Acta Scientific Clinical Case Reports

Review ArticleVolume 3 Issue 2

A Combination of Mechanisms Contributes to the Development of Tardive Dyskinesia: Management Implications

Matthias Oyigeya*

Department of Psychiatry, Federal Medical Centre, Makurdi, Benue State, Nigeria

*Corresponding Author: Matthias Oyigeya, Department of Psychiatry, Federal Medical Centre, Makurdi, Benue State, Nigeria.

Received: December 01, 2021; Published: January 06, 2022


Tardive Dyskinesia (TD) has defiled all forms of therapy and continues to constitute significant clinical problem. Existing hypotheses implicate dysregulations of both excitatory and inhibitory neurotransmitters, with consequent neuronal changes/damage. The present consensus is that a combination of mechanisms contributes to the development of TD. Authors advise on a combination therapy targeted at the cellular phenomena underlying the disease.

Keywords: Tardive Dyskinesia; Hypotheses; Glutamate; Dopamine (DA)


  1. Text Revision. 4th Washington: American Psychiatric Association; American Psychiatric Association. “Diagnostic and Statistical Manual of Mental Disorders” (2000).
  2. Arya D., et al. “Tardive Dyskinesia: Treatment Update”. Current Neurology and Neuroscience Reports 9 (2019): 69.
  3. Bashir HH and Jankovic J. “Treatment of Tardive Dyskinesia”. Neurology Clinical 2 (2000): 379-396.
  4. Tsai G., et al. “Markers of glutamatergic neurotransmission and oxidative stress associated with tardive dyskinesia”. The American Journal of Psychiatry 9 (1998): 1207-1213.
  5. Naidu PS., et al. “Carvedilol attenuates neuroleptic-induced orofacial dyskinesia: possible antioxidant mechanisms”. British Journal of Pharmacology 2 (2002): 193-200.
  6. Kang NR and Kim MD. “Tardive dyskinesia: treatment with aripiprazole”. Clinical Psychopharmacology and Neuroscience 1 (2011): 1-8.
  7. Lister J., et al. “Lipoic acid and haloperidol-induced vacuous chewing movements: Implications for prophylactic antioxidant use in tardive dyskinesia”. Progress in Neuro-Psychopharmacology and Biological Psychiatry 72 (2017): 23-29.
  8. Peckham AM and Nicewonder JA. “VMAT2 Inhibitors for Tardive Dyskinesia-Practice Implications”. Journal of Pharmacy Practice 4 (2019): 450-457.
  9. Teo JT., et al. “Tardive dyskinesia is caused by maladaptive synaptic plasticity: a hypothesis”. Movement Disorders 27 (10 (2012): 1205-1215.
  10. Sreeram V., et al. “Role of Vesicular Monoamine Transporter 2 Inhibitors in Tardive Dyskinesia Management”. Cureus8 (2019): e5471.
  11. Walther S and Strik W. “Motor Symptoms and Schizophrenia”. Neuropsychobiology 66 (2012): 77-92.
  12. Nakawah MO and Lai EC. “Post-stroke dyskinesias”. Neuropsychiatric Disease and Treatment 12 (2016): 2885-2893.
  13. Lanciego JL., et al. “Functional neuroanatomy of the basal ganglia”. Cold Spring Harbor Perspectives in Medicine 12 (2012): a009621.
  14. Gardoni F and Bellone C. “Modulation of the glutamatergic transmission by Dopamine: a focus on Parkinson, Huntington and Addiction diseases”. Frontiers in Cellular Neuroscience 9 (2015): 25.
  15. Fazl A and Fleisher J. “Anatomy, Physiology, and Clinical Syndromes of the Basal Ganglia: A Brief Review”. Seminars in Pediatric Neurology 25 (2018): 2-9.
  16. Lerner PP., et al. “Tardive dyskinesia (syndrome): Current concept and modern approaches to its management”. Psychiatry and Clinical Neurosciences 6 (2015): 321-334.
  17. Ali Z., et al. “A unifying theory for the pathoetiologic mechanism of tardive dyskinesia”. Medical Hypotheses 140 (2020): 109682.
  18. Javed N and Cascella M. “Neuroanatomy, Globus Pallidus. StatPearls”. Treasure Island (FL): StatPearls Publishing (2021).
  19. Villalba RM and Smith Y. “Loss and remodeling of striatal dendritic spines in Parkinson's disease: from homeostasis to maladaptive plasticity?” Journal of Neural Transmission (Vienna)3 (2018): 431-447.
  20. Ferré S and Ciruela F. “Functional and Neuroprotective Role of Striatal Adenosine A2A Receptor Heterotetramers”. Journal of Caffeine and Adenosine Research 3 (2019): 89-97.
