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Methylphenidate and Autism Ranking: Mildly Hazardous Strong positive evidence

methylphendiate

Methylphenidate is a form of medication known as a central nervous system (CNS) stimulant.  It is also known as methylphenidylacetate hydrochloride or MPH.

Methylphenidate is sold under various brand names including Concerta, Delmosart, Ritalin and Xaggitin.

Methylphenidate is believed to work by increasing the amount of dopamine, a natural chemical, found in the brain. Increasing the amount of dopamine is believed to improve self-control, attention and concentration.

Methylphenidate is commonly used to treat attention deficit hyperactivity disorder (ADHD), although it is also sometimes used to treat narcolepsy.

Some people believe that methylphenidate can be used with some individuals on the autism spectrum to reduce problem behaviours, such as hyperactivity, impulsivity and inattention.

Our Opinion

There is a limited amount of research evidence (10 group studies and eight case design studies with three or more participants) into the use of methylphenidate as an intervention for people on the autism spectrum.

This research suggests that methylphenidate may be beneficial for the treatment of hyperactivity, impulsivity and inattention in some children and young people on the autism spectrum.

There is almost no research evidence to suggest that methylphenidate may be useful for the treatment of adults on the autism spectrum.

There is evidence of significant side effects of methylphenidate in some individuals. Those side effects may include insomnia, nervousness, headache, decreased appetite, abdominal pain and other gastrointestinal symptoms, and cardiovascular effects such as tachycardia, palpitations and minor increases in blood pressure.

Further, large scale, double blind, randomised controlled trials of the effects of methylphenidate should be carried out on individuals on the autism spectrum to determine their effectiveness and safety.  These studies should investigate issues such as

  • The optimal dosage and length of treatment for different individuals on the autism.
  • The efficacy and tolerability of extended-release versus immediate-release formulations.
  • Comparison of methylphenidate with other central nervous system stimulants, such as dextroamphetamine, and with non-stimulants, such as atomoxetine and guanfacine.

We believe that methylphenidate should only be used as part of a comprehensive treatment programme for ADHD, under specialist supervision, where remedial measures alone prove insufficient.

Methylphenidate should be discontinued if there is no response after 1 month, and treatment should be suspended periodically to assess the child's condition

Disclaimer

Please read our Disclaimer on Autism Interventions


Aims and Claims

Aims

The aim of using a stimulant medication, such as methylphenidate, on individuals on the autism spectrum is to reduce behaviours such as hyperactivity, impulsivity and inattention.

According to NICE (2000)

“Methylphenidate is a CNS stimulant. It is licensed as part of a comprehensive treatment programme for ADHD, under specialist supervision, where remedial measures alone prove insufficient.”

Methylphenidate is believed to work by increasing the amount of dopamine, a natural chemical, found in the brain. Increasing the amount of dopamine is believed to improve self-control, attention and concentration.

Methylphenidate is commonly used to treat attention deficit hyperactivity disorder (ADHD), although it is also sometimes used to treat narcolepsy.

Some people believe that methylphenidate can be used with some individuals on the autism spectrum to reduce problem behaviours, such as hyperactivity, impulsivity and inattention.

Claims 

There have been a number of claims for the benefits of methylphenidate in individuals on the autism spectrum. For example,

Reichow, Volkmar and Bloch (2013) carried out a systematic review of the use of medications to treat ADHD in children on the autism spectrum and reported that “methylphenidate was effective in treating hyperactivity in children with PDDs”. They also reported that “methylphenidate was shown to have moderate, albeit not statistically significant, effects in treating irritability and stereotypies in children with PDDs”.

Audience

Stimulant medications (such as methylphenidate) are designed to help individuals with problem behaviours such as hyperactivity, impulsivity and inattention which affect the individual's ability to function.

According to the National Institute for Clinical Excellence (2000)

'Methylphenidate ... is not currently licensed for use in children less than 6 years old.'

