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Antipsychotics and Autism Ranking: Mildly Hazardous Unable to rate

Antipsychotic capsules

Antipsychotics, also known as neuroleptics or major tranquilisers, are types of medications.

They are normally used to help people with some mental health problems — mainly schizophrenia and bipolar affective disorder. They can also be used to help people with severe anxiety or depression.

There are two main types of antipsychotics.

1. The older, typical or conventional antipsychotics, which include chlorpromazine, flupenthixol, haloperidol, levomepromazine, pericyazine, perphenazine, pimozide, prochlorperazine, promazine, sulpiride, trifluoperazine and zuclopenthixol.

2. The newer, atypical antipsychotics, which include amisulpride, aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone and ziprasidone. 

Antipsychotics are sometimes used to treat some of the more challenging problems faced by individuals on the autism spectrum.  Those problems include aggression, irritability, hyperactivity, self injury, and repetitive behaviour.

Please note

The National Institute of Health and Care Excellence (NICE, 2012 and 2013) suggests that antipsychotic medication can be used for managing challenging behaviour in children, young people and adults on the autism spectrum. 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 very strong research evidence to suggest that some atypical antipsychotics (such as aripiprazole and risperidone) may be beneficial for the treatment of aggression, irritability, hyperactivity, self injury, and repetitive behaviour in some children and young people on the autism spectrum.

There is very little high quality research evidence on the effectiveness of most other antipsychotics as a treatment for anyone on the autism spectrum.

There is evidence of significant side effects of some antipsychotics in some children, young people and adults on the autism spectrum. Those side effects may include weight gain, hyperprolactinaemia (raised prolactin levels) and tachycardia  (abnormally fast heart rate).

We agree with NICE that antipsychotics should only be used as part of a comprehensive treatment programme, under specialist supervision, where other measures prove insufficient.

Antipsychotics should be discontinued if there is no response after six weeks, and treatment should be suspended periodically to assess the individual’s condition.

When choosing antipsychotic medication, you should take into account side effects, the costs, the individual’s preference, and their response to any previous treatment with an antipsychotic.

Future research should compare different antipsychotics with each other to determine which is most effective for the treatment of which issues in which individuals on the autism spectrum.  It should also investigate the optimal dosage and length of treatment for different individuals, while also investigating the long-term effects of antipsychotics on individuals.

Disclaimer

Please read our Disclaimer on Autism Interventions


Aims and Claims

Aims

According to Mind (2012), antipsychotics are designed to

  • control anxiety and serious agitation, so that you feel less threatened
  • reduce incoherent speech and muddled thinking
  • reduce confusion
  • lessen delusions and hallucinations
  • reduce violent, disruptive behaviour
  • reduce mania.

They are sometimes prescribed for anxiety, in very low doses, and to supplement antidepressants if you are severely depressed. They are also sometimes used to control agitation and psychotic experiences in dementia.

Antipsychotics are also sometimes used to treat some of the more challenging problems faced by individuals on the autism spectrum including aggression, irritability, hyperactivity, self injury, and repetitive behaviour.

Claims

There have been various claims made for the use of antipsychotics as a treatment for people on the autism spectrum. 

For example, according to NICE (2013), there is some evidence to suggest that risperidone and aripiprazole may be effective in reducing irritability, lethargy, stereotypic behaviour, hyperactivity, inappropriate speech and parent-defined target behaviours that challenge.

Audience

According to the Royal College of Psychiatrists (2012), antipsychotics are used to help people with “some types of mental distress or disorder - mainly schizophrenia and manic depression (bipolar disorder). They can also be used to help [people with] severe anxiety or depression.”

According to NICE (2012), antipsychotics are also commonly used to help people on the autism spectrum

“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.”

Key Features

Antipsychotics (also known as neuroleptics or major tranquillisers) are types of psychoactive medications used to treat a range of mental health problems including psychosis, anxiety and dementia.

