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Cited by 140Attention Deficit Hyperactivity DisorderBehavioral and Psychological StudiesDevelopmental and Educational Neuropsychology

Advances in understanding and treating ADHD

Open access
Antshel, Kevin M, Hargrave, Teresa M, Simonescu, Mihai, Kaul, Prashant, Hendricks, Kaitlin, Faraone, Stephen V·2011·BMC Medicine
DOI 10.1186/1741-7015-9-72PMC PMC3126733
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Abstract

Attention deficit hyperactivity disorder (ADHD) is a neurocognitive behavioral developmental disorder most commonly seen in childhood and adolescence, which often extends to the adult years. Relative to a decade ago, there has been extensive research into understanding the factors underlying ADHD, leading to far more treatment options available for both adolescents and adults with this disorder. Novel stimulant formulations have made it possible to tailor treatment to the duration of efficacy required by patients, and to help mitigate the potential for abuse, misuse and diversion. Several new non-stimulant options have also emerged in the past few years. Among these, cognitive behavioral interventions have proven popular in the treatment of adult ADHD, especially within the adult population who cannot or will not use medications, along with the many medication-treated patients who continue to show residual disability.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review summarizes advances in understanding ADHD as a complex neurobiological disorder and in treating it with stimulant and non-stimulant medications plus psychosocial approaches. It emphasizes that newer formulations and CBT expand options, but many patients still have residual impairment, comorbidity, and adherence problems.

Key findings

  • ADHD prevalence estimates have risen from 3 to 5% of school-age children to about 7 to 8% of school-age children and 4 to 5% of adults; “uncomplicated” ADHD may exist in about 20 to 25% of adults with ADHD.
  • Stimulants remain first-line and are more efficacious than non-stimulants; long-acting formulations and the prodrug lisdexamfetamine dimesylate may reduce abuse, misuse, and diversion risk.
  • In adults with ADHD, 12 sessions of CBT produced more treatment responders (53%) than relaxation training and educational support (23%), with gains maintained at 6 and 12 months; however, one group CBT workshop program had one-third of participants drop out.
  • Only 49% of adults with ADHD were prescribed long-acting agents, and even in non-comorbid ADHD, optimal functioning occurs in only roughly one in four children.

Methods

  • Design: narrative review of current conceptualizations of ADHD causes and advances in treatment, including stimulant and non-stimulant medication and cognitive behavioral therapy.
  • Data/sample: published literature and prior studies; no primary participant sample or systematic search strategy is reported.
  • Main analysis: qualitative synthesis, with tables summarizing DSM-IV diagnostic criteria, pharmacological treatments, and non-pharmacological interventions.

Limitations

  • The paper states that pharmacogenetics “cannot yet guide treatment choices,” that evidence for CBT as a stand-alone treatment is limited, that long-term cardiovascular side-effects are less certain, and that little is known about predictors of long-term adherence.
  • Evident from the text: as a narrative review, it does not report a systematic search, inclusion criteria, risk-of-bias assessment, or quantitative synthesis, so findings may be selectively presented.

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

Integrity signals

Registry

Crossref · 10.1186/1741-7015-9-72

Cites

137 of 137 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 100 cited sources checked · 0 supported · 0 flagged

  • Interpretationreasoning

    ADHD is a complex neurobiological disorder.

    “Current advances in cognitive neuroscience, neuroimaging, and behavioral and molecular genetics have provided evidence that ADHD is a complex neurobiological disorder.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Adult ADHD is associated with diagnoses of comorbid mood, anxiety and substance-use disorder.

    “Likewise, adult ADHD is also associated with diagnoses of comorbid mood, anxiety and substance-use disorder [11-17].”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [11] Borland BL, Heckman HK: Hyperactive boys and their brothers: A 25-year follow-up study. Archives of General Psychiatry. 1976, 33: 669-675. source

      Not checked in the free run.

    • cites [12] Morrison JR: Adult psychiatric disorders in parents of hyperactive children. American Journal of Psychiatry. 1980, 137: 825-827. source

      Not checked in the free run.

