Aripiprazole for schizophrenia

Abstract

Treatment of people with schizophrenia using older typical antipsychotic drugs such as haloperidol can be problematic. Many fail to respond and more experience disabling adverse effects. Aripiprazole is said to be one of a new generation of atypical antipsychotics with good antipsychotic properties and minimal adverse effects. To evaluate the effects of aripiprazole for people with schizophrenia and schizophrenia-like psychoses. The reviewers searched the Cochrane Schizophrenia Group's Register (May 2003) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. The authors contacted relevant pharmaceutical companies, the FDA and authors of trials for additional information. All clinical randomised trials comparing aripiprazole with placebo, typical or atypical antipsychotic drugs for schizophrenia and schizophrenia-like psychoses. We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). Despite the fact that 4125 people participated in ten 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. Study attrition was very large and data reporting poor. Compared with placebo, aripiprazole significantly decreased relapse in both the short and medium term (n=300, 1 RCT, RR 0.66 CI 0.53 to 0.81, NNT 5 CI 4 to 8). It also produced better compliance with study protocol (n=1348, 5 RCTs, RR 0.66 CI 0.49 to 0.88, NNT 15 CI 10 to 41). Aripiprazole may decrease prolactin levels below that expected from placebo (n=305, 1 RCT, RR 0.32 CI 0.13 to 0.81, NNT 14 CI 11 to 50). Compared with typical antipsychotics there were no significant benefits for aripiprazole with regards to global state, mental state, quality of life or leaving the study early. Both groups reported similar rates of adverse effects, including akathisia (RR 0.44 CI 0.17 to 1.12) and general extrapyramidal effects (RR 0.53 CI 0.18 to 1.53). Aripiprazole did however cause more insomnia than perphenazine (n=300, 1 RCT, RR 2.23 CI 1.57 to 3.18, NNH 4 CI 3 to 9) and less need for antiparkinson drugs than 10-20mg/day haloperidol (n=1854, 4 RCTs, RR 0.45 CI 0.33 to 0.60, NNT 4 CI 3 to 5). When compared with olanzapine and risperidone, aripiprazole was no better or worse on outcomes of global state and leaving the study early. The rates of adverse effects were also similar, with the exception of less elevation of prolactin (n=301, 1 RCT, RR 0.04 CI 0.02 to 0.08, NNT 2) and less prolongation of the average QTc (30mg/day) (n=200, 1 RCT, WMD -10.0, CI -16.99 to -3.01) compared with risperidone. Aripiprazole may be effective for the treatment of schizophrenia, but it is not much different from typical antipsychotics and atypical antipsychotics with respect to treatment response, efficacy or tolerability. In comparison with typical antipsychotics, aripiprazole may have a higher risk of insomnia, but in comparison to atypical antipsychotics, less risk of raised prolactin and prolongation of the QTc interval. Clearly reported pragmatic short, medium and long term randomised controlled trials should be carried out to determine its position in everyday clinical practice.