Thioridazine for schizophrenia.

Background: Thioridazine is a piperidine phenothiazine used for the treatment of people with schizophrenia. It has often been considered the drug of choice in the elderly because of reputed lower levels of extrapyramidal adverse events. It may, however, be more likely to cause cognitive adverse events, such as delirium or worsening of memory, and, on rare occasions, thioridazine has caused pigmentary retinopathy.

Objectives: To examine the effects of thioridazine for those with schizophrenia, and, in particular, elderly people with schizophrenia.

Search Strategy: Electronic searches of Biological Abstracts (1980-1999), CINAHL (1982-1999), The Cochrane Library (Issue 3, 1999), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974-1999) and Sociofile (1974-1999) were undertaken. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted.

Selection Criteria: All randomised clinical trials that compared thioridazine to other treatments for people with schizophrenia or other psychoses.

Data Collection And Analysis: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 40%. For homogeneous dichotomous data the Relative Risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity.

Main Results: 560 people from 11 studies were randomised to thioridazine or placebo. For change in global state, small, short term studies (three months or less) found no difference between groups (RR 0.66 CI 0.35-1.23, n=100). At six months, however, two small studies (n=65) favoured thioridazine (RR 0.34 CI 0.21-0. 56, NNT 2 CI 1-6). Fourteen percent in the thioridazine group left early compared to 32% of people allocated to placebo (RR 0.43 CI 0. 31-0.61, NNT 6 CI 4-10, n=510). Few differences in terms of adverse effects, between thioridazine and placebo, were apparent. Limited data from trials suggest that thioridazine is not strongly anticholinergic (blurred vision RR 2.01 CI 0.56-7.25, n=224). Thioridazine is not sedating (at three months to one year RR 2.48 CI 0.96-6.4, n=122). No data were presented on retinal changes. Two thousand three hundred ninety-seven patients from 26 studies were randomised to thioridazine versus typical antipsychotics. For the outcome 'no better or worse', those allocated to thioridazine were no better off than people given control typical neuroleptics (RR 0. 97 CI 0.78-1.21, n=771). There were no clear differences between thioridazine and other drugs for the outcome 'Mental state - no better or worse' on the BPRS by three months (RR 1.3 CI 0.8-2.11, n=208). Twenty-one studies (n=1737) had 19% attrition in both groups. Few differences were seen in the lists of adverse effects. As expected from the placebo comparison, thioridazine does not cause more anticholinergic-type symptoms than other drugs. About half of people given thioridazine felt drowsy or sedated but this was no different from other drugs (RR 1.06 CI 0.93-1.2, n=909). Parkinsonism was less common in the thioridazine group in the short term (RR 0.29 CI 0.12-0.7, n=340). One small study (n=40) found no clear differences between thioridazine and clozapine.

Reviewer's Conclusions: Although there are shortcomings and gaps in the data, there appears to be enough consistency over different outcomes and periods to confirm that thioridazine is an antipsychotic of similar efficacy to other commonly used neuroleptics for people with schizophrenia. Its adverse events profile is similar to that of other drugs, but it may have a lower level of extrapyramidal problems. (ABSTRACT TRU