CoChat
Sign Up
Cited by 0Attention Deficit Hyperactivity DisorderDevelopmental and Educational NeuropsychologyNeurotransmitter Receptor Influence on Behavior

Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD

Open access
El Masri, Sahid, Kowalczyk, Olivia S., Chiu, Tsz Hei, Criaud, Marion, Lukito, Steve, Mazibuko, Ndabezinhle, Salazar de Pablo, Gonzalo, Perez Rodriguez, Violeta +11 more·2025·Frontiers in Psychiatry
DOI 10.3389/fpsyt.2025.1676472PMC PMC12622228
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with cognitive difficulties which improve with traditional stimulant and non-stimulant medications. However, there is limited evidence on the cognitive effects of the newer licensed stimulant lisdexamfetamine and non-stimulant guanfacine in children with ADHD. Therefore, we compared differential single-dose effects of lisdexamfetamine and guanfacine on cognitive performance in youth with ADHD. Methods: In a randomized, placebo-controlled, double-blind, cross-over design, 22 children with ADHD were tested in tasks of sustained attention, vigilance, motor and interference inhibition, and time discrimination after single doses of guanfacine extended release, lisdexamfetamine, and placebo, with weekly washouts. Across tasks, composite measures of mean reaction time (MRT), intra-subject reaction time variability (coefficient of variation; CV), thought to reflect inattention, and premature responses were analyzed. Age-, IQ-, and sex- matched typically developing youth were assessed once without medication to test for potential drug normalization effects on performance differences compared to participants with ADHD on placebo. Results: Lisdexamfetamine significantly improved MRT and CV, while guanfacine worsened CV, compared with placebo and the other drug, with large effects. Although not reaching significance, there were moderate to large effects for lisdexamfetamine improving time discrimination and omission errors and for guanfacine to worsen omission errors in a sustained attention task relative to placebo and the other drug. Conclusion: These differential effects of lisdexamfetamine improving MRT and CV, while guanfacine worsening CV are clinically relevant, because they are the most replicated cognitive impairments in youth with ADHD. Findings suggest that guanfacine, unlike lisdexamfetamine, may not improve attention in children and adolescents with ADHD. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT03333668?term=NCT03333668&rank=1#study-plan , identifier NCT03333668.

AI snapshot

Written from the paper’s full text.

TL;DR

In a randomized, double-blind, placebo-controlled crossover trial in 22 children/adolescents with ADHD, single-dose lisdexamfetamine improved composite mean reaction time (MRT) and reaction-time variability (CV), whereas guanfacine worsened CV relative to placebo. The authors conclude that guanfacine, unlike lisdexamfetamine, may not improve attention in youth with ADHD.

Key findings

  • Repeated-measures ANOVA showed significant drug effects for MRT (p < 0.001, ES = 1.31) and CV (p < 0.001, ES = 1.34). Post-hoc tests showed lisdexamfetamine had faster MRT than placebo (t = −3.69, p = 0.003) and guanfacine (t = −3.31, p = 0.003), and lower CV than placebo (t = −1.78, p = 0.045) and guanfacine (t = −5.31, p = 0.031); guanfacine worsened CV relative to placebo (t = 2.17, p = 0.031).
  • Effects that did not reach significance but were medium-to-large: time discrimination errors (p = 0.080, ES = 0.72) and CPT omission errors (p = 0.054, ES = 0.82), descriptively with lisdexamfetamine improving and guanfacine worsening CPT omission errors.
  • No significant drug effects were found for Go/No-Go probability of inhibition, Simon RT interference, CPT commission errors, Mackworth Clock Task omission/commission errors, or premature responses.
  • Parents/carers reported more total adverse effects after lisdexamfetamine than placebo (t = 4.66, p = 0.002) and guanfacine (t = 3.48, p = 0.002); guanfacine and placebo did not differ (t = 1.31, p = 0.102). Drowsiness and fatigue items were not significant.

Methods

  • Randomized, placebo-controlled, double-blind, crossover design; 22 children/adolescents with ADHD (female = 6; mean age = 13.5, SD = 3.1) received single clinical doses of guanfacine extended release, lisdexamfetamine, and placebo with at least 7-day washouts; neurocognitive testing occurred 3 hours after administration. Trial preregistered as NCT03333668.
  • Cognitive battery included Maudsley Attention and Response Suppression tasks (Go/No-Go, Simon, CPT, time discrimination) and an adapted Mackworth Clock Vigilance task; composite scores for MRT, CV, and premature responses were calculated across Go/No-Go, Simon, and CPT.
  • Analyses used repeated-measures ANOVA on 10 cognitive variables, FDR-corrected post-hoc t-tests, and comparisons with 22 typically developing controls after excluding 2 outliers; regression examined ASD diagnosis/traits, with sensitivity analyses for order effects, non-normal data, and two participants who chewed capsules.

Limitations

  • Stated: the sample of 22 was powered for fMRI and relatively small for a neurocognitive study; the testing schedule at 3 hours may have favored lisdexamfetamine because guanfacine’s t-max is 5 hours versus lisdexamfetamine’s 3.5–4.5 hours; the age range was broad (8–20 years); comorbidities such as ASD were not excluded; order effects could not be completely ruled out.
  • Stated/evident: guanfacine takes longer than lisdexamfetamine to show behavioral effects, so acute comparative designs may favor stimulants.
  • Evident from the text: adverse effects were parent/carer-reported only, and the study recorded drowsiness/fatigue rather than sedation, limiting interpretation of guanfacine’s sedative effects.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3389/fpsyt.2025.1676472

Cites

90 of 90 references verified0 citation errors · 0 not checkable

Statistics

2 tests recomputed · 0 with the reported and recomputed p on opposite sides of .05

Claims the paper makes

58 of 113 cited sources checked · 22 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    Longer-term administration of both methylphenidate and atomoxetine improved MRT, attention and inhibition with statistically comparable small to medium effect sizes.