 

Key Features

Methylphenidate or methylphenidate hydrochloride is a central nervous system stimulant medication used to treat conditions such as ADHD and narcolepsy.

Methylphenidate is sold under various brand names including Concerta, Delmosart, Ritalin and Xaggitin.

It can be given as

  • Tablets (immediate release , intermediate - or long-acting)
  • Capsules ( intermediate or long-acting)
  • Transdermal patch (long-acting)

The exact amount of each dose needs to be carefully monitored and adjusted by a specialist.  This is especially true for individuals on the autism spectrum because, as Posey et al (2007) noted, 'Optimal dose analyses suggested significant interindividual variability in dose response'.

Di Martino (2004) suggested that 'Administering a single MPH test dose may be useful in identifying children with PDD who may benefit from prolonged therapy.' Individuals on the autism spectrum who respond can then be given further, low doses which can be gradually increased.

For the latest information on specific formulations and recommended dosages please see BNF: Methylphenidate Hydrochloride and BNF for Children: Methylphenidate Hydrochloride.

 

Cost and Time

Cost

The cost of using methylphenidate will depend on a number of factors including the supplier, the brand, the dosage, and the length and frequency of treatment.

According to the BNF website accessed on 21 May 2018, the NHS indicative price for three of the commonly used brands was as follows

  • Concerta XL 18mg tablets, £31.19 for 30 tablets
  • Delmosart 18mg modified-release tablets, £15.50 for 30 tablets
  • Xaggitin XL 18mg tablets, £15.58 for 30 tablets

Within the UK, methylphenidate is available free of charge to patients via the National Health Service. In other countries the costs may be covered by some insurance policies.

Time

The amount of time it takes to use methylphenidate will depend on a number of factors including the overall length of treatment, the frequency of treatments and the time taken to administer a single dose,  as well as the needs of the person undertaking it.

Methylphenidate Immediate action tablets or liquid are usually taken 2-3 times a day, preferably 35-40 minutes before meals, with the last dose several hours before bedtime. Intermediate or long acting methylphenidate in tablet or capsule form is usually taken once a day in the morning.

NICE (2000) recommended that

"Methylphenidate should be discontinued if there is no response after 1 month, and treatment should be suspended periodically to assess the child's condition."

In addition, the U.S. National Library of Medicine (2017) issued the following warning about prolonged use of methylphenidate.

“Methylphenidate can be habit-forming. Do not take a larger dose, take it more often, take it for a longer time, or take it in a different way than prescribed by your doctor. If you take too much methylphenidate, you may find that the medication no longer controls your symptoms, you may feel a need to take large amounts of the medication, and you may experience unusual changes in your behavior."

Risks and Safety

Hazards

According to NICE (2000)

“Common adverse effects of treatment include insomnia, nervousness, headache, decreased appetite, abdominal pain and other gastrointestinal symptoms, and cardiovascular effects such as tachycardia, palpitations and minor increases in blood pressure.”

According to the BNF website, accessed on 21 May 2018, side effects may include

“Uncommon: Abnormal dreams; confusion; constipation; dyspnoea; epistaxis; haematuria; muscle cramps; suicidal ideation; urinary frequency. Rare: Angina; sweating; visual disturbances. Very rare: Angle-closure glaucoma; blood disorders; cerebral arteritis; dependence; erythema multiforme; exfoliative dermatitis; hepatic dysfunction; leucopenia; myocardial infarction; neuroleptic malignant syndrome; psychosis; seizures; thrombocytopenia; tolerance; Tourette syndrome. Frequency not known: Bradycardia; convulsions; supraventricular tachycardia.”

The Royal College of Psychiatrists recommends that a child being treated with stimulants 'should have their height and weight measured regularly' because of possible effects on appetite.

Please see U.S. National Library of Medicine (2017) for a full list of other potential side effects.

- Individuals on the autism spectrum

Researchers have identified some potential hazards for individuals on the autism spectrum.  For example, Cortese et al (2012) reported

"The most common adverse events associated with the use of psychostimulants in children and adolescents with ASD include: appetite reduction, sleep-onset difficulties, irritability and emotional outbursts."

