Aripiprazole versus other atypical antipsychotics for schizophrenia

  • Review
  • Intervention




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.


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.

Plain language summary

Aripiprazole versus other atypical antipsychotics for schizophrenia

In many countries in the industrialised world there has been a huge growth in the prescription of medication for people with mental health problems, taken orally as a tablet or by injection. The atypical or second generation antipsychotics drugs have become ever more popular, because they are newer and thought to help people with mental health problems who do not respond quite so well to initial treatment with older drugs. Atypical antipsychotics hold the promise of both reducing symptoms, such as hearing voices or seeing things, and reducing problematic side-effects, such as sleepiness, weight gain, and shaking. However, there is little research and comparison of the ways in which antipsychotic drugs differ from one another. For people with schizophrenia it may be important to know that aripiprazole may not be as good or effective as another atypical antipsychotic but that it has less side-effects. This review includes 12 research trials with 6389 people. It evaluates whether aripiprazole is better than other atypical antipsychotic drugs. Aripiprazole was compared to three other new drugs: olanzapine; risperidone; and ziprasidone. Overall aripiprazole is similar in effectiveness to olanzapine and risperidone and somewhat better than ziprasidone. Aripiprazole had less side-effects than olanzapine and risperidone (for effects such as weight gain, sleepiness, heart problems, shaking and increased cholesterol). Aripiprazole was not as good as ziprasidone for dealing with restlessness or people’s inability to sit still. Comparison with other antipsychotic drugs as a group showed that people preferred taking aripiprazole. However, people with schizophrenia as well as mental health professionals and policy makers should know that the evidence is very limited and only based on a few studies. More trials and research is required, including on outcomes such as: quality of life; the views of service users and carers; and patient preference.

This plain language summary was written by a consumer, Ben Gray of RETHINK.