    “Our meta-analysis showed that longer-term administration of both methylphenidate and atomoxetine improved MRT, attention and inhibition with statistically comparable small to medium effect sizes (31).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [31] Isfandnia, 2024, The effects of chronic administration of stimulant and non-stimulant medications on executive functions in ADHD: A systematic review and meta-analysis, Neurosci Biobehav Rev source

      The available passage is title and author metadata, with no results section or page. Searches for MRT, attention, inhibition, the two medications, and comparable effect sizes found no passage in our copy that addresses the claimed outcomes. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
  • Premisecitation

    ADHD is associated with cognitive difficulties relative to typically developing controls, most consistently in executive functions including motor/interference inhibition, working memory, sustained attention, and timing.

    “Meta-analyses and systematic reviews have furthermore shown difficulties in children and adults with ADHD relative to those without ADHD in cognitive task performance, most consistently in executive functions, specifically in motor/interference inhibition (4, 5), working memory (WM) (6, 7), sustained attention (8) and timing (9, 10)”
    Quote in the paperSubstantial claim1 of 5 sources checked
    • cites [4] Alderson, 2007, Attention-deficit/hyperactivity disorder and behavioral inhibition: A meta-analytic review of the stop-signal paradigm, J Abnorm Child Psychol source
    • cites [5] Lijffijt, 2005, A meta-analytic review of stopping performance in attention-deficit/hyperactivity disorder: deficient inhibitory motor control, J Abnormal Psychol source
    • cites [6] Kasper, 2012, Moderators of working memory deficits in children with attention-deficit/hyperactivity disorder (ADHD): A meta-analytic review, Clin Psychol Review source
    • cites [7] Martinussen, 2005, A meta-analysis of working memory impairments in children with attention-deficit/hyperactivity disorder, J Am Acad Child Adolesc Psychiatry source
    • cites [8] Huang-Pollock, 2012, Evaluating vigilance deficits in ADHD: A meta-analysis of CPT performance, J Abnormal Psychol source

      The Summary and Conclusion reports large differences in sustained-attention task performance between school-age children with ADHD and controls. This supports the sustained-attention portion associated with citation (8), but this meta-analysis does not establish that finding for adults; the other cognitive domains have separate citations in the citing sentence. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Premisecitation

    Four meta-analyses testing predominantly single dose effects of stimulants on cognitive performance in children and adults with ADHD have most consistently found effects on mean reaction time (MRT), attention, inhibition and working memory (WM).

    “Four meta-analyses testing predominantly single dose effects of stimulants on cognitive performance in children and adults with ADHD, have most consistently found effects on mean reaction time (MRT), attention, inhibition and WM (17, 22, 29, 30).”
    Quote in the paperNot a substantial claim2 of 4 sources checked
    • cites [17] Pievsky, 2018, The neurocognitive profile of attention-deficit/hyperactivity disorder: A review of meta-analyses, Arch Clin Neuropsychology source
    • cites [22] Coghill, 2014, Effects of methylphenidate on cognitive functions in children and adolescents with attention-deficit/hyperactivity disorder: evidence from a systematic review and a meta-analysis, Biol Psychiatry source
    • cites [29] Tamminga, 2016, Effects of methylphenidate on executive functioning in attention-deficit/hyperactivity disorder across the lifespan: a meta-regression analysis, Psychol Med source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [30] Vertessen, 2022, Meta-analysis: dose-dependent effects of methylphenidate on neurocognitive functioning in children with attention-deficit/hyperactivity disorder, J Am Acad Child Adolesc Psychiatry source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
  • Premisecitation

    Most studies found no effects of guanfacine on cognition in people with ADHD.

    “The majority of studies found no effects of guanfacine on cognition; eight weeks of guanfacine compared to placebo did not improve WM performance, response inhibition, MRT, or RTV in 182 children with ADHD (39); likewise, 45 days of guanfacine relative to placebo had no effect on RT, sustained attention, spatial WM, and visual-motor processing in 178 children with ADHD (40).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [39] Bilder, 2016, Cognitive effects of stimulant, guanfacine, and combined treatment in child and adolescent attention-deficit/hyperactivity disorder, J Am Acad Child Adolesc Psychiatry source
    • cites [40] Kollins, 2011, Psychomotor functioning and alertness with guanfacine extended release in subjects with attention-deficit/hyperactivity disorder, J Child Adolesc Psychopharmacology source
  • Premisecitation

    Guanfacine reduces ADHD symptoms with medium effect sizes in children with ADHD.

    “The newer licensed non-stimulant guanfacine which is an α2-adrenergic receptor agonist reduces ADHD symptoms with medium effect-sizes (0.5) in children with ADHD (25).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [25] Cortese, 2018, Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis, Lancet Psychiatry source

      The Results (Table 1) report that guanfacine reduced clinician-rated ADHD symptoms versus placebo in children and adolescents, with a moderate effect size. The reported SMD is −0.67, not the cited 0.5; the Results also note that guanfacine was not superior to placebo on parents’ ratings. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • May combine two claims. 25
  • Classified as probably not a substantial claim. 29

  • May combine two claims.

    Premisecitation

    Out of the nine meta-analyzed fMRI studies that examined non-stimulants, eight studies tested atomoxetine and only one study tested guanfacine.

