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Risperidone and Autism Ranking: Mildly Hazardous Very strong positive evidence

Anti-psychotic, risperidone

Risperidone is a type of medication called an atypical antipsychotic. It is sold under a variety of brand names including Belivon, Rispen and Risperdal.

Risperidone is primarily used to treat some of the symptoms of schizophrenia, bipolar disorder and other mental health problems.

Risperidone is believed to work by changing the behaviour and characteristics of key neurotransmitters in the brain, in particular dopamine.

Risperidone is sometimes used to help children and adolescents who have been diagnosed with autistic disorder control behaviours such as aggression, self-injurious behaviours and sudden mood changes. 

Please note

The National Institute of Health and Care Excellence (NICE, 2012 and 2013) suggests that antipsychotic medications such as risperidone can be used for managing challenging behaviour in autistic children, young people and adults. However it recommends that antipsychotics should only be used after psychosocial or other interventions have been shown to be insufficient or could not be delivered because of the severity of the behaviour. If antipsychotics are used, they should only be used under very strictly controlled conditions and under the supervision of a paediatrician or psychiatrist.

Our Opinion

There is a considerable amount of high quality research evidence (more than 20 controlled and randomised controlled trials) and a considerable amount of low quality research (more than 20 single-case design studies with three or more participants) into the use of risperidone for autistic children and young people.

This research suggests that risperidone may be beneficial for the treatment of behaviours such as aggression, self-injurious behaviours and sudden mood changes in some autistic children and young people. 

There is insufficient evidence to determine if risperidone provides any benefits in other areas (such as social communication and social interaction) to autistic children and adolescents.  There is insufficient evidence to determine if risperidone provides any benefits to autistic adults.

There is a considerable amount of research evidence of significant side effects of risperidone in some autistic children and young people. Those side effects may include weight gain, drowsiness and raised serum prolactin levels.  

There is a need for further, large-scale, randomised, double-blind trials on the effectiveness of risperidone.   

These studies should

  • Investigate the optimal dosage and length of treatment of risperidone for different autistic individuals including adults.
  • Compare risperidone with other medications which are designed to achieve the same effects, that is, reduce behaviours such as aggression, self-injurious behaviours and sudden mood changes.
  • Compare risperidone with other types of interventions (such as behavioural programmes) which are designed to reduce these kind of behaviours. 
  • Investigate the use of combined, multi-component programmes which use risperidone alongside other types of interventions (such as parent training programmes). 
  • Use objective measures to monitor any potential behavioural and metabolic side effects over the longer term.

If you are considering using risperidone or any other type of antipsychotic medication, you should follow the guidance published by The National Institute of Health and Care Excellence (NICE, 2012 and 2013)

Disclaimer

Please read our Disclaimer on Autism Interventions


Audience

Risperidone is licenced by the US Federal Drugs Administration to treat a variety of mental health problems in adults, teenagers and children.

It is also licenced to treat children 6 to 17 years of age who have autistic disorder with irritable behaviour such as aggression, temper tantrums, and frequent mood changes.  In practice, it is sometimes used with older autistic people.

According to American Society of Health-System Pharmacists (2017),

“Risperidone is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions) in adults and teenagers 13 years of age and older. It is also used to treat episodes of mania (frenzied, abnormally excited, or irritated mood) or mixed episodes (symptoms of mania and depression that happen together) in adults and in teenagers and children 10 years of age and older with bipolar disorder (manic depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Risperidone is also used to treat behavior problems such as aggression, self-injury, and sudden mood changes in teenagers and children 5 to 16 years of age who have autism (a condition that causes repetitive behavior, difficulty interacting with others, and problems with communication).”

 

Aims and Claims

Aims

Risperidone, like other antipsychotic drugs, was developed to treat a wide variety of significant behavioural problems such as aggression, irritability and self-injury.

