CoChat
Sign Up
Cited by 45Attention Deficit Hyperactivity DisorderSchizophrenia research and treatmentNeuroethics, Human Enhancement, Biomedical Innovations

Self-Reported quality of life in adults with attention-deficit/hyperactivity disorder and executive function impairment treated with lisdexamfetamine dimesylate: a randomized, double-blind, multicenter, placebo-controlled, parallel-group study

Open access
Adler, Lenard A, Dirks, Bryan, Deas, Patrick, Raychaudhuri, Aparna, Dauphin, Matthew, Saylor, Keith, Weisler, Richard·2013·BMC Psychiatry
DOI 10.1186/1471-244x-13-253PMC PMC3854089
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: This study examined the effects of lisdexamfetamine dimesylate (LDX) on quality of life (QOL) in adults with attention-deficit/hyperactivity disorder (ADHD) and clinically significant executive function deficits (EFD). METHODS: This report highlights QOL findings from a 10-week randomized placebo-controlled trial of LDX (30-70 mg/d) in adults (18-55 years) with ADHD and EFD (Behavior Rating Inventory of EF-Adult, Global Executive Composite [BRIEF-A GEC] ≥65). The primary efficacy measure was the self-reported BRIEF-A; a key secondary measure was self-reported QOL on the Adult ADHD Impact Module (AIM-A). The clinician-completed ADHD Rating Scale version IV (ADHD-RS-IV) with adult prompts and Clinical Global Impressions-Severity (CGI-S) were also employed. The Adult ADHD QoL (AAQoL) was added while the study was in progress. A post hoc analysis examined the subgroup having evaluable results from both AIM-A and AAQoL. RESULTS: Of 161 randomized (placebo, 81; LDX, 80), 159 were included in the safety population. LDX improved AIM-A multi-item domain scores versus placebo; LS mean difference for Performance and Daily Functioning was 21.6 (ES, 0.93, P<.0001); Impact of Symptoms: Daily Interference was 14.9 (ES, 0.62, P<.0001); Impact of Symptoms: Bother/Concern was 13.5 (ES, 0.57, P=.0003); Relationships/Communication was 7.8 (ES, 0.31, P=.0302); Living With ADHD was 9.1 (ES, 0.79, P<.0001); and General Well-Being was 10.8 (ES, 0.70, P<.0001). AAQoL LS mean difference for total score was 21.0; for subscale: Life Productivity was 21.0; Psychological Health was 12.1; Life Outlook was 12.5; and Relationships was 7.3. In a post hoc analysis of participants with both AIM-A and AAQoL scores, AIM-A multi-item subgroup analysis scores numerically improved with LDX, with smaller difference for Impact of Symptoms: Daily Interference. The safety profile of LDX was consistent with amphetamine use in previous studies. CONCLUSIONS: Overall, adults with ADHD/EFD exhibited self-reported improvement on QOL, using the AIM-A and AAQoL scales in line with medium/large ES; these improvements were paralleled by improvements in EF and ADHD symptoms. The safety profile of LDX was similar to previous studies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01101022.

AI snapshot

Written from the paper’s full text.

TL;DR

In adults with ADHD and clinically significant executive function deficits, lisdexamfetamine dimesylate improved self-reported quality of life on AIM-A domains versus placebo over 10 weeks, with medium-to-large effect sizes. AAQoL total and subscale changes numerically favored LDX, but hierarchical testing precluded inferential analysis for that measure.

