Key messages
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Risperidone and aripiprazole may reduce irritability symptoms, while lurasidone probably results in little to no difference in children with autism.
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There is significant uncertainty about the effects of these drugs on aggression, weight gain and abnormal body movements (e.g. tremors) in children with autism.
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These medicines may decrease obsessive-compulsive symptoms (unwanted thoughts (obsessions) and repetitive behaviours (compulsions)) and inappropriate speech in children with autism.
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We could not thoroughly explore the benefits and harms of these medications in adults with autism as there were few data.
What is autism?
Autism, also known as autism spectrum disorder or autism spectrum condition, is a developmental disorder that affects communication, social interaction and behaviour.
What are atypical antipsychotic medicines?
Antipsychotic medications are primarily used to treat mental health problems, maintaining the balance of certain neurotransmitters (naturally occurring chemicals that allow nerves to communicate throughout the body; for example, dopamine) in the brain to improve a variety of symptoms. Atypical antipsychotics are medications with different benefits and harms compared to typical antipsychotics.
What did we want to find out?
We wanted to compare how well atypical antipsychotics work for reducing irritability in children and adults with autism spectrum disorder. Additionally, we wanted to understand their effectiveness and harms for other symptoms.
What did we do?
We looked for studies that compared different atypical antipsychotic medicines with a placebo (dummy treatment) or with another atypical antipsychotic medicine in people diagnosed with autism spectrum disorder.
What did we find?
We found 17 studies including 1027 people. Most studies focused on children, with only one study involving adults.
Some atypical antipsychotics, such as risperidone and aripiprazole, may reduce irritability in children with autism spectrum disorder over a short period, unlike lurasidone, which probably has little to no effect. Atypical antipsychotic medicines may improve obsessive-compulsive symptoms and may reduce inappropriate speech. We are very uncertain about the effects on aggression, weight gain and unwanted effects related to movement.
What are the limitations of the evidence?
Our confidence in the evidence ranged from moderate to very low. Although we have more confidence in some symptoms and measures, such as irritability, stronger evidence is still needed. We have even less confidence in measures such as weight gain and movement-related unwanted effects, mainly because the studies were small and results varied. In addition, most of the available data were from short-term studies.
How up to date is this information?
The information is current to January 2024.
Read the full abstract
Objectives
Primary: to assess the comparative benefits of atypical antipsychotics for irritability through network meta-analyses in children and adults with ASD at short-term follow-up.
Secondary: to assess the benefits and harms of atypical antipsychotics, compared to placebo or any other atypical antipsychotic, for different symptoms (e.g. aggression, obsessive-compulsive behaviours, inappropriate speech) and side effects (e.g. extrapyramidal symptoms, weight gain, metabolic side effects) in children and adults with ASD at short-, medium- and long-term follow-up.
Search strategy
We searched CENTRAL, MEDLINE, 10 other databases, and two trial registers, together with reference checking, citation searching and contact with study authors to identify studies for inclusion. The latest search was 3 January 2024.
Authors' conclusions
Risperidone and aripiprazole may reduce symptoms of irritability compared to placebo in children with ASD in the short term, but lurasidone probably has little to no effect on irritability compared to placebo. Other benefits and potential harms observed ranged from moderate- to very low-certainty evidence. The available data did not allow comprehensive subgroup analyses.
New randomised controlled trials with larger sample sizes are needed to balance the efficacy and safety of interventions with enough certainty, which are currently scarce (or even absent in the case of the adult population). Authors should report population and intervention characteristics transparently, providing disaggregated or individual patient data when possible. Furthermore, consistent measurement methods for each outcome should be reported to avoid problems during the data synthesis process.
Funding
This Cochrane review had no dedicated funding.
Registration
Protocol available via 10.1002/14651858.CD014965.
