Tardive Dyskinesia

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Continuing Education Activity

Tardive dyskinesia is a syndrome that includes a group of iatrogenic movement disorders caused by the blockade of dopamine receptors. The movement disorders include akathisia, dystonia, buccolingual stereotypy, myoclonus, chorea, tics, and other abnormal involuntary movements, which are commonly caused by the long-term use of typical antipsychotics. However, several other medications are also associated with tardive dyskinesia. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V) defines tardive dyskinesia as a medication-induced movement disorder that persists despite discontinuation or change of the medications. As per DSM-V, to confirm a diagnosis of tardive dyskinesia, symptoms must persist for a month after discontinuation of the drug. This activity reviews tardive dyskinesia and highlights the role of the interprofessional team in recognizing and managing patients affected by this condition.


  • Review the pathophysiology of tardive dyskinesia.
  • Describe exam findings consistent with tardive dyskinesia.
  • Outline management strategies for tardive dyskinesia.
  • Summarize strategies to educate interprofessional teams on common etiologies of tardive dyskinesia as well as common presentations so that efforts can be made to prevent it from developing in the first place and stop it from progressing if it has already developed.


Tardive dyskinesia (TD) is a syndrome that encompasses a constellation of iatrogenic movement disorders caused by the antagonism of dopamine receptors. The movement disorders include akathisia, dystonia, buccolingual stereotypy, chorea, tics, and other abnormal involuntary movements. Most often, these dyskinetic disorders precipitate following chronic antipsychotic administration; however, several other medications are also associated with tardive dyskinesia. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V) defines tardive dyskinesia as a medication-induced movement disorder that persists despite discontinuation or change of the medications. As per DSM-V, to confirm a diagnosis of tardive dyskinesia, symptoms must persist for at least one month after discontinuation of the medication.[1][2][3]

Tardive dyskinesia is most common in people with schizophrenia and bipolar patients treated with antipsychotic medications but can occur in the setting of any disorder. In addition, the medications that precipitate tardive dyskinesia can also induce parkinsonian symptoms. Although the precise pathogenesis continues to elude researchers, data suggest that tardive dyskinesia is induced by aberrant dopamine transporters.


Tardive dyskinesia is caused due to long-term exposure to first and second-generation neuroleptics, certain antidepressants, lithium, and some antiemetic medications. Typically, the first-generation antipsychotics with increased dopamine D2 receptor affinity are affiliated with a higher risk of inducing tardive dyskinesia. Atypical antipsychotics have been associated with a decreased tardive dyskinesia diathesis--as well as fewer extrapyramidal side effects compared to typical antipsychotics--due to their lower affinity for dopamine D2 receptors in the dorsal striatum and concomitant blockade of serotonin 5-HT2A/2C receptors.[4][5]

Metoclopramide can also cause tardive dyskinesia, especially in older individuals. The condition may also occur with certain antihistamines, amoxapine, and fluoxetine.


The average prevalence of tardive dyskinesia is estimated at least 20% of all patients treated with first-generation neuroleptics. However, other medications responsible for tardive dyskinesia have been less studied, and published data indicate a prevalence ranging from 1% to 10%. Women risk developing tardive dyskinesia more than men, especially in middle-aged to senior patients. Post-menopausal women have incidence rates as high as 30% after almost a year of exposure to antipsychotic medications suggesting estrogen may have an antioxidant effect protecting against tardive dyskinesia. Elderly patients are more likely to develop tardive dyskinesia due to age-related changes in the brain and body. Several studies indicate African Americans are more likely to develop tardive dyskinesia after long-term exposure to dopamine-blocking agents than White-race individuals.[6] 

Other factors increasing tardive dyskinesia diathesis include the duration of exposure to the neuroleptic agent, the manifestation of EPS, and using first-generation antipsychotics--instead of second-generation antipsychotics. Of note, the long-term use of anticholinergic medications may increase the risk of tardive dyskinesia. 