Key findings

  • On the AIM-A, LDX versus placebo LS mean differences were: Performance and Daily Functioning 21.6 (ES 0.93, P<.0001); Impact of Symptoms: Daily Interference 14.9 (ES 0.62, P<.0001); Impact of Symptoms: Bother/Concern 13.5 (ES 0.57, P=.0003); Relationships/Communication 7.8 (ES 0.31, P=.0302); Living With ADHD 9.1 (ES 0.79, P<.0001); and General Well-Being 10.8 (ES 0.70, P<.0001).
  • AAQoL total and subscale changes numerically favored LDX; LS mean differences were 14.7 (95% CI 5.9, 23.6) for total score and 21.0 for Life Productivity, 12.1 for Psychological Health, 12.5 for Life Outlook, and 7.3 for Relationships. No inferential testing was conducted for AAQoL due to the prespecified hierarchical testing procedure.
  • ADHD-RS-IV total score LS mean (SE) change at week 10/ET was -10.3 (1.38) for placebo and -21.4 (1.35) for LDX (P<.0001; ES 0.94). At week 10/ET, 22.7% of placebo and 51.9% of LDX participants were classified as not at all or borderline mentally ill on CGI-S.
  • TEAEs were reported by 47/80 (58.8%) placebo and 62/79 (78.5%) LDX participants; common TEAEs included decreased appetite (6.3% vs 32.9%), dry mouth (7.5% vs 31.6%), and headache (2.5% vs 25.3%). There were no deaths or serious AEs; severe TEAEs occurred in 3 (3.8%) LDX and 3 (3.8%) placebo participants.

Methods

  • This was a 10-week randomized, double-blind, multicenter, placebo-controlled, parallel-group study in adults aged 18–55 years with DSM-IV-TR ADHD, baseline ADHD-RS-IV total score ≥28, and clinically significant EFD (BRIEF-A GEC T-score ≥65). Participants were randomized 1:1 to placebo (n=81) or optimized LDX 30, 50, or 70 mg/d (n=80); the safety population included 159 participants and the full analysis set included 154 (75 placebo, 79 LDX).
  • QOL outcomes were self-reported AIM-A (key secondary measure) and self-reported AAQoL (added by protocol amendment, so not all participants completed it). A post hoc subgroup analysis examined participants with both baseline AIM-A and AAQoL scores (n=26 placebo; n=28 LDX).
  • Efficacy analyses used ANCOVA for change with treatment group as factor and baseline as covariate; effect size was the difference in mean change from baseline between LDX and placebo divided by pooled SD. A sequential, hierarchical hypothesis-testing procedure was prespecified to control Type I error.

Limitations

  • The paper states that adults with comorbid psychiatric disease and significant cardiovascular disease were excluded, and participants were required to meet a prespecified level of EFD, limiting generalization. It also notes the subjective, participant-reporting nature of the rating scales, the short trial duration for long-term effects, and that the hierarchical testing program precludes statistical inferences on some measures and post hoc analyses.
  • Evident from the text: the AAQoL was added while the study was in progress, so not all participants completed it; the post hoc subgroup with both AIM-A and AAQoL scores was small (26 placebo, 28 LDX). The paper also states that the small AIM-A Relationships/Communication effect may have been impacted by eligibility criteria requiring stable relationships and by the relatively short study duration.

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

Integrity signals

Registry

Crossref · 10.1186/1471-244x-13-253

Cites

43 of 43 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 22 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    At week 10/ET, 22.7% of placebo and 51.9% of LDX participants were classified as not at all or borderline mentally ill on CGI-S.

    “At baseline on the CGI-S, all participants were rated moderately to severely ill; whereas at week 10/ET, 22.7% of placebo and 51.9% of LDX participants were classified as not at all or borderline mentally ill.”
    Quote in the paperSubstantial claim
  • Findingown data

    ADHD-RS-IV total score LS mean change at week 10/ET was -10.3 for placebo and -21.4 for LDX (P<.0001; effect size 0.94).

    “At week 10/ET, LS mean (SE) changes in the ADHD-RS-IV total score were -10.3 (1.38) for placebo and -21.4 (1.35) for LDX (P<.0001; effect size of 0.94).”
    Quote in the paperSubstantial claim
  • Findingown data

    AAQoL Psychological Health subscale LS mean difference at week 10/ET was 12.1 (95% CI 1.6, 22.5).

