Abstract: The review includes 22 RCTs of varying quality and sample size studying Ginkgo biloba, N-acetyl cysteine (NAC), allopurinol, dehydroepiandrosterone (DHEA), vitamin C, vitamin E or selegiline. Median follow-up was eight weeks. Only three studies including a minority of the participants reported our a priori selected primary outcome of clinically important response. Short-term data for this outcome (measured as at least 20% improvement in scores on Positive and Negative Syndrome Scale (PANSS)) were similar (3 RCTs, n = 229, RR 0.77, 95% CI 0.53 to 1.12, low quality evidence). Studies usually reported only endpoint psychopathology rating scale scores. Psychotic symptoms were lower in those using an adjunctive antioxidant according to the PANSS ( 7 RCTS, n = 584, MD -6.00, 95% CI -10.35 to -1.65, very low quality evidence) and the Brief Psychiatric Rating Scale (BPRS) (8 RCTS, n = 843, MD -3.20, 95% CI -5.63 to -0.78, low quality evidence). There was no overall short-term difference in leaving the study early (16 RCTs, n = 1584, RR 0.73, 95% CI 0.48 to 1.11, moderate quality evidence), or in general functioning (2 RCTs, n = 52, MD -1.11, 95% CI -8.07 to 5.86, low quality evidence). Adverse events were generally poorly reported. Three studies reported useable data for 'any serious adverse effect', results were equivocal (3 RCTs, n = 234, RR 0.65, 95% CI 0.19 to 2.27, low quality evidence). No evidence was available for relapse, quality of life or service use. Although 22 trials could be included in this review, the evidence provided is limited and mostly not relevant to clinicians or consumers. Overall, although there was low risk of attrition and selective data reporting bias within the trials, the trials themselves were not adequately powered and need more substantial follow-up periods. There is a need for larger trials with longer periods of follow-up to be conducted. Outcomes should be meaningful for those with schizophrenia, and include measures of improvement and relapse (not just rating scale scores), functioning and quality of life and acceptability and, importantly, safety data.

Plain-language summary: Searches for randomised trials were run in 2010 and 2012, review authors found 22 relevant trials that randomised a total of 2041 people with schizophrenia. The trials compared the effects of taking a variety of antioxidants (allopurinol, Ginkgo biloba, N-acetyl cysteine (NAC), selegiline, vitamins C and E) compared with placebo. Most results showed no real differences between the antioxidants and placebo although there was evidence Ginkgo biloba had a positive effect on psychotic symptoms in the short term. The quality of this evidence was moderate. However, overall, the trials suffered from a lack of real-world outcomes, such as clinical response, rates of relapse, quality of life, functioning, safety and satisfaction or acceptability of treatment. Adverse effects were also poorly reported with some studies not providing any data for adverse effects. Ginkgo biloba and NAC emerged from the trials as the most promising, so should have priority in the design of future trials that are larger, longer and better reported than the 22 studies available at the present time. Ben Gray, Senior Peer Researcher, McPin Foundation: http://mcpin.org/