Course Of Tardive Dyskinesia Research Articles

Regional Homogeneity in schizophrenia patients with tardive dyskinesia: a resting-state fMRI study

Neuronal degeneration and apoptosis may play an important role in the pathogenesis of tardive dyskinesia (TD). Previous studies suggested brain structural and functional abnormalities in patients with TD. We investigated changes in cerebral regional homogeneity (ReHo) in patients with TD using resting-state functional magnetic resonance imaging (rs-fMRI). Imaging data were collected from schizophrenia patients with TD (TD group, n=58) and without TD (non-TD group, n=66) and healthy controls (HC group, n=67), processed with SPM, and evaluated at a corrected threshold. Psychopathology and severity of TD were assessed with the Positive and Negative Syndrome Scale (PANSS) and Abnormal Involuntary Movement Scale (AIMS), respectively. Results: TD vs. non-TD group showed significantly higher ReHo in the Left Inferior Semilunar Lobule and Right Fusiform Gyrus and lower ReHo in Left Supramarginal Gyrus, Right Inferior Tempotal Gyrus, and Left Medial Frontal Gyrus. The ReHo value in the Left Inferior Semilunar Lobule was negatively correlated with AIMS upper limbs scores. Conclusions: The findings suggest altered regional neural connectivities in association with TD and may inform research of the etiology and monitor the course of TD in patients with schizophrenia and potentially other psychotic disorders.

Treatment Outcomes of Patients With Tardive Dyskinesia and Chronic Schizophrenia

We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia (TD) and examined the course of TD. This analysis compared 200 patients with DSM-IV-defined schizophrenia and TD and 997 patients without TD, all of whom were randomly assigned to receive one of 4 second-generation antipsychotics. The primary clinical outcome measure was time to all-cause treatment discontinuation, and the primary measure for evaluating the course of TD was change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare treatment discontinuation between groups. Changes in Positive and Negative Syndrome Scale (PANSS) and neurocognitive scores were compared using mixed models and analysis of variance. Treatment differences between drugs in AIMS scores and all-cause discontinuation were examined for those with TD at baseline. Percentages of patients meeting criteria for TD postbaseline or showing changes in AIMS scores were evaluated with χ(2) tests. Data were collected from January 2001 to December 2004. Time to treatment discontinuation for any cause was not significantly different between the TD and non-TD groups (χ(2)(1) = 0.11, P = .743). Changes in PANSS scores were not significantly different (F(1,974) = 0.82, P = .366), but patients with TD showed less improvement in neurocognitive scores (F(1,359) = 6.53, P = .011). Among patients with TD, there were no significant differences between drugs in the decline in AIMS scores (F(3,151) = 0.32, P = .811); 55% met criteria for TD at 2 consecutive visits postbaseline, 76% met criteria for TD at some or all postbaseline visits, 24% did not meet criteria for TD at any subsequent visit, 32% showed a ≥ 50% decrease in AIMS score, and 7% showed a ≥ 50% increase in AIMS score. Schizophrenia patients with and without TD were similar in time to discontinuation of treatment for any cause and improvement in psychopathology, but differed in neurocognitive response. There were no significant differences between treatments in the course of TD, with most patients showing either persistence of or fluctuation in observable symptoms. clinicaltrials.gov Identifier: NCT00014001.

Ethnicity and the Course of Tardive Dyskinesia in Outpatients Presenting to the Motor Disorders Clinic at the Maryland Psychiatric Research Center

