Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips.
Additionally, there may be
rapid jerking movements or
slow writhing movements.
[ In about 20% of people with TD, the disorder interferes with daily functioning.]
Tardive dyskinesia occurs in some people as a result of long-term use of dopamine-receptor-blocking medications such as antipsychotics
Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...
and metoclopramide
Metoclopramide is a medication used for stomach and esophageal problems. It is commonly used to treat and prevent nausea and vomiting, to help with emptying of the stomach in people with delayed stomach emptying, and to help with gastroesoph ...
. These medications are usually used for mental illness
A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...
but may also be given for gastrointestinal or neurological problems.[ The condition typically develops only after months to years of use.][ The diagnosis is based on the symptoms after ruling out other potential causes.][
Efforts to prevent the condition include either using the lowest possible dose or discontinuing use of neuroleptics.][ Treatment includes stopping the neuroleptic medication if possible or switching to ]clozapine
Clozapine is a psychiatric medication and is the first atypical antipsychotic (also called second-generation antipsychotic). It is primarily used to treat people with schizophrenia and schizoaffective disorders who have had an inadequate respo ...
.[ Other medications such as ]valbenazine
Valbenazine, sold under the trade name Ingrezza, is a medication used to treat tardive dyskinesia. For label updates seFDA index page for NDA 209241/ref> It acts as a vesicular monoamine transporter 2 (VMAT2) inhibitor.
Medical use
Valbenazine i ...
, tetrabenazine
Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorders. It is sold under the brand names Nitoman and Xenazine among others. On August 15, 2008, the U.S. Food and Drug Administration approved the use of tetrabenaz ...
, or botulinum toxin
Botulinum toxin, or botulinum neurotoxin (BoNT), is a neurotoxic protein produced by the bacterium ''Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromusc ...
may be used to lessen the symptoms. With treatment, some see a resolution of symptoms, while others do not.[
Rates in those on ]atypical antipsychotic
The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...
s are about 20%, while those on typical antipsychotic
Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics ma ...
s have rates of about 30%. The risk of acquiring the condition is greater in older people,[ for women, as well as patients with mood disorders and/or medical diagnoses receiving antipsychotic medications. The term "tardive dyskinesia" first came into use in 1964.][
]
Signs and symptoms
Tardive dyskinesia is characterized by repetitive, involuntary movements. Some examples of these types of involuntary movements include:
* Grimacing
* Tongue movements
* Lip smacking
* Lip puckering
* Pursing of the lips
* Excessive eye blinking
* Rapid, involuntary movements of the limbs, torso, and fingers may also occur.[National Institutes of Health, National Institute of Neurological Disorders and Stroke. (2011). Ninds tardive dyskinesia information page. Retrieved from website: ]
In some cases, an individual's legs can be so affected that walking becomes difficult or impossible. These symptoms are the opposite of people who are diagnosed with Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
. People with Parkinson's have difficulty moving, whereas people with tardive dyskinesia have difficulty not moving.[Duke University Health System. (2010, May 17). Additional movement disorders. Retrieved from ]
Respiratory irregularity, such as grunting and difficulty breathing, is another symptom associated with tardive dyskinesia, although studies have shown that the rate of people affected is relatively low.
Tardive dyskinesia is often misdiagnosed as a mental illness
A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...
rather than a neurological disorder
A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weakn ...
, and as a result, people are prescribed neuroleptic
Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of oth ...
drugs, which increase the probability that the person will develop a severe and disabling case, and shortening the typical survival period.
Other closely related neurological disorders have been recognized as variants of tardive dyskinesia. Tardive dystonia
Dystonia is a neurological hyperkinetic movement disorder in which sustained or repetitive muscle contractions result in twisting and repetitive movements or abnormal fixed postures. The movements may resemble a tremor. Dystonia is often inten ...
is similar to standard dystonia
Dystonia is a neurological hyperkinetic movement disorder in which sustained or repetitive muscle contractions result in twisting and repetitive movements or abnormal fixed postures. The movements may resemble a tremor. Dystonia is often inten ...
but permanent. Tardive akathisia
Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back and ...
involves painful feelings of inner tension and anxiety and a compulsive drive to move the body. In some extreme cases, afflicted individuals experience so much internal tension that they lose their ability to sit still. Tardive tourettism
Tourettism refers to the presence of Tourette-like symptoms in the absence of Tourette syndrome, as the result of other diseases or conditions, known as "secondary causes".
