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Tardive Dyskinesia
Tardive dyskinesia is a movement disorder that can develop if you take
an antipsychotic medication and/or other types of medications. It’s
typically not reversible, but treatment may help manage the symptoms.
Overview
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.
Symptoms and Causes
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
female.
- 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.
Those over 65 are especially at risk due to age-related neurological
changes.
-
Sex: Females are more likely to develop TD. Those
in post-menopause 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.
Diagnosis and Tests
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.
Management and Treatment
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.
Outlook
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.
Usually, tardive dyskinesia is a long-term medical condition. But
your TD symptoms can go into remission, meaning your symptoms can go
away. If you're taking an antipsychotic or antiemetic medication, watch
for TD signs.
Tell your doctor right away if you notice any uncontrolled movements.
Early diagnosis gives you the best chance for treatment and remission.
Your doctor can help you decide on the best treatment option.
Prevention
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.
Living With TD
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.
Tardive Dyskinesia FAQ's
How to reverse tardive dyskinesia
Although potentially permanent, you can do some things to help
prevent or lower your chances for tardive dyskinesia. Monitor your
symptoms for early diagnosis. Watch out for any uncontrollable movements
and tell your doctor right away. Your doctor can help identify the cause
of your TD symptoms. With treatment, TD symptoms can go into remission
(a period without symptoms).
Is tardive dyskinesia permanent?
Tardive dyskinesia is potentially a permanent condition. But early
diagnosis and treatment can mean remission. Remission is when your TD
symptoms go away or lessen. Your doctor can help you decide on the best
treatment for your TD.
What kind of doctor treats tardive dyskinesia?
Most movement disorder specialists are doctors who treat brain
problems. This can include a neurologist (a doctor who treats your
brain, spinal cord, and nerves) or a psychiatrist (who specializes in
mental health).
One Final Note..
Tardive dyskinesia (TD) affects everyone differently. For some, it can
significantly affect their quality of life. Know that your healthcare
provider will be by your side to monitor and manage TD. They can
recommend and adapt treatment plans to fit your needs and suggest
self-care strategies that can help.
Other Tardive
Syndromes
Tardive akathisia: A state of mental agitation that
causes an inner sense of restlessness with an inability to sit still,
typically in the trunk or legs. It presents as body rocking movements,
shifting weight from one foot to another, marching in place, and/or
continual crossing and uncrossing of the legs. Sometimes it is
associated with moaning or repetitive touching movements. It is one of
the most disabling and difficult to treat tardive syndromes. (Founder’s
comment: Akathisia can also cause a debilitating inner terror and a
feeling as if the person is on fire or their blood is boiling, with or
without visible outer symptoms.
Tardive chorea: Random, jerking movements that flow
from one body region to the next, in an unpredictable manner.
Tardive dystonia: Usually presents as eye twitching,
oral and jaw muscle contractions, repetitive muscle contractions that
cause neck extension, trunk hyperextension, arm hyperextension and wrist
flexion. It can sometimes be severe enough to cause life-threatening
swallowing difficulties.
Tardive gait: Tripping and shuffling movements of
the feet with difficulty standing and moving from one place to the
other.
Tardive ocular deviations: Spasmodic movements of
the eyes with deviation in the upward direction that last for several
seconds or minutes.
Tardive myoclonus: Often presents as a brief,
jerk-like muscle contraction in the upper extremities, usually in the
arms and shoulders.
Tardive sensory syndrome (tardive pain): A chronic
burning sensation usually limited to the mouth and/or genitalia.
Tardive parkinsonism: Parkinsonism that persists
after discontinuation from dopamine receptor blocking agents (DRBAs),
with a normal SPECT scan. Other than the history of DRBAs use and the
presence of other tardive syndromes, there are no other features that
separate it from other causes of parkinsonism. Considered very rare.
Tardive tics (tardive Tourette’s): Sudden, brief,
sporadic involuntary movements or sounds.
Tardive tremor: A tremor that occurs while at
complete rest or with voluntary action. It may affect any part of the
body, but most often affects the arms and hands.
Copulatory dyskinesia: Thrusting movements of the
trunk and pelvis.
Esophageal dyskinesia: It can lead to asphyxiation
of food and is potentially life-threatening.
Rabbit syndrome: Fine, rhythmic actions at rest,
that mimic the chewing actions of a rabbit. The tongue is usually not
involved.
Respiratory dyskinesia: The respiratory pattern is
affected. It causes irregular inhalation and exhalation during
breathing. This leads to hyperventilation and hypoventilation, at
different times. It can also lead to aspiration pneumonia.
Stereotypy: Seeming purposeful, repetitive (rather
than random) and coordinated movements that can appear like rituals.
Though they seem purposeful, they are involuntary. Examples include the
“piano-playing fingers” and “hand clasping” sometimes seen in TD.
