Abstract: Four studies randomising a total of 202 people with schizophrenia are included. Oral fluphenazine was compared with oral amisulpride, risperidone, quetiapine and olanzapine. Comparing oral fluphenazine with amisulpride, there was no difference between groups for mental state using the Brief Psychiatric Rating Scale (BPRS) (1 RCT, n = 57, MD 5.10 95% CI -2.35 to 12.55, very low-quality evidence), nor was there any difference in numbers leaving the study early for any reason (2 RCTs, n = 98, RR 1.19 95% CI 0.63 to 2.28, very low-quality evidence). More people required concomitant anticholinergic medication in the fluphenazine group compared to amisulpride (1 RCT, n = 36, RR 7.82 95% CI 1.07 to 57.26, very low-quality evidence). No data were reported for important outcomes including relapse, changes in life skills, quality of life or cost-effectiveness. Comparing oral fluphenazine with risperidone, data showed no difference between groups for 'clinically important response' (1 RCT, n = 26, RR 0.67 95% CI 0.13 to 3.35, very low-quality evidence) nor leaving the study early due to inefficacy (1 RCT, n = 25, RR 1.08 95% CI 0.08 to 15.46, very low-quality evidence). No data were reported data for relapse; change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness. Once again there was no difference when oral fluphenazine was compared with quetiapine for clinically important response (1 RCT, n = 25, RR 0.62 95% CI 0.12 to 3.07, very low-quality evidence), nor leaving the study early for any reason (1 RCT, n = 25, RR 0.46 95% CI 0.05 to 4.46, very low-quality evidence). No data were reported for relapse; clinically important change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness. Compared to olanzapine, fluphenazine showed no superiority for clinically important response (1 RCT, n = 60, RR 1.33 95% CI 0.86 to 2.07, very low-quality evidence), in incidence of akathisia (1 RCT, n = 60, RR 3.00 95% CI 0.90 to 10.01, very low-quality evidence) or in people leaving the study early (1 RCT, n = 60, RR 3.00 95% CI 0.33 to 27.23, very low-quality evidence). No data were reported for relapse; change in life skills; quality of life; or cost-effectiveness. Measures of clinical response and mental state do not highlight differences between fluphenazine and amisulpride, risperidone, quetiapine or olanzapine. Largely measures of adverse effects are also unconvincing for substantive differences between fluphenazine and the newer drugs. All included trials carry a substantial risk of bias regarding reporting of adverse effects and this bias would have favoured the newer drugs. The four small short included studies do not provide much clear information about the relative merits or disadvantages of oral fluphenazine compared with newer atypical antipsychotics.

Plain-language summary: An electronic search of Cochrane Schizophrenia's register of studies was carried out in 2013. Review authors looked for trials that randomised people with schizophrenia to receive either oral fluphenazine or an atypical antipsychotic. Four studies with a total of 202 people with schizophrenia could be included. The trials compared fluphenazine with either amisulpride, risperidone, quetiapine or olanzapine. Results  Data showed oral fluphenazine is no better or worse in improving mental state than amisulpride but more people receiving oral fluphenazine did need to take additional anticholinergic medication (drugs used to help relieve a range of symptoms such as involuntary movements of the muscles, high blood pressure and insomnia). Data from the trials comparing oral fluphenazine with either risperidone, quetiapine or olanzapine also showed no superiority between the treatment groups for clinical improvement. Only the trial comparing oral fluphenazine with olanzapine provided adverse-effects data. Again, incidence of akathisia, a movement disorder, was similar between treatment groups. Quality of evidence  Evidence from these few trials is poor, of low quality and involves a small number of participants. It does not provide clear overall information about whether oral fluphenazine is better or worse than atypical antipsychotic drugs for treating people with schizophrenia. Data were not available for important outcomes such as such, relapse, hospital admission, satisfaction, costs and quality of life. Adverse-effects data were poorly reported. Future large-scale research should report on these important outcomes. Conclusions  Fluphenazine is low cost and widely available, so is likely to remain one of the most widely used treatments for schizophrenia worldwide. However, evidence currently available from randomised controlled trials about its effectiveness compared to atypical antipsychotics is unclear.