Skip to main content
SpringerLink
Log in

Atomoxetine

  • Adis Drug Profile
  • Published:
Pediatric Drugs Aims and scope Submit manuscript

Abstract

▴ Atomoxetine, formerly tomoxetine, is a selective norepinephrine reuptake inhibitor and a new, nonstimulant treatment for attention deficit hyperactivity disorder (ADHD).

▴ In vitro, ex vivo and in vivo studies have shown that atomoxetine is a highly selective antagonist of the presynaptic norepinephrine transporter with little or no affinity for other noradrenergic receptors or other neurotransmitter transporters or receptors.

▴ In four randomized, placebo-controlled clinical trials conducted over 6–9 weeks in children and adolescents with ADHD, atomoxetine (total daily dose 1–1.8 mg/kg administered in one or two doses daily) reduced symptoms (hyperactivity, impulsiveness and inattention) as determined by the reduction in ADHD total score (34–38% with atomoxetine versus 13–15.7% with placebo [p < 0.05]).

▴ Atomoxetine also significantly improved ADHD subscale rating scores (p < 0.05 and p < 0.001), psychosocial well-being (p < 0.05) and ADHD-related problem behavior according to parent and teacher ratings (p < 0.05).

▴ Atomoxetine was well tolerated in clinical trials and discontinuation rates due to adverse events were low (<5%). The most common treatment-related adverse event was decreased appetite.

▴ Atomoxetine shows no abuse potential and is not a controlled substance in the US.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Notes

  1. The use of tradenames is for product identification purposes only and does not imply endorsement.

References

  1. Spencer T, Biederman J, Wilens T, et al. Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle. J Am Acad Child Adolesc Psychiatry 1996 Apr; 35: 409–32

    Article  PubMed  CAS  Google Scholar 

  2. Biederman J, Spencer T. Non-stimulant treatments for ADHD. Eur Child Adolesc Psychiatry 2000; 9Suppl. 1: 151–9

    Google Scholar 

  3. Cyr M, Brown CS. Current drug therapy recommendations for the treatment of attention deficit hyperactivity disorder. Drugs 1998 Aug; 56: 215–23

    Article  PubMed  CAS  Google Scholar 

  4. Zametkin AJ, Ernst M. Problems in the management of attention-deficit-hyperactivity disorder. N Engl J Med 1999 Jan 7; 340: 40–6

    Article  PubMed  CAS  Google Scholar 

  5. Swanson JM, Sergeant JA, Taylor E, et al. Attention-deficit hyperactivity disorder and hyperkinetic disorder. Lancet 1998 Feb 7; 351: 429–33

    Article  PubMed  CAS  Google Scholar 

  6. Wilens TE, Biederman J, Spencer TJ. Pharmacotherapy of attention deficit hyperactivity disorder in adults. CNS Drugs 1998; 9(5): 347–56

    Article  CAS  Google Scholar 

  7. Spencer TJ, Biederman J, Wilens T, et al. Overview and neurobiology of attention/hyperactivity disorder. J Clin Psychiatry 2002; 63Suppl. 12: 3–9

    PubMed  Google Scholar 

  8. Spencer T, Heiligenstein JH, Biederman J, et al. Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. J Clin Psychiatry 2002 Dec; 63(12): 1140–7

    Article  PubMed  CAS  Google Scholar 

  9. Elia J, Ambrosini PJ, Rapoport JL. Treatment of attention-deficit-hyperactivity disorder. N Engl J Med 1999 Mar 11; 340: 780–8

    Article  PubMed  CAS  Google Scholar 

  10. Biederman J, Spencer TJ, Lombroso P. Genetics of childhood disorders: XIX. ADHD (Pt 3): is ADHD a noradrenergic disorder? J Am Acad Child Adolesc Psychiatry 2000; 39(10): 1330–3

    Article  PubMed  CAS  Google Scholar 

  11. Greenhill LL, Halperin JM, Abikoff H. Stimulant medications. J Am Acad Child Adolesc Psychiatry 1999 May; 38: 503–12

    Article  PubMed  CAS  Google Scholar 

  12. Safer DJ. Central stimulant treatment of childhood attention deficit hyperactivity disorder: issues and recommendations from a US perspective. CNS Drugs 1997 Apr; 7: 264–72

    Article  Google Scholar 

  13. Pliszka SR. The use of psychostimulants in the pediatric patient. Pediatr Clin North Am 1998 Oct; 45: 1085–98

    Article  PubMed  CAS  Google Scholar 

  14. Wong DT, Threlkeld PG, Best KL, et al. A new inhibitor of norepinephrine uptake devoid of affinity for receptors in rat brain. J Pharmacol Exp Ther 1982; 222(1): 61–5

    PubMed  CAS  Google Scholar 

  15. Biederman J, Spencer T. Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder. Biol Psychiatry 1999; 46(9): 1234–42

    Article  PubMed  CAS  Google Scholar 

  16. Iversen L. Neurotransmitter transporters: fruitful targets for CNS drug discovery. Mol Psychiatry 2000; 5: 357–62

    Article  PubMed  CAS  Google Scholar 

  17. Bolden-Watson C, Richelson E. Blockade by newly-developed antidepressants of biogenic amine uptake into rat brain synaptosomes. Life Sci 1993; 52(12): 1023–9

    Article  PubMed  CAS  Google Scholar 

  18. Bymaster FP, Katner JS, Nelson DL, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology 2002 Nov; 27(5): 699–711

