One of the most severe adverse effects of chronic treatment with antipsychotic drugs is the common movement disorder tardive dyskinesia (TD), which is characterized by orofacial and trunk/limb movement abnormalities of a choreiform nature.

The mean reported prevalence is approximately 20%. In the elderly population, the prevalence may be as high as 30–50%. Prospective studies suggest an incidence of 3–4% incidence each year in the first eight years or so of drug treatment.

TD is a late onset problem.  It can fluctuate in severity over days or even hours. Factors that influence this intrapatient variation include:

• Alteration of medication, such as change in dosage of antipsychotic or anticholinergic medication, and
• Changes in posture, mobility or level of physiological arousal.

Subsyndromes of tardive dyskinesia
Orofacial dyskinesia and trunk and limb dyskinesia have emerged as discrete phenomenological components or factors²⁴.  A number of studies have shown a discrepancy in response to drug treatment between orofacial dyskinesia and trunk and limb dyskinesia²⁵.  Several reasons suggest themselves :

• The pathophysiologies of the subsyndromes are different
• Finger and orofacial movements are ‘finer’ motor movements, which may be more vulnerable because of their pattern of representation in the brain
• Orofacial dyskinesia is a distinct and discrete phenomenon and is therefore very easy to identify and rate.  A host of motor abnormalities, such as akathisia, dystonia, and stereotypes and mannerisms, could confound the assessment of trunk and limb dyskinesia.

It used to be thought that females were more likely to develop TD.  The evidence suggests there is a greater prevalence of severe dyskinesia in females only within the geriatric age range (70+ years).

Anticholinergic drugs
Although it is well known that anticholinergic drugs worsen TD, it has not yet been established whether patients receiving antiparkinsonian medication in addition to antipsychotic medication are at a greater risk of developing the condition than those receiving antipsychotic medication alone²⁷.

Association with other antipsychotic-induced movement disorders
Recent prospective studies suggest that susceptibility to acute drug-induced EPS is a predictor of TD.  That is, patients who are susceptible to parkinsonism and akathisia may be more likely to develop TD later in life.

TD and akathisia tend to occur together in samples of patients receiving long-term treatment with antipsychotic drugs^28,29. In a follow-up study³⁰ of chronic akathisia and pseudo-akathisia in 120 long-stay patients, 27 (23%) patients exhibited chronic akathisia at baseline.  After a median follow-up period of 22 months, it had disappeared in 14 and was still there in ten.  When the baseline records were analyzed for differences in medication history, age, or other characteristics, the only significant difference was that those patients whose akathisia had persisted had significantly higher scores for TD.  From a clinical point of view, therefore, the patient with both conditions seems more likely to suffer persistent problems³⁰.

Association with negative symptoms
Studies of the clinical correlates of TD suggest an association with negative symptoms.  We therefore studied 179 inpatients with chronic schizophrenia in an attempt to establish whether negative symptoms could be considered a risk factor, and to establish whether the incidence of TD can be correlated with age³¹.  The findings supported the hypothesis that negative symptoms are a risk factor for an earlier onset of tardive dyskinesia³¹.

Cognitive function and TD
Waddington³² reviewed 21 studies in schizophrenic patients, and noted that a  broad range of neuropsychological tests were employed in samples that varied widely with respect to age range and chronicity of illness.  Seventeen studies reported that patients exhibiting abnormal involuntary movements showed significantly greater cognitive dysfunction.  He considered the association between cognitive dysfunction and involuntary movements to be particularly robust in relation to two subsyndromes :

• Orofacial dyskinesia rather than trunk and limb dyskinesia
• Persistent rather than transient dyskinesia.

Prospective study of TD
John Kane and colleagues³⁴ performed a
large-scale prospective study of TD in which they followed up 148 patients who developed TD.  The patients were examined at three-month intervals using the Simpson Dyskinesia Scale.  Over five years, approximately 40% showed persistent remission. Variables such as gender, age, diagnosis, or length of treatment showed no correlation with remission.  Variables related to the outcome of TD were drug dose and the proportion of time on medication following diagnosis of TD, i.e. the number and duration of  interruptions of drug treatment.  One interpretation of the data is that stopping and starting antipsychotic treatment may be inadvisable in terms of the persistence of TD that has already developed.

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