Prospective study of tardive dyskinesia in the elderly: rates and risk factors

Estimated incidence rates are presented for three human immunodeficiency virus (HIV)-associated cancers [Kaposi's sarcoma (KS), Burkitt's lymphoma (BL) and other non-Hodgkin's lymphomas (NHLs)] from across the African continent, based on data collected before the HIV epidemic. Mapping of the rates and comparisons with a range of geographical variables indicate completely different distributions for KS and BL but a degree of similarity in the occurrence of Burkitt's lymphoma and other NHLs. Comparisons with rates elsewhere in the world suggest, most notably, that KS was as common in some regions of sub-Saharan Africa as was cancer of the colon in much of Western Europe. Comparison with data from the era of AIDS indicates 20-fold increases in the occurrence of Kaposi's sarcoma in Uganda and Zimbabwe. The highest rates for BL were three to four times the rates for leukaemia at young ages in Western populations, but the general incidence of other NHL was no higher than in the West and very low rates were indicated for much of southern Africa.     

The prevention of tardive dyskinesia

The publication of numerous articles on tardive dyskinesia has had little effect on the excessive use of neurolepic drugs in psychiatric populations. If current prescribing patterns are not drastically changed, larger numbers of patients will be afflicted by conspicuous, sometimes disabling neurological side effects. The risk of permanent neurological disorder can be minimized by monitoring side effects and systematically reducing drug doses in hospitals, outpatient centers, and private practice. However, one should not underestimate the difficulty in implementing such a program in facilities that rely heavily on chemotherapy.     

Neuroleptic-induced acute extrapyramidal syndromes and tardive dyskinesia

Neuroleptic drug-induced acute extrapyramidal symptoms and later-onset tardive dyskinesia are major limitations to these valuable drugs. Each of these disorders can be described by special risk factors that include patient characteristics, drug factors, and temporal considerations. The limitations that derive from these motor side effects have been one of the major reasons propelling the search for neuroleptic drugs that are free of these side effects. Strategies for managing the acute and late-onset extrapyramidal syndromes are presented. Significantly more research is needed, however, on all these disorders before a unified and cohesive explanation can account for these seemingly disparate syndromes. New medications, which effectively treat schizophrenia and are free of acute extrapyramidal syndromes and tardive dyskinesia, will be a giant step forward in patient care and our knowledge of the mechanisms controlling both mental function and motor control.     

Effects of dopamine agonists in tardive dyskinesia

The authors used a combined behavioral and neuroendocrinological strategy to investigate the relevance of abnormalities in the brain dopaminergic systems to the pathophysiology of tardive dyskinesia by assessing the effects of apomorphine, a directly acting dopamine agonist, and d-amphetamine, an indirectly acting dopamine agonist, in patients with tardive dyskinesia. Administration of I.V. d-amphetamine increased dyskinetic movements in most patients with tardive dyskinesia, a finding consistent with the dopaminergic hypothesis. Contrary to predictions based on animal models, apomorphine did not increase dyskinetic movements in these patients but instead substantially reduced dyskinesia in some patients. Patients with tardive dyskinesia did not have a greater drop in serum prolactin or a greater rise in serum growth hormone after apomorphine than normal or chronic schizophrenic subjects without tardive dyskinesia.     

Current topics in tardive dyskinesia in Japan

This article reviews current topics in tardive dyskinesia (TD), a movement disorder associated with the prolonged use of neuroleptic agents, especially therapeutic and preventive strategies which have been or are now being studied in Japan. Tardive dyskinesia has become a major problem in the clinical psychiatric field since the early 1970s in Japan, lagging behind Western countries by more than 10 years. The average prevalence rate of TD has been estimated as 7.7% in Japan, while it has been reported in the English literature at around 15 to 20%. Clinical trials of treatments for TD have been or are now being performed in Japan with a number of novel compounds, such as ceruletide, meclofenoxate, and rolipram; however, no effective treatment has yet been established and measures to prevent TD have therefore been emphasized. These include (i) the development of new antipsychotic drugs which are free from TD, (ii) the identification of risk factors from prospective longitudinal studies, and (iii) the investigation of genetic variations that could act as a marker to identify especially vulnerable patients within the whole population of patients who need neuroleptic therapy.     

A neural systems theory of schizophrenia and tardive dyskinesia

Some systems ideas applied to individual persons are used to try to explain symptoms of schizophrenia and a syndrome of uncontrolled fragments of movement which sometimes occurs as a side effect of chronic, antipsychotic drug therapy. The behavior of normal organisms may be conceptualized in three echelons of control, with each successively higher echelon organizing, by selective disinhibition, semiautonomous, spontaneous fragments of activity which comprise the next lower echelon. It is hypothesized that schizophrenia involves a deficiency of inhibition by the frontal cortex, first echelon, on the corpus striatum, second echelon. This results first in insufficiently integrated fragments of behavior, and second in premature associative linkages among active elements. First echelon control develops as a normal person matures and gradually loses some of the playful activities of childhood. It is hypothesized that by disrupting certain aspects of activity in the corpus striatum, neuroleptic drugs reduce schizophrenic symptoms but also reduce the capacity of the second echelon to inhibit and integrate the smaller behavioral fragments wired into lower parts of the brain, third echelon. This results in uncontrolled movements. Though many researchers already favor the hypothesis that neuroleptic drugs act on the corpus striatum, the broader theory presented here is new and depends in large part on general living systems considerations. Emphasis is on conceptual decomposition of the integrated behavior of a whole organism into less complex subsystems. Individually, these have neither too much nor too little complexity to yield a plausible model. Some experimental predictions and predictions about possible therapies are made from the theory.     

