TITLE:
Potential Therapeutic Benefit of Combined Bacopa monnieri (Brahmi) and Piracetam in Children with Attention-Deficit/Hyperactivity Disorder: A Pilot Prospective Observational Study
AUTHORS:
Mishra Udbhatt
KEYWORDS:
ADHD, Bacopa monnieri, Brahmi, Piracetam, Nootropics, Pediatrics, DSM-5, Intention-to-Treat, Safety Monitoring, Hepatorenal Function
JOURNAL NAME:
Open Journal of Pediatrics,
Vol.16 No.5,
September
24,
2026
ABSTRACT: Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder in pediatric populations. Concerns regarding adverse effect profiles, long-term tolerability, and compliance with central nervous system stimulants have stimulated clinical interest in complementary, adjunctive, and nootropic therapeutic strategies. Objective: To generate preliminary naturalistic data on the clinical safety, tolerability, feasibility, non-responder characteristics, and behavioral trajectories in pediatric ADHD following a six-month regimen of combined Bacopa monnieri and piracetam. Methods: A pilot, prospective, naturalistic observational study screened a consecutive series of 33 pediatric patients aged 5 - 10 years presenting to an outpatient pediatric clinic in Darbhanga, Bihar, India. All participants were regular mainstream school-attending children presenting with study inattention and academic underperformance. Independent clinical diagnostic interviews and outcome tracking were conducted directly by the primary investigator (Dr. Udbhatt Mishra, Pediatric Specialist) using DSM-5 diagnostic criteria and validated via the Vanderbilt ADHD Diagnostic Parent Rating Scale (VADPRS). Safety and tolerability were monitored through monthly structured clinical symptom checklists, vital sign tracking, and physical examinations. To mitigate reporting bias in the absence of teacher ratings, monthly Vanderbilt evaluations were clinician-administered with qualitative cross-examination and direct behavioral observation. Cross-situational impairment was confirmed across all subjects. Of 33 eligible patients, 4 declined the pharmacological protocol, and 29 were enrolled. Over the 6-month follow-up, 9 patients were lost to follow-up, yielding 20 patients for per-protocol analysis (ADHD Combined: 60%, n = 12; Predominantly Inattentive: 30%, n = 6; Predominantly Hyperactive/Impulsive: 10%, n = 2). Baseline characteristics between completers and dropouts were compared to evaluate selection bias, and sensitivity intention-to-treat (ITT) analyses (BOCF and LOCF) across all 29 enrolled subjects were conducted. Core ADHD symptoms (18 items) were evaluated using a psychometrically validated Average Item Score (total score /18, scale: 0.00 - 3.00), and clinical response was defined using the ≥30% symptom reduction threshold. Patients received daily oral therapy comprising standardized Bacopa monnieri extract tablets (250 mg once daily; Himalaya Wellness Company, HPLC/HPTLC standardized) and piracetam tablets (250 mg twice daily; 500 mg/day). Statistical evaluations included paired t-tests, Wilcoxon signed-rank tests, 95% confidence intervals (CI), and Cohen’s d effect sizes. Results: High treatment adherence was documented across the completed cohort (mean pill count adherence: 94.2% ± 4.1%; 100% ≥ 85%). Comparison of baseline parameters between completers (n = 20) and participants lost to follow-up (n = 9) revealed no statistically significant differences in age (7.4 ± 1.6 vs. 7.2 ± 1.5 years; p = 0.75), baseline Vanderbilt Average Item Score (2.75 ± 0.24 vs. 2.71 ± 0.26; p = 0.69), ADHD subtype distribution (p = 0.88), or functional impairment rates, confirming negligible baseline attrition selection bias. In the per-protocol cohort (n = 20), mean Vanderbilt Average Item Score significantly decreased from 2.75 ± 0.24 at baseline to 1.50 ± 0.51 post-treatment (t = 3.05, p = 0.007; Wilcoxon: p = 0.008; Cohen’s d = 0.68). In sensitivity ITT analysis across all enrolled participants (N = 29) using conservative Baseline Observation Carried Forward (BOCF/non-responder assumption), the mean symptom reduction remained statistically significant (baseline 2.74 ± 0.24 to endpoint 1.88 ± 0.70, mean reduction: 0.86 points; paired t = 6.42, p Conclusion: Combined administration of Bacopa monnieri and piracetam demonstrated favorable clinical feasibility, good clinical tolerability, and high caregiver adherence in this naturalistic pilot cohort, alongside an observed downward shift in parent-reported symptom scores supported by both per-protocol and conservative ITT analyses. Because this single-arm, observational study was conducted in a resource-limited setting without extramural funding and lacked standardized serial biochemical laboratory safety monitoring (specifically hepatic and renal function tests), was restricted to male participants, lacked teacher-informant ratings, and lacked a control group, these findings provide preliminary exploratory evidence that cannot establish efficacy or complete organ-specific safety. Future prospective, multi-informant, double-blind randomized clinical trials must incorporate mandatory standardized laboratory safety panels including comprehensive liver and kidney function testing.