Psychiatry · Medical Literature
Probiotic Supplementation in Children and Adolescents with ADHD: A Systematic Review and Meta-Analysis of ADHD-Related and Emotional-Behavioral Outcomes.
Abstract
Dysregulation of the microbiota-gut-brain axis has been implicated in attention-deficit/hyperactivity disorder (ADHD), but randomized controlled trial evidence for probiotic supplementation remains inconsistent. This systematic review and meta-analysis evaluated the effects of probiotic supplementation on ADHD-related clinical outcomes and emotional-behavioral outcomes in children and adolescents. PubMed, Embase, Cochrane CENTRAL, Web of Science, PsycINFO, and EBSCO were searched from database inception to October 2025. Randomized controlled trials including participants under 18 years of age with DSM-defined ADHD were eligible. Pooled effects were calculated using standardized mean differences (SMDs) or mean differences (MDs) with 95% confidence intervals (CIs) under random-effects models. Nine RCTs involving 482 participants were included, with intervention durations ranging from 8 to 12 weeks. In the broad exploratory synthesis of ADHD-related clinical outcomes, probiotic supplementation did not show a clear benefit (SMD = -0.25, 95% CI: -0.57 to 0.07; p = 0.131). Because this analysis combined conceptually heterogeneous instruments, greater interpretive weight was placed on domain-specific analyses. No clear effects were observed for more specific core symptom-related measures, including SNAP-IV inattention scores and CPT-derived attention-related performance measures. In domain-specific exploratory analyses, CPRS total scores showed a small reduction following probiotic supplementation (SMD = -0.33, 95% CI: -0.65 to -0.01; p = 0.041), whereas CBCL total scores did not show a statistically significant effect under the random-effects model (MD = -1.93, 95% CI: -6.30 to 2.44; p = 0.386). The SNAP-IV hyperactivity finding was statistically significant but was largely driven by a single study and should be interpreted cautiously. Current 8-12-week RCT evidence does not demonstrate a clear benefit of probiotic supplementation for ADHD core symptom-related measures. However, exploratory findings suggest that probiotic supplementation may have potential for improving broad parent-reported emotional-behavioral outcomes, particularly CPRS-assessed behavioral symptoms. This potential benefit should be interpreted cautiously because it was based on a small number of heterogeneous trials and was not consistently supported by CBCL outcomes. Larger, rigorously designed trials are needed to confirm these broad parent-reported behavioral and emotional findings and clarify their clinical relevance.
Clinical relevance
Dysregulation of the microbiota-gut-brain axis has been increasingly implicated in ADHD pathophysiology, yet randomized controlled trial evidence for probiotic supplementation in pediatric ADHD remains inconsistent and undersynthesize. This meta-analysis addresses a clinically meaningful gap by pooling available RCT data in children and adolescents with DSM-defined ADHD, a population for whom non-pharmacological adjunct strategies are highly sought by families and clinicians alike. Given rising interest in gut-brain interventions and the limitations of current pharmacotherapy, clarifying the evidentiary status of probiotics is of immediate practical relevance to child and adolescent psychiatrists.
Key findings
1. Broad ADHD-related clinical outcomes (exploratory synthesis, 9 RCTs, n=482, intervention duration 8–12 weeks): probiotic supplementation showed no statistically significant benefit (SMD = -0.25, 95% CI: -0.57 to 0.07; p = 0.131); this analysis was limited by conceptual heterogeneity of instruments. 2. Domain-specific core symptom measures: no clear effect was observed for SNAP-IV inattention scores or CPT-derived attention-related performance measures following probiotic supplementation. 3. CPRS total scores (domain-specific exploratory analysis): a small but statistically significant reduction was observed with probiotic supplementation (SMD = -0.33, 95% CI: -0.65 to -0.01; p = 0.041), suggesting a modest potential benefit on broad parent-reported behavioral symptoms. 4. CBCL total scores: no statistically significant effect was demonstrated under the random-effects model (MD = -1.93, 95% CI: -6.30 to 2.44; p = 0.386), failing to corroborate the CPRS signal. 5. SNAP-IV hyperactivity subscale: a statistically significant finding was noted, but it was largely driven by a single study and was explicitly flagged by the authors as requiring cautious interpretation. 6. Overall evidence base limitations: only 9 RCTs with 482 total participants were eligible, all with short intervention durations (8–12 weeks), and heterogeneity across outcome instruments precluded definitive conclusions.
Practice implications
Clinicians should not recommend probiotic supplementation as a treatment for ADHD core symptoms (inattention, hyperactivity) in children and adolescents, as current 8–12-week RCT evidence does not demonstrate a clear benefit on these outcomes. The exploratory signal on CPRS-assessed broad behavioral and emotional outcomes is hypothesis-generating rather than practice-changing, and should not be used to justify routine adjunctive probiotic use given the small number of heterogeneous trials and lack of corroboration by CBCL data. When families inquire about gut-brain or nutraceutical interventions, clinicians should counsel that larger, rigorously designed trials with longer follow-up and standardized outcome measures are needed before any evidence-based recommendation can be made.