Patients with clozapine-resistant schizophrenia who are treated with adjuvant sodium benzoate demonstrate improvements in quality of life as well as improvements in schizophrenic symptoms such as delusions, hallucinations, excitement, suspiciousness/persecution, and hostility, according to the findings from a randomized, double-blind, placebo-controlled trial published in Biological Psychiatry.

A total of 59 Chinese inpatients with schizophrenia who had been stabilized on clozapine were included in this study. Participants were randomized to either 1 gram/day sodium benzoate (n=20), 2 grams/day sodium benzoate (n=20), or placebo (n = 19) for 6 weeks.

The investigators assessed changes in Positive and Negative Syndrome Scale (PANSS) total score, Scale for the Assessment of Negative Symptoms (SANS), Quality of Life Scale, and Global Assessment of Functioning. The PANSS-positive score consisted of schizophrenia symptoms such as delusions, conceptual disorganization, hallucinations, excitement, grandiosity, suspiciousness/persecution, and hostility.

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Following the 6-week treatment regimen, both 1 gram and 2 gram sodium benzoate resulted in greater improvements in SANS scores compared with placebo (mean differences from baseline, 5.8±7.5 and 5.0±6.5 vs 1.7±2.8, respectively).

The 2-gram dose of sodium benzoate also resulted in greater improvements in quality of life scores (mean differences from baseline to week 6, 3.6±3.6 vs 1.1±2.5) and PANSS-total score (mean differences from baseline to week 6, 6.9±4.7 vs 3.6±3.2) than placebo.

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In addition, changes in the catalase antioxidant were associated with improvements in PANSS-total score and PANSS-positive score in patients allocated to sodium benzoate.

The study’s small sample size as well as the short duration of treatment potentially underpowered findings and precluded the investigators’ ability to determine long-term cognitive effects of treatment. Also, there is speculation as to whether these findings can be generalized to patients who are not of Chinese descent.

If the findings from this study can be replicated in larger, longitudinal cohorts, the investigators believe that the “approach of applying a D-Amino Acid Oxidase (DAAO) inhibitor will bring hope for the patients who are resistant to clozapine treatment.”


Lin CH, Lin CH, Chang YC, et al. Sodium benzoate, a D-amino acid oxidase inhibitor, added to clozapine for the treatment of schizophrenia: a randomized, double-blind, placebo-controlled trial [published online December 26, 2017]. Biol Psychiatry. doi:10.1016/j.biopsych.2017.12.006