Tardive dyskinesia is a movement disorder that causes involuntary movements you cannot control, often affecting the face, tongue, and limbs. This condition typically develops after taking certain medications that block dopamine in the brain, and while it may be difficult to reverse, understanding the condition and available treatments can help people manage their symptoms and maintain quality of life.
Epidemiology
Tardive dyskinesia affects a substantial number of people who take certain medications over time. Researchers estimate that at least 20 percent of all people who take first-generation antipsychotic medications develop tardive dyskinesia. This means that out of every five people taking these older medications, at least one will experience this movement disorder.[1]
The risk varies depending on the type of medication used. Those taking atypical or newer antipsychotics face about a 20 percent risk, while people on typical or older antipsychotics have a higher risk of approximately 30 percent. Overall, more than 600,000 people in the United States are estimated to be living with tardive dyskinesia, though about 65 percent of people with the condition have never received a formal diagnosis.[6][14]
The condition is most commonly seen in people with schizophrenia and bipolar disorder (a mental health condition causing extreme mood swings) who have been treated with antipsychotic medications, but it can occur in anyone taking medications that block dopamine receptors. There aren’t as many studies on other medications that can cause the condition, so it’s difficult to estimate how frequently they result in tardive dyskinesia.[1][3]
Causes
The root cause of tardive dyskinesia lies in how certain medications affect the brain’s chemical messengers. The main theory is that the condition develops due to the use of dopamine receptor-blocking medications, also called dopamine antagonists (medications that block the action of dopamine, a chemical messenger in the brain). This includes both short-term and long-term use of these medications, though it’s more likely to develop after long-term use.[1]
When 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, which is a neurotransmitter (a chemical that carries messages between nerve cells), 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.[1]
Tardive dyskinesia can develop due to exposure to several types of medications. The most common culprits are antipsychotic medications, also called neuroleptics (medications mainly used to treat psychosis-related conditions). These include older medications like haloperidol, fluphenazine, chlorpromazine, perphenazine, prochlorperazine, and trifluoperazine. Newer antipsychotics such as olanzapine and risperidone can also cause the condition, though they seem less likely to do so.[1][2][5]
Other medications that can trigger tardive dyskinesia include metoclopramide and prochlorperazine, which are used to treat nausea and stomach problems. Certain antidepressant medicines such as amitriptyline, fluoxetine, phenelzine, sertraline, and trazodone have also been associated with the condition. In rare cases, tardive dyskinesia may develop due to other medications including lithium, antiseizure medications like phenobarbital and phenytoin, anti-Parkinson medicines such as levodopa, antihistamines (specifically hydroxyzine), and antimalarials.[1][5]
The condition can also develop after discontinuation of, a change in, or reduction in these medications. This delayed appearance is reflected in the name itself: “tardive” means delayed or late, while “dyskinesia” refers to involuntary muscle movements. Many people take a medication for years before developing the condition, but tardive dyskinesia can also occur after short-term medication use. When it develops after short-term use, it’s more likely to happen to people over 65 years of age.[1]
Risk Factors
Several factors can increase a person’s likelihood of developing tardive dyskinesia when taking medications that block dopamine. Age plays a significant role in risk. The condition is more likely to develop in older people, with the risk increasing substantially after age 40 and becoming even higher over age 65. Older adults who take these medications even for short periods face a greater risk than younger people.[1][2][6]
Gender also influences risk, as women are more likely to develop tardive dyskinesia than men. Women who have gone through menopause face an especially elevated risk. The longer you take medications that can cause tardive dyskinesia, the higher your chances of developing the condition. This is particularly true for people who take these medicines for many months or years, though symptoms have appeared after as little as six weeks of use or, in rare cases, even after a single dose.[2][5][6]
People with certain mental health conditions may face increased risk. Those with mood disorders receiving antipsychotic medications appear to be at higher risk. Research is ongoing, but some genetic factors may also raise a person’s risk for tardive dyskinesia, though a genetic basis to protect against the development of the condition through endogenous production of certain protective substances has not been confirmed.[6][9]
Having other medical conditions can increase risk as well. Oxidative stress, which occurs when harmful molecules called free radicals damage cells, may contribute to the development of tardive dyskinesia. The type of antipsychotic medication also matters. First-generation antipsychotics with increased dopamine receptor affinity are associated with a higher risk of inducing tardive dyskinesia compared to atypical or newer antipsychotics, though the newer medications are not entirely without risk.[3][9]
Symptoms
Tardive dyskinesia causes involuntary movements that a person cannot control. These movements can affect different parts of the body and range from mild and barely noticeable to severe. The condition is characterized by repetitive, involuntary movements that can significantly impact daily functioning in about 20 percent of people with tardive dyskinesia.[1][6]
The face is commonly affected by tardive dyskinesia. Facial involuntary movements may include lip-smacking or making sucking motions with the mouth, grimacing or frowning, sticking the tongue out or against the inside of the cheek, chewing movements, puffing the cheeks, and rapid eye blinking, which is called blepharospasm (involuntary, rapid blinking of the eyes). These facial movements are sometimes described as orofacial dyskinesia (uncontrolled movements in the face) or oro-bucco-lingual dyskinesia (uncontrolled movements specifically affecting the lips, jaw, or tongue).[1][2]
