Effects of Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, on Perceived Stress and Cognitive Function Among Patients With Late-Life Depression: A Randomized, Double-Blind, Sertraline- and Placebo-Controlled Trial.

Compared to general adults with depression, elderly depressive patients are prone to poor treatment response, more side effects, and early withdrawal with current antidepressants (which principally modulate monoamines). Whether N-methyl-D-aspartate receptor (NMDAR) enhancement can benefit treatment of late-life depression deserves study. This study aims to compare sodium benzoate (a D-amino acid oxidase [DAAO] inhibitor and an indirect NMDAR enhancer), sertraline (a selective serotonin reuptake inhibitor), and placebo in the treatment of late-life depression. In this randomized, double-blind trial, 117 patients with major depressive disorder aged 55 years or older received 8-week treatment of 250-1500 mg/day of sodium benzoate, 25-150 mg/day of sertraline, or placebo in two medical centers. The primary outcome measures were Hamilton Depression Rating Scale (HAMD) and Perceived Stress Scale (PSS) scores. Three treatments similarly decreased clinicians-rated HAMD scores. Compared to placebo, sodium benzoate but not sertraline substantially improved PSS scores and cognitive function. Sertraline, but not benzoate, significantly reduced self-report Geriatric Depression Scale (GDS) scores. Benzoate and placebo showed similar safety profiles, while sertraline was more likely to raise low-density lipoprotein than benzoate and placebo. Benzoate-treated patients were less likely to drop out than sertraline- or placebo-recipients. Sertraline can reduce subjective depressive symptoms, while benzoate can decrease perceived stress, improve cognitive function, and enhance treatment adherence in late-life depression patients. The results show promise for DAAO inhibition as a novel approach for perceived stress and cognitive decline among patients with late-life depression.