    “12.1 (1.6, 22.5) for Psychological Health”
    • Also stated in: § Results · plain
      “Psychological Health was 12.1”
    Quote in the paperNot a substantial claim
  • Findingown data

    LDX improved AIM-A Performance and Daily Functioning scores versus placebo at week 10/ET, with an LS mean difference of 21.6 (95% CI 13.5, 29.7), effect size 0.93, P<.0001.

    “LDX improved AIM-A multi-item domain scores versus placebo; LS mean difference for Performance and Daily Functioning was 21.6 (ES, 0.93, P<.0001)”
    • Also stated in: § Efficacy · plain
      “On the Performance and Daily Functioning Scale, LS mean (SE) change was 17.2 (2.91) for placebo and 38.8 (2.84) for LDX, with an LS mean difference (95% CI) of 21.6 (13.5, 29.7) and an effect size of 0.93.”
    Quote in the paperSubstantial claim
  • Findingown data

    LDX improved AIM-A Impact of Symptoms: Daily Interference scores versus placebo at week 10/ET, with an LS mean difference of 14.9 (95% CI 7.8, 22.0), effect size 0.62, P<.0001.

    “Impact of Symptoms: Daily Interference was 14.9 (ES, 0.62, P<.0001)”
    • Also stated in: § Efficacy · plain
      “For the Impact of Symptoms: Daily Interference Scale, the LS mean (SE) change was 15.7 (2.58) for placebo and 30.6 (2.52) for LDX and the LS mean difference (95% CI) was 14.9 (7.8, 22.0), with the effect size of 0.62.”
    Quote in the paperSubstantial claim
  • May combine two claims. 23
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 23

  • May combine two claims.

    Findingown data

    In a post hoc subgroup of participants with both AIM-A and AAQoL scores, all AIM-A multi-item scales were numerically improved from baseline for LDX versus placebo at week 10/ET and were similar in magnitude to FAS results.

    “For participants enrolled with baseline self-reported AIM-A and AAQoL scores (n=26 placebo; n=28 LDX), all post hoc subgroup AIM-A multi-item scales were numerically improved from baseline for LDX versus placebo at week 10/ET and were similar in magnitude to FAS results.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    AIM-A overall QOL question 4 LS mean difference at week 10/ET was -0.6 (95% CI -0.9, -0.3; P=.0004), effect size 0.44.

    “The LS mean difference (95% CI) was -0.6 (-0.9, –0.3) for Question 4 (P=.0004) and the effect size was 0.44.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    AAQoL total score change was numerically greater for LDX compared with placebo at week 10/ET, with an LS mean difference of 14.7 (95% CI 5.9, 23.6).

    “At week 10/ET, the self-reported AAQoL total score change was numerically greater compared with placebo for LDX participants (Figure 3A); the LS mean difference (95% CI) was 14.7 (5.9, 23.6).”
    Quote in the paperNot a substantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    In the post hoc subgroup, the AIM-A Impact of Symptoms: Daily Interference LS mean difference was 11.7 (95% CI -1.0, 24.3), smaller than in the FAS.

    “For the Impact of Symptoms: Daily Interference scale, the LS mean (SE) change was 20.1 (4.54) for placebo and 31.8 (4.38) for LDX, and the LS mean difference (95% CI) was 11.7 (-1.0, 24.3).”
    • Also stated in: § Results · plain
      “with smaller difference for Impact of Symptoms: Daily Interference.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At week 10/ET, LDX treatment resulted in numerical but not statistically significant improvements versus placebo on AIM-A question 1 (LS mean change 1.4 vs 0.8) and question 4 (LS mean change -1.0 vs -0.5).

    “were numerically but not statistically improved versus placebo with LDX at week 10/ET. The LS mean (SE) change at week 10/ET for placebo and LDX, respectively, were 0.8 (0.31) and 1.4 (0.30) for question 1, and -0.5 (0.22) and -1.0 (0.21) for question 4.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The AIM-A and AAQoL are valid and reliable measures of QOL in adults with ADHD.

  • May combine two claims.

