The Effect of Methylphenidate Treatment on Oxidative Stress Levels in Children Diagnosed with Attention-Deficit/Hyperactivity Disorder: An Observational Study

Abstract

Background:

Oxidative stress (OS) has been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), yet findings—particularly regarding treatment-related changes—remain inconsistent. This study evaluated short-term differences in circulating oxidant/antioxidant markers after methylphenidate (MPH) treatment and explored whether baseline biomarkers predict clinically significant symptom improvement.

Methods:

In this single-center, prospective observational cohort study, medication-naïve children aged 6–11 years diagnosed with DSM-5-TR ADHD were assessed at enrollment and after 3 months of conventional MPH treatment. Clinical severity was measured using the Conners’ Parent Rating Scale–Revised: Short Form (CPRS-R:S) and Conners’ Teacher Rating Scale–Revised: Short Form (CTRS-R:S). Serum biomarkers included total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), malondialdehyde (MDA), oxidized LDL (Ox-LDL), and the OS index (OSI = TOS/TAS). Changes were tested with paired analyses; correlations were examined between percent changes in scale scores and biomarkers; and ROC analyses evaluated baseline biomarkers’ ability to identify a >50% reduction in CPRS-R:S and CTRS-R:S total scores.

Results:

Thirty-nine participants completed both assessments (SOD analyses: n = 37). Significant reductions were observed in CPRS-R:S and CTRS-R:S total and subscale scores (all p < .001). TOS, TAS, SOD, MDA, and Ox-LDL decreased significantly over 3 months, while OSI showed a nonsignificant downward trend (p = 0.066). No significant correlations emerged between percent symptom change and percent biomarker change. In ROC analyses, baseline MDA, Ox-LDL, and TOS significantly discriminated >50% CPRS-R:S improvement (AUC ≈ 0.71–0.74), whereas for >50% CTRS-R:S improvement, several biomarkers demonstrated good discrimination (AUC ≈ 0.82–0.85).

Conclusions:

Three months of MPH treatment was associated with robust clinical improvement and parallel reductions in multiple oxidant and antioxidant biomarkers. Baseline OS markers may help identify children most likely to show marked symptom reduction, though findings should be interpreted cautiously, given the sample size.