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Cited by 137Attention Deficit Hyperactivity DisorderPharmaceutical studies and practicesBehavioral and Psychological Studies

Comparative efficacy and acceptability of methylphenidate and atomoxetine in treatment of attention deficit hyperactivity disorder in children and adolescents: a meta-analysis

Open access
Hanwella, Raveen, Senanayake, Madhri, de Silva, Varuni·2011·BMC Psychiatry
DOI 10.1186/1471-244x-11-176PMC PMC3229459
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Abstract

Background: Psychostimulants and non stimulants are effective in the treatment of ADHD. Efficacy of both methylphenidate and atomoxetine has been established in placebo controlled trials. Direct comparison of efficacy is now possible due to availability of results from several head-to-head trials of these two medications. Methods: All published, randomized, open label or double blind trials, comparing efficacy of methylphenidate with atomoxetine, in treatment of ADHD in children, diagnosed using DSM-IV™ criteria were included. The outcome studied was ADHDRS-IVParent:Inv score. The standardized mean difference (SMD) was used as a measure of effect size. Results: Nine randomized trials comparing methylphenidate and atomoxetine, with a total of 2762 participants were included. Meta-analysis did not find a significant difference in efficacy between methylphenidate and atomoxetine (SMD = 0.09, 95% CI -0.08-0.26) (Z = 1.06, p = 0.29). Synthesis of data from eight trials found no significant difference in response rates (RR = 0.93 95% CI 0.76-1.14, p = 0.49). Sub group analysis showed a significant standardized mean difference favouring OROS methylphenidate (SMD = 0.32, 95% CI 0.12-0.53 (Z = 3.05, p < 0.002). Immediate release methylphenidate was not superior to atomoxetine (SMD = -0.04, 95% CI -0.19-0.12) (Z = 0.46, p = 0.64). Excluding open label trials did not significantly alter the effect size (SMD = 0.08, 95% CI -0.04-0.21) (Z = 1.27, p = 0.20). All-cause discontinuation was used as a measure of acceptability. There was no significant difference in all cause discontinuation between atomoxetine and methylphenidate (RR 1.22, 95% CI 0.87-1.71). There was significant heterogeneity among the studies (p = 0.002, I 2 = 67%). Subgroup analysis demonstrated the heterogeneity to be due to the open label trials (p = 0.001, I 2 = 81%). Conclusions: In general atomoxetine and methylphenidate have comparable efficacy and equal acceptability in treatment of ADHD in children and adolescents. However OROS methylphenidate is more effective than atomoxetine and may be considered as first line treatment in treatment of ADHD in children and adolescents.

AI snapshot

Written from the paper’s full text.

TL;DR

This meta-analysis of nine randomized head-to-head trials in children and adolescents with ADHD found no overall significant efficacy difference between methylphenidate and atomoxetine, but OROS methylphenidate was superior in subgroup analysis. Acceptability, measured by all-cause discontinuation, did not differ significantly between the two medications.

Key findings

  • Overall efficacy did not differ significantly between methylphenidate and atomoxetine: SMD = 0.09 (95% CI -0.08–0.26; Z = 1.06, p = 0.29). Response rates also did not differ: RR = 0.93 (95% CI 0.76–1.14, p = 0.49).
  • Subgroup analysis favored OROS methylphenidate over atomoxetine: SMD = 0.32 (95% CI 0.12–0.53; Z = 3.05, p < 0.002). Immediate-release methylphenidate was not superior to atomoxetine: SMD = -0.04 (95% CI -0.19–0.12; Z = 0.46, p = 0.64).
  • All-cause discontinuation did not differ significantly: RR = 1.22 (95% CI 0.87–1.71, p = 0.25).
  • Significant heterogeneity was present (p = 0.002, I² = 67%), attributed to open-label trials (p = 0.001, I² = 81%); double-blind trials showed no significant heterogeneity (p = 0.48, I² = 0%).

Methods

  • Systematic review and meta-analysis of published randomized open-label or double-blind trials comparing methylphenidate with atomoxetine in children and adolescents diagnosed with ADHD using DSM-IV criteria; searches covered January 1995–December 2010 in PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and reference lists.
  • Nine trials with 2,762 participants aged 6–16 years were included. The primary outcome was ADHDRS-IV Parent:Inv score; random-effects meta-analysis used standardized mean difference, and dichotomous outcomes used risk ratios via Mantel-Haenszel method in RevMan 5.0.
  • Methodological quality was assessed with the Detsky Quality Scale; all included studies scored more than 12. Subgroup analysis examined methylphenidate formulation, and sensitivity analyses excluded open-label and crossover trials.