    Findingown data

    LDX treatment produced numerical improvements over placebo on the self-reported AAQoL total and subscale scores, but the prespecified testing hierarchy precludes inferential statistical analysis of the AAQoL.

    “Numerical improvements over placebo were also seen with LDX treatment on the self-reported AAQoL total and subscale scores, although the prespecified testing hierarchy precludes inferential statistical analysis of the AAQoL.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The AIM-A and AAQoL are valid and reliable measures of QOL in adults with ADHD.

  • May combine two claims.

    Findingown data

    In adults with ADHD and significant EF impairment, LDX significantly improved QOL versus placebo on the AIM-A subscales Performance and Daily Functioning, Impact of Symptoms: Daily Interference, Impact of Symptoms: Bother/Concern, and Relationships/Communications.

    “demonstrated significantly improved QOL versus placebo as assessed by the self-reported AIM-A in the subscales of Performance and Daily Functioning, Impact of Symptoms: Daily Interference, Impact of Symptoms: Bother/Concern, and Relationships/Communications.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The AIM-A and AAQoL are valid and reliable measures of QOL in adults with ADHD.

  • May combine two claims.

    Findingown data

    In this study, QOL measures improved along with improvements in self-reported EF (BRIEF-A) and investigator-reported symptom improvement (ADHD-RS-IV).

    “In the current study, QOL measures improved along with improvements in self-reported EF, using the BRIEF-A, and investigator-reported symptom improvement, using the ADHD-RS-IV with adult prompts.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The AIM-A and AAQoL are valid and reliable measures of QOL in adults with ADHD.

  • May combine two claims.

    Findingown data

    No deaths or serious adverse events occurred during the trial.

    “There were no deaths or serious AEs during the trial”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Adults with ADHD in this study reported significantly improved QOL with LDX treatment compared to placebo on the AIM-A Performance and Daily Functioning subscale and numerical improvement on the AAQoL Life Productivity domain.

    “Adults with ADHD in this study reported significantly improved QOL with LDX treatment compared to placebo on the AIM-A Performance and Daily Functioning subscale and numerical improvement on the AAQoL Life Productivity domain.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The AIM-A and AAQoL are valid and reliable measures of QOL in adults with ADHD.

  • May combine two claims.

    Findingown data

    At week 10/ET, mean increases from baseline in systolic blood pressure were 1.7 mm Hg for placebo and 2.6 mm Hg for LDX; in diastolic blood pressure were 1.5 mm Hg for placebo and 1.7 mm Hg for LDX; and in pulse rate were 3.3 bpm for placebo and 5.4 bpm for LDX.

    “mean (SD) increases from baseline in: SBP were 1.7 (9.22) and 2.6 (8.39) (mm Hg); DBP were 1.5 (8.85) and 1.7 (7.60) (mm Hg); and pulse rate were 3.3 (8.35) and 5.4 (10.79) (bpm).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Effect sizes were mostly medium to large in magnitude, except for the AIM-A relationships/communication global domain.

    “Effect sizes were mostly medium to large in magnitude, with the exception of the AIM-A relationships/communication global domain.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The AIM-A and AAQoL are valid and reliable measures of QOL in adults with ADHD.

  • May combine two claims.

    Findingown data

    At week 10/ET, 20% of participants in the placebo group and 39.2% in the LDX group reported 'yes, definitely' on the right track, and 69.3% on placebo and 54.4% on LDX responded 'yes, somewhat' on the right track.

    “At week 10/ET, there was a shift to improvement with 20% of participants in the placebo group and 39.2% in the LDX group reporting “yes, definitely,” and 69.3% on placebo and 54.4% on LDX responding “yes, somewhat” on the right track.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For the AIM-A, all 6 domains were above the prespecified cut-off threshold for hierarchical testing; changes were all statistically significant, with effect sizes ranging from 0.31 to 0.93.