    • cites [13] Biederman J, Faraone SV, Spencer T, Wilens T, Norman D, Lapey KA, Mick E, Lehman BK, Doyle A: Patterns of psychiatric comorbidity, cognition, and psychosocial functioning in adults with attention deficit hyperactivity disorder. Am J Psychiatry. 1993, 150 (12): 1792-1798. source

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    • cites [14] Heiligenstein E, Conyers LM, Berns AR, Miller MA: Preliminary normative data on DSM-IV attention deficit hyperactivity disorder in college students. J Am Coll Health. 1998, 46 (4): 185-188. 10.1080/07448489809595609. source

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    • cites [15] Murphy K, Barkley RA: Attention deficit hyperactivity disorder adults: comorbidities and adaptive impairments. Compr Psychiatry. 1996, 37 (6): 393-401. 10.1016/S0010-440X(96)90022-X. source

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    • cites [16] Shekim WO, Asarnow RF, Hess E, Zaucha K, Wheeler N: A clinical and demographic profile of a sample of adults with attention deficit hyperactivity disorder, residual state. Compr Psychiatry. 1990, 31 (5): 416-425. 10.1016/0010-440X(90)90026-O. source

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    • cites [17] Barkley R, Murphy K, Fischer M: ADHD in adults: what the science says. 2007, New York: Guilford Press

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  • Premisecitation

    Pediatric ADHD commonly co-occurs with multiple psychiatric disorders including mood, anxiety and disruptive behavioral disorders.

    “Pediatric ADHD commonly co-occurs with multiple psychiatric disorders including mood, anxiety and disruptive behavioral disorders [9,10].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [9] Angold A, Costello EJ, Erkanli A: Comorbidity. J Child Psychol Psychiatry. 1999, 40 (1): 57-87. 10.1111/1469-7610.00424. source

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    • cites [10] Biederman J, Newcorn J, Sprich S: Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders. American Journal of Psychiatry. 1991, 148 (5): 564-577. source

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  • Premisenone given

    The prefrontal cortex is relevant to understanding ADHD.

    “Neurologically, the prefrontal cortex seems to be relevant to understanding ADHD.”
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    Some brain regions are slightly smaller or have decreased activation in people with ADHD.

    “Research has indicated that some of these brain regions are slightly smaller or have decreased activation in people with ADHD.”
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  • Classified as probably not a substantial claim. 6
  • May combine two claims. 27

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

    Premisecitation

    Comorbidity rates in adult ADHD do not differ as a function of gender.

    “Comorbidity rates in adult ADHD do not differ as a function of gender [18].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Lahey BB, Applegate B, McBurnett K, Biederman J, Greenhill L, Hynd GW, Barkley RA, Newcorn J, Jensen P, Richters J, et al: DSM-IV field trials for attention deficit hyperactivity disorder in children and adolescents. Am J Psychiatry. 1994, 151 (11): 1673-1685. source

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

    Premisecitation

    Uncomplicated ADHD exists in about 20 to 25% of adults with ADHD.

    “some data suggest that 'uncomplicated' ADHD exists in about 20 to 25% of adults with ADHD [13].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Biederman J, Faraone SV, Spencer T, Wilens T, Norman D, Lapey KA, Mick E, Lehman BK, Doyle A: Patterns of psychiatric comorbidity, cognition, and psychosocial functioning in adults with attention deficit hyperactivity disorder. Am J Psychiatry. 1993, 150 (12): 1792-1798. source

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    Premisecitation

    OROS methylphenidate lessens ADHD symptoms throughout the day and has greater adherence, thought associated with convenience of once-daily dosing.

