Chirag Shah, PharmD, RPh
Head Medical Affairs & Medical Education
Neurocrine Biosciences

Jonathan Meyer, MD
Clinical Professor of Psychiatry
University of California San Diego

American Psychiatric Association’s new recommendations on the treatment of schizophrenia, released in May 2021, take into account more recent data on antipsychotics, treatment-resistant schizophrenia, and patient preference.  The decision for the new changes was largely sparked by a systematic review led by McDonagh et al, that had been commissioned by the Agency for Healthcare Research and Quality (AHRQ).3  McDonagh’s team reported on new antipsychotics released into the market, including the role of VMAT2 inhibitors in managing tardive dyskinesia (TD) symptoms, and provided a more in-depth summary of antipsychotics with regard to optimizing and individualizing medication choices.

In its 2020 treatment guidelines for schizophrenia, the American Psychiatric Association  recommended that a structured instrument such as the AIMS be administered at least every 12 months, and more frequently (at least every 6 months) in patients with higher TD risk.13,14 Using a modified Delphi process, a panel of psychiatrists and neurologists agreed that a less formal assessment could also be used for screening in clinical practice settings.15 ”

As presented in the real-world RE-KINECT study, these informal assessments could be based on a quick visual observation of the four major body regions (head/face, neck/trunk, upper extremities, lower extremities) and simple descriptors of severity (‘none’, ‘some’, or ‘a lot’),16″ says Jonathan Meyer, MD, Clinical Professor of Psychiatry, University of California San Diego.

 

“Ideally, patients should be assessed prior to initiating or modifying an antipsychotic treatment to establish baseline “normal” movements and then screened regularly during treatment for any changes. TD assessments can be incorporated into routine protocols that are already in place in many clinical practices, which are used to monitor other antipsychotic-associated adverse events.” Examples include orthostatic hypotension, hyperprolactinemia, weight gain, notes Dr. Meyer.

 

A critical element of the guidelines was for focus to also include psychological, social, and functional aspects of tardive dyskinesia. “As a movement disorder, TD can affect a patient’s ability to perform daily activities—and even impair basic functions such as walking, eating, and breathing,” says Chirag Shah, Head of Medical Affairs & Medical Education at Neurocrine Biosciences.31,32 Equally important, however, are the social and emotional impacts of TD.5,16,33″

“The use of SGAs is expanding in patients who would probably be aware of their abnormal movements, such as those with a mood disorder who are able to work, attend school, and/or manage a household (with appropriate antidepressant and antipsychotic treatment). For these patients, even “mild” TD symptoms can be highly distressing. Feelings of embarrassment or self-consciousness can cause these patients to withdraw from friends and family, which might not be good for their mental health. We are pleased that the APA has recognized the importance of considering functional ability and quality of life as important factors in treating TD. We strongly encourage all clinicians to do the same,” says Shah.

 