Limitations

  • Stated by the authors: substantial heterogeneity across studies, mainly from open-label trials; small numbers within subgroups may limit power; unpublished data, conference abstracts, dissertations, and pharmaceutical company data were not included, so publication bias is possible; funnel plot asymmetry tests were not done because fewer than 10 studies were included; many trials excluded comorbid subpopulations, limiting generalizability; seven studies were funded by Eli Lilly and one by McNeil; design features such as lack of teacher ratings disadvantaged methylphenidate.
  • Evident in the text: only one included study used teacher ratings; the largest trial was only 3 weeks long, which may be inadequate for atomoxetine’s optimal efficacy; some trials excluded prior poor methylphenidate responders, potentially favoring methylphenidate.

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

Integrity signals

Registry

Crossref · 10.1186/1471-244x-11-176

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

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

Claims the paper makes

0 of 30 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Subgroup analysis found the heterogeneity was due to the open label trials (p = 0.001, I2 = 81%).

    “Subgroup analysis demonstrated the heterogeneity to be due to the open label trials (p = 0.001, I2 = 81%).”
    • Also stated in: § Heterogeneity · plain
      “Subgroup analysis found that the heterogeneity was due to the open label trials (p = 0.001, I2 = 81%).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Open label trials introduce bias because patient and investigator expectations can influence outcome.
  • Findingown data

    There was no significant difference in all-cause discontinuation between atomoxetine and methylphenidate (RR = 1.22, 95% CI 0.87-1.71, p = 0.25).

    “There was no significant difference in all cause discontinuation between atomoxetine and methylphenidate (RR 1.22, 95% CI 0.87-1.71).”
    • Also stated in: § Acceptability · plain
      “There was no significant difference in all cause discontinuation between atomoxetine and methylphenidate (RR 1.22, 95% CI 0.87-1.71, p = 0.25).”
    Quote in the paperSubstantial claim
  • Findingown data

    Subgroup analysis showed a significant standardized mean difference favouring OROS methylphenidate over atomoxetine (SMD = 0.32, 95% CI 0.12-0.53, Z = 3.05, p < 0.002).

    “Sub group analysis showed a significant standardized mean difference favouring OROS methylphenidate (SMD = 0.32, 95% CI 0.12-0.53 (Z = 3.05, p < 0.002).”
    • Also stated in: § Sub group analysis · plain
      “Sub group analysis showed a significant standardized mean difference favouring OROS methylphenidate 0.32 (95% CI 0.12-0.53 (Z = 3.05, p < 0.002).”
    Quote in the paperSubstantial claim
  • Findingown data

    There was no significant heterogeneity among double blind trials (p = 0.48, I2 = 0%).

    “There was no significant heterogeneity among double blind trials (p = 0.48 I2 = 0%).”
    Quote in the paperSubstantial claim
  • Findingown data

    Immediate release methylphenidate was not superior to atomoxetine (SMD = -0.04, 95% CI -0.19-0.12, Z = 0.46, p = 0.64).

    “Immediate release methylphenidate was not superior to atomoxetine (SMD = -0.04, 95% CI -0.19-0.12) (Z = 0.46, p = 0.64).”
    • Also stated in: § Sub group analysis · plain
      “Immediate release methylphenidate was not superior to atomoxetine SMD -0.04 (95% CI -0.19-0.12) (Z = 0.46, p = 0.64).”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 13
  • May combine two claims. 11
  • The quote only partly states this claim. 1

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

    Findingown data

    Of all trial participants, 36% were diagnosed as having comorbid oppositional defiant disorder.

    “Comorbid oppositional defiant disorder was diagnosed in 36%.”
    • Also stated in: § Discussion · plain
      “Of all the trial participants 36% were diagnosed as having comorbid ODD.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Meta-analysis found no statistically significant difference in efficacy between methylphenidate and atomoxetine (SMD = 0.09, 95% CI -0.08 to 0.26, Z = 1.06, p = 0.29), although the effect size favoured methylphenidate.