    “However, out of the nine meta-analyzed fMRI studies that examined non-stimulants, eight studies tested atomoxetine and only one study tested guanfacine.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [93] Pan, 2024, Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: a comparative neuroimaging analysis, Psychol Med source

      The Results (‘Included studies and sample characteristics’; page unavailable) report nine nonstimulant studies, but Table 1 lists one fluoxetine study as well as the guanfacine study. It lists seven distinct atomoxetine studies; Fan et al. (2017) appears twice for different tasks. The claimed eight-atomoxetine, one-guanfacine breakdown therefore omits fluoxetine and counts Fan twice. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Lisdexamfetamine reduces ADHD symptoms with large effect sizes in children and adults.

    “Meta-analyses have shown efficacy of lisdexamfetamine in improving ADHD symptoms with large effect sizes (32, 33).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [32] Cortese, 2018, Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis, Lancet Psychiatry source

      The Abstract Findings and Results report that amphetamines, a group including lisdexamfetamine, improved clinician-rated ADHD symptoms in children and adolescents (SMD −1.02) and adults (SMD −0.79). They do not give a large efficacy effect size specifically for lisdexamfetamine in both groups; the Discussion cautions that too few studies were available to draw firm conclusions from the analysis separating it from other amphetamines. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [33] Stuhec, 2019, Efficacy, acceptability, and tolerability of lisdexamfetamine, mixed amphetamine salts, methylphenidate, and modafinil in the treatment of attention-deficit hyperactivity disorder in adults: A systematic review and meta-analysis, Ann Pharmacother source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The most replicated cognitive difference in ADHD is increased intra-subject reaction time variability (RTV).

    “the most replicated cognitive difference is a more variable response style reflected in increased intra-subject reaction time variability (RTV) (12–17)”
    Quote in the paperNot a substantial claim2 of 6 sources checked
    • cites [12] Faraone, 2021, The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder, Neurosci Biobehav Rev source

      In “Performance Deficits in Psychological Processes” (page unavailable), the paper reports a meta-meta-analysis finding moderate impairments in reaction time variability among people with ADHD. It lists several other impaired cognitive domains but does not say reaction time variability is the most replicated difference. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [13] Karalunas, 2014, Annual Research Review: Reaction time variability in ADHD and autism spectrum disorders: measurement and mechanisms of a proposed trans-diagnostic phenotype, J Child Psychol Psychiatry source

      The “RT variability in ADHD” section (page unavailable) reports consistent meta-analytic evidence that people with ADHD have greater reaction-time variability than typically developing controls, drawing on a meta-analysis of 283 studies. It does not compare this finding with other cognitive differences to establish that it is the *most* replicated. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [14] Kofler, 2013, Reaction time variability in ADHD: A meta-analytic review of 319 studies, Clin Psychol Review source
    • cites [15] Kuntsi, 2012, Intraindividual Variability in ADHD and Its Implications for Research of Causal Links source
    • cites [16] Leth-Steensen, 2000, Mean response times, variability, and skew in the responding of ADHD children: a response time distributional approach, Acta Psychologica source
    • cites [17] Pievsky, 2018, The neurocognitive profile of attention-deficit/hyperactivity disorder: A review of meta-analyses, Arch Clin Neuropsychology source

  • May combine two claims.

    Interpretationreasoning

    Guanfacine, while improving ADHD symptoms relative to placebo, may not be an optimal drug to improve specific attention measures.

    “Together, this suggests that guanfacine, while improving ADHD symptoms relative to placebo (39–41, 43, 44), may not be an optimal drug to improve specific attention measures.”
    Quote in the paperSubstantial claim2 of 5 sources checked
    • cites [39] Bilder, 2016, Cognitive effects of stimulant, guanfacine, and combined treatment in child and adolescent attention-deficit/hyperactivity disorder, J Am Acad Child Adolesc Psychiatry source
    • cites [40] Kollins, 2011, Psychomotor functioning and alertness with guanfacine extended release in subjects with attention-deficit/hyperactivity disorder, J Child Adolesc Psychopharmacology source
    • cites [41] Bedard, 2015, Neural mechanisms underlying the therapeutic actions of guanfacine treatment in youth with ADHD: A pilot fMRI study, Psychiatry Res Neuroimaging source
    • cites [43] Michelini, 2023, Methylphenidate, guanfacine, and combined treatment effects on electroencephalography correlates of spatial working memory in attention-deficit/hyperactivity disorder, J Am Acad Child Adolesc Psychiatry source
    • cites [44] Taylor, 2001, Comparing guanfacine and dextroamphetamine for the treatment of adult attention-deficit/hyperactivity disorder, J Clin Psychopharmacol source

  • May combine two claims.

    Premisecitation

    In the meta-analysis, both drugs normalized left SMA activation which overlapped with regions of the central executive control, but only non-stimulants normalized regions of the ventral attention and limbic systems (i.e. left superior frontal and mid-cingulate cortices and left amygdala).

    “While both drugs normalized left SMA activation which overlapped with regions of the central executive control, only non-stimulants normalized regions of the ventral attention and limbic systems (i.e. left superior frontal and mid-cingulate cortices and left amygdala).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [93] Pan, 2024, Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: a comparative neuroimaging analysis, Psychol Med source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    RTV has been associated with poorer academic performance, motor development, and motor timing in children with ADHD.

    “RTV likewise has been associated with poorer academic performance (64), motor development (65), and motor timing (21, 66) in children with ADHD.”
    Quote in the paperNot a substantial claim3 of 4 sources checked
    • cites [64] Wang, 2022, Intraindividual reaction time variability and academic achievement of primary school students: A longitudinal cross-lagged panel model, J Appl Dev Psychol source
    • cites [65] Klotz, 2012, Relationship between reaction time variability and motor skill development in ADHD, Child Neuropsychology source
    • cites [21] Rubia, 1999, Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: A study with functional MRI, AJP source

      The introduction (pp. 891–896) says hyperactive adolescents perform poorly on tasks requiring temporal accuracy of movement, supporting the motor-timing part of the claim. It does not link reaction-time variability (RTV) to poorer motor timing. The Delay task results report no significant group difference in timing variability. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [66] Rubia, 2003, Motor timing deficits in community and clinical boys with hyperactive behavior: the effect of methylphenidate on motor timing, J Abnormal Child Psychol source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    RTV has been associated with abnormalities in switching off the neural correlates of mind-wandering, the default mode network (DMN), during task performance in children and adults with ADHD.