    “Research has continued to suggest that osmotic-release oral system (OROS) methylphenidate lessens ADHD symptoms throughout the day and has greater adherence, thought to be associated with the convenience of once-daily dosing [39-41].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [39] Kim Y, Shin MS, Kim JW, Yoo HJ, Cho SC, Kim BN: Neurocognitive effects of switching from methylphenidate-IR to OROS-methylphenidate in children with ADHD. Hum Psychopharmacol. 2009, 24 (2): 95-102. 10.1002/hup.1010. source

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    • cites [40] Chou WJ, Chou MC, Tzang RF, Hsu YC, Gau SS, Chen SJ, Wu YY, Huang YF, Liang HY, Cheng H: Better efficacy for the osmotic release oral system methylphenidate among poor adherents to immediate-release methylphenidate in the three ADHD subtypes. Psychiatry Clin Neurosci. 2009, 63 (2): 167-175. 10.1111/j.1440-1819.2009.01937.x. source

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    • cites [41] Abikoff H, Nissley-Tsiopinis J, Gallagher R, Zambenedetti M, Seyffert M, Boorady R, McCarthy J: Effects of MPH-OROS on the organizational, time management, and planning behaviors of children with ADHD. J Am Acad Child Adolesc Psychiatry. 2009, 48 (2): 166-175. 10.1097/CHI.0b013e3181930626. source

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    Premisecitation

    Transdermal methylphenidate in short-term studies is associated with efficacy throughout the day, improved family quality of life, and little effect on sleep when carefully titrated.

    “Transdermal methylphenidate bypasses the oral route entirely, and in short-term studies is associated with efficacy throughout the day, with improved family quality of life, and when carefully titrated, little effect on sleep [44-46].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [44] Faraone SV, Glatt SJ, Bukstein OG, Lopez FA, Arnold LE, Findling RL: Effects of once-daily oral and transdermal methylphenidate on sleep behavior of children with ADHD. J Atten Disord. 2009, 12 (4): 308-315. source

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    • cites [45] Wilens TE, Hammerness P, Martelon M, Brodziak K, Utzinger L, Wong P: A controlled trial of the methylphenidate transdermal system on before-school functioning in children with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 71 (5): 548-556. source

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    • cites [46] Manos M, Frazier TW, Landgraf JM, Weiss M, Hodgkins P: HRQL and medication satisfaction in children with ADHD treated with the methylphenidate transdermal system. Curr Med Res Opin. 2009, 25 (12): 3001-3010. 10.1185/03007990903388797. source

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    Interpretationreasoning

    Long-acting stimulants are less prone to diversion than short-acting stimulants, probably because extraction of active drug is more difficult and delivery to the brain is slower.

    “Long-acting stimulants are less prone to diversion, probably because extraction of active drug is more difficult, and for some, the delivery of drug to the brain is slower.”
    Quote in the paperNot a substantial claim

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    Interpretationreasoning

    LDX requires gut metabolism to reach its active form, and hence lessens the likelihood of abuse and overdose.

    “LDX requires gut metabolism to reach its active form, and hence lessens the likelihood of abuse and overdose.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Short/medium term cardiovascular side-effects of stimulants are usually of no clinical significance, but long-term potential side-effects are less certain.

    “The general consensus on cardiovascular side-effects at this point is that the short/medium term side-effects are usually of no clinical significance, but the long-term potential side-effects are less certain [63].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] Graham J, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, Dittmann RW, Dopfner M, Hamilton R, Hollis C, Holtmann M, et al: European guidelines on managing adverse effects of medication for ADHD. Eur Child Adolesc Psychiatry. 2011, 20 (1): 17-37. 10.1007/s00787-010-0140-6. source

      Not checked in the free run.

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    Premisecitation

    Treatment with stimulants in childhood modestly reduced expected height and weight; effects were dose-dependent and attenuated over time.

    “However, a recent review article has shown that treatment with stimulants in childhood modestly reduced expected height and weight [62]. These effects were dose-dependent and attenuated over time.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [62] Faraone SV, Biederman J, Morley CP, Spencer TJ: Effect of stimulants on height and weight: a review of the literature. J Am Acad Child Adolesc Psychiatry. 2008, 47 (9): 994-1009.

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    Premisecitation

    The efficacy and side-effects of LDX are similar to the other long-acting stimulant preparations.

