The efficacy of sulpiride augmentation for schizophrenia

Schizophrenia is a serious and chronic illness in which psychotic symptoms are prominent. The psychotic symptoms are often managed with drugs. Not all people with schizophrenia respond well to treatment with antipsychotic drugs and sulpiride is often used as an add-on drug for promoting the efficacy of another medication. Several clinical trials reported effects of sulpiride augmentation for management of schizophrenia. We included four small trials which compared sulpiride plus clozapine with clozapine alone for very ill people. Evidence from the present review suggested that short-term sulpiride plus clozapine probably is more effective than clozapine alone in producing clinical improvement in some people. The evidence is, however, weak and prone to considerable bias. This is a good area for more research.

Authors' conclusions: 

Sulpiride plus clozapine is probably more effective than clozapine alone in producing clinical improvement in some people whose illness has been resistant to other antipsychotic drugs including clozapine. However, much more robust data are needed.

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Sulpiride may be used in combination with other antipsychotic drugs in the hope of augmenting effectiveness – especially for those whose schizophrenia has proved resistant to treatment.


To evaluate the effects of sulpiride augmentation versus monotherapy for people with schizophrenia.

Search strategy: 

We searched the Cochrane Schizophrenia Group Trials Register (July 2009) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO.

Selection criteria: 

All relevant randomised clinical trials (RCTs).

Data collection and analysis: 

We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) based on a fixed-effect model. For continuous data, we calculated weighted mean differences (WMD) again based on a fixed-effect model.

Main results: 

We included three short-term and one long-term trial (total N=221). All participants had schizophrenia that was either treatment-resistant or with prominent negative symptoms. All studies compared sulpiride plus clozapine with clozapine (+/- placebo), were small and at considerable risk of bias.

Short-term data of 'no clinically significant response' in global state tended to favour sulpiride augmentation of clozapine compared with clozapine alone (n=193, 3 RCTs, RR 0.58 CI 0.3 to 1.09).

People allocated to sulpiride plus clozapine had more movement disorders (n=70, 1 RCT, RR 48.24 CI 3.05 to 762.56) and an increase in serum prolactin (skewed data, 1 RCT), but less incidence of hypersalivation (n=162, 3 RCTs, RR 0.49 CI 0.29 to 0.83) and less weight gain (n=64, 1 RCT, RR 0.30 CI 0.09 to 0.99). The augmentation of clozapine by sulpiride also caused less appetite loss (n=70, 1 RCT, RR 0.09 CI 0.01 to 0.70, NNT 4 CI 4 to 12, Z=2.31, P=0.02) and less abdominal distension (n=70, 1 RCT, RR 0.10 CI 0.01 to 0.78, NNT 5 CI 4 to 19, Z=2.20, P=0.03).

Long-term data showed no significant difference in global state (n=70, 1 RCT, RR 0.67 CI 0.42 to 1.08) and relapse (n=70, 1 RCT, RR 0.85 CI 0.5 to 1.3).