Abstract | Summary | Original Article

A 3-year naturalistic study of 53 preschool children with pervasive developmental disorders treated with risperidone.

Masi G, Cosenza A, Mucci M, Brovedani P.

Journal of Clinical Psychiatry 2003; 64(9): 1039-1047

Question: What are the outcomes at three years for children with PDD-NOS or autism who have been prescribed Risperidone?

Background: Clinical research trials always have a specific follow-up period and usually little or nothing is known about how the participants do after the trial has ended. These authors followed up over a three year period preschool children who had been treated with Risperidone for aggression, hyperactivity, and tantruming. The reason for the study was to see if there was continued treatment effect as time passed and to see how many children remained on the drug and what reasons caused them to discontinue it.

Participants: The participants were 45 boys and 8 girls between the ages of 3 and 6 years. All had a confirmed diagnosis of either PDD-NOS or autistic disorder and all had a CARS score above 30, meaning they had at least mild to moderate autistic symptoms. None of the children had a medical condition that could worsen their symptoms, and all had severe behaviour problems at the start of the study. The children were initially recruited as appropriate for a study of risperidone from a group of 120 preschool children who had been referred to a clinic because of their severe behavioural problems.

Design: This was a naturalistic study; that is, no experiment was conducted. Observations of behaviours of interest were recorded. This design is particularly useful for looking at the long-term effectiveness of treatment because it gives a picture of what actually occurs over time.

Methods: Data were collected from March 1999 until April 2002 on 53 children prescribed Risperidone for symptoms of aggression. The children had medical and psychological testing done before the start of the study and then again at the end of the 8 week study period. Children were then assessed at varying times during the follow up portion of the study.

Main Results: Of the original 53 participants in the study, 25 (47.2%) continued on risperidone for at least 8 months, with a range of 3 to 32 months. 28 (52.8%) of the participants discontinued using the drug, most before 6 months had passed. Most of the children who discontinued the drug did so because of side effects, while others were removed from treatment by their physician's decision, or because they did not improve on the medication. Many of the children removed from treatment by their physicians were re-started on the drug as their behaviour deteriorated.

The behaviour of most of the children who remained on the drug was found to be "much improved" or "very much improved," although the effect declined somewhat as time passed. The domains most likely to be positively affected were hyperactivity, anger, and rapid changes in mood. None of the children worsened on medication. The behaviour of some of the children who were removed from treatment deteriorated. Children with a diagnosis of PDD-NOS were more likely to respond to treatment than were children with a diagnosis of autistic disorder. The major side effect leading to discontinuation was raised levels of prolactin. Prolactin is a hormone associated in females with breast milk production. If levels are raised in males, it can lead to delayed onset of puberty and later infertility. In this study none of the children with raised levels of prolactin suffered any obvious physical effects, but the blood test results caused the parents sufficient concern that the children were removed from the study. Other side effects that caused parents to remove their children were flushing, fainting, and rapid heart beat. The ECG abnormalities previously reported were not seen in this study, nor were abnormal liver function tests. Although a large percentage of children experienced significant weight gain, none was removed from the study because of it. In fact, the weight gain in this study's participants and in those in previous studies has been positively correlated with response to the drug.

Conclusions: This study contributes to the view that Risperidone does provide relief of symptoms of aggression in children with PDD-NOS and autistic disorder, but likely should be used as a treatment of last resort when behavioural interventions have failed. The need for medication should be reevaluated periodically. This study has also contributed data to the overall safety profile of this drug in children, but has not definitively answered concerns about raised prolactin levels. More should be known about the effects of weight gain in this population.