    “Meta-analysis did not find a significant difference in efficacy between methylphenidate and atomoxetine (SMD = 0.09, 95% CI -0.08-0.26) (Z = 1.06, p = 0.29).”
    • Also stated in: § Meta-analysis · plain
      “Meta-analysis did not find a significant difference in efficacy between methylphenidate and atomoxetine when standardized mean difference (SMD) was used as a measure of effect size 0.09 (95% CI -0.08-0.26) (Z = 1.06, p = 0.29).”
    • Also stated in: § Discussion · plain
      “This meta-analysis shows that in children and adolescents with ADHD, although the effect size favours methylphenidate the difference was not statistically significant.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Nine randomized trials comparing methylphenidate and atomoxetine in ADHD children and adolescents were included, with a total of 2762 participants.

    “Nine randomized trials comparing methylphenidate and atomoxetine, with a total of 2762 participants were included.”
    • Also stated in: § Study characteristics · plain
      “Nine randomized trials comparing methylphenidate and atomoxetine in the treatment of ADHD in children and adolescents were identified (total participants 2762) [18-21,27-30].”
    Quote in the paperSubstantial claim0 of 8 sources checked
    • cites [18] Sangal RB, Owens J, Allen AJ, Sutton V, Schuh K, Kelsey D: Effects of atomoxetine and methylphenidate on sleep in children with ADHD. Sleep. 2006, 29 (12): 1573-1585. source

      Not checked in the free run.

    • cites [19] Kemner JE, Starr HL, Ciccone PE, Hooper-Wood CG, Crockett RS: Outcomes of OROS methylphenidate compared with atomoxetine in children with ADHD: a multicenter, randomized prospective study. Adv Ther. 2005, 22 (5): 498-512. 10.1007/BF02849870. source

      Not checked in the free run.

    • cites [20] Prasad S, Harpin V, Poole L, Zeitlin H, Jamdar S, Puvanendran K: A multi-centre, randomised, open-label study of atomoxetine compared with standard current therapy in UK children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Curr Med Res Opin. 2007, 23 (2): 379-394. 10.1185/030079906X167309. source

      Not checked in the free run.

    • cites [21] Spencer T, Heiligenstein JH, Biederman J, Faries DE, Kratochvil CJ, Conners CK, Potter WZ: Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2002, 63 (12): 1140-1147. 10.4088/JCP.v63n1209. source

      Not checked in the free run.

    • cites [27] Kratochvil CJ, Heiligenstein JH, Dittmann R, Spencer TJ, Biederman J, Wernicke J, Newcorn JH, Casat C, Milton D, Michelson D: Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry. 2002, 41 (7): 776-784. 10.1097/00004583-200207000-00008. source

      Not checked in the free run.

    • cites [28] Newcorn JH, Kratochvil CJ, Allen AJ, Casat CD, Ruff DD, Moore RJ, Michelson D: Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: acute comparison and differential response. Am J Psychiatry. 2008, 165 (6): 721-730. 10.1176/appi.ajp.2007.05091676. source

      Not checked in the free run.

    • cites [29] Wang Y, Zheng Y, Du Y, Song DH, Shin YJ, Cho SC, Kim BN, Ahn DH, Marquez-Caraveo ME, Gao H, et al: Atomoxetine versus methylphenidate in paediatric outpatients with attention deficit hyperactivity disorder: a randomized, double-blind comparison trial. Aust N Z J Psychiatry. 2007, 41 (3): 222-230. 10.1080/00048670601057767. source

      Not checked in the free run.

    • cites [30] Yildiz O, Sismanlar SG, Memik NC, Karakaya I, Agaoglu B: Atomoxetine and Methylphenidate Treatment in Children with ADHD: The Efficacy, Tolerability and Effects on Executive Functions. Child Psychiatry Hum Dev. 2010

      Not checked in the free run.

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

    Findingown data

    Response rates were available for eight trials, and the definition of response varied between trials.

    “Response rates were available for eight trials. Definition of response varied between trials.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The different definitions of response used across trials are sufficiently comparable to be pooled in a single risk ratio.

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

    Study design and conductnone given

    Data was double entered by two authors.

    “Data was double entered by two authors.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The standardized mean difference in ADHD scores between atomoxetine and methylphenidate using parent ratings was relatively small, and the difference may have been larger if studies had used teacher ratings.

