Tardive Dyskinesia: Symptoms, Causes, and Treatment

What Is Tardive Dyskinesia?

Tardive dyskinesia (TD) is a neurological condition in which there are involuntary (uncontrollable) abnormal movements.

Taking an antipsychotic drug to treat mental disorders can cause tardive dyskinesia. But there are other medications that can cause this neurological syndrome as well.

Tardive means delayed and dyskinesia means abnormal movements. The condition is called tardive dyskinesia because there is typically a delay between starting an antipsychotic medication and developing TD. Some people can take antipsychotic medications for years before developing tardive dyskinesia. However, TD can also occur after short-term use of antipsychotic drugs.

Notably, typical (or first-generation) antipsychotics come with the highest risk for TD. While atypical (or second-generation) antipsychotics can also cause TD, these newer antipsychotics have a lower TD risk.

Symptoms of Tardive Dyskinesia

Common Symptoms: What is a Tardive Dyskinesia Episode?

Symptoms of tardive dyskinesia (TD) include involuntary movements of the mouth, face, neck, trunk, and limbs. These can include tardive dystonia, myoclonus, buccolingual stereotypy, and tics.

A tardive dyskinesia episode may result in dyskinetic symptoms such as:

Abnormal movements of the facial muscles, including:

Lip-smacking
Sucking motions
Tongue movements like sticking out the tongue or pushing the tongue into the cheek
Chewing movements
Cheek puffing
Facial grimacing or frowning
Rapid eye blinking

Other involuntary movements can also occur after developing TD, such as:

Repetitive finger movements (as if the person is playing a piano)
Walking like a duck
Rocking or thrusting the pelvis

Psychological Impact

The symptoms of tardive dyskinesia can be mild and barely noticeable in some people, while others can develop severe involuntary movements that affect their daily functioning and quality of life.

TD is not a life-threatening condition, but severe involuntary movements can impact a person’s physical and psychological health as well as their social and professional lives. Many people with TD are unable to hold down a job due to the uncontrollable movements. In addition, stigma, discrimination, and embarrassment can affect the social life of affected individuals.

Impact on Management of Underlying Conditions

Tardive dyskinesia affects the management of the underlying condition for which the person is taking an antipsychotic drug. Some patients need to continue taking the causative drug because stopping it can be dangerous. In many people, TD is irreversible and persists long after the medications causing it have been stopped. The development of symptoms of tardive dyskinesia can, therefore, complicate the treatment of the underlying condition.

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Causes and Risk Factors for Developing Tardive Dyskinesia

Why Does Tardive Dyskinesia Develop?

Researchers haven’t identified the exact reason why movement disorders like tardive dyskinesia develop. However, evidence suggests it is due to the use of dopamine antagonists, which are drugs that block dopamine receptors. Long-term use of these dopamine receptor-blocking drugs makes the dopamine system in the brain extra sensitive, specifically in a part of the brain called the basal ganglia that can control movement. The high sensitivity of the dopamine receptors in the basal ganglia causes a person to develop tardive dyskinesia.

Scientists believe other neurotransmitter receptors in the nervous system besides dopamine, such as serotonin, acetylcholine, and gamma-aminobutyric acid (GABA), may also be involved in the development of tardive dyskinesia. This would explain how other medications besides antipsychotic medications can also cause this side effect.

Antipsychotic Induced Tardive Dyskinesia

Antipsychotic medications—also called neuroleptics or major tranquilizers—are the most common cause of tardive dyskinesia. These drugs are used to treat psychiatric conditions such as schizophrenia spectrum disorders. Other uses of antipsychotic drugs include the treatment of:

Acute mania in people with bipolar disorder
Major depressive disorder with psychotic features
Tourette syndrome
Delusional disorder
Borderline personality disorder
Severe agitation
Dementia and delirium
Substance-induced psychotic disorders

First-generation or typical antipsychotics are more likely to cause antipsychotic-induced tardive dyskinesia compared to second-generation or atypical antipsychotics. Researchers estimate that approximately 1 in 5 people taking a first-generation antipsychotic medication develop tardive syndromes. This is because first-generation antipsychotics have a higher affinity for dopaminergic receptors.