Withdrawal emergent syndrome: Occurs in patients
rapidly withdrawn from DRBAs. The movements usually mainly involve the
neck, trunk and limbs. The oral-buccal-lingual muscles are rarely
involved. It is usually time-limited to four to eight weeks, but when it
persists more than eight weeks it is considered tardive dyskinesia. The
slow tapering of DRBAs reduces the risk of this syndrome.
A look at the big picture
Tardive dyskinesia affects an estimated 500,000
persons in the United States. About 60% to 70% of cases are mild, and
about 3% are extremely severe. Particularly at risk are patients who
have been treated for schizophrenia, schizoaffective disorder, or
bipolar disorder. Persistent and irreversible tardive dyskinesia is most
likely to develop in older persons.
Significance questioned
Tardive dyskinesia’s relative significance as a clinical
problem and the need for treatment have been questioned since the
disorder was first recognized, according to Stanley N. Caroff, MD,
Perelman School of Medicine, University of Pennsylvania, in a recent article in
Neuropsychiatric Disease and
Treatment. Tardive dyskinesia had been thought to be uncommon and
restricted to patients with chronic mental illness, but recent evidence
has shown that anyone exposed to dopamine-receptor blocking drugs, not
just persons with chronic mental illness, may be at risk.
Some key statistics:
- The cumulative incidence is about 4%
to 5% annually; the prevalence rate is 20% to 30%.
- Younger patients are at risk and may
be particularly susceptible to more generalized and dystonic movements,
but older age is a major risk factor.
- The annual incidence in patients
older than 45 years is 15% to 30% after 1 year of treatment; the
prevalence rate is about 50% to 60%.
- Tardive dyskinesia has been linked
with female gender, race, higher ratings of negative symptoms and
thought disorder, greater cognitive impairments, acute drug-induced
movement disorders, substance abuse, and diabetes.
- Older adults and patients with
schizophrenia may be at greatest risk, but patients with mood disorders
are at risk and have been considered to be at high risk.
- Regardless of diagnosis, tardive
dyskinesia is not rare and anyone exposed to treatment with
antipsychotics is at risk.
First- vs second-generation antipsychotics
- A 6- to 12-fold reduction in tardive
dyskinesia risk was found with newer second-generation antipsychotics
(SGAs) compared with haloperidol.
- The relative risk of tardive
dyskinesia with SGAs is significantly less on average than that with
older first-generation antipsychotics. The risk associated with
clozapine is probably least.
- The SGAs retain some risk. No
currently available antipsychotic is risk-free.
- Additional risk factors for the
development and persistence of tardive dyskinesia are longer duration of
antipsychotic treatment and greater cumulative drug doses.
Objective severity and functional impact
The conventional wisdom that tardive dyskinesia is
unimportant may be the result of patient selection bias or the lack of
rigorous investigations, Dr Caroff noted. In the early reports of older
patients with chronic illnesses showing indifference, up to two-thirds
seemed unaware of tardive dyskinesia movements. However, in a recent
survey of outpatients with possible tardive dyskinesia, 70% to 80% were
aware of their movements and 50% to 60% felt self-conscious or
embarrassed by them.
As clinicians assess the seriousness of tardive
dyskinesia and the need for treatment, they should consider the
objective severity of the movements and the functional impact on
patients, Dr Caroff suggested.
He added that correlations between tardive dyskinesia
and impaired cognition, poor response to treatment, risk of relapse, and
other factors are confounded by the effect of the underlying psychiatric
illness-patients with severe psychoses and poor prognoses receive higher
doses of antipsychotics for longer periods with poor adherence,
resulting secondarily in a greater incidence of tardive dyskinesia.
Adverse effects on quality of life
RealâWorld Evaluation Screening Study and Registry of
Dyskinesia in Patients Taking Antipsychotic Agents (RE-KINECT) study
data showed the following effects of involuntary movements on patient
health-related quality of life (HRQoL):
- Close to 30% of patients who had
possible tardive dyskinesia reported moderate-to-extreme problems in
performing their usual activities (eg, work, housework, and leisure
activities) compared with just under 20% of patients who did not.
- Almost half of patients who had
possible tardive dyskinesia experienced moderate-to-extreme anxiety or
depression compared with just under 40% of patients who did not.
- Just more than 20% of patients who
had possible tardive dyskinesia reported moderate-to-extreme mobility
problems compared with about 12% of patients who did not.
- Utility scores in a regression model
showed poorer perceived QoL in patients who had possible tardive
dyskinesia and reported “a lot” of severity or “a lot” of impact on
daily activities compared with patients who did not.
“The RE-KINECT study provides valuable insights into the
real-world and personal impact the involuntary movements from possible
tardive dyskinesia may have on the everyday life of a patient,” said Dr
Caroff. “The findings from RE-KINECT are valuable for informing
treatment decisions in clinical practice and demonstrate the importance
of including assessments from patients and caregivers on the severity
and social impact of the stigmatizing movements of tardive dyskinesia.”
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