Valbenazine for the Treatment of Adults with Tardive Dyskinesia

Purpose of review
This a comprehensive review of the literature regarding the use of Valbenazine in treating tardive dyskinesia. A primarily oral movement disorder induced by chronic exposure to certain classes of medications, tardive dyskinesia is often resistant to many therapeutic approaches. This review presents the background, evidence, and indications for the use of Valbenazine as a treatment option for this condition.
Recent Findings
Tardive dyskinesia is a disorder arising from long-term exposure to medications that blocked dopamine receptors, primarily antipsychotics. It is characterized by abnormal movements of the oral-buccal-lingual structures as well as associated pain and hypertrophy. Simply stopping the use of the dopamine blocking agents effectively alleviates the symptoms but is not always reliable hence the need for another therapeutic approach.
Valbenazine is thought to function as a highly selective inhibitor of the VMAT2 vesicular monoamine transporter resulting in decreased availability of dopamine in the presynaptic cleft. This leads to decreased dopaminergic activation of the striatal motor pathway. The FDA approved Valbenazine in 2017 to treat tardive dyskinesia in adults and needs to be evaluated with existing therapeutic approaches.
Summary
The chronic use of dopamine receptor blocking agents, most commonly antipsychotics, can lead to a movement disorder called tardive dyskinesia. Once symptom onset has occurred, these movement abnormalities can persist for years to permanently, depending on the speed and effectiveness of treatment. Valbenazine is a relatively newer option for the treatment of tardive dyskinesia in adults. Compared to other pharmaceutical agents, it is more selective and has limited toxicities making it an effective treatment regimen. However, further research, including additional direct comparison studies, should be conducted to fully evaluate this drug’s usefulness.
1. Frei K, Truong DD, Fahn S, Jankovic J, Hauser RA. The nosology of tardive syndromes. Journal of the Neurological Sciences. 2018;389:10-16. doi:10.1016/j.jns.2018.02.008
2. Savitt D, Jankovic J. Tardive syndromes. Journal of the Neurological Sciences. 2018;389:35-42. doi:10.1016/j.jns.2018.02.005
3. McEvoy J, Gandhi SK, Rizio AA, et al. Effect of tardive dyskinesia on quality of life in patients with bipolar disorder, major depressive disorder, and schizophrenia. Quality of Life Research. 2019;28(12):3303-3312. doi:10.1007/s11136-019-02269-8
4. Medication-Induced Movement Disorders and Other Adverse Effects of Medication. In: Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013.
5. Hauser RA, Truong D. Tardive dyskinesia: Out of the shadows. Journal of the Neurological Sciences. 2018;389:1-3. doi:10.1016/j.jns.2018.02.009
6. Carbon M, Hsieh CH, Kane JM, Correll CU. Tardive Dyskinesia Prevalence in the Period of Second-Generation Antipsychotic Use. The Journal of Clinical Psychiatry. 2017;78(3):e264-e278. doi:10.4088/JCP.16r10832
7. D'Abreu A, Akbar U, Friedman JH. Tardive dyskinesia: Epidemiology. Journal of the Neurological Sciences. 2018;389:17-20. doi:10.1016/j.jns.2018.02.007
8. Cornett EM, Novitch M, Kaye AD, Kata V, Kaye AM. Medication-Induced Tardive Dyskinesia: A Review and Update. The Ochsner journal. 2017;17(2):162-174.
