Statistics from Altmetric.com
What are the effects of aripiprazole compared with other atypical antipsychotics in people with schizophrenia and schizophrenia-like psychoses?
Efficacy (as defined by each study), adverse effects.
Systematic review with meta-analysis.
Cochrane Schizophrenia Group's Specialised Register was searched from inception to March 2007 for randomised controlled trials (RCTs). Reference lists of identified studies were hand searched. First authors of included studies were contacted for missing information, and drug companies were contacted for additional data.
Study selection and analysis:
Reviewers appraised studies and selected RCTs comparing oral aripiprazole with oral forms of risperidone, quetiapine, olanzapine, amisulpride, aripiprazole, clozapine, sertindole, ziprasidone or zotepine in people with schizophrenia and schizophrenia-like psychoses. Data were extracted independently. Weighted mean differences (MD) were calculated for continuous data. Dichotomous data were used to calculate RR using a random-effects model. Heterogeneity was investigated using the I2 statistic.
Four RCTs met inclusion criteria (n = 1,404). Data were available that compared aripiprazole with olanzapine and risperidone. Overall, 38.5% of participants left the included studies prematurely, but there were no significant differences between groups. Aripiprazole was less effective than olanzapine in terms of positive and negative symptoms of Schizophrenia total scores (n = 794; 2 RCTs; MD = 4.96, 95% CI = 1.85–8.06). Risk of increased cholesterol levels was lower with aripiprazole, compared with olanzapine (n = 223; 1 RCT; RR = 0.32, 95% CI = 0.19–0.54; NNH = 4, 95% CI = 3–6). Prolactin-level increase was less likely with aripiprazole, compared with olanzapine (n = 317; 1 RCT; RR = 0.27, 95% CI = 0.12–0.60, NNT = 8, 95% CI = 5–17). Participants were less likely to gain weight of 7% or more of total body weight with aripiprazole, compared with olanzapine (n = 317; 1 RCT; RR = 0.37, 95% CI = 0.24–0.58; NNT = 4, 95% CI = 3–8). Risk of increased cholesterol levels was lower with aripiprazole, compared with risperidone (n = 83; 1 RCT; MD = −22.30, 95% CI = −39.69 to −4.91; NNH = 4, 95% CI = 3–6). People taking aripiprazole had reduced dystonia, compared with risperidone (n = 301; 1 RCT; RR = 0.14, 95% CI = 0.05–0.41; NNT = 8, 95% CI = 5–20). People taking aripiprazole were morel likely to have tremor than did those who took risperidone (n = 301; 1 RCT; RR = 4.66, 95% CI = 1.11–19.59; NNH = 14, 95% CI = 8–50). Prolactin-level increase was less likely with the use of aripiprazole, compared with risperidone (n = 301; 1 RCT; RR = 0.04, 95% CI = 0.02–0.08; NNH = 1, 95% CI = not estimable).
Aripiprazole is as effective as risperidone and has better tolerability, though tremor is a more frequent outcome in the case of aripiprazole. Efficacy of aripiprazole may be marginally lower compared with olanzapine, but metabolic effects and sedation are less pronounced. Randomised comparisons with other atypical antipsychotics are not yet available.
Authors note the high rate of study discontinuation limits the validity of findings beyond dropout and that the small number of trials precluded reduces the robustness of the evidence.
In recent years, new drugs have been marketed for the treatment of schizophrenia, and others are expected to be approved in the near future. It is, therefore, clinically relevant to ascertain how each of these new agents compares with those already in the market. The Cochrane review carried out by Komossa and colleagues investigated the relative efficacy and tolerability of aripiprazole, a recently marketed antipsychotic drug, versus other new-generation antipsychotic drugs. The review identified four trials comparing aripiprazole with olanzapine or risperidone. In terms of treatment response (the primary outcome employed in the Cochrane review), there was enough evidence to show that there was no difference between aripiprazole and olanzapine. The point estimate is close to 1 and the CI around this treatment estimate is very narrow (RR = 1.05, 95% CI = 0.95–1.17; two studies, 1,020 participants). However, it is worth noting that in terms of continuous outcome (rating-scale score) aripiprazole was less effective than olanzapine. In comparison with risperidone, the evidence appears inconclusive (the CI ranges from appreciable benefit for aripiprazole to appreciable benefit for risperidone).
These results prompt two reflections. First, considering this review together with other systematic reviews of clinical trial data, it is possible to state that aripiprazole is not more effective than both old- and new-generation antipsychotics.1 By contrast, aripiprazole might have a beneficial effect in terms of depressive symptoms. These two factors – lack of added value in patients with schizophrenia and possible role against depressive symptoms – might be the reason why aripiprazole has been increasingly studied either as add-on treatment to antidepressants in individuals with major depressive disorder or as combination strategy with other antipsychotics, including clozapine, in individuals with schizophrenia.
A second consideration refers to the approval requirements needed to grant marketing authorisation. Currently, the demonstration of a difference against placebo, and not necessarily against an active comparator, makes a new drug eligible for registration. Although this may be reasonable in areas where no active treatments are available, this produces a high degree of uncertainty in areas where many active agents are available (such as schizophrenia), leading to a high risk of marketing drugs that might be less effective than those already available on the market.
Sources of funding Psychiatrische Klinik, Klinikum rechts der Isar, TU München, Freistaat Bayern, Germany. Bundesministerium für Bildung und Forschung, Nr FKZ: 01KG 0606, GZ:GF-GFKG01100506, Germany.
Competing interests None
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.