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eCase: Impact of TD on Patients With Mood Disorders
  • CME
  • CE

Joseph P. McEvoy, MD
Released: February 28, 2022
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Key Research

In the past, people thought of TD as something that happens only to people with very severe, chronic illness who are on high doses of strong antipsychotic medications. In recent years, however, there has been an increase in evidence of therapeutic effect of SGAs in a number of psychiatric conditions, including affective disorders.

Low-dose SGA augmentation of a mood stabilizer has led to higher remission rates and more rapid remission in both manic and depressive exacerbations of bipolar disorder.1

In maintenance treatment of bipolar disorder, augmentation with a low-dose SGA delays or prevents relapse vs treatment with a mood stabilizer alone.2 Similarly, augmentation with a low-dose SGA significantly increases the likelihood of remission vs treatment with antidepressants alone in patients with recurrent MDD who have had an inadequate therapeutic response to antidepressants.3,4

According to some treatment algorithms for depression and bipolar disorder, low-dose SGAs are now a second step after initial antidepressant treatment for MDD or lithium treatment for bipolar disorder.2,5

Patients with bipolar disorder or recurrent MDD are more likely to achieve sustained remission than are patients with schizophrenia.6 Because patients with mild bipolar disorder or MDD tend to have more insight and better cognition than those with schizophrenia or psychotic bipolar disorder, they are more likely to be socially active and participate more fully in personal relationships, school, or work.6,7 Similarly, they are more likely to be aware of abnormal movements, even movements that are rated “mild” on the AIMS exam, and are more likely to feel the social and emotional impact of their dyskinetic movements.8

In the majority of cases, TD is irreversible. This severity and permanence make it the most important extrapyramidal adverse event of antipsychotics. The movements commonly involve the face and may include excessive blinking, grimacing, chewing, lip-smacking, and tongue-protruding movements that are disfiguring and socially embarrassing. Even mild movements may interfere with social and occupational functioning. The increased use of dopamine receptor antagonist and partial agonist agents in patients with affective disorders has increased the population at risk for developing TD and the total incidence of TD. Although first-generation antipsychotics show higher risk for and severity of TD, it does still occur in patients treated with SGAs.2 One of the most consistently found risk factors for the development of TD is being 55 years of age or older9,10; another is the past or current presence of current extrapyramidal symptoms including akathisia, parkinsonism, or dystonic reactions.11 There has also been some evidence that females may be more susceptible to developing TD than males.10

There are currently 2 FDA-approved treatments for TD.12-14  Deutetrabenazine and valbenazine, which are VMAT2 inhibitors, have both demonstrated continued efficacy for a year.15-17 Both also have had impressive safety profiles, with very low rates of treatment discontinuation during the preapproval trials and postmarketing surveillance. Upon discontinuation, abnormal movements can return, making long-term treatment with a VMAT2 inhibitor necessary. TD is debilitating, has an impact on social and emotional functioning, and increases overall disease burden. Treatment with an FDA-approved VMAT2 inhibitor can have a positive impact on quality of life of those who develop TD.


  1. Philip NS, Carpenter LL, Tyrka AR, et al. Augmentation of antidepressants with atypical antipsychotics: a review of the current literature. J Psychiatr Pract. 2008;14:34-44.
  2. Fountoulakis KN, Grunze H, Vieta E, et al. The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 3: the clinical guidelines. Int J Neuropsychopharmacol. 2017;20:180-195.
  3. Han C, Wang S-M, Kato M, et al. Second-generation antipsychotics in the treatment of major depressive disorder: current evidence. Expert Rev Neurother. 2013;13:851-870.
  4. Ruberto VL, Jha MK, Murrough JW. Pharmacological treatments for patients with treatment-resistant depression. Pharmaceuticals. 2020;13:116.
  5. Hirschfeld RMA, Bowden CL, Gitlin MJ, et al. Practice Guideline for the Treatment of Patients With Bipolar Disorder. Second. Washington, DC: American Psychiatric Association; 2010.
  6. Spellmann I, Schennach R, Seemüller F, et al. Validity of remission and recovery criteria for schizophrenia and major depression: comparison of the results of two one-year follow-up naturalistic studies. Eur Arch Psychiatry Clin Neurosci. 2017;267:303-313.
  7. Braw Y, Sitman R, Sela T, et al. Comparison of insight among schizophrenia and bipolar disorder patients in remission of affective and positive symptoms: analysis and critique. Eur Psychiatry. 2012;27:612-618.
  8. Mishra DK, Alreja S, Sengar KS, et al. Insight and its relationship with stigma in psychiatric patients. Ind Psychiatry J. 2009;18:39-42.
  9. Woerner MG, Alvir JM, Saltz BL, et al. Prospective study of tardive dyskinesia in the elderly: rates and risk factors. Am J Psychiatry. 1998;155:1521-1528.
  10. Frei K. Tardive dyskinesia: Who gets it and why. Parkinsonism Relat Disord. 2019;59:151-154
  11. Miller DD, McEvoy JP, Davis SM, et al. Clinical correlates of tardive dyskinesia in schizophrenia: baseline data from the CATIE schizophrenia trial. Schizophr Res. 2005;80:33-43.
  12. Fernandez HH, Factor SA, Hauser RA, et al. Randomized controlled trial of deutetrabenazine for tardive dyskinesia: The ARM-TD study. Neurology. 2017;88:2003-2010.
  13. 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. Lancet Psychiatry. 2017;4:595-604.
  14. Hauser RA, Factor SA, Marder SR, et al. KINECT 3: a phase 3 randomized, double-blind, placebo-controlled trial of valbenazine for tardive dyskinesia. Am J Psychiatry. 2017;174:476-484.
  15. Dorfman BJ, Jimenez-Shahed J. Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia. Expert Rev Neurother. 2021;21:9-20.
  16. 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. J Clin Psychiatry. 2017;78:1344-1350.
  17. 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;39:620-627.
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