Sodium benzoate
Slows the breakdown of D-serine, which the NMDA receptor needs to work. Small trials in Taiwan were positive; larger company trials stopped without results.
At a glance
- Type
- Medicine: D-amino acid oxidase (DAAO) inhibitor
- Used for
- Tested as an add-on to antipsychotics, including clozapine
- Status
- In trials
- Evidence
- EarlyHow evidence is rated
- Administration
- By mouth, added to an antipsychotic. In the trials, for 6 to 8 weeks
- In Europe
- Company trials registered in Poland, Germany and the UK have published no results
Clinical summaryFor health professionals
- Inhibits D-amino acid oxidase, which degrades D-serine and D-alanine, co-agonists at the NMDA receptor (Lane 2013).
- Lane 2013 (Taiwan): 52 patients, 1 g a day for 6 weeks; PANSS total improved by 21%, with gains in processing speed and visual learning.
- Lin 2018 (Taiwan): 60 inpatients on clozapine, 1 or 2 g a day for 6 weeks; both doses improved negative symptoms; 2 g also improved PANSS total and positive symptoms.
- SyneuRx phase 2/3: adult trial (280 enrolled) and adolescent trial (60) terminated in 2023 'due to commercial strategy'; no results published.
- Meta-analysis of 5 DAAO-inhibitor trials, 530 patients: small benefit on symptoms and cognition (Chang 2025). Luvadaxistat, another DAAO inhibitor, failed in two phase 2 trials and was discontinued (Khin 2026).
What it is
Sodium benzoate blocks D-amino acid oxidase (DAAO), the enzyme that breaks down D-serine. D-serine helps glutamate activate the NMDA receptor, which is thought to work too weakly in schizophrenia. Blocking its breakdown should leave more D-serine to support the receptor.1 Sodium benzoate may also act as an antioxidant.2
How it works
The NMDA receptor works only when a second substance, D-serine or glycine, is bound to it alongside glutamate. Why a weak NMDA receptor may matter in schizophrenia is explained in Beyond dopamine (opens in a new tab). Sodium benzoate raises the supply of D-serine indirectly, by slowing its removal.1
How well it works
Most of the evidence comes from one research group in Taiwan. In their first trial, 52 people with long-standing schizophrenia took sodium benzoate or a placebo for six weeks; symptoms improved by about a fifth, and processing speed and visual learning improved too.1 In a second trial, 60 people in hospital whose symptoms persisted on clozapine took one of two doses or a placebo for six weeks. Both doses improved negative symptoms, and the higher dose also eased hallucinations and delusions.3
Larger trials by the company SyneuRx, including hospitals in Poland and the UK, were stopped in 2023 for commercial reasons, and their results have not been published.4
Pooled across five trials of DAAO blockers with 530 people, symptoms and thinking skills improved slightly.5 Another DAAO blocker, luvadaxistat, did not improve negative symptoms or thinking skills in two trials with sites in Bulgaria, Czechia, Serbia, Spain and the United States, and its development was stopped.6,7
Side effects
In the Taiwanese trials, sodium benzoate was well tolerated, without clear side effects.1
Alternatives
Other medicines aimed at the NMDA receptor include D-serine and sarcosine (opens in a new tab) and memantine (opens in a new tab). For treatment-resistant schizophrenia, clozapine (opens in a new tab) is the approved medicine.
What we don’t know yet
- Whether the results hold in larger trials outside Taiwan.
- What the stopped company trials found.
