CNS Drugs

, Volume 30, Issue 4, pp 343–354 | Cite as

Lisdexamfetamine: A Review in ADHD in Adults

Adis Drug Evaluation


Lisdexamfetamine dimesylate (lisdexamfetamine) is a long-acting amfetamine prodrug with a convenient once-daily oral regimen that offers the potential for improved adherence and reduced abuse compared with short-acting preparations of amfetamines. Lisdexamfetamine (as Elvanse Adult®; Tyvense Adult™) has been approved for use in adults with attention-deficit hyperactivity disorder (ADHD) under the EU decentralization procedure, with the first approvals in the UK, Sweden and Denmark. This approval reflects the results of three short-term trials in adults with ADHD in which fixed- or flexible-dose lisdexamfetamine produced significantly greater improvements than placebo in ADHD symptoms, overall functioning, executive functioning (including in patients with significant pre-existing impairment) and quality of life. Of note, a post hoc analysis of one of these studies suggested that the response to lisdexamfetamine was generally similar in treatment-naïve patients and those who had already received—and not responded satisfactorily to—previous ADHD therapies, including methylphenidate (MPH). Two further studies demonstrated the longer-term effectiveness of flexible-dose lisdexamfetamine in reducing ADHD symptoms, albeit maintenance of efficacy required ongoing treatment with the drug. Lisdexamfetamine was generally well tolerated in clinical trials, with an adverse event profile typical of that reported for other long-acting stimulants. Head-to-head comparisons with other long-acting agents, notably MPH and atomoxetine, are lacking. Nonetheless, on the basis of the available data, lisdexamfetamine provides a useful alternative option for the treatment of adults with ADHD, including those who have not responded adequately to previous ADHD therapies, including MPH.


ADHD Symptom Executive Functioning Atomoxetine Pittsburgh Sleep Quality Index Hippuric Acid 



During the peer review process, the manufacturer of lisdexamfetamine was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Compliance with Ethical Standards


The preparation of this review was not supported by any external funding.

Conflicts of interest

James Frampton is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.


