Abstract: Of the 12 records retrieved by the search, three trials published in 2001, 2003 and 2007, involving 80 inpatients with schizophrenia, aged 18 to 71 years, admitted in a psychiatric facility and followed up for a period nine weeks to 26 weeks, were included. Overall, pyridoxal 5 phosphate produced a significant improvement in tardive dyskinesia symptoms when compared with placebo, assessed by a change in Extrapyramidal Symptoms Rating Scale (ESRS) scores from baseline to the end of the first phase of the included studies (2 RCTs n = 65, RR 19.97, CI 2.87 to 139.19, low quality evidence). The endpoint tardive dyskinesia score (a measure of its severity) assessed with the ESRS, was significantly lower among participants on pyridoxal 5 phosphate compared to those on placebo (2 RCTs n = 60, MD -4.07, CI -6.36 to -1.79, low quality evidence). It was unclear whether pyridoxal 5 phosphate led to more side effects (n = 65, 2 RCTs, RR 3.97, CI 0.20 to 78.59, low quality evidence) or caused deterioration in tardive dyskinesia symptoms when compared to placebo (n = 65, 2 RCTs, RR 0.16, CI 0.01 to 3.14, low quality evidence). Five participants taking pyridoxal 5 phosphate withdrew from the study because they were not willing to take more medications while none of the participants taking placebo discontinued their medications (n = 65, 2 RCTs, RR 8.72, CI 0.51 to 149.75, low quality evidence). There was no significant difference in the endpoint positive and negative psychiatric symptoms scores, measured using the Positive and Negative symptoms Scale (PANSS) between participants taking pyridoxal 5 phosphate and those taking placebo. For the positive symptoms: (n = 15, 1 RCT, MD -1.50, CI -4.80 to 1.80, low quality evidence). For negative the symptoms: (n = 15, 1 RCT, MD -1.10, CI -5.92 to 3.72, low quality evidence). Pyridoxal 5 phosphate may have some benefits in reducing the severity of tardive dyskinesia symptoms among individuals with schizophrenia. However, the quality of evidence supporting the effectiveness of pyridoxal 5 phosphate in treating tardive dyskinesia is low, based on few studies, short follow-up periods, small sample sizes and inadequate adherence to standardised reporting guidelines for randomised controlled trials among the included studies.

Plain-language summary: . A search for relevant randomised studies was conducted in January 2013. The review includes three studies with 80 participants. All participants had tardive dyskinesia as a result of taking antipsychotic medication and were randomised into treatment groups. One group received pyridoxal 5 phosphate, the other group received a placebo. Antipsychotic treatment continued as usual throughout the trials. . People taking pyridoxal 5 phosphate in these studies experienced more than 40% improvement in their tardive dyskinesia compared to those on placebo, so had less severe tardive dyskinesia. Experience of side effects were similar between treatment groups with participants taking pyridoxal 5 phosphate experiencing no more or less side effects than participants in the placebo group and they did not experience greater worsening of their psychiatric symptoms than those on placebo. Evidence from the studies is weak, but suggests pyridoxal 5 phosphate may be effective in the treatment of tardive dyskinesia. . Evidence is weak. The number of studies and participants is few. The quality of studies is low. Better evidence could be gathered by better designed, conducted and reported trials. Ben Gray, Senior Peer Researcher, McPin Foundation. http://mcpin.org/.