NMDA Modulation in Major Depressive Disorder in Late- Life

Summary

Major depressive disorder (MDD) is a complex and multi-factorial disorder. Most of the current antidepressants are based upon the monoamine hypothesis which cannot fully explain the etiology of depression. Many elderly patients have significant side effects after treatment with antidepressants which hamper the motivation for treatment and medication adherence. NMDA hypofunction has been implicated in the pathophysiology of depression. MDD in the elderly is often associated with cognitive deficits which are not necessarily recovered by current antidepressants. The NMDA receptor regulates synaptic plasticity, memory, and cognition. In our previous studies, cognitive improvement has been observed with treatment of NMDA enhancers. Therefore, this study will examine the efficacy and safety as well as cognitive function improvement of NMDAE in the treatment of MDD in the elderly by comparing with sertraline (a selective serotonin reuptake inhibitor \[SSRI\]) and placebo. The investigator will enroll elderly patients with MDD for an 8-week treatment. All patients will be randomly assigned into three groups: NMDAE, sertraline, or placebo. The investigator will biweekly measure clinical performances. Cognitive functions will be assessed at baseline and at endpoint of treatment by a battery of tests. The investigator hypothesize that NMDAE can safely yield better efficacy than placebo and sertraline for elderly patients with MDD.

Timeline

Start

2016-01

Primary completion

2020-11

Completion

2020-11

Outcome

Mixed primary results

paper The primary outcome measures were Hamilton Depression Rating Scale and Perceived Stress Scale scores. PMID 35023557 ↗

paper Three treatments similarly decreased clinicians-rated Hamilton Depression Rating Scale scores. PMID 35023557 ↗

paper Compared with placebo, sodium benzoate but not sertraline substantially improved Perceived Stress Scale scores and cognitive function. PMID 35023557 ↗

Publications

• Lin CH, Wang SH, Lane HY. 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. Int J Neuropsychopharmacol. 2022 Aug 4;25(7):545-555. doi: 10.1093/ijnp/pyac006.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Sertraline	Small molecule	25 mg	—
Comparator	Sertraline	Small molecule	150 mg	—
Subject	Sodium Benzoate	Small molecule	250 mg	—
Subject	Sodium Benzoate	Small molecule	1500 mg	—

Indications