A New Treatment Approach for Schizophrenia

Steven Dubovsky, MD

A commonly used food preservative is put to an early test.

Antipsychotic drugs can improve psychosis, but they do not have an impressive impact on the cognitive and negative dimensions of schizophrenia. With data accumulating on reduced signaling of the N-methyl-D-aspartate receptor (NMDAR) in schizophrenia, investigators in Taiwan conducted a 6-week, placebo-controlled study of sodium benzoate, a food preservative that inhibits the enzyme D-amino acid oxidase (DAAO). Because DAAO metabolizes the NMDA co-agonist D-serine, sodium benzoate facilitates NMDA activity. One author has commercial interests in the treatment.

Sodium benzoate (1 g/day) or placebo was given to 52 participants with schizophrenia, who were on stable doses of antipsychotic drugs (mostly haloperidol and risperidone); 47 patients completed the trial. Add-on benzoate was superior to placebo at 6 weeks in decreasing total scores on the primary outcome measure, the Positive and Negative Syndrome Scale (PANSS), by 21%, with a large effect size (1.53). Negative symptoms, global assessment, and quality of life also improved more with benzoate, with large effect sizes (1.56, 1.20–1.21, and 1.50, respectively). Depression, speed of cognitive processing, and visual learning and memory also improved significantly more with benzoate than with placebo, with medium-to-large effect sizes (0.74, 0.65, and 0.70, respectively).

Citation(s):

Lane H-Y et al. Add-on treatment of benzoate for schizophrenia: A randomized, double-blind, placebo-controlled trial of D-amino acid oxidase inhibitor. JAMA Psychiatry 2013 Oct 2; [e-pub ahead of print].