Tardive (meaning "late onset") dyskinesia (meaning "abnormal involuntary movement") is a term used to describe a syndrome occurring as a result of treatment with medications that block the receptors for the neurotransmitter dopamine in the brain. Dopamine is involved in producing movement. If the receptors are blocked over a period of time, some individuals may develop uncontrolled involuntary movements. Onset of symptoms can range from a few months to several years after initiation of drug therapy. In contrast to a tardive syndrome (which as the name implies occurs only after extended exposure to a causative agent), symptoms may also occur within a few hours to days after initiation of drug therapy. This is called an acute reaction. Acute reactions are more easily managed and usually completely resolve within a few days.
Tardive dyskinesia was first described in the 1950s in patients treated with antipsychotic medications. The tardive syndromes can affect anyone exposed to medications that block dopamine receptors; however, women, the elderly and persons with psychiatric disorders (particularly affective disorders) are at increased risk. The incidence is difficult to estimate as symptoms and severity can vary widely and many cases are probably undiagnosed, but it is believed that up to 50 % of persons with prolonged exposure to medications that block dopamine receptors will develop a tardive syndrome. The tardive syndromes include classic tardive dyskinesia, tardive dystonia, and tardive akathisia.
Classic tardive dyskinesia most commonly appears as repetitive, somewhat rhythmical involuntary movements. Typical involuntary movements include tongue thrusting, lip smacking, lip pursing, grimacing and chewing movements, rocking of the trunk, pelvic thrusting, rotation of the ankles or legs, marching in place, irregular respirations, and repetitive sounds such as humming or grunting.
Tardive dystonia may also be seen as part of the tardive syndrome. Dystonia is characterized by sustained muscle spasms causing involuntary movement and abnormal postures of the affected area. Some examples include torticollis (the head and neck are turned to the side), retrocollis (the head and neck are pulled back between the shoulder blades) and blepharospasm (the eyelids are squeezed forcefully shut). It can also cause excessive arching of the back. Tardive dystonia clinically appears identical to idiopathic or primary dystonia (meaning "of unknown cause") but is classified as a secondary dystonia since it is the result of a known agent.
Tardive akathisia is the third type of tardive syndrome. Akathisia refers to a feeling of restlessness often accompanied by anxiety. In milder cases, the individual may complain of a sensation of inner restlessness and be unable to sit quietly without fidgeting . In more severe cases, the individual may actually be unable to remain seated and must pace or march around the room. Their sense of anxiety increases if they are unable to move about.
While the above tardive syndromes are characterized by excessive movements, individuals may also experience a drug-induced parkinsonism which appears clinically like Parkinson’s's disease. With drug-induced parkinsonism, there is an absence of movement. Individuals have slow movements with rigid or stiff muscles and tremor. When walking, a shuffling gait is present with a stooped posture and diminished arm swing. Facial expression is blunted causing a very solemn appearance. Of all the tardive syndromes, drug-induced parkinsonism is the most reversible. It resolves after the medication is stopped, but this may take up to 18 months.
Some medications that are known to cause tardive syndromes include:
Medications for gastrointestinal problems
Medications for cough
Medications for depression
Antipsychotics or Neuroleptics
Diagnosis is based on the patient's history and a thorough clinical examination. The criteria for diagnosing a tardive syndrome can vary but is generally agreed to be exposure of an individual to a dopamine receptor blocking agent within 6 months of onset of symptoms which persist at least 1 month after stopping the offending drug. There is no laboratory test or x-ray to confirm the diagnosis; although, such tests may rule out other conditions if the diagnosis is questionable.
The longer the drug is taken, the greater the chance of developing a tardive syndrome. Once the symptoms are noticed, the best course of action is to stop the medication if possible. Your physician will work out a tapering schedule to discontinue the drug as most should not be abruptly stopped. With chronic psychiatric conditions, this may not be an option and in these instances the medication should be kept at the lowest possible dose.
Symptoms may temporarily worsen after the medication is stopped, but avoiding this type of medication offers the best hope for a remission. Symptoms may lessen or even disappear if the medication is restarted or the dose is increased, but movements will eventually break through with an increase in severity and be more resistant to treatment.
For some, symptoms may first be noticed after the medication has been stopped (withdrawal emergent tardive dyskinesia). Once again, the best course of action is to remain off the offending drug.
Tardive dyskinesias are challenging both to the patient and medical profession. The best treatment may simply be to withdraw the offending medication and allow the symptoms to resolve on their own. If symptoms are intolerable to the patient, oral medications may be used. Some studies suggest vitamin E may hasten the resolution of symptoms. Benzodiazepines such as clonazepam (Klonopin) may provide some relief of involuntary movements and anxiety. The main side effect seen with this type of drug is drowsiness. Dopamine depleting drugs are probably the most effective medications used to treat tardive dyskinesia. Two commonly used drugs in this class are reserpine and methyldopa. These medications have side effects including depression, apathy, lowered blood pressure and parkinsonism.
Tardive akathisia may be treated with beta blockers such as propranolol (Inderal). Side effects can include slowed heart rate, lowered blood pressure and depression. It should be used cautiously in persons with certain types of heart and respiratory diseases.
Tardive dystonia may be relieved with anticholinergics such as trihexyphenidyl (Artane) or benztropine (Cogentin). If is important to note that these medications (while beneficial in some cases of tardive dystonia) will typically worsen tardive dyskinesia. Certain types of tardive dystonia may also be treated effectively with local injections of botulinum toxin.
Treatment may require trials of different medications at different doses and a great deal of patience. Just as each individual is unique, so must the medication regimen be tailored to their specific needs. While some tardive syndromes are persistent, most individuals gain some degree of relief with oral medications and the natural resolution of symptoms as time off the offending agent increases. Some experts believe the time an affected individual was exposed to the causative medication can be correlated to the length of time needed for symptoms to resolve.
Research is currently underway in both the treatment and prevention of tardive syndromes. As our understanding of the neurochemistry of the brain increases, new medications are being developed that spare the dopamine receptors involved in syndromes such as tardive dyskinesia
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The University of Kansas Medical Center