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Improving Outcomes in TD

CE / CME

Case Challenge: Irregular, Uncontrolled Movements Impairing Social Life

Physician Assistants/Physician Associates: 0.75 AAPA Category 1 CME credit

Social Workers: 0.75 ASWB ACE CE Credit

Pharmacists: 0.75 contact hour (0.075 CEUs)

Psychologists: 0.75 APA CE Credit

Nurses: 0.75 Nursing contact hour, including 0.75 hour of pharmacotherapy credit 

Physicians: Maximum of 0.75 AMA PRA Category 1 Credit™

Released: December 08, 2022

Expiration: December 07, 2023

CME/CE Information

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Tardive dyskinesia (TD), a debilitating, iatrogenic movement disorder, was first described in clinical reports during the 1950s. The term “tardive” dyskinesia was coined in the literature by Faurbye and colleagues in 1964, indicating that motor symptom onset occurred late after starting the offending agent.1

There are several theories on the pathophysiology of TD, including γ-aminobutyric acid depletion, cholinergic deficiency, oxidative stress, altered synaptic plasticity, neurotoxicity, and defective neuroadaptive signaling.2 However, the most prominent theory is that TD occurs after prolonged postsynaptic dopaminergic antagonism. This is thought to play a role in synaptic plasticity and is hypothesized to cause an upregulation of dopamine receptors, hypersensitivity of dopamine receptors, or a combination of the two.3-5 TD occurs when dopamine agonizes these upregulated/hypersensitive receptors.

Due to its apparent relation to dopamine receptors and sensitivity, TD predominately occurs in patients with chronic exposure to dopamine receptor blocking agents (eg, antipsychotics) but has also been seen in people receiving tricyclic antidepressants or agents intended to treat gastrointestinal ailments (eg, metoclopramide, promethazine). There are also reports and cases in the literature on the development of TD from agents such as lithium, selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, and calcium channel blockers.3

Broadly speaking, TD affects approximately 500,000 people in the United States.6 It most commonly affects people being treated for psychiatric disorders, as this often involves a dopamine receptor blocking agent.7,8 Statistically, first-generation antipsychotic (FGA) use carries a prevalence rate of 30.0%. Although reduced in people who have never been exposed to FGAs, the prevalence rate with second-generation antipsychotic (SGA) use is 7.2%.8 In one retrospective observational study (164,417 patients) isolating patients prescribed antipsychotics, TD had a greater incidence of comorbid schizophrenia, schizophrenia-like disorders, drug dependence, neurotic/anxiety disorders, personality disorders, mood disorders, and alcohol use than in patients without TD.10 It is expected that the overall incidence of TD will continue to rise due to the increased utilization of SGAs secondary to expanded FDA-approved indications (ie, mood disorders), off-label usage (eg, anxiety, insomnia), and perceived safety. During the past decade, SGA prescription volume has more than tripled.1

TD commonly presents as persistent, involuntary, repetitive, athetotic, and choreiform movements in the face, tongue, lips, trunk, and extremities.8,9,11,12 Involuntary movements are only part of the problem once patients develop TD. Psychosocial complications are also part of the burden of this condition, and there is often a negative impact on health-related quality of life and daily functioning with increased social stigma and embarrassment.4,12

There have been several agents studied to determine treatment effectiveness for TD, but only 2 agents currently have FDA approval and level A recommendation for use in this setting: deutetrabenazine and valbenazine. Regarding other agents, often the studies were small, the results were lackluster, and thus the agents were not granted FDA approval and never achieved a level A recommendation for the treatment of TD. Of note, for patients who cannot tolerate or access deutetrabenazine or valbenazine, ginkgo biloba and clonazepam both carry a level B recommendation for use in TD treatment.13