Antipsychotic medication for childhood-onset schizophrenia

Schizophrenia is a serious mental illness which can cause hallucinations, fixed false beliefs (delusions) and/or apathy, slowing and less movement or thought. For the majority of people, its onset is in the late teens or early twenties. However, although rare, the illness can appear in childhood, where it is generally more severe and the long term prospects are poorer. Childhood-onset is defined in this case as the illness appearing before the age of 13 years.

This review looks at the use of antipsychotic medication for those whose schizophrenia developed in childhood. Six trials were found containing a total of 256 children and adolescents. They were carried out in the USA or China and all lasted less than 12 weeks. All studies compared one antipsychotic against another, with the older first generation (typical) being compared against each other, first generation compared to second generation (atypical) and second generation compared to other second generation drugs. Two of the trials (46 children) compared these medications in participants for whom at least two other antipsychotics had not worked (treatment resistant schizophrenia).

It is difficult to draw general conclusions from this group of trials as they compare outcomes for different drugs, range from the 1970s to 2006 (during this time the diagnosis of childhood schizophrenia has changed) and mostly have only small numbers of participants. The data suggests that the atypical antipsychotic clozapine shows a better general outcome when compared to typical antipsychotics.  However, this depended on how the children in the trial were rated. Those on clozapine were more likely to show the adverse effects of sleepiness, decreased white blood cell count (agranulocytosis) and increased heartbeat (tachycardia) when compared to those on haloperidol. In another trial it was shown that haloperidol is more likely to cause movement side effects than risperidone. When comparing typical with typical, and atypical with atypical antipsychotics, no medication showed a significant improvement over another for the outcomes reported.

Although childhood-onset schizophrenia is rare, a large trial over multiple sites, where outcomes are measured over months rather than weeks would help establish which antipsychotics are helpful for this group of people.

(Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org).

Authors' conclusions: 

There are few relevant trials and, presently, there is little conclusive evidence regarding the effects of antipsychotic medication for those with early onset schizophrenia. Some benefits were identified in using the atypical antipsychotic clozapine compared with haloperidol but the benefits were offset by an increased risk of serious adverse effects. Larger, more robust, trials are required.

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Background: 

Childhood-onset schizophrenia is schizophrenia with onset prior to the age of 13 years. Although it is rare, people who suffer from schizophrenia at an early age appear to have a clinically severe form of the illness with poor long-term prognosis. Antipsychotic medication is one way of managing this rare but serious mental illness.

Objectives: 

To examine the effects of antipsychotic medication for childhood-onset schizophrenia.

Search strategy: 

We searched the Cochrane Schizophrenia Group Trials Register (November 2006 and February 2007), inspected references of all identified studies for further trials and contacted relevant pharmaceutical companies and authors of trials for additional information.

Selection criteria: 

We included all randomised clinical trials involving children and young people with a diagnosis of childhood onset schizophrenia (i.e. with a diagnosis of schizophrenia before the age of 13) comparing any antipsychotic drug with another antipsychotic or placebo.

Data collection and analysis: 

We reliably selected, quality assessed and extracted data from trials. We excluded data where more than 50% of participants in any group were lost to follow up. For homogenous dichotomous data we calculated random effects, relative risk (RR) and its 95% confidence interval (CI) and, where appropriate, number needed to treat (NNT) on an intention-to-treat basis. For normal continuous data we calculated the weighted mean difference (WMD).

Main results: 

From a total of 2062 citations, we identified six relevant trials. We categorised trials into three comparisons: atypical versus typical, atypical versus atypical and typical versus typical antipsychotic drugs. The only comparison to find any differences between treatment groups was atypical versus typical antipsychotic drugs. A few results from one study favoured the atypical antipsychotic clozapine over haloperidol in treating treatment resistant childhood-onset schizophrenia (n=21, WMD CGAS 17.00 CI 7.74 to 26.26; n=21, WMD Bunney-Hamburg Psychosis Rating Scale -3.60 CI -6.64 to -0.56). Participants on clozapine, however, were three times more likely to have drowsiness (1 RCT, n=21, RR 3.30 CI 1.23 to 8.85, NNH 2 CI 2 to 17) and half of the children receiving clozapine had neutropenia (1 RCT, n=21, RR 12, CI 0.75 to192.86).

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