The effect of clozapine on preexisting tardive dyskinesia

Since the 1950s, the main treatment for schizophrenia has been the use of neuroleptic therapy. However, these medications may produce tardive dyskinesia in those patients who require prolonged neuroleptic treatment. With the advent of clozapine, patients with preexisting tardive dyskinesia began therapy and their symptoms did not worsen--and, in many cases, their symptoms improved dramatically. In this study, the mean Abnormal Involuntary Movement Scale (AIMS) scores from baseline to 6 months are compared for 12 patients in a private partial hospitalization program for schizophrenia. The findings reveal a drastic decrease in AIMS scores after 1 month of clozapine therapy and a steady decrease in scores throughout the 6 months of analysis.     

Tardive dyskinesia in dopa-responsive dystonia: a reappraisal of the dopamine hypothesis of tardive dyskinesia

Dopa-responsive dystonia, an autosomal-dominant disorder caused by mutations in the guanosine triphosphate (GTP)-cyclohydrolase I gene, is characterized by severe striatal dopamine depletion. Tardive dyskinesia, on the other hand, has often been associated with striatal dopamine overactivity. This article reports on a 44-year-old man with dopa-responsive dystonia who developed tardive dyskinesia on long-term haloperidol therapy. Nigrostriatal dopamine deficiency may be necessary for the development of tardive dyskinesia.     

Intermittent neuroleptic treatment and risk for tardive dyskinesia: Cura?ao Extrapyramidal Syndromes Study III

OBJECTIVE: The authors examined the association between three lifetime medication variables (cumulative amount of neuroleptics, number of interruptions in neuroleptic treatment, cumulative amount of anticholinergics) and the occurrence and severity of tardive dyskinesia. METHOD: The study was conducted in the only psychiatric hospital of a well-defined catchment area (the Netherlands Antilles). For all patients who had a history of taking neuroleptics for at least 3 months and were currently using neuroleptics (N = 133, mean age = 51.5 years), the presence and severity of tardive dyskinesia were measured with the Abnormal Involuntary Movement Scale. RESULTS: Of the three lifetime medication variables, only the number of neuroleptic interruptions was significantly related to tardive dyskinesia. The risk of tardive dyskinesia was three times as great for patients with more than two neuroleptic interruptions as for patients with two or fewer interruptions. CONCLUSIONS: This finding supports the schizophrenia protocol of long-term neuroleptic treatment rather than targeted or intermittent neuroleptic treatment.     

Effectiveness of vitamin E for treatment of long-term tardive dyskinesia

Eleven patients with tardive dyskinesia were treated in a double-blind study of vitamin E or placebo for 12 weeks. Abnormal Involuntary Movement Scale (AIMS) ratings were performed before and after treatment. Patients receiving vitamin E showed a significant reduction in their AIMS scale score, but patients receiving placebo showed no significant change. Vitamin E had a helpful effect even for patients whose tardive dyskinesia was mild and long-term.     

Effects of monosialoganglioside on a new model of tardive dyskinesia

1- The effects of monosialoganglioside GM1 were studied on a new model of tardive dyskinesia, i.e., the frequency of spontaneous tongue protrusions in rats repeatedly treated with reserpine. 2- Rats were co-treated with vehicle (VEH) or reserpine (RES) (0.1 mg/kg, s.c., every other day) and saline (SAL) or GM1 (5 mg/kg, i.p., every day) for 30 days and observed for tongue protrusions on days 10, 20 and 30. 3- During each test day animals of the RES + SAL group exhibited an increase in tongue protrusions relative to rats of the VEH + SAL group. However, rats of the RES + GM1 group showed an increased frequency of tongue protrusions only on day 10, when compared to animals of the VEH + SAL group. There were no significant differences in tongue protrusion frequency between the VEH + GM1 and the VEH + SAL groups. 4- These results differ from previous studies which reported a facilitatory effect of GM1 co-administration on conventional behavioral animal models of tardive dyskinesia. The possibility is raised that GM1 attenuates the reserpine-induced increase in tongue protrusions through its protective effect on glutamate/oxidative stress neurotoxicity.     

The role of parkinsonism and antiparkinsonian therapy in the subsequent development of tardive dyskinesia

Tardive dyskinesia (TD) is a side effect of prolonged neuroleptic treatment presenting as abnormal involuntary movements. This troublesome disorder occurs in only 15-30% of patients taking neuroleptics, suggesting that these individuals may be physiologically distinct so as to be predisposed. This study analyzed possible factors contributing to TD development. Fifty patients on depot neuroleptics for more than 7.1 years were prospectively examined for TD and drug-induced parkinsonism (DIP) using the Smith-Trims rating scale for an average of 5 years. The patients were assessed for the severity of the movement and if the movement increased or decreased with respect to neuroleptic dosage, anticholinergic dosage, parkinsonism, and other related factors. Both TD and DIP increased over time. In the patients whose dose of neuroleptic decreased, the increase in TD ratings was not significant. Using a forward stepwise regression DIP was found to increase as TD worsened but did not appear to predict subsequent TD development. Anticholinergic treatment showed a less significant correlation with the change in TD. These results have implications for the management of combined TD and DIP presentation.     

Diurnal and weekly variation of tardive dyskinesia measured by digital image processing

The causes and clinical manifestations of Clostridium difficile infection in children are described in this report. The studies were performed on three children aged up to 3 years. Risk factors as well as possible diagnostic and therapeutic procedures are discussed.