| Tardive dyskinesia | |
|---|---|
| Other names | Linguofacial dyskinesia, tardive dystonia, tardive oral dyskinesia |
 | |
| Tardive dyskinesia is believed to involve the neurotransmitter dopamine. | |
| Pronunciation | |
| Specialty | Neurology, psychiatry |
| Symptoms | Involuntary, repetitive body movements |
| Causes | Neuroleptic medications (antipsychotics, metoclopramide) |
| Diagnostic method | Based on symptoms after ruling out other potential causes |
| Differential diagnosis | Huntington's disease, cerebral palsy, Tourette syndrome, dystonia |
| Prevention | Using lowest possible dose of neuroleptic medication |
| Treatment | Stopping neuroleptic medication if possible, switching to clozapine |
| Medication | Valbenazine, tetrabenazine, botulinum toxin |
| Prognosis | Variable |
| Frequency | 20% (atypical antipsychotics) 30% (typical antipsychotics) |
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, 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 and metoclopramide. These medications are usually used for mental illness 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. Other medications such as valbenazine, tetrabenazine, or botulinum toxin may be used to lessen the symptoms. With treatment, some see a resolution of symptoms, while others do not.
Rates in those on atypical antipsychotics are about 20%, while those on typical antipsychotics have rates of about 30%. The risk of acquiring the condition is greater in older people. 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:
Rapid, involuntary movements of the limbs, torso, and fingers may also occur. 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. People with Parkinson's have difficulty moving, whereas people with tardive dyskinesia have difficulty not moving.
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 rather than a neurological disorder, and as a result, people are prescribed neuroleptic
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 is similar to standard dystonia but permanent. Tardive akathisia
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 torture that they lose their ability to sit
still. Tardive tourettism is a tic disorder featuring the same symptoms as Tourette syndrome.
The two disorders are extremely close in nature and often can only be
differentiated by the details of their respective onsets. Tardive myoclonus, 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 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 and other antipsychotic drugs.
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 supersensitivity in the nigrostriatal pathway,
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, 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, mental retardation,
alcohol and drug abuse, 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 can cause tardive dyskinesia, such as metoclopramide and promethazine, used to treat gastrointestinal disorders. Atypical antipsychotics
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.[18] Quetiapine and clozapine are considered the lowest risk agents for precipitating TD.[18] From 2008, there have been reported cases of the anti-psychotic medication aripiprazole, a partial agonist at D2 receptors, leading to tardive dyskinesia.[19]
As of 2013, reports of tardive dyskinesia in aripiprazole have grown in number.[20]
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.[21][22]
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 peoples 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.
Prevention
Prevention of tardive dyskinesia is achieved by using the lowest effective dose of a neuroleptic
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 physicians should consider using atypical antipsychotics as a substitute to typical antipsychotics
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, high dosage vitamins, and different antioxidants in concurrence with antipsychotic drugs (often used to treat schizophrenia)
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 for prevention.
Treatment
Valbenazine was approved by the FDA for tardive dyskinesia in April 2017. Tetrabenazine,
which is a dopamine depleting drug, is sometimes used to treat tardive
dyskinesia and other movement disorders (e.g. Huntington's chorea). Deutetrabenazine, an isotopic isomer of tetrabenazine, was approved by the FDA for tardive dyskinesia in August 2017. Vitamin B6 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 may also be useful in the treatment of TD, although dose-limiting hypotension and sedation may hinder its usage. Botox 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, baclofen, progabide, sodium valproate, gaboxadol, or calcium channel blockers (e.g. diltiazem).
Epidemiology
Tardive dyskinesia most commonly occurs in people with psychiatric conditions who are treated with antipsychotic
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 or have a history of diabetes or alcohol abuse 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 physician can evaluate and diagnose a person with tardive
dyskinesia by conducting a systematic examination. The physician 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
physician 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
(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.
