Tardive dyskinesia

For patient information click here

Tardive dyskinesia
ICD-10	G24.0
ICD-9	333.85
OMIM	272620
DiseasesDB	12909

WikiDoc Resources for Tardive dyskinesia
Articles
Most recent articles on Tardive dyskinesia Most cited articles on Tardive dyskinesia Review articles on Tardive dyskinesia Articles on Tardive dyskinesia in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on Tardive dyskinesia Images of Tardive dyskinesia Photos of Tardive dyskinesia Podcasts & MP3s on Tardive dyskinesia Videos on Tardive dyskinesia
Evidence Based Medicine
Cochrane Collaboration on Tardive dyskinesia Bandolier on Tardive dyskinesia TRIP on Tardive dyskinesia
Clinical Trials
Ongoing Trials on Tardive dyskinesia at Clinical Trials.gov Trial results on Tardive dyskinesia Clinical Trials on Tardive dyskinesia at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Tardive dyskinesia NICE Guidance on Tardive dyskinesia NHS PRODIGY Guidance FDA on Tardive dyskinesia CDC on Tardive dyskinesia
Books
Books on Tardive dyskinesia
News
Tardive dyskinesia in the news Be alerted to news on Tardive dyskinesia News trends on Tardive dyskinesia
Commentary
Blogs on Tardive dyskinesia
Definitions
Definitions of Tardive dyskinesia
Patient Resources / Community
Patient resources on Tardive dyskinesia Discussion groups on Tardive dyskinesia Patient Handouts on Tardive dyskinesia Directions to Hospitals Treating Tardive dyskinesia Risk calculators and risk factors for Tardive dyskinesia
Healthcare Provider Resources
Symptoms of Tardive dyskinesia Causes & Risk Factors for Tardive dyskinesia Diagnostic studies for Tardive dyskinesia Treatment of Tardive dyskinesia
Continuing Medical Education (CME)
CME Programs on Tardive dyskinesia
International
Tardive dyskinesia en Espanol Tardive dyskinesia en Francais
Business
Tardive dyskinesia in the Marketplace Patents on Tardive dyskinesia
Experimental / Informatics
List of terms related to Tardive dyskinesia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]

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

Differential Diagnosis of Fever and Stiffness

Disease	Diagnosis			Treatment
	Symptoms	Signs	Laboratory Findings
Tetanus	Tonic contraction of muscles between the spasmodic episodes Trismus or lockjaw Neck stiffness Swallowing difficulty Stiffening of the calf and pectoral muscle groups	Opisthotonos Leg extension with arm flexion Risus sardonicus respiratory distress	Not significant	Diazepam Magnesium  Human TIG
Neuroleptic Malignant Syndrome	History of intake of offending drugs e.g neuroleptics like: Fluphenazine Haloperidol Olanzapine Risperidone Autonomic instability Rigidity Disorientation Fever	Dysphagia Pallor Dyspnea Shuffling gait Agitation	Myoglobinemia Elevated LDH Elevated creatine kinase Hyperkalemia Elevated AST and ALT Hyperphosphatemia Elevated alkaline phosphatase Hyperuricemia	Supportive therapy Stop the offending agent Medical Therapy Dantrolene Amantadine Bromocriptine
Viral Meningitis	Fever Irritability Lack of appetite Lethargy Disoriented High grade fever Severe headache Stiff neck Sensitivity to bright light Nausea Vomiting	Headache Photophobia Phonophopia Pharyngitis in case of enterovirus infeciton Orchitis (In mumps) Vesicular or macular skin rash Petichiae Nuchal rigidity Signs of meningeal irritation: Kernig's sign Brudzinski's sign Altered mental status Hypotonia	CSF / plasma glucose ratio (>0.6) Lactate (mmols/l) (<2.1) Lymphocytes > granulocytes	Supportive Analgesics for pain. Acetaminophen for fever. Anti-viral therapy: Acyclovir Pleconaril
Stiff man syndrome	Marked rigidity Spasms Intermittent Painful Absent during sleep	Diaphoresis Arterial hypertension Tachypnea Cyanosis Apnea, tachypnea Respiratory arrest Dilatation of the pupils Tachycardia	CSF has Elevated IgG Oligoclonal bands Positive anti-GAD antibodies Elevated creatine kinase Normal CBC & ESR	Benzodiazepines Baclofen Vigabatrin  Valproic Acid, Neurontin Injected botulinum toxin  Prednisone, plasmapheresis, IVIG ( some success)
Drug induced (Tardive dyskinesia)	History of intake of the offending drug for at least one month Neuroleptics (antipsychotics) Metoclopramide Eye deviation Head and neck jerky movements No tonic contraction of the muscles between the spasms	Dyskinesia of the tongue and lips Dyskinesia of the limbs Dyskinesia of the neck	It is a clinical diagnosis depending on Dyskinetic movements Hx of > 1 month of antipsychotic use Labs may be done to rule out other differentials	Stop the offending agent Benztropine Benzodiazepines Injection of botulinum toxin Valbenzine Tetrabenazine
Strychnine poisoning	Hx of up to date tetanus immunizations History of intentional or accidental intake Strychnos nux vomica seeds Rodenticide	Hypervigilance Anxiety Mydriasis Hypereflexia Clonus Facial and neck stiffness	Blood assay Tissue assay Urine assay	Initial stabilization High dose Benzodiazepines Intubation and airway securing
Hypocalcaemia	Muscle twitching and cramping Circumoral and extremity paresthesia or tingling Altered mental status Irritability Depression Psychosis Seizure	Tetany (carpopedal spasm) Latent tetany Trousseau sign of latent tetany  Chvostek's sign  Hyperactive tendon reflexes	Decreased blood calcium levels	Two ampules of intravenous calcium gluconate 10% is given slowly in a period of 10 minutes, or If hypocalcemia is severe, calcium chloride is given instead Maintenance doses of both calcium and vitamin-D
Parkinson's disease	Stiffness Inability to write Jerky movements at rest Constipation Sleeping difficulty Walking difficulty	Tremor Rigidity Bradykinesia Postural instability Shuffling gait	Clinical diagnosis Improvement with dopaminergic therapy confirms diagnosis	Symptomatic therapy Dopamine agonists Levodopa Amantadine MAO inhibitors COMT inhibitors Anticholinergics

Causes

Cardiovascular	No underlying causes
Chemical / poisoning	No underlying causes
Dermatologic	No underlying causes
Drug Side Effect	Asenapine maleate, Chlorpromazine, Clozapine, Fluphenazine, Iloperidone, Loxapine, Metoclopramide, Olanzapine, Perphenazine, Prochlorperazine, Thioridazine hydrochloride, Thiothixene, Trifluoperazine
Ear Nose Throat	No underlying causes
Endocrine	No underlying causes
Environmental	No underlying causes
Gastroenterologic	No underlying causes
Genetic	No underlying causes
Hematologic	No underlying causes
Iatrogenic	No underlying causes
Infectious Disease	No underlying causes
Musculoskeletal / Ortho	No underlying causes
Neurologic	No underlying causes
Nutritional / Metabolic	No underlying causes
Oncologic	No underlying causes
Opthalmologic	No underlying causes
Overdose / Toxicity	No underlying causes
Psychiatric	No underlying causes
Pulmonary	No underlying causes
Renal / Electrolyte	No underlying causes
Rheum / Immune / Allergy	No underlying causes
Trauma	No underlying causes
Miscellaneous	No underlying 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.

See also

• Primary ciliary dyskinesia
• Athetosis
• Asterixis

References

Template:WS