Low-Dose antipsychotics in the treatment of tardive dyskinesia: an expanded narrative review of the literature
DOI:
https://doi.org/10.25118/2763-9037.2026.v16.1555Keywords:
tardive dyskinesia, antipsychotics, low dose, dopamine D2 receptor, narrative reviewAbstract
Introduction: Tardive dyskinesia (TD) is a movement disorder associated with chronic exposure to dopamine receptor–blocking agents, particularly antipsychotics, with higher prevalence among older adults, women, and patients with mood disorders. Management remains challenging when antipsychotic discontinuation increases psychiatric relapse risk. Objective: To provide an in-depth narrative review of the literature on low-dose antipsychotic use as a therapeutic strategy for TD, integrating pathophysiological and pharmacodynamic concepts with clinical evidence. Methods: The SANRA (Scale for the Assessment of Narrative Review Articles) methodology was used. Narrative review of PubMed and Cochrane databases (2010–2025), including studies in English, Portuguese, and Spanish. Results and Discussion: In selected clinical scenarios, low-dose antipsychotic reintroduction or maintenance may suppress TD manifestations, likely through modulation of dopaminergic hypersensitivity. This approach is suppressive rather than disease-modifying and requires careful individualized risk–benefit assessment. Conclusion: Low-dose antipsychotic use may represent a pragmatic and transitional strategy in complex TD cases. Further longitudinal and controlled studies are required.
Downloads
Metrics
References
1. Waln O, Jankovic J. An update on tardive dyskinesia: from phenomenology to treatment. Tremor Other Hyperkinet Mov. 2013;3: tre-03-161-4138-1. https://doi.org/10.7916/D88P5Z71 PMID: 23858394 PMCID: PMC3709416
2. Crane GE. Tardive dyskinesia in patients treated with major neuroleptics. Am J Psychiatry. 1968;124(Suppl):40-48. https://doi.org/10.1176/ajp.124.8S.40 PMid:4865731
3. Frei. K. Tardive dyskinesia: who gets it and why. Parkinsonism Relat Disord. 2019:59:151-54. https://doi.org/10.1016/j.parkreldis.2018.11.017 PMID: 30522959
4. Tenback DE, van Harten PN. Epidemiology and risk factors for (tardive) dyskinesia. Int Rev Neurobiol. 2011;98:211-230. https://doi.org/10.1016/B978-0-12-381328-2.00009-2 PMid:21907089
5. Dinan TG, Kohen D. Tardive dyskinesia in bipolar affective disorder: relationship to lithium therapy. Br J Psychiatry. 1989;155:55-7. https://doi.org/10.1192/bjp.155.1.55 PMid:2575003
6. Jeste DV, Wyatt RJ. Dogma disputed: is tardive dyskinesia due to postsynaptic dopamine receptor supersensitivity? J Clin Psychiatry. 1981;42(12):455-7. https://pubmed.ncbi.nlm.nih.gov/6118358/ PMID: 6118358
7. Takeuchi H, Mori Y, Tsutsumi Y. Pathophysiology, prognosis and treatment of tardive dyskinesia. Ther Adv Psychopharmacol. 2022;12:20451253221117313. https://doi.org/10.1177/20451253221117313 PMID: 36312846 PMCID: PMC9597038
8. Owens DC. Tardive dyskinesia: update on mechanisms and management. BJPsych Advances. 2019;25(6):367-76. https://doi.org/10.1192/bja.2018.46
9. Yoshida K, Bies RR, Suzuki T, Remington G, Pollock BG, Mizuno Y, Mimura M, Uchida H. Tardive dyskinesia in relation to estimated dopamine D2 receptor occupancy in patients with schizophrenia: analysis of the CATIE data. Schizophr Res. 2014;153(1-3):184-8. https://doi.org/10.1016/j.schres.2014.01.017 PMID: 24491908 PMCID: PMC3960457
10. Peluso MJ, Lewis SW, Barnes TR, Jones PB. Extrapyramidal motor side-effects of first- and second-generation antipsychotic drugs. Br J Psychiatry. 2012;200(5):387-92. https://doi.org/10.1192/bjp.bp.111.101485 PMid:22442101
11. Karaş H, Güdük M, Saatcioğlu Ö. Withdrawal-Emergent Dyskinesia and Supersensitivity Psychosis Due to Olanzapine Use. Noro Psikiyatr Ars. 2016;53(2):178-80. https://doi.org/10.5152/npa.2015.10122 PMID: 28360793 PMCID: PMC5353025