Although newly emergent tardive dyskinesia (TD) is less of a concern, about one-fourth to one-third of patients on or previously on chronic first-generation antipsychotic agents have TD. The long-term course and outcome, as well as their predictors, are unknown. Earlier studies identify ethnicity as one of the risk factors for the development of TD, and case reports have noted a preponderance of African-American males in cohorts of patients with tardive dystonia. The current study examines the anatomic distribution and course of TD in a cohort of schizophrenia patients of European and African descent with TD who were referred to the Motor Disorders Clinic (MDC). We evaluated data collected on 1149 TD patients who were given a focused neurologic examination for movement disorders. Movements were evaluated with the MPRC Scale for Involuntary Movements (IMS). All patients met RDC-TD criteria for diagnosis of persistent TD. One to 10-year follow-up data on 528 patients were evaluated to examine the course of TD following recommendations made to referring primary clinicians. Suggested interventions to referring primary clinicians included dose reduction of first-generation antipsychotic medication, or switching to a second-generation antipsychotic. Initial evaluation included 701 European American (EA) patients and 448 African-American (AA) patients. AA patients had a significantly higher proportion of males [chi(1) = 7.50, P < 0.05]. EA subjects had a higher mean age than AA patients 42.8 +/- 11.2 and 39.8 +/- 10.4, respectively [F(1,1147) = 22.27, P < 0.05]. Mean neuroleptic exposure (chlorpromazine equivalents) was similar in both groups after controlling for differences in age.Follow-up data analyzed in 528 patients (329 EA and 199AA) showed a significant ethnicity by TD interaction [F(1,504) = 4.26, P < 0.05]. Examination of body distribution of dyskinetic movements showed an effect of ethnicity. Subsequent analyses suggest EA patients experienced more improvement in TD over the course of follow up [F(1,319) = 22.39, P < 0.05] compared with AAs [F(1,189) = 1.58, P > 0.05]. These findings were unchanged when age, change in antipsychotic drug dose, and duration of follow-up were covaried. Reports from earlier studies note ethnicity (African descent) as a risk factor in the development of TD. Our study findings suggest ethnicity might be an important factor in predicting a poor course of TD.

Tardive Dyskinesia in Elderly Patients:

The use of antipsychotic agents can be limited by side effects, particularly extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). These neurologic movement disorders can occur early in the course of treatment (often as EPS) or as a more latent effect (TD). TD can be debilitating, and several patient-related and treatment-related factors have been associated with an increased risk for its development. Of these, older age has been strongly linked to TD. The advent of novel antipsychotics for the treatment of schizophrenia and severe behavioral disorders permits the use of such agents with reduced risk of EPS and TD. Most clinical trials of the novel antipsychotics have enrolled younger patients, but some data on their efficacy and safety in the elderly are now available. This article reviews the relationship between TD and aging and its treatment in elderly patients.

Treatment predictors of extrapyramidal side effects in patients with tardive dyskinesia: results from Veterans Affairs Cooperative Study 394.

Predictors for the development of tardive dyskinesia (TD) have been studied extensively over the years, yet there are few studies of predictors of the course of TD after it has developed. Moreover, few studies have examined predictors of the course of other extrapyramidal side effects (EPS) in patients maintained on neuroleptics. The purpose of this study was to determine which modifiable variables are important in the prediction of EPS in patients with persistent TD over a period of as long as 2 years. One hundred fifty-eight patients enrolled in the Veterans Affairs Cooperative Study 394 were included in this study. A linear mixed-effects (LME) analysis to estimate the Abnormal Involuntary Movement Scale score (for TD severity), Simpson-Angus Scale (for parkinsonism severity), and Barnes Akathisia Scale at any given time after intake assessment was performed. The severity of each of the TD and EPS outcomes at any given visit was predicted by their respective baseline severity scores. Additional predictors of a favorable course of TD included lower doses of antipsychotic medications and use of anticholinergic medications. Other predictors of a favorable course of EPS included younger age and the use of atypical antipsychotic medication (for rigidity) and the use of anticholinergic medication (for tremor). These findings indicate that clinician-modifiable factors related to medication usage can influence the outcome of TD and EPS in patients with persistent TD.

The course of tardive dyskinesia and parkinsonism in psychiatric inpatients: 14-year follow-up.

Tardive dyskinesia and parkinsonism were assessed in 53 patients residing in a state psychiatric hospital in 1984 and 1998. A 4.0-point decrease in the mean Abnormal Involuntary Movement Scale score (6.0 versus 2.0; p < 0.001) and a 3.5-point increase in the Rating Scale for Extrapyramidal Signs score (2.8 versus 6.3; p < 0.001) were noted between 1984 and 1998. Over a 14-year period, tardive dyskinesia improved and parkinsonism worsened in patients who continued to receive neuroleptic drugs.