Tourette syndrome (TS) is an inherited neurological condition of multiple ...
is a tic
A tic is a sudden, repetitive, nonrhythmic motor movement or vocalization involving discrete muscle groups.American Psychiatric Association (2000)DSM-IV-TR: Tourette's Disorder.''Diagnostic and Statistical Manual of Mental Disorders'', 4th ed., ...
disorder featuring the same symptoms as Tourette syndrome
Tourette syndrome or Tourette's syndrome (abbreviated as TS or Tourette's) is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) ...
. The two disorders are extremely close in nature and often can only be differentiated by the details of their respective onsets. Tardive myoclonus
Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, is ...
, a rare disorder, presents as brief jerks of muscles in the face, neck, trunk, and extremities.
"AIMS Examination": This test is used when psychotropic medications have been prescribed because people sometimes develop tardive dyskinesia due to prolonged use of antipsychotic medications. The Abnormal Involuntary Movement Scale (AIMS) examination is a test used to identify the symptoms of tardive dyskinesia (TD). The test is not meant to tell whether there is an absence or presence of tardive dyskinesia. It just scales to the level of symptoms indicated by the actions observed. The levels range from none to severe. The AIMS examination was constructed in the 1970s to measure involuntary facial, trunk, and limb movements. It is best to do this test before and after the administration of the psychotropic drugs. Taking the AIMS consistently can help to track severity of TD over time.
Causes
Tardive dyskinesia was first described in the 1950s shortly after the introduction of chlorpromazine
Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar dis ...
and other antipsychotic drugs
Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of oth ...
. However, the exact mechanism of the disorder remains largely uncertain. The most compelling line of evidence suggests that tardive dyskinesia may result primarily from neuroleptic-induced dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
supersensitivity in the nigrostriatal pathway The nigrostriatal pathway is a bilateral dopaminergic pathway in the brain that connects the substantia nigra pars compacta (SNc) in the midbrain with the dorsal striatum (i.e., the caudate nucleus and putamen) in the forebrain. It is one of the fou ...
, with the D2 dopamine receptor being most affected. Neuroleptics act primarily on this dopamine system, and older neuroleptics, which have greater affinity for the D2 binding site, are associated with high risk for tardive dyskinesia. The D2 hypersensitivity hypothesis is also supported by evidence of a dose–response relationship
The dose–response relationship, or exposure–response relationship, describes the magnitude of the response of an organism, as a function of exposure (or doses) to a stimulus or stressor (usually a chemical) after a certain exposure time. ...
, withdrawal effects, studies on D2 agonists and antagonists, animal studies, and genetic polymorphism research.
Given similar doses of the same neuroleptic, differences among individuals still exist in the likelihood of developing tardive dyskinesia. Such individual differences may be due to genetic polymorphisms, which code for D2 receptor binding site affinity, or prior exposure to environmental toxins. Decreased functional reserve or cognitive dysfunction, associated with aging, intellectual disability, alcohol and drug use, or traumatic head injuries, has also been shown to increase risk of developing the disorder among those treated with neuroleptics. Antipsychotic drugs can sometimes camouflage the signs of tardive dyskinesia from occurring in the early stages; this can happen from the individual having an increased dose of an antipsychotic drug. Often the symptoms of tardive dyskinesia are not apparent until the individual comes off of the antipsychotic drugs; however, when tardive dyskinesia worsens, the signs become visible.
Other dopamine antagonists and antiemetics
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They may be ...
can cause tardive dyskinesia, such as metoclopramide
Metoclopramide is a medication used for stomach and esophageal problems. It is commonly used to treat and prevent nausea and vomiting, to help with emptying of the stomach in people with delayed stomach emptying, and to help with gastroesoph ...
and promethazine
Promethazine is a first-generation antihistamine, antipsychotic, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold and may also be used for sedating people ...
, used to treat gastrointestinal disorder
Gastrointestinal diseases (abbrev. GI diseases or GI illnesses) refer to diseases involving the Human gastrointestinal tract, gastrointestinal tract, namely the oesophagus, stomach, small intestine, large intestine and rectum, and the accessory org ...
s. Atypical antipsychotic
The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...
s are considered lower-risk for causing TD than their typical counterparts with their relative rates of TD of 13.1% and 32.4% respectively in short-term trials with haloperidol being the main typical antipsychotic utilised in said trials.[ Quetiapine and clozapine are considered the lowest risk agents for precipitating TD.][ From 2008, there have been reported cases of the anti-psychotic medication ]aripiprazole
Aripiprazole, sold under the brand names Abilify and Aristada among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder. Other uses include as an add-on treatment in major depressiv ...
