Atypical antipsychotics for psychosis in adolescents.
Author(s): Kumar A(1), Datta SS, Wright SD, Furtado VA, Russell PS.
Affiliation(s): Author information:
(1)Psychiatry, Leeds and York Partnership NHS Foundation Trust, Linden House, St
Mary's Hospital, Green Hill Road, Leeds, UK, LS12 3QE.
Publication date & source: 2013, Cochrane Database Syst Rev. , 10:CD009582
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 METHODS: 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).
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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