  1. 1.
    Faraone SV, Biederman J, Mick E. The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol Med. 2006;36(2):159–65.CrossRefPubMedGoogle Scholar
  2. 2.
    Fayyad J. Cross-national prevalence and correlates of adult attention-deficit hyperactivity disorder. Br J Psychiatry. 2007;190:402–9.CrossRefPubMedGoogle Scholar
  3. 3.
    National Institute for Health and Care Excellence. Attention deficit hyperactivity disorder: diagnosis and management of ADHD in children, young people and adults. NICE guidelines [CG72]. 2008. Accessed 7 Dec 2015.
  4. 4.
    All Wales Therapeutics and Toxicology Centre. AWMSG secretariat assessment report: Lisdexamfetamine dimesylate (Elvanse Adult®) 30 mg, 50 mg and 70 mg hard capsules. Reference number: 2534. 2015. http://www.awmsg.or. Accessed 14 Dec 2015.
  5. 5.
    Kolar D, Keller A, Golfinopoulos M, et al. Treatment of adults with attention-deficit/hyperactivity disorder. Neuropsychiatr Dis Treat. 2008;4(2):389–403.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Brown TE. Executive functions and attention deficit hyperactivity disorder: implications of two conflicting views. Int J Disabil Dev Educ. 2006;53(1):35–46.CrossRefGoogle Scholar
  7. 7.
    Castellanos FX, Sonuga-Barke E, Milham MP, et al. Characterizing cognition in ADHD: beyond executive dysfunction. Trends Cogn Sci. 2006;10(3):117–23.CrossRefPubMedGoogle Scholar
  8. 8.
    Barkley RA. Differential diagnosis of adults with ADHD: the role of executive function and self-regulation. J Clin Psychiatry. 2010;71(7):e17.CrossRefPubMedGoogle Scholar
  9. 9.
    Biederman J, Faraone SV, Spencer TJ, et al. Functional impairments in adults with self-reports of diagnosed ADHD: a controlled study of 1001 adults in the community. J Clin Psychiatry. 2006;67(4):524–40.CrossRefPubMedGoogle Scholar
  10. 10.
    Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry. 2006;163:716–23.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Biederman J, Petty CR, Fried R, et al. Educational and occupational underattainment in adults with attention-deficit/hyperactivity disorder: a controlled study. J Clin Psychiatry. 2008;69(8):1217–22.CrossRefPubMedGoogle Scholar
  12. 12.
    Adler LA, Spencer TJ, Levine LR, et al. Functional outcomes in the treatment of adults with ADHD. J Atten Disord. 2008;11(6):720–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Adler LA, Dirks B, Deas PF, et al. Lisdexamfetamine dimesylate in adults with attention-deficit/ hyperactivity disorder who report clinically significant impairment in executive function: results from a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2013;74(7):694–702.CrossRefPubMedGoogle Scholar
  14. 14.
    Weber J, Siddiqui MAA. Lisdexamfetamine dimesylate: in attention-deficit hyperactivity disorder in adults. CNS Drugs. 2009;23(5):419–25.CrossRefPubMedGoogle Scholar
  15. 15.
    Banaschewski T, Coghill D, Santosh P, et al. Long-acting medications for the hyperkinetic disorders. A systematic review and European treatment guideline. Eur Child Adolesc Psychiatry. 2006;15(8):476–95.CrossRefPubMedGoogle Scholar
  16. 16.
    Steer C, Froelich J, Soutullo CA, et al. Lisdexamfetamine dimesylate: a new therapeutic option for attention-deficit hyperactivity disorder. CNS Drugs. 2012;26(8):691–705.CrossRefPubMedGoogle Scholar
  17. 17.
    Childress AC, Sallee FR. The use of lisdexamfetamine for the treatment of ADHD. Expert Rev Neurother. 2012;12(1):13–26.CrossRefPubMedGoogle Scholar
  18. 18.
    Blick SKA, Keating GM. Lisdexamfetamine. Pediatric Drugs. 2007;9(2):129–35.CrossRefPubMedGoogle Scholar
  19. 19.
    Shire. Elvanse 30 mg, 50 mg and 70 mg capsules, hard. UK summary of product characteristics 2015. Accessed 24 Feb 2016.
  20. 20.
    Shire Pharmaceuticals Limited. Elvanse Adult 30 mg, 50 mg and 70 mg capsules, hard: UK summary of product characteristics. 2015. Accessed 25 Feb 2016.
  21. 21.
    Shire Pharmaceutical Contracts Limited. Elvanse vuxen 30, 50, 70 mg kapslar,hårda. Swedish summary of product characteristics 2015. Accessed 25 Feb 2016.
  22. 22.
    Shire Sweden AB. Elvanse (Lisdexamfetamin). Danish summary of product characteristics. 2015. Accessed 25 Feb 2016.
  23. 23.
    Shire US Inc. Vyvanse® (lisdexamfetamine dimesylate) capsules, for oral use. US prescribing information. 2015. Accessed 25 Feb 2016.
  24. 24.
