Sulpiride versus placebo for schizophrenia

Schizophrenia is a severe mental illness with ‘positive symptoms’ such as hallucinations (hearing voices and seeing things) and delusions (having strange beliefs). People with schizophrenia also suffer from disorganisation and ‘negative symptoms’ (such as tiredness, apathy and loss of emotion). People with schizophrenia may find it hard to socialise and find employment. Schizophrenia is considered one of the most burdensome illnesses in the world. For some people it can be a lifelong condition.

People with schizophrenia are usually treated with antipsychotic drugs. More recently developed antipsychotic drugs (second generation or atypical) are more expensive and thought to have fewer side effects than the older ones (first generation or typical). These side effects can include distressing movement disorders; as a results, many people find the older drugs difficult to tolerate and prefer the second generation drugs. However, in many developing countries the cost of medication can be a major factor in prescribing, so the first generation drugs are the most widely used.

Sulpiride is a first generation antipsychotic drug, but is said to cause fewer side effects. It has been suggested that sulpiride may be more effective than other older drugs (such as chlorpromazine and haloperidol) for treating the negative symptoms and social withdrawal of schizophrenia.

The aim of this review was to evaluate the effects of sulpiride for schizophrenia compared to placebo (‘dummy’ treatment). Two short-term (12 weeks) studies with a total of 113 people are included. Information was limited and poorly reported. The inclusion of two small studies with small sample sizes meant that resulting data were not overly robust or meaningful. Overall no clear difference was noted between those receiving sulpiride and those receiving placebo for mental state or for leaving the study early. There was no information on other important outcomes, including: general functioning, service use, hospital admission, employment, family burden, satisfaction with care and side effects. The use of sulpiride seems to be based on clinical experience rather than strong evidence. Its widespread use in developing countries might have more to do with its lower cost than its effectiveness. Longer, well-planned, better conducted and reported randomised control trials would contribute to our knowledge about the effectiveness and potential side effects of this drug.

This plain language summary has been written by a consumer Benjamin Gray: Service User and Service User Expert: Rethink Mental Illness. Email:

Authors' conclusions: 

Sulpiride may be an effective antipsychotic drug but evidence of its superiority over placebo from randomised trials is very limited. Practice will have to use evidence from sources other than trials until better evidence is generated.

Read the full abstract...

Sulpiride is a relatively old antipsychotic drug reputed to have a low incidence of adverse effects and an effect on the negative symptoms of schizophrenia. This relatively inexpensive antipsychotic drug has a similar neuropharmacological profile to several novel atypical drugs.


To evaluate the effects of sulpiride for schizophrenia and other similar serious mental illnesses in comparison with placebo.

Search strategy: 

We searched the Cochrane Schizophrenia Group Trials Register (September 2008) and references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information. We updated this search 7th November 2012.

Selection criteria: 

We included all randomised controlled trials (RCTs) comparing sulpiride with placebo for people with schizophrenia and other types of schizophrenia-like psychoses. The primary outcome of interest was clinically significant response in global state.

Data collection and analysis: 

We independently inspected citations and abstracts, ordered papers, re-inspected and quality-assessed these. IMO and JW extracted data. We analysed dichotomous data using a random-effects risk ratio (RR) and estimated the 95% confidence interval (CI) around this. Where continuous data were included, we analysed these data using random-effects mean difference (MD) with a 95% CI.

Main results: 

No new trials were included from the 2012 search. The review still includes two trials of short duration comparing sulpiride with placebo (total n = 113). No study reported our primary outcome of interest of 'global state: clinically significant response', nor our secondary outcomes of interest of 'quality of life', 'severe adverse effects', and 'safety assessments'. As regards mental state, there were no clear differences between groups for either positive or negative symptoms; measured positive symptoms using the Manchester scale were skewed and therefore not included in meta-analysis (n = 18, 1 RCT, very low quality evidence). Measured negative symptoms using the Manchester scale also demonstrated no clear difference (n = 18, 1 RCT, MD -3.0 CI -1.66 to 1.06, very low quality evidence). Few people left these studies by three months (n = 113, 2 RCTs, RR 1.00 CI 0.25 to 4.00). One subscore finding demonstrated a significant improvement in social behaviour using the Current Behaviour Schedule (CBS) when receiving placebo (n = 18, 1 RCT, MD -2.90 CI -5.60 to -0.20). There were no data for many important outcomes such as global outcomes, service use or adverse effects.