Sodium benzoate treatment linked to increased glutathione levels and improved positive and negative symptoms, global function, and quality of life in patients with clozapine-resistant schizophrenia: secondary analysis of a randomized clinical trial.

Oxidative stress is implicated in schizophrenia. Glutathione (GSH), a crucial endogenous antioxidant, is usually reduced in individuals with schizophrenia. GSH and its precursor, N-acetyl cysteine, have demonstrated potential as adjunctive treatment for schizophrenia; however, their effectiveness appears inconsistent, possibly because of their limited ability to penetrate the blood-brain barrier (BBB). Administration of sodium benzoate, capable of crossing BBB, enhanced GSH capacity and antipsychotic-like activity in animals. Further, adjunctive benzoate therapy improved clinical and functional outcomes in patients with schizophrenia, including clozapine-resistant schizophrenia (CRS). Whether sodium benzoate can also boost GSH to exert its therapeutic efficacy for schizophrenia deserves elucidation. This secondary analysis used data from a double-blind trial, in which 60 patients with CRS were randomized to receive addon treatment of sodium benzoate (n = 40) or placebo (n = 20) for 6 weeks. Clinical and functional assessments were conducted bi-weekly. Plasma levels of GSH were assayed at baseline and endpoint. As a result, six-week treatment of sodium benzoate was linked to increased GSH levels than placebo. Among the 40 benzoate receivers, the changes in GSH levels were correlated with the improvements in positive symptoms, negative symptoms, quality of life, and global function. In comparison, among placebo recipients, GSH changes were not associated with any changes in clinical or functional variables. The findings suggest that benzoate treatment may be related with elevation in GSH levels in CRS patients and improvement in functional outcomes as well as positive and negative symptoms. Longer-term studies in other populations are necessary in the future.