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Psychostimulants / (ADD/ADHD)

Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity. Methylphenidate belongs to the piperidine class of compounds and increases the levels of dopamine and norepinephrine in the brain through reuptake inhibition of the monoamine transporters. Methylphenidate possesses structural similarities to amphetamine, but its pharmacological effects are more similar to those of cocaine, though MPH is less potent and longer in duration of action. 

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.

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. There is a lack of evidence of the effectiveness in the long term of beneficial effects of methylphenidate with regard to learning and academic performance. One study found that pharmacological treatment of ADHD in childhood reduces the risk that children will resort to substance abuse in adolescence by 85%, while untreated ADHD was a significant risk factor in developing substance abuse. 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. 


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.


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 treatment-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.


The U.S. Food and Drug Administration (FDA) gives methylphenidate a pregnancy category of C, and women are advised to only use the drug if the benefits outweigh the potential risks. Intravenous methylphenidate abuse was confounded with the concurrent use of other substances (e.g., cigarettes, alcohol) during pregnancy.

Adverse effects:

Some adverse effects may emerge during chronic use of methylphenidate so a constant watch for adverse effects is recommended. 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.The most common side effects of methylphenidate are nervousness, drowsiness and insomnia. Other adverse reactions include:

  • Abdominal pain
  • Akathisia
  • Alopecia
  • Angina
  • Appetite loss
  • Anxiety
  • Blood pressure and pulse changes (both up and down)
  • Cardiac arrhythmia
  • Diaphoresis (sweating)
  • Dizziness
  • Dyskinesia
  • Headaches
  • Hypersensitivity (including skin rash, urticaria, fever, arthralgia, exfoliative dermatitis, erythema multiforme, necrotizing vasculitis, and thrombocytopenic purpura)
  • Lethargy
  • Libido increased or decreased
  • Nausea
  • Palpitations
  • Pupil dilation
  • Psychosis
  • Short-term weight loss
  • Somnolence
  • Stunted growth
  • Tachycardia
  • Xerostomia (dry mouth)

Long-term effects:

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.

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. 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.


Tolerance and behavioural sensitisation may occur with long-term use of methylphenidate.The withdrawal or rebound symptoms of methylphenidate can include psychosis, depression, irritability and a temporary worsening of the original ADHD symptoms. Methylphenidate, due to its very short elimination half life, may be more prone to rebound effects than d-amphetamine.Up to a third of children with ADHD experience a rebound effect when methylphenidate dose wears off.


Intake of adrenergic agonist drugs or pemoline with methylphenidate increases the risk of liver toxicity.Antidepressants taken in conjunction with methylphenidate may cause hypertension, hypothermia and convulsions.


Methylphenidate should not be prescribed concomitantly with tricyclic antidepressants, such as desipramine, or monoamine oxidase inhibitors, such as phenelzine or tranylcypromine, as methylphenidate may dangerously increase plasma concentrations, leading to potential toxic reactions (mainly, cardiovascular effects). Methylphenidate should not be prescribed to patients who suffer from severe arrhythmia, hypertension or liver damage. It should not be prescribed to patients who demonstrate drug-seeking behaviour, pronounced agitation or nervousness.Care should be taken while prescribing methylphenidate to children with a family history of Paroxysmal Supraventricular Tachycardia (PSVT).

Special precautions:

Special precaution is recommended in individuals with epilepsy with additional caution in individuals with uncontrolled epilepsy due to the potential for methylphenidate to lower the seizure threshold.

Abuse potential:

Methylphenidate has high potential for abuse due to its pharmacological similarity to cocaine and amphetamines.Methylphenidate, like other stimulants, increases dopamine levels in the brain, but at therapeutic doses this increase is slow, and thus euphoria does not typically occur except in rare instances. The abuse potential is increased when methylphenidate is crushed and insufflated (snorted), or when it is injected, producing effects somewhat similar to cocaine. Cocaine-like effects can also occur with very large doses taken orally. However, the dose that produces euphoric effects varies between individuals. Methylphenidate is actually more potent than cocaine in its effect on dopamine transporters. Methylphenidate should not be viewed as a weak stimulant as has previously been hypothesised.

Abuse of prescription stimulants is higher amongst college students than non-college attending young adults. College students use methylphenidate either as a study aid or to stay awake longer. Increased alcohol consumption due to stimulant misuse has additional negative effects on health. Methylphenidate's pharmacological effect on the central nervous system is almost identical to that of cocaine. Studies have shown that the two drugs are nearly indistinguishable when administered intravenously to cocaine addicts.

Methylphenidate is sometimes used by students to enhance their mental abilities, improving their concentration and helping them to study. Professor John Harris, an expert in bioethics, has said that it would be unethical to stop healthy people taking the drug. He also argues that it would be "not rational" and against human enhancement to not use the drug to improve people's cognitive abilities.Professor Anjan Chatterjee however has warned that there is a high potential for abuse and may cause serious adverse effects on the heart, meaning that only people with an illness should take the drug. 


An overdose manifests in agitation, hallucinations, psychosis, lethargy, seizures, tachycardia, dysrhythmias, hypertension, and hyperthermia. Benzodiazepines may be used as treatment if agitation, dystonia, or convulsions are present.


Methylphenidate has been the subject of controversy in relation to its use in the treatment of ADHD. One such criticism is prescribing psychostimulants medication to children to reduce ADHD symptoms.Calls have been made that methylphenidate be severely restricted in its use.The pharmacological effects of methylphenidate resemble closely those of cocaine and amphetamines,which is the desired effect in the treatment of ADHD, and how methylphenidate works.

The abuse pattern of methylphenidate is very similar to heroin and amphetamines.A 2002 study showed that rats treated with methylphenidate are more receptive to the reinforcing effects of cocaine.The contention that methylphenidate acts as a gateway drug has been discredited by multiple sources,according to which abuse is statistically very low and "stimulant therapy in childhood does not increase the risk for subsequent drug and alcohol abuse disorders later in life".

Another controversial idea surrounding ADHD is that a group of ADHD children have, in general, healthy brains with no gross neurological deficits. This concept, however, is seen as outdated by a few scientists in current medical research, who claim they can identify an ADHD child's brain using CT brain scans,and how methylphenidate interacts with it. The problem herein is that no control was used in the cited research that would differentiate an ADHD child's brain from one that had been treated with stimulants beforehand.

Treatment of ADHD by way of Methylphenidate has led to legal actions including malpractice suits regarding informed consent, inadequate information on side effects, misdiagnosis, and coercive use of medications by school systems.In the U.S. and the United Kingdom, it is approved for use in children and adolescents. The FDA recently approved the use of methylphenidate for use in treating adult ADHD.Methylphenidate has been approved for adult use in the treatment of narcolepsy.