Types

There are two main types of antipsychotics.

1. The older, typical or conventional antipsychotics, which include chlorpromazine, flupenthixol, haloperidol, levomepromazine, pericyazine, perphenazine, pimozide, prochlorperazine, promazine, sulpiride, trifluoperazine and zuclopenthixol.

2. The newer, atypical antipsychotics, which amisulpride, aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone and ziprasidone. 

Mechanism – how they work

Antipsychotics work by changing the amounts and the effects of different neurotransmitters (chemicals in the brain).  Traditional antipsychotics work mainly by reducing the amount and the action of dopamine. Atypical antipsychotics work mainly by changing the amount and the action of a range of neurotransmitters including dopamine, serotonin, noradrenaline and acetylcholine.

Format and Brands

Antipsychotics are available as tablets, capsules, liquids, intravenous injections and depot injections (long-acting).

The same antipsychotic may have several different brand names. For example, haloperidol is marketed as Dozic, Haldol and Serenace.

Dosage

According to Mind (2012)

“The British National Formulary (BNF – the main drug reference book for prescribers) gives maximum doses for some, but not all, of the antipsychotics. Generally, the drugs aren’t licensed for use above these dosages, but doctors can give you a higher dose, at their discretion. If you are in hospital, they may also prescribe medication to be given ‘as necessary’ (usually referred to as p.r.n.) which can mean in addition to your regular dose. As a result, your total dose could be above the BNF maximum. In this case, your psychiatrist has a duty to review your total dosage daily.”

For the latest information on specific formulations and recommended dosages please see our website entries on specific antipsychotics or refer to the BNF.

Usage

NICE (2013) has provided clinical guidance re the use of pharmacological interventions (such as antipsychotics) for behaviour that challenges in children and young people on the autism spectrum.  The clinical guidance for the use of antipsychotics in adults on the autism spectrum is very similar.

This guidance suggests that you consider antipsychotic medication for managing behaviour that challenges in children and young people with autism when psychosocial or other interventions are insufficient or could not be delivered because of the severity of the behaviour.

Antipsychotic medication should be initially prescribed and monitored by a paediatrician or psychiatrist who should identify the target behaviour, decide on an appropriate measure to monitor effectiveness, review the effectiveness and any side effects of the medication after 3–4 weeks and stop treatment if there is no indication of a clinically important response at 6 weeks.

If antipsychotic medication is prescribed, you should start with a low dose, use the minimum effective dose needed and regularly review the benefits of the antipsychotic medication and any adverse events.

When choosing antipsychotic medication, you should take into account side effects, the costs, the individual’s preference, and their response to any previous treatment with an antipsychotic.

Cost and Time

Cost

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

For the latest information on costs please see BNF (British National Formulary) and BNF for Children.

Time

Some people on the autism spectrum may be prescribed antipsychotics to help them at times of crisis or to help them overcome a particular challenging behaviour. Other people may be prescribed antipsychotics for longer periods.

NICE (2013) recommends that you should review the effectiveness and any side effects of the medication after 3–4 weeks and stop treatment if there is no indication of a clinically important response at 6 weeks.

Parental/carer involvement in the use of antipsychotics is minimal since the person on the autism spectrum usually takes them once a day.

Risks and Safety

Hazards

According to the Royal College of Psychiatrists (2011), the side-effects of the older, typical antipsychotics can include:

  • stiffness and shakiness, like Parkinson’s disease
  • feeling sluggish and slow in your thinking
  • akathisia  (uncomfortable restlessness)
  • problems with your sex life.
  • tardive dyskinesia (continual movements of the mouth, tongue and jaw).

The side-effects of the newer, atypical antipsychotics can include:

  • sleepiness and slowness
  • weight gain
  • interference with your sex life
  • increased chance of developing diabetes
  • in high doses, some have the same Parkinsonian side-effects as the older medications
  • long-term use can produce tardive dyskinesia and, rarely, of the arms or legs.