First-generation antipsychotics bind more tightly to dopamine D2 receptors in comparison to second-generation antipsychotics, and for this reason, the typical antipsychotics have a higher tendency to cause tardive dyskinesia. Some evidence suggests the presence of extrapyramidal symptoms during neuroleptic treatment predicts the development of tardive dyskinesia. In addition to dopamine, the other neurotransmitter receptors that may be involved in causing tardive dyskinesia include 5-hydroxytryptophan receptors found in the striatum. These receptors interact with dopaminergic neurons and are considered to be involved in regulating motor activity.

Upregulation of dopamine receptors due to chronic dopamine blockade can result in an exaggerated response to the postsynaptic receptors to dopamine, causing tardive dyskinesia. Another hypothesis is the resulting oxidative stress due to antidepressants blocking dopamine receptors which causes an increase in dopamine metabolism, and this subsequently results in free radical production. The consequential oxidative stress on the basal ganglia--striatum and substantial nigra--results in the manifestation of tardive dyskinesia. Evidence also suggests that antipsychotic medications and their metabolites can also be directly toxic to neurons through oxidative stress. It is known that removing the agent that causes tardive dyskinesia can exacerbate the symptoms, and this is defined as withdrawal dyskinesia. It is theorized that this is due to dopamine D2 receptor upregulation and postsynaptic receptor super sensitivities. However, this does not explain why tardive dyskinesia remains for many years after the offending drug has been discontinued.[3]

History and Physical

Physicians should examine all patients for any movement disorders before initiating treatment with dopamine D2 receptor antagonists. Tardive dyskinesia presents clinically as stereotypical involuntary movements of the tongue, neck, and facial muscles, truncal musculature, and limbs. Buccolingual movements, including masticatory muscles, are characterized by lip-smacking, tongue protrusion, perioral movements, chewing movements, or a puffing of cheeks. Sometimes these movements may be hard to distinguish from stereotype posturing seen in chronic psychotic patients. However, tardive dyskinesia is seen in patients with chronic exposure to dopamine D2 receptor blockade.

The onset of tardive dyskinesia is insidious and can be difficult to distinguish as the nascent stages demonstrate only subtle deviant motion. Tardive dyskinesia can manifest as early as 1 to 6 months following the initiation of a dopamine receptor antagonist. Diagnosis of acute or chronic dyskinesias may be challenging without a careful history. A thorough history of movement disorders and medication history will aid in diagnosing tardive dyskinesia accurately. 

Specific conditions that can occur with anti-dopaminergic agents include:

  • Tardive akathisia
  • Tardive orofacial dyskinesia
  • Tardive dystonia
  • Tardive blepharospasm
  • Tardive tics


Numerous rating scales determine the presence and severity of tardive dyskinesia. The most widely used instrument is the Abnormal Involuntary Movement Scale (AIMS). It is recommended to administer the AIMS at baseline before initiating antipsychotic medications, with a follow-up screening performed no longer than three months later. Upon evaluation of the patient, it can be noted that tardive dyskinesia is present at rest and somewhat diminished when there is any form of volitional movement. For example, tongue dyskinesias reduce when the patient is asked to protrude their tongue.

If tardive dyskinesia is present in conjunction with dementia, one should consider Huntington's disease, Wilson's disease, or a central nervous system tumor. A diagnosis of antipsychotic-induced tardive dyskinesia is made after the symptoms have persisted for at least one month and required exposure to neuroleptics for at least three months. Tardive dyskinesia should be distinguished from withdrawal dyskinesias as these most likely remit soon after the termination of the antipsychotic. 

