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  • Clinical Implications
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Clinical Implication

Clinical implications of pharmacogenomics for tardive dyskinesia

The Pharmacogenomics Journal volume 4, pages 77–87 (2004)Cite this article

Spontaneous dyskinetic (or abnormal) movements have been associated with schizophrenia (or to some subforms) independently of the use of antipsychotics. It has been suggested that some forms of dyskinesia may at least partially be intrinsic to the pathophysiology of schizophrenia, perhaps reflecting basal ganglia pathology. However, up to 50% of patients affected with schizophrenia typically develop dyskinesia in combination with long-term exposure (ie months to years) of traditional or ‘typical’ antipsychotics. The term tardive dyskinesia (TD) refers to this potentially irreversible complication that is, by definition, caused by the long-term use of antipsychotic medication. TD consists of hyperkinetic involuntary movements, most commonly characterized by orofacial dyskinesia, but it may include tics, chorea and/or athetosis or a combination of these.1 For obvious reasons, TD may be extremely distressing to patients as it substantially debilitates motor performances in normal life. Furthermore, TD may lead to social stigmatization or to difficulties in finding employment. The presence of schizophrenia is not necessary to develop antipsychotic induced dyskinesias, as these occur also in patients treated with antipsychotics for other conditions than schizophrenia. A meta-analysis including 76 studies on 39 187 patients with chronic antipsychotic treatment reported TD rates that ranged from 3 to 70% and an overall prevalence of 24.2%.2 Prevalence rates are, however, difficult to estimate because of the fluctuating course of TD and heterogeneities across studies with respect to study population, diagnostic criteria used, type and dose of (co-)medications, etc. Age, regardless of the duration of treatment, is an important risk factor for TD, as TD is five to six times more prevalent in the elder (>45 years) than in younger patients.3,4

Even though newer (or ‘atypical’) antipsychotics have a lower or perhaps negligible risk to induce TD,5 classical (or typical) antipsychotics are, however, currently still prescribed for many reasons: Typical antipsychotics are less expensive than atypical antipsychotics, which may globally be one leading reason. Moreover, some patients do not respond or tolerate treatment with atypical antipsychotics that may cause side effects as weight gain or diabetes mellitus. Finally, if patients are treated by intramuscular application of antipsychotics (ie with depot formula), this particular pharmacopeia is mostly composed of classical antipsychotics. Therefore, TD still represents a serious and prevalent adverse effect. The prevention of TD and the detection of associated risk factors are of great clinical importance as no uniformly safe and effective treatment for TD is available yet.

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Acknowledgements

This work was supported by the Canadian Institutes of Health Research (CIHR) operating grant to JLK, and DJM is the recipient of a CIHR postdoctoral fellowship award. We thank Mary Smirniw for assistance in preparation of this manuscript.

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  1. Clarke Division, Department of Psychiatry, Neurogenetics Section, University of Toronto, Centre for Addiction and Mental Health, Toronto, ON, Canada

    D J Müller, T Shinkai, V De Luca & J L Kennedy

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Müller, D., Shinkai, T., De Luca, V. et al. Clinical implications of pharmacogenomics for tardive dyskinesia. Pharmacogenomics J 4, 77–87 (2004). https://doi.org/10.1038/sj.tpj.6500233

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