BACKGROUND Long-acting depot injections of drugs such as flupenthixol decanoate are extensively used as a means of long-term maintenance treatment for schizophrenia. OBJECTIVE To evaluate the effects of 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. METHODS We identified relevant trials by searching the Cochrane Schizophrenia Group Trials Register in March 2009 and then for this update version, a search was run in April 2013. The register is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. We contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. METHODS All randomised controlled trials that focused on people with schizophrenia or other similar psychotic disorders where flupenthixol decanoate had been compared with placebo or other antipsychotic drugs were included. All clinically relevant outcomes were sought. METHODS Review authors independently selected studies, assessed trial quality and extracted data. For dichotomous data we estimated risk ratios (RR) with 95% confidence intervals (CI) using a fixed-effect model. Analysis was by intention-to-treat. We summated normal continuous data using mean difference (MD), and 95% CIs using a fixed-effect model. We presented scale data only for those tools that had attained prespecified levels of quality. Using Grading of Recommendations Assessment, Development and Evaluation (GRADE) we created 'Summary of findings tables and assessed risk of bias for included studies. RESULTS The review currently includes 15 randomised controlled trials with 626 participants. No trials compared flupenthixol decanoate with placebo.One small study compared flupenthixol decanoate with an oral antipsychotic (penfluridol). Only two outcomes were reported with this single study, and it demonstrated no clear differences between the two preparations as regards leaving the study early (n = 60, 1 RCT, RR 3.00, CI 0.33 to 27.23,very low quality evidence) and requiring anticholinergic medication (1 RCT, n = 60, RR 1.19, CI 0.77 to 1.83, very low quality evidence).Ten studies in total compared flupenthixol decanoate with other depot preparations, though not all studies reported on all outcomes of interest. There were no significant differences between depots for outcomes such as relapse at medium term (n = 221, 5 RCTs, RR 1.30, CI 0.87 to 1.93, low quality evidence), and no clinical improvement at short term (n = 36, 1 RCT, RR 0.67, CI 0.36 to 1.23, low quality evidence). There was no difference in numbers of participants leaving the study early at short/medium term (n = 161, 4 RCTs, RR 1.23, CI 0.76 to 1.99, low quality evidence) nor with numbers of people requiring anticholinergic medication at short/medium term (n = 102, 3 RCTs, RR 1.38, CI 0.75 to 2.25, low quality evidence).Three studies in total compared high doses (100 to 200 mg) of flupenthixol decanoate with the standard doses (˜40mg) per injection. Two trials found relapse at medium term (n = 18, 1 RCT, RR 1.00, CI 0.27 to 3.69, low quality evidence) to be similar between the groups. However people receiving a high dose had slightly more favourable medium term mental state results on the Brief Psychiatric Rating Scale (BPRS) (n = 18, 1 RCT, MD -10.44, CI -18.70 to -2.18, low quality evidence). There was also no significant difference in the use of anticholinergic medications to deal with side effects at short term (2 RCTs n = 47, RR 1.12, CI 0.83 to 1.52 very low quality evidence). One trial comparing a very low dose of flupenthixol decanoate (˜6 mg) with a low dose (˜9 mg) per injection reported no difference in relapse rates (n = 59, 1 RCT, RR 0.34, CI 0.10 to 1.15, low quality evidence). CONCLUSIONS In the current state of evidence, there is nothing to choose between flupenthixol decanoate and other depot antipsychotics. From the data reported in clinical trials, it would be understandable to offer standard dose rather than the high dose depot flupenthixol as there is no difference in relapse. However, data reported are of low or very low quality and this review highlights the need for large, well-designed and reported randomised clinical trials to address the effects of flupenthixol decanoate.