    “Furthermore, increased RTV has been shown to be a behavioral index of increased mind-wandering in adults with ADHD (71–73), and has been associated with abnormalities in “switching off” the neural correlates of mind-wandering, the default mode network (DMN) (74) during task performance in children and adults with ADHD (19, 20).”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [74] Christoff, 2009, Experience sampling during fMRI reveals default network and executive system contributions to mind wandering, Proc Natl Acad Sci USA source
    • cites [19] Christakou, 2013, Disorder-specific functional abnormalities during sustained attention in youth with Attention Deficit Hyperactivity Disorder (ADHD) and with Autism, Mol Psychiatry source

      The Discussion reports that boys with ADHD had higher reaction-time variability and showed abnormal precuneus activation during sustained attention, interpreted as impaired DMN suppression. However, the paper studied boys, not adults with ADHD, and its Results do not establish a direct correlation between reaction-time variability and DMN activation in the ADHD group. Page numbers are unavailable in our copy. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [20] Rubia, 2014, Imaging the ADHD brain: disorder-specificity, medication effects and clinical translation, Expert Rev Neurotherapeutics source

  • May combine two claims.

    Interpretationcitation

    The findings of improved RT and CV under lisdexamfetamine relative to guanfacine and placebo and deterioration of CV under guanfacine relative to placebo are highly relevant because slower and more variable processing speed are among the most consistent findings in ADHD.

    “The findings of improved RT and CV under lisdexamfetamine relative to guanfacine and placebo and in particular the deterioration of CV under guanfacine relative to placebo are highly relevant because slower and in particular more variable processing speed are among the most consistent findings in the cognitive literature of ADHD (4, 5, 12, 13, 15–17).”
    Quote in the paperSubstantial claim2 of 7 sources checked
    • cites [4] Alderson, 2007, Attention-deficit/hyperactivity disorder and behavioral inhibition: A meta-analytic review of the stop-signal paradigm, J Abnorm Child Psychol source
    • cites [5] Lijffijt, 2005, A meta-analytic review of stopping performance in attention-deficit/hyperactivity disorder: deficient inhibitory motor control, J Abnormal Psychol source
    • cites [12] Faraone, 2021, The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder, Neurosci Biobehav Rev source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [13] Karalunas, 2014, Annual Research Review: Reaction time variability in ADHD and autism spectrum disorders: measurement and mechanisms of a proposed trans-diagnostic phenotype, J Child Psychol Psychiatry source
    • cites [15] Kuntsi, 2012, Intraindividual Variability in ADHD and Its Implications for Research of Causal Links source
    • cites [16] Leth-Steensen, 2000, Mean response times, variability, and skew in the responding of ADHD children: a response time distributional approach, Acta Psychologica source
    • cites [17] Pievsky, 2018, The neurocognitive profile of attention-deficit/hyperactivity disorder: A review of meta-analyses, Arch Clin Neuropsychology source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The study's findings could extend evidence for acute and chronic methylphenidate administration significantly improving timing and attention functions in children with ADHD including the same tasks.

    “These findings could extend evidence for acute and chronic methylphenidate administration significantly improving timing (66, 94) and attention functions in children with ADHD including the same tasks (22, 29–31).”
    Quote in the paperNot a substantial claim5 of 6 sources checked
    • cites [66] Rubia, 2003, Motor timing deficits in community and clinical boys with hyperactive behavior: the effect of methylphenidate on motor timing, J Abnormal Child Psychol source

      The Medication Effect section reports improved motor-timing variability after persistent methylphenidate use, but says a single dose was no more effective than placebo. The Conclusions likewise limit the improvement to persistent administration. This source therefore supports the chronic-timing part, not the claim that acute administration significantly improved timing. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [94] Luman, 2015, The unique and combined effects of reinforcement and methylphenidate on temporal information processing in attention-deficit/hyperactivity disorder, J Clin Psychopharmacology source

      The available copy contains the paper’s title and bibliographic details (passages [1]–[3]), but no methods or findings. Searches for acute and chronic methylphenidate effects did not yield passages establishing significant improvements in timing or attention, so the attributed finding cannot be checked from this copy. (LLM, conf=0.72)

      Experimental — accuracy not yet measured
    • cites [22] Coghill, 2014, Effects of methylphenidate on cognitive functions in children and adolescents with attention-deficit/hyperactivity disorder: evidence from a systematic review and a meta-analysis, Biol Psychiatry source
    • cites [29] Tamminga, 2016, Effects of methylphenidate on executive functioning in attention-deficit/hyperactivity disorder across the lifespan: a meta-regression analysis, Psychol Med source

      The Results section, “Effect of MPH on response inhibition, working memory and sustained attention” (page unavailable), reports a significant improvement in sustained attention. But the Conclusions (page unavailable) explicitly say timing was not included in the analysis because too few studies addressed it. The pooled finding also spans children and adults; it does not establish that both acute and chronic administration significantly improved the specified functions in children using the same tasks. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [30] Vertessen, 2022, Meta-analysis: dose-dependent effects of methylphenidate on neurocognitive functioning in children with attention-deficit/hyperactivity disorder, J Am Acad Child Adolesc Psychiatry source

      The paper’s Conclusion reports that methylphenidate improved a broad range of neurocognitive functions in children with ADHD, and its study table includes attention-related tasks (Variability in Responding). But the Discussion says the meta-analysis could assess only short-term effects, so it does not establish significant improvement after chronic administration. In the citing sentence, the timing claim is attached to other citations, not this paper. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [31] Isfandnia, 2024, The effects of chronic administration of stimulant and non-stimulant medications on executive functions in ADHD: A systematic review and meta-analysis, Neurosci Biobehav Rev source

      Our indexed copy returns only the paper’s title and author metadata, with no Results passage. Searches for methylphenidate’s effects on attention, timing, and the same tasks found no substantive text, so the claimed improvement cannot be checked against this copy. (LLM, conf=0.77)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    There is evidence that guanfacine decreases arousal in animal models and people with addiction, and decreases physiological parameters related to arousal like blood pressure and pulse in children with ADHD.

