Evidence map›Paper›PMID 39875750›Full record

SynthesisCNS drugs2025

Raynaud Syndrome Associated with Medication for Attention-Deficit/Hyperactivity Disorder: A Systematic Review.

Frank M C Besag, Michael J Vasey, Sulagna Roy, Samuele Cortese

Abstract readSystematic Review
PubMed Publisher
In one paragraph

Synthesis in CNS drugs, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2026
    Article
  2. Drug-induced Raynaud phenomenon following initiation of metoprolol succinate.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2026
    Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Frank M C BesagEast London NHS Foundation Trust, Bedford, UK. fbesag@aol.com.ORCID 0000-0002-4530-7933
Michael J VaseyEast London NHS Foundation Trust, Bedford, UK.ORCID 0000-0003-1983-3531
Sulagna RoyFaculty of Environmental and Life Sciences, Centre for Innovation in Mental Health, School of Psychology, University of Southampton, Southampton, UK.ORCID 0009-0005-6824-7266
Samuele CorteseFaculty of Environmental and Life Sciences, Centre for Innovation in Mental Health, School of Psychology, University of Southampton, Southampton, UK.ORCID 0000-0001-5877-8075

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRaynaud syndrome (RS) is a peripheral vasculopathy characterised be impaired acral perfusion typically manifesting as skin discolouration with pallor, cyanosis and/or erythema, and increased sensitivity to cold. RS may be primary or secondary to systemic disease, lifestyle and environmental factors or medication. RS has been reported with medication to treat ADHD, but we found no recent comprehensive overview of the literature. The aim of this review is to evaluate the evidence in the published literature for Raynaud syndrome associated with medication for ADHD.

methodsWe systematically searched PubMed and Embase from inception to 12 June 2024 for articles published in English describing cases of RS in individuals treated with stimulant medication, atomoxetine, guanfacine or clonidine. Identified cases were assessed against the Naranjo Adverse Drug Reaction Scale criteria to determine the probability of a causal relationship with the medication.

resultsThe initial search identified 197 articles. A total of 61 cases were identified from 15 case reports, 5 case series, 1 retrospective case-control study, and 1 retrospective cohort study. No randomised, controlled studies were identified. Implicated medications included methylphenidate, (dex)amfetamine and, more rarely, atomoxetine. Most cases were mild and resolved within weeks of discontinuation, dose reduction or switch to an alternative medication. A few cases associated with systemic disease were reported, leading to ulceration, gangrene and the need for amputation or revascularisation in some individuals. Assessment of 28 cases using the Naranjo criteria suggested a 'possible' causative role of ADHD medication in 13 cases, a 'probable' role in 13 cases and a 'definite' role in two cases.

conclusionsDue to the uncontrolled nature of all but one of the available studies, a causal relationship between medication for ADHD and RS could not be determined reliably. However, in view of the possibility of severe sequelae, albeit in rare cases, routine monitoring for signs of RS is recommended in individuals treated with CNS stimulants or atomoxetine, especially when initiating treatment or increasing the dose. Large database studies in which individuals act as their own controls should be conducted to clarify any association between treatment with these medications and RS, controlling for confounding factors.

Indexed as

Attention Deficit Disorder with HyperactivityCentral Nervous System StimulantsRaynaud DiseaseAtomoxetine HydrochlorideHumansAtomoxetine HydrochlorideCentral Nervous System Stimulants

Identifiers

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.