Contraindications

There are some contraindications (something which makes a particular treatment or procedure potentially inadvisable) for methylphenidate. For example, according to the BNF website, accessed on 21 May 2018, methylphenidate may be contraindicated in individuals with the following conditions: 

“Anorexia nervosa; arrhythmias; cardiomyopathy; cardiovascular disease; cerebrovascular disorders; heart failure; hyperthyroidism; phaeochromocytoma; psychosis; severe depression; severe hypertension; structural cardiac abnormalities; suicidal ideation; uncontrolled bipolar disorder; vasculitis.”

Notes

Angina (chest pain caused by reduced blood flow to the heart muscles); angle-closure glaucoma (damage to the optic nerve caused by pressure of the fluid inside the eye); anorexia nervosa (eating disorder); arrhythmias (irregular heartbeats); bipolar disorder ( condition that affects your moods, which can swing from one extreme to another); bradycardia (slow heart beat); cardiomyopathy (diseases of the heart muscle) ; cardiovascular disease(disease affecting the heart or blood vessels); cerebral arteritis (inflammation of the blood vessel wall affecting the brain); cerebrovascular disorders (diseases that affect the blood vessels of the brain and blood circulation); dyspnoea (difficult or laboured breathing); epistaxis (nosebleed); erythema multiforme (skin condition); exfoliative dermatitis (redness and peeling of the skin); haematuria (presence of blood in the urine); hepatic dysfunction (liver failure); hyperthyroidism (excessive production of thyroid hormone); leucopenia (reduction in the number of white cells in the blood); myocardial infarction (heart attack); neuroleptic malignant syndrome (life-threatening reaction to antipsychotics); phaeochromocytoma (rare tumour of adrenal gland tissue); psychosis (mental health problem in which a person's perception of reality becomes distorted); hypertension (high blood pressure); structural cardiac abnormalities (defect or abnormality of the heart that does not affect the blood vessels in the heart); suicidal ideation (suicidal thoughts); supraventricular tachycardia (abnormally fast heart beat);  thrombocytopenia (low blood platelet count); Tourette syndrome (condition characterised by a combination of involuntary noises and movements called tics); vasculitis (inflammation of the blood vessel wall).

Suppliers and Availability

Methylphenidate is a powerful drug with many potential side effects and contraindications. For this reason it should only be obtained on prescription from either a paediatrician or psychiatrist, or from a GP on the advice / recommendation of a psychiatrist.

According to NICE (2000),

“On the basis of evidence from experts, the Committee concluded that [methylphenidate] treatment should only be initiated by an appropriately qualified healthcare professional with expertise in ADHD and should be based on a comprehensive assessment and diagnosis.”

 

History

Methylphenidate was patented in1954 in the United States by the Ciba-Geigy Pharmaceutical Company, now known as Novartis.

It is marketed under various brand names including Concerta, Delmosart, Ritalin and Xaggitin.

 

Current Research

Description of Studies

We have identified 18 articles on the use of methylphenidate as a treatment for people on the autism spectrum in peer-reviewed journals published in English. 

Four of the articles (Jahromi et al, 2009; Posey et al, 2007; Research Units on Pediatric Psychopharmacology Autism Network, 2005; Scahill et al) reported on the same clinical trial.

These studies we identified included more than 600 individuals on the autism spectrum aged from three years old to 18 years old, although the bulk of studies looked at primary school children and adolescents.  Individuals with specific diagnoses included people with autistic disorder, Asperger syndrome or pervasive developmental disorder - not otherwise specified.  Most of the participants in these studies were also diagnosed with attention deficit hyperactivity disorder (ADHD).

The length of intervention varied between a single, one-off dose to multiple doses delivered over three years. However, in most cases, the intervention lasted between four to six weeks. The dosage of methylphenidate varied from 0.21 mg per kg body with per day to 1.5 mg per kg body weight per day. Younger children received smaller doses than adolescents and adults. In most cases, the medication was started at a low dose and gradually increased to a higher maximum dose. 

