Tardive Dyskinesia

What is tardive dyskinesia?

Tardive dyskinesia (TD) is a neurological syndrome that involves involuntary (out of your control) movements. Taking antipsychotic (neuroleptic) medications is the main cause of this condition. But other medications can cause it as well.

“Tardive” means delayed or late. “Dyskinesia” refers to involuntary muscle movements. With this condition, there’s typically a delay between when you start a medication and when you develop dyskinesia. Many people take a medication for years before developing the condition. But you can also develop TD after short-term medication use. TD after short-term medication use is more likely to happen to people over 65.

How common is tardive dyskinesia?

Researchers estimate that at least 20% of all people who take first-generation antipsychotic medications develop tardive dyskinesia. There aren’t as many studies on the other medications that can cause the condition, so it’s difficult to estimate how frequently they result in tardive dyskinesia.

What are the symptoms of tardive dyskinesia?

Tardive dyskinesia causes involuntary movements of your:

• Facial muscles.
• Tongue.
• Neck.
• Trunk muscles.
• Limbs.

Facial involuntary movements may include:

• Lip-smacking or making sucking motions with your mouth.
• Grimacing or frowning.
• Sticking your tongue out or against the inside of your cheek.
• Chewing movements.
• Puffing your cheeks.
• Rapid eye blinking (blepharospasm).

Other involuntary movements may include:

• Making repetitive finger movements like you’re playing the piano.
• Thrusting or rocking your pelvis.
• Walking with a duck-like gait.
• Inability to remain physically still (akathisia).

These symptoms can range from mild and barely noticeable to severe.

Healthcare providers may describe these symptoms as:

• Dystonia (uncontrollable muscle contractions).
• Myoclonus (brief, sudden muscle movement).
• Buccolingual stereotypy (repetitive movements of your mouth).
• Tics (habitual contractions of your muscles, often in your face).

What causes tardive dyskinesia?

Researchers don’t know the exact cause of tardive dyskinesia. But the main theory is that it can develop due to the use of dopamine receptor-blocking medications (dopamine antagonists). This includes short-term and long-term use of the medications, though it’s more likely to develop after long-term use. TD can also happen after discontinuation of, a change in or reduction in medications.

Dopamine antagonists block dopamine for a long time. This may make the dopamine receptors in your brain extra sensitive, especially in your basal ganglia (a part of your brain that helps control movement). Excess dopamine (a neurotransmitter) — or extra sensitive receptors — leads to involuntary movements.

In addition to dopamine, other neurotransmitter receptors may be involved in the condition, including serotonin, acetylcholine and GABA. This may explain why medications other than antipsychotics can occasionally lead to tardive dyskinesia.

What drugs cause tardive dyskinesia?

Tardive dyskinesia can develop due to exposure to the following medications:

• Antipsychotic medications (neuroleptics).
• Metoclopramide or other anti-nausea medications.
• Certain antidepressants.

In rare cases, TD may also develop due to other medications:

• Lithium.
• Antiseizure medications.
• Antihistamines, specifically hydroxyzine.
• Antimalarials.

Antipsychotic medications and TD

Antipsychotic medications (neuroleptics) mainly treat psychosis-related conditions, like schizophrenia. These medications are the most common cause of tardive dyskinesia.

First-generation (“typical”) antipsychotics are considered more likely to cause tardive dyskinesia than second-generation (“atypical”) antipsychotics.

Examples of first-generation antipsychotics include:

• Chlorpromazine.
• Fluphenazine.
• Haloperidol.
• Perphenazine.
• Prochlorperazine.
• Thioridazine.
• Trifluoperazine.

Metoclopramide and tardive dyskinesia

Metoclopramide is a medication that can relieve GERD (chronic acid reflux). It can also help treat diabetes-related gastroparesis.

Metoclopramide is strongly linked to TD. Risk factors for developing metoclopramide-induced TD include:

• Being 65 or older.
• Being assigned female at birth.
• Having diabetes.
• Taking metoclopramide for 12 or more weeks.

Antidepressants and TD

Antidepressants help treat depression and other conditions like anxiety and obsessive-compulsive disorder. Antidepressant-induced TD is more likely to affect people over 65 due to age-related brain changes. In general, this is much more rare than TD due to antipsychotic medications. The following antidepressants are associated with TD:

• Trazodone, which is a serotonin modulator.
• Amitriptyline, clomipramine and doxepin, which are tricyclic antidepressants.
• Fluoxetine and sertraline, which are SSRIs.
• Phenelzine and rasagiline, which are MAOIs.
• Selegiline (an MAOI) is associated with TD when you use it in combination with levodopa.

Lithium and TD

Lithium, a medication that helps treat bipolar disorder, is linked to TD. But your risk of developing TD is much higher if you take lithium in combination with an antipsychotic medication.

Antiseizure medications and TD

Antiseizure medications help treat and prevent seizures. Carbamazepine and lamotrigine are associated with TD, but it’s rare for them to cause it. Phenytoin is also associated with TD.