    “The efficacy and side-effects of LDX are similar to the other long-acting stimulant preparations [68-72].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [68] Najib J: The efficacy and safety profile of lisdexamfetamine dimesylate, a prodrug of d-amphetamine, for the treatment of attention-deficit/hyperactivity disorder in children and adults. Clin Ther. 2009, 31 (1): 142-176. 10.1016/j.clinthera.2009.01.015. source

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    • cites [69] Antonucci D, Kunins C, Manos M, Lopez FA, Kerney DL: Assessing effects of treatment with lisdexamfetamine dimesylate for pediatric ADHD using a parental survey. CNS Spectr. 2010, 15 (4): 248-256. source

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    • cites [70] Findling RL, Ginsberg LD, Jain R, Gao J: Effectiveness, safety, and tolerability of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: an open-label, dose-optimization study. J Child Adolesc Psychopharmacol. 2009, 19 (6): 649-662. 10.1089/cap.2008.0165. source

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    • cites [71] Faraone SV, Spencer TJ, Kollins SH, Glatt SJ: Effects of lisdexamfetamine dimesylate treatment for ADHD on growth. J Am Acad Child Adolesc Psychiatry. 49 (1): 24-32. source

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    • cites [72] Boellner SW, Stark JG, Krishnan S, Zhang Y: Pharmacokinetics of lisdexamfetamine dimesylate and its active metabolite, d-amphetamine, with increasing oral doses of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: a single-dose, randomized, open-label, crossover study. Clin Ther. 32 (2): 252-264. source

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    Premisecitation

    Atomoxetine has been rarely associated with acute suicidality and has a black box warning.

    “Because atomoxetine has been rarely associated with acute suicidality [86], it has been given a 'black box' warning.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [86] Paxton GA, Cranswick NE: Acute suicidality after commencing atomoxetine. J Paediatr Child Health. 2008, 44 (10): 596-598. 10.1111/j.1440-1754.2008.01389.x. source

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    Premisecitation

    When atomoxetine is administered once daily, morning dosing may be more efficacious, but evening dosing may be more tolerable.

    “When atomoxetine is administered once daily, some evidence suggests that morning dosing may be more efficacious, but evening dosing may be more tolerable [84].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [84] Block SL, Kelsey D, Coury D, Lewis D, Quintana H, Sutton V, Schuh K, Allen AJ, Sumner C: Once-daily atomoxetine for treating pediatric attention-deficit/hyperactivity disorder: comparison of morning and evening dosing. Clin Pediatr (Phila). 2009, 48 (7): 723-733. 10.1177/0009922809335321. source

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    Premisecitation

    Modafinil and reboxetine have both shown some promise in the treatment of ADHD.

    “Modafinil [73] and reboxetine [74,75] have both shown some promise in the treatment of ADHD.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [73] Kahbazi M, Ghoreishi A, Rahiminejad F, Mohammadi MR, Kamalipour A, Akhondzadeh S: A randomized, double-blind and placebo-controlled trial of modafinil in children and adolescents with attention deficit and hyperactivity disorder. Psychiatry Res. 2009, 168 (3): 234-237. 10.1016/j.psychres.2008.06.024. source

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    • cites [74] Arabgol F, Panaghi L, Hebrani P: Reboxetine versus methylphenidate in treatment of children and adolescents with attention deficit-hyperactivity disorder. Eur Child Adolesc Psychiatry. 2009, 18 (1): 53-59. 10.1007/s00787-008-0705-9. source

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    • cites [75] Cohen-Yavin I, Yoran-Hegesh R, Strous RD, Kotler M, Weizman A, Spivak B: Efficacy of reboxetine in the treatment of attention-deficit/hyperactivity disorder in boys with intolerance to methylphenidate: an open-label, 8-week, methylphenidate-controlled trial. Clin Neuropharmacol. 2009, 32 (4): 179-182. 10.1097/WNF.0b013e318183796d. source

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    Premisecitation

    Adding clonidine to methylphenidate, extended-release guanfacine to stimulants, or OROS methylphenidate to atomoxetine improved residual ADHD symptoms and was well tolerated.