    “There is evidence that guanfacine decreases arousal in animal models (82) and people with addiction (83), and decreases physiological parameters that are related to arousal like blood pressure and pulse in children with ADHD (40, 84).”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [82] Shinba, 2001, Clonidine immediately after immobilization stress prevents long-lasting locomotion reduction in the rat, Prog Neuropsychopharmacol Biol Psychiatry source
    • cites [83] Fox, 2014, Sex differences in guanfacine effects on drug craving and stress arousal in cocaine-dependent individuals, Neuropsychopharmacol source
    • cites [40] Kollins, 2011, Psychomotor functioning and alertness with guanfacine extended release in subjects with attention-deficit/hyperactivity disorder, J Child Adolesc Psychopharmacology source
    • cites [84] Scahill, 2015, Extended-release guanfacine for hyperactivity in children with autism spectrum disorder, AJP source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Methylphenidate both in acute and longer-term dosage has been shown to improve inhibitory measures.

    “This was also unexpected as methylphenidate both in acute and longer-term dosage has been shown to improve inhibitory measures (17, 22, 29–31).”
    Quote in the paperNot a substantial claim3 of 5 sources checked
    • cites [17] Pievsky, 2018, The neurocognitive profile of attention-deficit/hyperactivity disorder: A review of meta-analyses, Arch Clin Neuropsychology source
    • cites [22] Coghill, 2014, Effects of methylphenidate on cognitive functions in children and adolescents with attention-deficit/hyperactivity disorder: evidence from a systematic review and a meta-analysis, Biol Psychiatry source
    • cites [29] Tamminga, 2016, Effects of methylphenidate on executive functioning in attention-deficit/hyperactivity disorder across the lifespan: a meta-regression analysis, Psychol Med source
    • cites [30] Vertessen, 2022, Meta-analysis: dose-dependent effects of methylphenidate on neurocognitive functioning in children with attention-deficit/hyperactivity disorder, J Am Acad Child Adolesc Psychiatry source

      The Discussion (page unavailable) reports a small overall beneficial effect of methylphenidate on inhibitory control. Table 1 lists inhibitory-control studies with treatment periods ranging from one day to 14 days, but the paper does not establish a separate longer-term effect; its analysis concerns dose rather than treatment duration. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [31] Isfandnia, 2024, The effects of chronic administration of stimulant and non-stimulant medications on executive functions in ADHD: A systematic review and meta-analysis, Neurosci Biobehav Rev source

      The supplied passage and all retrieved passages contain only the paper’s title and author information, with no findings on inhibitory measures. Searches for acute and chronic methylphenidate effects and response inhibition found no relevant text in the accessible copy, so the claim cannot be checked. (LLM, conf=0.72)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    On a neural level, RTV has been associated with smaller white matter tracts in the late developing fronto-parietal attention (superior longitudinal fasciculus) and cortico-thalamic cognitive control tracts and reduced activation in fronto-striatal and superior temporal activation in children and adults with ADHD.

    “In line with a role in attention and self-control, on a neural level, RTV has been associated with smaller white matter tracts in the late developing fronto-parietal attention (superior longitudinal fasciculus) and cortico-thalamic cognitive control tracts and reduced activation in fronto-striatal and superior temporal activation in children and adults with ADHD (18, 67–70), suggesting an”
    Quote in the paperNot a substantial claim2 of 5 sources checked
    • cites [18] Wolfers, 2015, Lower white matter microstructure in the superior longitudinal fasciculus is associated with increased response time variability in adults with attention-deficit/hyperactivity disorder, jpn source

      Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [67] Dipnall, 2023, Fronto-parietal white matter microstructure associated with working memory performance in children with ADHD, Cortex source
    • cites [68] Kölle, 2022, Lower fractional anisotropy of the corticothalamic tract and increased response time variability in adult patients with ADHD, jpn source

      Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [69] Rubia, 2007, Temporal lobe dysfunction in medication-naïve boys with attention-deficit/hyperactivity disorder during attention allocation and its relation to response variability, Biol Psychiatry source
    • cites [70] Shang, 2018, Differential brain activations in adult attention-deficit/ hyperactivity disorder subtypes: a counting Stroop functional MRI study, Brain Imaging Behavior source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    RTV has been shown to be specific to ADHD rather than ASD traits.

    “RTV has furthermore been shown to be specific to ADHD rather than ASD traits (13, 61).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [13] Karalunas, 2014, Annual Research Review: Reaction time variability in ADHD and autism spectrum disorders: measurement and mechanisms of a proposed trans-diagnostic phenotype, J Child Psychol Psychiatry source

      In “Moderators of between-study heterogeneity for ASD-control group comparisons” (page unavailable), the review reports increased RTV in ASD only when children with comorbid ADHD were included, supporting a stronger association with ADHD than with ASD alone. But it says the evidence concerns diagnostic groups, not ASD traits, and calls for dimensional studies; it does not establish that RTV is specific to ADHD rather than ASD traits. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [61] Adamo, 2019, Ex-gaussian, frequency and reward analyses reveal specificity of reaction time fluctuations to ADHD and not autism traits, J Abnorm Child Psychol source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Increased RTV has been shown to be a behavioral index of increased mind-wandering in adults with ADHD.