    “Our meta-analysis found that the standardized mean difference in ADHD scores between atomoxetine and methylphenidate using parent ratings were relatively small and the difference may have been much larger if studies had used teacher ratings, because teacher ratings evaluate behavior during school hours.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Parent ratings evaluate behaviours occurring outside school hours.
    • Rests on an assumption: Teacher ratings evaluate behavior during school hours.

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

    Study design and conductnone given

    Data was extracted independently by two authors using a predesigned data extraction form.

    “Data was extracted independently by two authors using a predesigned data extraction form.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    Several design features would have influenced the outcome of trials, including non-inclusion of teacher rating scales, which would have been a disadvantage for methylphenidate.

    “In addition several design features would have influenced the outcome of trials including non- inclusion of teacher rating scales which would have been a disadvantage for methylphenidate.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    Seven studies were funded by Eli Lilly and Company, and one study was sponsored by McNeil Consumer and Specialty Pharmaceuticals.

    “Seven studies were funded by Eli Lilly and Company manufacturers of atomoxetine and one study was sponsored by McNeil Consumer and Specialty Pharmaceuticals [19].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Kemner JE, Starr HL, Ciccone PE, Hooper-Wood CG, Crockett RS: Outcomes of OROS methylphenidate compared with atomoxetine in children with ADHD: a multicenter, randomized prospective study. Adv Ther. 2005, 22 (5): 498-512. 10.1007/BF02849870. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    In general, atomoxetine and methylphenidate have comparable efficacy and equal acceptability in treatment of ADHD in children and adolescents.

    “In general atomoxetine and methylphenidate have comparable efficacy and equal acceptability in treatment of ADHD in children and adolescents.”
    • Also stated in: § Discussion · plain
      “The results from the meta-analysis show that in general atomoxetine and methylphenidate have comparable efficacy and equal acceptability in treatment of ADHD in children and adolescents.”
    • Also stated in: § Discussion · plain
      “In general atomoxetine and methylphenidate have comparable efficacy and equal acceptability in treatment of ADHD in children and adolescents.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Methodological quality of included studies was evaluated using the Detsky Quality Scale, and all selected studies scored more than 12 and were included.

    “Methodological quality of the included studies was evaluated using the Detsky Quality Scale for Randomized Trials [17].”
    • Also stated in: § Study selection · plain
      “Since all selected studies scored more than 12 on the Detsky quality scale, all were included in the meta-analysis.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbe KA: Incorporating variations in the quality of individual randomized trials into meta-analysis. J Clin Epidemiol. 1992, 45 (3): 255-265. 10.1016/0895-4356(92)90085-2. source

      Not checked in the free run.

    • Rests on an assumption: A Detsky Quality Scale score greater than 12 indicates adequate methodological quality for inclusion.

  • May combine two claims.

    Study design and conductreasoning

    Unpublished data from conference abstracts, dissertations and unpublished pharmaceutical company data were not included, so publication bias is a distinct possibility.

    “We did not include unpublished data from conference abstracts, dissertations and unpublished pharmaceutical company data, therefore publication bias is a distinct possibility.”
    Quote in the paperSubstantial claim

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

    Study design and conductcitation

    Tests for funnel plot asymmetry were not done because the Cochrane handbook recommends at least 10 studies.

    “Tests for funnel plot asymmetry were not done as the Cochrane handbook for systematic reviews recommends that tests for funnel plot asymmetry should be used only when there are at least 10 studies included in the meta-analysis [45].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Higgins JPT, Green S, Cochrane Collaboration: Cochrane handbook for systematic reviews of interventions. 2008, Chichester, England; Hoboken, NJ: Wiley-Blackwell source

      Not checked in the free run.

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

    Interpretationnone given

    Use of higher doses of atomoxetine administered twice daily may result in better outcome.

    “Use of higher doses of atomoxetine administered twice daily may result in better outcome.”
    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 conductcitation

    When data on standard deviations were missing, study authors were contacted or data were calculated using standard error of subgroups or confidence intervals.

    “When data on standard deviations were missing, study authors were contacted to provide missing data [18] or it was calculated using the standard error of subgroups or confidence intervals [19-21].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [18] Sangal RB, Owens J, Allen AJ, Sutton V, Schuh K, Kelsey D: Effects of atomoxetine and methylphenidate on sleep in children with ADHD. Sleep. 2006, 29 (12): 1573-1585. source

      Not checked in the free run.