    “For the AIM-A, all 6 domains were above the prespecified cut-off threshold for hierarchical testing; changes were all statistically significant, with effect sizes ranging from 0.31 to 0.93.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The AIM-A and AAQoL are valid and reliable measures of QOL in adults with ADHD.

  • May combine two claims.

    Findingown data

    At week 10/ET, there was a shift to improvement in both groups with 62% to 64% reporting 'a lot' or 'some' limitation and the proportions reporting little or no limitations in both groups increasing from 10%-11% to 36%-37.9%.

    “At week 10/ET, there was a shift to improvement in both groups with 62% to 64% reporting “a lot” or “some” limitation and the proportions reporting little or no limitations in both groups increasing from 10%–11% to 36%–37.9%.”
    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

    Sample size was determined assuming a treatment effect size of 0.56 by a 2-sided, 2-sample t-test at significance level 0.05, requiring at least 52 participants per group for 80% power, and was adjusted up to 80 participants per group to account for key secondary endpoints and anticipated early dropouts.

    “Sample size was determined assuming a treatment effect size of 0.56 by a 2-sided, 2-sample t-test at the significance level of 0.05 requiring at least 52 participants in each treatment group to provide 80% power. The sample size was adjusted up to 80 participants per group to account for key secondary endpoints and anticipated early dropouts.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    A sequential, hierarchical hypothesis testing of the multiple efficacy endpoints was prespecified to maintain control of Type I errors based on multiple hypothesis testing.

    “A sequential, hierarchical hypothesis testing of the multiple efficacy endpoints was prespecified to maintain control of Type I errors based on multiple hypothesis testing.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Adults with symptoms of ADHD may display impairments in executive functioning and in QOL.

    “Adults with symptoms of ADHD may display impairments in executive functioning and in QOL [19].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Adler LA, Spencer TJ, Levine LR, Ramsey JL, Tamura R, Kelsey D, Ball SG, Allen AJ, Biederman J: Functional outcomes in the treatment of adults with ADHD. J Atten Disord. 2008, 11 (6): 720-727. source

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

    Study design and conductnone given

    For the AAQoL, no hypothesis testing or inferential assessments were conducted based on the sequential hierarchical hypothesis testing procedure.

    “For the AAQoL, no hypothesis testing or inferential assessments were conducted based on the sequential hierarchal hypothesis testing procedure used in this study.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    EFD affects outcomes in education, work, social relationships, and psychosocial functioning.

    “EFD affects outcomes in education, work, social relationships, and psychosocial functioning [11,12].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [11] Biederman J, Petty C, Fried R, Fontanella J, Doyle AE, Seidman LJ, Faraone SV: Impact of psychometrically defined deficits of executive functioning in adults with attention deficit hyperactivity disorder. Am J Psychiatry. 2006, 163 (10): 1730-1738. 10.1176/appi.ajp.163.10.1730. source
    • cites [12] Biederman J, Monuteaux MC, Doyle AE, Seidman LJ, Wilens TE, Ferrero F, Morgan CL, Faraone SV: Impact of executive function deficits and attention-deficit/hyperactivity disorder (ADHD) on academic outcomes in children. J Consult Clin Psychol. 2004, 72 (5): 757-766. source

  • Classified as probably not a substantial claim.

    Premisecitation

    Improvements in ADHD symptoms may coincide with improvements in both EF and QOL.

    “Moreover, improvements in ADHD symptoms may coincide with improvements in both EF and QOL [20].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Brown TE, Landgraf JM: Improvements in executive function correlate with enhanced performance and functioning and health-related quality of life: evidence from 2 large, double-blind, randomized, placebo-controlled trials in ADHD. Postgrad Med. 2010, 122 (5): 42-51. 10.3810/pgm.2010.09.2200. source

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

    Study design and conductnone given

    For AIM-A overall QOL questions 2 and 3, no hypothesis testing or inferential assessment was conducted based on the sequential hierarchical hypothesis testing procedure.