    “Furthermore, increased RTV has been shown to be a behavioral index of increased mind-wandering in adults with ADHD (71–73), and has been associated with abnormalities in “switching off” the neural correlates of mind-wandering, the default mode network (DMN) (74) during task performance in children and adults with ADHD (19, 20).”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [71] Bozhilova, 2021, Electrophysiological modulation of sensory and attentional processes during mind wandering in attention-deficit/hyperactivity disorder, NeuroImage: Clinical source
    • cites [72] Bozhilova, 2020, Electrophysiological correlates of spontaneous mind wandering in attention-deficit/hyperactivity disorder, Behav Brain Res source

      The Discussion (page unavailable) reports a novel association between increased spontaneous mind-wandering and RTV in a sample of adults with and without ADHD. It does not establish RTV as an index of mind-wandering specifically within the ADHD group: the association was assessed across the entire sample, and the Results (Analysis 3; page unavailable) found that mind-wandering did not explain additional RTV variance after ADHD status was included. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [73] van Vugt, 2016, Self-reported stickiness of mind-wandering affects task performance, Front Psychol source

  • May combine two claims.

    Premisecitation

    Out of six studies testing effects of mostly longer-term guanfacine effects on cognition, four reported sedative symptoms or fatigue while two other studies did not record or report them.

    “Out of six studies testing effects of mostly longer-term guanfacine effects on cognition, four reported sedative symptoms (39, 40, 43) or fatigue (44) while two other studies did not record or report them (39, 42).”
    Quote in the paperNot a substantial claim3 of 5 sources checked
    • cites [39] Bilder, 2016, Cognitive effects of stimulant, guanfacine, and combined treatment in child and adolescent attention-deficit/hyperactivity disorder, J Am Acad Child Adolesc Psychiatry source
    • cites [40] Kollins, 2011, Psychomotor functioning and alertness with guanfacine extended release in subjects with attention-deficit/hyperactivity disorder, J Child Adolesc Psychopharmacology source
    • cites [43] Michelini, 2023, Methylphenidate, guanfacine, and combined treatment effects on electroencephalography correlates of spatial working memory in attention-deficit/hyperactivity disorder, J Am Acad Child Adolesc Psychiatry source

      The Methods (Procedures) describe an eight-week guanfacine trial assessing cognition, and the Discussion mentions sedative effects commonly observed with guanfacine. This paper does not report sedative symptoms or fatigue among its own participants, nor does it establish the citing sentence’s counts across six studies. Its mention of sedation is background, not a reported study result. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [44] Taylor, 2001, Comparing guanfacine and dextroamphetamine for the treatment of adult attention-deficit/hyperactivity disorder, J Clin Psychopharmacol source
    • cites [42] Ikeda, 2021, Visualizing neuropharmacological effects of guanfacine extended release in attention deficit hyperactivity disorder using functional near-infrared spectroscopy, Front Neuroergonomics source

  • May combine two claims.

    Findingown data

    In children and adolescents with ADHD, lisdexamfetamine improved time discrimination errors relative to placebo and guanfacine, although the effect did not reach significance.

    “Although not reaching significance, there were moderate to large effects for lisdexamfetamine improving time discrimination and omission errors and for guanfacine to worsen omission errors in a sustained attention task relative to placebo and the other drug.”
    • Also stated in: § Test of within-subject medication effects on cognitive performance in the ADHD group · plain
      “Exploratory FDR-corrected post-hoc t-tests showed the same tendency, with lisdexamfetamine improving time discrimination compared to both placebo (t = –1.869, p = .078) and guanfacine (t = –1.695, p = .078)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In children and adolescents with ADHD, lisdexamfetamine reduced CPT omission errors relative to placebo and guanfacine, although the effect did not reach significance.

    “reducing CPT omission errors compared to placebo (t = –1.308, p = .103) and guanfacine (t = –2.122, p = .069)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The medication effects on some attentional and timing measures had moderate to large effect sizes but were slightly above the threshold of significance.

    “We also showed medication effects on some attentional and timing measures with moderate to large effect sizes which were, however, slightly above the threshold of significance.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neither lisdexamfetamine nor guanfacine improved inhibitory measures in this study.

    “None of the drugs improved inhibitory measures.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In this study, lisdexamfetamine numerically improved time discrimination and CPT omission errors.

    “Thus, we found that lisdexamfetamine numerically improved time discrimination and CPT omission errors, the latter of which were numerically worsened with guanfacine.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Seven days between visits was chosen as sufficient to avoid drug interactions based on 6.5 times the half-life of each drug.

    “Calculating washout period as 6.5 times the half-life of each drug, seven days was chosen as both pragmatic and sufficient to avoid drug interactions.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Findings did not change substantially when non-normal data were analyzed with non-parametric tests or when the two participants who chewed capsules were excluded.

    “Findings did not change substantially when non-normal distributed data was analyzed with non-parametric tests (see supplemental data C) or when the two participants who chewed capsules of guanfacine were excluded from all analyses (see supplemental data D-E).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Guanfacine has mild sedative properties.

    “Guanfacine also has mild sedative properties (27), potentially underlying its positive impact on behavioral ADHD symptoms, especially hyperactivity (28).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Intuniv Prescribing information Label 2019

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    All analyses were repeated without the two participants who chewed capsules to ensure validity of the results.

    “Nonetheless, all analyses were repeated without the two participants to ensure validity of the results.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Nonparametric tests were conducted to ensure validity of the results given non-normality.

