Abstract: We included 15 randomised trials (1437 participants) of WDD for schizophrenia. There was a high risk of performance bias within the trials but overall, risk for selection, attrition and reporting bias was low or unclear. Data showed WDD improved the short-term global state of participants compared with placebo or no treatment (1 RCT n = 72, RR 0.53, 95% CI 0.39 to 0.73, low-quality evidence). When WDD was compared with antipsychotic drugs, such as chlorpromazine or risperidone, no difference in short-term global state of participants was observed (2 RCTs n = 140, RR 1.18 95% CI 0.98 to 1.43, moderate-quality evidence) and mental state (total endpoint Positive and Negative Syndrome Scale (PANSS): 2 RCTs, n = 140, MD 0.84, 95% CI -4.17 to 5.84, low-quality evidence). However, WDD was associated with fewer people experiencing extrapyramidal effects (EPS) compared with other treatments (2 RCTs 0/70 versus 47/70, n = 140, RR 0.02, 95% CI 0.00 to 0.15, moderate-quality evidence). WDD is often used as an add-on intervention alongside antipsychotics. When WDD + antipsychotic was compared to antipsychotic alone, the combination group had better global state (short-term results, 6 RCTs, n = 684, RR 0.60, 95% CI 0.50 to 0.72, moderate-quality evidence) and mental state (short-term total endpoint PANSS: 5 RCTs, n = 580, MD -11.64, 95% CI -13.33 to - 9.94, low-quality evidence), fewer people with EPS (2 RCTs n = 308, RR 0.46, 95% CI 0.30 to 0.70, moderate-quality evidence) and reduction of the mean use of risperidone (1 RCT n = 107, MD -0.70, 95% CI -0.87 to -0.53, low-quality evidence). But, there was no effect on weight gain (1 RCT n = 108, RR 0.50, 95% CI 0.20 to 1.24, low-quality evidence). When WDD + low-dose antipsychotic was compared with normal-dose antipsychotic alone, the combination again showed benefits for short-term global state (7 RCTs n = 522, RR 0.69, 95% CI 0.51 to 0.93, moderate-quality evidence), mental state (total endpoint PANSS: 4 RCTs n = 250, MD -9.53, 95% CI -17.82 to -1.24, low-quality evidence), and fewer participants with EPS (3 RCTS n = 280, RR 0.29, 95% CI 0.16 to 0.51, moderate-quality evidence). Across all comparisons, we found no data on outcomes directly reporting quality of life, hospital service use and economics. Limited evidence suggests that WDD may have some positive short-term antipsychotic global effects compared to placebo or no treatment. However when WDD was compared with other antipsychotics there was no effect on global or mental state, but WDD was associated with fewer adverse effects. When WDD was combined with an antipsychotic, positive effects were found for global and mental state and the combination caused fewer adverse effects. The available evidence is not high quality. Better designed large studies are needed to fully and fairly test the effects of WDD for people with schizophrenia.

Plain-language summary: In Feburary 2016, the Information Specialist of the Cochrane Schizophrenia Group ran an electronic search for trials that randomised people with schizophrenia to receive either WDD, placebo/no treatment or antipsychotic drugs. We screened all records found in this search and included those that met our inclusion criteria and reported useful data. Fifteen trials (with a total of 1437 participants) provided useable, but limited, data. Results showed that WDD may have some beneficial effects on short-term global outcomes and mental state of people with schizophrenia compared to placebo or no treatment but did not show a benefit when compared to antipsychotics - although WDD did cause fewer adverse effects. When WDD was combined with an antipsychotic, there were observed benefits for WDD on improving global state and reducing the side effects caused by antipsychotics. Results of this review suggest WDD may be helpful for people with schizophrenia, but these results are based on low to moderate evidence and there is not enough high-quality evidence to make firm conclusions. Better-designed large studies are needed to fully and fairly test the effects of WDD for people with schizophrenia.