10 of the studies used a group design, usually comparing a specific dose of methylphenidate with a placebo and/or with a different dosage of methylphenidate. Nine of these group studies used a crossover design in which the participants received first one treatment and then another. One of the studies used a parallel group design in which different groups of participants received different dosages of methylphenidate. Eight of the studies used a single case design in which the participants only received methylphenidate or another stimulant but nothing else.

Outcomes of Studies

  • The majority of the studies (such as Birmaher, Quintana, Greenhill, 1988; Di Martino, 2004; Handen, Johnson, Lubetsky, 2000) reported reduced hyperactivity in some of the participants.
  • A minority of the studies (such as Hoshino et al 1977; Jahromi et al. 2009; Nickels et al, 2008) reported reduced impulsivity in some participants.
  • A minority of the studies (such as Pearson et al, 2013; Santosh et al, 2006) reported increased attention in some participants.
  • A minority of studies reported other effects. For example, Handen, Johnson, Lubetsky (2000) reported reduced stereotypy and inappropriate speech in some participants. Hoshino et al (1977) reported improved autistic behavior and speech disorder in some participants. 
  • A minority of the studies (such as Aykol et al, 2017) reported a deterioration in the participants. 
  • The majority of the studies reported adverse effects in the participants. For example, Ghuman et al, 2009 observed that “Half of the preschoolers experienced side effects with MPH, including reports of increased stereotypic behavior, upset stomach, sleep-related difficulties, and emotional lability.”

 

Status Research

There are a number of limitations to all of the research studies published to date. For example

Type of study

  • Eight of the studies used single-case designs, that is, they did not have a control group of participants who did not receive the intervention.
  • Some of the single case design studies used relatively weak, non-experimental methodologies. For example the study by Nickels et al, 2008 and the study by Stigler et al, 2004 used retrospective chart reviews.
  • One of the randomised controlled studies (Kim et al, 2017) was non-blinded, meaning the participants and researchers may have known which participants received which dosage of methylphenidate.
  • Some of the randomised controlled studies (such as Pearson et al, 2013) did not adequately describe the randomisation process. This means that the participants may not have been properly randomised between the groups.
  • Some of the randomised controlled studies (such as Handen et al, 2000) did not adequately describe the blinding process. This means that the participants and researchers may not have actually been blind (unaware of which participant received which intervention).
  • Some of the randomised controlled studies (such as the RUUP, 2005) may have been subject to performance bias. That is, the participants may have been able to guess whether they were taking the medication or the placebo because of the side effects of the methylphenidate.

Participants

  • All of the randomised controlled studies except two included fewer than 30 participants. Four of the single-case design studies included fewer than 20 participants and one (Birmaher et al, 1998) included only nine participants.
  • Some of the studies were restricted to specific groups of participants. For example, Quintana H. et al, 1995 looked only at primary school age children diagnosed with autistic disorder.
  • Some of the studies examined participants with a range of conditions, only a proportion of whom were on the autism spectrum. For example, Simonoff et al (2013) included a large number of participants with ADHD, only some of whom were autistic..

Intervention/s

  • Some of the studies investigated a range of stimulant medications, making it difficult to know if any reported effects were produced by methylphenidate and/or by another stimulant. For example, the study by Nickel et al, 2008 included participants who were taking methylphenidate, dextroamphetamine, mixed amphetamine salts, pemoline and/or methamphetamine. 
  • Most of the studies ran for relatively short periods of time (four to eight weeks). 
  • Some of the studies examined participants who received one or more other interventions at the same time as they received methylphenidate. For example, Ghuman et al, 2009 included participants who were receiving one or more medications (such as prednisone, albuterol, flonase, atropine and melatonin) and/or other therapies (such as special education services, speech and language therapy, occupational therapy, physiotherapy and behaviour therapy).
  • Some of the studies (such as Research Units on Pediatric Psychopharmacology Autism Network, 2005) used a cross-over design with no washout phase between the methylphenidate and the placebo.

