Risperidone versus typical antipsychotic medication for schizophrenia.
BACKGROUND
The 'conventional' neuroleptic drugs, such as haloperidol and chlorpromazine, are frequently used as the first line treatment for people with schizophrenia. However, about 5-25% of these people show poor response to these treatments and side effects often makes compliance with the 'older generation' of drug treatment problematic. Although the efficacy of these medications with respect to 'positive' symptoms is well described, little evidence exists that 'conventional' antipsychotic treatment has any effect on the 'negative' symptoms of schizophrenia. Risperidone is one of the 'new generation' neuroleptic compounds. As well as its reputed tendency to cause fewer movement disorders it is claimed that risperidone may improve negative symptoms.


OBJECTIVE
To evaluate the effectiveness of risperidone for schizophrenia in comparison to 'conventional' neuroleptic drugs.


METHODS
Electronic searches of Biological Abstracts (1980-1997), Cochrane Schizophrenia Group's Register (1997), The Cochrane Library (1997, Issue1), EMBASE (1980-1997), MEDLINE (1966-1997), PsycLIT (1974-1997), and SCISEARCH (1997) were undertaken. References of all identified studies were searched for further trial citations. Pharmaceutical companies and authors of trials were contacted.


METHODS
All randomised trials comparing risperidone to any 'conventional' neuroleptic treatment for those with schizophrenia or other serious mental illnesses.


METHODS
Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were also independently extracted. Sensitivity analyses on dose of risperidone, haloperidol and duration of illness were undertaken for the primary outcomes of clinical improvement, side effects (movement disorders) and acceptability of treatment. For homogeneous dichotomous data the odds ratio (OR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis.


RESULTS
Twelve short-term studies and two long term studies provided data on 3401 people. This review provides no evidence relating to the effect of risperidone on cognitive or social functioning, quality of life, employment status, discharge from hospital and relapse rates. Risperidone increases the odds of moderate clinical improvement (OR 0.65, CI 0.55-0.77, NNT 10, CI 7-16). It appears to have little or no additional effect on the positive and negative symptoms of schizophrenia but did have less tendency to cause movement disorders, largely in comparison with haloperidol (OR 0.43, CI 0.34-0.55, NNT 7, CI 5-10) for use of antiparkinsonian medication. Risperidone seems to be more acceptable to those with schizophrenia (OR 0.69 CI 0.57-0.83, NNT 15, CI 10-30, 30% baseline risk of dropping out). Those taking risperidone are also marginally less likely to experience somnolence (OR 0.78, CI 0. 61-0.99, NNT 22). Weight gain, however, is more likely with risperidone (OR 1.51 CI 1.14-2.00, NNT 13). Funnel plots show that smaller studies generally show greater benefit for risperidone than larger studies. A publication bias in favour of risperidone amongst the included studies may explain this effect. Sensitivity analyses on dose of risperidone (excluding those receiving 1 or 2 mg) did not materially change the results for the principal outcomes. Excluding data from those on higher doses of haloperidol (>10mg/day) does marginally change the results. Risperidone is less effective in achieving clinical improvement and preventing dropout but outcomes relating to movement disorders change little.


CONCLUSIONS
Little can be concluded about the long term effects of risperidone and generalising results beyond a comparison with haloperidol would be imprudent. Risperidone may be more acceptable to those with schizophrenia and have marginal benefits in terms of limited clinical improvement and side
Kennedy
E
E
Research and Development Directorate, Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow, UK, G12 0XH. jcahoon@udcf.gla.ac.uk
Song
F
F
Hunter
R
R
Clarke
A
A
Gilbody
S
S
D014150:Antipsychotic Agents / Q000627:therapeutic use*; D006801:Humans; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D018967:Risperidone