Perazine for schizophrenia

Schizophrenia is often a severe and disabling illness that affects approximately one per cent of the worldwide population. Schizophrenia has 'positive' symptoms, such as strange and fixed beliefs (delusions), as well as hearing voices and seeing things (hallucinations). Schizophrenia also has 'negative' symptoms such as apathy, loss of emotion, lack of drive and disorganisation of behaviour and thought. The degree of disability is considerable with 80% - 90% not working and up to 10% dying.

Antipsychotic drugs are the main treatment for schizophrenia, and are grouped into older drugs (first generation or ‘typical’) and newer drugs (second generation or ‘atypical’). However, antipsychotic drugs also have serious side effects, particularly movement disorders such as uncontrollable shaking, tremors, muscle stiffness, tiredness, weight gain and the inability to sit still.

Perazine is an older antipsychotic drug first introduced in the 1950s. It is suggested to have a low level of side effects (especially for movement disorders). Its use is regional and restricted to countries like Germany, Poland, the Netherlands and the former Yugoslavia.

A search for trials was carried out in July 2012. The review now includes seven studies with a total of 479 participants and assesses the effects of perazine for people with schizophrenia. Comparisons of perazine versus placebo (‘dummy’ treatment) and versus other antipsychotic drugs revealed no clear differences or superiority of perazine. However, only a handful of studies have been undertaken and the number of participants in each study was small. In addition the studies avialable were of limited quality with data for the main outcomes of interest rated as low or very low quality. As perazine is a cheap drug and there is some limited evidence that it may cause less side effects than other older antipsychotic drugs, further large scale, well designed and well-reported studies are much needed.

This plain language summary has been written by a consumer Benjamin Gray from Rethink Mental Illness,

Email: ben.gray@rethink.org.

Authors' conclusions: 

The number, size and reporting of randomised controlled perazine trials are insufficient to present firm conclusions about the properties of this antipsychotic. It is possible that perazine is associated with a similar risk of extrapyramidal side-effects as some atypical antipsychotics but this is based on small comparisons. This should be clarified in larger, well-designed trials.

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Background: 

Perazine is an old phenothiazine derivative used for the treatment of people with schizophrenia and is reputed to have a low level of extrapyramidal adverse effects. As far as we are aware, its use is limited to Germany, Poland, the former Yugoslavia and the Netherlands.

Objectives: 

To examine the effects of perazine for those with schizophrenia or related psychoses in comparison with placebo, no treatment or other antipsychotic medications.

Search strategy: 

We searched the Cochrane Schizophrenia Group Trials Register, which includes relevant randomised controlled trials from the bibliographic databases Biological Abstracts, CINAHL, The Cochrane Library, EMBASE, MEDLINE, PsycLIT, LILACS, PSYNDEX, Sociological Abstracts and Sociofile. We searched the references of all included studies for further trials. We contacted pharmaceutical companies and authors of trials. We updated this search on 16th July 2012.

Selection criteria: 

We selected all randomised controlled trials that compared perazine with other treatments for people with schizophrenia or schizophrenia-like psychoses, or both.

Data collection and analysis: 

The review authors (SL, BH, BHe) independently inspected the citations and where possible abstracts and ordered papers for re-inspection and quality assessment. We independently extracted data. We calculated the risk ratio (RR) and 95% confidence interval (CI) using a random-effects model. For continuous data, we calculated mean differences (MD). We inspected all data for heterogeneity, assessed trials for risk of bias and created summary of findings tables using GRADE.

Main results: 

The review now includes seven trials with a total of 479 participants. In only one trial, with 95 participants, perazine appeared superior to 'active placebo' (trimipramine) at five weeks for the outcome of 'no important global improvement' (n = 95, RR 0.43 CI 0.2 to 0.8, low quality evidence), but there was no statistically significant difference in most measures of mental state. Perazine did not induce more general adverse events than placebo but more participants received at least one dose of antiparkinson medication (n = 95, RR 4.50 CI 1.0 to 19.5, very low quality evidence).

Six small trials comparing perazine with other antipsychotics, including 384 participants in total, were incompletely reported and the outcomes were presented in various ways so that meta-analysis was not possible on most occasions. In the six studies, a similar number of participants receiving perazine or comparator antipsychotics (amisulpride, haloperidol, olanzapine, ziprasidone, zotepine) left the studies early (n = 384, RR 0.97 CI 0.68 to 1.38, low quality evidence). The results on efficacy could not be meta-analysed because the authors presented their results in very different ways. No obvious differences in adverse events between perazine and other antipsychotics could be derived from the limited data. Two haloperidol comparisons did not present extrapyramidal side-effects in a way that was suitable for use in meta-analysis, but three small comparisons with the second-generation antipsychotics zotepine and amisulpride showed no higher risk of akathisia (n = 111, RR 0.31 CI 0.1 to 1.1), dyskinesia (n = 111, RR 0.47 CI 0.1 to 3.5), parkinsonism (n = 81, RR 1.21 CI 0.5 2.8) or tremor (n = 40, RR 0.80 CI 0.3 to 2.6) with perazine.

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