    Wigal SB, Raja P, Shukla A. An update on lisdexamfetamine dimesylate for the treatment of attention deficit hyperactivity disorder. Expert Opin Pharmacother. 2013;14(1):137–45.CrossRefPubMedGoogle Scholar
  25. 25.
    Ermer J, Haffey MB, Richards C, et al. Double-blind, placebo-controlled, two-period, crossover trial to examine the pharmacokinetics of lisdexamfetamine dimesylate in healthy older adults. Neuropsychiatr. 2013;9:219–29.Google Scholar
  26. 26.
    Krishnan SM, Stark JG. Multiple daily-dose pharmacokinetics of lisdexamfetamine dimesylate in healthy adult volunteers. Curr Med Res Opin. 2008;24(1):33–40.CrossRefPubMedGoogle Scholar
  27. 27.
    Krishnan S, Zhang Y. Relative bioavailability of lisdexamfetamine 70-mg capsules in fasted and fed healthy adult volunteers and in solution: a single-dose, crossover pharmacokinetic study. J Clin Pharmacol. 2008;48(3):293–302.CrossRefPubMedGoogle Scholar
  28. 28.
    Ermer J, Homolka R, Martin P, et al. Lisdexamfetamine dimesylate: linear dose-proportionality, low intersubject and intrasubject variability, and safety in an open-label single-dose pharmacokinetic study in healthy adult volunteers. J Clin Pharmacol. 2010;50(9):1001–10.CrossRefPubMedGoogle Scholar
  29. 29.
    Krishnan SM, Pennick M, Stark JG. Metabolism, distribution and elimination of lisdexamfetamine dimesylate: open-label, single-centre, phase I study in healthy adult volunteers. Clin Drug Investig. 2008;28(12):745–55.CrossRefPubMedGoogle Scholar
  30. 30.
    Pennick M. Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine. Neuropsychiatr. 2010;6:317–27.Google Scholar
  31. 31.
    Haffey MB, Buckwalter M, Zhang P, et al. Effects of omeprazole on the pharmacokinetic profiles of lisdexamfetamine dimesylate and extended-release mixed amphetamine salts in adults. Postgrad Med. 2009;121(5):11–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Najib J. Lisdexamfetamine in the treatment of adolescents and children with attention-deficit/hyperactivity disorder. Adolesc Health Med Ther. 2012;3:51–66.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Adler LA, Goodman DW, Kollins SH, et al. Double-blind, placebo-controlled study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2008;69(9):1364–73.CrossRefPubMedGoogle Scholar
  34. 34.
    Brams M, Weisler R, Findling RL, et al. Maintenance of efficacy of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: randomized withdrawal design. J Clin Psychiatry. 2012;73(7):977–83.CrossRefPubMedGoogle Scholar
  35. 35.
    Wigal T, Brams M, Gasior M, et al. Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design. Behav Brain Funct. 2010;6:34.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Weisler R, Young J, Mattingly G, et al. Long-term safety and effectiveness of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder. CNS spectrums. 2009;14(10):573–85.PubMedGoogle Scholar
  37. 37.
    Fridman M, Hodgkins PS, Kahle JS, et al. Predicted effect size of lisdexamfetamine treatment of attention deficit/hyperactivity disorder (ADHD) in European adults: estimates based on indirect analysis using a systematic review and meta-regression analysis. Eur Psychiatry. 2015;30(4):521–7.CrossRefPubMedGoogle Scholar
  38. 38.
    US National Institutes of Health. identifier NCT00697515. 2011. Accessed 18 Nov 2015.
  39. 39.
    US National Institutes of Health. identifier NCT00334880. 2009. Accessed 18 Nov 2015.
  40. 40.
    US National Institutes of Health. identifier NCT01101022. 2014. Accessed 18 Nov 2015.
  41. 41.
    Mattingly GW, Weisler RH, Young J, et al. Clinical response and symptomatic remission in short- and long-term trials of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder. BMC Psychiatry. 2013;13:39.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Babcock T, Dirks B, Adeyi B, et al. Efficacy of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder previously treated with amphetamines: analyses from a randomized, double-blind, multicenter, placebo-controlled titration study. BMC Pharmacol Toxicol. 2012;13:18.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Waxmonsky JG, Waschbusch DA, Glatt SJ, et al. Prediction of placebo response in 2 clinical trials of lisdexamfetamine dimesylate for the treatment of ADHD. J Clin Psychiatry. 2011;72(10):1366–75.CrossRefPubMedGoogle Scholar
  44. 44.
