Quetiapine for schizophrenia.

BACKGROUND: Quetiapine is a novel atypical antipsychotic with, theoretically, a low propensity for movement disorder adverse effects. It is used for treatment of schizophrenia and other psychoses.

OBJECTIVES: To determine the effects of quetiapine for schizophrenia in comparison to placebo, classical and other atypical antipsychotics.

SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-2000), CINAHL (1982-2000), the Cochrane Library (2000, Issue 1), the Cochrane Schizophrenia Group's Register of trials (Feb 2000), EMBASE (1980-2000), MEDLINE (1966-2000), PsycLIT (1974-2000), SIGLE on CD (1980-1997), SocioFile (1974-1997) and many conference proceedings and hand searches of specific journals were undertaken. AstraZeneca Pharmaceuticals was contacted for information regarding unpublished trials.

SELECTION CRITERIA: All controlled trials where adults with schizophrenia or similar illnesses were randomised to quetiapine, placebo or other neuroleptic drugs and where clinically relevant outcomes were reported.

DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were also independently extracted. The Relative Risk (RR) with 95% confidence intervals (CI) was used. A fixed effect model was used for a data set with non-significant heterogeneity. A random effect model was used for data sets with significant heterogeneity. In addition, as a measure of efficacy, the number needed to treat (NNT) was also calculated. For a continuous outcome, a weighted mean difference (WMD) between groups was estimated. A fixed effect model was used for a data set with non-significant heterogeneity. A random effect model was used for a data set with significant heterogeneity.

MAIN RESULTS: Forty-two papers and reports (11 randomised controlled trials) were included in the review while 155 were excluded. Apart from the outcome, 'leaving the study early', all other results may be prone to bias and should be viewed with caution since dropout rates are high (36-64%) in these trials of short duration. In comparison to placebo, there are data suggesting that people allocated to quetiapine are less likely to leave the study early (RR 0.84, CI 0.73 to 0.97) particularly when the reason given was due to treatment failure. Dichotomous data relating to psychotic symptoms show a significant improvement in the quetiapine group (RR 0.79, CI 0.67 to 0.92, NNT 8). No significant difference could be found in respect of needing medication for extrapyramidal side effects, as well as for incidences of parkinsonism, akathisia and dystonia. In comparison to classical antipsychotics, the proportion of people leaving the studies early is significantly, but marginally, less for the quetiapine group (RR 0.87, CI 0.76 to 0.99). No significant difference between the two groups shows with regard to global state and mental state. Quetiapine may produce lower incidences of using medication for extrapyramidal side effects such as parkinsonism, akathisia and dystonia. Most data are very short term. In comparison to the low dose quetiapine group, the number of people leaving the three studies is significantly smaller in the high dose group (RR 0. 84, CI 0.75 to 0.94). The improvement on mental state was significantly higher in the high dose group. Incidences of akathisia, dystonia, parkinsonism and needing medication for extrapyramidal side effects were the same for both doses of quetiapine.

REVIEWER'S CONCLUSIONS: High dropout rates in short quetiapine studies are a major problem, and makes interpreting any results problematic. Before quetiapine's use can be recommended, more large, well conducted trials that provide short, medium and long term outcomes relevant to carers and clinicians are necessary.