Perazine for schizophrenia

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.

To examine the effects of perazine for those with schizophrenia, and schizophrenia-like psychoses.

We searched the Cochrane Schizophrenia Group's 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 (last update of the review March 2005). We searched references of all included studies for further trials. We contacted pharmaceutical companies and authors of trials.

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

We independently (SL, BH) inspected citations and where possible abstracts and ordered papers for re-inspection and quality assessment. We independently extracted data. We excluded data if loss to follow up was greater than 50%. For homogeneous dichotomous data we calculated the Relative Risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We inspected all data for heterogeneity.

We included six trials with a total of 288 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, NNT 4 CI 2 to 13), 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, NNH 6 CI 4 to 33). Five small trials comparing perazine with other antipsychotics, including in total only 193 participants, were incompletely reported and the outcomes were presented in various ways so that meta-analysis was not possible in most occasions. A similar number of participants receiving perazine or comparator antipsychotics left the studies early (n=193, RR 0.85, CI 0.5 to 1.4). The results on efficacy were controversial and need further assessment by randomised controlled trials. 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 suitable way for use in meta-analysis, but three small comparisons with the atypical 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.

The number, size and reporting of randomised controlled perazine trials is 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, and this should be clarified in larger, well-designed trials.