12. Horowitz MA, Taylor D. A method for tapering antipsychotic treatment that may minimize the risk of relapse. Schizophr Bull. 2021;47(4):1116-29. https://doi.org/10.1093/schbul/sbab017 PMid:33754644 PMCid:PMC8266572
13. Horowitz MA, Murray RM, Taylor D. Tapering Antipsychotic Treatment. Jama Psychiatry. 2021;78;(2):125-26. https://doi.org/10.1001/jamapsychiatry.2020.2166
14. Bergman H, Rathbone J, Agarwal V, Soares‐Weiser K. Antipsychotic reduction and/or cessation and antipsychotics-specific treatments for tardive dyskinesia. Cochrane Database Syst Rev. 2018;(2):CD000459. https://doi.org/10.1002/14651858.CD000459.pub3 PMid:29409162
15. Soares-Weiser K, Rathbone J. Miscellaneous treatments for antipsychotic-induced tardive dyskinesia. Cochrane Database Syst Rev. 2018;(3):CD000208. https://doi.org/10.1002/14651858.CD000208.pub2 PMid:29552749 PMCid:PMC6494382
16. Hauser RA, Factor SA, Marder SR, Knesevich MA, Ramirez PM, Jimenez R, Burke J, Liang GS, O'Brien CF. KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia. Am J Psychiatry. 2017;174(5):476-84. https://doi.org/10.1176/appi.ajp.2017.16091037 PMid:28320223
17. Fernandez HH, Factor SA, Hauser RA, Jimenez-Shahed J, Ondo WG, Jarskog L, Meltzer HY, Woods SW, Bega D, LeDoux MS, Shprecher DR, Davis C, Davis MD, Stamler D, Anderson KE. Randomized controlled trial of deutetrabenazine for tardive dyskinesia The ARM-TD study. Neurology. 2017;88(21):2003-10. https://doi.org/10.1212/WNL.0000000000003960 PMid:28446646 PMCid:PMC5440239
18. Fernandez HH, Stamler D, Davis M, Factor SA, Hauser RA, Jimenez-Shahed J, Ondo WG, Jarskog LF, Woods SW, Bega D, LeDoux MS, Shprecher DR, Anderson KE. Long-term safety and efficacy of deutetrabenazine for tardive dyskinesia. J Neurol Neurosurg Psychiatry. 2019;90(12):1317-23. https://doi.org/10.1136/jnnp-2018-319918 PMid:31296586 PMCid:PMC6902058
19. Solmi F, Pigato G, Kane JM, Correll CU. Treatment of tardive dyskinesia with VMAT-2 inhibitors: a systematic review and meta-analysis. Drug Des Devel Ther. 2018;12:1215-38. https://doi.org/10.2147/DDDT.S133205 PMid:29795977 PMCid:PMC5958944
20. Saklad SR. Identifying tardive dyskinesia: risk factors, functional impact, and diagnostic tools. J Clin Psychiatry. 2020;81(1):TV18059BR1C. https://doi.org/10.4088/JCP.TV18059BR1C
21. Lieberman JA, Saltz BL, Johns CA, Pollack S, Borenstein M, Kane J. The effects of clozapine on tardive dyskinesia. Br J Psychiatry. 1991;158:503-10. https://doi.org/10.1192/bjp.158.4.503 PMid:1675900
22. Tarsy D, Baldessarini RJ. Tardive dyskinesia. Annu Rev Med. 1984;35:605-23. https://doi.org/10.1146/annurev.me.35.020184.003133
23. Hazari N, Kate N, Grover S. Clozapine and tardive movement disorders: a review. Asian J Psychiatry. 2013;6(6):439-51. https://doi.org/10.1016/j.ajp.2013.08.067 PMID: 24309853
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Tauãna Otarãn Savian, Alexei Gil, Julia Hoefel Paes, Luiza Martins Barbosa, Lara Vitória Haubert Cassel, Marina Pimentel Beber de Mattos
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Debates em Psiquiatria allows the author (s) to keep their copyrights unrestricted. Allows the author (s) to retain their publication rights without restriction. Authors should ensure that the article is an original work without fabrication, fraud or plagiarism; does not infringe any copyright or right of ownership of any third party. Authors should also ensure that each one complies with the authorship requirements as recommended by the ICMJE and understand that if the article or part of it is flawed or fraudulent, each author shares responsibility.
Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) - Debates em Psiquiatria is governed by the licencse CC-By-NC
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material
The licensor cannot revoke these freedoms as long as you follow the license terms. Under the following terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- NonCommercial — You may not use the material for commercial purposes.
No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