    “Recent studies have shown that adding clonidine to methylphenidate [95], extended-release guanfacine to stimulants [96], or OROS methylphenidate to atomoxetine [97] improved residual ADHD symptoms and was well tolerated.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [95] Cannon M, Pelham WH, Sallee FR, Palumbo DR, Bukstein O, Daviss WB: Effects of clonidine and methylphenidate on family quality of life in attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2009, 19 (5): 511-517. 10.1089/cap.2009.0008. source

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    • cites [96] Spencer TJ, Greenbaum M, Ginsberg LD, Murphy WR: Safety and effectiveness of coadministration of guanfacine extended release and psychostimulants in children and adolescents with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2009, 19 (5): 501-510. 10.1089/cap.2008.0152. source

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    • cites [97] Wilens TE, Hammerness P, Utzinger L, Schillinger M, Georgiopoulous A, Doyle RL, Martelon M, Brodziak K: An open study of adjunct OROS-methylphenidate in children and adolescents who are atomoxetine partial responders: I. Effectiveness. J Child Adolesc Psychopharmacol. 2009, 19 (5): 485-492. 10.1089/cap.2008.0125. source

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    Premisecitation

    Atomoxetine efficacy has been confirmed in populations around the world, including for children with oppositional defiant disorder or those who have received previous stimulant therapy.

    “studies in populations around the world have continued to confirm its efficacy [78-81], including for children with oppositional defiant disorder [82] or those who have received previous stimulant therapy [83].”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [78] Svanborg P, Thernlund G, Gustafsson PA, Hagglof B, Poole L, Kadesjo B: Efficacy and safety of atomoxetine as add-on to psychoeducation in the treatment of attention deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled study in stimulant-naive Swedish children and adolescents. Eur Child Adolesc Psychiatry. 2009, 18 (4): 240-249. 10.1007/s00787-008-0725-5. source

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    • cites [79] Martenyi F, Zavadenko NN, Jarkova NB, Yarosh AA, Soldatenkova VO, Bardenstein LM, Kozlova IA, Neznanov NG, Maslova OI, Petrukhin AS, et al: Atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder: a 6-week, randomized, placebo-controlled, double-blind trial in Russia. Eur Child Adolesc Psychiatry. 2010, 19 (1): 57-66. 10.1007/s00787-009-0042-7. source

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    • cites [80] Takahashi M, Takita Y, Yamazaki K, Hayashi T, Ichikawa H, Kambayashi Y, Koeda T, Oki J, Saito K, Takeshita K, et al: A randomized, double-blind, placebo-controlled study of atomoxetine in Japanese children and adolescents with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2009, 19 (4): 341-350. 10.1089/cap.2008.0154. source

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    • cites [81] Durell TM, Pumariega AJ, Rothe EM, Tamayo JM, Baron D, Williams D: Effects of open-label atomoxetine on African-American and Caucasian pediatric outpatients with attention-deficit/hyperactivity disorder. Ann Clin Psychiatry. 2009, 21 (1): 26-37.

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    • cites [82] Dell'Agnello G, Maschietto D, Bravaccio C, Calamoneri F, Masi G, Curatolo P, Besana D, Mancini F, Rossi A, Poole L, et al: Atomoxetine hydrochloride in the treatment of children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder: A placebo-controlled Italian study. Eur Neuropsychopharmacol. 2009, 19 (11): 822-834. 10.1016/j.euroneuro.2009.07.008. source

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    • cites [83] Hammerness P, Doyle R, Kotarski M, Georgiopoulos A, Joshi G, Zeitlin S, Biederman J: Atomoxetine in children with attention-deficit hyperactivity disorder with prior stimulant therapy: a prospective open-label study. Eur Child Adolesc Psychiatry. 2009, 18 (8): 493-498. 10.1007/s00787-009-0017-8. source

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    Premisecitation

    Once-daily extended-release guanfacine has proven effective in both short-term and long-term studies.

