Abstract: This review now includes 73 randomised studies, with 4870 participants. Overall, the quality of the evidence is low to very low. Compared with placebo, use of fluphenazine decanoate does not result in any significant differences in death, nor does it reduce relapse over six months to one year, but one longer-term study found that relapse was significantly reduced in the fluphenazine arm (n = 54, 1 RCT, RR 0.35, CI 0.19 to 0.64, very low quality evidence). A very similar number of people left the medium-term studies (six months to one year) early in the fluphenazine decanoate (24%) and placebo (19%) groups, however, a two-year study significantly favoured fluphenazine decanoate (n = 54, 1 RCT, RR 0.47, CI 0.23 to 0.96, very low quality evidence). No significant differences were found in mental state measured on the Brief Psychiatric Rating Scale (BPRS) or in extrapyramidal adverse effects, although these outcomes were only reported in one small study each. No study comparing fluphenazine decanoate with placebo reported clinically significant changes in global state or hospital admissions. Fluphenazine decanoate does not reduce relapse more than oral neuroleptics in the medium term (n = 419, 6 RCTs, RR 1.46 CI 0.75 to 2.83, very low quality evidence). A small study found no difference in clinically significant changes in global state. No difference in the number of participants leaving the study early was found between fluphenazine decanoate (17%) and oral neuroleptics (18%), and no significant differences were found in mental state measured on the BPRS. Extrapyramidal adverse effects were significantly less for people receiving fluphenazine decanoate compared with oral neuroleptics (n = 259, 3 RCTs, RR 0.47 CI 0.24 to 0.91, very low quality evidence). No study comparing fluphenazine decanoate with oral neuroleptics reported death or hospital admissions. No significant difference in relapse rates in the medium term between fluphenazine decanoate and fluphenazine enanthate was found (n = 49, 1 RCT, RR 2.43, CI 0.71 to 8.32, very low quality evidence), immediate- and short-term studies were also equivocal. One small study reported the number of participants leaving the study early (29% versus 12%) and mental state measured on the BPRS and found no significant difference for either outcome. No significant difference was found in extrapyramidal adverse effects between fluphenazine decanoate and fluphenazine enanthate. No study comparing fluphenazine decanoate with fluphenazine enanthate reported death, clinically significant changes in global state or hospital admissions. There are more data for fluphenazine decanoate than for the enanthate ester. Both are effective antipsychotic preparations. Fluphenazine decanoate produced fewer movement disorder effects than other oral antipsychotics but data were of low quality, and overall, adverse effect data were equivocal. In the context of trials, there is little advantage of these depots over oral medications in terms of compliance but this is unlikely to be applicable to everyday clinical practice.

Plain-language summary: This review aimed to investigate the effects of fluphenazine (decanoate and enanthate) for schizophrenia. Searches for relevant randomised controlled trials was run in February 2011 and October 16, 2013. Authors could include and extract data from 73 studies with a total of 4870 participants. There were more studies on fluphenazine decanoate than enanthate.The review authors rated the quality of the evidence in the included trials to be low or very low. A long-term result from only one trial indicated fluphenazine decanoate reduces the rate of relapse when compared with placebo (‘dummy treatment’). Three studies found that fluphenazine decanoate produced fewer general movement disorders than oral antipsychotics. However, other results showed, overall, the effects and outcomes, including adverse effects for fluphenazine (decanoate and enanthate) are similar to other oral and depot antipsychotics. Important outcomes and information about use of services, going into hospital, satisfaction with care and costs were not reported in any study. Depot injections may offer an advantage over tablets (oral medication) in terms of people taking their medication (complying and adhering to treatment). However, this needs to be balanced with the likelihood of serious side effects, such as involuntary shaking, muscle stiffness, the inability to sit still and lowering in people’s mood. Results did not show any strong evidence that depot fluphenazine produced more adverse effects than other antipsychotics. This should be addressed in future large scale and high quality studies. This plain language summary has been written by a consumer Ben Gray from Rethink Mental Illness.