, a partial agonist at D2 receptors, leading to tardive dyskinesia.
As of 2013, reports of tardive dyskinesia in aripiprazole have grown in number.
The available research seems to suggest that the concurrent prophylactic use of a neuroleptic and an antiparkinsonian drug is useless to avoid early extrapyramidal side-effects and may render the person more sensitive to tardive dyskinesia. Since 1973 the use of these drugs has been found to be associated with the development of tardive dyskinesia.
Risk factors
An increased risk of tardive dyskinesia has been associated with smoking in some studies, although a negative study does exist. There seems to be a cigarette smoke-exposure-dependent risk for TD in people who are antipsychotic-treated . Elderly people are also at a heightened risk for developing TD,[ as are females and those with organic brain injuries or diabetes mellitus and those with the negative symptoms of schizophrenia.] TD is also more common in those that experience acute neurological side effects from antipsychotic drug treatment.[ Racial discrepancies in TD rate also exist, with Africans and African Americans having higher rates of TD after exposure to antipsychotics.][ Certain genetic risk factors for TD have been identified including polymorphisms in the genes encoding the D3, 5-HT2A and 5-HT2C receptors.]
Diagnosis
Prevention
Prevention of tardive dyskinesia is achieved by using the lowest effective dose of a neuroleptic
Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of oth ...
for the shortest time. However, with diseases of chronic psychosis such as schizophrenia, this strategy must be balanced with the fact that increased dosages of neuroleptics are more beneficial in preventing recurrence of psychosis. If tardive dyskinesia is diagnosed, the causative drug should be discontinued. Tardive dyskinesia may persist after withdrawal of the drug for months, years or even permanently. Some studies suggest that practitioners should consider using atypical antipsychotic
The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...
s as a substitute to typical antipsychotic
Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics ma ...
s for people requiring medication. These agents are associated with fewer neuromotor side effects and a lower risk of developing tardive dyskinesia.
Studies have tested the use of melatonin
Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle.
In vertebrates ...
, high dosage vitamins
A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. Essential nutrien ...
, and different antioxidants
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
in concurrence with antipsychotic drugs (often used to treat schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...
) as a way of preventing and treating tardive dyskinesia. Although further research is needed, studies reported a much lower percentage of individuals developing tardive dyskinesia than the current rate of people for those taking antipsychotic drugs. Tentative evidence supports the use of vitamin E
Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vitami ...
for prevention.
Treatment
Valbenazine
Valbenazine, sold under the trade name Ingrezza, is a medication used to treat tardive dyskinesia. For label updates seFDA index page for NDA 209241/ref> It acts as a vesicular monoamine transporter 2 (VMAT2) inhibitor.
Medical use
Valbenazine i ...
was approved by the FDA
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...
for tardive dyskinesia in April 2017. Tetrabenazine
Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorders. It is sold under the brand names Nitoman and Xenazine among others. On August 15, 2008, the U.S. Food and Drug Administration approved the use of tetrabenaz ...
, which is a dopamine depleting drug, is sometimes used to treat tardive dyskinesia and other movement disorders (e.g. Huntington's chorea). Deutetrabenazine
Deutetrabenazine (trade name Austedo) is a vesicular monoamine transporter 2 inhibitor which is used for the treatment of chorea associated with Huntington's disease and tardive dyskinesia.
Chemically, deutetrabenazine is an isotopic isomer of ...
, an isotopic isomer of tetrabenazine, was approved by the FDA for tardive dyskinesia in August 2017. Vitamin B6
Vitamin B6 is one of the B vitamins, and thus an essential nutrient. The term refers to a group of six chemically similar compounds, i.e., "vitamers", which can be interconverted in biological systems. Its active form, pyridoxal 5′-phosphat ...
has been reported to be an effective treatment for TD in two randomised double-blind placebo-controlled trials, but the overall evidence for its effectiveness is considered "weak." Clonidine
Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal ( alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, and c ...
may also be useful in the treatment of TD, although dose-limiting hypotension and sedation may hinder its usage. Botox
Botulinum toxin, or botulinum neurotoxin (BoNT), is a neurotoxic protein produced by the bacterium ''Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neurom ...
injections are used for minor focal dystonia, but not in more advanced tardive dyskinesia.[ As of 2018 evidence is insufficient to support the use of ]benzodiazepines
Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, i ...