    “Recently, once-daily extended-release guanfacine has proven effective in both short-term [90,91] and long-term studies [92,93].”
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    • cites [90] Sallee FR, McGough J, Wigal T, Donahue J, Lyne A, Biederman J: Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: a placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2009, 48 (2): 155-165. 10.1097/CHI.0b013e318191769e. source

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    • cites [91] Biederman J, Melmed RD, Patel A, McBurnett K, Konow J, Lyne A, Scherer N: A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics. 2008, 121 (1): e73-84. 10.1542/peds.2006-3695. source

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    • cites [92] Sallee FR, Lyne A, Wigal T, McGough JJ: Long-term safety and efficacy of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2009, 19 (3): 215-226. 10.1089/cap.2008.0080. source

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    • cites [93] Biederman J, Melmed RD, Patel A, McBurnett K, Donahue J, Lyne A: Long-term, open-label extension study of guanfacine extended release in children and adolescents with ADHD. CNS Spectr. 2008, 13 (12): 1047-1055. source

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    Premisecitation

    Atomoxetine rarely completely normalizes behavior, but symptom improvement is often reflected in gains in social and behavioral function.

    “As with stimulant treatment, atomoxetine rarely completely normalizes behavior [87], but symptom improvement is often reflected in gains in social and behavioral function [88].”
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    • cites [87] Whalen CK, Henker B, Ishikawa SS, Emmerson NA, Swindle R, Johnston JA: Atomoxetine versus stimulants in the community treatment of children with ADHD: an electronic diary study. J Atten Disord. 2010, 13 (4): 391-400. 10.1177/1087054708325118. source

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    • cites [88] Buitelaar JK, Wilens TE, Zhang S, Ning Y, Feldman PD: Comparison of symptomatic versus functional changes in children and adolescents with ADHD during randomized, double-blind treatment with psychostimulants, atomoxetine, or placebo. J Child Psychol Psychiatry. 2009, 50 (3): 335-342. 10.1111/j.1469-7610.2008.01960.x. source

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    Premisecitation

    Sedation is a common side-effect of guanfacine, which diminishes over time.

    “Sedation is a common side-effect, which diminishes over time [94].”
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    • cites [94] Faraone SV, Glatt SJ: Effects of extended-release guanfacine on ADHD symptoms and sedation-related adverse events in children with ADHD. J Atten Disord. 2010, 13 (5): 532-538. 10.1177/1087054709332472. source

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    Premisecitation

    Stimulant misuse seems to be more common in those with comorbid alcohol-, drug- and cigarette-related problems, and those with higher levels of ADHD symptoms.

    “Stimulant misuse seems to be more common in those with comorbid alcohol-, drug- and cigarette-related problems, and those with higher levels of ADHD symptoms [115].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [115] Wilens TE, Adler LA, Adams J, Sgambati S, Rotrosen J, Sawtelle R, Utzinger L, Fusillo S: Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature. J Am Acad Child Adolesc Psychiatry. 2008, 47 (1): 21-31. 10.1097/chi.0b013e31815a56f1. source

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    Premisecitation

    When compared with adults with ADHD who received relaxation training and educational support, adults with ADHD who received 12 sessions of CBT had lower self-reported ADHD symptoms and greater functional improvements as rated by a blinded assessor.

    “A recently published study suggests that, when compared with adults with ADHD who received relaxation training and educational support, adults with ADHD who received 12 sessions of CBT had lower self-reported ADHD symptoms and greater functional improvements as rated by a blinded assessor [119].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [119] Safren SA, Sprich S, Mimiaga MJ, Surman C, Knouse L, Groves M, Otto MW: Cognitive behavioral therapy vs relaxation with educational support for medication-treated adults with ADHD and persistent symptoms: a randomized controlled trial. Jama. 2010, 304 (8): 875-880. 10.1001/jama.2010.1192. source

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    Interpretationnone given

    The consensus for most alternative and complementary therapies is that they are best used as a complement to ongoing pharmacotherapy rather than as an alternative.

