Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, Added to Clozapine for the Treatment of Schizophrenia

A Randomized, Double-Blind, Placebo-Controlled Trial

Chieh Hsin Lin, Ching Hua Lin, Yue Cune Chang, Yu Jhen Huang, Po Wei Chen, Hui Ting Yang, Hsien Yuan Lane

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Clozapine is the last-line antipsychotic agent for refractory schizophrenia. To date, there is no convincing evidence for augmentation on clozapine. Activation of N-methyl-D-aspartate receptors, including inhibition of D-amino acid oxidase 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 D-amino acid oxidase 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 6 weeks’ add-on treatment of 1 g/day sodium benzoate, 2 g/day sodium benzoate, or placebo. The primary outcome measures were Positive and Negative Syndrome Scale (PANSS) total score, Scale for the Assessment of Negative Symptoms, Quality of Life Scale, and Global Assessment of Functioning. Side effects and cognitive functions were also measured. Results: Both doses of sodium benzoate produced better improvement than placebo in the Scale for the Assessment of Negative Symptoms. The 2 g/day sodium benzoate also produced better improvement than placebo in PANSS-total score, PANSS-positive score, and Quality of Life Scale. 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 score and PANSS-positive score in the sodium benzoate group. Conclusions: 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.

Original languageEnglish
Pages (from-to)422-432
Number of pages11
JournalBiological Psychiatry
Volume84
Issue number6
DOIs
Publication statusPublished - Sep 15 2018
Externally publishedYes

Fingerprint

D-Amino-Acid Oxidase
Sodium Benzoate
Clozapine
Schizophrenia
Placebos
Symptom Assessment
Therapeutics
Antipsychotic Agents
Quality of Life
N-Methyl-D-Aspartate Receptors
Catalase
Cognition
Inpatients
Antioxidants
Outcome Assessment (Health Care)

Keywords

  • Antioxidant
  • Clinical trial
  • D-amino acid oxidase (DAAO) inhibitor
  • N-methyl-D-aspartate
  • Refractory schizophrenia
  • Sodium benzoate

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, Added to Clozapine for the Treatment of Schizophrenia : A Randomized, Double-Blind, Placebo-Controlled Trial. / Lin, Chieh Hsin; Lin, Ching Hua; Chang, Yue Cune; Huang, Yu Jhen; Chen, Po Wei; Yang, Hui Ting; Lane, Hsien Yuan.

In: Biological Psychiatry, Vol. 84, No. 6, 15.09.2018, p. 422-432.

Research output: Contribution to journalArticle

Lin, Chieh Hsin ; Lin, Ching Hua ; Chang, Yue Cune ; Huang, Yu Jhen ; Chen, Po Wei ; Yang, Hui Ting ; Lane, Hsien Yuan. / Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, Added to Clozapine for the Treatment of Schizophrenia : A Randomized, Double-Blind, Placebo-Controlled Trial. In: Biological Psychiatry. 2018 ; Vol. 84, No. 6. pp. 422-432.
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