Sertindole for schizophrenia.
BACKGROUND
Sertindole is an atypical antipsychotic, which is thought to give a lower incidence of extrapyramidal side effects at clinically effective doses than typical antipsychotic drugs. In December 1998, Lundbeck Ltd., the manufacturers of sertindole, voluntarily suspended the availability of the drug due to concerns about cardiac arrhythmia and sudden cardiac death associated with its use. Sertindole has therefore been withdrawn from the market pending discussion with the European Regulatory Authority over cardiac safety.


OBJECTIVE
To determine the effects of sertindole compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses.


METHODS
Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), LILACS (1982-1996), MEDLINE (1966-1999), PSYNDEX (1977-1995) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. The manufacturer of sertindole and authors of trials were contacted.


METHODS
All randomised controlled trials that compared sertindole to placebo or other antipsychotic drug treatments were included by independent assessment.


METHODS
Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) or numbers needed to harm (NNH) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences (WMD) were calculated. All data were inspected for heterogeneity.


RESULTS
Two large important studies were excluded, because they did not report any usable data. The two that were included suggested that sertindole was more antipsychotic than placebo, as acceptable as placebo and better tolerated than haloperidol (NNT=9, RR 0.63 CI 0.41 to 0.96). Sertindole was associated with fewer movement disorders than haloperidol but was shown to cause more weight gain (NNH=9 RR 6.33, CI 1.92 to 20.92), rhinitis (NNH=8, RR 1.74, CI 1,28 to 2.36) and possibly male sexual dysfunction. Cardiac problems (QTc intervals of at least 500msec) were evident even in the randomised trials (NNH=13 RR 23, CI 1.37 to 386.60).


CONCLUSIONS
Because of the cardiac problems, even evident within poorly reported studies, at present sertindole should, if possible, be avoided. If sertindole is to be reintroduced, gold-standard evidence of its clinical benefits will need to far outweigh its real risks.
Lewis
R
R
NHS Centre for Reviews and Dissemination, University of York, York, North Yorkshire, UK, YO10 5DD. rl14@york.ac.uk
Bagnall
A
A
Leitner
M
M
D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; C066304:sertindole