According to Jesner et al (2007), atypical antipsychotics like risperidone

‘… act by blocking dopamine receptors (D2) in the brain, and may also affect cholinergic, alpha-adrenergic, histaminergic and serotonergic receptors.”*

Claims 

There have been various claims made for the use of risperidone as a treatment for autistic people. For example

  • Boon-Yasidhi V. et al. (2002) claimed that risperidone “… produced clinically meaningful decreases in problem behaviors including hyperactivity, irritability, and aggressiveness”.
  • Capone et al (2008) claimed that risperidone produced “… improvement on important target behaviors such as aggression, disruptiveness, self-injury, stereotypy, and social withdrawal.”
  • Fayyazi et al (2014) claimed that risperidone was effective in “… reducing … hyperactivity disruptive/stereotypic, and conduct problems.”
  • McDougle et al (1997) claimed “Significant improvement was seen in measures of interfering repetitive behavior, aggression and impulsivity, and some elements of impaired social relatedness.”
  • Williams et al (2006) claimed that risperidone produced “significant increases in adaptive behavior in the areas of communication, daily living skills, and socialization.”

*Notes: acetylcholine, alpha-adrenergics, dopamine, histamine and serotonin are all neurotransmitters which play a key part in regulating how the body functions. They work by acting on special parts of cells within the brain and the central nervous system.

Key Features

Risperidone is a type of medication called an atypical antipsychotic. It is sold under a variety of brand names including Belivon, Rispen and Risperdal.

Risperidone comes in a variety of forms including as a tablet, a solution (liquid), an orally disintegrating tablet (tablet that dissolves quickly in the mouth) or a depot (long lasting, intramuscular) injection.

Individuals are usually started on a low dose of risperidone which is gradually increased or decreased depending on how well the medication works and what side effects are experienced.

For the latest information on specific formulations please see the British National Formulary (BNF) information: BNF: Risperidone and BNF for Children: Risperidone

 

Cost and Time

Cost

The cost of using risperidone will depend on a number of factors including the supplier, the brand, the dosage, and the length and frequency of treatment. Newer antipsychotics such as risperidone are generally more expensive than older antipsychotics such as haloperidol or chlorpromazine.  

In the UK medications such as risperidone are available free of charge to patients within the NHS. In other countries the costs may be covered by some insurance policies.

According to the BNF website accessed on 20 April 2018, the NHS indicative price for risperidone varies depending on the brand and the dosage. For example, 20 x 500 microgram tablets may cost £0.59; 20 x 1 mg tablets may cost £8.36; and 60 x 3 mg tablets may cost £1.55.

Time

The amount of time required to administer risperidone will depend to a certain extent on how it is administered.  Tablets and drops are normally taken daily and can be administered by a parent if necessary. Depot injections can be given every few weeks or months but should only be administered by an appropriately trained health care worker.  

Risks and Safety

Hazards

According to the American Society of Health-System Pharmacists (2017), risperidone can cause a number of side effects including: “nausea; vomiting; diarrhea; constipation; heartburn; dry mouth; increased saliva; increased appetite; weight gain; stomach pain; anxiety; agitation; restlessness; dreaming more than usual; difficulty falling asleep or staying asleep; breast enlargement or discharge; late or missed menstrual periods; decreased sexual ability; vision problems; muscle or joint pain; dry or discolored skin; difficulty urinating; dizziness, feeling unsteady, or having trouble keeping your balance.”

More seriously it can sometimes cause “fever; muscle stiffness; falling; confusion; fast or irregular pulse; sweating; unusual movements of your face or body that you cannot control; faintness; seizures; slow movements or shuffling walk; rash; hives; itching; difficulty breathing or swallowing; painful erection of the penis that lasts for hours.”

Even more seriously risperidone can cause significant side effects in some older adults with dementia.

“Studies have shown that older adults with dementia (a brain disorder that affects the ability to remember, think clearly, communicate, and perform daily activities and that may cause changes in mood and personality) who take antipsychotics (medications for mental illness) such as risperidone have an increased risk of death during treatment. Older adults with dementia may also have a greater chance of having a stroke or ministroke during treatment.”

Contraindications

There are some contraindications (something which makes a particular treatment or procedure potentially inadvisable) for risperidone. For example, according to American Society of Health-System Pharmacists (2017), risperidone should be used with caution in people who

