J Affect Disord

D-serine boost: New hope for patients with severe depression?

June 12, 2025

Though not superior to placebo in the overall patient sample, d-serine may offer meaningful adjunctive benefits for patients with severe major depressive disorder (MDD), particularly when combined with robust pharmacologic regimens. These findings support further investigation into glutamatergic modulation as a targeted strategy for treatment-resistant or severe depression subtypes.

Study details: This six-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of d-serine (2 g/day) as an adjunct to treatment-as-usual (TAU) in 44 inpatients with MDD. Primary and secondary outcomes included clinician- and self-rated depression, anxiety, and anhedonia scores.

Results: While both d-serine and placebo groups showed significant symptom reductions, no overall between-group differences were observed. However, subgroup analysis revealed that patients with severe MDD experienced significantly greater improvements in depressive symptoms with d-serine. These benefits were more pronounced in individuals receiving higher doses of TAU medications, with a trend toward improved anhedonia.

Source:

Sempach L, et al. (2025, May 26). J Affect Disord. Adjunctive d-serine treatment for major depressive disorder: A randomized clinical trial. https://pubmed.ncbi.nlm.nih.gov/40436209/