    “For AIM-A overall QOL questions 2 and 3, there was no hypothesis testing or inferential assessment conducted based on the sequential hierarchal hypothesis testing procedure used in this study.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Randomization was stratified by cohabitation status (married/cohabitating, not married/cohabitating).

    “Randomization was stratified by cohabitation status (married/cohabitating, not married/cohabitating); within-strata participants were randomized to placebo or LDX groups based on a 4-digit randomization code assigned once eligibility was established.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Overall, adults with ADHD/EFD exhibited self-reported improvement on QOL, using the AIM-A and AAQoL scales in line with medium/large ES; these improvements were paralleled by improvements in EF and ADHD symptoms.

    “Overall, adults with ADHD/EFD exhibited self-reported improvement on QOL, using the AIM-A and AAQoL scales in line with medium/large ES; these improvements were paralleled by improvements in EF and ADHD symptoms.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The safety profile of LDX was consistent with amphetamine use in previous studies.

    “The safety profile of LDX was consistent with amphetamine use in previous studies.”
    • Also stated in: § Conclusions · plain
      “The safety profile of LDX was similar to previous studies.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Blinded assignment of treatment groups was accomplished through an interactive voice/web response system.

    “Blinded assignment of treatment groups was accomplished through an interactive voice/web response system.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    All adult participants and adult informants provided written informed consent.

    “Following detailed explanation of the study, all adult participants and adult informants provided written informed consent.”
    Quote in the paperNot a substantial claim

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

    Study design and conductcitation

    The study was conducted in accordance with the International Conference on Harmonisation Guideline for Good Clinical Practice E6.

    “The study was conducted in accordance with the International Conference on Harmonisation Guideline for Good Clinical Practice E6 [34].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use: ICH Harmonised Tripartite Guideline. Guideline for Good Clinical Practice E6(R1). 2013, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073122.pdf . Accessed May 19, 2013

      Not checked in the free run.

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

    Study design and conductnone given

    The study protocol was approved by the independent Institutional Review Board, Copernicus Group Independent Review Board.

    “The study protocol was approved by the independent Institutional Review Board, Copernicus Group Independent Review Board (Research Triangle Park, NC).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All efficacy assessments presented were for the full analysis set (FAS), which included all participants who took 1 treatment dose in the double-blind evaluation phase and had 1 postbaseline/randomization primary efficacy assessment.

    “All efficacy assessments presented were for the full analysis set (FAS), which included all participants who took 1 treatment dose in the double-blind evaluation phase and had 1 postbaseline/randomization primary efficacy assessment.”
    Quote in the paperSubstantial claim

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

    Interpretationreasoning

    The relatively short study duration may have impacted the change scores and effect size for the AIM-A relationships/communication global domain.

    “Also, the relatively short study duration may have impacted the change scores and hence the effect size for the AIM-A relationships/communication global domain.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The AIM-A and AAQoL are valid and reliable measures of QOL in adults with ADHD.

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

    Premisecitation

    The AAQoL scale exhibited responsiveness to ADHD treatment in an 8-week, randomized, placebo-controlled trial of the nonstimulant atomoxetine.

    “Another validated QOL measure, the 29-item self-reported Adult ADHD QoL (AAQoL) scale [24], exhibited responsiveness to ADHD treatment in an 8-week, randomized, placebo-controlled trial of the nonstimulant atomoxetine [21].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [24] Brod M, Johnston J, Able S, Swindle R: Validation of the Adult Attention-Deficit/Hyperactivity Disorder Quality-of-Life Scale (AAQoL): a disease-specific quality-of-life measure. Qual Life Res. 2006, 15 (1): 117-129. 10.1007/s11136-005-8325-z. source
    • cites [21] Matza LS, Johnston JA, Faries DE, Malley KG, Brod M: Responsiveness of the Adult Attention-Deficit/Hyperactivity Disorder Quality of Life Scale (AAQoL). Qual Life Res. 2007, 16 (9): 1511-1520. 10.1007/s11136-007-9254-9. source

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

    Study design and conductnone given

    The predefined hierarchical statistical testing program precludes statistical inferences on some measures, and no statistical inferences were made based on post hoc analyses.