  • are already using or planning to use one of the following medications or dietary supplements: “antidepressants; carbamazepine (Tegretol); cimetidine (Tagamet); clozapine (Clozaril); dopamine agonists such as bromocriptine (Parlodel), cabergoline (Dostinex), levodopa (Dopar, Larodopa), pergolide (Permax), and ropinirole (Requip); medications for anxiety, high blood pressure, or seizures; other medications for mental illness; paroxetine (Paxil); phenobarbital (Luminal, Solfoton); phenytoin (Dilantin); quinidine (Quinaglute, Quinidex); ranitidine (Zantac); rifampin (Rifadin, Rimactane); sedatives; sleeping pills; tranquilizers; and valproic acid (Depakote, Depakene).”
  • “use or have ever used street drugs or large amounts of alcohol; have ever overused prescription medications; have or have ever had Parkinson's disease (PD; a disorder of the nervous system that causes difficulties with movement, muscle control, and balance); dyslipidemia (high cholesterol levels); a low level of white blood cells in your blood or a decrease in white blood cells; difficulty swallowing; trouble keeping your balance; breast cancer; angina (chest pain); irregular heartbeat; high or low blood pressure; heart failure; a heart attack; a stroke; seizures; heart, kidney or liver disease; or if you or anyone in your family has or has ever had diabetes.”

Please see American Society of Health-System Pharmacists (2017), for a full list of potential hazards and contraindications.

Suppliers and Availability

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

History

Risperidone (Belivon, Rispen, Risperdal in the United States) was developed as an atypical antipsychotic medication by Janssen Pharmaceutica. It was approved by the United States Food and Drug Administration (FDA) in 1993 for use in adults.

According to NICE, antipsychotic drugs, such as risperidone, are now in common use to treat autistic people.

"Antipsychotic drugs have been widely used in people with autism; for instance, a longitudinal study of 286 adolescents and adults in the US found that they were the second most commonly taken drug among people aged over 20 years (38%), after antidepressants (44%) (Esbensen et al., 2009). In a UK audit of drug use for challenging behaviour in a learning disabilities sample (in which the commonest coexisting diagnosis was autism), 96% were prescribed antipsychotic medication (Marshall, 2004). In another community sample of people with a learning difficulty, Dhumad and Markar (2007) reported that autism was the reason for prescribing antipsychotic medication in 20% of people."

 

Current Research

Description of studies

We have identified more than 60* research papers on risperidone as an intervention for autistic people published in English-language, peer-reviewed journals.

These papers included more than 1,000 individuals aged from 3 to 48 years old, although the majority were primary school children or adolescents. These individuals included people with autistic disorder, Asperger syndrome and pervasive developmental disorder - not otherwise specified. 

The majority of studies were carried out by single research teams on single sites but some of the larger studies were carried out by several researchers on several sites. In the case of the series of studies carried out by the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network we have identified more than 10 different papers. Some of these papers set out the rationale for the studies and explained the methodologies that would be used. Some of these papers reported on different parts of the studies (which included several controlled trials and several open trials). Some of the papers investigated the effects of risperidone on specific issues (such as adaptive behaviours, social communication and social interaction or repetitive and restricted behaviours). Some of the papers evaluated whether risperidone caused specific adverse effects (such as weight gain, somnolence and raised serum prolactin levels).

The length of treatment described in the papers we identified varied between six weeks and three years, although in most cases the treatment lasted between six to eight weeks. The dosage of risperidone varied from 0.75 mg per day to 3.5 mg per day, with younger children receiving smaller doses than adolescents and adults. In most cases, risperidone was started at a low dose and gradually increased to a higher maximum dose. 

Approximately half of the studies used a group design (usually comparing a group of people receiving risperidone to a different group receiving a placebo). Approximately half of the studies used singe case designs (usually in the form of an open trial of risperidone within a single group). 

A minority of the group studies compared risperidone with other antipsychotics (such as aripiprazole or haloperidol) or with other types of medication (such as buspirone or memantine). One of the studies compared low dose risperidone against high dose risperidone. Two of the studies compared risperidone combined with a parent training programme against risperidone alone.

*Please note: we have not included studies with fewer than three autistic participants and we have not included studies which combined risperidone with one or more other substances (including other medications or dietary supplements).  We have also not included any of the papers from the Research Units on Paediatric Psychopharmacology Autism Network studies where these did not measure the efficacy or otherwise of risperidone.

