Atypical antipsychotic medications for adolescents with psychosis

Schizophrenia and other serious mental illnesses often begin in adolescence, and treatment of adolescents with psychosis usually involves use of antipsychotic drugs. Newer drugs (atypical antipsychotics) are more popular than older ones (typical antipsychotics). However, this determination is based on the generalisation of adult treatment to a younger age group, with evidence from studies on adults generally guiding the treatment of adolescents.  Adolescents may respond differently to medication compared with adults. This review looks at evidence derived from trials in which the participants are adolescents receiving atypical or typical antipsychotics or a placebo (dummy treatment) and/or high or low doses of medication. A total of 13 trials consisting of 1112 people between 13 and 18 years of age are included. Most studies were short-term trials (completed within 12 weeks). In the main, no convincing evidence shows that newer drugs (atypical antipsychotics) are better than older ones (typical antipsychotics) in terms of their ability to treat the symptoms of psychosis. However, newer drugs may be more acceptable for young people to take because they produce fewer side effects in the short term. Furthermore, very little evidence is available to support the superiority of one atypical antipsychotic over another atypical antipsychotic. The nature of side effects also differs markedly between medications. For example, treatment with olanzapine, risperidone and clozapine is associated with weight gain, but aripiprazole is not associated with weight gain. Some evidence indicates that adolescents respond better to standard-dose as opposed to lower-dose risperidone. However, for aripiprazole and ziprasidone, a lower dose and a standard dose may be equally effective. Longer, clearer and more detailed research trials that use systematic ways of reporting and comparing the side effects of different antipsychotic drugs are much needed. So too is a research focus on other important outcomes such as hospital admission, service use, costs, behaviour change and possible improvements in people’s thinking. Until such research is completed, very little evidence suggests that newer drugs (atypical antipsychotics) are better than older drugs (typical antipsychotics) for the treatment of adolescents with schizophrenia.    

This plain language summary has been written by Benjamin Gray, Service User and Service User Expert, Rethink Mental Illness (Email: ben.gray@rethink.org).

Authors' conclusions: 

No convincing evidence suggests that atypical antipsychotic medications are superior to typical medications for the treatment of adolescents with psychosis. However, atypical antipsychotic medications may be more acceptable to young people because fewer symptomatic adverse effects are seen in the short term. Little evidence is available to support the superiority of one atypical antipsychotic medication over another, but side effect profiles are different for different medications. Treatment with olanzapine, risperidone and clozapine is often associated with weight gain. Aripiprazole is not associated with increased prolactin or with dyslipidaemia. Adolescents may respond better to standard-dose as opposed to lower-dose risperidone, but for aripiprazole and ziprasidone, lower doses may be equally effective. Future trials should ensure uniform ways of reporting.

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Background: 

Schizophrenia often presents in adolescence, but current treatment guidelines are based largely on studies of adults with psychosis. Over the past decade, the number of studies on treatment of adolescent-onset psychosis has increased. The current systematic review collates and critiques evidence obtained on the use of various atypical antipsychotic medications for adolescents with psychosis.

Objectives: 

To investigate the effects of atypical antipsychotic medications in adolescents with psychosis. We reviewed in separate analyses various comparisons of atypical antipsychotic medications with placebo or a typical antipsychotic medication or another atypical antipsychotic medication or the same atypical antipsychotic medication but at a lower dose.

Search strategy: 

We searched the Cochrane Schizophrenia Group Register (October 2011), which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies and contacted study authors and relevant pharmaceutical companies to ask for more information.

Selection criteria: 

We included all relevant randomised controlled trials (RCTs) that compared atypical antipsychotic medication with placebo or another pharmacological intervention or with psychosocial interventions, standard psychiatric treatment or no intervention in children and young people aged 13 to 18 years with a diagnosis of schizophrenia, schizoaffective disorder, acute and transient psychoses or unspecified psychosis. We included studies published in English and in other languages that were available in standardised databases.

Data collection and analysis: 

Review authors AK and SSD selected the studies, rated the quality of the studies and performed data extraction. For dichotomous data, we estimated risk ratios (RRs) with 95% confidence intervals (CIs) using a fixed-effect model. When possible, for binary data presented in the 'Summary of findings' table, we calculated illustrative comparative risks. We summated continuous data using the mean difference (MD). Risk of bias was assessed for included studies.

Main results: 

We included 13 RCTs, with a total of 1112 participants. We found no data on service utilisation, economic outcomes, behaviour or cognitive response. Trials were classified into the following groups.

1. Atypical antipsychotics versus placebo
Only two studies compared one atypical antipsychotic medication with placebo. In one study, the number of non-responders treated with olanzapine was not different from the number treated with placebo (1 RCT, n = 107, RR 0.84, 95% CI 0.65 to 1.10); however, significantly more (57% vs 32%) people left the study early (1 RCT, n = 107, RR 0.56, 95% CI 0.36 to 0.87) from the placebo group compared with the olanzapine group. With regard to adverse effects, young people treated with aripiprazole had significantly lower serum cholesterol compared with those given placebo (1 RCT, n = 302, RR 3.77, 95% CI 1.88 to 7.58).

2. Atypical antipsychotics versus typical antipsychotics
When the findings of all five trials comparing atypical antipsychotic medications with a typical antipsychotic medication were collated, no difference in the mean end point Brief Psychiatric Rating Scale (BPRS) score was noted between the two arms (5 RCTs, n = 236, MD -1.08, 95% CI -3.08 to 0.93). With regard to adverse effects, the mean end point serum prolactin concentration was much higher than the reference range for treatment with risperidone, olanzapine and molindone in one of the studies. However, fewer adolescents who were receiving atypical antipsychotic medications left the study because of adverse effects (3 RCTs, n = 187, RR 0.65, 95% CI 0.36 to 1.15) or for any reason (3 RCTs, n = 187, RR 0.62, 95% CI 0.39 to 0.97).

3. One atypical antipsychotic versus another atypical antipsychotic
The mean end point BPRS score was not significantly different for people who received risperidone compared with those who received olanzapine; however, the above data were highly skewed. Overall no difference was noted in the number of people leaving the studies early because of any adverse effects between each study arm in the three studies comparing olanzapine and risperidone (3 RCTs, n = 130, RR 1.15, 95% CI 0.44 to 3.04). Specific adverse events were not reported uniformly across the six different studies included in this section of the review; therefore it was difficult to do a head-to-head comparison of adverse events for different atypical antipsychotic medications.

4. Lower-dose atypical antipsychotic versus standard/higher-dose atypical antipsychotic
Three studies reported comparisons of lower doses of the atypical antipsychotic medication with standard/higher doses of the same medication. One study reported better symptom reduction with a standard dose of risperidone as compared with a low dose (1 RCT, n = 257, RR -8.00, 95% CI -13.75 to -2.25). In another study, no difference was reported in the number of participants not achieving remission between the group receiving 10 mg/d and those who received 30 mg/d of aripiprazole (1 RCT, n = 196, RR 0.84, 95% CI 0.48 to 1.48). Similarly in the other study, authors reported no statistically significant difference in clinical response between the two groups receiving lower-dose (80 mg/d) and higher-dose (160 mg/d) ziprasidone, as reflected by the mean end point BPRS score (1 RCT, n = 17, MD -4.40, 95% CI -19.20 to 10.40).

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