Tardive dyskinesia (TD) is a form of drug-induced (iatrogenic) movement disorder that is one form of tardive syndrome. Other forms of tardive syndrome include tardive stereotypy, tardive chorea, tardive tremor, tardive tics, tardive myoclonus, tardive parkinsonism and other movement disorders that persist even after the offending drug is discontinued. 鈥淭ardive鈥 means delayed and 鈥渄yskinesia鈥 means abnormal involuntary movement. The problem is caused by exposure to medications that block dopamine receptors (most commonly certain antidepressant, antipsychotic, and anti-nausea medications) but drugs with other mechanisms of action can also cause tardive syndrome. This group of disorders is often referred to in the literature as 鈥渆xtrapyramidal syndromes鈥 or 鈥淓PS鈥, but this term should be retired from the literature as it has never been well defined and lacks specificity.
Drug-induced movement disorders have gradually emerged as a major problem in clinical psychiatry and medicine. A variety of movement disorders have been characterized and linked to different dopamine receptor blocking agents (DRBAs), also referred to as neuroleptics. These drugs are primarily categorized as antipsychotic agents, but DRBAs are also used to treat a variety of gastrointestinal disorders such as nausea and gastroparesis. Although the new "atypical" neuroleptics purport to have a lower risk for TD, their widespread use still makes TD a common and distressing movement disorder.
Diagnosis
TD typically consists of involuntary, irregular, continuous, coordinated, slow or fast movements that may be random and unpredictable (choreiform) or patterned (stereotypies). The frequency of TD has been estimated to occur in between 20 and 50 percent of patients receiving antipsychotic medications, with an average estimate at approximately 20 percent. This marked variability is due to differences in diagnostic criteria for TD, patient populations, types of medication, and methods of ascertainment. For example, the risk of TD is much greater with the older (first-generation) antipsychotics than the more recent (second- and third-generation antipsychotics).The risk of TD increases with age and with the dose of DRBA and is particularly high in non-whites and elderly women. In contrast, persistent tardive syndromes are uncommon in children.
The most common type of involuntary movement associated with TD is classified as stereotypy or "an involuntary, coordinated, patterned, repetitive, rhythmic, ritualistic, purposeless (but seemingly purposeful) movement, posture or utterance." Simple stereotypies involve only one body part, such as the mouth or hand, whereas complex stereotypies affect more than one body region and may involve the whole body. The oro-facial-lingual (OFL) movement, most typically seen in TD, is one of the best examples of stereotypies and is present in over 80 percent of patients with TD.
In a videotape review of 100 patients with TD evaluated at the Baylor Medicine Movement Disorders Clinic, 78 exhibited some stereotypies, and 61 of these involved the OFL region. The following OFL stereotypies were observed: chewing, blowing, licking, lip-smacking and pursing, facial grimacing, tongue protruding ("fly-catcher's tongue"), and coordinated tongue and mouth movements ("bon-bon sign"). Other stereotypies included hand and toe waving, touching and picking, rubbing of face, scalp, and other body parts, head nodding, body rocking, shallow and rapid breathing ("respiratory dyskinesia"), pelvic thrusting ("copulatory dyskinesia"), crossing and uncrossing of legs, shifting of body weight from one to the other leg, pacing or marching in place, alternating sitting, and standing, and a variety of vocalizations and noises, such as humming, moaning and belching. While TD can result in severe disability, such as shortness of breath due to respiratory dyskinesia, up to two-thirds of patients are not even aware of the abnormal involuntary movements. Similar to other hyperkinetic movement disorders, tardive stereotypies are usually exacerbated during stress, disappear during sleep, and may be volitionally suppressed, at least temporarily.
Other involuntary movements associated with TD include chorea (dance-like movements flowing randomly from body part to body part), dystonia (involuntary muscle contractions producing a variety of movements, such as facial spasms, eyelid contractions, clenching of jaws and grinding of teeth, arching of the neck and back, extension of arms), akathisia (feeling of restlessness, inability to stand or sit still, and a need to move), tics (jerk-like coordinated movements often preceded by premonitory sensations), myoclonus (jerk-like simple movements), and a variety of other movements and abnormal, often uncomfortable, sensations.
Cause
As discussed above, any medication that blocks dopamine receptors in the brain has the potential of causing TD. It is thought that blockade of dopamine receptors in the brain leads to hypersensitivity of the same dopamine receptors such that any exposure to dopamine will produce an exaggerated response which manifests as involuntary movements. This theory, however, does not explain why TD persists after the offending agent has been withdrawn, and complimentary theories involving other neurotransmitter systems, free radicals, genetic susceptibility, and brain plasticity, have thus emerged.
Treatment
Prevention, rather than treatment, is the ultimate goal of any therapeutic program and this is particularly relevant to TD. Whenever possible, the DRBA should be avoided and used only if other drugs are not available or have failed to control the condition. Once the patient develops symptoms of TD, the responsible neuroleptic should be discontinued if at all possible. The risks of continued exposure the DRBA must be carefully weighed against the possibility of exacerbating the underlying psychiatric or gastrointestinal condition. Discontinuation of DRBA may also cause transient exacerbation of the TD. Nevertheless, slowly withdrawing the offending drug is usually considered prudent clinical practice. In some patients with psychiatric illness, withdrawal of the antipsychotic agents may not be possible. To minimize TD in such patients, switching to newer, also called atypical neuroleptics might be the only solution. Clozapine and quetiapine are considered the neuroleptics with the lowest risk of developing drug-induced movement disorders.
When treatment is required, dopamine-depleting drugs, such as tetrabenazine (Xenazine), deutetrabenazine (Austedo), and valbenazine (Ingrezza) provide the most effective treatment of the TD-related involuntary movements. However, these drugs may not completely suppress the involuntary movements and may produce a variety of adverse effects such as daytime drowsiness, insomnia, depression, parkinsonism and akathisia. These adverse effects seem to be less of a problem with the newer dopamine-depleting drugs (deutetrabenazine and valbenazine).
The second-line agents include amantadine, clonazepam, gingko biloba and zolpidem. Propranolol, clonidine, gabapentin, opioids have been found useful in some cases of akathisia. Anticholinergic drugs, such as trihexyphenidyl and benztropine, may ameliorate symptoms of tardive dystonia and parkinsonism, but they should not be prescribed routinely because they may possibly exacerbate TD and worsen thinking and memory. Cholinergic drugs have been extensively tested in the treatment of TD, but they have not been found effective in most recent trials. Injections of botulinum toxin are very effective in the treatment of focal dystonia, such as tardive jaw and face (oromandibular) dystonia. Some cases of disabling TD, resistant to the treatment options listed above, can be potentially treated with a deep brain stimulation surgery.
References
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