Sultopride for schizophrenia

Antipsychotic medications are the cornerstone in treating people with schizophrenia. These medications fall into two main categories; typical and atypical. The term 'typical antipsychotics' refers to older antipsychotics such as haloperidol or chlorpromazine. Atypical antipsychotics are the relatively newer generation of antipsychotics, which began with the introduction of clozapine in the late 1950s. They have a higher potency and lower risk of movement disorders than the older generation of antipsychotics (Takano 2005).

The classification of sultopride into one of these groups is still debatable (Takano 2005). First introduced into psychiatry in Europe in the 1970s, sultopride showed a powerful and constant efficacy in trials and was found to be more effective and rapidly acting than the phenothiazines (Morel 1983); the prototype of typical antipsychotics. Furthermore, based on D2 receptor occupancy, sultopride is about 50 times more potent than sulpiride (Takano 2005), which has a similar neuropharmacological profile to several of the atypical antipsychotic drugs.

Despite being FDA approved, sultopride was not widely used. A maximum of 2% usage was reported in treating acute psychosis (Scotto 1984, Huf 2002, Hardman 1996). It was also later suspended due to undesirable side effects such as cardiacXXXXX (Titier 2005). However, justification for this suspension is still under debate (Titier 2005). Reliable evidence of both sultopride's efficacy and side effects are needed to determine whether its suspension is sufficiently justified.

Technical Background:

Sultopride's International Union of Pure and Applied Chemistry (IUPAC) name is [N-(ethyl-1-pyrrolidinyl- 2-methyl) methoxy-2-ethylsulfonyl-5-benzamide] and its Molecular Weight is 354.465 g/mol (CTD 2006, NCBI 2006). It is an antagonist of the D2-like dopamine receptors, and is a member of a large family of receptors that interact with specific intracellular signalling pathways through coupling with G proteins. It is a substituted benzamide related to Sulpiride and presents a high selectivity for D2 and D3 dopaminergic receptor subtypes (Blomme 1998). Sultopride may be given orally or intramuscular. Its half-life is three to five hours and its plasma half-life is about 11 hours. Ninety percent of its excretion is via the kidneys and 5-10% is via the faecal route (Martindale 1989, Kobari 1985 a, Kobari 1985 b).

Objectives

To evaluate the effects of sultopride compared to placebo and other antipsychotic drugs in the treatment of schizophrenia and other types of schizophrenia-like psychoses.

Criteria for considering studies for this review

Types of studies
We included all relevant randomised controlled trials. Where a trial was described as 'double-blind', but it was implied that the study was randomised, we included the trial in a sensitivity analysis. If there was no substantive difference within primary outcomes (see 'types of outcome measures') when these 'implied randomisation' studies were added, then we included these in the final analysis. If there was a substantive difference, we only analysed clearly randomised trials and described the results of the sensitivity analysis in the text. We excluded quasi-randomised studies, such as those allocating by using alternate days of the week.