  21. Steiner H and Gerfen CR. “Role of dynorphin and enkephalin in the regulation of striatal output pathways and behavior”. Experimental Brain Research 1-2 (1998): 60-76.
  22. Schiffmann SN., et al. “Adenosine A2A receptors and basal ganglia physiology”. Progress in Neurobiology 5 (2007): 277-292.
  23. Bamford NS., et al. “Heterosynaptic dopamine neurotransmission selects sets of corticostriatal terminals”. Neuron4 (2004): 653-663.
  24. Biggs CS., et al. “Extracellular levels of glutamate and aspartate in the entopeduncular nucleus of the rat determined by microdialysis: regulation by striatal dopamine D2 receptors via the indirect striatal output pathway?” Brain Research1 (1997): 163-175.
  25. Marti M., et al. “Striatal dopamine-NMDA receptor interactions in the modulation of glutamate release in the substantia nigra pars reticulata in vivo: opposite role for D1 and D2 receptors”. Journal of Neurochemistry 3 (2002): 635-644.
  26. Mela F., et al.In vivo evidence for a differential contribution of striatal and nigral D1 and D2 receptors to L-DOPA induced dyskinesia and the accompanying surge of nigral amino acid levels”. Neurobiology of Disease 1 (2012): 573-582.
  27. Caroff SN. “Recent Advances in the Pharmacology of Tardive Dyskinesia”. Clinical Psychopharmacology and Neuroscience 4 (2020): 493-506.
  28. Lewerenz J and Maher P. “Chronic Glutamate Toxicity in Neurodegenerative Diseases-What is the Evidence?” Frontiers in Neuroscience 9 (2015): 469.
  29. Spencer S and Kalivas PW. “Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse”. International Journal of Neuropsychopharmacology10 (2017): 797-812.
  30. Armada-Moreira A., et al. “Going the Extra (Synaptic) Mile: Excitotoxicity as the Road Toward Neurodegenerative Diseases”. Frontiers in Cellular Neuroscience 14 (2020): 90.
  31. Lewerenz J., et al. “Cooperative action of glutamate transporters and cystine/glutamate antiporter system Xc- protects from oxidative glutamate toxicity”. Journal of Neurochemistry 3 (2006): 916-925.
  32. Mori A and Shindou T. “Modulation of GABAergic transmission in the striatopallidal system by adenosine A2A receptors: a potential mechanism for the antiparkinsonian effects of A2A antagonists”. Neurology11-6 (2003): S44-48.
  33. Oyigeya M. “Reflex memory theory of acquired involuntary motor and sensory disorders”. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery (2021): 57-59.
  34. Bellfy L and Kwapis JL. “Molecular Mechanisms of Reconsolidation-Dependent Memory Updating”. International Journal of Molecular Sciences 18 (2020): 6580.
  35. Mansuy IM and Mohanna S. “Epigenetics and the human brain: where nurture meets nature”. Cerebrum 2011 (2011): 8.
  36. Briggs SB., et al. “The role of nonmuscle myosin II in polydrug memories and memory reconsolidation”. Learning and Memory 9 (2018): 391-398.
  37. Young EJ., et al. “Nonmuscle myosin IIB as a therapeutic target for the prevention of relapse to methamphetamine use”. Molecular Psychiatry 5 (2016): 615-623.
  38. Young EJ., et al. “Nonmuscle myosin II inhibition disrupts methamphetamine-associated memory in females and adolescents”. Neurobiology of Learning and Memory 139 (2017): 109-116.
  39. Adamczyk AK and Zawadzki P. “The Memory-Modifying Potential of Optogenetics and the Need for Neuroethics”. NanoEthics 14 (2020)207-225.
  40. Ordaz JD., et al. “Optogenetics and its application in neural degeneration and regeneration”. Neural Regeneration Research 12 (2017): 1197-1209.
  41. Rossi MA., et al. “Spotlight on movement disorders: What optogenetics has to offer”. Movement Disorders 5 (2015): 624-631.
  42. Andres DS and Darbin O. “Complex Dynamics in the Basal Ganglia: Health and Disease Beyond the Motor System”. The Journal of Neuropsychiatry and Clinical Neurosciences 2 (2018): 101-114.

Citation: Matthias Oyigeya. “A Combination of Mechanisms Contributes to the Development of Tardive Dyskinesia: Management Implications". Acta Scientific Clinical Case Reports 3.2 (2022): 12-20.

Copyright: © 2022 Matthias Oyigeya. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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