    “The predefined hierarchical statistical testing program precludes statistical inferences on some of the measures, and no statistical inferences were made based on the post hoc analyses.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    For the post hoc analysis, there were no multiplicity adjustments performed on the subgroup statistical comparisons.

    “For the post hoc analysis, there were no multiplicity adjustments performed on the subgroup statistical comparisons.”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    There was no hypothesis testing or inferential assessment conducted for the remaining endpoints and the corresponding null hypotheses were not rejected.

    “There was no hypothesis testing or inferential assessment conducted for the remaining endpoints and the corresponding null hypotheses were not rejected.”
    Quote in the paperSubstantial claim

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

    Interpretationreasoning

    Because adults with comorbid psychiatric disease and significant cardiovascular disease were excluded, results should be generalized to the overall population with caution.

    “Since adults with comorbid psychiatric disease and significant cardiovascular disease were excluded from the current study population, caution should be taken when generalizing results to the overall population.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The BRIEF-A scoring employs T-scores, where the normative population mean is set at 50, with a SD of 10; a T-score ≥65 indicates clinically significant EF impairments.

    “The BRIEF-A scoring employs T-scores, where the normative population mean is set at 50, with a SD of 10. A T-score ≥65 indicates clinically significant EF impairments [15]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Roth RM, Isquith PK, Gioia GA: Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A). 1999, Lutz, FL: Psychological Assessment Resources, Inc.

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    When a nonsignificant difference was first observed at a P>.05 level, no further testing of the remaining hypotheses was allowed.

    “When a nonsignificant difference was first observed at a P>.05 level, no further testing of the remaining hypotheses was allowed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The AIM-A multi-item scale is a validated QOL measure that has demonstrated treatment sensitivity in a double-blind, placebo-controlled study of a long-acting psychostimulant.

    “The self-reported Adult ADHD Impact Module (AIM-A) [22] multi-item scale is a validated QOL measure that has demonstrated treatment sensitivity in a double-blind, placebo-controlled study of a long-acting psychostimulant [23].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [22] Landgraf JM: Monitoring quality of life in adults with ADHD: reliability and validity of a new measure. J Atten Disord. 2007, 11 (3): 351-362. 10.1177/1087054707299400. source
    • cites [23] Spencer TJ, Landgraf JM, Adler LA, Weisler RH, Anderson CS, Youcha SH: Attention-deficit/hyperactivity disorder–specific quality of life with triple-bead mixed amphetamine salts (SPD465) in adults: results of a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2008, 69 (11): 1766-1775. 10.4088/JCP.v69n1112. source

  • May combine two claims.

    Interpretationreasoning

    LDX treatment might result in improvements in multiple functional areas affected by ADHD, and researchers and clinicians have available tools to monitor such improvements.

    “Overall, these findings suggest that LDX treatment might result in improvements in multiple functional areas affected by ADHD, and that researchers as well as clinicians have available tools and resources to monitor such improvements [41].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] Ramos-Quiroga JA, Casas M: Achieving remission as a routine goal of pharmacotherapy in attention-deficit hyperactivity disorder. CNS Drugs. 2011, 25 (1): 17-36. 10.2165/11538450-000000000-00000. source
    • Rests on an assumption: The AIM-A and AAQoL are valid and reliable measures of QOL in adults with ADHD.

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

    Interpretationreasoning

    The subjective, participant-reporting nature of the rating scales limits interpretation because variability in rating scores among individual participants cannot be accounted for.

    “The subjective, participant-reporting nature of such rating scales should also be considered because it is not possible to account for variability in rating scores among individual participants.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Since deficits in EF domains may impact QOL across various life domains, concurrent assessments of EF and QOL may more fully quantify patient improvement on ADHD treatment.