    • cites [19] Kemner JE, Starr HL, Ciccone PE, Hooper-Wood CG, Crockett RS: Outcomes of OROS methylphenidate compared with atomoxetine in children with ADHD: a multicenter, randomized prospective study. Adv Ther. 2005, 22 (5): 498-512. 10.1007/BF02849870. source

      Not checked in the free run.

    • cites [20] Prasad S, Harpin V, Poole L, Zeitlin H, Jamdar S, Puvanendran K: A multi-centre, randomised, open-label study of atomoxetine compared with standard current therapy in UK children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Curr Med Res Opin. 2007, 23 (2): 379-394. 10.1185/030079906X167309. source

      Not checked in the free run.

    • cites [21] Spencer T, Heiligenstein JH, Biederman J, Faries DE, Kratochvil CJ, Conners CK, Potter WZ: Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2002, 63 (12): 1140-1147. 10.4088/JCP.v63n1209. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Two trials excluded participants with previous poor response to methylphenidate, a design feature that would have favoured methylphenidate.

    “Two trials excluded participants with previous poor response to methylphenidate, a design feature which would have favoured methylphenidate [27,28].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [27] Kratochvil CJ, Heiligenstein JH, Dittmann R, Spencer TJ, Biederman J, Wernicke J, Newcorn JH, Casat C, Milton D, Michelson D: Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry. 2002, 41 (7): 776-784. 10.1097/00004583-200207000-00008. source

      Not checked in the free run.

    • cites [28] Newcorn JH, Kratochvil CJ, Allen AJ, Casat CD, Ruff DD, Moore RJ, Michelson D: Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: acute comparison and differential response. Am J Psychiatry. 2008, 165 (6): 721-730. 10.1176/appi.ajp.2007.05091676. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The effect of immediate release methylphenidate may wear off later in the day, which could account for its lower efficacy when administered only once or twice daily.

    “The effect of IR MPH may wear off later in the day and this could account for the lower efficacy when IR MPH was administered only once or twice daily.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The effect of immediate release methylphenidate wears off later in the day.

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

    Study design and conductnone given

    Disagreement about selection of articles was resolved by discussion between two authors and, if needed, by the third author.

    “Disagreement about selection of articles was resolved by discussion between two authors and if agreement could not be reached, by the third author.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Titles and abstracts of selected studies were reviewed independently by two authors.

    “Titles and abstracts of selected studies were reviewed independently by two authors.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    There are reports that osmotically released methylphenidate is more effective than immediate release methylphenidate.

    “There are reports that osmotically released methylphenidate is more effective than immediate release methylphenidate (IR MPH) [26].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Steele M, Weiss M, Swanson J, Wang J, Prinzo RS, Binder CE: A randomized, controlled effectiveness trial of OROS-methylphenidate compared to usual care with immediate-release methylphenidate in attention deficit-hyperactivity disorder. Can J Clin Pharmacol. 2006, 13 (1): e50-62.

      Not checked in the free run.

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

    Study design and conductreasoning

    A sensitivity analysis excluding the cross-over trial was conducted because study results may be affected by a carry-over effect.

    “One study used a cross-over design. As study results may be affected by a carry-over effect, we also conducted a sensitivity analysis excluding the cross-over trial.”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    A sensitivity analysis excluding open label trials was carried out because of the difference in methodological quality between double blind and open label trials.

    “Because of the difference in methodological quality between double blind studies and open label trials, a sensitivity analysis was carried out excluding open label trials.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Open label trials introduce bias because patient and investigator expectations can influence outcome.
22 of 22

  • The paper relies on this without support.

    The different definitions of response used across trials are sufficiently comparable to be pooled in a single risk ratio.

    “Definition of response varied between trials.”

  • The paper relies on this without support.

    OROS methylphenidate provides coverage in the late afternoon and evening.

    “In contrast long acting OROS-methylphenidate which provides coverage in the late afternoon and evening may have an advantage over the immediate release form.”

  • The paper relies on this without support.

    A Detsky Quality Scale score greater than 12 indicates adequate methodological quality for inclusion.

    “Since all selected studies scored more than 12 on the Detsky quality scale, all were included in the meta-analysis.”