Tardive dyskinesia and atypical antipsychotic drugs

Typical antipsychotic agents produce central nervous system effects, especially extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). Nearly every patient who receives neuroleptic therapy has one or more identifiable risk factors for TD, among the most significant of which are older age, female gender, presence of EPS, diabetes mellitus, affective disorders, and certain parameters of neuroleptic exposure (i.e. dose and duration of therapy). The typical course of TD is a gradual onset after several years of drug therapy, followed by slow improvement or remission, but a large number of patients have persistent TD with irreversible symptoms. In the management of TD, the patient's mental status is of primary concern. Currently, no uniformly safe and effective therapies for TD exist, though a variety of therapeutic agents, including some of the atypical neuroleptics, have been reported to treat TD successfully in some patients. Because TD liability is so much lower with novel antipsychotic therapy, all patients who have TD or are at risk for TD, as well as EPS, should be considered candidates for switching to these new drugs.

Markers of glutamatergic neurotransmission and oxidative stress associated with tardive dyskinesia.

Tardive dyskinesia is a movement disorder affecting 20%-40% of patients treated chronically with neuroleptic drugs. The dopamine supersensitivity hypothesis cannot account for the time course of tardive dyskinesia or for the persistence of tardive dyskinesia and the associated structural changes after neuroleptics are discontinued. The authors hypothesized that neuroleptics enhance striatal glutamatergic neurotransmission by blocking presynaptic dopamine receptors, which causes neuronal damage as a consequence of oxidative stress. CSF was obtained from 20 patients with schizophrenia, 11 of whom had tardive dyskinesia. Markers for oxidative stress, including superoxide dismutase, lipid hydroperoxide, and protein carbonyl groups, and markers for excitatory neurotransmission, including N-acetylaspartate, N-acetylaspartylglutamate, aspartate, and glutamate, were measured in the CSF specimens. Patients were also rated for tardive dyskinesia symptoms with the Abnormal Involuntary Movement Scale. Tardive dyskinesia patients had significantly higher concentrations of N-acetylaspartate, N-acetylaspartylglutamate, and aspartate in their CSF than patients without tardive dyskinesia when age and neuroleptic dose were controlled for. The significance of the higher levels of protein-oxidized products associated with tardive dyskinesia did not pass Bonferroni correction, however. Tardive dyskinesia symptoms correlated positively with markers of excitatory neurotransmission and protein carbonyl group and negatively with CSF superoxide dismutase activity. These findings suggest that there are elevated levels of oxidative stress and glutamatergic neurotransmission in tardive dyskinesia, both of which may be relevant to the pathophysiology of tardive dyskinesia.

Course of tardive dyskinesia in schizophrenic patients attending a motor disorder clinic for two years

Course of tardive dyskinesia in schizophrenic patients attending a motor disorder clinic for two years

Tardive dyskinesia.

Neuroleptic-induced tardive dyskinesia (TD) continues to be a serious problem in the psychopharmacology of schizophrenia. The overall mean prevalence of TD among chronically neuroleptic-treated patients is approximately 24 percent. The annual incidence in younger adults is 4 to 5 percent. Aging is a major risk factor for TD. Our ongoing prospective study suggests that the annual incidence in patients over age 45 is over 30 percent. Other likely risk factors include female gender, mood disorders, "organic" brain dysfunction or damage, diabetes mellitus, and early extrapyramidal side effects. Metoclopramide, a D2-receptor blocker commonly used in non-psychiatric medical patients, can also produce persistent TD. TD can best be assessed for research purposes by a combination of subjective and objective methods. In recent years, several instrumental procedures have been developed to objectively quantify various abnormal movements. The advantages and limitations of the traditional rating scales and the newer instrumental approaches are discussed. The course of TD is variable but often not progressive. The early theory that striatal dopamine receptor supersensitivity causes TD has now given way to the hypothesis of multiple neurotransmitter system involvement. Several animal studies have reported striatal neuronal damage with prolonged neuroleptic treatment, although its relevance to TD remains unclear. Treatments for TD, other than neuroleptic withdrawal, are still experimental.