    Article  PubMed  CAS  Google Scholar 

  19. Zerbe RL, Rowe H, Enas GG, et al. Clinical pharmacology of tomoxetine, a potential antidepressant. J Pharmacol Exp Ther 1985 Jan; 232(1): 139–43

    PubMed  CAS  Google Scholar 

  20. Gehlert DR, Gackenheimer SL, Robertson DW. Localization of rat brain binding sites for [3H] tomoxetine, an enantiomerically pure ligand for epinephrine reuptake sites. Neurosci Lett 1993 Jul 23; 157(2): 203–6

    Article  PubMed  CAS  Google Scholar 

  21. Gehlert DR, Schober DA, Gackenheimer SL. Comparison of (R)-[3H]tomoxetine and (R/S)-[3H]nisoxetine binding in rat brain. J Neurochem 1995 Jun; 64(6): 2792–800

    Article  PubMed  CAS  Google Scholar 

  22. Stahl SM. Neurotransmission of cognition (Pt 2). Selective NRIs are smart drugs: exploiting regionally selective actions on both dopamine and norepinephrine to enhance cognition. J Clin Psychiatry 2003 Feb; 64(2): 110–1

    Article  PubMed  Google Scholar 

  23. Fuller RW, Hemrick-Luecke SK. Antagonism by tomoxetine of the depletion of norepinephrine and epinephrine in rat brain by α-methyl-m-tyrosine. Res Commun Chem Pathol Pharmacol 1983 Jul; 41(1): 169–72

    PubMed  CAS  Google Scholar 

  24. Cusack B, Nelson A, Richelson E. Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl) 1994 May; 114(4): 559–65

    Article  CAS  Google Scholar 

  25. Michelson D, Allen AJ, Busner J, et al. Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study. Am J Psychiatry 2002 Nov; 159(11): 1896–901

    Article  PubMed  Google Scholar 

  26. Michelson D, Faries D, Wernicke J, et al. Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Pediatrics 2001 Nov; 108(5): E83–91

    Article  PubMed  CAS  Google Scholar 

  27. Wernicke JF, Faries D, Kovacs R, et al. Cardiovascular effects of atomoxetine in children and adolescents [abstract no. A21]. 49th Annual Meeting of the American Academy of Child and Adolescent Pyschiatry; 2002 Oct 22–27; San Fransisco, 92

  28. Wernicke JF, Kratochvil CJ. Safety profile of atomoxetine in the treatment of children and adolescents with ADHD. J Clin Psychiatry 2002; 63Suppl. 12: 50–5

    PubMed  CAS  Google Scholar 

  29. Wernicke JF, Schuh KJ, Zhang S, et al. Safety of atomoxetine in children and adolescents treated for at least 1 year for attention-deficit/hyperactivity disorder [abstract no. P.3.W.018 and poster]. Collegium Internationale Neuro-Psychopharmcologium (CINP); 2002 Jun 23–27; Montreal, S163

  30. Belle DJ, Ernest CS, Sauer J-M, et al. Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics. J Clin Pharmacol 2002 Nov; 42(11): 1219–27

    Article  PubMed  CAS  Google Scholar 

  31. Witcher JW, Kurtz DL, Sauer J-M, et al. Pharmacokinetic/dynamic relationship of atomoxetine exposure and efficacy [abstract no. NR450]. American Psychiatric Association 2002 Annual Meeting; 2002 May 18–23; Philadelphia, 121–2

  32. Desager J, Desager J-P, Chalon S, et al. Pharmacokinetics (PK) of atomoxetine (ATM) in hepatically impaired (HI) patients [abstract no. WPIII-85]. 2002 Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics; 2002 Mar 24–27; Atlanta, P99

  33. Eli Lilly, Strattera R (omoxetine HCl) [online]. Available from URL: www.lilly.com [Accessed 2003 Feb 10]

  34. Kratochvil CJ, Bohac D, Harrington M, et al. An open-label trial of tomoxetine in pediatric attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 2001 Summer; 11(2): 167–70

    Article  PubMed  CAS  Google Scholar 

  35. Spencer T, Biederman J, Heiligenstein J, et al. An open-label, dose-ranging study of atomoxetine in children with attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 2001 Fall; 11(3): 251–65

    Article  PubMed  CAS  Google Scholar 

  36. Kratochvil CJ, Heiligenstein JH, Dittmann R, et al. Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry 2002 Jul; 41(7): 776–84

    Article  PubMed  Google Scholar 

  37. Biederman J, Heiligenstein JH, Faries DE, et al. Efficacy of atomoxetine versus placebo in school-age girls with attention-deficit/hyperactivity disorder. Pediatrics 2002 Dec; 110(6): E75–81

    Article  PubMed  Google Scholar 

  38. Heil SH, Holmes HW, Bickel WK, et al. Comparison of the subjective, physiological, and psychomotor effects of atomoxetine and methylphenidate in light drug users. Drug Alcohol Depend 2002 Jul 1; 67(2): 149–56

    Article  PubMed  CAS  Google Scholar 

  39. Chalon SA, Desager J-P, DeSante KA, et al. Effect of hepatic impairment on the pharmacokinetics of atomoxetine and its metabolites. Clin Pharmacol Ther 2003 Mar; 73(3): 178–91

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis International Inc., 770 Township Line Road, Suite 300, Yardley, Pennsylvania, 19067, USA

    Dene Simpson & Caroline M. Perry

Authors
  1. Dene Simpson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Caroline M. Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dene Simpson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Simpson, D., Perry, C.M. Atomoxetine. Pediatr-Drugs 5, 407–415 (2003). https://doi.org/10.2165/00128072-200305060-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00128072-200305060-00005

Keywords

Search

Navigation