Workup for tardive dyskinesia may include selected laboratory studies and imaging. Typically, brain CT and MRI are normal in patients with tardive dyskinesia. However, they may assist in ruling out other conditions such as Huntington's disease, where atrophy of the caudate nucleus is seen, and Fahr syndrome, where calcification is noted in the basal ganglia.[1][5][7]

Treatment / Management

Dopamine receptor antagonists should be avoided whenever possible by selecting other medications that have a lower potential to cause tardive dyskinesia. Furthermore, chronic use of first-generation antipsychotics should be avoided whenever possible. To date, treatment options remain sparse. The American Academy of Neurology only recommends a few treatment options, which include clonazepam and ginkgo biloba. Valbenazine, a vesicular monoamine transport type 2 (VMAT2) inhibitor, was approved by the FDA on April 11, 2017, to treat tardive dyskinesia. The KINECT 3 trial results revealed valbenazine improved tardive dyskinesia when compared to the placebo drug. However, the best treatment option is primary prevention.[8][9][10]

Differential Diagnosis

  • Chorea
  • Complex seizure
  • Essential tremor
  • Tourette syndrome
  • Tic disorder
  • Wilson disease
  • Sydenham chorea


Unfortunately, tardive dyskinesia is considered a chronic and unremitting disorder. Nothing has yet been proven to resolve tardive dyskinesia, but as mentioned previously, supportive measures can attenuate the severity.


Tardive dyskinesia is primarily a progressive disturbance that causes unmeasurable discomfort and potential embarrassment. Fortunately, it is generally not life-threatening. However, severe tardive dyskinesia of the larynx and diaphragm may prove fatal.


  • Ophthalmologist to assess the eye for Wilson disease
  • Neurologist
  • Movement disorder specialist
  • Psychiatrist consult

Deterrence and Patient Education

The best means of obviating tardive dyskinesia is primary prevention. Primary prevention of tardive dyskinesia includes using the lowest effective dose of an antipsychotic agent for the shortest period possible. If tardive dyskinesia develops, it is recommended to decrease the dose or even discontinue the offending agent and switch to clozapine. Clozapine is recommended in patients with tardive dyskinesia who continue to require antipsychotics as the incidence of tardive dyskinesia with clozapine is significantly less than with other antipsychotics.

Enhancing Healthcare Team Outcomes

The diagnosis and management of tardive dyskinesia are best made with an interprofessional team. In most cases, the primary clinician may suspect the diagnosis during follow-up. It is crucial to consult collaboratively with a pharmacist as part of the interprofessional team approach to managing the medication profile for patients who have developed tardive dyskinesia or are at risk for developing the condition.

Movement disorders like tardive dyskinesias are frequently aggravated by the use of drugs that block dopamine. In susceptible patients, even a single dose of an anti-dopaminergic drug can quickly develop disabling movement disorders. Thus, besides the clinician, the role of the pharmacist is critical. Patients vulnerable to tardive dyskinesia include people with schizophrenia and those with developmental disabilities who may develop the movement disorder when administered a dopamine blocking agent. The pharmacist must note these patients and with which medications they are treated. The caregiver should be informed about the possibility of this adverse effect and the alternatives. Nursing can also monitor the patients for symptomatic improvement or decline and immediately report their observations to the prescriber and/or pharmacist to enact appropriate therapeutic interventions.

Clinicians should be advised not to start such medications if there are other options. Plus, the pharmacist must educate the patient about wearing an alert bracelet that warns against the administration of such drugs. Once the patient is started on neuroleptic, close monitoring is essential because with early diagnosis, the drug may be discontinued or the dose lowered to prevent full-blown tardive dyskinesia.[11][12] [Level 5]


Data on the management of tardive dyskinesia are inconsistent and difficult to understand. Some studies show an improvement when the antipsychotic drug is decreased in dose or discontinued, and other studies show no change. Long-term studies suggest that tardive dyskinesia persists at tardive dyskinesia persists in at least 10 to 30% of patients. Recent studies show that the outcomes of tardive dyskinesia are improved in younger patients treated with low doses for shorter periods. Switching to low potency antipsychotic drugs has been shown to lower the risk of tardive dyskinesia. Recently the FDA approved the drug valbenazine to treat tardive dyskinesia. Early data from the clinical trial reveals that the drug effectively alleviates tardive dyskinesia and is safe. However, the study was conducted by many physicians who also received some type of compensation from the pharmaceutical companies- so one has to take this data with a grain of salt until more long-term data are available.[2][13] [Level 5]



Sarayu Vasan


Ranjit K. Padhy


4/24/2023 12:38:20 PM



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