Predictors of the course of tardive dyskinesia in patients receiving neuroleptics

As many patients still require maintenance neuroleptic medication, it is important to determine what factors affect the course of tardive dyskinesia (TD) during ongoing neuroleptic treatment. In this study the data are from a series of annual examinations using the Abnormal Involuntary Movement Scale (AIMS) in a cohort of outpatients. Average neuroleptic exposure at the commencement of the examinations was 10 yr. The data on AIMS scores at successive visits are analysed using autoregressive modeling. Two hundred thirty-five patients contributed the 678 pairs of examinations. Separate analyses are reported for orofacial, limb-truncal, and total AIMS scores. Different predictor variables emerged as important for orofacial and limb-truncal dyskinesia. Age, sex, being on anticholinergic medication, and two variables describing duration of neuroleptic exposure contributed to the outcome score for total AIMS score after 1 yr.

The course of tardive dyskinesia in newly treated psychogeriatric patients

The author reports on the course of tardive dyskinesia in 10 newly treated psychogeriatric patients. Of the 5 whose medication was discontinued, 3 improved; TD continued unchanged in the other 5 patients whose neuroleptics were not discontinued. The author recommends that neuroleptics be discontinued whenever possible in this patient population.

Predictors of Improvement in Tardive Dyskinesia Following Discontinuation of Neuroleptic Medication

Forty-nine chronic psychiatric out-patients (ten were schizophrenic) with tardive dyskinesia (TD) were examined monthly for a mean of 40 weeks (range 1-59 months) after discontinuation of neuroleptic medication. Complete and persistent reversibility of TD was rare (2%), but many patients showed noticeable improvement in movements within the first year of discontinuation, which was sometimes interrupted by psychological relapse. Using three separate outcome measures and appropriate model-fitting techniques for each, we identified several predictors of improvement in TD, including an affective or schizoaffective psychiatric diagnosis, chronic (over 20 years) psychiatric illness, being employed, younger age, and increased neuroleptic dose before discontinuation. Consistent findings emerging from these analyses suggest that the type and history of psychiatric illness affect the course of TD.

Changes in Tardive Dyskinesia After Fluphenazine Decanoate Discontinuation

AbstractWe followed the course of tardive dyskinesia (TD) in 21 schizophrenic patients with abnormal involuntary movements who were discontinued from depot fluphenazine for up to 1 year. Over time there was a statistically significant decrease in TD ratings following discontinuation; in 7 of the 21 patients clinically meaningful decreases in the abnormal involuntary movements occurred. Unfortunately, 15 of the 21 patients relapsed and had to be put back on neuroleptics within that year. In contrast, a group of ten patients with abnomal involuntary movements were kept on fluphenazine decanoate (average dose 45 mg intramuscularly every 2 weeks) for 1 year. Only one of these ten patients relapsed and a clinically significant decrease in TD did not occur as only one patient had a clinically meaningful worsening of abnormal involuntary movements.

Predictors of Occurrence, Severity, and Course of Tardive Dyskinesia in an Outpatient Population

This paper summarizes the results of three different studies of tardive dyskinesia conducted within a single-source, outpatient population at the Connecticut Mental Health Center in New Haven. Emerging themes from this work suggest that prevalence, severity and course of tardive dyskinesia are influenced--probably in different ways--by treatment, psychiatric illness, and other personal characteristics.

Overview: public health issues in tardive dyskinesia.

Public health concern over tardive dyskinesia has been rising, but the magnitude of the problem has been undetermined. The incidence of tardive dyskinesia is unknown, and prevalence rates yield conflicting and possibly misleading estimates. The natural course of tardive dyskinesia is highly variable: in some patients (probably many fewer than previously believed) it is irreversible. No currently available therapeutic agent satisfies the criteria of safety, marked effectiveness, and prolonged efficacy in the treatment of tardive dyskinesia. Primary prevention involves reducing antipsychotic drug exposure, secondary prevention involves early diagnosis and prompt intervention, and tertiary prevention involves clinical measures to reduce disability and to treat severe cases vigorously. Educational methods that disseminate knowledge and influence prescribing habits need to be identified and used more widely.