Aripiprazole versus placebo for schizophrenia

Schizophrenia is one of the major psychiatric disorders; it affects individuals' thinking, perception, affect and behaviour. It can occur in around 1% of the population. Aripiprazole is one of the newer antipsychotic medications introduced for the treatment of schizophrenia. When compared with placebo, people taking aripiprazole had fewer relapses, smaller numbers of participants left study early, and needed less additional antipsychotic medications. Insomnia and headache were the most commonly reported side effects, but were not much difference to placebo. Side effects such as akathisia, nausea and weight gain occurred more in the aripripazole group as compared to placebo. There has been a worry with newer antipsychotic medications and their effect on conductance problems in the heart, impaired glucose levels and excessive production of prolactin (which can cause unpleasant breast pain and secretion). On the limited evidence available (due to participants leaving early and fewer studies) aripiprazole appears to have a similar effect to that of placebo. The overall finding on its efficacy in treating schizophrenia is unchanged from those found in the original review.

Authors' conclusions: 

Aripiprazole may be effective for the treatment of schizophrenia. Aripiprazole has a lower risk of raised prolactin and prolongation of the QTc interval. Clearly reported pragmatic short-, medium- and long-term randomised controlled trials should be undertaken to determine its position in everyday clinical practice.

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Background: 

First generation 'typical' antipsychotics such as chlorpromazine and haloperidol have been the mainstay of treatment up until the introduction of the second generation 'atypical' antipsychotics such as risperidone and olanzapine. Typical and atypical antipsychotics do provide a treatment response for most people with schizophrenia, whether a reduction in psychotic episodes or a lessening in the severity of their illness. However, a proportion of people still do not respond adequately to antipsychotic medication. Additionally, atypical and especially typical antipsychotics are associated with serious adverse effects, which can often compromise compliance with medication and therefore increase the incidences of relapse. In this review we examine the effects of aripiprazole compared with placebo.

Objectives: 

To evaluate the effects of aripiprazole compared with placebo for people with schizophrenia and schizophrenia-like psychoses.

Search strategy: 

We searched the Cochrane Schizophrenia Group Trials Register (January 2008) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. For this update, we carried out an initial search in May 2007 and a second search in August 2008.

Selection criteria: 

We included all randomised trials comparing aripiprazole with placebo in people with schizophrenia or schizophrenia-like psychosis.

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 fixed-effect model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) again based on a fixed-effect model.

Main results: 

Despite the fact that 2585 people participated in nine randomised aripiprazole studies, we were unable to extract any usable data on death, service outcomes, general functioning, behaviour, engagement with services, satisfaction with treatment; economic outcomes or cognitive functioning. In general, study attrition was very large for all studies over four weeks' duration. There was high attrition in most of the included studies. Fewer people left the aripiprazole group compared with those in the placebo group (n = 2585, 9 RCTs, RR 0.73 CI 0.60 to 0.87). Compared with placebo, aripiprazole significantly decreased relapse in both the short (n = 310, 1 RCT, RR 0.59 CI 0.45 to 0.77) and medium term (n = 310, 1 RCT, RR 0.66 CI 0.53 to 0.81). It also produced better compliance with study protocol (n = 2275, 8 RCTs, RR 0.74 CI 0.59 to 0.93). Aripiprazole may decrease prolactin levels below those expected from placebo (n = 305, 2 RCT, RR 0.21 CI 0.11 to 0.37). Insomnia (~23%) and headaches (~15%) were commonly reported in both groups, with no significant difference.

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