Antihistamines and TD

Antihistamines help treat allergy symptoms. Hydroxyzine in particular is associated with TD after prolonged use.

People over the age of 65 with previous exposure to phenothiazines (typical antipsychotics) have a higher likelihood of developing TD after taking hydroxyzine.

Antimalarials and TD

Antimalarials treat or prevent malaria. Chloroquine and amodiaquine are associated with TD.

What are the risk factors for tardive dyskinesia?

Certain factors may increase your risk of developing tardive dyskinesia, including:

• Age: People over 40 are more likely to develop TD than people under 40. People over 65 are especially at risk due to age-related changes in their brains.
• Sex: Women and people assigned female at birth (AFAB) are more likely to develop TD than men and people assigned male at birth (AMAB). Postmenopausal people AFAB have rates of TD as high as 30% after almost a year of exposure to antipsychotic medications.
• Race: Studies show that Black Americans are more likely to develop TD than white Americans. And people of Filipino and Asian descent have a lower risk of developing TD than people of Caucasian descent.
• Bipolar disorder: People with bipolar disorder who take antipsychotic medications are more sensitive to developing TD compared to other people taking the same medications.

Researchers are currently studying genetic factors that may increase or decrease your chance of developing TD.

What are the complications of tardive dyskinesia?

The uncontrollable movements of tardive dyskinesia can be uncomfortable and affect your social and emotional well-being. This can significantly impact your mental health. It can also make it difficult to do everyday tasks.

TD generally isn’t fatal. But severe TD that affects your larynx (laryngospasm) and diaphragm can very rarely cause breathing issues that can be life-threatening.

How is tardive dyskinesia diagnosed?

Your healthcare provider will ask about your symptoms, medical history and medication history. If you take a medication that’s known to cause tardive dyskinesia, your provider will likely suspect TD. They’ll also do a physical exam and a neurological exam. They may refer you to a specialist, like a neurologist, movement disorder specialist or psychiatrist.

Healthcare providers refer to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to diagnose tardive dyskinesia. It states that symptoms of TD must last for at least one month after stopping the medication to get a diagnosis of the condition. You must have been on the medication for at least three months if you’re 40 or younger or one month if you’re over 40.

Your provider may recommend other tests to confirm TD or rule out other conditions with similar symptoms, like Huntington’s disease. These may include laboratory tests and imaging tests, like a brain CT scan and/or MRI. But TD is typically a clinical diagnosis. This means that providers make the diagnosis after obtaining an accurate medical history and detailed physical exam without any additional testing.

What is the treatment for tardive dyskinesia?

Studies on the management of tardive dyskinesia are inconsistent. Some studies show an improvement when you decrease the dose or stop taking the antipsychotic medication. Other studies show no change.

Your provider may recommend stopping the medication causing TD, if possible. Unfortunately, this approach isn’t always feasible, as it can worsen the underlying condition it’s meant to treat.

If you develop TD while taking a first-generation antipsychotic medication, your provider may switch you to a second-generation antipsychotic medication.

Other than stopping or switching antipsychotic medication, the strongest current evidence for TD treatment is the use of the VMAT inhibitors, deutetrabenazine and valbenazine. These medications have now been proven to be safe and effective. Your provider may recommend these medications if you have moderate to severe TD that’s affecting your quality of life.

Is tardive dyskinesia reversible?

Unfortunately, most cases of tardive dyskinesia are chronic (long-term). While medication may help manage the condition, it can’t cure or reverse it.

Is tardive dyskinesia preventable?

Tardive dyskinesia is unpredictable. Not everyone who takes certain medications develops it.

If you have risk factors that make you more prone to this condition, talk to your healthcare provider. You may be able to prevent tardive dyskinesia by taking a different medication. To lower your risk of developing TD, your provider will prescribe the lowest effective dose of an antipsychotic medication for the shortest period possible.

If you have to take a medication known to cause TD, talk to your provider about routine screenings of movement symptoms. Recognizing the symptoms of TD early can help lessen their severity. It’s best to get these screenings every three to six months after starting a medication that can cause TD.

What can I expect if I have tardive dyskinesia?

Tardive dyskinesia affects everyone differently. The symptoms can range from mild to severe. In addition, treatment helps manage the symptoms for some but not for others. Your healthcare provider will work with you to find the best treatment plan. They’ll be able to give you a better idea of what to expect.

How can I take care of myself if I have tardive dyskinesia?

Your healthcare provider will work with you to adjust your treatment plan as needed. Other steps you can take to manage TD include:

• Making sure you have a routine symptom assessment by your provider every three to six months.
• Keeping track of your symptoms and letting your provider know if you develop new ones.
• Practicing self-care that includes physical activity. Exercise can help relieve some movement symptoms.
• Talking to your provider about your daily functioning and quality of life
• Seeking help from a mental health professional if TD is affecting your mental and social health.

When should I go to the ER?

If tardive dyskinesia is making it difficult to breathe, call 911 or go to the nearest emergency room as soon as possible.