References

  1. American Psychiatric Association. DSM-5 Task Force. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed. Washington, D.C.: American Psychiatric Association; 2013.
  2. Waln O, Jankovic J. An update on tardive dyskinesia: from phenomenology to treatment. Tremor Other Hyperkinet Mov (NY). 2013;3.
  3. Savitt D, Jankovic J. Tardive syndromes. J Neurol Sci. 2018;389:35-42.
  4. Hauser RA, Meyer JM, Factor SA, et al. Differentiating tardive dyskinesia: a video-based review of antipsychotic-induced movement disorders in clinical practice. CNS Spectr. 2020:1-10.
  5. 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. Qual Life Res. 2019;28(12):3303-3312.
  6. Carton L, Cottencin O, Lapeyre-Mestre M, et al. Off-label prescribing of antipsychotics in adults, children and elderly Individuals: a systematic review of recent prescription trends. Curr Pharm Des. 2015;21(23):3280-3297.
  7. Lunsky Y, Khuu W, Tadrous M, Vigod S, Cobigo V, Gomes T. Antipsychotic use with and without comorbid psychiatric diagnosis among adults with intellectual and developmental disabilities. Can J Psychiatry. 2018;63(6):361-369.
  8. Loy JH, Merry SN, Hetrick SE, Stasiak K. Atypical antipsychotics for disruptive behaviour disorders in children and youths. Cochrane Database Syst Rev. 2017;8:CD008559.
  9. Carbon M, Hsieh CH, Kane JM, Correll CU. Tardive dyskinesia prevalence in the period of second-generation antipsychotic use: a meta-analysis. J Clin Psychiatry. 2017;78(3):e264-e278.
  10. Frei K, Truong DD, Fahn S, Jankovic J, Hauser RA. The nosology of tardive syndromes. J Neurol Sci. 2018;389:10-16.
  11. Solmi M, Pigato G, Kane JM, Correll CU. Clinical risk factors for the development of tardive dyskinesia. J Neurol Sci. 2018;389:21-27.
  12. Caroff SN, Campbell EC. Drug-Induced Extrapyramidal Syndromes: Implications for Contemporary Practice. Psychiatr Clin North Am. 2016;39(3):391-411.
  13. Abnormal Involuntary Movement Scale (117-AIMS). In: Guy W, ed. ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: National Institute of Mental Health; 1976:534-537.
  14. Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. Am J Psychiatry. 2020;177(9):868-872.
  15. Caroff SN, Citrome L, Meyer J, et al. A modified delphi consensus study of the screening, diagnosis, and treatment of tardive dyskinesia. J Clin Psychiatry. 2020;81(2).
  16. Caroff SN, Yeomans K, Lenderking WR, et al. RE-KINECT: a prospective study of the presence and healthcare burden of tardive dyskinesia in clinical practice settings. J Clin Psychopharmacol. 2020;40(3):259-268.
  17. Meyer JM. Future directions in tardive dyskinesia research. J Neurol Sci. 2018;389:76-80.
  18. 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. J Neurol Sci. 2018;389:67-75.
  19. Schneider F, Bradbury M, Baillie TA, et al. Pharmacokinetic and metabolic profile of deutetrabenazine (TEV-50717) compared with tetrabenazine in healthy volunteers. Clin Transl Sci. 2020;13(4):707-717.
  20. 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? CNS Spectr. 2018;23(4):239-247.
  21. Grigoriadis DE, Smith E, Hoare SR, Madan A, Bozigian H. Pharmacologic characterization of valbenazine (NBI-98854) and its metabolites. -J Pharmacol Exp Ther. 2017;361(3):454-461.
  22. Skor H, Smith EB, Loewen G, O’Brien CF, Grigoriadis DE, Bozigian H. Differences in dihydrotetrabenazine isomer concentrations following administration of tetrabenazine and valbenazine. Drugs in R&D. 2017;17(3):449-459.
  23. 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. Psychopharmacol Bull. 2017;47(3):44-52.
  24. Harriott ND, Williams JP, Smith EB, Bozigian HP, Grigoriadis DE. VMAT2 Inhibitors and the Path to Ingrezza (Valbenazine).Prog Med Chem. 2018;57(1):87-111.
  25. Marder SR, Singer C, Lindenmayer JP, et al. A phase 3, 1-year, open-label trial of valbenazine in adults with tardive dyskinesia. J Clin Psychopharmacol. 2019;39(6):620-627.
  26. Stacy M, Sajatovic M, Kane JM, et al. Abnormal Involuntary Movement Scale in tardive dyskinesia: minimal clinically important difference. Mov Disord. 2019;34(8):1203-1209.
  27. Correll CU, Carmack T, Shah C, Lundt L. Patterns of improvement in tardive dyskinesia: post-hoc analysis of a long-term study with valbenazine (KINECT 4) [poster]. Presented virtually at the American Psychatric Association annnual meeting; May 1-3, 2021.
  28. AUSTEDO® (deutetrabenazine) tablets. Prescribing information. Teva Neuroscience, Inc.; December 2020.
  29. INGREZZA®(valbenazine) capsules. Prescribing information. Neurocrine Biosciences, Inc.; April 2021
  30. El-Mallakh RS, Belnap A, Iyer S, Shah C, Lundt L. Telepscyhiatry for assessing and managing tardive dyskinesia: expert insights form a cross-disciplinary virtual treatment panel [poster]. Presented virtually at the American Psychiatry Association annual meeting; May 1-3, 2021.
  31. Yassa R. Functional impairment in tardive dyskinesia: medical and psychosocial dimensions. Acta Psychiatr Scand. 1989;80(1):64-67.
  32. Yassa R, Lal S. Respiratory irregularity and tardive dyskinesia. A prevalence study. Acta Psychiatr Scand. 1986;73(5):506-510.
  33. Lundt L, Franey E, Yonan C. Real-world use and impact of VMAT2 inhibitors in patients with tardive dyskinesia [poster]. Presented virtually at the International Parkinson and Movement Diosrder Society annual congress; Sep 12-16, 2020.

Author