    “At this point, the consensus for most alternative and complementary therapies is that these therapies are best used as a complement to ongoing pharmacotherapy rather than as an alternative.”
    Quote in the paperSubstantial claim

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

    Premisenone given

    The only non-stimulant with FDA approval for adults with ADHD is atomoxetine.

    “However, the only non-stimulant with FDA approval for adults with ADHD is atomoxetine.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    The potential for diversion and misuse may be greater in adults than in children, as parents might control the medications for the latter.

    “The potential for diversion and misuse may be greater in adults than in children, as parents might control the medications for the latter.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Short-chain fatty acids and omega-3/omega-6 fatty acids have not been found to be efficacious in treating ADHD.

    “Short-chain fatty acids [108] and omega-3/omega-6 fatty acids [109] have not been found to be efficacious.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [108] Raz R, Carasso RL, Yehuda S: The influence of short-chain essential fatty acids on children with attention-deficit/hyperactivity disorder: a double-blind placebo-controlled study. J Child Adolesc Psychopharmacol. 2009, 19 (2): 167-177. 10.1089/cap.2008.070. source

      Not checked in the free run.

    • cites [109] Johnson M, Ostlund S, Fransson G, Kadesjo B, Gillberg C: Omega-3/omega-6 fatty acids for attention deficit hyperactivity disorder: a randomized placebo-controlled trial in children and adolescents. J Atten Disord. 2009, 12 (5): 394-401. 10.1177/1087054708316261. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Most people with ADHD will respond favorably to pharmacological interventions, but optimal functioning may not be attained.

    “Although most people with ADHD will respond favorably to pharmacological interventions [126], optimal functioning may not be attained.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [126] Elia J, Borcherding BG, Rapoport JL, Keysor CS: Methylphenidate and dextroamphetamine treatments of hyperactivity: are there true nonresponders?. Psychiatry Res. 1991, 36 (2): 141-155. 10.1016/0165-1781(91)90126-A. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both groups reported less depression and anxiety; both groups had improved self-esteem at the end of the study, but the intervention group reported a greater improvement in self-esteem.

    “Furthermore, both groups reported less depression and anxiety. Both groups also had improved self-esteem at the end of the study, but the intervention group reported a greater improvement in self-esteem [120].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [120] Bramham J, Young S, Bickerdike A, Spain D, McCartan D, Xenitidis K: Evaluation of group cognitive behavioral therapy for adults with ADHD. J Atten Disord. 2009, 12 (5): 434-441. 10.1177/1087054708314596. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Medications may improve some but not all aspects of cognitive functioning, and even when both symptoms and cognitive function are improved, the two are not necessarily correlated.

    “Likewise, medications may improve some but not all aspects of cognitive functioning, and even when both symptoms and cognitive function are improved, the two are not necessarily correlated [130].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [130] Coghill DR, Rhodes SM, Matthews K: The neuropsychological effects of chronic methylphenidate on drug-naive boys with attention-deficit/hyperactivity disorder. Biol Psychiatry. 2007, 62 (9): 954-962. 10.1016/j.biopsych.2006.12.030. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There were more treatment responders in the CBT group (53%) relative to the relaxation training and educational support group (23%), and gains were maintained over periods of 6 and 12 months.

    “There were more treatment responders in the CBT group (53%) relative to the relaxation training and educational support group (23%), and gains were maintained over periods of 6 and 12 months [119].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [119] Safren SA, Sprich S, Mimiaga MJ, Surman C, Knouse L, Groves M, Otto MW: Cognitive behavioral therapy vs relaxation with educational support for medication-treated adults with ADHD and persistent symptoms: a randomized controlled trial. Jama. 2010, 304 (8): 875-880. 10.1001/jama.2010.1192. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    New stimulant formulations have made it possible to tailor treatment to the duration of efficacy required by patients and to help mitigate the potential for abuse, misuse and diversion.

    “New stimulant formulations have made it possible to tailor treatment to the duration of efficacy required by patients and to help mitigate the potential for abuse, misuse and diversion.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Although non-stimulants tend to be less efficacious than stimulants, new non-stimulant options allow for extended duration of treatment without the adverse consequences associated with stimulant therapy.

