Risperidone proven to be effective in treating behavioral disturbances in autism
Child Health Monitor, Volume 3, Issue 6
Autism is a permanent neurodevelopmental condition characterised by marked difficulties in the ability to relate to others, delayed language, and restricted patterns of behaviour. The true frequency of autism is unknown, but core autism (as opposed to autism spectrum disorders, which include sufferers with subtypes of autism) probably affects around one in 500 children and adolescents.
The treatment of autism consists of speech therapy, occupational and physiotherapy, psychological help for the sufferer and family plus drug treatment if appropriate. Sadly, some drugs recently touted as being cures for autism, such as secretin, have proven to be largely ineffective. However, drug treatment is often used when children or young people have serious behavioral problems that cannot be treated psychologically. These problems include self-injurious behaviour, aggression, and tantrums in response to routine environmental demands. These behavioral problems pose great challenges for caregivers, and also interfere with other aspects of treatment. Behavioural therapy often helps control such behaviours, but drugs are needed when this fails or only controls problems partially.
The issue of which drug is best for controlling behaviour in autism is a difficult one. Many drugs have been tried with varying degrees of success, but it is important that good evidence is provided to guide quality practice. The only drug shown to be effective in more than one high quality study (i.e. randomised controlled trials) is Haloperidol, a postsynaptic dopamine-receptor antagonist that is generally used for the treatment of psychotic disorders such as schizophrenia. However, many doctors dont like using Haloperidol in children as it has many side effects.
Newer anti-psychotic drugs are replacing Haloperidol and other older drugs in the treatment of psychotic disorders in adults, largely because they are often more effective and certainly have fewer side effects. Risperidone is one such drug, and there has been great interest in its possible use to control behaviours in autism. There has been only one high quality trial of Risperidone in autism however it was undertaken in adults. Some smaller case reports of using Risperidone in children with autism have suggested that the drug may be useful for controlling problem behaviours, so a high quality randomised controlled trial is required to provide good evidence of effectiveness.
These US researchers undertook a large randomised controlled trial of Risperidone compared with placebo for the treatment of autistic disorder accompanied by severe tantrums, aggression, or self-injurious behaviour in 101 children and young people aged between five and 17. The young people were drawn from many autism clinics and all had proven core autism by the standard definitions. They were randomly assigned to receive either Risperidone for eight weeks (dose range, 0.5 to 3.5 mg per day) or an identical placebo for the same period. Both the patient, family and the treating doctors were blinded to whether the young person was on the drug or the placebo. They assessed whether behaviour had improved by having the treating professionals and/ or parents fill out a scale to measure behavioral problems: the Aberrant Behavior Checklist [ABC]; and a general impression of functioning in autism: the Clinical Global Impressions Improvement (CGI-I). Scales were filled out before and after the treatment to assess improvement.
They found that the group that had Risperidone improved by nearly 60% (56.9%) on the Irritability score on the ABC compared with a small worsening of the Irritability score in the group that had placebo (14%). They defined a positive response to treatment as at least a 25% improvement in the Irritability score and a rating of Much Improved or Very Much Improved on the CGI-I scale. Defined in this way, 69% of the children given Risperidone had a positive response compared to only 12% of the placebo group. These findings were all highly statistically significant.
The researchers extended the trial for six months to see if the response to Risperidone was maintained. They found that the positive response to Risperidone was maintained in only two-thirds of those who responded during the initial eight weeks. There were some side effects noted with Risperidone, particularly weight gain, (those on Risperidone gained an average of 2.7kg whereas those on placebo only gained an average of 0.8kg), fatigue, drowsiness, dizziness, and drooling.
The researchers concluded that Risperidone was effective and well tolerated for the treatment of tantrums, aggression, and self-injurious behavior in children with autistic disorder. They acknowledged that as this study only went for six months, they could say nothing about the long-term side effects of Risperidone.
This is high quality evidence that finally shows us where Risperidone fits for the treatment of behavioral problems in core autism. The drug made a significant difference in just over two-thirds of the young people during the first two months, but it continued to produce improvement in only two-thirds of these (around 44% of the original group). Thus the long-term benefit of the drug is seen in just under half the patients.
Risperidone is not side effect free, as was seen in this trial, with weight gain the most problematic consequence. Weight gain is a problem with any child or young person with intellectual disability or behavioral problems, as it can also make them much more difficult for others to handle.
Risperidone clearly has a place for the treatment of very difficult behaviour. But other strategies should certainly be tried first for the control of difficult behaviour.
McCracken et al. Risperidone in Children with Autism and Serious Behavioral Problems. New England Journal of Medicine 1 August 2002; 347:314-321.
- Behavioural problems in children and young people with autism should first be tackled with behaviour therapy. If this is not effective, drug treatment may help.
- Risperidone has a long-term beneficial effect in just under half of children and young people with core autism.
- Risperidone has mild side effects compared to other older drugs such as Haloperidol, but weight gain can be a problem.
Reproduced with permission of ChildHealthMonitor.org, which translates pediatric journal articles into everyday language providing comprehensive information on research breakthroughs ranging from general nutrition to rare diseases. A great resource for busy Pediatricians and also for parents who want to learn how best to care for their children's medical and parenting problems.