In people on the autism spectrum

According to NICE (2013),

“There ... are robust data suggestive of adverse events associated with risperidone or aripiprazole, in particular, weight gain, prolactin concentration [which can cause various problems] and tachycardia (abnormally fast heart rate). It is also important to note that these trials were run over short time periods and very little is known about the long-term effects of antipsychotic drugs in children and young people with autism.”

For details of the side effects of specific antipsychotics, please see our detailed website entries on those specific antipsychotics.

Contraindications

Some antipsychotics may be contraindicated (something which makes a particular treatment or procedure potentially inadvisable) in certain groups of people.  For example, MIND (2012) recommends that if you have any of the following, you should use antipsychotics with caution:

  • liver or kidney disease
  • cardiovascular (heart and circulation) disease
  • family history of diabetes
  • Parkinson’s disease
  • epilepsy
  • depression
  • myasthenia gravis (a rare disease affecting nerves and muscles)
  • an enlarged prostate
  • a history of glaucoma, an eye disease
  • lung disease with breathing problems
  • some blood disorders.

According to Rethink Mental Illness (2012)

“Some antipsychotics can interact with tricylic antidepressants and so they should not normally be prescribed together. Due to the sedative effect of some antipsychotics, doctors should take care when prescribing sleeping tablets, tricylic antidepressants and benzodiazepines among other medications. There are a number of possible interactions between antipsychotics and other medications, so it is important that your doctor knows about all the medicines you are taking.”

For details of the contraindications of specific antipsychotics, please see our detailed website entries on those specific antipsychotics.

Suppliers and Availability

Suppliers

In the UK antipsychotics are available free of charge to patients within the NHS.

Credentials

Antipsychotics are very powerful psychoactive medications with many potential side effects and contradictions. For this reason they should only be obtained on prescription from a paediatrician or psychiatrist.

History

Most of the older, typical antipsychotics (such as haloperidol) were first used in the 1950’s. They were designed to block the action of the neurotransmitter dopamine. These older antipsychotics are sometimes called conventional or first generation antipsychotics.

Most of the newer, atypical antipsychotics (such as risperidone) were developed in the 1970’s, although aripiprazole was not developed until the 2000’s. These second generation antipsychotics were designed to block or increase the action of one or more neurotransmitters including dopamine, serotonin, noradrenaline and acetylcholine. They were also designed to have fewer side effects than the older antipsychotics.

Risperidone was approved as a treatment for irritability associated with autistic disorder in children by the United States Food and Drug Administration (FDA) in 2006. 

Aripiprazole was approved for the treatment of irritability associated with autistic disorder in children by the FDA in 2009.

Current Research

Current Research Studies

We carried out a systematic search for research reviews, and clinical guidance, on the topic of antipsychotics as a treatment for people on the autism spectrum in 2014.  We identified more than 60 scientific reviews on the topic of medications for autism, seven of which looked specifically at antipsychotics. We also examined the clinical guidance published by NICE. 

NICE (2012) reported

“The majority of the evidence on the use of antipsychotics for behaviour management in adults with autism compared risperidone with placebo, and there is limited evidence for a modest treatment effect of risperidone on irritability and aggression. In addition, there is some evidence that autistic behaviours, the core autistic symptom of repetitive behaviour, and global symptom severity may respond favourably to treatment with risperidone. However, the data from placebo-controlled and observational studies of risperidone in adults with a learning disability is inconsistent. In addition, most of the studies in autism and learning disabilities populations report data suggestive of adverse events associated with risperidone, in particular, sedation and weight gain. (Note, this is consistent with the evidence of adverse effects associated with the use of these drugs for schizophrenia.) It is also important to note that these trials were run over short time periods and very little is known about the long-term effects of antipsychotics in adults with autism. The evidence for haloperidol was very limited and inconsistent, with no evidence for significant treatment effects in adults with autism. The results for clopenthixol provided limited evidence ...   for a beneficial effect on the management of challenging behaviour in adults with a learning disability. The evidence for olanzapine for behaviour management is extremely limited ... with just one open-label study.”