Outcomes from studies

  • Most of the studies (such as Boon-Yasidhi et al, 2002) found that risperidone was effective in reducing irritable behaviour  such as aggression, self-injurious behaviours and sudden mood changes in some autistic people.
  • Some of the studies (such as Williams et al, 2006) found that risperidone was effective in increasing adaptive behaviours in a range of areas, including communication, daily living skills, and socialisation in some autistic children and young people.
  • The single study (Kent et al, 2013) which compared low dose risperidone (0.125-0.175 mg/day ) against high dose risperidone (0.5–3 mg/day) found that the high dose was more effective in reducing irritability in children and young people with autistic disorder, although the high dose also led to more frequent side effects.
  • The studies which compared risperidone with aripiprazole (such as Ghanizadeh et al, 2014) found that these two antipsychotics were equally effective in treating irritability in autistic children.
  • Most of the studies which compared risperidone with the older types of antipsychotics (such as haloperidol) or with other types of medication (such as buspirone) found that risperidone was more effective than the other medications.
  • There was a single study (Nikvarz et al, 2017) which found that memantine was almost as effective as risperidone in reducing a range of symptoms in autistic children and young people.
  • There was a single study (Tyrer et al, 2008) which found that a placebo was more effective than either risperidone or haloperidol in reducing challenging behaviour in patients with a learning disability (some of whom were autistic).
  • The initial study which compared risperidone combined with a parent training programme against risperidone alone (RUPP AN, 2009) found that the combined package was more effective. However the follow up study (Arnold et al, 2012) found that the combined package was no more or less effective than risperidone alone.
  • Many of the studies reported significant adverse effects. For example, the Research Units on Paediatric Psychopharmacology Autism Network studies reported a range of adverse side effects including weight gain, increased appetite, fatigue, drowsiness, dizziness and drooling. 

Status Research

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

Type of study

  • Approximately half of the studies used single-case designs, that is, they did not have a control group of participants who did not receive risperidone. 
  • Four of the single case design studies used relatively weak methodologies - such as non-experimental case series.
  • Four of the randomised controlled studies were non-blinded.
  • Some of the randomised, controlled studies did not follow methodologies expected within a randomised controlled trial. For example, the study by Ghanizadeh et al (2013) did not provide details of the randomisation and allocation concealment process used.

Participants

  • Six of these single case design studies included fewer than 10 autistic participants.
  • Four of the randomised controlled studies had fewer than thirty autistic participants. 
  • Some of the studies had a high dropout rate. For example, one study (McDougle et al, 1998) had a dropout rate of 33% (with 7 of 21 participants being unable to complete the treatment).
  • Some of the studies examined participants with a range of conditions, only a proportion of whom were autistic. For example, the study by Tyrer et al, 2008 had 86 participants but only 14 of these were classed as being autistic.
  • Some of the studies were restricted to specific groups of participants. For example, one study (Alexander et al, 2004) looked only at adults with Asperger syndrome.
  • Some of the studies (such as King et al, 2003) did not appear to have independently verified the diagnosis of autism using established diagnostic tools like the ADOS or ADI-R. 

Interventions

  • Some of the studies gave very little detail about the risperidone and how it was administered. For example, Lemmon et al, 2011 did not state the length of treatment, the frequency of treatment or the dosage of risperidone that was given to the participants. 
  • Some of the studies (such as Mukaddes et al, 2004) lasted for relatively short periods of time (six weeks) and did not appear to follow up the participants once the treatment had completed.
  • One of the studies (Fayyazi et al, 2013) used a crossover design (alternating between risperidone and buspirone) but provided insufficient details about the washout period (the period when no medication was provided) between the medications. 

Comparators

  • Some of the group studies had unevenly matched participant groups. For example, in the study by Luby et al (2006) the group of pre-schoolers treated with risperidone showed significantly greater severity of autism symptoms at baseline than the group which received the placebo.

Outcomes

  • Some of the studies used a small number of outcome measures and/or used less robust outcome measures. For example McDougle et al, 1997 used only one outcome measure, the Clinical Global Impression Scale. This is less robust than some other measures because it relies on the subjective judgement of the clinician.
  • Some of the studies did not provide adequate data on the baseline and outcome characteristics of the participants. For example, Vercellino et al (2001) used three different behavioural measures for the participants but did not provide detailed, tabulated data for any of these measures at the baseline or at the endpoint of the study.
  • Some of the studies (such as Ghaeli et al, 2014) did not report objective measures of potential adverse side effects (such as changes to blood glucose levels etc.) but relied on the participants to report their subjective views of any adverse side effects.
  • Some of the studies did not identify if risperidone had any beneficial effects in the medium to long term (six months or longer).

Other

  • Very few of the studies appeared to involve autistic people or parents and carers in the design, development and evaluation of those studies.
  • Some of the studies (such as Shea et al, 2004) were funded by Janssen-Ortho Inc, a manufacturer of one of the commercial brands of risperidone.  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 autism research studies are flawed."