Outcomes

  • Some of the studies (such as Quintana et al, 1995) said that they used a range of outcome measures but did not provide data for all of those measures.
  • Some of the studies did not break down outcome data by specific groups of participants. For example, the study by Simonoff et al (2013) did not provide separate outcome data for the participants on the autism spectrum.
  • Most of the studies did not identify if methylphenidate had any beneficial effects in the medium to long term (six months or longer).

Other

  • Very few of the studies appeared to involve people on the autism spectrum and/or parents and carers in the design, development and evaluation of those studies.
  • Many of the studies were funded by the manufacturer and suppliers of methylphenidate.  The researchers involved may therefore have been biased towards the intervention, however unconsciously.

For a comprehensive list of potential flaws in research studies, please see Why some research studies are flawed.

Ongoing Research

  • Massachusetts General Hospital is running a study to determine whether methylphenidate hydrochloride extended release liquid formulation is safe and effective in the treatment of attention-deficit/hyperactivity disorder (ADHD) in high-functioning adults with autism spectrum disorders (ASD). Clinical Trials Gov Ref: NCT02096952. For more details, please see Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD Full Item(Open in New Window)
  • Yale University is running a study to determine whether guanfacine by itself or in combination with methylphenidate is helpful for treating hyperactivity in children and adolescents with a pervasive developmental disorders (PDDs). Clinical Trials Gov Ref: NCT01238575. For more details, please see Guanfacine for the Treatment of Hyperactivity in Pervasive Developmental Disorder Full Item(Open in New Window)

Future Research

Summary of Existing Research

There is a limited amount of research evidence (10 group studies and eight case design studies with three or more participants) into the use of methylphenidate as an intervention for people on the autism spectrum.

This research suggests that methylphenidate may be beneficial for the treatment of hyperactivity, impulsivity and inattention in some children and young people on the autism spectrum.

There is almost no research evidence to suggest that methylphenidate may be useful for the treatment of adults on the autism spectrum.

There is evidence of significant side effects of methylphenidate in some individuals. Those side effects may include insomnia, nervousness, headache, decreased appetite, abdominal pain and other gastrointestinal symptoms, and cardiovascular effects such as tachycardia, palpitations and minor increases in blood pressure.

Recommendations for Future Research

Further, large scale, double blind, randomised controlled trials of the effects of methylphenidate should be carried out on individuals on the autism spectrum to determine their effectiveness and safety.  These studies should

  • Investigate the optimal dosage and length of treatment for different individuals on the autism spectrum.
  • Compare the efficacy, tolerability and safety of extended-release versus immediate-release formulations over the short, medium and long-term.
  • Compare methylphenidate with other central nervous system stimulants, such as dextroamphetamine, and with non-stimulants, such as atomoxetine and guanfacine.
  • Use a range of well-established outcome measures, ensuring that data from all of the measures is reported and compared to the baseline measures.
  • Be independent of the manufacturers or suppliers of methylphenidate.
  • Involve people on the autism spectrum (and parents and carers) in the design, development and evaluation of those studies.

 

Studies and Trials

This section provides details of scientific studies into the effectiveness of this intervention for people with autism which have been published in English-language, peer-reviewed journals. If you know of any other studies we should include please email info@researchautism.net with the details. Thank you.

Please note that we are unable to supply publications unless we are listed as the publisher. However, if you are a UK resident you may be able to obtain them from your local public library, your college library or direct from the publisher.

Related Studies and Trials


Other Reading

This section provides details of other publications on this topic. If you know of any other publications we should include please email info@researchautism.net with the details. Thank you.

Please note that we are unable to supply publications unless we are listed as the publisher. However, if you are a UK resident you may be able to obtain them from your local public library, your college library or direct from the publisher.

Related Other Reading


Updated
24 Dec 2018
Last Review
01 Dec 2018
Next Review
01 Dec 2021