9. Scorr LM, Factor SA. VMAT2 inhibitors for the treatment of tardive dyskinesia. Journal of the Neurological Sciences. 2018;389:43-47. doi:10.1016/j.jns.2018.02.006
10. Citrome L. Clinical management of tardive dyskinesia: Five steps to success. Journal of the Neurological Sciences. 2017;383:199-204. doi:10.1016/j.jns.2017.11.019
11. Correll CU, Schenk EM. Tardive dyskinesia and new antipsychotics. Current Opinion in Psychiatry. 2008;21(2):151-156. doi:10.1097/YCO.0b013e3282f53132
12. Frei K. Tardive dyskinesia: Who gets it and why. Parkinsonism and Related Disorders. 2019;59:151-154. doi:10.1016/j.parkreldis.2018.11.017
13. Stahl SM. Neuronal traffic signals in tardive dyskinesia: not enough “stop” in the motor striatum. CNS Spectrums. 2017;22(6):427-434. doi:10.1017/S109285291700061X
14. Ward KM, Citrome L. Antipsychotic-Related Movement Disorders: Drug-Induced Parkinsonism vs. Tardive Dyskinesia-Key Differences in Pathophysiology and Clinical Management. Neurology and Therapy. 2018;7(2):233-248. doi:10.1007/s40120-018-0105-0
15. Mahmoudi S, Lévesque D, Blanchet PJ. Upregulation of dopamine D3, not D2, receptors correlates with tardive dyskinesia in a primate model. Movement Disorders. 2014;29(9):1125-1133. doi:10.1002/mds.25909
16. Levesque C, Hernandez G, Mahmoudi S, et al. Deficient striatal adaptation in aminergic and glutamatergic neurotransmission is associated with tardive dyskinesia in non-human primates exposed to antipsychotic drugs. Neuroscience. 2017;361:43-57. doi:10.1016/j.neuroscience.2017.07.068
17. Solmi M, Pigato G, Kane JM, Correll CU. Clinical risk factors for the development of tardive dyskinesia. Journal of the Neurological Sciences. 2018;389:21-27. doi:10.1016/j.jns.2018.02.012
18. Vancampfort D, Correll CU, Galling B, et al. Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: A systematic review and large scale meta-analysis. World Psychiatry. 2016;15(2):166-174. doi:10.1002/wps.20309
19. Jain R, Correll CU. Tardive Dyskinesia: Recognition, Patient Assessment, and Differential Diagnosis. The Journal of Clinical Psychiatry. 2018;79(2):16-23. doi:10.4088/JCP.nu17034ah1c
20. Margolius A, Fernandez HH. Current treatment of tardive dyskinesia. Parkinsonism and Related Disorders. 2019;59:155-160. doi:10.1016/j.parkreldis.2018.12.022
21. Peselow ED, Angrist BM, Rotrosen J. Changes in tardive dyskinesia after fluphenazine decanoate discontinuation. Annals of Clinical Psychiatry. 1989;1(3):187-191. doi:10.3109/10401238909149978
22. Bhidayasiri R, Fahn S, Weiner WJ, Gronseth GS, Sullivan KL, Zesiewicz TA. Evidence-based guideline: Treatment of tardive syndromes: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013;81(5):463-469. doi:10.1212/WNL.0b013e31829d86b6
23. Shenoy RS, Sadler AG, Goldberg SC, Hamer RM, Ross B. Effects of a six-week drug holiday on symptom status, relapse, and tardive dyskinesia in chronic schizophrenics. Journal of Clinical Psychopharmacology. 1981;1(3):141-145. doi:10.1097/00004714-198105000-00005
24. Waln O, Jankovic J. An Update on Tardive Dyskinesia: From Phenomenology to Treatment. Tremor and Other Hyperkinetic Movements. 2013;3(0):03. doi:10.5334/tohm.165
25. Emsley R, Ch MBB, Med M, Psych FCJ, Turner MB. A Single-Blind, Randomized Trial Comparing Quetiapine and Haloperidol in the Treatment of Tardive Dyskinesia. Vol 65. Physicians Postgraduate Press, Inc.; 2004.
26. Chan HY, Chiang SC, Chang CJ, et al. A Randomized Controlled Trial of Risperidone and Olanzapine for Schizophrenic Patients With Neuroleptic-Induced Tardive Dyskinesia. The Journal of Clinical Psychiatry. 2010;71(09):1226-1233. doi:10.4088/JCP.09m05155yel
27. Simpson GM, Lee JH, Shrivastava RK. Clozapine in tardive dyskinesia. Psychopharmacology. 1978;56(1):75-80. doi:10.1007/BF00571412
28. Bhidayasiri R, Jitkritsadakul O, Friedman JH, Fahn S. Updating the recommendations for treatment of tardive syndromes: A systematic review of new evidence and practical treatment algorithm. Journal of the Neurological Sciences. 2018;389:67-75. doi:10.1016/j.jns.2018.02.010
29. Angus S, Sugars J, Boltezar R, Koskewich S, Schneider NM. A controlled trial of amantadine hydrochloride and neuroleptics in the treatment of tardive dyskinesia. Journal of Clinical Psychopharmacology. 1997;17(2):88-91. doi:10.1097/00004714-199704000-00004
30. Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends in Neurosciences. 1989;12(10):366-375. doi:10.1016/0166-2236(89)90074-X
