IMPORTANCE: Attention-deficit/hyperactivity disorder (ADHD) is associated with adverse life outcomes and increased mortality. Clarifying the magnitude of mortality risks using international data and the potential association between medication and mortality is essential to inform clinical care and motivate public health strategies to address mortality.
OBJECTIVES: To examine the association between ADHD and all-cause and cause-specific mortality and to assess whether mortality risk differs according to ADHD medication use.
DATA SOURCES: A comprehensive search of PubMed, Web of Science, PsycINFO, EMBASE, MEDLINE, and CINAHL was conducted from database inception to July 8, 2025.
STUDY SELECTION: Eligible studies included quantitative research across all age groups reporting all-cause and/or cause-specific mortality in individuals with ADHD, defined via diagnostic criteria, self-identification, trait measures, or ADHD polygenic risk scores. Exclusion criteria were nonoriginal research, qualitative studies, non-peer-reviewed publications, and studies not reporting mortality outcomes.
DATA EXTRACTION AND SYNTHESIS: Data extraction was conducted independently by 2 reviewers. Study quality was assessed by 1 reviewer. Summary data were extracted from published reports, and pooled hazard ratios (HRs) were calculated using random-effects model meta-analysis.
MAIN OUTCOMES AND MEASURES: The primary outcomes were all-cause mortality and cause-specific mortality (suicide, unintentional or intentional injury, and natural causes), measured using HRs with 95% CIs.
RESULTS: Nineteen studies including 15 920 970 participants (36.1% female) were included. ADHD was associated with increased all-cause mortality (HR, 1.71; 95% CI, 1.31-2.24; P < .001). Significant associations were also observed for suicide (HR, 1.89; 95% CI, 1.21-2.95; P = .005), unintentional or intentional injury (HR, 1.55; 95% CI, 1.22-2.00; P < .001), and natural-cause mortality (HR, 1.27; 95% CI, 1.16-1.38; P < .001). ADHD medication use in people with ADHD was associated with reduced all-cause mortality (HR, 0.75; 95% CI, 0.64-0.87; P < .001). Substantial heterogeneity was observed across studies.
CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of ADHD and mortality, ADHD was associated with increased mortality across multiple causes; and ADHD medication was associated with a decreased all-cause mortality risk, underscoring the importance of timely diagnosis and treatment. However, the heterogeneity observed across studies highlights the need for standardized methods and improved control of confounding factors to better characterize mortality risk among individuals with ADHD.
The meta-analysis found higher rates of all-cause mortality in individuals with ADHD (hazard ratio [HR], 1.71; 95% CI, 1.31-2.24; P < .001).
heterogeneous observational evidence with an unresolved analytic study set
findings highlighted associations between ADHD and higher rates of mortality across multiple causes, including all-cause mortality, suicide, unintentional or intentional injury, and natural causes.
small observational cause-specific pools with high heterogeneity for suicide and injury
ADHD medication use in people with ADHD was associated with reduced all-cause mortality (HR, 0.75; 95% CI, 0.64-0.87; P < .001).
three observational studies subject to residual confounding and confounding by indication
Derived from the full evaluation — not a separate score.
Strengths
Six databases were searched without language or date limits, reference lists were checked, and two reviewers independently extracted data.
↳ Methods, Systematic Search and Study Selection; Data Extraction
The synthesis distinguishes suicide, injury, and natural-cause mortality and adds a medication-associated mortality analysis beyond the prior review.
↳ Results, Meta-Analyses; Discussion, comparison with Catalá-López et al
The Discussion identifies residual confounding and confounding by indication, then explicitly states that the medication finding is not evidence of causal protection.
↳ Discussion, medication analysis
Limitations
References 30–33 appear both among the 12 meta-analysed studies and among studies excluded from pooling. The text does not establish the corrected allocation or its effect on the pooled estimates.
↳ Results, Study Selection; Meta-Analyses
All-cause, suicide, and injury analyses report I² values of 98%, 93%, and 87%, respectively, with limited sensitivity exploration. Newcastle-Ottawa ratings are summarized but not used to qualify the synthesis through an overall certainty assessment.
↳ Results, Characteristics of Studies and Meta-Analyses; Limitations
The abstract links lower medication-associated mortality to timely diagnosis and treatment. That implication exceeds what three confounded observational studies can establish, despite the more careful Discussion.
↳ Abstract, Conclusions and Relevance; Discussion, medication analysis
Separate cause-specific estimates and a medication analysis provide a bounded update to the earlier ADHD mortality synthesis. The six-database search and dual extraction support the review, but pooling at I² values of 98%, 93%, and 87% leaves substantial uncertainty about the numerical averages. Study-quality ratings are not integrated into certainty judgments, and overlapping inclusion and exclusion lists prevent clear identification of the analytic sets. The Discussion appropriately rejects causal protection from medication, while the abstract retains a stronger treatment-oriented implication.
Nabu’s assessment, alongside the field’s view.
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Sound3.1
Confidence mediumThe synthesis adds separate cause-specific mortality estimates and a medication analysis to an acknowledged prior review. The advance remains bounded by unresolved variation in effect magnitude and a medication pool containing three studies.
Six-database searching and dual extraction support the synthesis, but very high heterogeneity receives limited exploration and study appraisal is not integrated into certainty judgments. Predominantly single-reviewer screening and conflicting analytic study lists further limit auditability.
Outcome-specific estimates are presented in a readable structure, but conflicting study lists impede following the analysis. The abstract's treatment implication is stronger than the explicitly noncausal medication interpretation in the Discussion.
The Discussion substantively compares the prior synthesis and connects confounding and heterogeneity to interpretation. Coverage remains incomplete for review-process limitations, possible registry overlap, and medication-related time biases identified in the assessments.
Caveats4 of 4 checks
3 reported values do not reconcile, but the key claims do not rest on them.
No specific research-conduct reliability finding is established. Unavailable declarations and supplement-only materials are assessability gaps rather than evidence of misconduct or unreliable results.
67 references in manuscript 63 of 63 checkable references found in an index 4 have no canonical index record — counted, but not index-checkable 1 reference confirmed by manual review
References not verified automatically are resolved manually within 24 hours.
No retraction or expression of concern found in Crossref (includes Retraction Watch).
Sources: Crossref (incl. Retraction Watch) ✓
Where this paper’s evidence sits on the path from initial observation to real-world use.
The estimates can inform recognition of excess mortality but do not establish treatment effects. The three-study medication analysis and absence of an integrated certainty assessment limit direct clinical action.
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