off quickly. I was quickly bumped up to 54 mg. At that dosage, I felt great. Too great. Yes, I was able to focus, but the problem was that absolutely everything became interesting. I was unable to differentiate between important tasks like homework and unimportant ones like computer games. I also felt very "speedy" and noticed myself talking a lot. As the drug wore off there was a very uncomfortable crash, with symptoms of fatigue combined with insomnia, irritability, and confusion. This crash leads one with an addictive mindset to re-dose, and that becomes highly problematic. Another side effect is appetite suppression. Overall I felt very out-of-control and the ADHD benefits were minimal. I do have an addictive personality, and thus I advise anyone with addiction problems to avoid this medicine like the plague.

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More than 2 years
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