Aripiprazole versus other atypical antipsychotics for schizophrenia

Priya Khanna, Katja Komossa, Christine Rummel-Kluge, Heike Hunger, Sandra Schwarz, Hany George El-Sayeh, Stefan Leucht
Cochrane Database of Systematic Reviews 2013 February 28, (2): CD006569

BACKGROUND: In most western industrialised countries, second generation (atypical) antipsychotics are recommended as first line drug treatments for people with schizophrenia. In this review we specifically examine how the efficacy and tolerability of one such agent - aripiprazole - differs from that of other comparable second generation antipsychotics.

OBJECTIVES: To evaluate the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses.

SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (November 2011), inspected references of all identified studies for further trials, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information.

SELECTION CRITERIA: We included all randomised clinical trials (RCTs) comparing aripiprazole (oral) with oral and parenteral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine for people with schizophrenia or schizophrenia-like psychoses.

DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. Where possible, we calculated illustrative comparative risks for primary outcomes. For continuous data, we calculated mean differences (MD), again based on a random-effects model. We assessed risk of bias for each included study.

MAIN RESULTS: We included 12 trials involving 6389 patients. Aripiprazole was compared to olanzapine, risperidone and ziprasidone. All trials were sponsored by an interested drug manufacturer. The overall number of participants leaving studies early was 30% to 40%, limiting validity (no differences between groups).When compared with olanzapine no differences were apparent for global state (no clinically important change: n = 703, 1 RCT, RR short-term 1.00 95% CI 0.81 to 1.22; n = 317, 1 RCT, RR medium-term 1.08 95% CI 0.95 to 1.22) but mental state tended to favour olanzapine (n = 1360, 3 RCTs, MD total Positive and Negative Syndrome Scale (PANSS) 4.68 95% CI 2.21 to 7.16). There was no significant difference in extrapyramidal symptoms (n = 529, 2 RCTs, RR 0.99 95% CI 0.62 to 1.59) but fewer in the aripiprazole group had increased cholesterol levels (n = 223, 1 RCT, RR 0.32 95% CI 0.19 to 0.54) or weight gain of 7% or more of total body weight (n = 1095, 3 RCTs, RR 0.39 95% CI 0.28 to 0.54).When compared with risperidone, aripiprazole showed no advantage in terms of global state (n = 384, 2 RCTs, RR no important improvement 1.14 95% CI 0.81 to 1.60) or mental state (n = 372, 2 RCTs, MD total PANSS 1.50 95% CI -2.96 to 5.96).One study compared aripiprazole with ziprasidone (n = 247) and both the groups reported similar change in the global state (n = 247, 1 RCT, MD average change in Clinical Global Impression-Severity (CGI-S) score -0.03 95% CI -0.28 to 0.22) and mental state (n = 247, 1 RCT, MD change PANSS -3.00 95% CI -7.29 to 1.29).When compared with any one of several new generation antipsychotic drugs the aripiprazole group showed improvement in global state in energy (n = 523, 1 RCT, RR 0.69 95% CI 0.56 to 0.84), mood (n = 523, 1 RCT, RR 0.77 95% CI 0.65 to 0.92), negative symptoms (n = 523, 1 RCT, RR 0.82 95% CI 0.68 to 0.99), somnolence (n = 523, 1 RCT, RR 0.80 95% CI 0.69 to 0.93) and weight gain (n = 523, 1 RCT, RR 0.84 95% CI 0.76 to 0.94). Significantly more people given aripiprazole reported symptoms of nausea (n = 2881, 3 RCTs, RR 3.13 95% CI 2.12 to 4.61) but weight gain (7% or more of total body weight) was less common in people allocated aripiprazole (n = 330, 1 RCT, RR 0.35 95% CI 0.19 to 0.64). Aripiprazole may have value in aggression but data are limited. This will be the focus of another review.

AUTHORS' CONCLUSIONS: Information on all comparisons are of limited quality, are incomplete and problematic to apply clinically. Aripiprazole is an antipsychotic drug with a variant but not absent adverse effect profile. Long-term data are sparse and there is considerable scope for another update of this review as new data emerges from the many Chinese studies as well as from ongoing larger, independent pragmatic trials.

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