31. Pappa S, Tsouli S, Apostolou G, Mavreas V, Konitsiotis S. Effects of amantadine on tardive dyskinesia: A randomized, double-blind, placebo-controlled study. Clinical Neuropharmacology. 2010;33(6):271-275. doi:10.1097/WNF.0b013e3181ffd e32
32. Thaker GK, Nguyen JA, Strauss ME, Jacobson R, Kaup BA, Tamminga CA. Clonazepam treatment of tardive dyskinesia: A practical GABAmimetic strategy. American Journal of Psychiatry. 1990;147(4):445-451. doi:10.1176/ajp.147.4.445
33. Soares-Weiser K, Fernandez HH. Tardive dyskinesia. Seminars in Neurology. 2007;27(2):159-169. doi:10.1055/s-2007-971169
34. Adler LA, Peselow E, Rotrosen J, et al. Vitamin E treatment of tardive dyskinesia. In: American Journal of Psychiatry. Vol 150.; 1993:1405-1407. doi:10.1176/aip.150.9.1405
35. Adler LA, Rotrosen J, Edson R, et al. Vitamin E treatment for tardive dyskinesia. Archives of General Psychiatry. 1999;56(9):836-841. doi:10.1001/archpsy c.56.9.836
36. Zhang WF, Tan YL, Zhang XY, Chan RCK, Wu HR, Zhou DF. Extract of Ginkgo biloba Treatment for Tardive Dyskinesia in Schizophrenia. The Journal of Clinical Psychiatry. 2011;72(05):615-621. doi:10.4088/JCP.09m05125yel
37. van Harten PN, Hovestadt A. Botulinum toxin as a treatment for tardive dyskinesia. Movement Disorders. 2006;21(8):1276-1277. doi:10.1002/mds.20904
38. Rapaport A, Sadeh M, Stein D, et al. Botulinum toxin for the treatment of oro-facial-lingual-masticatory tardive dyskinesia. Movement Disorders. 2000;15(2):352-355. doi:10.1002/1531-8257(200003)15:23.0.CO;2-X
39. Peng LY, Lee Y, Lin PY. Electroconvulsive therapy for a patient with persistent tardive dyskinesia: A case report and literature review. Journal of ECT. 2013;29(3). doi:10.1097/YCT.0b013e31829e0aea
40. Yasui-Furukori N, Nakamura K, Katagai H, Kaneko S. The effects of electroconvulsive therapy on tardive dystonia or dyskinesia induced by psychotropic medication: a retrospective study. Neuropsychiatric Disease and Treatment. 2014;10:1209. doi:10.2147/NDT.S62490
41. Kefalopoulou Z, Paschali A, Markaki E, Vassilakos P, Ellul J, Constantoyannis C. A double-blind study on a patient with tardive dyskinesia treated with pallidal deep brain stimulation. Acta Neurologica Scandinavica. 2009;119(4):269-273. doi:10.1111/j.1600-0404.2008.01115.x
42. Schrader C, Peschel T, Petermeyer M, Dengler R, Hellwig D. Unilateral deep brain stimulation of the internal globus pallidus alleviates tardive dyskinesia. Movement Disorders. 2004;19(5):583-585. doi:10.1002/mds.10705
43. Pouclet-Courtemanche H, Rouaud T, Thobois S, et al. Long-term efficacy and tolerability of bilateral pallidal stimulation to treat tardive dyskinesia. Neurology. 2016;86(7):651-659. doi:10.1212/WNL.0000000000002370
44. Damier P, Thobois S, Witjas T, et al. Bilateral deep brain stimulation of the globus pallidus to treat tardive dyskinesia. Archives of General Psychiatry. 2007;64(2):170-176. doi:10.1001/archpsyc.64.2.170
45. Deng ZD, Li D, Zhang C, Pan YX, Zhang J, Jin H. Long-term follow-up of bilateral subthalamic deep brain stimulation for refractory tardive dystonia. Parkinsonism & related. Published online 2017.
46. Shaikh AG, Mewes K, DeLong MR, Gross RE. Temporal profile of improvement of tardive dystonia after globus pallidus deep brain stimulation. Parkinsonism & related. Published online 2015.
47. Ondo WG, Hanna PA, Jankovic J. Tetrabenazine treatment for tardive dyskinesia: Assessment by randomized videotape protocol. American Journal of Psychiatry. 156(8):1279-1281. doi:10.1176/ajp.156.8.1279
48. Leung JG, Breden EL. Tetrabenazine for the treatment of tardive dyskinesia. The Annals of pharmacotherapy. 2011;45(4):525-531. doi:10.1345/ap h.1P312
49. Stamler D, Bradbury M, Brown F. The pharmacokinetics and safety of deuterated-tetrabenazine (P07.210). Published online 2013.
50. Fernandez HH, Factor SA, Hauser RA, et al. Randomized controlled trial of deutetrabenazine for tardive dyskinesia (ARM-TD study). Neurology. 2017;88(21):2003-2010. doi:10.1212/WNL.0000000000003960
51. Anderson KE, Stamler D, Davis MD, et al. Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomised, placebo-controlled, phase 3 trial. The Lancet Psychiatry. 2017;4(8):595-604. doi:10.1016/S2215-0366(17)30236-5
52. Uhlyar S, Rey JA. Valbenazine (Ingrezza): The first FDA-approved treatment for tardive dyskinesia. P and T. 2018;43(6):328-331.
