Tardive dyskinesia
Tardive dyskinesia (TD) is a movement disorder characterized by involuntary muscle movements that typically arise after long-term use of certain medications, particularly neuroleptics (antipsychotics) and, to a lesser extent, the anti-nausea drug metoclopramide. First identified in the 1960s, TD is classified as a medication-induced movement disorder by the American Psychiatric Association. The risk of developing TD is higher among individuals who have used multiple neuroleptic drugs, are older (especially those over 50), and among females, particularly postmenopausal women. Symptoms may develop either suddenly or gradually, and they often affect the face, mouth, and limbs.
Diagnosis involves a thorough evaluation to rule out other disorders with similar symptoms, typically using the Abnormal Involuntary Movement Scale (AIMS) for ongoing assessment. Treatment primarily focuses on discontinuing the offending medication, although symptoms may persist even after cessation. Alternative medications may be needed to manage the underlying condition or alleviate symptoms if TD develops. Ongoing research aims to better understand the mechanisms behind TD and develop safer treatment options.
Tardive dyskinesia
Disease/Disorder
Anatomy or system affected: Nervous system disorder, extrapyramidal disorder
Definition: A medication-induced movement disorder characterized by involuntary movements.
Key terms:
antipsychotics: a group of medications used to treat the symptoms of psychosis
DSM-5: the fifth edition of theDiagnostic and Statistical Manual of Mental Disorders(2013), which includes behavioral diagnostic criteria for determining psychiatric illnesses
neuroleptics: another term for classes of drugs used to treat psychosis
neurotransmitters: chemicals manufactured by the brain for the purpose of facilitating or inhibiting neural signals
Background Information
The term tardive dyskinesia was coined in the early 1960s by Arbild Faurbye to refer to a movement disorder that occurred sometime after exposure to certain drugs. Today tardive dyskinesia is classified by the American Psychiatric Association’s DSM-5 as a medication-induced movement disorder. It is characterized by involuntary movements that are associated with the long-term use of neuroleptic drugs (also known as antipsychotic medications or major tranquilizers), and is a reasonably common side effect. It is also seen as a side effect of the antinausea drug metaclopramide. According to the National Alliance on Mental Illness (NAMI) in 2015, some studies indicate that tardive dyskinesia is seen in up to 30 to 50 percent of all individuals on neuroleptics. Tardive dyskinesia is categorized as a rare disease by the National Organization for Rare Disorders (NORD) indicating that there are under 200,000 people suffering from this disorder in the United States.
Causes and Risk Factors
The causes of tardive dyskinesia are unclear. While some believe that neuroleptics stimulate the production of dopamine receptors in the part of the brain controlling movement, others hypothesize that it is more likely linked to serotonin receptors. Some recent evidence suggests that rather than being tied to one of the major neurotransmitters per se, tardive dyskinesia may be related to a problem with an inhibitory neurotransmitter. If this is the case, the culprit is felt to be gamma-aminobutyric acid (GABA).
There are multiple risk factors for tardive dyskinesia. Obviously occurring in people who are using neuroleptics, certain factors seem to make this side effect of the medications more likely to occur. It is more commonly seen in people who have used more than one neuroleptic drug as well as in individuals who have had a substance use disorder (drug, alcohol, or cigarettes) during their lifetime. It is also seen more commonly in people of advanced age, with evidence indicating that it is much more common in people over the age of 50. Tardive dyskinesia is found more commonly in females, especially if they are postmenopausal. It has also been found more commonly in individuals who are developmentally disabled. Currently, it is unclear whether these factors actually increase the likelihood of developing this disorder as a side effect of the drugs, or whether they merely increase the likelihood of being prescribed neuroleptic drugs long term.
Symptoms
Individuals with tardive dyskinesia display sudden, often continuous, uncontrollable movements of groups of voluntary muscles. Individuals with tardive dyskinesia may develop their symptoms very abruptly or gradually over time. Patients who are on drugs known to cause tardive dyskinesia should be advised to keep a record of any symptoms that they develop, being sure to describe the symptom, note the date and time that it occurred, the body part affected, and the severity of the symptom. The involuntary movements occur most often in the area of the face (especially the mouth, jaw, and eyelids). Such movements have also been found to occur in the neck, any or all limbs, and the torso.
Screening and Diagnosis
When an individual is placed on neuroleptics they are typically evaluated using a tool known as the Abnormal Involuntary Movement Scale (AIMS) to obtain baseline level functioning and then followed up with this tool on a yearly basis. This screening may allow early identification of tardive dyskinesia. Alternatively, an individual who becomes aware of symptoms like those noted above should clearly be seen by a physician immediately. In order to make a differential diagnosis the physician would need to rule out a number of other disorders with similar symptoms. To make this diagnosis of exclusion (eliminating other possible etiologies) one would typically do blood work, electroencephalograms (EEGs), computed tomography (CT) scans, or magnetic resonance imaging (MRI). If most other causes are eliminated, and if the patient has been on one of the drugs known to cause medication induced movement disorders, then the diagnosis will likely be tardive dyskinesia. Typically by the time this diagnosis is made the patient has been seen by a psychiatrist and a neurologist. Once this diagnosis has been made, the patient will continue to be evaluated using the AIMS in order to determine the severity of the disorder.
Treatment and Therapy
Since the onset of tardive dyskinesia is clearly medication related, the first order of treatment is to identify and discontinue the offending medication. The most common offenders are older antipsychotic drugs, such as chlorpromazine, fluphenazine, haloperidol, and trifluoperazin. Flunarizine, metoclopramide, and prochlorperazine are other similar drugs that may cause tardive dyskinesia. The process of identifying and discontinuing the offending medication can be very complex, and should only be done under the direct supervision of a physician. Symptoms may often persist after the medication is discontinued. Hopefully, other medications can be prescribed to deal with the underlying disorder. Newer neuroleptics (antipsychotics) are less likely to produce tardive dyskinesia, but it may still occur. Antipsychotic medications that may help with movement disorders include sulpriride, oxypertine, and tiapride. When alternative drug use is not a possibility or does not treat the underlying disorder, the offending medication may still have to be taken. If that is the case or if the symptoms do not subside long after the medication is discontinued, there are medications that may help lessen symptoms. These include trihexyphenidyl, reserpine, propanolol, clonidine, baclofen, melatonin, and diphenhydramine. Certain sedatives and antiseizure medications may also alleviate symptoms. Tetrabenazine is widely used in Canada for this purpose, but is available only for use as an orphan drug in the United States to treat tardive dyskinesia. Currently this is an off-label use for tetrabenazine, which is approved in this country only for the treatment of Huntington’s chorea.
Perspective and Prospects
As indicated above, symptoms may disappear soon after the offending drug is discontinued. Yet in other cases, symptoms may persist for years. At present, research is being done to definitively determine the underlying mechanism of the disorder, develop drugs that do not create these side effects, and find ways to alleviate the symptoms should they occur.
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