Add-On Preservative May Improve Outcomes in Refractory Schizophrenia Interview with:

Hsien-Yuan Lane

Dr. Hsien-Yuan Lane

Hsien-Yuan Lane, MD,PhD
Distinguished Professor, Director, Graduate Institute of Biomedical Sciences
China Medical University, Taichung, Taiwan
Director, Brain Diseases Research Center (BDRC), Addiction Research Center, and Department of Psychiatry,
China Medical University and Hospital, Taichung, Taiwan
PI, Taiwan Clinical Trial Consortium for Mental Disorders What is the background for this study? What are the main findings?

Response: Schizophrenia is a chronic and severe mental illness affecting more than 21 million people worldwide. Clozapine has been regarded as the last-line antipsychotic agent for patients with refractory schizophrenia. However, an estimated 40–70% of patients with refractory schizophrenia fail to improve even with clozapine , referred to as “clozapine-resistant”. To date, there is no convincing evidence for augmentation on clozapine.

Activation of N-methyl-D-aspartate (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.

Sodium benzoate is a DAAO inhibitor. A recent randomized, double-blind, placebo-controlled clinical trial found that add-on sodium benzoate improved the clinical symptoms in patients with clozapine-resistant schizophrenia, possibly through DAAO inhibition and antioxidation as well. What should clinicians and patients take away from your report?

Response: The study is the first to demonstrate that sodium benzoate—which has been shown to enhance other antipsychotic drugs—can also help clozapine-resistant patients.

Importantly, benzoate had no side effects among the patients in the study, indicating the treatment is safe at the doses of 1 and 2 g per day for 6 weeks. What recommendations do you have for future research as a result of this study?

Response: More studies are warranted to elucidate the mechanisms of sodium benzoate for the treatment of schizophrenia and thereby the etiology of this severe brain disease. Is there anything else you would like to add?

Response: If the finding can be reconfirmed, this approach may bring new hope for the treatment of the most refractory schizophrenia.

No disclosures Thank you for your contribution to the community.


Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, Added to Clozapine for the Treatment of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Trial

Chieh-HsinLin Yue-CuneChang Yu-JhenHuang Po-WeiCheng Hui-TingYang Hsien-Yuan Lane
Biological Psychiatry Available online 26 December 2017

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.


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Last Updated on February 5, 2018 by Marie Benz MD FAAD