Effect of probiotic supplement on improvement of depressive symptoms in patients with substance-induced depressive disorder: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND

Substance-Induced Depressive Disorder (SIDD) accounts for a high health burden and requires new therapies. Bidirectional communications between the gut and the brain mediated by the microbiota point to a possible influence of probiotics as a tool for preserving mental health.

MATERIALS AND

METHODS

Double-blind, placebo-controlled, randomized clinical trial on a sample of 40 patients with SIDD. Patients were then randomly assigned into probiotic and placebo arms and underwent interventions for four continuous weeks. The clinical assessment was done using BDI and HAM-A. Immunologic outcomes were measured through analysis of inflammatory markers, cytokines, and other immunological parameters. The trial was registered with ClinicalTrials.gov, under the identifier NCT06790823 (18/1/2025).

RESULTS

The change in the intensity of depression and anxiety in both probiotic and placebo groups was statistically significant after intervention. No differences were also noted between the two groups. Immunologic results showed a suggestive changes in IL6 and INFG levels in the probiotic group as compared with placebo, which may indicate possible immune-modulating effects.

CONCLUSION

In this randomized, double‑blind, placebo‑controlled pilot trial, both probiotic and placebo groups showed significant improvements in depressive and anxiety symptoms over time, with no significant between‑group differences. Probiotic supplementation was associated with non‑significant trends in selected inflammatory markers, suggesting possible immunological effects that warrant further investigation. Larger, multicenter trials with comprehensive microbiome and immunologic assessments are needed to clarify the potential role of probiotics as an adjunctive strategy in substance‑induced depressive disorder.