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. 2025 Jun;34(6):1917-1929.
doi: 10.1007/s00787-024-02610-8. Epub 2024 Nov 11.

Stimulant medication and symptom interrelations in children, adolescents and adults with attention-deficit/hyperactivity disorder

Zarah van der Pal  1 , Hilde M Geurts  2 , Jonas M B Haslbeck  3   4 , Alex van Keeken  5 , Anne Marijn Bruijn  5 , Linda Douw  6 , Daan van Rooij  7 , Barbara Franke  8 , Jan Buitelaar  7 , Nanda Lambregts-Rommelse  7 , Catharina Hartman  9 , Jaap Oosterlaan  10 , Marjolein Luman  10 , Liesbeth Reneman  5 , Pieter J Hoekstra  11 , Tessa F Blanken #  3 , Anouk Schrantee #  5
Affiliations

Stimulant medication and symptom interrelations in children, adolescents and adults with attention-deficit/hyperactivity disorder

Zarah van der Pal et al. Eur Child Adolesc Psychiatry. 2025 Jun.

Abstract

Stimulant medication is effective in alleviating overall symptom severity of attention-deficit/hyperactivity disorder (ADHD), yet interindividual variability in treatment response and tolerability still exists. While network analysis has identified differences in ADHD symptom relations, the impact of stimulant medication remains unexplored. Increased understanding of this association could provide valuable insights for optimizing treatment approaches for individuals with ADHD. In this study, we compared and characterized ADHD symptom networks (including 18 ADHD symptoms) between stimulant-treated (n = 348) and untreated (n = 70) individuals with ADHD and non-ADHD controls (NACs; n = 444). Moreover, we compared symptom networks between subgroups defined by their stimulant treatment trajectory (early-and-intense use, late-and-moderate use). Stimulant-treated individuals with ADHD showed stronger associations between symptoms, compared with untreated individuals with ADHD and NACs. We found no differences in symptom networks between the stimulant treatment trajectory subgroups. Prospective longitudinal studies are needed to disentangle whether the identified differences stem from treatment or pre-existing factors.

Keywords: Attention-deficit/hyperactivity disorder; Psychopharmacology; Stimulant medication; Symptom networks.

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Conflict of interest statement

Declarations. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the medical ethical committees of the VU University Medical Centre and Radboud University Medical Centre (NL23894.091.08). Informed consent: We obtained written informed consent from all participants aged 12 years and older, and from parents for participants under 18, for participation in the NeuroIMAGE study and use of their de-identified data in analysis and publications. Competing interests: JB has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Takeda, Medice, Angelini, Boehringer-Ingelheim, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, and royalties. All other authors have no competing interest or industry support to report.

Figures

Fig. 1
Fig. 1
Symptom networks of stimulant-treated (ADHD-stim) and untreated (ADHD-nostim) individuals with attention-deficit/hyperactivity disorder (ADHD) and non-ADHD controls (NACs). (A) ADHD symptom network visualized for NACs. (B) ADHD symptom network visualized for ADHD-nostim participants. (C) ADHD symptom network visualized for ADHD-stim participants. (D) Difference in symptom networks of the ADHD-nostim group compared with the NAC and ADHD-stim groups, reflecting the moderation effects identified when comparing the NAC, ADHD-nostim, ADHD-stim networks. Edges represent the associations between symptoms while controlling for all other variables in the network and edge thickness represents correlation strength. In all three networks, all associations between symptoms were positive. All moderation effects were positive, indicating stronger associations between symptoms in the ADHD-stim network compared with the NAC and ADHD-nostim networks. The maximum edge weight was 0.29 for the NAC, ADHD-nostim and ADHD-stim networks, and 0.09 for the network of moderated edges
Fig. 2
Fig. 2
Local network properties of symptom networks in stimulant-treated (ADHD-stim) and untreated (ADHD-nostim) individuals with ADHD and non-ADHD controls (NACs). Standardized local network metrics (node strength and local clustering coefficients) describing local network properties, calculated from the NAC, ADHD-nostim and ADHD-stim networks. Note that the symptom networks and local network properties did not differ between the NAC and ADHD-nostim groups. The Pearson correlation coefficient between the local network properties of the ADHD-stim and NAC/ADHD-nostim groups was 0.88 for node strength and 0.93 for local clustering coefficients
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