Efficacy of multimodal interventions for adult attention-deficit hyperactivity disorder: research plan for a systematic review and network meta-analysis

Introduction

Attention-deficit hyperactivity disorder (ADHD) in adulthood is a prevalent neurodevelopmental condition characterized by persistent inattention, impulsivity, and executive dysfunction, often accompanied by affective symptoms, emotion dysregulation, and impaired quality of life [1], [2]. Although pharmacological interventions were shown to be effective in reducing ADHD core symptoms, additional symptoms remain unchanged. A possible solution to this is multimodal therapy, combining pharmacological and psychotherapeutic interventions, however, the comparative efficacy remains unclear.

Aims

To compare the efficacy of pharmacological, psychotherapeutic, and multimodal interventions for adults with attention-deficit hyperactivity disorder across core symptoms, affective symptoms, emotion dysregulation, and quality of life.

Methods

This systematic review and network meta-analysis is being conducted according to PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD420251232986). Embase, CENTRAL, and the Cochrane Library were searched from inception to 8 December 2025. The Population, Intervention, Comparator, Outcome framework. The population comprised adults with ADHD. Eligible interventions included approved pharmacological treatments, psychotherapeutic interventions, and combined pharmacological–psychotherapeutic interventions, compared with placebo, waitlist, treatment as usual, or another active eligible intervention. Outcomes included core attention-deficit hyperactivity disorder symptoms, affective symptoms, emotion dysregulation, and quality of life. Titles and abstracts were screened independently by six reviewers, followed by full-text assessment. Disagreements were resolved by consensus or by a third reviewer. Forward and backward citation chasing is ongoing. Where sufficient data are available, random-effects pairwise and network meta-analyses will be conducted using a frequentist framework. Effect sizes will be expressed as mean differences or standardised mean differences with 95% confidence intervals. Heterogeneity, inconsistency, network geometry, and treatment ranking will be assessed where appropriate.

Results

Title and abstract screening has been completed, while full-text assessment, citation chasing, data extraction, and quantitative synthesis are ongoing. Several methodological challenges have been identified during screening and protocol implementation. Intervention categories are heterogeneous, including pharmacological treatments, psychotherapy, psychoeducation, cognitive behavioural approaches, coaching, and multimodal combinations. Outcome reporting also varies substantially across studies, with differences in scales, time points, and definitions of core symptoms, affective symptoms, emotion dysregulation, and quality of life. Comparator groups differ across trials, including placebo, treatment as usual, waitlist, and active interventions, which may affect network connectivity and transitivity assumptions. These challenges will inform the final synthesis strategy, including the feasibility of network meta-analysis versus pairwise meta-analysis for specific outcomes.

Conclusions

This ongoing review will provide a comprehensive comparison of pharmacological, psychotherapeutic, and multimodal interventions for adult attention-deficit hyperactivity disorder. The findings may help clarify whether combined treatment approaches provide additional benefit beyond monotherapy across core symptom, emotional, and quality-of-life outcomes. Final conclusions will depend on the availability, quality, and consistency of the included evidence. This review and meta-analysis will provide a comprehensive comparative evaluation of pharmacological and psychotherapeutic treatments for adult attention-deficit hyperactivity disorder across multiple clinically meaningful outcomes and subnetworks. It is anticipated that both treatment modalities will demonstrate efficacy, with multimodal approaches potentially offering enhanced benefits. Final conclusions will be drawn following completion of the data analysis, and interpretations will be presented cautiously, taking into account the quality and consistency of the available evidence.

References

1. Ayano, G., Tsegay, L., Gizachew, Y., Necho, M., Yohannes, K., Abraha, M., … Alati, R. (2023). Prevalence of attention deficit hyperactivity disorder in adults: Umbrella review of evidence generated across the globe. Psychiatry Research, 328, Article 115449. https://doi.org/10.1016/j.psychres.2023.115449
2. Katzman, M. A., Bilkey, T. S., Chokka, P. R., Fallu, A., & Klassen, L. J. (2017). Adult ADHD and comorbid disorders: Clinical implications of a dimensional approach. BMC Psychiatry, 17(1), 302. https://doi.org/10.1186/s12888-017-1463-3