Elsevier

Schizophrenia Research

Volume 80, Issue 1, 1 December 2005, Pages 33-43
Schizophrenia Research

Clinical correlates of tardive dyskinesia in schizophrenia: Baseline data from the CATIE schizophrenia trial

https://doi.org/10.1016/j.schres.2005.07.034Get rights and content

Abstract

Objective

To examine the clinical characteristics of individuals with schizophrenia that develop tardive dyskinesia (TD) associated with antipsychotic treatment.

Methods

Baseline data on 1460 patients with schizophrenia were collected as part of the Clinical Antipsychotic Trials of Intervention Effectiveness schizophrenia study. Subjects who met Schooler–Kane criteria for probable TD were compared to those without TD. Multiple regression analyses were used to examine the relationship between TD and clinical variables.

Results

212 subjects met the Schooler–Kane criteria for probable TD and 1098 had no history or current evidence of TD. Subjects with TD were older, had a longer duration of receiving antipsychotic medication, and were more likely to have been receiving a conventional antipsychotic and an anticholinergic agent. After controlling for important baseline covariates, diabetes mellitus (DM) and hypertension did not predict TD, whereas substance abuse significantly predicted TD. Differences in cognitive functioning were not significantly different after controlling for baseline covariates. The TD subjects also had higher ratings of psychopathology, EPSE, and akathisia.

Conclusion

Our results confirm the established relationships between the presence of TD and age, duration of treatment with antipsychotics, treatment with a conventional antipsychotic, treatment with anticholinergics, the presence of EPS and akathisia, and substance abuse. Subjects with TD had higher ratings of psychopathology as measured by the PANSS. We found no support for DM or hypertension increasing the risk of TD, or for TD being associated with cognitive impairment.

Introduction

Tardive dyskinesia (TD) was first described in the late 1950's almost a decade after the introduction of the antipsychotic medications (Sigwald et al., 1959, Druckman et al., 1962). Nonetheless, there is clear evidence that motor disorders are inherent in schizophrenia, as dyskinetic movements were recognized years before the advent of antipsychotic medications and are seen in patients who have never received antipsychotics. While schizophrenia appears to be associated with a tendency to develop abnormal involuntary movements, antipsychotics promote or exacerbate this tendency in at least some forms of the illness (Owens, 1985).

After over 40 years of research, we still do not understand why some patients, but not others, develop these involuntary movements. Previous studies have suggested an association of TD with increasing age, female gender, longer duration of antipsychotic treatment, higher ratings of negative symptoms and thought disorder, greater cognitive impairments, presence of early onset extrapyramidal side effects (EPSE), and a diagnosis of diabetes mellitus (DM). Chronic antipsychotic exposure and aging are the most consistently implicated risk factors for tardive dyskinesia. In the present study we utilized the National Institute of Mental Health initiated Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial baseline data to examine the clinical correlates that are associated with the presence of TD.

Section snippets

Patient population

Patients were participants in the CATIE Schizophrenia Trial which was designed to evaluate the comparative effectiveness and tolerability of antipsychotic drugs in typical clinical settings and populations. To make the results of the trials generalizable and representative of the broad group of patients with chronic schizophrenia, subjects with comorbid psychiatric disorders, substance use disorders, or stable medical disorders, were allowed to participate. Details of the study design have been

Statistical methods

Our primary hypotheses followed two lines of reasoning: first, we hypothesized that conditions known to be detrimental to brain function (DM, hypertension, or current substance abuse disorder) would be associated with higher prevalence rates of TD; and, second, we hypothesized that if, indeed, “injury” had occurred in the brains of patients with TD, this would also be manifested in other areas of brain function (impaired cognition, as measured by the overall neurocognitive functioning score and

Results

Of the 1460 patients analyzed, 212 met modified Schooler–Kane criteria for probable TD and 1098 had neither a history nor current evidence of TD. Sixty-eight patients who had a chart history of TD but did not currently meet modified Schooler–Kane criteria, and 80 patients who had no history of TD but had one AIMS item rated = 2, were considered indeterminate, and were excluded from the present analyses. Two patients were excluded due to missing data. There are 67 patients in our population whose

Discussion

We found that 15% of the population had probable TD at baseline, 75% had neither a history nor current evidence of TD, and 10% either had a chart history of TD without current evidence or current sub-threshold evidence of TD. As would be predicted from previous studies, the patients with TD were older, had a longer duration since first being treated with an antipsychotic, were more likely to be currently treated with a conventional antipsychotic, had signs of EPS and were more likely to be

Conclusion

In conclusion, our results confirm previously suggested relationships between age, duration of treatment with an antipsychotic, treatment with a conventional antipsychotic, treatment with an anticholinergic agent, presence of EPS, increased psychopathology, current substance abuse, and the presence of TD. We found no support for the hypothesis that DM or hypertension increase the risk for TD, or that TD is associated with cognitive impairment. This suggests that older patients with

Acknowledgements

This article was based on results from the Clinical Antipsychotic Trials of Intervention Effectiveness project, supported with Federal funds from the National Institute of Mental Health under contract NO1 MH90001. The aim of this project is to examine the comparative effectiveness of antipsychotic drugs in conditions for which their use is clinically indicated, including schizophrenia and Alzheimer's disease. The project was carried out by principal investigators from the University of North

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