Gosling, Corentin J., Garcia-Argibay, Miguel and De Prisco, Michele , (2025) Benefits and harms of ADHD interventions: umbrella review and platform for shared decision-making. The BMJ. (In Press)
Abstract
Objective: to assess the effects and evidence certainty for attention-deficit/hyperactivity disorder (ADHD) interventions across the lifespan, and to disseminate findings through a continuously updated web platform.
Design: umbrella review of systematic reviews with meta-analyses of randomised controlled trials (RCTs).
Data sources: six databases were searched through January 19, 2025. Study authors were contacted for unpublished data/information.
Eligibility criteria for selecting studies: systematic reviews with meta-analyses of RCTs were eligible if they evaluated pharmacological or non-pharmacological intervention against passive control in individuals diagnosed with ADHD using internationally recognised criteria. Co-primary outcomes were ADHD symptom severity (analysed by rater type and time-point), acceptability (all-cause dropouts), and tolerability (dropouts due to adverse events). Secondary outcomes included daily functioning, quality of life, comorbid symptoms, and key adverse events.
Data synthesis strategy: eligible meta-analyses were re-estimated with a standardised statistical approach. Their methodological quality was assessed using AMSTAR-2. Evidence certainty was evaluated using an algorithmic version of the GRADE framework adapted for pharmacological and non-pharmacological interventions.
Results: from 414 full-text articles, 115 were deemed eligible and 299 were excluded on the basis of the pre-specified criteria. Amongst eligible articles, which encompassed 221 unique comparisons (based on age, intervention type and outcome), the most recent and methodologically robust meta-analysis was selected for re-estimation for each comparison. This process yielded 221 re-estimated meta-analyses, exploring 31 interventions on 24 outcomes. In the short-term, alpha-2 agonists, amphetamines, atomoxetine, methylphenidate, and viloxazine showed medium-to-large effect sizes in reducing the severity of ADHD symptoms in children/adolescents, with moderate-to-high certainty evidence. With the exception of methylphenidate and atomoxetine, for which the effects did not reach statistical significance, these interventions exhibited reduced tolerability in comparison with the placebo. In adults, only atomoxetine, CBT, methylphenidate, and -when restricting analyses to high-quality trials- amphetamines, showed at least moderate-certainty evidence of efficacy on ADHD symptoms, with medium effect sizes. These interventions, except CBT, had worse tolerability than placebo. Some non-pharmacological interventions (acupuncture and CBT in children/adolescents, and mindfulness in adults) appeared to have large effect sizes for ADHD symptoms, but with low-certainty evidence. No high-certainty evidence in the longer-term was found. An online platform displaying effects and evidence certainty of each intervention across age groups, time-points, and outcomes (https://ebiadhd-database.org/).
Conclusions and relevance: this comprehensive synthesis, displayed in the online platform, provides updated evidence to inform service users, practitioners, and guideline developers. This should facilitate the implementation of shared decision-making in daily practice.
Study registration: https://osf.io/ugqy6/
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