53. Jankovic J. Dopamine depleters in the treatment of hyperkinetic movement disorders. Expert Opinion on Pharmacotherapy. 2016;17(18):2461-2470. doi:10.1080/14656566.2016.1258063
54. Müller T. Valbenazine granted breakthrough drug status for treating tardive dyskinesia. Expert Opinion on Investigational Drugs. 2015;24(6):737-742. doi:10.1517/13543784.2015.1029573
55. O’Brien CF, Jimenez R, Hauser RA, et al. NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: A randomized, double-blind, placebo-controlled study. Movement Disorders. 2015;30(12):1681-1687. doi:10.1002/mds.26330
56. Hauser RA, Factor SA, Marder SR, et al. KINECT 3: A phase 3 randomized, double-blind, placebo-controlled trial of valbenazine for tardive dyskinesia. American Journal of Psychiatry. 2017;174(5):476-484. doi:10.1176/appi.ajp.2017.16091037
57. FDA. Valbenazine Drug Information.
58. Grigoriadis DE, Smith E, Hoare SRJ, Madan A, Bozigian H. Pharmacologic characterization of valbenazine (NBI-98854) and its metabolites. Journal of Pharmacology and Experimental Therapeutics. 2017;361(3):454-461. doi:10.1124/jpet.116.239160
59. Stahl SM. Comparing pharmacologic mechanism of action for the vesicular monoamine transporter 2 (VMAT2) inhibitors valbenazine and deutetrabenazine in treating tardive dyskinesia: does one have advantages over the other? Published online 2018. doi:10.1017/S1092852918001219
60. Stahl SM. Dazzled by the dominions of dopamine: Clinical roles of D3, D2, and D1 receptors. CNS Spectrums. 2017;22(4):305-311. doi:10.1017/S1092852917000426
61. Huang M, He W, Rajagopal L, Kudwa A, Grigoriadis DE, Meltzer HY. Effects of NBI-98782, a selective vesicular monoamine transporter 2 (VMAT2) inhibitor, on neurotransmitter efflux and phencyclidine-induced locomotor activity: Relevance to tardive dyskinesia and antipsychotic action. Pharmacology Biochemistry and Behavior. 2020;190:172872. doi:10.1016/j.pbb.2020.172872
62. Stahl SM. Neuronal traffic signals in tardive dyskinesia: Not enough stop in the motor striatum. CNS Spectrums. 2017;22(6):427-434. doi:10.1017/S109285291700061X
63. Luo R, Bozigian H, Jimenez R, Loewen G, O’Brien CF. Single dose and repeat once-daily dose safety, tolerability and pharmacokinetics of valbenazine in healthy male subjects. Psychopharmacology Bulletin. 2017;47(3):44-52.
64. Stahl SM. Mechanism of action of vesicular monoamine transporter 2 (VMAT2) inhibitors in tardive dyskinesia: reducing dopamine leads to less “go” and more “stop” from the motor striatum for robust therapeutic effects. Published online 2017. doi:10.1017/S1092852917000621
65. Caroff SN, Campbell EC. Drug-Induced Extrapyramidal Syndromes: Implications for Contemporary Practice. Psychiatric Clinics of North America. 2016;39(3):391-411. doi:10.1016/j.psc.2016.04.003
66. Neurocrine Biosciences. Highlights of prescribing information. INGREZZA (valbenazine) capsules, for oral use. Published online 2017.
67. Thai-Cuarto D, O’Brien CF, Jimenez R, Liang GS, Burke J. Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three Randomized, Double-Blind, Placebo-Controlled Trials. Drug Safety. 2018;41(4):429-440. doi:10.1007/s40264-017-0623-1
68. Solmi M, Pigato G, Kane JM, Correll CU. Treatment of tardive dyskinesia with VMAT-2 inhibitors: A systematic review and meta-analysis of randomized controlled trials. Drug Design, Development and Therapy. 2018;12:1215-1238. doi:10.2147/DDDT.S133205
69. Factor SA, Remington G, Comella CL, et al. The Effects of Valbenazine in Participants with Tardive Dyskinesia: Results of the 1-year KINECT 3 Extension Study. Journal of Clinical Psychiatry. 2017;78:9 (November/December):1344-1350. doi:10.4088/JCP.17m11777
70. Correll CU, Josiassen RC, Liang GS, Burke J, O’Brien CF. Efficacy of valbenazine (NBI-98854) in treating subjects with tardive dyskinesia and schizophrenia or schizoaffective disorder. Psychopharmacology Bulletin. 2017;47(3):69-76.
71. Citrome L. Valbenazine for tardive dyskinesia: A systematic review of the efficacy and safety profile for this newly approved novel medication-What is the number needed to treat, number needed to harm and likelihood to be helped or harmed? International Journal of Clinical Practice. 2017;71(7):1-14. doi:10.1111/ijcp.12964