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Record W4411909346 · doi:10.1038/s41380-025-03080-3

Long term safety of ADHD medication in patients with schizophrenia spectrum disorders

2025· article· en· W4411909346 on OpenAlexaff
Jurjen J. Luykx, Olivier Corbeil, Olli Kärkkäinen, Antti Tanskanen, Ellenor Mittendorfer‐Rutz, Jari Tiihonen, Heidi Taipale

Bibliographic record

VenueMolecular Psychiatry · 2025
Typearticle
Languageen
FieldMedicine
TopicAttention Deficit Hyperactivity Disorder
Canadian institutionsUniversité LavalInstitut Universitaire en Santé Mentale de QuébecDouglas Mental Health University Institute
Fundersnot available
KeywordsMethylphenidateMedicineHazard ratioSchizophrenia spectrumSchizophrenia (object-oriented programming)AtomoxetinePsychosisProportional hazards modelAttention deficit hyperactivity disorderPsychiatryConcomitantInternal medicinePediatricsConfidence interval

Abstract

fetched live from OpenAlex

Attention-deficit hyperactivity disorder (ADHD) is frequently comorbid with schizophrenia spectrum disorders (SSDs) and is associated with poorer outcomes. Yet, its pharmacological treatment in patients with SSDs has been hampered by safety concerns. We therefore examined whether psychiatric, cardiovascular and other medical outcomes are associated with the use of ADHD medications in people with SSDs (N = 131,476). The main outcome was all-cause hospitalization/mortality. Secondary outcomes were hospitalization for psychosis, somatic hospitalization, and cardiovascular hospitalization. Adjusted hazard ratios (aHRs) were calculated for the association between the outcomes and the different exposure categories (compared with non-use of ADHD medication) using within-individual Cox regression analyses. Lisdexamphetamine was associated with a decreased risk of all-cause hospitalization/mortality (aHR = 0.89, 95%CI = 0.84-0.94) and methylphenidate with a slightly increased risk (aHR = 1.04 [1.01-1.08]), while for the other exposures the 95%CI of the HRs encompassed 1. Atomoxetine was associated with a reduced risk of hospitalization for psychosis (aHR = 0.87 [0.78-0.98]), lisdexamphetamine with a reduced risk of somatic hospitalizations (aHR = 0.70 [0.58-0.84]), and ADHD polytherapy with an increased risk of somatic hospitalizations (aHR = 1.37 [1.07-1.74]). No other statistically significant associations were found between the exposures and outcomes (including cardiovascular hospitalizations). Furthermore, increased all-cause hospitalization/mortality risks for methylphenidate were only found with doses ≥95 mgs/day (aHR 1.08 [1.03-1.14]) or during use periods of this agent without concomitant use of an antipsychotic (aHR = 1.06 [1.01-1.12]). Finally, for methylphenidate and lisdexamphetamine, we found evidence of U-shaped associations between doses used and risks of all-cause hospitalization/mortality and psychosis. In conclusion, we find that for people with SSDs, the use of ADHD medication (particularly lisdexamphetamine in all dosages and long-acting methylphenidate in low to medium doses) is safer than generally conceived. The benefits of its use for patients with SSD and comorbid ADHD should therefore be weighed against the risks in a shared decision-making process aimed at improving patients' chances of recovery.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.006
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.011
Threshold uncertainty score0.022

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.006
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.005
GPT teacher head0.265
Teacher spread0.260 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations3
Published2025
Admission routes1
Has abstractyes

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