Wendan decoction for schizophrenia

Review question

Is there trial-based evidence that a traditional Chinese herbal medicine, Wendan decoction (WDD) is effective for treatment of people with schizophrenia?

Background

Schizophrenia is a severe mental illness, characterised by profound disruptions in thinking that affects language, perception, and sense of self. People with schizophrenia often hear voices or see things that are not present (hallucinations) and have strange beliefs (delusions). The main treatment for schizophrenia are antipsychotic drugs, However, antipsychotic drugs can cause unpleasant side effects, particularly movement disorders, which can be severe enough to stop people from continuing treatment. Experiences from China suggest some Traditional Chinese medicine (TCM - a system of medicine originated in China and encompassing characteristics of traditional Chinese philosophy and culture) approaches can have an antipsychotic effect while causing fewer side effects. Wendan decoction is one of the classical TCM prescriptions for severe mental illness such as schizophrenia.

Searching for evidence

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.

Evidence found

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.

Conclusions

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.

Authors' conclusions: 

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.

Read the full abstract...
Background: 

Wendan decoction (WDD) is one of the classical Chinese herb formulas used for psychotic symptoms. It is thought to be safe, accessible and inexpensive.

Objectives: 

To investigate the effects of WDD for treatment of people with schizophrenia or schizophrenia-like illness compared with placebo, antipsychotic drugs and other interventions for outcomes of clinical importance.

Search strategy: 

We searched the Cochrane Schizophrenia Group's Trials Register (February 2016), which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, China biomedical databases group (SinoMed, CNKI, VIP, Wanfang) and clinical trials registries. There are no language, date, document type, or publication status limitations for inclusion of records in the register. We also inspected references of identified studies and contacted relevant authors for additional information.

Selection criteria: 

Randomised controlled trials with useable data comparing WDD with antipsychotics, placebo or other interventions for people with schizophrenia.

Data collection and analysis: 

We extracted data independently. For binary outcomes, we calculated risk ratios (RR) and 95% confidence intervals (CIs), on an intention-to-treat basis. For continuous data, we estimated mean differences (MD) between groups and their 95% CIs. We employed a random-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.

Main results: 

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.

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