Tardive dyskinesia

 

Appears to be more frequent with high-potency first-generation antipsychotics, such as haloperidol, and tends to appear after chronic and not acute treatment.

 

It is characterized by slow, repetitive, involuntary and purposeless movements, most often of the face, lips, legs, or torso, which tend to resist treatment and are frequently irreversible. 

 

The rate of appearance of TD is about 5% per year of use of antipsychotic drug.

Annualized incidence of tardive dyskinesia is 3.9% with second generation antipsychotic drugs, and 5.5% with first generation drugs.

Tardive dyskinesia appears to be more frequent with first-generation antipsychotics, after chronic use.

 

 

It is characterized by slow, repetitive, involuntary and purposeless movements, most often of the face, lips, legs, or torso, which tend to resist treatment and are frequently irreversible.

 

The rate of appearance of TD is about 5% per year of use of antipsychotic drug.

Believed to be particularly uncommon with atypical antipsychotics, especially quetiapine and clozapine.

Movements are usually slow and athetoid or rapid choreiform jerks: both types of movements manifest in the mouth, face, jaw, tongue, hands, or feet.

May be related to alterations in D2 receptors.

Older patients and those with a history of acute extrapyramidal symptoms are at higher risk.

Ingrezza (valbenazine) capsules approved for the treatment of adults with tardive dyskinesia.

Ingrezza is the first drug approved by the FDA to treat tardive dyskinesia.

The efficacy of Ingrezza was analyzed in a placebo-controlled clinical trial of 234 participants.

After 6 weeks, individuals who received Ingrezza showed improvement in the severity of involuntary movements compared with those who received placebo.

Serious adverse effects that could occur with Ingrezza include sleepiness and heart rhythm problem.

Ingrezza should not be taken by patients with congenital long QT syndrome or with abnormal heartbeats.

Believed to involve the neurotransmitter dopamine.

A difficult-to-treat and often incurable form of dyskinesia.

Results in involuntary, repetitive body movements.

The involuntary movements are tardive, meaning they have a slow or belated onset.

Most frequently occurs as the result of long-term, usually at least 3 months duration, or high-dose use of antipsychotic drugs,

or in children and infants as a side effect from usage of drugs for gastrointestinal disorders.

Characterized by repetitive, involuntary movements which 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.

In some cases, legs can be so affected that walking becomes difficult or impossible.

Symptoms of tardive dyskinesia are the opposite of patients who are diagnosed with Parkinson’s disease.

Parkinson’s patients have difficulty moving, whereas tardive dyskinesia patients have difficulty not moving.

Respiratory irregularity, such as grunting and difficulty breathing, is another symptom associated with tardive dyskinesia.

Often misdiagnosed as a mental illness rather than a neurological disorder, and as a result patients are prescribed neuroleptic drugs, which increase the probability that the patient will develop a severe and disabling case, and shortening the typical survival period.

Other closely related neurological disorders are 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, Tardive tourettism is a tic disorder featuring the same symptoms as Tourette syndrome, Tardive myoclonus, a rare disorder, presents as brief jerks of muscles in the face, neck, trunk, and extremities.

The Abnormal Involuntary Movement Scale (AIMS) examination is a test used to identify the symptoms of tardive dyskinesia.

The exact mechanism of the disorder remains largely uncertain.

Evidence suggests that it 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.

Given similar doses of the same neuroleptic, different individuals have different likelihoods of developing tardive dyskinesia due to genetic polymorphisms, which code for D2 receptor binding site affinity, or prior exposure to environmental toxins.

Additionally, cognitive dysfunction, associated with aging, mental retardation, alcohol and drug abuse, or traumatic head injuries, has also been shown to increase risk of developing TD.

Often symptoms are not apparent until the patient comes off antipsychotic drugs.

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.

Quetiapine and clozapine are considered the lowest risk agents for precipitating TD.

An increased risk of tardive dyskinesia has been associated with smoking in some studies, and it is suggested that a cigarette smoke-exposure-dependent risk for TD in antipsychotic-treated patients.

Elderly patients are also at a higher risk for developing TD

Females and those with organic brain injuries, diabetes mellitus and those with symptoms of schizophrenia, and those that experience acute neurological side effects from antipsychotic drug treatment are at higher risk of developing TD.

Africans and African Americans having higher rates of TD after exposure to antipsychotics.

Genetic risk factors for TD have been identified including polymorphisms in the genes encoding the D3, 5-HT2A and 5-HT2C receptors.

Prevention is achieved by using the lowest effective dose of a neuroleptic for the shortest period of time.

If diagnosed, the causative drug should be discontinued.

Tardive dyskinesia may persist after withdrawal of the drug for months, years or even permanently.

One should consider using atypical antipsychotics as a substitute to typical antipsychotics since these agents are associated with fewer neuromotor side effects and a lower risk of developing tardive dyskinesia.

Tetrabenazine, a dopamine depleting drug, is sometimes used to treat tardive dyskinesia.

Reserpine, has also been tried as a treatment for TD with success,[29] as has ?-methyldopa.

Ondansetron has some benefit in experimental studies on tardive dyskinesia, as does a variety of anti-Parkinsonian medications are used such as donepezil, baclofen, clonidine and pramipexole.

Benzodiazepines are an effective treatment for TD, but

requires increasing doses to attenuate symptoms.

Vitamin B6 has been reported to be an effective treatment.

Tardive dyskinesia most commonly occurs in patients with psychiatric conditions who are treated with antipsychotic medications for many years.

The average prevalence rate is estimated to be around 30% for individuals taking antipsychotic medications.

It is suggested the majority of patients will eventually develop the disorder if they remain on the drugs long enough.

The elderly are more prone to develop tardive dyskinesia.

Elderly women are more at-risk than elderly men for TD.

The risk of TD is much lower for younger people and also more equal across the sexes.

Patients who have previously undergone electro-convulsive therapy or have a history of diabetes or alcohol abuse also have a higher risk.

Newer antipsychotics appear to have a substantially reduced potential for causing tardive dyskinesia.

Apart from the underlying psychiatric disorder, it may cause afflicted people to become socially isolated.

Increases the risk of dysmorphophobia and can even lead to suicide.

Stress increases the severity of dyskinetic movements, whereas relaxation and sedation have the opposite effect.