    “Since deficits in EF domains may impact QOL across various life domains, concurrent assessments of EF and QOL may more fully quantify patient improvement on ADHD treatment.”
    Quote in the paperNot a substantial claim
42 of 42

  • The paper relies on this without support.

    The subset of participants who completed the AAQoL (added mid-study) is representative of the full study population.

    “The AAQoL was added to the study as a protocol amendment and was not used on all participants.”
    “Only new participants, who performed the assessment at baseline, were able to complete the AAQoL.”

  • The paper relies on this without support.

    The post hoc subgroup of participants with both AIM-A and AAQoL scores is representative of the full analysis set.

    “For participants enrolled with baseline self-reported AIM-A and AAQoL scores (n=26 placebo; n=28 LDX), all post hoc subgroup AIM-A multi-item scales were numerically improved from baseline for LDX versus placebo at week 10/ET and were similar in magnitude to FAS results.”

  • The paper relies on this without support.

    The enrolled sample is representative of adults with ADHD and EFD in general.

    “Enrolled eligible adults (aged 18 to 55 years inclusive at time of consent) met full Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) [33] criteria for a diagnosis of ADHD and had clinically significant EFD [32].”

  • The paper relies on this without support.

    The AIM-A and AAQoL are valid and reliable measures of QOL in adults with ADHD.

    “Real-life outcomes, such as productivity, can be assessed using these validated QOL scales”
4 of 4

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.

  • AAQoL total-score difference reported as both 21.0 and 14.7

    Minor

    The abstract reports an AAQoL total-score LS mean difference of 21.0, whereas the Results section reports 14.7 for the same measure at week 10/ET. The abstract also gives 21.0 for the Life Productivity subscale, suggesting the total-score value was duplicated from that subscale.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. Brown TE: Brown Attention-Deficit Hyperactivity Disorder Scales for Adolescents and Adults. 1996, San Antonio, TX: The Psychological Corporation
  2. Wayne PA: Vyvanse [package insert]. 2012, Wayne, PA: Shire US Inc
  3. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use: ICH Harmonised Tripartite Guideline. Guideline for Good Clinical Practice E6(R1). 2013, http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073122.pdf . Accessed May 19, 2013

Cited by

Sorted by citations

Related

Authors
Adler, L. A., Dirks, B., Deas, P., Raychaudhuri, A., Dauphin, M., Saylor, K., & Weisler, R.
Affiliations
  • VA NY Harbor Healthcare System (US)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
Adler, Lenard A
ORCID
Venue
BMC Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2013-10-09
Volume
13
Issue
1
Pages
253-253
ISSN
1471-244X (ISSN-L)
DOI
10.1186/1471-244x-13-253
PMC
PMC3854089
OpenAlex
W2090246833
Semantic Scholar
3948ed3b5d33d8c5d4700678991b6799c313d700
Cited by
45
References
43
Citations by year
2026: 3 · 2025: 4 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 7 · 2016: 3 · 2015: 3 · 2014: 2
FWCI
1.90
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Psychiatry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
  • Bristol-Myers Squibb
  • Eli Lilly and Company
  • Pfizer
  • GlaxoSmithKline
  • Sanofi
  • CeNeRx
  • Sunovion
  • Otsuka America
  • Dainippon Sumitomo Pharma
  • Eisai
  • H. Lundbeck A/S
  • Centers for Disease Control and Prevention
  • National Institute of Mental Health
  • UCB Pharma
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neuroethics, Human Enhancement, Biomedical Innovations
Keywords
lisdexamfetamine dimesylate, adult ADHD, executive dysfunction, quality of life, stimulant medication, BRIEF-A, symptom interference, daily functioning, mental health, well-being, placebo comparison, subgroup analysis
MeSH terms
Lisdexamfetamine Dimesylate, Activities of Daily Living, Adult, Central Nervous System Stimulants, Attention, Attention Deficit Disorder with Hyperactivity, Dextroamphetamine, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Male, Neuropsychological Tests, Quality of Life, Treatment Outcome, Executive Function, Self Report

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 2026-10-27.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-27.

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