A randomized, double-blind eight-week trial depicted that sertraline (a selective serotonin reuptake inhibitor) can decrease subjective depressive symptoms, while benzoate (D-amino acid oxidase inhibitor and an indirect N-methyl-D-aspartate receptor enhancer) can reduce perceived stress, and improve cognitive function and treatment adherence in people with late-life depression.

Researchers undertook this study for comparing the safety and efficacy of sodium benzoate (250-1500 mg/day), sertraline (25-150 mg/day), and placebo in 117 people with major depressive disorder. Participants (aged 55 years or above) were randomized (39 participants in each group) to get sodium benzoate, sertraline, and placebo. Estimation of clinical improvement via Perceived Stress Scale (PSS) scores and Hamilton Depression Rating Scale (HAMD) was the major endpoint ascertained.

All three therapies led to a similar reduction in clinicians-rated HAMD scores. In comparison with placebo, sodium benzoate but not sertraline led to remarkable improvements in cognitive function and PSS scores. Notably, sertraline, but not benzoate, resulted in a substantial drop in the self-report Geriatric Depression Scale (GDS) scores. Placebo and benzoate displayed equivalent safety profiles, while sertraline was more likely to increase low-density lipoprotein when compared to placebo and benzoate.

Benzoate seemed to be safer than sertraline. When compared to sertraline- or placebo-recipients, benzoate-treated people were less likely to drop out. The findings thus illustrated the promising potential of D-amino acid oxidase inhibition as a new approach to reduce perceived stress and improve cognitive dysfunction in people affected with late-life depression.