NICE (2013) reported

“There is evidence for positive treatment effects of antipsychotic drugs on behaviour that challenges. The majority of the evidence on the use of antipsychotics for behaviour that challenges in children and young people with autism compared risperidone or aripiprazole with placebo, and there is moderate to low quality evidence for treatment effects on irritability, lethargy, stereotypic behaviour, hyperactivity, inappropriate speech and parent-defined target behaviours that challenge. However, there are also robust data suggestive of adverse events associated with risperidone or aripiprazole, in particular, weight gain, prolactin concentration and tachycardia. It is also important to note that these trials were run over short time periods and very little is known about the long-term effects of antipsychotic drugs in children and young people with autism.”

Barnard et al (2002) reported

“Conventional antipsychotic medication is commonly prescribed to patients with autistic spectrum disorder. However, a high incidence of severe adverse reactions highlights the need to find more favourable treatments. Atypical antipsychotics may combine efficacy in ameliorating some autistic symptoms with a lower incidence of some adverse reactions. This article reviews the use of atypical antipsychotics in autistic disorder, with particular focus on behaviour, cognition and physical well-being. Thirteen studies using risperidone, three using olanzapine, one using clozapine, one using amisulpride and one using quetiapine were identified. Few firm conclusions can be drawn due to the limitations of the studies; however, there is an indication that risperidone may be effective in reducing hyperactivity, aggression and repetitive behaviours, often without inducing severe adverse reactions. Olanzapine and clozapine may also be effective; however, there is little evidence for using amisulpride or quetiapine in this population. Randomized trials are required to clarify the effectiveness of these agents.”

Chavez et al (2007) reported

“Of the AAs [atypical antipsychotics], risperidone has the largest amount of evidence with five published double-blinded, placebo-controlled trials and nine open-label trials. These risperidone trials have consistently shown improvements in aggression, irritability, self-injurious behavior, temper tantrums, and quickly changing moods associated with autistic disorder and other PDDs. Data for the other AAs are limited, but ziprasidone and aripiprazole appear to be promising treatment options. Based on clinical trials, olanzapine and quetiapine have shown minimal clinical benefit and a high incidence of weight gain and sedation. It should be noted that all AAs do have a risk of metabolic syndrome, and patients should be monitored appropriately while receiving these medications. Overall, AAs can be beneficial in alleviating behavioral symptoms, and should be considered an appropriate therapeutic option, as part of a comprehensive treatment strategy, for children with PDD.”

Malone et al (2009) reported

“Antipsychotics are beneficial for reducing problematic behaviours and improving overall functioning in patients with autism. These drugs should always be used as an adjunctive treatment to other interventions such as psychosocial and educational programmes. Among antipsychotics, the second-generation agents appear promising, especially risperidone, which has recently gained FDA approval for treatment in youths with autistic disorder. Most second generation agents have the potential to cause weight gain and associated metabolic syndrome. Therefore, regular monitoring of weight, blood pressure, glucose and lipids is required. Among the second-generation agents, ziprasidone and aripiprazole appear to have a lesser risk of metabolic adverse effects. More controlled studies are needed to assess efficacy and safety of these agents on a short- and long-term basis. Also needed are head-to-head studies of antipsychotics to address differences.”

Politte and McDougle (2014) reported

“The efficacy and tolerability of risperidone and aripiprazole for the treatment of irritability in autism have been established with multi-site, randomized, controlled trials. Studies supporting the use of other atypical antipsychotics are either limited in scope or less robust in their findings, though newer agents such as ziprasidone and paliperidone show promise. Atypical antipsychotics are currently first-line pharmacological agents for the treatment of irritability and associated behaviors in children with PDD. Further placebo controlled studies are warranted to characterize the efficacy and tolerability of the majority of these medications. There is also a need for the development of novel, targeted drugs with more favorable long-term side effect profiles.”

