Skip to main content
SpringerLink
Log in

Therapeutic administration of atomoxetine combined with rTMS and occupational therapy for upper limb hemiparesis after stroke: a case series study of three patients

  • Original Article
  • Published:
Acta Neurologica Belgica Aims and scope Submit manuscript

Abstract

Atomoxetine, a selective noradrenaline reuptake inhibitor, has been reported to enhance brain plasticity, but has not yet been used in stroke patients. We reported the feasibility and clinical benefits on motor functional recovery of the combination of repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) in stroke patients. This pilot study was designed to evaluate the additive effects of oral atomoxetine to rTMS/OT in post-stroke hemiparetic patients. The study included three post-stroke patients with upper limb hemiparesis. Treatment with 40 mg/day atomoxetine commenced 2 weeks before admission. After confirming tolerance, the dose was increased to 120 mg/day. Low-frequency rTMS/OT was provided daily for 15 days during continued atomoxetine therapy. Motor function of the affected upper limb was evaluated with the Fugl-Meyer Assessment and Wolf Motor Function test. All patients completed the protocol and showed motor improvement up to 4 weeks after the treatment. No atomoxetine-related side effects were noted. Our protocol of triple therapy of atomoxetine, low-frequency rTMS, and OT is safe and feasible intervention for upper limb hemiparesis after stroke.

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

References

  1. Abo M, Kakuda W (2012) Rehabilitation for cerebrovascular disease: current and new methods in Japan. Jpn Med Assoc J 55:240–245

    Google Scholar 

  2. Wieloch T, Nikolich K (2006) Mechanisms of neural plasticity following brain injury. Curr Opin Neurobiol 16:258–264

    Article  CAS  PubMed  Google Scholar 

  3. Pekna M, Pekny M, Nilsson M (2012) Modulation of neural plasticity as a basis for stroke rehabilitation. Stroke 43:2819–2828

    Article  PubMed  Google Scholar 

  4. Tegenthoff M, Cornelius B, Pleger B, Malin JP, Schwenkreis P (2004) Amphetamine enhances training-induced motor cortex plasticity. Acta Neurol Scand 109:330–336

    Article  CAS  PubMed  Google Scholar 

  5. Boyeson MG, Feeney DM (1989) Intraventricular norepinephrine facilitates motor recovery following sensorimotor cortex injury. Pharmacol Biochem Behav 35:497–501

    Article  Google Scholar 

  6. Papadopoulos CM, Tsai S, Guillen V, Ortega J, Gwendolyn L, Wolf WA (2009) Motor recovery and axonal plasticity with short-term amphetamine after stroke. Stroke 40:294–302

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Martinsson L, Hardemark H, Eksborg S (2007) Amphetamines for improving recovery after stroke. Cochrane Database Syst Rev. doi:10.1002/14651858.CD002090.pub2

    PubMed  Google Scholar 

  8. Lokk J, Salman RR, Delbari A (2011) Effect of methylphenidate and/or levodopa coupled with physiotherapy on functional and motor recovery after stroke. A randomized, double-blind, placebo controlled trial. Acta Neurol Scand 123:266–273

    Article  CAS  PubMed  Google Scholar 

  9. Schuster C, Maunz G, Lutz K, Kischka U, Sturzenegger R, Ettlin T (2011) Dexamphetamine improves upper extremity outcome during rehabilitation after stroke: a pilot randomized controlled trial. Neurorehabil Neural Repair 25:749–755

    Article  PubMed  Google Scholar 

  10. Kollins SH, MacDonald EK, Rush CR (2001) Assessing the abuse potential of methylphenidate in nonhuman and human subjects: a review. Pharmacol Biochem Behav 68:611–627

    Article  CAS  PubMed  Google Scholar 

  11. Westover AN, Halm EA (2012) Do prescription stimulants increase the risk of adverse cardiovascular events? A systematic review. BMC Cardiovasc Disord 12:41

    Article  PubMed Central  PubMed  Google Scholar 

  12. Gehlert DR, Schober DA, Hemrick-Luecke SK, Krushinski J, Howbert JJ, Robertson DW, Fuller RW, Wong DT (1995) Novel halogenated analogs of atomoxetine that are potent and selective inhibitors of norepinephrine uptake in brain. Neurochem Int 26:47–52

    Article  CAS  PubMed  Google Scholar 

  13. Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, Morin SM, Gehlert DR, Perry KW (2002) Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology 27:699–711

    Article  CAS  PubMed  Google Scholar 

  14. Wernicke JF, Faries D, Girod D, Brown J, Gao H, Kelsey D, Quintana H, Lipetz R, Michelson D, Heiligenstein J (2003) Cardiovascular effects of atomoxetine in children, adolescents and adults. Drug Saf 26:729–740

    Article  CAS  PubMed  Google Scholar 

  15. Upadhyaya HP, Desaiah D, Schuh KJ, Bymaster FP, Kallman MJ, Clarke DO, Durell TM, Trzepacz PT, Calligaro DO, Nisenbaum ES, Emmerson PJ, Schuh LM, Bickel WK, Allen AJ (2013) A review of the abuse potential assessment of atomoxetine: a nonstimulant medication for attention-deficit/hyperactivity disorder. Psychopharmacology 226:189–200