    “ANOVA is robust against violations of the normality assumption (59); however to ensure validity of the results, we also conducted nonparametric tests.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [59] Blanca, 2017, Non-normal data: Is ANOVA still a valid option, Psicothema source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The study was preregistered on ClinicalTrials.gov before data collection commenced.

    “This study was preregistered on ClinicalTrials.gov (Identifier: NCT03333668) before data collection commenced.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The study used a randomized, placebo-controlled, double-blind, crossover design with weekly washouts.

    “In a randomized, placebo-controlled, double-blind, cross-over design, 22 children with ADHD were tested in tasks of sustained attention, vigilance, motor and interference inhibition, and time discrimination after single doses of guanfacine extended release, lisdexamfetamine, and placebo, with weekly washouts.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    A computer-generated randomization list was given to the pharmacy for over-encapsulation, blinding and dispensing.

    “A computer-generated randomization list was given to the Maudsley pharmacy for over-encapsulation, blinding and dispensing of the capsules.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    Neurocognitive testing was conducted at three hours after drug administration, which was compromised relative to the time to peak drug concentration.

    “There was a discrepancy between the time to peak drug concentration (t-max) of lisdexamfetamine (3.5 – 4.5h) and guanfacine (5h) and since the schedule was mainly tailored toward the fMRI (4.5h after medication administration), the neurocognitive testing was compromised to be at three hours after drug administration.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The study used a within-group, counterbalanced, 1-week washout, repeated measures design.

    “This study was an experimental pharmacological study testing the effects of a single clinical dose of either lisdexamfetamine, guanfacine and placebo on a range of cognitive functions and on brain activation in fMRI, in children and adolescents with ADHD, in a within-group, counterbalanced, 1-week washout, repeated measures design.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    There is limited evidence on the cognitive effects of the newer licensed stimulant lisdexamfetamine and non-stimulant guanfacine in children with ADHD.

    “However, there is limited evidence on the cognitive effects of the newer licensed stimulant lisdexamfetamine and non-stimulant guanfacine in children with ADHD.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Significant main effects of order were found only in CPT commission errors and MCT omission errors, which were not affected by either drug.

    “Significant main effects for order were only found in CPT commission errors (F (5, 15) = 2.57, p = 0.030, partial η² = 0.531) and MCT omission errors (F (5, 15) = 3.39, p = 0.030, partial η² = 0.487), which were not affected by either drug in the within-subject ANOVA.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Neither the researcher nor the participants and parents/carers were aware of dosing information throughout data acquisition.

    “Neither the researcher nor the participants and parents/carers were aware of dosing information throughout data acquisition.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Regression analyses were included to examine the potential impact of ASD diagnosis and high ASD traits.

    “Because 50% of participants with ADHD had a diagnosis of ASD and scored high on the SCQ (>12), we included regression analyses to examine the potential impact of the ASD diagnosis and high ASD traits in the SCQ.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    This is the first study directly comparing the differential effects of single doses of lisdexamfetamine and guanfacine relative to placebo on cognitive performance in children with ADHD.

    “This is the first study directly comparing the differential effects of single doses of lisdexamfetamine and guanfacine relative to placebo on cognitive performance in children with ADHD.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The worsening effects of guanfacine on CV need to be considered in light of the relatively small subject numbers.

    “The worsening effects of guanfacine on CV, while concerning, need, however, be considered in light of the relatively small subject numbers.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The age range of participants (8-20 years) was relatively broad.

    “Third, the age range of participants (8–20 years) was relatively broad.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The study did not exclude comorbidities like ASD, which may have confounded the findings.

    “Fourth, we did not exclude comorbidities like ASD which may have confounded the findings.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The study did not ask children with ADHD about side effects but only their parents, and recorded drowsiness and fatigue instead of sedation.

    “It is noteworthy, however, that we did not ask the children with ADHD but their parents only and we recorded drowsiness and fatigue, instead of sedation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The study's findings of improved MRT and CV with lisdexamfetamine, but worsened CV with guanfacine, may be interpreted in light of differential effects on brain activation observed in fMRI studies comparing stimulants and non-stimulants.

    “Our findings of improved MRT and CV with lisdexamfetamine, but worsened CV with guanfacine may also be interpreted in light of differential effects on brain activation observed in fMRI studies comparing stimulants and non-stimulants.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The sample size of 22 children and adolescents with ADHD was powered for fMRI and was relatively small for a neurocognitive study.

    “First, the sample size of 22 children and adolescents with ADHD was powered for fMRI and was therefore relatively small for a neurocognitive study and might explain the non-significance of some findings that were of medium (time discrimination) to large effects sizes (CPT omission errors).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Only one small study of 17 adults with ADHD showed improvement in focused attention and interference inhibition in the Stroop task after two weeks of both guanfacine and dextroamphetamine relative to placebo, with guanfacine being superior to dextroamphetamine.

    “Only one small study of 17 adults with ADHD showed improvement in focused attention and interference inhibition in the Stroop task after two weeks of both guanfacine and dextroamphetamine relative to placebo, with guanfacine being superior to dextroamphetamine (44).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Taylor, 2001, Comparing guanfacine and dextroamphetamine for the treatment of adult attention-deficit/hyperactivity disorder, J Clin Psychopharmacol source

  • May combine two claims.

    Interpretationreasoning

    The differential effects of lisdexamfetamine improving MRT and CV, while guanfacine worsening CV, are clinically relevant because they are the most replicated cognitive impairments in youth with ADHD.

    “These differential effects of lisdexamfetamine improving MRT and CV, while guanfacine worsening CV are clinically relevant, because they are the most replicated cognitive impairments in youth with ADHD.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Because the negative effects of guanfacine on cognition were opposite to the initial hypothesis, analyses were repeated using two-tailed tests, and non-parametric analyses confirmed the same pattern of effects.

