Food Preservative for Schizophrenia?
An overview of the first study to demonstrate benefits of sodium benzoate--an NMDA enhancer--in patients with clozapine-resistant schizophrenia.
RESEARCH UPDATE
Clozapine is currently the “gold standard” for treatment-resistant schizophrenia. However, many patients have persistent psychotic symptoms despite treatment with clozapine, and evidence for augmentation strategies in clozapine non-responders remains
Inhibition of the enzyme D-amino acid oxidase (DAAO) represents a new mechanism for enhancing NMDA signaling. Sodium benzoate, a commonly used food preservative, is a DAAO inhibitor with good CNS bioavailability. A
Study design
Subjects were randomized in a double-blind fashion to receive 6 weeks of adjunctive sodium benzoate (1g or 2g/day) or placebo in a 1:1:1 ratio. Efficacy and safety were evaluated at baseline and at weeks 2, 4, and 6. The primary outcome measures were PANSS total score, SANS, Quality of Life Scale (QOLS), and Global Assessment of Functioning (GAF) scores. Secondary outcome measures were PANSS subscales, the Hamilton Depression Rating Scale, and cognitive function. Changes in outcome measures were analyzed using a multiple linear regression model.
Findings
Eighty-three inpatients were screened, and 60 patients were randomized. A total of 59 subjects completed the 6-week trial. The mean subject age was 45; 68% were male; and the mean clozapine dose was 260 mg/day.
After 6 weeks of treatment, both dosages of sodium benzoate were associated with significant improvements in SANS scores compared to placebo (effect sizes of 0.72 and 0.65 for 1g and 2g/day, respectively). Sodium benzoate 2g/day was also associated with a significant improvement in PANSS total and positive scores and QOLS compared to placebo (effect sizes of 0.8 for each). There were no differences in GAF scores between subject groups. For other secondary outcomes, including depression and cognition, there were also no differences between subject groups.
There were no changes in extrapyramidal symptoms, routine laboratory studies, or ECG parameters with adjunctive sodium benzoate treatment. One patient in the sodium benzoate 2g/day group reported having difficulty concentrating, and 1 patient in the placebo group reported palpitations.
The bottom line
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