Abstract
Background: The treatment of refractory schizophrenia is a great challenge. Clozapine is the only approved antipsychotics for refractory schizophrenia; however, its efficacy is unsatisfactory. Enhancing N-methyl-D-aspartate receptor (NMDAR) activation, including inhibition of D-amino acid oxidase (DAAO), has been reported to improve the clinical symptoms and cognitive function of patients with schizophrenia. This study examined the efficacy and safety of a DAAO inhibitor, sodium benzoate, for the treatment of refractory schizophrenia.
Methods: We conducted a randomized, double-blind, placebo-controlled trial in four major centers in Taiwan. Sixty patients with refractory schizophrenia treated with clozapine were randomly allocated to sodium benzoate 1-g/d, sodium benzoate 2-g/d or placebo for a 6-weeks add-on therapy. The primary outcome measures including Positive and Negative Syndrome Scale (PANSS) total score, Scales for the Assessment of Negative symptoms (SANS), Quality of Life Scale (QOL) and Global Assessment of Function were assessed every two weeks.
Results: Both sodium benzoate 1-g/d and 2-g/d produced better improvement than placebo in SANS (p = 0.024 and 0.027 at endpoint, respectively). Sodium benzoate 2-g/d also produced better improvement than placebo in PANSS total score and QOL (p = 0.005 and 0.008 at endpoint, respectively). However, sodium benzoate 2-g/d was not significantly better than 1-g/d in all primary and secondary outcome measures. Sodium benzoate was well tolerated without evident side-effects.
Conclusions: Sodium benzoate adjuvant therapy significantly improved the negative symptoms of patients with refractory schizophrenia. The differences in efficacy domains between the two dose groups were insignificant.
Key words: N-methyl-D-aspartate, refractory schizophrenia, D-amino acids oxidase (DAAO) inhibitor, sodium benzoate, clinical trial