Depot flupenthixol decanoate for schizophrenia or other similar psychotic disorders

BACKGROUND: Anti-psychotic drugs are the mainstay treatment for schizophrenia and similar psychotic disorders. Long-acting depot injections of drugs such as flupenthixol decanoate are extensively used as a means of long-term maintenance treatment. OBJECTIVES: To evaluate the effects flupenthixol decanoate in comparison with placebo, oral antipsychotics and other depot neuroleptic preparations for people with schizophrenia and other severe mental illnesses, in terms of clinical, social and economic outcomes. SEARCH STRATEGY: Relevant trials were identified by searching Biological Abstracts (1982-1998), Cochrane Library (Issue 2, 1998), Cochrane Schizophrenia Group's Register (December 1998), EMBASE (1980-1998), MEDLINE (1966-1998) and PsycLIT (1974-1998). The references of all identified trials were inspected for more studies and the first author of each included trial and relevant pharmaceutical companies were contacted. SELECTION CRITERIA: All randomised controlled trials that focused on people with schizophrenia or other similar psychotic disorders where flupenthixol decanoate had been compared to placebo or other antipsychotic drugs. All clinically relevant outcomes were sought. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, quality rated and data extracted. For dichotomous data Peto odds ratios (OR) with 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was also calculated. Analysis was by intention-to-treat. Normal continuous data were summated using the weighted mean difference (WMD). Scale data were presented only for those tools that had attained pre-specified levels of quality. MAIN RESULTS: No trials compared flupenthixol decanoate to placebo. One small study compared flupenthixol decanoate with an oral antipsychotic (penfluridol). There were no clear differences between the two preparations. When flupenthixol decanoate was compared to other depot preparations, there were no differences between depots for outcomes such as death, global impression, relapse (OR 1.16 CI 0.7-1.9) or leaving the study early (OR 1.00 CI 0.6-1.7). Two small studies suggest that flupenthixol decanoate is responsible for less movement disorders than other depot antipsychotic drugs (OR 0.23 CI 0.08-0.7, NNT 5). This finding did not hold for specific side effects, such as tremor (OR 1.2 CI 0.3-4) and tardive dyskinesia (OR 1.60 CI 0.4-6). Two trials comparing high doses of flupenthixol decanoate to the standard approximately 40mg per injection reported no significant difference for the outcome of relapse (OR 0.32 CI 0.09-1.2). One small (n=59) trial comparing a very low dose of flupenthixol decanoate ( approximately 6 mg/IM) to a very low dose approximately 9 mg per injection also reported no difference in relapse rates (OR 0.3 CI 0.1-1.1). REVIEWER'S CONCLUSIONS: From the data reported in clinical trials, it would be understandable if those suffering from schizophrenia, who are willing to take flupenthixol decanoate, would request the standard dose rather than the high dose. In the current state of evidence, there is nothing to choose between flupenthixol decanoate and other depot antipsychotics. The choice of which depot to use must therefore be based on clinical judgement and the preferences of people with schizophrenia and their carers. Managers and policy makers should expect better data than the research community has provided thus far. This review highlighted the need for large, well-designed and reported randomised clinical trials to address the effects of flupenthixol decanoate, in particular when compared to oral antipsychotics. Future studies should also consider hospital and service outcomes, satisfaction with care and record economic data.