Clozapine is the last-line antipsychotic agent for refractory schizophrenia. To date, there is no convincing evidence for augmentation on clozapine. Activation of NMDA receptors, including inhibition of D-amino acid oxidase (DAAO) that may metabolize D-amino acids, has been reported to be beneficial for patients receiving antipsychotics other than clozapine. This study aimed to examine the efficacy and safety of a DAAO inhibitor, sodium benzoate, for schizophrenia patients who had poor response to clozapine.
Methods
We conducted a randomized, double-blind, placebo-controlled trial. Sixty schizophrenia inpatients that had been stabilized with clozapine were allocated into three groups for six weeks add-on treatment of 1-g/d sodium benzoate, 2-g/d sodium benzoate, or placebo. The primary outcome measures were 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. Side-effect and cognitive functions were also measured.
Results
Both doses of sodium benzoate produced better improvement than placebo in SANS. 2-g/d sodium benzoate also produced better improvement than placebo in PANSS total score, PANSS-positive score, and QOL. Sodium benzoate was well tolerated without evident side-effects. The changes of catalase, an antioxidant, were different among the three groups and correlated with the improvement of PANSS total and PANSS-positive score in the sodium benzoate group.
Conclusion
Sodium benzoate adjuvant therapy improved symptomatology of patients with clozapine-resistant schizophrenia. Further studies are warranted to elucidate the optimal dose and treatment duration as well as the mechanisms of sodium benzoate for clozapine-resistant schizophrenia.
Key words:
N-methyl-D-aspartate, refractory schizophrenia, D-amino acids oxidase (DAAO) inhibitor, sodium benzoate, clinical trial, antioxidant
http://www.biologicalpsychiatryjournal.com/article/S0006-3223(17)32297-7/fulltext?rss=yes