Posey et al (2008) reported

“Both haloperidol and risperidone have been shown to be efficacious for treating several of the behavioral symptoms associated with autism. The current role of haloperidol is limited due to the risk of EPS, especially TD. Because of this, atypical antipsychotics are more commonly used today in treating persons with autism. Despite the efficacy of risperidone, the decision to prescribe this drug needs to include consideration of the potential side effects, especially those of weight gain, hyperprolactinemia, and TD... Despite its efficacy for reducing behavioral symptoms, it is unclear whether risperidone improves the core social and communication impairment of autism. Indeed, a study that included less irritable children found a lower rate or magnitude of response. Additional studies of risperidone and other atypical antipsychotics in nonirritable children with autism or studies using other measures of social impairment might be informative. It also remains to be determined whether atypical antipsychotics other than risperidone are effective in the treatment of disruptive science in medicine behavior in autism. Large placebo-controlled studies of olanzapine and aripiprazole are underway. The long-term significance of hyperprolactinemia, as well as the long-term risk of TD, needs to be determined in either prospectively defined cohorts or via larger controlled studies of longer duration. Finally, further research that informs the clinical management of weight gain occurring with these drugs when used in autism is needed. This might include identifying patients who are genetically more susceptible to this side effect as well as determining the best approach to management (e.g., diet and/or exercise, switching drugs, or pharmacologic treatments).”

Sochocky and Milin (2013) reported

“There is a lack of robustly conducted trials on the use of SGAs in the management of AD and HFA. More research in pharmacological and psychosocial treatments is warranted. Clinicians are cautioned to approach pharmacological treatment prudently balancing benefit with potential cardiometabolic risk.”

Stachnik and Nunn-Thompson (2007) (reported)

“Based on available information, atypical antipsychotics may improve behavior in individuals with AD, but do not affect the core symptoms of the disorder. However, given that AD requires life-long treatment and that data are limited on the safety of these agents in children, vigilance is especially necessary when prescribing any of the atypical antipsychotics. Long-term clinical trials that incorporate realistic inclusion criteria and uniform outcome and safety assessment tools are critical before these drugs can be broadly recommended for chronic administration to children with AD.”

Future Research

Summary of Existing Research

There is very strong research evidence to suggest that some atypical antipsychotics (such as aripiprazole and risperidone) may be beneficial for the treatment of aggression, irritability, hyperactivity, self injury, and repetitive behaviour in some children and adults on the autism spectrum.

There is very little high quality research evidence on the effectiveness of most other antipsychotics as a treatment for people on the autism spectrum.

There is evidence of significant side effects of some antipsychotics in some children/adults on the autism spectrum. Those side effects may include weight gain, hyperprolactinaemia (raised prolactin levels) and tachycardia (abnormally fast heart rate).

Recommendations for Future Research

Future research should

  • Compare different antipsychotics with each other to determine which is most effective for the treatment of which issues in which individuals on the autism spectrum. 
  • Investigate the optimal dosage and length of treatment for different individuals on the autism spectrum.
  • Investigate the long-term effects of antipsychotics in children and young people and adults on the autism spectrum ensuring that any side effects are monitored carefully.

Further research is also required to fully evaluate the role of antipsychotics in managing challenging behaviour in people with autism. Such research should include comparative studies to determine which antipsychotics are most effective for the treatment of which issues and in which individuals on the autism spectrum

Studies and Trials

Please see research studies on specific antipsychotics as interventions for people on the autism spectrum listed below.

Personal Accounts

We have been unable to identify any personal accounts about the use of antipsychotics for people on the autism spectrum.

If you know of any personal accounts we should include please email info@researchautism.net

Updated
01 Nov 2017
Last Review
01 Nov 2016
Next Review
01 Nov 2019