  • The paper relies on this without support.

    Open label trials introduce bias because patient and investigator expectations can influence outcome.

    “Open label studies introduce bias as patient and investigator expectations can influence outcome.”

  • The paper relies on this without support.

    Parent ratings evaluate behaviours occurring outside school hours.

    “Symptom severity was assessed using the parent version of ADHDRS-IV and parents are likely to evaluate behaviours occurring outside school hours.”

  • The paper relies on this without support.

    Teacher ratings evaluate behavior during school hours.

    “because teacher ratings evaluate behavior during school hours.”

  • The paper relies on this without support.

    The effect of immediate release methylphenidate wears off later in the day.

    “The effect of IR MPH may wear off later in the day and this could account for the lower efficacy when IR MPH was administered only once or twice daily.”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Statistics that don’t add up

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

  • p-value fits an unstated one-tailed test: (Z = 3.05, p < .002

    Minor

    The paper reports p < .002 here; recomputing from the test statistic and its degrees of freedom gives p = .002 (two-tailed). The reported value is what a one-tailed test gives, but the paper does not say near this result that a one-tailed test was used.

    Reported p < .002 · recomputed p = .002

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 upz = 3.05reported p < .002 · recomputed p = .002

    “(Z = 3.05, p < .002”

  • Consistentz = 1.06reported p = .29 · recomputed p = .289

    “(Z = 1.06, p = .29”

  • Consistentz = 0.46reported p = .64 · recomputed p = .646

    “(Z = 0.46, p = .64”

  • Consistentz = 1.27reported p = .2 · recomputed p = .204

    “(Z = 1.27, p = .20”

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.

  • Atomoxetine dose range excludes the Kemner trial

    Minor

    The stated lower bound is 1.28 mg/kg, apart from a noted exception for slow metabolizers. Table 2 lists a mean dose of 1.08 mg/kg for Kemner 2005.

  • Reported trial-duration range excludes a 12-week trial

    Minor

    The stated maximum duration is 10 weeks, but Table 2 lists Yildiz2010 as lasting 12 weeks.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. Faraone SV, Sergeant J, Gillberg C, Biederman J: The worldwide prevalence of ADHD: is it an American condition?. World Psychiatry. 2003, 2 (2): 104-113.
  2. Turgay: Disruptive Behavior Disorders Child and Adolescent Screening and Rating Scales for Children, Adolescents, Parents, and Teachers. 1994, West Blomfield: Integrative Therapy Institute Publication
  3. The Nordic Cochrane Centre: Review Manager (RevMan) [ComputerProgram] Version 5.0. 2008, Copenhagen: The Cochrane Collaboration, Version 5.0
  4. Cheng JY, Chen RY, Ko JS, Ng EM: Efficacy and safety of atomoxetine for attention-deficit/hyperactivity disorder in children and adolescents-meta-analysis and meta-regression analysis. Psychopharmacology (Berl). 2007, 194 (2): 197-209. 10.1007/s00213-007-0840-x. · DOI · Paper page

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Related

Authors
Hanwella, R., Senanayake, M., & de Silva, V.
Affiliations
University of Colombo (LK)
ORCID
Hanwella, Raveen
Venue
BMC Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2011-11-10
Volume
11
Issue
1
Pages
176-176
ISSN
1471-244X (ISSN-L)
DOI
10.1186/1471-244x-11-176
PMC
PMC3229459
OpenAlex
W2066232148
Semantic Scholar
b5909f8ef65679f083267a805d00534d5a14c992
Cited by
137
References
44
Citations by year
2026: 2 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 7 · 2016: 15 · 2015: 28 · 2014: 16 · 2013: 16 · 2012: 9
FWCI
1.72
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)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
  • Social Sciences › Psychology › Developmental and Educational Psychology › Behavioral and Psychological Studies
Keywords
methylphenidate, atomoxetine, attention deficit hyperactivity disorder, children and adolescents, psychostimulants, non-stimulant medication, OROS methylphenidate, immediate-release methylphenidate, treatment efficacy, treatment acceptability, drug discontinuation, head-to-head comparison, subgroup analysis, heterogeneity
MeSH terms
Atomoxetine Hydrochloride, Adolescent, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Child, Humans, Methylphenidate, Propylamines, Treatment Outcome

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 2026-10-10.

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

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 ›

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