Tardive dyskinesia
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# Overview
Tardive dyskinesia is a neurological disorder caused by the long-term or high-dose use of dopamine antagonists, usually antipsychotics. These neuroleptic drugs are generally prescribed for psychiatric disorders. Other dopamine antagonists that can cause tardive dyskinesia are drugs for gastrointestinal disorders (for example metoclopramide) and neurological disorders. Some drugs that are not intended to affect dopamine, such as SSRI antidepressants, may also cause tardive dyskinesia. While newer atypical antipsychotics such as olanzapine and risperidone appear to have less dystonic effects, only clozapine has been shown to have a lower risk of tardive dyskinesia than older antipsychotics.
The term tardive dyskinesia was introduced in 1964. Dyskinesia refers to an impairment of voluntary movement. The resultant tics and other movements are often referred to as dyskinesias. Dyskinesia is sometimes caused by long-term use of anti-psychotic drugs or other dopamine antagonists like the antiemetic metoclopramide. The effect of these drugs can be tardive, meaning the dyskinesia continues or appears even after the drugs are no longer taken. As far as treatment of iatrogenic tardive dyskinesia is concerned, neuroleptic drugs should be withdrawn for a period of 3-6 months to see if this resolves the issue, but the problem may fail to improve or may even exacerbate. In this situation, it would be sensible to trial the patient on tetrabenazine 25-50 mg/8h PO.(Oxford Handbook of Clinical Medicine).
In context of Parkinson's disease, dyskinesias are often the result of chronic levodopa (L-dopa) therapy. These motor fluctuations occur in more than half of PD patients after 5 to 10 years of levodopa therapy, with the percentage of affected patients increasing over time.
Dyskinesias most commonly occur at the time of peak L-dopa plasma concentrations and are thus referred to as peak-dose dyskinesias. As patients advance, they may evidence diphasic dyskinesias, which occur when the drug concentration rises or falls.
The use of MDMA has been shown to enhance the effects of L-Dopa while reducing the associated dyskinesia in primates with simulated Parkinson's disease.

# Features
Tardive dyskinesia is characterized by repetitive, involuntary, purposeless movements. Features of the disorder may include grimacing, tongue protrusion, lip smacking, puckering and pursing of the lips, and rapid eye blinking. Rapid movements of the arms, legs, and trunk may also occur. Impaired movements of the fingers may appear as though the patient is playing an invisible guitar or piano. Patients with Parkinson's disease have difficulty moving, while patients with tardive dyskinesia have difficulty not moving.
Other closely related neurological disorders have been recognized as variants of tardive dyskinesia. Tardive akathisia involves painful feelings of inner tension and anxiety and a compulsive drive to move the body. In the extreme, the individual undergoes internal torture and can no longer sit still. Tardive tourettism is a tic disorder that can closely mimic Tourette Syndrome, sometimes to the point where the two can only be distinguished by the details of their onsets.

# Cause
The cause of tardive dyskinesia appears to be related to damage to the system that uses and processes the neurotransmitter dopamine. It is thought that postsynaptic dopaminergic receptors become supersensitive to stimulation as a result of the use of neuroleptic drugs and that this supersensitivity causes the symptoms of tardive dyskinesia.  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 patient more sensitive to tardive dyskinesia. Since 1973 the use of these drugs have been found to be associated with the development of tardive dyskinesia (Crane, 1973). Since some of the symptoms of tardive dyskinesia can be interpreted as schizophrenia by doctors, they may prescribe additional neuroleptic drugs to treat it, leading to increased risk of more prevalent tardive dyskinesia. Several studies have indicated that long-term neuroleptic use is associated with both cognitive deterioration and atrophy of the brain.

# Differential Diagnosis of Tardive dyskinesia
One the basis of stiffness and fever it can be differentiated from:
- Tetanus
- Stiff man syndrome
- Meningitis
- Hypocalcemia
- Parkinsonism
- Neuroleptic malignant syndrome

# Causes

# Treatment
Primary prevention of tardive dyskinesia is achieved by using the lowest effective dose of a neuroleptic for the shortest time. If tardive dyskinesia is diagnosed, the causative drug should be reduced or discontinued if possible. Tardive dyskinesia may persist after withdrawal of the drug for months, years, or even permanently. There is no known cure for tardive dyskinesia, but preliminary research suggests that the atypical neuroleptic clozapine (Clozaril) may improve the state of the patient. Improvements are also seen in some cases, if the high potency benzodiazepines - lorazepam (Ativan), diazepam (Valium), or clonazepam (Klonopin)--are used. The findings about the effects of natural substances, such as vitamin E (Alpha-Tocopherol) or melatonin, are inconclusive.
Natural remedies are unproven, since they are seldom tested in a controlled setting such as a drug trial. Preliminary research indicates that alternating rest, and regular exercise also negate the symptoms of tardive dyskinesia, necessary for all mental health outpatients who maintain anti-psychotic neuroleptic drug regimes, for on-going 'wellness'. Switching to a newer drug with fewer side effects might be an option for a patient in a controlled or monitored environment.

# Epidemiology
Tardive dyskinesia most commonly occurs in patients with psychiatric conditions who are treated with antipsychotic medications for many years.  Some estimates suggest that it occurs in 15-30% of patients receiving treatment with antipsychotic neuroleptic medications for 3 months or longer. 
A study being conducted at the Yale University School of Medicine has estimated that 32% of patients develop persistent tics after 5 years on major tranquilizers, 57% by 15 years, and 68% by 25 years.
Other estimates suggest that with each year of neuroleptic use, 5% of the patients will show signs of tardive dyskinesia, i.e., 5% after one year, 10% after two years, 15% after three years with no clear upper limit. Eventually, according to these estimates, if on the drugs long enough, the majority of patients will develop the disorder.  The incidence of tardive dyskinesia varies with the type of neuroleptic (e.g., haloperidol (Haldol) more often than perphenazine (Trilafon)), daily dose and duration of treatment (the higher the daily dose and the longer the duration of treatment, the higher the risk).
The elderly and female patients are more prone to develop tardive dyskinesia. Cigarette smokers also have a higher prevalence of tardive dyskinesia. Children and adolescents are much more sensitive to the early and late extrapyramidal side-effects of neuroleptics than adults. Because of this, treatment of youngsters with neuroleptics may be contraindicated, and many authorities believe that they should be initiated only as a last resort, using the lowest dose regime possible and the shortest duration of treatment in accordance with good patient management.
Tardive dyskinesia can become a social handicap. Patients and/or their families (guardians and/or caregivers/nurses) should receive full information about the neuroleptic before starting treatment (informed consent). The benefits need to be weighed by the individual patient/guardian and their physician.

# Controversy
Peter Breggin has discussed tardive dyskinesia in the context of his criticism of biological psychiatry.  However, his hypotheses are not widely accepted by mainstream psychiatric professionals.