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Plewnia C, Hoppe J, Hiemke C, Bartels M, Cohen LG, Gerloff C (2002) Enhancement of human cortico-motoneuronal excitability by the selective norepinephrine reuptake inhibitor reboxetine. Neurosci Lett 330:231–234

    Article  CAS  PubMed  Google Scholar 

  17. Foster DJ, Good DC, Fowlkes A, Sawaki L (2006) Atomoxetine enhances a short-term model of plasticity in humans. Arch Phys Med Rehabil 87:216–221

    Article  PubMed  Google Scholar 

  18. Gilbert DL, Ridel KR, Sallee FR, Zhang J, Lipps TD, Wassermann EM (2006) Comparison of the inhibitory and excitatory effects of ADHD medications methylphenidate and atomoxetine on motor cortex. Neuropsychopharmacology 31:442–449

    Article  CAS  PubMed  Google Scholar 

  19. Sczesny-Kaiser M, Bauknecht A, Höffken O, Tegenthoff M, Dinse HR, Jancke D, Funke K, Schwenkreis P (2014) Synergistic effects of noradrenergic modulation with atomoxetine and 10 Hz repetitive transcranial magnetic stimulation on motor learning in healthy humans. BMC Neurosci 15:46

    Article  PubMed Central  PubMed  Google Scholar 

  20. Kakuda W, Abo M, Kobayashi K, Momosaki R, Yokoi A, Fukuda A, Umemori T (2011) Application of combined 6-Hz primed low-frequency rTMS and intensive occupational therapy for upper limb hemiparesis after stroke. NeuroRehabilitation 29:365–371

    PubMed  Google Scholar 

  21. Kakuda W, Abo M, Shimizu M, Sasanuma J, Okamoto T, Yokoi A, Taguchi K, Mitani S, Harashima H, Urushidani N, Urashima M, Investigators NEURO (2012) A multi-center study on low-frequency rTMS combined with intensive occupational therapy for upper limb hemiparesis in post-stroke patients. J Neuroeng Rehabil 9:4

    Article  PubMed Central  PubMed  Google Scholar 

  22. Abo M, Kakuda W, Momosaki R, Harashima H, Kojima M, Watanabe S, Sato T, Yokoi A, Umemori T, Sasanuma J (2014) Randomized, multicenter, comparative study of NEURO versus CIMT in poststroke patients with upper limb hemiparesis: the NEURO-VERIFY study. Int J Stroke 9:607–612

    Article  PubMed  Google Scholar 

  23. Wassermann EM (1998) Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5–7, 1996. Electroencephalogr Clin Neurophysiol 108:1–16

    Article  CAS  PubMed  Google Scholar 

  24. Gladstone DJ, Danells CJ, Black SE (2002) The Fugl-Meyer assessment of motor recovery after stroke: a critical review of its measurement properties. Neurorehabil Neural Repair 16:232–240

    Article  PubMed  Google Scholar 

  25. Wolf SL, Catlin PA, Ellis M, Archer AL, Morgan B, Piacentino A (2001) Assessing wolf motor function test as outcome measure for research in patients after stroke. Stroke 32:1635–1639

    Article  CAS  PubMed  Google Scholar 

  26. Pandyan AD, Johnson GR, Price CI, Curless RH, Barnes MP, Rodgers H (1999) A review of the properties and limitations of the Ashworth and modified Ashworth scales as measures of spasticity. Clin Rehabil 13:373–383

    Article  CAS  PubMed  Google Scholar 

  27. Corti M, Patten C, Triggs W (2012) Repetitive transcranial magnetic stimulation of motor cortex after stroke: a focused review. Am J Phys Med Rehabil 91:254–270

    Article  PubMed  Google Scholar 

  28. Yamada N, Kakuda W, Senoo A, Kondo T, Mitani S, Shimizu M, Abo M (2013) Functional cortical reorganization after low-frequency repetitive transcranial magnetic stimulation plus intensive occupational therapy for upper limb hemiparesis: evaluation by functional magnetic resonance imaging in poststroke patients. Int J Stroke 8:422–429

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the participation and the support of the patients in the study.

Author information

Authors and Affiliations

  1. Department of Rehabilitation Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-Ku, Tokyo, 105-8461, Japan

    Shoji Kinoshita, Wataru Kakuda, Naoki Yamada, Ryo Momosaki, Ryo Okuma, Shu Watanabe & Masahiro Abo

Authors
  1. Shoji Kinoshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wataru Kakuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naoki Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ryo Momosaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ryo Okuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shu Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Masahiro Abo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masahiro Abo.

Ethics declarations

Conflict of interest

The authors report no conflicts of interest.

Ethical approval

The study protocol and intervention were approved by the ethics committee of our university.

Informed consent

Informed consent was obtained from the all of three patients.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kinoshita, S., Kakuda, W., Yamada, N. et al. Therapeutic administration of atomoxetine combined with rTMS and occupational therapy for upper limb hemiparesis after stroke: a case series study of three patients. Acta Neurol Belg 116, 31–37 (2016). https://doi.org/10.1007/s13760-015-0503-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13760-015-0503-3

Keywords

Search

Navigation