The tongue is particularly affected in many cases. People may stick out their tongue without trying, move it repetitively, or thrust it forward involuntarily. The mouth may make chewing motions even when the person is not eating, or the lips may smack or pucker on their own. Some people may grunt or make other vocal sounds they cannot control.[2][6]
Beyond the face, tardive dyskinesia can cause involuntary movements of the neck, trunk muscles, and limbs. This is sometimes called dyskinesia of the limbs (uncontrolled movements affecting arms, legs, fingers, and toes). Other involuntary movements may include making repetitive finger movements that look like playing the piano, tapping the feet, flapping the arms, crossing the legs repeatedly, shrugging the shoulders, twisting or stretching the neck, thrusting or rocking the pelvis, or swaying from side to side. Some people develop a duck-like gait when walking.[1][2]
In some cases, a person’s legs can be so affected that walking becomes difficult or impossible. People may also experience an inability to remain physically still, a symptom called akathisia (a feeling of inner restlessness and an inability to stay still). The movements can be fast or slow, and they may make it hard to work and stay active.[2][6]
Healthcare providers may describe these symptoms using various medical terms. They might refer to dystonia (uncontrollable muscle contractions), myoclonus (brief, sudden muscle movement), buccolingual stereotypy (repetitive movements of the mouth), or tics (habitual contractions of muscles, often in the face). The condition may also include additional motor symptoms such as chorea (irregular, flowing movements) or athetosis (slow, writhing movements).[1][6]
Prevention
The most effective way to prevent tardive dyskinesia is to minimize exposure to medications that can cause it. Healthcare providers should obtain informed written consent before administering any treatment that may block dopamine receptors. This consent should acknowledge the risk of possible tardive dyskinesia from patients treated with dopamine antagonists for any diagnosis, including conditions like migraine, hiccups, and gastroesophageal reflux.[9]
Efforts to prevent the condition include either using the lowest possible dose of antipsychotic medication or discontinuing use of antipsychotics when feasible. Throughout the course of therapy, healthcare providers should reevaluate the need for continuation of neuroleptic medications. All patients currently treated with dopamine antagonists, even those with schizophrenia treated with traditional neuroleptics for many years, merit reevaluation for possible change of medication.[6][9]
Atypical or newer antipsychotics appear to have a lower risk of causing tardive dyskinesia compared to typical or first-generation antipsychotics. When antipsychotic treatment is necessary, choosing these newer medications may help reduce risk. However, these medications are not entirely without risk, so ongoing monitoring remains important.[1][9]
Before and during treatment with any psychoactive medication, healthcare providers should assess the need for continued treatment. Administration of any medication to pregnant women, including dopamine antagonists, may be dangerous to the fetus, so special caution is warranted in this population. Regular monitoring can help detect early signs of tardive dyskinesia, allowing for prompt intervention. If movement disorders are detected, the medication regimen should be reviewed and adjusted as appropriate.[9]
Pathophysiology
The changes in normal bodily functions that occur in tardive dyskinesia center on how the brain controls movement. The condition involves complex alterations in brain chemistry and receptor sensitivity that lead to the characteristic involuntary movements. While researchers don’t know the exact pathophysiology, several mechanisms are believed to be involved.[1]
The primary mechanism involves dopamine receptors in the brain. When dopamine-receptor-blocking medications are used over time, they continuously prevent dopamine from binding to its receptors. This prolonged blockade may cause the brain to compensate by making these receptors extra sensitive or by increasing their number. This phenomenon is called receptor upregulation or supersensitivity. The basal ganglia, a part of the brain that plays a crucial role in controlling movement, is particularly affected by these changes.[1][3]
When the dopamine receptors become supersensitive, even normal levels of dopamine can trigger excessive stimulation. This excessive stimulation leads to the involuntary movements characteristic of tardive dyskinesia. The condition can be thought of as the opposite of Parkinson’s disease. While people with Parkinson’s have difficulty initiating movement due to insufficient dopamine activity, people with tardive dyskinesia have excessive, uncontrolled movements due to overstimulation of dopamine pathways.[1][6]
The neurotransmitter system in tardive dyskinesia is not limited to dopamine alone. Other neurotransmitter receptors appear to be involved in the condition, including serotonin, acetylcholine, and GABA (gamma-aminobutyric acid). The involvement of these additional neurotransmitters may explain why medications other than antipsychotics can occasionally lead to tardive dyskinesia. The balance between these different neurotransmitter systems is critical for normal movement control, and disruption of this balance contributes to the development of the disorder.[1]
Oxidative stress may also contribute to the pathophysiology of tardive dyskinesia. Oxidative stress occurs when there’s an imbalance between harmful molecules called free radicals and the body’s ability to neutralize them with antioxidants. This imbalance can damage brain cells and contribute to the development of movement disorders. Some research has explored whether substances like dehydroepiandrosterone (DHEA), an endogenous antioxidant, might function as a neuroprotective agent against tardive dyskinesia, though this has not been definitively confirmed.[9]
The condition typically develops with a delay after starting medication, which is reflected in the term “tardive.” There’s usually a delay between when a person starts a medication and when they develop dyskinesia. This delay can range from months to years, though in rare cases symptoms can appear much sooner. The condition can also emerge after discontinuation of, a change in, or reduction in medications, suggesting that the underlying brain changes may persist even after the medication is no longer being taken.[1]
