Tardive Dyskinesia (TD)

What causes tardive dyskinesia

Dopamine is a chemical messenger that controls movement. Medicines that block dopamine D2 receptors for long periods cause the receptors to become oversensitive, and the movement circuits in the basal ganglia become dysregulated. The result is excessive, involuntary movement.

Medicines linked to TD

• first-generation antipsychotics: haloperidol, chlorpromazine, fluphenazine, perphenazine. Highest risk
• second-generation antipsychotics: risperidone, olanzapine, aripiprazole and others. Lower risk but not zero. Clozapine and quetiapine have the lowest risk
• metoclopramide: used for nausea and gastroparesis. The FDA warns against use for more than 12 weeks
• prochlorperazine and promethazine for nausea
• less commonly, amoxapine and some other medicines

Risk factors

• older age, particularly over 55
• female sex, especially after menopause
• longer duration and higher doses of treatment
• diabetes
• mood disorders such as bipolar disorder
• early drug-induced movement side effects (parkinsonism, akathisia)
• alcohol or substance use

Symptoms

Movements are typically repetitive, irregular and involuntary:

• face and mouth: lip smacking, puckering, chewing, tongue thrusting or rolling, puffing cheeks, grimacing, rapid blinking
• limbs: finger "piano playing," foot tapping, ankle movements
• trunk: rocking, swaying, pelvic thrusting
• breathing: irregular breathing or grunting (respiratory dyskinesia)

Movements often lessen with concentration on a task, worsen with stress, and stop during sleep. Many people are unaware of mild movements. TD can cause embarrassment, difficulty eating, speaking and dental problems, and social stigma.

Related tardive syndromes

• tardive dystonia: sustained twisting postures of the neck or trunk
• tardive akathisia: persistent inner restlessness
• tardive tics and myoclonus

Diagnosis

TD is diagnosed by examination and history. Clinicians use the Abnormal Involuntary Movement Scale (AIMS) to rate movements and track changes. The movements must develop during or within weeks of stopping a dopamine-blocking medicine, after at least a few months of exposure (shorter in older adults). Other causes are ruled out, including Huntington's disease, Wilson disease, thyroid problems, ill-fitting dentures and stimulant use.

Treatment

Review the causing medicine

• for metoclopramide, stop it if possible
• for antipsychotics, do not stop suddenly. A psychiatrist may lower the dose or switch to a lower-risk medicine such as clozapine or quetiapine, balancing the risk of psychiatric relapse
• stopping an antipsychotic can temporarily worsen TD (withdrawal-emergent dyskinesia)

Medicines that treat TD

• VMAT2 inhibitors: valbenazine and deutetrabenazine are FDA-approved and reduce movements in many people. They work by reducing dopamine release. Side effects can include sleepiness and, for some, depression or heart rhythm changes, so they are monitored
• botulinum toxin injections for focal tardive dystonia
• other options with weaker evidence include clonazepam, amantadine and ginkgo biloba extract

Supportive care

• dental care and well-fitted dentures
• speech and swallowing therapy
• psychological support for stigma and self-image

Prevention

• use dopamine-blocking medicines only when clearly needed, at the lowest effective dose
• prefer lower-risk antipsychotics where appropriate
• limit metoclopramide to 12 weeks or less
• screen for abnormal movements at baseline and regularly during treatment

Outlook

TD may improve, stabilize or persist. Early detection and medicine changes improve the chances of improvement. VMAT2 inhibitors have substantially improved symptom control for many patients.

Frequently asked questions

What is tardive dyskinesia?

Tardive dyskinesia is a movement disorder that causes involuntary, repetitive movements, usually of the mouth, tongue and face, sometimes the limbs and trunk. It develops after long-term use of dopamine-blocking medicines such as antipsychotics or metoclopramide.

What are the early signs of tardive dyskinesia?

Early signs are often subtle movements of the tongue or mouth, such as lip pursing, chewing motions or the tongue pushing against the cheek, frequent blinking, or finger and toe tapping. Family members often notice before the person does.

Is tardive dyskinesia reversible?

Sometimes. Stopping or reducing the causing medicine early may lead to improvement over months, but TD can be persistent. VMAT2 inhibitor medicines such as valbenazine and deutetrabenazine can significantly reduce movements even when TD persists.

Which medications cause tardive dyskinesia?

The main causes are antipsychotics, especially older first-generation types such as haloperidol, and the anti-nausea medicine metoclopramide. Newer antipsychotics carry lower risk. Clozapine and quetiapine have the lowest risk among antipsychotics.

Should I stop my antipsychotic if I develop tardive dyskinesia?

Do not stop it on your own. Stopping suddenly can cause psychiatric relapse and temporarily worsen movements. Talk to your prescriber, who may adjust the dose, switch medicines or add a VMAT2 inhibitor to treat the movements.