    “Although they tend to be less efficacious than stimulants, new non-stimulant options also allow for extended duration of treatment without the adverse consequences associated with stimulant therapy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Poor treatment adherence and psychiatric comorbidity complicate treatment and negatively affect outcomes.

    “Poor treatment adherence and psychiatric comorbidity clearly complicate treatment and negatively affect outcomes.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    ADHD symptoms, especially hyperactive-impulsive symptoms, tend to decline through adolescence into adulthood, so that the adult presentation of ADHD differs somewhat from the childhood presentation.

    “ADHD symptoms, especially hyperactive-impulsive symptoms, tend to decline through adolescence into adulthood, so that the adult presentation of ADHD differs somewhat from the childhood presentation.”
    Quote in the paperNot a substantial claim
31 of 31

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?

  • Treatment strategies for ADHD symptoms include medication-based, behavior-based, and combined interventions.

    “Treatment strategies for ADHD symptoms include medication-based, behavior-based, and combined interventions (Antshel et al., 2011; Sibley et al., 2014).”

    From A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) (2019) · cites this paper as Antshel et al., 2011

  • As a result of internalising neurodivergent traits and stress, unsupported neurodivergent adults are at risk for co-morbid mental health disorders such as anxiety, depression, and post-traumatic stress, and suicide.

    “As a result of internalising neurodivergent traits and stress [72], unsupported neurodivergent adults are at risk for co-morbid mental health disorders such as anxiety, depression, and post-traumatic stress [6, 47, 70] and suicide [35].”

    From Burnout by Design: How Digital Systems Overburden Neurodivergent Students in Higher Education (2025) · cites this paper as [6]

    Citation [72] is attached to the phrase about internalising neurodivergent traits and stress, not to the later list of mental health risks. The Introduction’s “Comorbid conditions” section reports mood and anxiety comorbidity in adults with ADHD, but neither it nor the passages found by searching for internalising and stress address that attributed explanation. No page numbers are available in our copy. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

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.

  • SNRI is defined two different ways

    Minor

    The text expands SNRI as "selective norepinephrine reuptake inhibitor" when describing atomoxetine, but the abbreviations list defines it as "Serotonin-norepinephrine reuptake inhibitor."

1 of 1

Cites

Flagged first, then by citations

2 of the 139 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. APA: DSM-IV-TR. 2000, Washington, DC: American Psychiatric Association
  2. 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.

Cited by

Sorted by citations

Related

Authors
Antshel, K. M., Hargrave, T. M., Simonescu, M., Kaul, P., Hendricks, K., & Faraone, S. V.
Affiliations
SUNY Upstate Medical University (US)
Corresponding author
Antshel, Kevin M
ORCID
Venue
BMC Medicine
Publisher
Springer Science and Business Media LLC
Published
2011-06-10
Volume
9
Issue
1
Pages
72-72
ISSN
1741-7015 (ISSN-L)
DOI
10.1186/1741-7015-9-72
PMC
PMC3126733
OpenAlex
W2164896423
Cited by
140
References
139
Citations by year
2026: 1 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 10 · 2021: 7 · 2020: 5 · 2019: 3 · 2018: 11 · 2017: 19 · 2016: 17 · 2015: 9 · 2014: 13 · 2013: 13 · 2012: 15
FWCI
1.72
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Eli Lilly and Company
  • Pfizer
  • National Institutes of Health
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Social Sciences › Psychology › Developmental and Educational Psychology › Behavioral and Psychological Studies
  • Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Developmental and Educational Neuropsychology
Keywords
attention deficit hyperactivity disorder, adult ADHD, ADHD treatment, stimulant medication, non-stimulant medication, cognitive-behavioral intervention, ADHD pathophysiology, residual disability
MeSH terms
Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Humans, Cognitive Behavioral Therapy, Adrenergic Uptake Inhibitors, Biomedical Research

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.

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