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eCase: Treatment of Tardive Dyskinesia Using Valbenazine in a Patient With Schizophrenia
  • CME
  • CE

John M. Kane, MD
Released: November 3, 2021
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Key Research

Anticholinergics are efficacious in treating parkinsonism, but they generally worsen TD. It is a common mistake for HCPs to prescribe them for the abnormal involuntary movements associated with TD, although they may be of some benefit in tardive dystonia.3

TD is thought to result from nigrostriatal D2 blockade leading to postsynaptic upregulation/hypersensitivity. These supersensitive receptors then overreact to dopamine, leading to abnormal involuntary movements. Parkinsonism, on the other hand, is due to low postsynaptic dopamine stimulation. Medications that increase dopamine release (eg, anticholinergics) exacerbate TD.4,5

Second-generation antipsychotics have been associated with a significant reduction in the risk of TD,6 but TD still can occur with these agents. In addition, although switching from first-generation to second-generation medications initially was hoped to be helpful, meta-analysis suggests that such switching did not improve TD.7 Clozapine has been shown to be of some benefit in moderate to severe cases of TD, but there is considerable variability in response.8

VMAT is a protein integrated into the membrane of synaptic vesicles of presynaptic neurons that transports monoamine neurotransmitters (dopamine, 5-hydroxytryptamine, norepinephrine, epinephrine, and histamine) into vesicles. There are 2 forms: VMAT1 and VMAT2. VMAT1 is expressed mainly in the peripheral nervous system, and VMAT2 is expressed mainly in monoaminergic cells of the central nervous system.1 Deutetrabenazine and valbenazine both are VMAT2 inhibitors that were approved by the FDA for the treatment of TD in 2017; deutetrabenazine also is approved by the FDA for Huntington disease. Deutetrabenazine and valbenazine have been shown to be effective in well-designed clinical trials,9,10 with good long-term safety and efficacy.11,12 With both medications, there is some reemergence of involuntary movements after discontinuation, so continued therapy is likely needed.11,13 Valbenazine is dosed once daily with a 1-week titration from 40 mg/day to 80 mg/day. Deutetrabenazine requires twice-daily dosing with food, with a longer titration period to reach the effective dose range of 36-48 mg/day. There are no direct head-to-head comparisons of these agents.

In summary, TD remains a persistent clinical problem due to the widespread use of second-generation antipsychotics. HCPs should be cautious in the use of antipsychotic medications, reserving them for situations in which they are clearly indicated and beneficial. TD is generally not reversible, even with antipsychotic discontinuation. There is limited benefit with switching to clozapine, but not to other second-generation antipsychotics. HCPs must learn to recognize TD and identify other movement disorders commonly seen with psychotropic treatment. Anticholinergics used for parkinsonism exacerbate TD. VMAT2 inhibitors represent the first class of medications with regulatory approval for the treatment of TD.

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  2. Zutshi D, Cloud LJ, Factor SA. Tardive syndromes are rarely reversible after discontinuing dopamine receptor blocking agents: experience from a university-based movement disorder clinic. Tremor Other Hyperkinet Mov (N Y). 2014;4:266.
  3. Mentzel CL, Bakker PR, van Os J, et al. Effect of antipsychotic type and dose changes on tardive dyskinesia and parkinsonism severity in patients with a serious mental illness: The Curaçao Extrapyramidal Syndromes Study XII. J Clin Psychiatry. 2017;78:e279-e285.
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  8. Mentzel TQ, van der Snoek R, Lieverse R, et al. Clozapine monotherapy as a treatment for antipsychotic-induced tardive dyskinesia: a meta-analysis. J Clin Psychiatry. 2018;79:17r11852.
  9. Citrome L. Deutetrabenazine 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? Int J Clin Pract. 2017;71:e13030.
  10. Caroff SN, Aggarwal S, Yonan C. Treatment of tardive dyskinesia with tetrabenazine or valbenazine: a systematic review. J Comp Eff Res. 2018;7:135-148.
  11. Fernandez HH, Stamler D, Davis MD, et al. Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia. J Neurol Neurosurg Psychiatry. 2019;90:1317-1323.
  12. 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.
  13. 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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