, baclofen
Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity such as from a spinal cord injury or multiple sclerosis. It may also be used for hiccups and muscle spasms near the end of life. It is ta ...
, progabide
Progabide (INN; trade name Gabrene, Sanofi-Aventis) is an analogue and prodrug of γ-aminobutyric acid (GABA) used in the treatment of epilepsy. Via conversion into GABA, progabide behaves as an agonist of the GABAA, GABAB, and GABAA-ρ re ...
, sodium valproate
Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those ...
, gaboxadol
Gaboxadol, also known as 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP), is a conformationally constrained derivative of the alkaloid muscimol that was first synthesized in 1977 by the Danish chemist Povl Krogsgaard-Larsen. In the early 19 ...
, or calcium channel blockers
Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...
(e.g. diltiazem
Diltiazem, sold under the brand name Cardizem among others, is a calcium channel blocker medication used to treat high blood pressure, angina, and certain heart arrhythmias. It may also be used in hyperthyroidism if beta blockers cannot be used ...
).
Epidemiology
Tardive dyskinesia most commonly occurs in people with psychiatric conditions who are treated with antipsychotic
Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...
medications for many years. The average rate of people affected has been estimated to be around 30% for individuals taking antipsychotic medication, such as that used to treat schizophrenia. A study being conducted at the Yale University School of Medicine has estimated that "32% of people develop persistent tics after 5 years on major tranquilizers, 57% by 15 years, and 68% by 25 years." More drastic data was found during a longitudinal study conducted on individuals 45 years of age and older who were taking antipsychotic drugs. According to this research study, 26% of people developed tardive dyskinesia after just one year on the medication. Another 60% of this at-risk group developed the disorder after 3 years, and 23% developed ''severe'' cases of tardive dyskinesia within 3 years. According to these estimates, the majority of people will eventually develop the disorder if they remain on the drugs long enough.
Elderly people are more prone to develop tardive dyskinesia, and elderly women are more at-risk than elderly men. The risk is much lower for younger men and women, and also more equal across the sexes. People who have undergone electroconvulsive therapy
Electroconvulsive therapy (ECT) is a psychiatry, psychiatric treatment where a generalized seizure (without muscular convulsions) is electrically induced to manage refractory mental disorders.Rudorfer, MV, Henry, ME, Sackeim, HA (2003)"Electroco ...
or have a history of diabetes or heavy alcohol use also have a higher risk of developing tardive dyskinesia.[
Several studies have recently been conducted comparing the number of people affected of tardive dyskinesia with second generation, or more modern, antipsychotic drugs to that of first generation drugs. The newer antipsychotics appear to have a substantially reduced potential for causing tardive dyskinesia. However, some studies express concern that the number of people affected has decreased far less than expected, cautioning against the overestimation of the safety of modern antipsychotics.]
A practitioner can evaluate and diagnose a person with tardive dyskinesia by conducting a systematic examination. The practitioner should ask the person to relax, and look for symptoms like facial grimacing, eye or lip movements, tics, respiratory irregularities, and tongue movements. In some cases, people experience nutritional problems, so a practitioner can also look for a gain or loss in weight.[
Apart from the underlying psychiatric disorder, tardive dyskinesia may cause afflicted people to become socially isolated. It also increases the risk of ]body dysmorphic disorder
Body dysmorphic disorder (BDD), occasionally still called dysmorphophobia, is a mental disorder characterized by the obsessive idea that some aspect of one's own body part or appearance is severely flawed and therefore warrants exceptional meas ...
(BDD) and can even lead to suicide. Emotional or physical stress can increase the severity of dyskinetic movements, whereas relaxation and sedation have the opposite effect.
References
External links
{{Medical resources
, DiseasesDB = 12909
, ICD10 = {{ICD10, G, 24, 0, g, 20
, ICD9 = {{ICD9, 333.85
, ICDO =
, OMIM = 272620
, MedlinePlus = 000685
, eMedicineSubj = neuro
, eMedicineTopic = 362
, MeshID =
Neurological disorders
Symptoms and signs: Nervous system
Syndromes
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