Amisulpride for schizophrenia

The treatment of schizophrenia with old, 'typical' antipsychotic drugs such as haloperidol can be problematic, because many people treated with these drugs will suffer from movement disorders. Amisulpride is said to be an "atypical" antipsychotic which induces less movement disorder and which is effective for the negative symptoms of schizophrenia.

To evaluate the effects of amisulpride as compared with placebo, typical and atypical antipsychotic drugs for schizophrenia.

The authors carried out electronic searches of Biological Abstracts (1982-1999), CINAHL (1982-1999), Cochrane Library (Issue 4, 1999), Cochrane Schizophrenia Group's Register (November 2000), EMBASE (1980-1999), LILACS(1982-1999), MEDLINE (1966-1999) and PsycLIT (1974-1999). They checked all identified studies for further trial citations, and sought these studies in the Science Citation Index. They also contacted authors of trials and the manufacturer of amisulpride.

All randomised controlled trials comparing amisulpride to placebo, typical or atypical antipsychotic drugs for schizophrenia or other non-affective serious mental illnesses.

Data were independently extracted and analysed on an intention-to-treat basis. The relative risk (RR) and 95% confidence intervals (CI) of dichotomous data were calculated using a random effects model, and, where possible, the number needed to treat was calculated. Weighted mean differences (WMD) were calculated for continuous data.

This review currently includes 19 randomised studies with a total of 2443 participants. Most trials were of short duration. Data from 4 trials with 514 participants with predominantly negative symptoms suggest that low-dose (up to 300mg/day) amisulpride was a more acceptable treatment than placebo (n=514, RR 0.6 CI 0.5 to 0.8, NNT 3 CI 3 to 7), the improvement of the participants' global state (n=242, RR 0.6 CI 0.5 to 0.8, NNT 3 CI 2 to 6) and the treatment of negative symptoms (n=177, WMD -10.1 CI -16.6 to -3.5). Amisulpride was shown to be more likely to cause extrapyramidal symptoms than placebo in two studies (n=269, RR 2.2 CI 1.2 to 4.2), but this result did not hold calculating the risk reduction so that an NNT-statistic could not be indicated. Compared to typical antipsychotics, the pooled results of a total of fourteen trials suggest that amisulpride was more effective in improving global state (n=651, RR 0.7 CI 0.5 to 0.9, NNT 6 CI 4 to 11), the general mental state (n=695, WMD -4.2 CI -6.5 to -1.9) and the negative symptoms of schizophrenia (n=506, WMD -2.8 CI -4.3 to -1.3). Regarding positive symptoms, amisulpride was as effective as typical antipsychotics. Amisulpride was less prone to cause at least one general adverse event (n=751, RR 0.9 CI 0.8 to 0.97, NNH 9 CI 6 to 18), one extrapyramidal symptom (n=771, RR 0.7 CI 0.6 to 0.9, NNH 5 CI 4 to 9) or to require the use of antiparkinson medication (n=851, RR 0.6 CI 0.5 to 0.8, NNH 4 CI 3 to 6). No clear differences in other adverse events compared to typical drugs were found. Amisulpride also seemed to be more acceptable than conventional drugs as measured by the outcome 'leaving the studies early' (n=1512, RR 0.8 CI 0.7 to 0.9, NNT 16 CI 9 to 69) than conventional drugs, but this result might have been overestimated due to a publication bias which could not be excluded with certainty. A single trial compared amisulpride to another 'atypical' antipsychotic, risperidone. With the exception of agitation, which was more frequent in the amisulpride group (n=228, RR 3.4 CI 1.2 to 10.1, NNH 11 CI 6 to 50) no significant differences were recorded on efficacy or acceptability.

This systematic review confirms that amisulpride is an effective 'atypical' antipsychotic drug for those with schizophrenia. Amisulpride may offer a good general profile, at least compared to high-potency 'typical' antipsychotics. It may also yield better results in some specific outcomes related to efficacy, such as improvement of global state and general negative symptoms. It might be more acceptable and more tolerable than high-potency conventional antipsychotics, especially regarding extrapyramidal side-effects. Longer term randomised trials are needed to evaluate the comparative value of amisulpride, particularly compared to other expensive atypical antipsychotics. These should focus on important outcomes which have not been sufficiently monitored such as service use, family burden and quality of life.