Add-On D-Serine Shows Promise in Severe Depression

TOPLINE:

D-serine as an adjunctive treatment did not outperform placebo overall in patients with major depressive disorder (MDD), a new trial showed. However, depressive symptoms and anhedonia were significantly alleviated among patients with severe MDD, particularly among those on higher doses of standard medications.

METHODOLOGY:

• Researchers conducted a 6-week, randomised, double-blind, placebo-controlled trial including 44 adult inpatients (mean age, 43.55 years; 45% women) diagnosed with moderate to severe MDD from Basel, Switzerland.
• Participants were randomly assigned in a 1:1 ratio to receive either D-serine (2 g/d) or placebo alongside standard treatment.
• The primary outcome was the change in clinician-rated depressive symptoms from baseline to post-intervention, measured using the 17-item Hamilton Depression Rating Scale.
• Secondary outcomes were self-reported depressive symptoms, anxiety, and anhedonia, measured using the Beck Depression Inventory-II, State-Trait Anxiety Inventory-1, and Snaith-Hamilton Pleasure Scale, respectively.

TAKEAWAY:

• Both D-serine and placebo groups showed a significant reduction in symptoms across all measures, with no significant differences observed in the overall sample.
• In the subgroup analysis, D-serine significantly alleviated depressive symptoms in participants with severe MDD (P = .02), with a trend towards reduction in anhedonia.
• In the D-serine group, clinical improvements were correlated with higher baseline depression severity and higher doses of standard medication.
• No serious adverse events were reported.

IN PRACTICE:

“DS [D-serine] may offer therapeutic benefits for patients with severe MDD, particularly when used alongside greater doses of TAU [treatment as usual] medication. These findings support the potential of DS as a synergistic adjunctive strategy to enhance the therapeutic effect of pharmacological interventions, especially in severe cases,” the authors wrote.

SOURCE:

This study was led by Lukas Sempach, University of Basel, Basel, Switzerland. It was published online on May 26 in the Journal of Affective Disorders.

LIMITATIONS:

The small sample size limited the study’s generalisability and reduced its power to detect small to moderate treatment effects, particularly in patients with severe depression. Additionally, the relatively low dose of D-serine used, along with its metabolism, may have limited its engagement with N-methyl-D-aspartate receptors.

DISCLOSURES:

This study was supported by the Gertrud Thalmann Foundation of the University Psychiatric Clinics Basel and the Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowie der medizinischen Bildauswertung. The authors reported having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.