    Kollins SH, Youcha S, Lasser R, et al. Lisdexamfetamine dimesylate for the treatment of attention deficit hyperactivity disorder in adults with a history of depression or history of substance use disorder. Innov Clin Neurosci. 2011;8(2):28–32.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Adler L, Wu J, Madhoo M, et al. Post hoc analyses of the efficacy of lisdexamfetamine dimesylate in adults previously treated with attention-deficit/hyperactivity disorder medication [poster]. In: 23rd European Congress of Psychiatry. 2015.Google Scholar
  46. 46.
    Adler LA, Dirks B, Deas P, et al. 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. BMC Psychiatry. 2013;13:253.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Ginsberg L, Katic A, Adeyi B, et al. Long-term treatment outcomes with lisdexamfetamine dimesylate for adults with attention-deficit/hyperactivity disorder stratified by baseline severity. Curr Med Res Opin. 2011;27(6):1097–107.CrossRefPubMedGoogle Scholar
  48. 48.
    Mattingly G, Weisler R, Dirks B, et al. Attention deficit hyperactivity disorder subtypes and symptom response in adults treated with lisdexamfetamine dimesylate. Innov Clin Neurosci. 2012;9(5–6):22–30.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Coghill DR, Caballero B, Sorooshian S, et al. A systematic review of the safety of lisdexamfetamine dimesylate. CNS Drugs. 2014;28(6):497–511.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Adler LA, Weisler RH, Goodman DW, et al. Short-term effects of lisdexamfetamine dimesylate on cardiovascular parameters in a 4-week clinical trial in adults with attention-deficit/ hyperactivity disorder. J Clin Psychiatry. 2009;70(12):1652–61.CrossRefPubMedGoogle Scholar
  51. 51.
    Hammerness P, Zusman R, Systrom D, et al. A cardiopulmonary study of lisdexamfetamine in adults with attention-deficit/hyperactivity disorder. World J Biol Psychiatr. 2013;14(4):299–306.CrossRefGoogle Scholar
  52. 52.
    Adler LA, Goodman D, Weisler R, et al. Effect of lisdexamfetamine dimesylate on sleep in adults with attention-deficit/hyperactivity disorder. Behav Brain Funct. 2009;5:34.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Hodgkins P, Shaw M, McCarthy S, et al. The pharmacology and clinical outcomes of amphetamines to treat ADHD. CNS Drugs. 2012;26(3):245–58.CrossRefPubMedGoogle Scholar
  54. 54.
    Lopez FA, Leroux JR. Long-acting stimulants for treatment of attention-deficit/hyperactivity disorder: a focus on extended-release formulations and the prodrug lisdexamfetamine dimesylate to address continuing clinical challenges. Atten Deficit Hyperact Disord. 2013;5(3):249–65.CrossRefGoogle Scholar
  55. 55.
    Shier AC. Pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: clinical strategies. J Cent Nerv Syst Dis. 2013;5:1–17.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Goodman DW. Lisdexamfetamine dimesylate. The first prodrug stimulant. Psychiatry (Edgemont). 2007;4(8):39–45.Google Scholar
  57. 57.
    Medicines and Healthcare Products Regulatory Agency. Public assessment report decentralized procedure. Elvanse adult 30, 50 and 70 mg capsules, hard (lisdexamfetamine dimesylate). Procedure no.: UK/H/5567/001-03/DC. Accessed 15 Nov 2015.
  58. 58.
    Weyandtt LL, Marraccini ME, Gudmundsdottir BG, et al. Pharmacological interventions for adolescents and adults with ADHD: stimulant and nonstimulant medications and misuse of prescription stimulants. Psychol Res Behav Manag. 2014;7:223–49.CrossRefGoogle Scholar
  59. 59.
    Elia J, Easley C, Kirkpatrick P. Lisdexamfetamine dimesylate. Nat Rev Drug Discov. 2007;6:343–4.CrossRefPubMedGoogle Scholar
  60. 60.
    Wu EQ, Hodgkins P, Ben-Hamadi R, et al. Cost effectiveness of pharmacotherapies for attention-deficit hyperactivity disorder: a systematic literature review. CNS Drugs. 2012;26(7):581–600.CrossRefPubMedGoogle Scholar
  61. 61.
    Brod M, Pohlman B, Lasser R, et al. Comparison of the burden of illness for adults with ADHD across seven countries: a qualitative study. Health Qual Life Outcomes. 2012;10:47.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Matsa LS, Paramore C, Prasad M. A review of the economic burden of ADHD. Cost Eff Resour Alloc. 2005;3:5.CrossRefGoogle Scholar
  63. 63.
    Zimovetz EA, Bischof M, Joseph A, et al. Cost-utility analysis of lisdexamfetamine dimesylate in the treatment of adults with attention-deficit/hyperactivity disorder in the United Kingdom. Eur Psychiatr. 2015;30(Suppl 1):1607. doi: 10.1016/S0924-9338(15)31240-2 CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

Personalised recommendations