Examples of first-generation antipsychotics include chlorpromazine, haloperidol, fluphenazine (Prolixin), prochlorperazine, trifluoperazine, perphenazine, and thioridazine.

Examples of second-general (newer) antipsychotics include risperidone, clozapine, aripiprazole, olanzapine, asenapine, and paliperidone.

Find out what are the antipsychotic medications with the least side effects.

Other Medications That Can Induce Tardive Dyskinesia

In addition to neuroleptic drugs, patients treated with the following medications can develop uncontrolled movements or tardive dyskinesia:

Anti-nausea medications such as metoclopramide
Lithium (a mood stabilizer used to treat bipolar disorder)
Certain antidepressants such as trazodone, doxepin, clomipramine, amitriptyline, fluoxetine, and sertraline
Monoamine oxidase inhibitors (MAOIs) such as selegiline, rasagiline, and phenelzine
Certain anti-seizure medications such as phenytoin
Certain antihistamines such as hydroxyzine
Decongestants such as pseudoephedrine, phenylephrine, and phenylpropanolamine
Certain antimalarials such as chloroquine and amodiaquine
Parkinson’s disease medications such as levodopa (L-DOPA)
Anticholinergic agents such as procyclidine
Anti-anxiety medications (benzodiazepines) such as clonazepam (reversible TD can occur after stopping the medication suddenly)
Legal and illegal stimulants, including nicotine, caffeine, ginseng, guarana, ephedrine, prescription amphetamines, and illegal amphetamines and methamphetamine

Underlying Conditions

Other movement disorders and underlying conditions can cause uncontrollable movements resembling tardive dyskinesia, such as:

Tremor
Ataxia (imbalance and clumsy movements of the limbs)
Athetosis (slow, writhing, involuntary movements)
Dystonia (uncontrollable muscle contractions)
Myoclonus (sudden, brief muscle movements)
Buccolingual stereotypy (repetitive movements involving the mouth)
Tourette syndrome and tics (repetitive muscle contractions, typically involving the facial muscles)
Akathisia (restlessness or inability to remain still)
Chorea (unpredictable, irregular, dance-like movements of the arms, legs, and torso commonly seen in people with Huntington’s disease)
Orofacial dyskinesia
Functional movement disorders

Environmental and Genetic Factors

Taking antipsychotic medications to treat psychiatric conditions is linked to an increased risk of developing tardive dyskinesia. Additional risk factors for medication-induced tardive dyskinesia include:

Older age (elderly patients are at an increased risk of developing TD due to age-related brain changes)
Female sex
African-American race
Previous brain injury
Dementia
Early extrapyramidal symptoms (motor symptoms)

Can Anxiety Cause Tardive Dyskinesia?

Anxiety is not a common cause of tardive dyskinesia, but it may worsen the symptoms of TD. Many people with tardive dyskinesia report their TD symptoms are worse during periods of stress and anxiety. In addition, some medications used to treat anxiety and depression can lead to TD.

What Worsens Tardive Dyskinesia?

Risk factors for worsening tardive dyskinesia (TD) include:

Older patients, female patients, and African-American patients are at an increased risk of developing severe TD.
Long-term and high-dose use of antipsychotic medications (neuroleptics).
Taking first-generation (older) antipsychotics.
Discontinuation of an antipsychotic drug, change in antipsychotic agents, or a reduction in the dose of an antipsychotic medication.
Medical conditions such as bipolar disorder, diabetes, HIV, substance use disorders, traumatic brain injury, and developmental disabilities.

