Adjunctive Probiotic Therapy in Major Depressive Disorder: A Randomized Controlled Trial (ProMOOD)

Adjunctive Probiotic Therapy in Major Depressive Disorder: A Randomized Controlled Trial (ProMOOD)

A double-blind, randomized controlled trial (RCT) aimed at evaluating the efficacy of probiotic supplementation in patients undergoing concurrent antidepressant therapy.

The study will also assess gut microbiome composition and function, and correlate microbiome changes with clinical and psychological outcomes.

Participants will be evaluated by a psychiatrist/clinician, alongside standardized psychological assessments at:

• Baseline (inclusion)
• Week 4
• Week 12

The following validated instruments will be used:

• HAM-D - Hamilton Depression Rating Scale (clinician-rated depression severity)
• BDI - Beck Depression Inventory (self-reported severity of depression)
• PSS - Perceived Stress Scale (self-reported stress perception)

Inclusion Criteria

• Age 18-65 years
• Confirmed diagnosis of depression according to ICD 11 (International Classification of Diseases) criteria
• Written informed consent
• Stable antidepressant therapy (same medication for at least 6 weeks to ensure stable clinical response)

Exclusion Criteria

• Acute suicidality
• Severe cardiovascular disease
• Pregnancy or breastfeeding
• Substance/ alcohol abuse
• Severe neurological or systemic disease
• Recent antibiotic use
• Probiotic use in past year
• Treatment resistant depression
• Psychotic depression

Sample Size

• Initial recruitment target: 150-200 participants
• Expected dropout rate: approximately 50%, based on similar studies
• Final expected sample size: ~100 participants
• Sample size calculation based on Nikolova et al., 2023.

Primary outcome Change in Hamilton Depression Rating Scale (HAM-D-17) score from baseline to Week 12.

Secondary outcomes Change in Beck Depression Inventory-II (BDI-II) score from baseline to Week 12. Change in Perceived Stress Scale (PSS-10) score from baseline to Week 12. Changes in gut microbiome composition and diversity (α-diversity, β-diversity and relative abundance of bacterial taxa) between baseline and Week 12.

Safety and tolerability of probiotic supplementation, assessed by adverse events and treatment discontinuation.

Intervention:

OmniBiotic Stress Repair

Microbiome Analysis Subgroup

Stool samples will be collected at:

• Baseline
• 1 month
• 3 months Analysis will follow methodologies similar to Mörkl S et al. (2025).

Remark: Additional sampling at 1 week (as done in the referenced study) is considered unnecessary, as it falls outside routine clinical monitoring.

Antidepressant Strategy

• Include patients receiving SSRI (Selective Serotonin Reuptake Inhibitors) and possibly SNRI (Serotonin-Norepinephrine Reuptake Inhibitors)
• Advantage: broader applicability
• Limitation: increased variability

Inclusion Criteria:

- Age 18-65 years

• Confirmed diagnosis of depression according to ICD 11 (International Classification of Diseases) criteria
• Written informed consent
• Stable antidepressant therapy (same medication for at least 6 weeks to ensure stable clinical response)

Exclusion Criteria:

• - Acute suicidality
• Severe cardiovascular disease
• Pregnancy or breastfeeding
• Substance/ alcohol abuse
• Severe neurological or systemic disease
• Recent antibiotic use
• Probiotic use in past year
• Treatment resistant depression
• Psychotic depression