Clinical correlates of tardive dyskinesia in schizophrenia: Baseline data from the CATIE schizophrenia trial
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
References (64)
Increased tardive dyskinesia in alcohol-abusing schizophrenic patients
Compr. Psychiatry
(1992)Defect symptoms and abnormal involuntary movement in schizophrenia
Biol. Psychiatry
(1986)Olanzapine treatment for tardive dyskinesia in schizophrenia patients: a prospective clinical trial with patients randomized to blinded dose reduction periods
Prog. Neuro-Psychopharmacol. Biol. Psychiatry
(2004)Positive and negative subtypes in acute schizophrenia
Compr. Psychiatry
(1984)Abnormal involuntary movements and chronic schizophrenic disorders
Biol. Psychiatry
(1990)Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort
Am. J. Psychiatry
(1998)Diagnostic and Statistical Manual on Mental and Disorders
(1994)A rating scale for drug-induced akathisia
Br. J. Psychiatry
(1989)- et al.
Drug addiction
N. Engl. J. Med.
(2003) Incidence and correlates of tardive dyskinesia in first episode of schizophrenia
Arch. Gen. Psychiatry
(1996)
Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
JAMA
Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies
Am. J. Psychiatry
Prevention and management of tardive dyskinesia
Am. J. Psychiatry
Does tardive dyskinesia exist?
Mod. Probl. Pharmacopsychiatry
Serum neuroleptic activity, prolactin, and tardive dyskinesia in schizophrenic outpatients
Psychopharmacology (Berlin)
Tardive dyskinesia and type II schizophrenia
Br. J. Psychiatry
Diagnosis of alcohol use disorders in schizophrenia
Schizophr. Bull.
Chronic involuntary movements induced by phenothiazines
J. of Nerv. Ment. Dis.
Report of the expert committee on the diagnosis and classification of diabetes mellitus
Diabetes Care, Suppl.
Structural Clinical Interview for DSM-IV (SCID-I): User's Guide and Interview- Research Version
The prevalence of tardive dyskinesia in neuroleptic treated diabetics
Arch. Gen. Psychiatry
Tardive dyskinesia and anticholinergic drugs
Am. J. Psychiatry
Tardive dyskinesia. A discontinuation study
Arch. Gen. Psychiatry
Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex
Am. J. Psychiatry
Tiapride: effects on tardive dyskinesia and on prolactin plasma concentrations
Neuropsychobiology
The prevalence of abnormal involuntary movements among chronic schizophrenics
Int. Clin. Psychopharmacol.
A sharper Bonferroni procedure for multiple tests of significance
Biometrika
Changing epidemiology of tardive dyskinesia: an overview
Am. J. Psychiatry
Association of abnormal involuntary movements and negative symptoms
Psychopharmacol. Bull.
Risk of tardive dyskinesia in older patients. A prospective longitudinal study of 266 outpatients
Arch. Gen. Psychiatry
Incidence of tardive dyskinesia in early stages of low-dose treatment with typical neuroleptics in older patients
Am. J. Psychiatry
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