Diagnosis and Assessment

Diagnostic Criteria (DSM-V)

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) is a diagnostic tool published by the American Psychiatric Association. Health professionals use it to diagnose mental health conditions and neurological disorders. DSM-V classifies tardive dyskinesia (TD) as a medication-induced movement disorder that can develop after short-term and long-term use of medications as well as after discontinuation of, change in, or reduction in medications. For a diagnosis of TD, the symptoms must persist for at least one month after the drug causing tardive dyskinesia is discontinued.

Clinical Evaluation

Your healthcare provider can diagnose tardive dyskinesia based on your symptoms, medical history, medication history, physical exam, and neurological exam. The diagnosis can usually be made clinically without the need for further testing. However, your primary care physician may refer you to a neurologist, psychiatrist, or movement disorders center for differential diagnosis (to rule out similar conditions).

Diagnostic Tools and Tests: Abnormal Involuntary Movement Scale

Healthcare providers use tools such as the Abnormal Involuntary Movement Scale (AIMS) to assess the severity of dyskinesias (uncontrollable movements) and the distress caused by them. This is a 12-item scale commonly used in patients taking neuroleptic medications. It is simple and quick to administer and can be integrated into the patient’s routine clinical evaluation.

How Do You Fix Tardive Dyskinesia?

To treat TD, your healthcare provider may recommend stopping the medication causing tardive dyskinesia. But, unfortunately, this is not always possible, as stopping the causative medicine may worsen the underlying condition.

If you develop tardive dyskinesia on a first-generation antipsychotic medication, your doctor may try switching you to a second-generation (newer) antipsychotic medication.

Medications to Treat Tardive Dyskinesia

The U.S. Food and Drug Administration (FDA) approved a drug class called vesicular monoamine transporter type 2 (VMAT2) inhibitors to treat tardive dyskinesia. The two FDA-approved VMAT2 inhibitors are deutetrabenazine (Austedo XR) and valbenazine (Ingrezza), while a third agent, tetrabenazine (Xenazine), is used off-label for tardive dyskinesia. Your doctor may prescribe these drugs to manage moderate to severe symptoms of tardive dyskinesia.

Other Therapeutic Interventions

Your doctor may recommend therapeutic interventions such as deep brain stimulation (DBS) to treat severe tardive dyskinesia in people who do not respond to other treatments. Deep brain stimulation involves implanting a small wire in the area of the brain causing the tardive dyskinesia symptoms. This wire is attached to a pulse generator that sends electrical pulses to regulate the brain’s electrical activity in overactive areas, thus relieving TD symptoms.

Botox (botulinum toxin) injections may be used for a specific muscle or muscle group to weaken them briefly, thus helping with involuntary movements.

Learn about Using DBS (Deep Brain Stimulation) to Treat Parkinson’s.

Non-Pharmacological Therapies

Some of the non-drug ways to improve TD symptoms include:

Engage in regular physical activity. Exercise can help to relieve some tardive dyskinesia symptoms.
Make attempts to stop smoking, if you smoke. Nicotine exposure is linked to a higher incidence of TD.
If you have developed involuntary movements on antipsychotics or other such medications, talk to your healthcare provider about ways to improve your functioning in day-to-day life as well as your overall quality of life.
Seek care from a mental health professional if TD symptoms are affecting your mental health.

Does Tardive Dyskinesia Ever Go Away?

If drug-induced tardive dyskinesia is identified early and the drug causing it is stopped, the uncontrolled movements may improve or go away. But this is not always the case. In many people, TD is irreversible or incurable.

Monitoring and Follow-Up

If you are taking drugs that can cause movement disorders such as tardive dyskinesia, talk to your doctor about undergoing a routine assessment every 3-6 months to identify tardive symptoms early.
If you have tardive dyskinesias, keep your doctor updated about your symptom severity as well as any new symptoms.

Recent Advancements and Clinical Trials

Clinical trials on newer TD medications are underway. A phase 3, randomized, double-blind, placebo-controlled, parallel, fixed-dose study is assessing the safety, efficacy, and tolerability of a drug called NBI-98854 for the treatment of tardive dyskinesia caused by antipsychotic agents.

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