    “Because the negative effects of guanfacine on cognition were opposite to our initial hypothesis, we repeated the analyses using two-tailed tests showing that non-parametric analyses confirmed the same pattern of effects.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    RTV is associated with ADHD diagnosis and symptoms.

    “Increased RTV in particular is the most replicated finding in individuals with ADHD compared to TD (12, 14, 16, 17); it has frequently been related to excessively slow RTs in individuals with ADHD (14) and is associated with ADHD diagnosis and symptoms (14, 15), with some considering it to underlie behavioral inattention in ADHD (16, 60).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14] Kofler, 2013, Reaction time variability in ADHD: A meta-analytic review of 319 studies, Clin Psychol Review source
    • cites [15] Kuntsi, 2012, Intraindividual Variability in ADHD and Its Implications for Research of Causal Links source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Meta-analytic evidence shows that poor processing speed in children with ADHD is strongly negatively correlated with academic skills and with clinical problems such as poorer adaptive skills, increased self-reported anxiety and overestimating social competence.

    “Meta-analytic evidence shows that poor processing speed in children with ADHD is strongly negatively correlated with academic skills and with clinical problems such as poorer adaptive skills, increased self-reported anxiety and overestimating social competence (63).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] Cook, 2018, Clinical and functional correlates of processing speed in pediatric Attention-Deficit/Hyperactivity Disorder: a systematic review and meta-analysis, Child Neuropsychology source
46 of 46

  • The paper relies on this without support.

    Guanfacine takes longer to show behavioral effects than lisdexamfetamine (several weeks vs 24h).

    “Furthermore, guanfacine takes longer to show behavioral effects than lisdexamfetamine (several weeks vs 24h) and hence comparative studies on acute effects of stimulants versus non-stimulants may favor stimulant medication.”

  • The paper relies on this without support.

    This is the first study comparing differential acute effects of GXR and lisdexamfetamine, relative to placebo.

    “This is the first study comparing differential acute effects of GXR and lisdexamfetamine, relative to placebo.”

  • The paper relies on this without support.

    Clonidine, similarly to guanfacine, is an α2-adrenergic receptor agonist and can cause sedation.

    “which similarly to guanfacine, is also an α2-adrenergic receptor agonist and can cause sedation.”
3 of 3

Statistics that don’t add up

Each reported p-value recomputed from its test statistic and degrees of freedom.

  • Statistic does not fit its p-value and effect size: F (5, 15) = 2.57, p = .030

    Minor

    The paper reports p = .03 here; recomputing from the test statistic and its degrees of freedom gives p = .072. The partial eta squared printed with it (ηp² = .531) corresponds to F ≈ 3.40 and p = .030, which fits the reported p-value and not the statistic: the statistic appears to be the misprint.

    Reported p = .03 · recomputed p = .072

1 of 1

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Doesn’t add upF(5, 15) = 2.57reported p = .03 · recomputed p = .072

    “F (5, 15) = 2.57, p = .030”

  • ConsistentF(5, 15) = 3.39reported p = .03 · recomputed p = .030

    “F (5, 15) = 3.39, p = .030”

2 of 2

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • TD group has two different mean ages after exclusions

    Major

    The statistical-analysis section says the remaining 22 TD participants had a mean age of 14.3 years; Table 1 reports 15.1 years for 22 TD participants.

  • Limitations deny significant order effects reported in Results

    Minor

    The Limitations section says the analysis found no significant order effects, while the Results report significant order effects for two measures.

  • Adverse-effect percentages use a different denominator from the stated N

    Minor

    Table 3 states N = 21 for each condition, but 13 reports of poor appetite are listed as 65.0%; 13 of 21 is 61.9%. The displayed percentage corresponds to a denominator of 20.

    Reported 65 · recomputed 61.904762

  • ADHD group has two different mean ages

    Minor

    The Methods give a mean age of 13.5 years for the 22 participants with ADHD, whereas Table 1 gives 14.0 years for the same-sized group.

  • Study 39 is said both to report and not report sedative symptoms

    Minor

    The discussion includes study 39 among studies reporting sedative symptoms, then includes it among studies that did not record or report them.

5 of 5

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. Cortese, 2018, Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis, Lancet Psychiatry, 5, 727, 10.1016/s2215-0366(18)30269-4 · DOI · Paper page
  2. DuPaul, 1998, ADHD Rating Scale—IV: Checklists, norms, and clinical interpretation, 79
  3. Rutter, 2003, The Social Communication Questionnaire: Manual

Authors
El Masri, S., Kowalczyk, O. S., Chiu, T. H., Criaud, M., Lukito, S., Mazibuko, N., Salazar de Pablo, G., Perez Rodriguez, V., Makos, O., Lam, S.-L., Westwood, S., Eaton-Turner, A., Bozhilova, N., Conti, A., Santosh, P., Roessner, V., Kohls, G., Mehta, M. A., & Rubia, K.
Affiliations
  • Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London
  • King's College London (GB)
  • Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King’s College London
Corresponding author
Rubia, Katya
ORCID
Venue
Frontiers in Psychiatry
Publisher
Frontiers Media SA
Published
2025-11-03
Volume
16
Pages
1676472-1676472
ISSN
1664-0640 (ISSN-L)
DOI
10.3389/fpsyt.2025.1676472
PMC
PMC12622228
OpenAlex
W4415818227
Cited by
0
References
87
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Psychiatry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Research Portal (King's College London) (submittedVersion, cc-by)
Funders
Takeda Pharmaceutical Company (IISR-2016-104081)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Developmental and Educational Neuropsychology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
lisdexamfetamine, guanfacine, attention deficit hyperactivity disorder, children and adolescents, cognitive function, reaction time variability, inattention, sustained attention, omission errors, temporal discrimination, stimulant medication, non-stimulant medication

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-16.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-16.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review