Ongoing Research

We have identified the following studies into risperidone as an intervention for autistic people that are currently underway or which have yet to report. If you know of any other studies we should include please email info@researchautism.net with the details. 

  • Janssen Pharmaceutical K.K. is running a study to evaluate the efficacy of risperidone compared with placebo in children and adolescents with irritability associated with autistic disorder..  Clinical Trials Gov Ref: NCT01624675.  For more details, please see A Study to Evaluate the Efficacy and Safety of Risperidone (R064766) in Children and Adolescents With Irritability Associated With Autistic Disorder  https://clinicaltrials.gov/ct2/show/study/NCT01624675
  • Janssen-Ortho Inc., Canada is running a study to evaluate the effectiveness of an oral solution of risperidone, an antipsychotic medication) versus placebo in the treatment of behavioral symptoms in children with Pervasive Developmental Disorders (PDD). Clinical Trials Gov Ref: NCT00261508. For more details please see  Treatment of Autism in Children and Adolescents A Study of the Effectiveness and Safety of Risperidone Versus Placebo in the Treatment of Children With Autistic Disorder and Other Pervasive Developmental Disorders (PDD) https://clinicaltrials.gov/ct2/show/NCT00261508
  • The National Institute of Mental Health is running a study to determine the effectiveness of risperidone, a drug treatment for the interfering symptoms of Autistic Disorder in children and adolescents between the ages of 5 and 17. Clinical Trials Gov Ref: NCT00005014.  For more details please see  Treatment of Autism in Children and Adolescents https://clinicaltrials.gov/ct2/show/NCT00005014
  • The Washington University School of Medicine is running a study to compare applied behavioral analysis (ABA) versus ABA and risperidone in preschool children on the autism spectrum. Clinical Trials Gov Ref: NCT00374764.   For more details, please see Comparison of Applied Behavioral Analysis (ABA) Versus ABA and Risperidone https://clinicaltrials.gov/ct2/show/study/NCT00374764
  • Yale University is running a study to compare the safety and effectiveness of medication treatment alone (risperidone or aripiprazole) to medication treatment in combination with a parent management training program. Clinical Trials Gov Ref: NCT00080145 For more details, please see RUPP PI PDD: Drug and Behavioral Therapy for Children With Pervasive Developmental Disorders https://clinicaltrials.gov/ct2/show/results/NCT00080145 

Future Research

Summary of Existing Research

There is a considerable amount of high quality research evidence (more than 20 controlled and randomised controlled trials) and a considerable amount of low quality research (more than 20 single-case design studies with three or more participants) into the use of risperidone for autistic children and young people.

This research suggests that risperidone may be beneficial for the treatment of behaviours such as aggression, self-injurious behaviours and sudden mood changes in some autistic children and young people.

There is insufficient evidence to determine if risperidone provides any benefits in other areas (such as social communication and social interaction) to autistic children and adolescents. There is insufficient evidence to determine if risperidone provides any benefits to autistic adults.

There is a considerable amount of research evidence of significant side effects of risperidone in some autistic children and young people. Those side effects may include weight gain, drowsiness and raised serum prolactin levels.

Recommendations for Future Research

There is a need for further, large-scale, randomised, double-blind trials on the effectiveness of risperidone. These studies should

  • Investigate the optimal dosage and length of treatment of risperidone for different autistic individuals including adults.
  • Compare risperidone with other medications which are designed to achieve the same effects, that is, reduce behaviours such as aggression, self-injurious behaviours and sudden mood changes in some autistic children and young people.
  • Compare risperidone with other types of interventions (such as behavioural programmes) which are designed to reduce these kind of behaviours.
  • Investigate the use of combined, multi-component programmes which use risperidone alongside other types of interventions (such as parent training programmes).
  • Use objective measures to monitor any potential behavioural and metabolic side effects over the longer term.
  • Involve autistic people 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 risperidone for people with autism which have been published in English-language, peer-reviewed journals.

If you know of any other publications we should list on this page please email info@informationautism.org

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.

You can find more publications on this topic in our publications database.

If you know of any other publications we should list on this page please email info@informationautism.org

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
17 Jun 2022
Last Review
01 Jul 2018
Next Review
01 Jul 2024